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Zhong J, Xu P, Li X, Wang M, Chen X, Liang H, Chen Z, Yuan J, Xiao Y. Construction of a diagnostic model utilizing m7G regulatory factors for the characterization of diabetic nephropathy and the immune microenvironment. Sci Rep 2025; 15:9208. [PMID: 40097518 PMCID: PMC11914462 DOI: 10.1038/s41598-025-93811-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 03/10/2025] [Indexed: 03/19/2025] Open
Abstract
Diabetic nephropathy (DN), a prevalent and severe complication of diabetes, is associated with poor prognosis and limited treatment options. N7-Methylguanosine (m7G) modification plays a crucial role in regulating RNA structure and function, linking it closely to metabolic disorders. However, despite its biological significance, the interplay between m7G methylation and immune status in DN remains largely unexplored. Leveraging data from the GEO database, we conducted consensus clustering of m7G regulators in DN patients to identify distinct molecular subtypes. To construct and validate m7G-related prognostic features and risk scores, we integrated multiple machine learning approaches, including Support Vector Machine-Recursive Feature Elimination, Random Forest, LASSO, Cox regression, and ROC curves analysis. In addition, we employed GSVA, ssGSEA, CIBERSORT, and Gene Set Enrichment Analysis to investigate the associated biological pathways and the immune landscape, providing deeper insights into the role of m7G methylation in DN. Based on the expression levels of 18 m7G-related regulatory factors, we identified nine key regulators. Through machine learning techniques, we identified four significant regulators (METTL1, CYFIP2, EIF3D, and NUDT4). Consensus clustering classified these genes into two distinct m7G-related clusters. To characterize these subtypes, we conducted immune infiltration analysis, differential expression analysis, and enrichment analysis, uncovering significant biological differences between the clusters. Additionally, we developed an m7G-related risk scoring model using the PCA algorithm. The differential expression of the four key regulators was further validated through in vivo experiments, reinforcing their potential role in disease progression. The m7G-related genes METTL1, CYFIP2, EIF3D, and NUDT4 may serve as potential diagnostic biomarkers for DN, providing new insights into its molecular mechanisms and immune landscape.
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Affiliation(s)
- Jingying Zhong
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Pengli Xu
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Xuanyi Li
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Meng Wang
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Xuejun Chen
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Huiyu Liang
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Zedong Chen
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
| | - Jing Yuan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ya Xiao
- School of Traditional Chinese Medicine, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China.
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Ma X, Yu J, Ma Y, Huang X, Zhu K, Jiang Z, Zhang L, Liu Y. Explore the mechanism of yishenjiangya formula in the treatment of senile hypertension based on multi-omics technology. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118886. [PMID: 39362324 DOI: 10.1016/j.jep.2024.118886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 09/19/2024] [Accepted: 09/30/2024] [Indexed: 10/05/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Yishenjiangya formula (YSJ) is a traditional Chinese medicine (TCM) primarily composed of qi-tonifying components. This classic formula is commonly utilized to treat kidney qi deficiency in elderly patients with hypertension. According to TCM, maintaining a balance between qi and blood is crucial for stable blood pressure. Kidney qi deficiency can disrupt this balance, altering fluid shear force and, ultimately, leading to hypertension, particularly in elderly populations. Despite YSJ's efficacy in treating hypertension, its specific anti-hypertensive mechanisms remain unclear. AIM OF THE STUDY YSJ is commonly prescribed for elderly patients with hypertension. Earlier metabolomics studies demonstrated that YSJ exerts antihypertensive effects by influencing four key pathways: linoleic acid metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. This study aims to combine metabolomic and proteomic analyses to thoroughly understand the molecular biological mechanisms responsible for YSJ's anti-hypertensive properties. METHODS Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) metabolomics, combined with Label-Free Quantitation (LFQ) proteomics, was employed to analyze serum samples from elderly individuals with and without hypertension pre- and post-YSJ intervention. Serum levels of candidate proteins were assessed using enzyme-linked immunosorbent assay, and receiver operating characteristic curves were used to evaluate the diagnostic performance of the target proteins. RESULTS Eight differentially expressed metabolites and three differentially expressed proteins were identified as potential therapeutic targets of YSJ. These substances are primarily involved in unsaturated fatty acid metabolism, fluid shear stress and atherosclerosis pathway, primary bile acid biosynthesis, proline metabolism, apoptosis, and endoplasmic reticulum stress. YSJ exerts its therapeutic effects on hypertension in the elderly by modulating these pathways. CONCLUSIONS YSJ effectively treats senile hypertension. By analyzing the correlation between therapeutic targets and pathways, YSJ's anti-hypertensive effect was achieved by inhibiting lipid peroxidation and matrix degeneration. Combining metabolomics and proteomics provides an effective method for uncovering YSJ's anti-hypertensive mechanisms.
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Affiliation(s)
- Xu Ma
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Jie Yu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China
| | - Yongbo Ma
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, Shanghai, China
| | - Xinyu Huang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Kunpeng Zhu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Zhen Jiang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Lei Zhang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China.
| | - Yingying Liu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China.
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Zhang XT, Luan XP, Wei JH, Zhang PP, Guo JM, Keesey IW, Gao Y, Yan Q, Zhang J, Dong SL. Identification of a Soybean Volatile Attractive for Riptortus pedestris Using Reverse Chemical Ecology Approach. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:27084-27093. [PMID: 39601774 DOI: 10.1021/acs.jafc.4c07789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
The bean bug Riptortus pedestris is a major soybean pest and a cause of the stay-green symptoms. However, the molecular mechanisms underlying its olfaction-mediated host-seeking behavior remain unclear. In this study, we compared the antennae transcriptomes of starved and nonstarved adult R. pedestris, identifying four differentially expressed odorant receptor (OR) genes. Among these, RpedOR13 showed a strong response to the host volatile 2-phenylethanol (2-PE) in Xenopus oocyte assays, while electroantennography and behavioral tests confirmed 2-PE as an effective attractant. Next, phylogenetic analysis identified RpedOR72b as a paralog of RpedOR13, with subsequent Xenopus oocyte assays confirming its specific response to 2-PE. Additionally, RNA interference experiments highlighted the crucial role of RpedOR72b in detecting 2-PE. Taken together, these findings provide new insights into the molecular mechanisms of host-seeking behavior in R. pedestris and highlight the successful application of reverse chemical ecology in OR-based screening of bioactive compounds.
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Affiliation(s)
- Xiao-Tong Zhang
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
- Sanya Institute of Nanjing Agricultural University, Nanjing Agricultural University, Nanjing 210095, China
| | - Xuan-Pu Luan
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
| | - Jia-Hang Wei
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
| | - Pan-Pan Zhang
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
| | - Jin-Meng Guo
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
| | - Ian W Keesey
- School of Biological Sciences, University of Nebraska-Lincoln (UNL), Lincoln, Nebraska 68588, United States
| | - Yu Gao
- College of Plant Protection, Jilin Agricultural University, Changchun 130062, China
| | - Qi Yan
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
- Sanya Institute of Nanjing Agricultural University, Nanjing Agricultural University, Nanjing 210095, China
| | - Jin Zhang
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
- Sanya Institute of Nanjing Agricultural University, Nanjing Agricultural University, Nanjing 210095, China
- Key Laboratory of Soybean Disease and Pest Control (Ministry of Agriculture and Rural Affairs), Nanjing Agricultural University, Nanjing 210095, China
| | - Shuang-Lin Dong
- Key Laboratory of Integrated Management of Crop Disease and Pests, Ministry of Education/College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
- Sanya Institute of Nanjing Agricultural University, Nanjing Agricultural University, Nanjing 210095, China
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Liu Y, Yuan J, Li Y, Bi Y, Prusky DB. The sensor protein AaSho1 regulates infection structures differentiation, osmotic stress tolerance and virulence via MAPK module AaSte11-AaPbs2-AaHog1 in Alternaria alternata. Comput Struct Biotechnol J 2024; 23:1594-1607. [PMID: 38680872 PMCID: PMC11047198 DOI: 10.1016/j.csbj.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 04/01/2024] [Accepted: 04/11/2024] [Indexed: 05/01/2024] Open
Abstract
The high-osmolarity-sensitive protein Sho1 functions as a key membrane receptor in phytopathogenic fungi, which can sense and respond to external stimuli or stresses, and synergistically regulate diverse fungal biological processes through cellular signaling pathways. In this study, we investigated the biological functions of AaSho1 in Alternaria alternata, the causal agent of pear black spot. Targeted gene deletion revealed that AaSho1 is essential for infection structure differentiation, response to external stresses and synthesis of secondary metabolites. Compared to the wild-type (WT), the ∆AaSho1 mutant strain showed no significant difference in colony growth, morphology, conidial production and biomass accumulation. However, the mutant strain exhibited significantly reduced levels of melanin production, cellulase (CL) and ploygalacturonase (PG) activities, virulence, resistance to various exogenous stresses. Moreover, the appressorium and infection hyphae formation rates of the ∆AaSho1 mutant strain were significantly inhibited. RNA-Seq results showed that there were four branches including pheromone, cell wall stress, high osmolarity and starvation in the Mitogen-activated Protein Kinase (MAPK) cascade pathway. Furthermore, yeast two-hybrid experiments showed that AaSho1 activates the MAPK pathway via AaSte11-AaPbs2-AaHog1. These results suggest that AaSho1 of A. alternata is essential for fungal development, pathogenesis and osmotic stress response by activating the MAPK cascade pathway via Sho1-Ste11-Pbs2-Hog1.
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Affiliation(s)
- Yongxiang Liu
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China
- College of Horticulture, Xinyang Agriculture and Forestry University, Xinyang, China
| | - Jing Yuan
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China
| | - Yongcai Li
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China
| | - Yang Bi
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China
| | - Dov B. Prusky
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China
- Institute of Postharvest and Food Sciences, Agricultural Research Organization Volcani Center Information Center, Rishon LeZion, Israel
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Xu J, He Q, Gong J, Chai X, Xu Q, Xiong X. SFMBT2 regulates plumage color via serum metabolites in Chinese Anyi tile-like gray chickens. Poult Sci 2024; 103:104391. [PMID: 39427420 PMCID: PMC11533533 DOI: 10.1016/j.psj.2024.104391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/20/2024] [Accepted: 10/02/2024] [Indexed: 10/22/2024] Open
Abstract
Plumage color is an important characteristic of chicken breeds, and molecular genetic research is significant for resource conservation and product quality control. Anyi tile-like gray chicken is a high-quality local chicken breed resource generated through long-term natural selection and artificial breeding in China. However, the molecular mechanisms underlying plumage color formation in Anyi tile-like gray chickens remain unclear. In this study, nontargeted liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed to identify serum metabolites associated with plumage color in 93 Anyi tile-like gray chickens, including 60 tile-like gray and 33 black chickens. Notably, 12 serum metabolites were significantly enriched in Anyi tile-like gray chickens, including deoxyuridine and inosine, which were the key biomarkers distinguishing tile-like gray chickens from black chickens. Additionally, nine serum metabolites were significantly enriched in black chickens. Moreover, we identified 225 significant SNPs (P < 9.71 × 10-8) on chromosomes 1, 2, 3, 4, 11, 15, and 21 that were associated with deoxyuridine, inosine, 3-hydroxybenzoic acid, and L-methionine S-oxide through metabolome genome-wide association studies (mGWAS). Importantly, chromosome 1 harbored a region, 172.79-kb, which was the most likely quantitative trait locus (QTL) interval. RNA sequencing (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that SFMBT2 was the only differentially expressed gene in the QTL interval, and its expression was correlated with the abundance of specific serum metabolites. Conclusively, SFMBT2-mediated changes in serum metabolites contribute to plumage color development in Anyi tile-like gray chicken. This study provides important insights into the interaction between serum metabolites and host genes, and offers a theoretical basis for the breeding of Anyi tile-like gray chickens.
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Affiliation(s)
- Jiguo Xu
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China
| | - Qin He
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China
| | - Jishang Gong
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China
| | - Xuewen Chai
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China
| | - Qiao Xu
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China
| | - Xinwei Xiong
- Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China.
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Li M, Freeman S, Franco-Barraza J, Cai KQ, Kim A, Jin S, Cukierman E, Ye K. A bioprinted sea-and-island multicellular model for dissecting human pancreatic tumor-stroma reciprocity and adaptive metabolism. Biomaterials 2024; 310:122631. [PMID: 38815457 PMCID: PMC11186049 DOI: 10.1016/j.biomaterials.2024.122631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 05/18/2024] [Accepted: 05/23/2024] [Indexed: 06/01/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents a formidable clinical challenge due to its intricate microenvironment characterized by desmoplasia and complex tumor-stroma interactions. Conventional models hinder studying cellular crosstalk for therapeutic development. To recapitulate key features of PDAC masses, this study creates a novel sea-and-island PDAC tumor construct (s&i PTC). The s&i PTC consists of 3D-printed islands of human PDAC cells positioned within an interstitial extracellular matrix (ECM) populated by human cancer-associated fibroblasts (CAFs). This design closely mimics the in vivo desmoplastic architecture and nutrient-poor conditions. The model enables studying dynamic tumor-stroma crosstalk and signaling reciprocity, revealing both known and yet-to-be-discovered multicellular metabolic adaptations. Using the model, we discovered the orchestrated dynamic alterations of CAFs under nutrient stress, resembling critical in vivo human tumor niches, such as the secretion of pro-tumoral inflammatory factors. Additionally, nutrient scarcity induces dynamic alterations in the ECM composition and exacerbates poor cancer cell differentiation-features well-established in PDAC progression. Proteomic analysis unveiled the enrichment of proteins associated with aggressive tumor behavior and ECM remodeling in response to poor nutritional conditions, mimicking the metabolic stresses experienced by avascular pancreatic tumor cores. Importantly, the model's relevance to patient outcomes is evident through an inverse correlation between biomarker expression patterns in the s&i PTCs and PDAC patient survival rates. Key findings include upregulated MMPs and key ECM proteins (such as collagen 11 and TGFβ) under nutrient-avid conditions, known to be regulated by CAFs, alongside the concomitant reduction in E-cadherin expression associated with a poorly differentiated PDAC state under nutrient deprivation. Furthermore, elevated levels of hyaluronic acid (HA) and integrins in response to nutrient deprivation underscore the model's fidelity to the PDAC microenvironment. We also observed increased IL-6 and reduced α-SMA expression under poor nutritional conditions, suggesting a transition of CAFs from myofibroblastic to inflammatory phenotypes under a nutrient stress akin to in vivo niches. In conclusion, the s&i PTC represents a significant advancement in engineering clinically relevant 3D models of PDAC masses. It offers a promising platform for elucidating tumor-stroma interactions and guiding future therapeutic strategies to improve patient outcomes.
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Affiliation(s)
- Ming Li
- Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Binghamton University, SUNY, Binghamton, NY, USA
| | - Sebastian Freeman
- Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Binghamton University, SUNY, Binghamton, NY, USA
| | - Janusz Franco-Barraza
- Cancer Signaling and Microenvironment Program, Marvin and Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Lewis Katz Temple School of Medicine, Philadelphia, PA, USA
| | - Kathy Q Cai
- Cancer Signaling and Microenvironment Program, Marvin and Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Lewis Katz Temple School of Medicine, Philadelphia, PA, USA
| | - Amy Kim
- Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Binghamton University, SUNY, Binghamton, NY, USA
| | - Sha Jin
- Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Binghamton University, SUNY, Binghamton, NY, USA
| | - Edna Cukierman
- Cancer Signaling and Microenvironment Program, Marvin and Concetta Greenberg Pancreatic Cancer Institute, Fox Chase Cancer Center, Lewis Katz Temple School of Medicine, Philadelphia, PA, USA.
| | - Kaiming Ye
- Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Binghamton University, SUNY, Binghamton, NY, USA.
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7
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Da Silva E, Martín-Cano FE, Gómez-Arrones V, Gaitskell-Phillips G, Alonso JM, Rey J, Becerro L, Gil MC, Peña FJ, Ortega-Ferrusola C. Bacterial endometritis-induced changes in the endometrial proteome in mares: Potential uterine biomarker for bacterial endometritis. Theriogenology 2024; 226:202-212. [PMID: 38909435 DOI: 10.1016/j.theriogenology.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 06/10/2024] [Accepted: 06/12/2024] [Indexed: 06/25/2024]
Abstract
Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics.
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Affiliation(s)
- E Da Silva
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - F E Martín-Cano
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - V Gómez-Arrones
- CENSYRA, Centro de Selección y Reproducción Animal de Extremadura, Badajoz, Spain
| | - G Gaitskell-Phillips
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - J M Alonso
- Unit of Infectious Diseases, University of Extremadura, Caceres, Spain
| | - J Rey
- Unit of Infectious Diseases, University of Extremadura, Caceres, Spain
| | - L Becerro
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - M C Gil
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - F J Peña
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain
| | - C Ortega-Ferrusola
- Laboratory of Equine Reproduction and Equine Spermatology, Department of Animal Medicine, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.
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Lin Y, Huo X, Xu J, Li Y, Zhu H, Yu Y, Tang L, Wang X. A soybean bZIP transcription factor is involved in submergence resistance. Biochem Biophys Res Commun 2024; 722:150151. [PMID: 38801801 DOI: 10.1016/j.bbrc.2024.150151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 05/29/2024]
Abstract
Although the functions of basic leucine zipper (bZIP) family transcription factors in the regulation of various abiotic stresses are beginning to be unveiled, the precise roles of bZIP proteins in plants coping with submergence stress remain unclear. Here we identified a bZIP gene GmbZIP71-4 from soybean, which localized in the nucleus. The GmbZIP71-4 over-expressed tabocco line showed reduced submergence resistance due to the decreased abscisic acid (ABA) content. GO and KEGG pathway analysis based on chromatin immunoprecipitation assay sequencing (ChIP-seq) indicated that the differences expressed genes between submergence treatment and control groups were specially enriched in plant hormone signal transduction items, especially those in response to ABA. Electrophoretic mobility shift assays (EMSA) demonstrated that GmbZIP71-4 bound to the promoter of GmABF2 gene, which is consistent with the ChIP-qPCR results. GmbZIP71-4 function as a negative regulator of soybean in responding to submergence stress through manipulating ABA signaling pathway. This findings will set a solid foundation for the understanding of submergence resistance in plants.
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Affiliation(s)
- Yanhui Lin
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China.
| | - Xing Huo
- Rice Research Institute, Guangdong Academy of Agricultural Sciences, Guangdong Key Laboratory of New Technology in Rice Breeding, Guangdong Rice Engineering Laboratory, Guangzhou, 510640, China.
| | - Jing Xu
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China.
| | - Yapeng Li
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China; Sanya Research Institute of Hainan Academy of Agricultural Sciences, Sanya, 572000, China.
| | - Honglin Zhu
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China.
| | - Yongmei Yu
- College of Agriculture, South China Agricultural University, Guangzhou, 510642, China.
| | - Liqiong Tang
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China.
| | - Xiaoning Wang
- Institute of Food Crops, Hainan Academy of Agricultural Sciences/Hainan Key Laboratory of Crop Genetics and Breeding/Hainan Scientific Research Station of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture, Haikou, 571100, China; Sanya Research Institute of Hainan Academy of Agricultural Sciences, Sanya, 572000, China.
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Mao G, Xu W, Wan L, Wang H, Xu S, Zhang L, Li S, Zhang J, Lai Z, Lan Y, Liu J. Unveiling the bioinformatic genes and their involved regulatory mechanisms in type 2 diabetes combined with osteoarthritis. Front Immunol 2024; 15:1353915. [PMID: 39176085 PMCID: PMC11338775 DOI: 10.3389/fimmu.2024.1353915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 07/24/2024] [Indexed: 08/24/2024] Open
Abstract
Background Type 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA. Methods T2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking. Results In this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA. Conclusion This study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition.
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Affiliation(s)
- Guangming Mao
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Wenhao Xu
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Lingli Wan
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Hongpin Wang
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Shutao Xu
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Liangming Zhang
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Shiyang Li
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
- Department of Pharmacy, Dali University, Dali, China
| | - Jifa Zhang
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Zhongming Lai
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Yuping Lan
- Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China
| | - Jianhui Liu
- College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China
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Wu T, Wu Y, Li Y, Du Y, Feng S, Wang D, Zhou L. Genome-wide analysis of two different regions of brain reveals the molecular changes of fertility related genes in rln3a -/- mutants in male Nile tilapia (Oreochromis niloticus). Gen Comp Endocrinol 2024; 354:114543. [PMID: 38692521 DOI: 10.1016/j.ygcen.2024.114543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/26/2024] [Accepted: 04/28/2024] [Indexed: 05/03/2024]
Abstract
Relaxin3 (rln3) has been associated with various emotional and cognitive processes, including stress, anxiety, learning, memory, motivational behavior, and circadian rhythm. Notably, previous report revealed that Rln3a played an indispensable role in testicular development and male fertility in Nile tilapia (Oreochromis niloticus). However, the underlying molecular mechanisms remain largely unknown. We found that Rln3a is expressed exclusively in the diencephalon* (Di*) of the brain. Deficiency of Rln3a resulted in a significant increase in serum dopamine level and an upregulation of gene expression of gnrh1 and kisspeptin2. To further elucidate the role of Rln3a in fish fertility, we collected two different regions of Di* and hypothalamus (Hyp) tissues for subsequent RNA-seq analysis of both wild-type (rln3a+/+) and rln3a-/- male tilapia. Upon the transcriptomic data, 1136 and 755 differentially expressed genes (DEGs) were identified in the Di* and Hyp tissues, respectively. In Di*, the up-regulated genes were enriched in circadian rhythm, chemical carcinogenesis, while the down-regulated genes were enriched in type II diabetes mellitus, dopaminergic synapse, and other pathways. In Hyp, the up-regulated genes were enriched in circadian rhythm, pyrimidine metabolism, while the down-regulated genes were enriched in type I diabetes mellitus, autoimmune thyroid disease, and other pathways. Subsequently, the results of both qRT-PCR and FISH assays highlighted a pronounced up-regulation of core circadian rhythm genes, cry1b and per3, whereas genes such as clocka, clockb, and arntl exhibited down-regulation. Furthermore, the genes associated with dopamine biosynthesis were significantly increased in the Hyp. In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.
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Affiliation(s)
- Tengfei Wu
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China
| | - You Wu
- Fisheries Engineering Institute, Chinese Academy of Fishery Sciences, Beijing, China; Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China
| | - Yanlong Li
- Fisheries Engineering Institute, Chinese Academy of Fishery Sciences, Beijing, China; Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China
| | - Yiyun Du
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China
| | - Saining Feng
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China
| | - Deshou Wang
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, Chongqing 400715, China.
| | - Linyan Zhou
- Fisheries Engineering Institute, Chinese Academy of Fishery Sciences, Beijing, China.
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Guo Z, Zhao Z, Wang X, Zhou J, Liu J, Plunet W, Ren W, Tian L. Identification of mitophagy-related hub genes during the progression of spinal cord injury by integrated multinomial bioinformatics analysis. Biochem Biophys Rep 2024; 38:101654. [PMID: 38375420 PMCID: PMC10875195 DOI: 10.1016/j.bbrep.2024.101654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/24/2024] [Accepted: 01/25/2024] [Indexed: 02/21/2024] Open
Abstract
Spinal cord injury (SCI) is a disturbance of peripheral and central nerve conduction that causes disability in sensory and motor function. Currently, there is no effective treatment for SCI. Mitophagy plays a vital role in mitochondrial quality control during various physiological and pathological processes. The study aimed to elucidate the role of mitophagy and identify potential mitophagy-related hub genes in SCI pathophysiology. Two datasets (GSE15878 and GSE138637) were analyzed. Firstly, the differentially expressed genes (DEGs) were identified and mitophagy-related genes were obtained from GeneCards, then the intersection between SCI and mitophagy-related genes was determined. Next, we performed gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI network), least absolute shrinkage and selection operator (LASSO), and cluster analysis to identify and define the hub genes in SCI. Finally, the link between hub genes and infiltrating immune cells was investigated and the potential transcriptional regulation/small molecular compounds to target hub genes were predicted. In total, SKP1 and BAP1 were identified as hub genes of mitophagy-related DEGs during SCI development and regulatory T cells (Tregs)/resting NK cells/activated mast cells may play an essential role in the progression of SCI. LINC00324 and SNHG16 may regulate SKP1 and BAP1, respectively, through miRNAs. Eleven and eight transcriptional factors (TFs) regulate SKP1 and BAP1, respectively, and six small molecular compounds target BAP1. Then, the mRNA expression levels of BAP1 and SKP1 were detected in the injured sites of spinal cord of SD rats at 6 h and 72 h after injury using RT-qPCR, and found that the level were decreased. Therefore, the pathways of mitophagy are downregulated during the pathophysiology of SCI, and SKP1 and BAP1 could be accessible targets for diagnosing and treating SCI.
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Affiliation(s)
- Zhihao Guo
- The Department of Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
| | - Zihui Zhao
- Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
| | - Xiaoge Wang
- Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
| | - Jie Zhou
- The Department of Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
| | - Jie Liu
- Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
- Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
| | - Ward Plunet
- International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Center, Vancouver, British Columbia, Canada
| | - Wenjie Ren
- Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
- Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
| | - Linqiang Tian
- The Department of Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
- Institute of Trauma & Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
- Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
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Zhang Z, Yi Y, Wang Z, Zhang H, Zhao Y, He R, Luo Y, Cui Z. LncRNA MAGI2-AS3-Encoded Polypeptide Restrains the Proliferation and Migration of Breast Cancer Cells. Mol Biotechnol 2024; 66:1409-1423. [PMID: 37358745 DOI: 10.1007/s12033-023-00801-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 06/20/2023] [Indexed: 06/27/2023]
Abstract
Accumulating articles have reported the coding potential of long non-coding RNAs (lncRNAs). However, only a few lncRNAs-encoded peptides have been studied. Breast cancer (BRCA) progression-related gene modules were determined by weighted gene co-expression network analysis (WGCNA). Cell viability, proliferation, and migration capacities were assessed by Cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Immunofluorescence (IF) assay was implemented to observe protein expression. Co-immunoprecipitation (Co-IP) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) were employed to analyze MAGI2 antisense RNA 3 (MAGI2-AS3)-ORF5-interacted proteins. WGCNA identified that MEpurple and MEblack modules were significantly negatively correlated with T stage in BRCA patients. MAGI2-AS3 was screened as one of the differentially expressed (DE) lncRNAs with translational potential in MEblack and MEpurple modules in BRCA. The data in The Cancer Genome Atlas (TCGA) uncovered that MAGI2-AS3 abundance was significantly decreased in invasive BRCA patients, and it had high diagnostic and prognostic values. MAGI2-AS3-ORF5 notably restrained BRCA cell viability, proliferation, and migration. Mechanically, MAGI2-AS3-ORF5 might affect the progression of BRCA cells by binding to extracellular matrix (ECM)-related proteins. MAGI2-AS3-ORF5 played an anti-tumor role by inhibiting BRCA cell viability, proliferation, and migration. MAGI2-AS3-ORF5 might modulate BRCA cell migration through ECM-associated proteins.
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Affiliation(s)
- Zhiwei Zhang
- Department of Oncology, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Yanli Yi
- Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Zai Wang
- Science and Education Division, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Haoyun Zhang
- Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Yanchun Zhao
- Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Ruijing He
- Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China
| | - Yan Luo
- Department of Reproductive Genetic, Hebei General Hospital, Shijiazhuang, 050000, Hebei, China
| | - Zhiqiang Cui
- Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering, Handan, 056000, Hebei, China.
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Sun Z, Aschalew ND, Cheng L, Xia Y, Zhang L, Yin G, Wang S, Wang Z, Dong J, Zhang W, Zhao W, Qin G, Zhang X, Zhong R, Wang T, Zhen Y. Dietary 5-hydroxytryptophan improves sheep growth performance by enhancing ruminal functions, antioxidant capacity, and tryptophan metabolism: in vitro and in vivo studies. Front Immunol 2024; 15:1398310. [PMID: 38835767 PMCID: PMC11148369 DOI: 10.3389/fimmu.2024.1398310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 05/03/2024] [Indexed: 06/06/2024] Open
Abstract
Background Hydroxytryptophan (5-HTP) can regulate the synthesis of 5-Hydroxytryptamine (5-HT) and melatonin (MT). In a previous metabolome analysis, we found that 5-HTP is an effective ingredient in yeast culture for regulating rumen fermentation. However, research on the effect of this microbial product (5-HTP) as a functional feed additive in sheep production is still not well explained. Therefore, this study examined the effects of 5-HTP on sheep rumen function and growth performance using in vitro and in vivo models. Methods A two-factor in vitro experiment involving different 5-HTP doses and fermentation times was conducted. Then, in the in vivo experiment, 10 sheep were divided into a control group which was fed a basal diet, and a 5-HTP group supplemented with 8 mg/kg 5-HTP for 60 days. Results The results showed that 5-HTP supplementation had a significant effect on in vitro DMD, pH, NH3-N, acetic acid, propionic acid, and TVFA concentrations. 5-HTP altered rumen bacteria composition and diversity indices including Chao1, Shannon, and Simpson. Moreover, the in vivo study on sheep confirmed that supplementing with 8 mg/kg of 5-HTP improved rumen fermentation efficiency and microbial composition. This led to enhanced sheep growth performance and increased involvement in the tryptophan metabolic pathway, suggesting potential benefits. Conclusion Dietary 5-HTP (8 mg/kg DM) improves sheep growth performance by enhancing ruminal functions, antioxidant capacity, and tryptophan metabolism. This study can provide a foundation for the development of 5-HTP as a functional feed additive in ruminants' production.
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Affiliation(s)
- Zhe Sun
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun, China
- Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co. Ltd., Changchun, China
| | - Natnael D Aschalew
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- College of Agriculture and Environmental Science, Dilla University, Dilla, Ethiopia
| | - Long Cheng
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Yuanhong Xia
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Longyu Zhang
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Guopei Yin
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Shikun Wang
- College of Life Sciences, Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun, China
| | - Ziyuan Wang
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Jianan Dong
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Weigang Zhang
- Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co. Ltd., Changchun, China
| | - Wei Zhao
- Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co. Ltd., Changchun, China
| | - Guixin Qin
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Xuefeng Zhang
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Rongzhen Zhong
- Jilin Province Feed Processing and Ruminant Precision Breeding Cross-Regional Cooperation Technology Innovation Center, Jilin Provincial Key Laboratory of Grassland Farming, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, China
| | - Tao Wang
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co. Ltd., Changchun, China
| | - Yuguo Zhen
- Jilin Agricultural University (JLAU)-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Key Laboratory of Animal Production Product Quality and Security Ministry of Education, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co. Ltd., Changchun, China
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Shanmugam NRS, Kulandaisamy A, Veluraja K, Gromiha MM. CarbDisMut: database on neutral and disease-causing mutations in human carbohydrate-binding proteins. Glycobiology 2024; 34:cwae011. [PMID: 38335248 DOI: 10.1093/glycob/cwae011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/03/2024] [Indexed: 02/12/2024] Open
Abstract
Protein-carbohydrate interactions are involved in several cellular and biological functions. Integrating structure and function of carbohydrate-binding proteins with disease-causing mutations help to understand the molecular basis of diseases. Although databases are available for protein-carbohydrate complexes based on structure, binding affinity and function, no specific database for mutations in human carbohydrate-binding proteins is reported in the literature. We have developed a novel database, CarbDisMut, a comprehensive integrated resource for disease-causing mutations with sequence and structural features. It has 1.17 million disease-associated mutations and 38,636 neutral mutations from 7,187 human carbohydrate-binding proteins. The database is freely available at https://web.iitm.ac.in/bioinfo2/carbdismut. The web-site is implemented using HTML, PHP and JavaScript and supports recent versions of all major browsers, such as Firefox, Chrome and Opera.
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Affiliation(s)
- N R Siva Shanmugam
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
| | - A Kulandaisamy
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
- Basic and Translational Research, Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, United States
| | - K Veluraja
- PSN College of Engineering and Technology, Melathediyoor, Tirunelveli, Tamil Nadu 627451, India
| | - M Michael Gromiha
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India
- Department of Computer Science, Tokyo Tech World Research Hub Initiative (WRHI), Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
- Department of Computer Science, National University of Singapore, 117417, Singapore
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15
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Zhang F, Pei S, Xiao M. Identification of functional genes in liver fibrosis based on bioinformatics analysis of a lncRNA-mediated ceRNA network. BMC Med Genomics 2024; 17:56. [PMID: 38378545 PMCID: PMC10877760 DOI: 10.1186/s12920-024-01813-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 01/20/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Liver fibrosis is a major global healths problem; nevertheless, its molecular mechanism are not completely clear. This study aimed to build a lncRNA-miRNA-mRNA network, identify potentially related lncRNAs, and explore the pathogenesis of liver fibrosis. MATERIALS AND METHODS We used the Gene Expression Omnibus databases and bioinformatics analysis to identify differentially expressed genes (DEGs) between liver fibrosis and normal tissues. The ceRNA network was constructed according to the interactions between DElncRNA, miRNA, and DEmRNA. Then, these DEGs were identified using functional enrichment analysis, and a protein-protein interaction (PPI) network was established. The critical lncRNAs were verified using the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The ceRNA network was composed of three lncRNAs, five miRNAs, and 93 mRNAs. Gene Ontology functional enrichment analysis revealed significant enhancement in cell components, molecular function, and biological process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed pathways associated with transcriptional misregulation in cancer, including the Rap1 signaling pathway, proteoglycans in cancer, mineral absorption, HTLV-l infection, and central carbon metabolism in cancer. According to the PPI network and the GSE84044 database, seven hub genes associated with liver fibrosis were identified. In addition, qRT-PCR revealed that lncRNA AC100861 (lncRNA TNFRSF10A-DT) was explicitly decreased in liver fibrosis tissues and activated hepatic stellate cells. CONCLUSIONS In summary, this study preliminarily found that lncRNA TNFRSF10A-DT may be a biomarker for the diagnosis and outcome of liver fibrosis. We uncovered a novel lncRNA-mediated ceRNA regulatory mechanism in the pathogenesis of liver fibrosis.
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Affiliation(s)
- Feng Zhang
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China
| | - Siya Pei
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China
- Department of Infection Diseases, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China
| | - Meifang Xiao
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China.
- Department of Health Management Center, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China.
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Qi P, Huang M, Ren X, Zhai Y, Qiu C, Zhu H. Identification of potential biomarkers and therapeutic targets related to post-traumatic stress disorder due to traumatic brain injury. Eur J Med Res 2024; 29:44. [PMID: 38212778 PMCID: PMC10782540 DOI: 10.1186/s40001-024-01640-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 01/03/2024] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Post-traumatic stress disorder (PTSD), a disease state that has an unclear pathogenesis, imposes a substantial burden on individuals and society. Traumatic brain injury (TBI) is one of the most significant triggers of PTSD. Identifying biomarkers associated with TBI-related PTSD will help researchers to uncover the underlying mechanism that drives disease development. Furthermore, it remains to be confirmed whether different types of traumas share a common mechanism of action. METHODS For this study, we screened the eligible data sets from the Gene Expression Omnibus (GEO) database, obtained differentially expressed genes (DEGs) through analysis, conducted functional enrichment analysis on the DEGs in order to understand their molecular mechanisms, constructed a PPI network, used various algorithms to obtain hub genes, and finally evaluated, validated, and analyzed the diagnostic performance of the hub genes. RESULTS A total of 430 upregulated and 992 down-regulated differentially expressed genes were extracted from the TBI data set. A total of 1919 upregulated and 851 down-regulated differentially expressed genes were extracted from the PTSD data set. Functional enrichment analysis revealed that the differentially expressed genes had biological functions linked to molecular regulation, cell signaling transduction, cell metabolic regulation, and immune response. After constructing a PPI network and introducing algorithm analysis, the upregulated hub genes were identified as VNN1, SERPINB2, and ETFDH, and the down-regulated hub genes were identified as FLT3LG, DYRK1A, DCN, and FKBP8. In addition, by comparing the data with patients with other types of trauma, it was revealed that PTSD showed different molecular processes that are under the influence of different trauma characteristics and responses. CONCLUSIONS By exploring the role of different types of traumas during the pathogenesis of PTSD, its possible molecular mechanisms have been revealed, providing vital information for understanding the complex pathways associated with TBI-related PTSD. The data in this study has important implications for the design and development of new diagnostic and therapeutic methods needed to treat and manage PTSD.
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Affiliation(s)
- Peng Qi
- Department of Emergency, First Medical Center of Chinese, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Mengjie Huang
- Department of Nephrology, First Medical Center of Chinese, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Xuewen Ren
- Department of Emergency, First Medical Center of Chinese, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Yongzhi Zhai
- Department of Emergency, First Medical Center of Chinese, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Chen Qiu
- Department of Orthopedics, Fourth Medical Center of Chinese, PLA General Hospital, Beijing, 100853, China.
| | - Haiyan Zhu
- Department of Emergency, First Medical Center of Chinese, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
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Li H, Li P, Li S, Zhang X, Dong X, Yang M, Shen W. Mechanism of transforming growth factor- β1 induce renal fibrosis based on transcriptome sequencing analysis. Zhejiang Da Xue Xue Bao Yi Xue Ban 2023; 52:594-604. [PMID: 37916309 PMCID: PMC10630056 DOI: 10.3724/zdxbyxb-2022-0672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 08/24/2023] [Indexed: 10/08/2023]
Abstract
OBJECTIVES To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis. METHODS Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.
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Affiliation(s)
- Huanan Li
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China.
| | - Peifen Li
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China
| | - Shanyi Li
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China
| | - Xueying Zhang
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China
| | - Xinru Dong
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China
| | - Ming Yang
- Department of Nephrology, Affiliated Hospital of Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Weigan Shen
- Department of Cell Biology, School of Medicine, Yangzhou University, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225009, Jiangsu Province, China.
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Qi P, Huang M, Zhu H. Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy. Front Med (Lausanne) 2023; 10:1191354. [PMID: 37457560 PMCID: PMC10346863 DOI: 10.3389/fmed.2023.1191354] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 06/15/2023] [Indexed: 07/18/2023] Open
Abstract
Background The negative impact of long COVID on social life and human health is increasingly prominent, and the elevated risk of cardiovascular disease in patients recovering from COVID-19 has also been fully confirmed. However, the pathogenesis of long COVID-related inflammatory cardiomyopathy is still unclear. Here, we explore potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy. Methods Datasets that met the study requirements were identified in Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were obtained by the algorithm. Then, functional enrichment analysis was performed to explore the basic molecular mechanisms and biological processes associated with DEGs. A protein-protein interaction (PPI) network was constructed and analyzed to identify hub genes among the common DEGs. Finally, a third dataset was introduced for validation. Results Ultimately, 3,098 upregulated DEGs and 1965 downregulated DEGs were extracted from the inflammatory cardiomyopathy dataset. A total of 89 upregulated DEGs and 217 downregulated DEGs were extracted from the dataset of convalescent COVID patients. Enrichment analysis and construction of the PPI network confirmed VEGFA, FOXO1, CXCR4, and SMAD4 as upregulated hub genes and KRAS and TXN as downregulated hub genes. The separate dataset of patients with COVID-19 infection used for verification led to speculation that long COVID-associated inflammatory cardiomyopathy is mainly attributable to the immune-mediated response and inflammation rather than to direct infection of cells by the virus. Conclusion Screening of potential biomarkers and therapeutic targets sheds new light on the pathogenesis of long COVID-associated inflammatory cardiomyopathy as well as potential therapeutic approaches. Further clinical studies are needed to explore these possibilities in light of the increasingly severe negative impacts of long COVID.
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Affiliation(s)
- Peng Qi
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mengjie Huang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Haiyan Zhu
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
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Liu P, Zhang M, Gao H, Han S, Liu J, Sun X, Zhao L. Regulation of whole-transcriptome sequencing expression in COPD after personalized precise exercise training: a pilot study. Respir Res 2023; 24:156. [PMID: 37312153 DOI: 10.1186/s12931-023-02461-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 05/23/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is one of the world's leading causes of death and a major chronic respiratory disease. Aerobic exercise, the cornerstone of pulmonary rehabilitation, improves prognosis of COPD patients; however, few studies have comprehensively examined the changes in RNA transcript levels and the crosstalk between various transcripts in this context. This study identified the expression of RNA transcripts in COPD patients who engaged in aerobic exercise training for 12 weeks, and further constructions of the possible RNAs networks were made. METHODS Peripheral blood samples for all four COPD patients who benefited from 12 weeks of PR were collected pre- and post-aerobic exercises and evaluated for the expression of mRNA, miRNA, lncRNA, and circRNA with high-throughput RNA sequencing followed by GEO date validation. In addition, enrichment analyses were conducted on different expressed mRNAs. LncRNA-mRNA and circRNA-mRNA coexpression networks, as well as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA competing expression networks (ceRNAs) in COPD were constructed. RESULTS We identified and analyzed the differentially expressed mRNAs and noncoding RNAs in the peripheral blood of COPD patients' post-exercise. Eighty-six mRNAs, 570 lncRNAs, 8 miRNAs, and 2087 circRNAs were differentially expressed. Direct function enrichment analysis and Gene Set Variation Analysis showed that differentially expressed RNAs(DE-RNAs) correlated with several critical biological processes such as chemotaxis, DNA replication, anti-infection humoral response, oxidative phosphorylation, and immunometabolism, which might affect the progression of COPD. Some DE-RNAs were validated by Geo databases and RT-PCR, and the results were highly correlated with RNA sequencing. We constructed ceRNA networks of DE-RNAs in COPD. CONCLUSIONS The systematic understanding of the impact of aerobic exercise on COPD was achieved using transcriptomic profiling. This research offers a number of potential candidates for clarifying the regulatory mechanisms that exercise has on COPD, which could ultimately help in understanding the pathophysiology of COPD.
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Affiliation(s)
- Panpan Liu
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 MiaoPu Road, Shanghai, 200315, People's Republic of China
| | - Meilan Zhang
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 MiaoPu Road, Shanghai, 200315, People's Republic of China
| | - Hongchang Gao
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 MiaoPu Road, Shanghai, 200315, People's Republic of China
| | - Shaojun Han
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 MiaoPu Road, Shanghai, 200315, People's Republic of China
| | - Jinming Liu
- Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital Affiliated to TongJi University, Shanghai, China
| | - Xingguo Sun
- Department of Physiology and Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences National Center of Cardiovascular Diseases, Beijing, People's Republic of China.
| | - Lei Zhao
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 MiaoPu Road, Shanghai, 200315, People's Republic of China.
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Yin J, He W, Zhang M, He W, Zhang G, Ni B. https://elsevier.proofcentral.com/en-us/landing-page.html?token=baf280639f2773e07701834b1c13daInhibition of spermatogenesis by hypoxia is mediated by V-ATPase via the JNK/c-Jun pathway in mice. Reprod Biol 2023; 23:100761. [PMID: 37023662 DOI: 10.1016/j.repbio.2023.100761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 04/07/2023]
Abstract
Spermatocyte apoptosis is the primary cause of a poor outcome after hypoxia-triggered spermatogenesis reduction (HSR). Vacuolar H+-ATPase (V-ATPase) is involved in the regulation of hypoxia-induced spermatocyte apoptosis; however, the underlying mechanism remains to be elucidated. The aim of this study was to investigate the effect of V-ATPase deficiency on spermatocyte apoptosis and the relationship between c-Jun and apoptosis in primary spermatocytes induced by hypoxia. We found that mice under hypoxia exposure for 30 days demonstrated a marked spermatogenesis reduction and downregulation of V-ATPase expression, which were assessed by a TUNEL assay and western blotting, respectively. V-ATPase deficiency resulted in more severe spermatogenesis reduction and spermatocyte apoptosis after hypoxia exposure. We also observed that silencing V-ATPase expression enhanced JNK/c-Jun activation and death receptor-mediated apoptosis in primary spermatocytes. However, inhibition of c-Jun attenuated V-ATPase deficiency-induced spermatocyte apoptosis in primary spermatocytes. In conclusion, the data in this study suggest that V-ATPase deficiency aggravated hypoxia-induced spermatogenesis reduction by promoting spermatocyte apoptosis in mice via the JNK/c-Jun pathway.
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Affiliation(s)
- Jun Yin
- Department of Pathophysiology/Key Laboratory of High Altitude Environment Medicine, Ministry of Education/Key Laboratory of High Altitude Medicine, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, PR China
| | - Wenjuan He
- Department of Pathophysiology/Key Laboratory of High Altitude Environment Medicine, Ministry of Education/Key Laboratory of High Altitude Medicine, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, PR China
| | - Mengjie Zhang
- Department of Pathophysiology/Key Laboratory of High Altitude Environment Medicine, Ministry of Education/Key Laboratory of High Altitude Medicine, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, PR China
| | - Wei He
- Chongqing ILinda Biomedical Research Corporation Limited, PR China
| | - Gang Zhang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, PR China.
| | - Bing Ni
- Department of Pathophysiology/Key Laboratory of High Altitude Environment Medicine, Ministry of Education/Key Laboratory of High Altitude Medicine, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, PR China.
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Zhao T, Zhang Z, Li Y, Sun Z, Liu L, Deng X, Guo J, Zhu D, Cao S, Chai Y, Nikolaevna UV, Maratbek S, Wang Z, Zhang H. Brucella abortus modulates macrophage polarization and inflammatory response by targeting glutaminases through the NF-κB signaling pathway. Front Immunol 2023; 14:1180837. [PMID: 37325614 PMCID: PMC10266586 DOI: 10.3389/fimmu.2023.1180837] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/05/2023] [Indexed: 06/17/2023] Open
Abstract
Objectives The mechanism of Brucella infection regulating macrophage phenotype has not been completely elucidated until now. This study aimed to determine the mechanism of Brucella abortus in the modulation of macrophage phenotype using RAW264.7 cells as a model. Materials and methods RT-qPCR, ELISA and flow cytometry were used to detect the inflammatory factor production and phenotype conversion associated with M1/M2 polarization of macrophages by Brucella abortus infection. Western blot and immunofluorescence were used to analyze the role of nuclear factor kappa B (NF-κB) signaling pathway in regulation of Brucella abortus-induced macrophage polarization. Chromatin immunoprecipitation sequencing (Chip-seq), bioinformatics analysis and luciferase reporter assay were used to screen and validate NF-κB target genes associated with macrophage polarization and further verify its function. Results The results demonstrate that B. abortus induces a macrophage phenotypic switch and inflammatory response in a time-dependent manner. With the increase of infection time, B. abortus infection-induced M1-type increased first, peaked at 12 h, and then decreased, whereas the M2-type decreased first, trough at 12 h, and then increased. The trend of intracellular survival of B. abortus was consistent with that of M2 type. When NF-κB was inhibited, M1-type polarization was inhibited and M2-type was promoted, and the intracellular survival of B. abortus increased significantly. Chip-seq and luciferase reporter assay results showed that NF-κB binds to the glutaminase gene (Gls). Gls expression was down-regulated when NF-κB was inhibited. Furthermore, when Gls was inhibited, M1-type polarization was inhibited and M2-type was promoted, the intracellular survival of B. abortus increased significantly. Our data further suggest that NF-κB and its key target gene Gls play an important role in controlling macrophage phenotypic transformation. Conclusions Taken together, our study demonstrates that B. abortus infection can induce dynamic transformation of M1/M2 phenotype in macrophages. Highlighting NF-κB as a central pathway that regulates M1/M2 phenotypic transition. This is the first to elucidate the molecular mechanism of B. abortus regulation of macrophage phenotype switch and inflammatory response by regulating the key gene Gls, which is regulated by the transcription factor NF-κB.
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Affiliation(s)
- Tianyi Zhao
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Zedan Zhang
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Yitao Li
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Zhihua Sun
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Liangbo Liu
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Xingmei Deng
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Jia Guo
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Dexin Zhu
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Shuzhu Cao
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Yingjin Chai
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Usevich Vera Nikolaevna
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
- College of Veterinary, Ural State Agricultural University, Yekaterinburg, Russia
| | - Suleimenov Maratbek
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
- College of Veterinary, National Agricultural University of Kazakhstan, Nur Sultan, Kazakhstan
| | - Zhen Wang
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Hui Zhang
- State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China
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Wu Z, Ge L, Song Y, Deng S, Duan P, Du T, Wu Y, Zhang Z, Hou X, Ma L, Zhang S. ATAD2 promotes glycolysis and tumor progression in clear cell renal cell carcinoma by regulating the transcriptional activity of c-Myc. Discov Oncol 2023; 14:79. [PMID: 37233956 DOI: 10.1007/s12672-023-00696-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 05/19/2023] [Indexed: 05/27/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urogenital tract. Given that ccRCC is often resistant to radiotherapy and traditional chemotherapy, the clinical treatment of patients with ccRCC remains a challenge. The present study found that ATAD2 was significantly upregulated in ccRCC tissues. In vitro and in vivo experiments showed that the inhibition of ATAD2 expression mitigated the aggressive phenotype of ccRCC. ATAD2 was also associated with glycolysis in ccRCC. Interestingly, we found that ATAD2 could physically interact with c-Myc and promote the expression of its downstream target gene, thereby enhancing the Warburg effect of ccRCC. Overall, our study emphasizes the role of ATAD2 in ccRCC. The targeted expression or functional regulation of ATAD2 could be a promising method to reduce the proliferation and progression of ccRCC.
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Affiliation(s)
- Zonglong Wu
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Liyuan Ge
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Yimeng Song
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Shaohui Deng
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Peichen Duan
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Tan Du
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Yaqian Wu
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Zhanyi Zhang
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Xiaofei Hou
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China
| | - Lulin Ma
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China.
| | - Shudong Zhang
- Department of Urology, Peking University Third Hospital, Beijing, 100191, P.R. China.
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Rao L, Peng B, Li T. Nonnegative matrix factorization analysis and multiple machine learning methods identified IL17C and ACOXL as novel diagnostic biomarkers for atherosclerosis. BMC Bioinformatics 2023; 24:196. [PMID: 37173646 PMCID: PMC10176911 DOI: 10.1186/s12859-023-05244-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/21/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Atherosclerosis is the common pathological basis for many cardiovascular and cerebrovascular diseases. The purpose of this study is to identify the diagnostic biomarkers related to atherosclerosis through machine learning algorithm. METHODS Clinicopathological parameters and transcriptomics data were obtained from 4 datasets (GSE21545, GSE20129, GSE43292, GSE100927). A nonnegative matrix factorization algorithm was used to classify arteriosclerosis patients in GSE21545 dataset. Then, we identified prognosis-related differentially expressed genes (DEGs) between the subtypes. Multiple machine learning methods to detect pivotal markers. Discrimination, calibration and clinical usefulness of the predicting model were assessed using area under curve, calibration plot and decision curve analysis respectively. The expression level of the feature genes was validated in GSE20129, GSE43292, GSE100927. RESULTS 2 molecular subtypes of atherosclerosis was identified, and 223 prognosis-related DEGs between the 2 subtypes were identified. These genes are not only related to epithelial cell proliferation, mitochondrial dysfunction, but also to immune related pathways. Least absolute shrinkage and selection operator, random forest, support vector machine- recursive feature elimination show that IL17C and ACOXL were identified as diagnostic markers of atherosclerosis. The prediction model displayed good discrimination and good calibration. Decision curve analysis showed that this model was clinically useful. Moreover, IL17C and ACOXL were verified in other 3 GEO datasets, and also have good predictive performance. CONCLUSION IL17C and ACOXL were diagnostic genes of atherosclerosis and associated with higher incidence of ischemic events.
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Affiliation(s)
- Li Rao
- Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Bo Peng
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
- Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, Hubei, China
- Hubei Key Laboratory of Cardiology, Wuhan, 430060, Hubei, China
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Tao Li
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
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Cao M, Liu Z, You D, Pan Y, Zhang Q. TMT-based quantitative proteomic analysis of spheroid cells of endometrial cancer possessing cancer stem cell properties. Stem Cell Res Ther 2023; 14:119. [PMID: 37143105 PMCID: PMC10161517 DOI: 10.1186/s13287-023-03348-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 04/19/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Cancer stem cells (CSCs) play an important role in endometrial cancer progression and it is potential to isolate CSCs from spheroid cells. Further understanding of spheroid cells at protein level would help find novel CSC markers. METHODS Spheroid cells from endometrial cancer cell lines, Ishikawa and HEC1A, exhibited increased colony forming, subsphere forming, chemo-drug resistance, migration, invasion ability and tumorigenicity, verifying their cancer stem-like cell properties. The up-regulated CD90, CD117, CD133 and W5C5 expression also indicated stemness of spheroid cells. TMT-based quantitative proteomic analysis was performed to explore the potential alterations between parent cells and cancer stem-like spheroid cells. HK2-siRNA was transfected to Ishikawa and HEC1A cells to explore the roles and molecular mechanism of HK2 in endometrial cancer. RESULTS We identified and quantified a total of 5735 proteins and 167 overlapped differentially expressed proteins of two cell types, 43 proteins were up-regulated and 124 were down-regulated in spheroid cells comparing with parent cells. KEGG pathway revealed a significant role of HIF-1 pathway in spheroid cells. qRT-PCR and western blot results of GPRC5A, PFKFB3 and HK2 of HIF-1 pathway confirmed their elevated expressions in spheroid cells which were consistent with proteomic results. HK2 promoted cancer stemness in endometrial cancer. CONCLUSION These findings indicate that spheroid cells from endometrial cancer cell lines possess cancer stem-like cell properties and enrich CSCs. HIF-1 pathway is activated in endometrial cancer stem-like spheroid cells.
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Affiliation(s)
- Mingzhu Cao
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, No.63, Duobao Road, Guangzhou, China
- Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhi Liu
- Department of Ultrasound, Nanfang Hospital, Southern Medical University, No.1838, Baiyun Road North, Guangzhou, China
| | - Danming You
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yingying Pan
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Qingyan Zhang
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 1, Zhongshan 2nd Road, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Reproductive Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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Qi P, Huang M, Li T. Identification of potential biomarkers and therapeutic targets for posttraumatic acute respiratory distress syndrome. BMC Med Genomics 2023; 16:54. [PMID: 36918848 PMCID: PMC10012314 DOI: 10.1186/s12920-023-01482-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 03/08/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Despite improved supportive care, posttraumatic acute respiratory distress syndrome (ARDS) mortality has improved very little in recent years. Additionally, ARDS diagnosis is delayed or missed in many patients. We analyzed co-differentially expressed genes (co-DEGs) to explore the relationships between severe trauma and ARDS to reveal potential biomarkers and therapeutic targets for posttraumatic ARDS. METHODS Two gene expression datasets (GSE64711 and GSE76293) were downloaded from the Gene Expression Omnibus. The GSE64711 dataset included a subset of 244 severely injured trauma patients and 21 healthy controls. GSE76293 specimens were collected from 12 patients with ARDS who were recruited from trauma intensive care units and 11 age- and sex-matched healthy volunteers. Trauma DEGs and ARDS DEGs were identified using the two datasets. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses were performed to elucidate the molecular functions of the DEGs. Then, hub genes of the co-DEGs were identified. Finally, to explore whether posttraumatic ARDS and septic ARDS are common targets, we included a third dataset (GSE100159) for corresponding verification. RESULTS 90 genes were upregulated and 48 genes were downregulated in the two datasets and were therefore named co-DEGs. These co-DEGs were significantly involved in multiple inflammation-, immunity- and neutrophil activation-related biological processes. Ten co-upregulated hub genes (GAPDH, MMP8, HGF, MAPK14, LCN2, CD163, ENO1, CD44, ARG1 and GADD45A) and five co-downregulated hub genes (HERC5, IFIT2, IFIT3, RSAD2 and IFIT1) may be considered potential biomarkers and therapeutic targets for posttraumatic ARDS. Through the verification of the third dataset, posttraumatic ARDS may have its own unique targets worthy of further exploration. CONCLUSION This exploratory analysis supports a relationship between trauma and ARDS pathophysiology, specifically in relationship to the identified hub genes. These data may serve as potential biomarkers and therapeutic targets for posttraumatic ARDS.
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Affiliation(s)
- Peng Qi
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Mengjie Huang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Tanshi Li
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
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Fazliana M, Nor Hanipah Z, Mohd Yusof BN, Zainal Abidin NA, Tan YZ, Mohkiar FH, Liyana AZ, Mohd Naeem MN, Mohmad Misnan N, Ahmad H, Draman MS, Tsen PY, Lim SY, Gee T. Molecular, Metabolic, and Nutritional Changes after Metabolic Surgery in Obese Diabetic Patients (MoMen): A Protocol for a Multicenter Prospective Cohort Study. Metabolites 2023; 13:metabo13030413. [PMID: 36984853 PMCID: PMC10059761 DOI: 10.3390/metabo13030413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/26/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
Metabolic surgery is an essential option in the treatment of obese patients with type 2 diabetes (T2D). Despite its known advantages, this surgery still needs to be introduced in Malaysia. In this prospective study, the pathophysiological mechanisms at the molecular level will be studied and the metabolomics pathways of diabetes remission will be explored. The present study aims to evaluate the changes in the anthropometric measurements, body composition, phase angle, diet intake, biochemistry parameters, adipokines, microRNA, and metabolomics, both pre- and post-surgery, among obese diabetic patients in Malaysia. This is a multicenter prospective cohort study that will involve obese patients (n = 102) with a body mass index (BMI) of ≥25 kg/m2 (Asian BMI categories: WHO/IASO/IOTF, 2000) who will undergo metabolic surgery. They will be categorized into three groups: non-diabetes, prediabetes, and diabetes. Their body composition will be measured using a bioimpedance analyzer (BIA). The phase angle (PhA) data will be analyzed. Venous blood will be collected from each patient for glycated hemoglobin (HbA1c), lipids, liver, renal profile, hormones, adipokines, and molecular and metabolomics analyses. The serum microRNA will be measured. A gene expression study of the adipose tissue of different groups will be conducted to compare the groups. The relationship between the 1HNMR-metabolic fingerprint and the patients’ lifestyles and dietary practices will be determined. The factors responsible for the excellent remission of T2D will be explored in this study.
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Affiliation(s)
- Mansor Fazliana
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
- Correspondence:
| | - Zubaidah Nor Hanipah
- Department of Surgery, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Barakatun Nisak Mohd Yusof
- Department of Surgery, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Nur Azlin Zainal Abidin
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - You Zhuan Tan
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - Farah Huda Mohkiar
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - Ahmad Zamri Liyana
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - Mohd Nawi Mohd Naeem
- Nutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - Norazlan Mohmad Misnan
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
| | - Haron Ahmad
- KPJ Damansara Specialist Hospital, 119, Jalan SS 20/10, Petaling Jaya 47400, Selangor, Malaysia
| | - Mohd Shazli Draman
- KPJ Damansara Specialist Hospital, 119, Jalan SS 20/10, Petaling Jaya 47400, Selangor, Malaysia
| | - Poh Yue Tsen
- Sunway Medical Centre, No. 5 Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
- iHeal Medical Centre, Menara IGB, Mid Valley City, Lingkaran Syed Putra, Kuala Lumpur 59200, Malaysia
- Sunway Velocity Medical Centre, Lingkaran SV2, Sunway Velocity, Kuala Lumpur 55100, Malaysia
| | - Shu Yu Lim
- Sunway Medical Centre, No. 5 Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
- iHeal Medical Centre, Menara IGB, Mid Valley City, Lingkaran Syed Putra, Kuala Lumpur 59200, Malaysia
- Sunway Velocity Medical Centre, Lingkaran SV2, Sunway Velocity, Kuala Lumpur 55100, Malaysia
| | - Tikfu Gee
- Sunway Medical Centre, No. 5 Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
- iHeal Medical Centre, Menara IGB, Mid Valley City, Lingkaran Syed Putra, Kuala Lumpur 59200, Malaysia
- Sunway Velocity Medical Centre, Lingkaran SV2, Sunway Velocity, Kuala Lumpur 55100, Malaysia
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Peng Y, Liu Z, Fu G, Zhao B, Gong M, Lu Z, Zhou Y, Chen L, Su H, Lou W, Chen G, He X, Gu J, Kong J. Identification microenvironment immune features and key genes in elderly stroke patients. Medicine (Baltimore) 2023; 102:e33108. [PMID: 36862915 PMCID: PMC9981407 DOI: 10.1097/md.0000000000033108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND The purpose of this study was to identify the signaling pathways and immune microenvironments related to elderly stroke patients. METHODS We downloaded the public transcriptome data (GSE37587) from the gene expression omnibus and divided the patients into young and old groups and identified differentially expressed genes (DEGs). Gene ontology function analysis, Kyoto encyclopedia of genes and genomes pathway analysis, and gene set enrichment analysis (GSEA) were performed. A protein-protein interaction network was constructed and hub genes were identified. Gene-miRNA, gene-TF, and gene-drug networks were constructed using the network analyst database. The immune infiltration score was evaluated using single-sample gene set enrichment analysis GSEA, its correlation with age was computed and visualized using R software. RESULTS We identified 240 DEGs, including 222 upregulated and 18 downregulated DEGs. Gene ontology enrichment was significantly enriched in response to the virus, type I interferon signaling pathway, cytological component, focal adhesion, cell-substrate adherents junction, and the cytosolic ribosome. GSEA identified the following mechanisms: heme metabolism, interferon gamma response, and interferon alpha response. Ten hub genes included interferon alpha-inducible protein 27, human leucocyte antigen-G, interferon-induced protein with tetratricopeptide repeats 2, 2'-5'-oligoadenylate synthetase 2, interferon alpha-inducible protein 6, interferon alpha-inducible protein 44-like, interferon-induced protein with tetratricopeptide repeats 3, interferon regulatory factor 5, myxovirus resistant 1, and interferon-induced protein with tetratricopeptide repeats 1. Quantitative analysis of immune infiltration showed that increased age was significantly positively correlated with myeloid-derived suppressor cells and natural killer T cells, and negatively correlated with immature dendritic cells. CONCLUSION The present research could help us better understand the molecular mechanisms and immune microenvironment of elderly patients with stroke.
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Affiliation(s)
- Yisheng Peng
- Department of Radiological Intervention, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, P.R. China
| | - Zhengli Liu
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Guanqi Fu
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Boxiang Zhao
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Maofeng Gong
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Zhaoxuan Lu
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Yangyi Zhou
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Liang Chen
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Haobo Su
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Wensheng Lou
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Guoping Chen
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Xu He
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Jianping Gu
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Jie Kong
- Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
- * Correspondence: Jie Kong, Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China (e-mail: )
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Mai Y, Sun P, Suo Y, Li H, Han W, Diao S, Wang L, Yuan J, Wang Y, Ye L, Zhang Y, Li F, Fu J. Regulatory mechanism of MeGI on sexuality in Diospyros oleifera. FRONTIERS IN PLANT SCIENCE 2023; 14:1046235. [PMID: 36909399 PMCID: PMC9994623 DOI: 10.3389/fpls.2023.1046235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 02/09/2023] [Indexed: 06/18/2023]
Abstract
Dioecy system is an important strategy for maintaining genetic diversity. The transcription factor MeGI, contributes to dioecy by promoting gynoecium development in Diospyros lotus and D. kaki. However, the function of MeGI in D. oleifera has not been identified. In this study, we confirmed that MeGI, cloned from D. oleifera, repressed the androecium development in Arabidopsis thaliana. Subsequently, chromatin immunoprecipitation-sequencing (ChIP-seq), DNA affinity purification-sequencing (DAP-seq), and RNA-seq were used to uncover the gene expression response to MeGI. The results showed that the genes upregulated and downregulated in response to MeGI were mainly enriched in the circadian rhythm-related and flavonoid biosynthetic pathways, respectively. Additionally, the WRKY DNA-binding protein 28 (WRKY28) gene, which was detected by ChIP-seq, DAP-seq, and RNA-seq, was emphasized. WRKY28 has been reported to inhibit salicylic acid (SA) biosynthesis and was upregulated in MeGI-overexpressing A. thaliana flowers, suggesting that MeGI represses the SA level by increasing the expression level of WRKY28. This was confirmed that SA level was lower in D. oleifera female floral buds than male. Overall, our findings indicate that the MeGI mediates its sex control function in D. oleifera mainly by regulating genes in the circadian rhythm, SA biosynthetic, and flavonoid biosynthetic pathways.
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Affiliation(s)
- Yini Mai
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Peng Sun
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Yujing Suo
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Huawei Li
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Weijuan Han
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Songfeng Diao
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Liyuan Wang
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
- Chinese Academy of Sciences (CAS) Engineering Laboratory for Vegetation Ecosystem Restoration on Islands and Coastal Zones, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China
| | - Jiaying Yuan
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Yiru Wang
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Lingshuai Ye
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Yue Zhang
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Fangdong Li
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
| | - Jianmin Fu
- State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Non-timber Forest Germplasm Enhancement and Utilization of National Forestry and Grassland Administration, Research Institute of Non-timber Forestry, Chinese Academy of Forestry, Zhengzhou, China
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Fereshteh S, Noori Goodarzi N, Kalhor H, Rahimi H, Barzi SM, Badmasti F. Identification of Putative Drug Targets in Highly Resistant Gram-Negative Bacteria; and Drug Discovery Against Glycyl-tRNA Synthetase as a New Target. Bioinform Biol Insights 2023; 17:11779322231152980. [PMID: 36798081 PMCID: PMC9926382 DOI: 10.1177/11779322231152980] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 12/24/2022] [Indexed: 02/17/2023] Open
Abstract
Background Gram-negative bacterial infections are on the rise due to the high prevalence of multidrug-resistant bacteria, and efforts must be made to identify novel drug targets and then new antibiotics. Methods In the upstream part, we retrieved the genome sequences of 4 highly resistant Gram-negative bacteria (e.g., Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter cloacae). The core proteins were assessed to find common, cytoplasmic, and essential proteins with no similarity to the human proteome. Novel drug targets were identified using DrugBank, and their sequence conservancy was evaluated. Protein Data Bank files and STRING interaction networks were assessed. Finally, the aminoacylation cavity of glycyl-tRNA synthetase (GlyQ) was virtually screened to identify novel inhibitors using AutoDock Vina and the StreptomeDB library. Ligands with high binding affinity were clustered, and then the pharmacokinetics properties of therapeutic agents were investigated. Results A total of 6 common proteins (e.g., RP-L28, RP-L30, RP-S20, RP-S21, Rnt, and GlyQ) were selected as novel and widespread drug targets against highly resistant Gram-negative superbugs based on different criteria. In the downstream analysis, virtual screening revealed that Rimocidin, Flavofungin, Chaxamycin, 11,11'-O-dimethyl-14'-deethyl-14'-methylelaiophylin, and Platensimycin were promising hit compounds against GlyQ protein. Finally, 11,11'-O-dimethyl-14'-deethyl-14'-methylelaiophylin was identified as the best potential inhibitor of GlyQ protein. This compound showed high absorption capacity in the human intestine. Conclusion The results of this study provide 6 common putative new drug targets against 4 highly resistant and Gram-negative bacteria. Moreover, we presented 5 different hit compounds against GlyQ protein as a novel therapeutic target. However, further in vitro and in vivo studies are needed to explore the bactericidal effects of proposed hit compounds against these superbugs.
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Affiliation(s)
| | - Narjes Noori Goodarzi
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Hourieh Kalhor
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Hamzeh Rahimi
- Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Texas Biomedical Research Institute, San Antonio, TX, USA
| | | | - Farzad Badmasti
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
- Farzad Badmasti, Department of Bacteriology, Pasteur Institute of Iran, Tehran Province, Tehran, 12 Farvardin St, Tehran 1316943551, Iran.
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Zhang R, Di C, Gao H, Zhu Y, Li C, Zhu Z, Wang Q, Wang J, Zhou F, Wang S. Identification of iron metabolism-related genes in the circulation and myocardium of patients with sepsis via applied bioinformatics analysis. Front Cardiovasc Med 2023; 10:1018422. [PMID: 36937929 PMCID: PMC10017502 DOI: 10.3389/fcvm.2023.1018422] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Background Early diagnosis of septic cardiomyopathy is essential to reduce the mortality rate of sepsis. Previous studies indicated that iron metabolism plays a vital role in sepsis-induced cardiomyopathy. Here, we aimed to identify shared iron metabolism-related genes (IMRGs) in the myocardium and blood monocytes of patients with sepsis and to determine their prognostic signature. Methods First, an applied bioinformatics-based analysis was conducted to identify shared IMRGs differentially expressed in the myocardium and peripheral blood monocytes of patients with sepsis. Second, Cytoscape was used to construct a protein-protein interaction network, and immune infiltration of the septic myocardium was assessed using single-sample gene set enrichment analysis. In addition, a prognostic prediction model for IMRGs was established by Cox regression analysis. Finally, the expression of key mRNAs in the myocardium of mice with sepsis was verified using quantitative polymerase chain reaction analysis. Results We screened common differentially expressed genes in septic myocardium and blood monocytes and identified 14 that were related to iron metabolism. We found that HBB, SLC25A37, SLC11A1, and HMOX1 strongly correlated with monocytes and neutrophils, whereas HMOX1 and SLC11A1 strongly correlated with macrophages. We then established a prognostic model (HIF1A and SLC25A37) using the common differentially expressed IMRGs. The prognostic model we established was expected to better aid in diagnosing septic cardiomyopathy. Moreover, we verified these genes using datasets and experiments and found a significant difference between the sepsis and control groups. Conclusion Common differential expression of IMRGs was identified in blood monocytes and myocardium between sepsis and control groups, among which HIF1A and SLC25A37 might predict prognosis in septic cardiomyopathy. The study may help us deeply understand the molecular mechanisms of iron metabolism and aid in the diagnosis and treatment of septic cardiomyopathy.
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Affiliation(s)
| | | | | | | | | | | | | | - Junjie Wang
- *Correspondence: Junjie Wang, ; Feng Zhou, ; Sheng Wang,
| | - Feng Zhou
- *Correspondence: Junjie Wang, ; Feng Zhou, ; Sheng Wang,
| | - Sheng Wang
- *Correspondence: Junjie Wang, ; Feng Zhou, ; Sheng Wang,
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Zhang R, Hao C, Ji Z, Qu Y, Zuo W, Yang M, Zuo P, Carvalho A, Ma G, Li Y. Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related Cardiotoxicity. Mediators Inflamm 2023; 2023:8347759. [PMID: 37009626 PMCID: PMC10063360 DOI: 10.1155/2023/8347759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 10/13/2022] [Accepted: 01/10/2023] [Indexed: 04/04/2023] Open
Abstract
Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity's side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of "dendritic cells activated" in the heart was significantly elevated, while "macrophage M1" and "monocytes" declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with "dendritic cells activation' and negatively correlated with "monocytes" and "macrophages M1'. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.
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Affiliation(s)
- Rui Zhang
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Chunshu Hao
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Zhenjun Ji
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Yangyang Qu
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Wenjie Zuo
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Mingming Yang
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Pengfei Zuo
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Abdlay Carvalho
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Genshan Ma
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
| | - Yongjun Li
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Hunan Road, Nanjing, Jiangsu 210000, China
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Wang G, Weng W, Jia Z, Zhang J, Wang T, Xuan J. Identification of Candidate Genes Associated with Pulp Color by Transcriptomic Analysis of 'Huaxiu' Plum ( Prunus salicina Lindl.) during Fruit-Ripening. Curr Issues Mol Biol 2022; 44:6368-6384. [PMID: 36547095 PMCID: PMC9776821 DOI: 10.3390/cimb44120434] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/06/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
The plum (Prunus salicina Lindl.) is one of the traditional and economically important stone fruit trees in China. Anthocyanins are important pigments in plums. However, little is known about the molecular mechanisms underlying anthocyanin accumulation in plum fruits, which has hindered research on the molecular mechanism of its utilization. Our research shows that the chlorophyll content was gradually decreased and the contents of anthocyanin and flavonoid increased during the coloring process of the pulp in 'Huaxiu' plums (P. salicina). Then, the RNA-Seq technique was used to analyze the transcriptome of pulp color changes with three different stages (yellow, orange, and red) in the 'Huaxiu' plum (P. salicina). A total of 57,119 unigenes with a mean length of 953 bp were generated, and 61.6% of them were annotated to public databases. The Gene Ontology (GO) database assigned 21,438 unigenes with biological process, cellular components, and molecular function. In addition, 32,146 unigenes were clustered into 25 categories for functional classification by the COG database, and 7595 unigenes were mapped to 128 KEGG pathways by the KEGG pathway database. Of these, 1095 (YS-versus-OS), 4947 (YS-versus-RS), and 3414 (OS-versus-RS) genes were significantly expressed differentially between two coloration stages. The GO and KEGG pathway enrichment analysis revealed that 20 and 1 differentially expressed genes (DEG) are involved in flavonoid biosynthesis and anthocyanin biosynthesis, respectively. Finally, we mainly identified three structural genes as candidate genes. The transcriptome information in this study provide a basis for further studies of pulp colors in plum and contribute to our understanding of the molecular mechanisms underlying anthocyanin biosynthesis in pulp.
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Integrating Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Hydroxysafflor Yellow A in Delaying Liver Aging. Int J Mol Sci 2022; 23:ijms232214281. [PMID: 36430769 PMCID: PMC9697017 DOI: 10.3390/ijms232214281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/03/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Aging affects the structure and function of the liver. Hydroxysafflor yellow A (HSYA) effectively improves liver aging (LA) in mice, but the potential mechanisms require further exploration. In this study, an integrated approach combining network pharmacology and transcriptomics was used to elucidate the potential mechanisms of HSYA delay of LA. The targets of HSYA were predicted using the PharmMapper, SwissTargetPrediction, and CTD databases, and the targets of LA were collected from the GeneCards database. An ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of genes related to HSYA delay of LA were performed using the DAVID database, and Cytoscape software was used to construct an HSYA target pathway network. The BMKCloud platform was used to sequence mRNA from mouse liver tissue, screen differentially expressed genes (DEGs) that were altered by HSYA, and enrich their biological functions and signaling pathways through the OmicShare database. The results of the network pharmacology and transcriptomic analyses were combined. Then, quantitative real-time PCR (qRT-PCR) and Western blot experiments were used to further verify the prediction results. Finally, the interactions between HSYA and key targets were assessed by molecular docking. The results showed that 199 potentially targeted genes according to network pharmacology and 480 DEGs according to transcriptomics were involved in the effects of HSYA against LA. An integrated analysis revealed that four key targets, including HSP90AA1, ATP2A1, NOS1 and CRAT, as well as their three related pathways (the calcium signaling pathway, estrogen signaling pathway and cGMP-PKG signaling pathway), were closely related to the therapeutic effects of HSYA. A gene and protein expression analysis revealed that HSYA significantly inhibited the expressions of HSP90AA1, ATP2A1 and NOS1 in the liver tissue of aging mice. The molecular docking results showed that HSYA had high affinities with the HSP90AA1, ATP2A1 and NOS1 targets. Our data demonstrate that HSYA may delay LA in mice by inhibiting the expressions of HSP90AA1, ATP2A1 and NOS1 and regulating the calcium signaling pathway, the estrogen signaling pathway, and the cGMP-PKG signaling pathway.
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Bioinformatics Analysis Identifies TNFRSF1A as a Biomarker of Liver Injury in Sepsis TNFRSF1A is a Biomarker for Septic Liver Injury. Genet Res (Camb) 2022; 2022:1493744. [PMID: 36299685 PMCID: PMC9587912 DOI: 10.1155/2022/1493744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/18/2022] Open
Abstract
Sepsis is a severe disease with high mortality, and liver injury is an independent risk factor for sepsis morbidity and mortality. We analyzed co-differentially expressed genes (co-DEGs) to explore potential biomarkers and therapeutic targets for sepsis-related liver injury. Three gene expression datasets (GSE60088, GSE23767, and GSE71530) were downloaded from the Gene Expression Omnibus (GEO). DEGs were screened between sepsis and control samples using GEO2R. The association of these DEGs with infection and liver disease was analyzed by using the CTD database. GO functional analysis, KEGG pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate the potential molecular mechanism of DEGs. DEGs of different tissues in GSE60088 were analyzed again to obtain specific markers of septic liver injury. Mouse model of sepsis was also established by cecal ligation and puncture (CLP), and the expression of specific markers in liver, lung, and kidney tissues was analyzed using Western blot. Here, we identified 21 DEGs in three datasets with 8 hub genes, all of which showed higher inference scores in liver diseases than bacterial infections. Among them, only TNFRSF1A had a liver-specific differential expression. TNFRSF1A was also confirmed to be specifically reduced in septic liver tissues in mice. Therefore, TNFRSF1A may serve as a potential biomarker for septic liver injury.
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Wang Y, Wang J, Chen L, Meng X, Zhen X, Liang Y, Han Y, Li H, Zhang B. Identification and function analysis of yellow-leaf mutant (YX-yl) of broomcorn millet. BMC PLANT BIOLOGY 2022; 22:463. [PMID: 36167497 PMCID: PMC9513943 DOI: 10.1186/s12870-022-03843-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 09/12/2022] [Indexed: 05/30/2023]
Abstract
BACKGROUND Broomcorn millet is highly tolerant to drought and barren soil. Changes in chlorophyll content directly affect leaf color, which subsequently leadsleading to poor photosynthetic performance and reduced crop yield. Herein, we isolated a yellow leaf mutant (YX-yl) using a forward genetics approach and evaluated its agronomic traits, photosynthetic pigment content, chloroplast ultrastructure, and chlorophyll precursors. Furthermore, the molecular mechanism of yellowing was explored using transcriptome sequencing. RESULTS The YX-yl mutant showed significantly decreased plant height and low yield. The leaves exhibited a yellow-green phenotype and poor photosynthetic capacity during the entire growth period. The content of chlorophyll a, chlorophyll b, and carotenoids in YX-yl leaves was lower than that in wild-type leaves. Chlorophyll precursor analysis results showed that chlorophyll biosynthesis in YX-yl was hindered by the conversion of porphobilinogen to protoporphyrin IX. Examination of chloroplast ultrastructure in the leaves revealed that the chloroplasts of YX-yl accumulated on one side of the cell. Moreover, the chloroplast structure of YX-yl was degraded. The inner and outer membranes of the chloroplasts could not be distinguished well. The numbers of grana and grana thylakoids in the chloroplasts were low. The transcriptome of the yellowing mutant YX-yl was sequenced and compared with that of the wild type. Nine chlorophyll-related genes with significantly different expression profiles were identified: PmUROD, PmCPO, PmGSAM, PmPBDG, PmLHCP, PmCAO, PmVDE, PmGluTR, and PmPNPT. The proteins encoded by these genes were located in the chloroplast, chloroplast membrane, chloroplast thylakoid membrane, and chloroplast matrix and were mainly involved in chlorophyll biosynthesis and redox-related enzyme regulation. CONCLUSIONS YX-yl is an ideal material for studying pigment metabolism mechanisms. Changes in the expression patterns of some genes between YX-yl and the wild type led to differences in chloroplast structures and enzyme activities in the chlorophyll biosynthesis pathway, ultimately resulting in a yellowing phenotype in the YX-yl mutant. Our findings provide an insight to the molecular mechanisms of leaf color formation and chloroplast development in broomcorn millet.
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Affiliation(s)
- Yushen Wang
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
- Shanxi Key Laboratory of Germplasm Innovation and Molecular Breeding of Minor Crop, Taigu, Shanxi, China, 030801
- Ministerial and Provincial Co-Innovation Centre for Endemic Crops Production With High-Quality and Efficiency in Loess Plateau, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Junjie Wang
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Liqing Chen
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Xiaowei Meng
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Xiaoxi Zhen
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Yinpei Liang
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Yuanhuai Han
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
- Shanxi Key Laboratory of Germplasm Innovation and Molecular Breeding of Minor Crop, Taigu, Shanxi, China, 030801
| | - Hongying Li
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801
| | - Bin Zhang
- College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China, 030801.
- Shanxi Key Laboratory of Germplasm Innovation and Molecular Breeding of Minor Crop, Taigu, Shanxi, China, 030801.
- Ministerial and Provincial Co-Innovation Centre for Endemic Crops Production With High-Quality and Efficiency in Loess Plateau, Shanxi Agricultural University, Taigu, Shanxi, China, 030801.
- Institute of Agricultural Bioengineering, Shanxi Agricultural University, Taigu, Shanxi, China, 030801.
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Wang X, Kong C, Liu P, Zhou B, Geng W, Tang H. Therapeutic Effects of Retinoic Acid in Lipopolysaccharide-Induced Cardiac Dysfunction: Network Pharmacology and Experimental Validation. J Inflamm Res 2022; 15:4963-4979. [PMID: 36105385 PMCID: PMC9467448 DOI: 10.2147/jir.s358374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions. However, the treatment efficacy and potential causal links of RA in SIC are still elusive. Methods By virtue of the STITCH database, we identified the targets of RA. Differentially expressed genes in SIC were acquired from the GEO database. The PPI network of intersected targets was established. GO and KEGG pathway enrichment analysis was completed. Hub genes were analyzed by cytoHubba plug-in. In the process of experimental validation, a mouse sepsis model was established by lipopolysaccharide (LPS), and the treated mice were intraperitoneally injected with RA or Dexamethasone (DEX) 60 min prior to LPS injections. Survival conditions, cardiac functions and antioxidant levels of the mice were assessed. Cardiac inflammation and injury were detected by HE and TUNEL. The levels of key genes and signal pathway expression were analyzed by RT-PCR and Western blot. Results PPARA, ITGAM, VCAM-1, IGF-1 and IL-6 were identified as key therapeutic targets of RA by network pharmacology. PI3K-Akt signaling pathway is the main regulatory pathway of RA. In vivo researches unraveled that RA can improve the survival rate and cardiac function of LPS-treated mice, inhibit inflammatory factors and myocardial injury, and regulate the expression of key therapeutic targets and key pathways, which is PI3K-Akt signaling pathway. Conclusion Network pharmacological method offers a predicative strategy to explore the treatment efficacy and causal links of RA in endotoxemic myocarditis. Through experimental verification, we discover that RA can reduce lipopolysaccharide-induced cardiac dysfunction by regulating the PI3K-Akt signaling pathway and key genes.
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Affiliation(s)
- Xi Wang
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou, People’s Republic of China
| | - Chang Kong
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, People’s Republic of China
| | - Pan Liu
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou, People’s Republic of China
| | - Baofeng Zhou
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou, People’s Republic of China
| | - Wujun Geng
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou, People’s Republic of China
| | - Hongli Tang
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou, People’s Republic of China
- Correspondence: Hongli Tang; Wujun Geng, Doctor’s Degree, Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13587436057; +86 15325502139, Fax +86 0577-88069555, Email ;
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Zaidi S, Aswal M, Kumar M, Rashid F, Khan AU. Protein expression profiling, in silico classification and pathway analysis of cariogenic bacteria Streptococcus mutans under bacitracin stress conditions. J Med Microbiol 2022; 71. [PMID: 36040855 DOI: 10.1099/jmm.0.001572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Introduction. Streptococcus mutans is a cariogenic bacterium that causes dental caries as well as being implicated in other dental pathologies and infective endocarditis. Bacitracin is a bactericidal antibiotic that induces cell wall stress in Gram-positive bacteria.Gap Statement. S. mutans is among the most characterized Gram-positive bacteria. However, the transcriptome and proteome of S. mutans have received less attention, and they are actually key in understanding the pathogenesis of any bacteria. In this study, we extracted the whole proteome of S. mutans grown under bacitracin stress. Such a proteome is anticipated to offer deep insights related to physiological dynamic fluctuations and, consequently, it may provide 'proteomic signatures' to be identified as potential targets.Aim. The aim of the study is to explore the general stress response that S. mutans exhibits at the proteome level when cell wall stress is imposed on it.Methodology. A sub-MIC concentration of bacitracin was added to the growth media of S. mutans followed by whole-cell protein extraction. The proteome was then subjected to high-throughput proteomics analysis, i.e. liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins obtained through LC-MS/MS underwent analyses such as gene ontology, KEGG (Kyoto Encyclopaedia of Genes and Genomes) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analysis, and STRING for functional annotation, pathway enrichment and protein-protein interaction (PPI) networks, respectively. These proteins were also categorized into functional classes using the PANTHER (Protein Annotation Through Evolutionary Relationship) classification system.Result. LC-MS/MS produced data from 321 identified proteins. From these, 41 and 30 were found to be significantly over- (≥2 fold change) and underexpressed (≤0.4 fold change), respectively. In the upregulated proteins we mostly observed sortases and proteins involved in the EPS biosynthesis pathway, whereas among the downregulated proteins the majority related to glycolysis.Conclusion. The sortase family of proteins appear to be potential targets because they regulate various virulence factors and therefore can be targeted to inhibit multiple virulence pathways simultaneously. This study offers an understanding of proteomic fluctuations in response to cell wall stress and can thus help in identifying key players mediating virulence.
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Affiliation(s)
- Sahar Zaidi
- Medical Microbiology and Molecular Biology, Laboratory Interdisciplinary, Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP, India
| | - Manisha Aswal
- Department of Biophysics, University of Delhi South Campus, New Delhi, 110021, India
| | - Manish Kumar
- Department of Biophysics, University of Delhi South Campus, New Delhi, 110021, India
| | - Faraz Rashid
- Henry Ford Health System, Detroit, MI 48202, USA
| | - Asad U Khan
- Medical Microbiology and Molecular Biology, Laboratory Interdisciplinary, Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP, India
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Zhen Z, Li M, Zhong M, Liu J, Huang W, Ye L. Expression and prognostic potential of TMEM204: a pan-cancer analysis. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2022; 15:258-271. [PMID: 35949807 PMCID: PMC9360586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 05/24/2022] [Indexed: 06/15/2023]
Abstract
TMEM204 (Transmembrane Protein 204) is a member of the TMEM family that regulates cell function and angiogenesis. Previous studies showed that TMEM204 is related to pancreatic cancer, but its roles in other cancers remain unknown. To reveal this relationship, we conducted a pan-cancer analysis by several online databases. The expression of TMEM204 was analyzed by Oncomine and Tumor Immune Estimation Resource2.0 (TIMER2.0). The prognostic potential of TMEM204 was evaluated by the GEPIA2, UALCAN, and Oncolnc. The methylation level of gene expression was analyzed by UALCAN, and the relationship between cancer and immune invasion was displayed by TIMER2.0. The Protein-Protein Interactions Network and functional analysis of TMEM204 and its related genes were conducted by STRING and Webgestalt. We found that TMEM204 expression was up-regulated and correlated with prognosis in multiple cancers. In liver hepatocellular carcinoma (LIHC), high TMEM204 expression was associated with a good prognosis, and with high infiltrating levels of CD8+ T and CD4+ T cells, macrophages, neutrophils, and myeloid dendritic cells. In addition, the methylation level in LIHC was higher than in normal tissues. p53 signaling pathway and Fanconi anemia pathway were implicated by KEGG pathway analysis. These results indicate that TMEM204 is associated with the prognosis, methylation, and immune invasion of cancers, especially LIHC. TMEM204 may act as a prognostic marker of LIHC and its role in other cancers should be studied.
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Affiliation(s)
- Zicheng Zhen
- Zhongshan School of Medicine, Sun Yat-sen UniversityGuangzhou 510060, Guangdong, China
| | - Minghao Li
- The Second Clinical Medical School, Guangdong Medical UniversityDongguan 523808, Guangdong, China
| | - Muyan Zhong
- The Second Clinical Medical School, Guangdong Medical UniversityDongguan 523808, Guangdong, China
| | - Jiaqi Liu
- Zhongshan School of Medicine, Sun Yat-sen UniversityGuangzhou 510060, Guangdong, China
| | - Wendu Huang
- The First School of Clinical Medicine, Southern Medical UniversityGuangzhou 510515, Guangdong, China
| | - Liqun Ye
- Endoscopic Center, The Six Affiliated Hospital, South China University of Technology (People’s Hospital of Nanhai District)Foshan 528200, Guangdong, China
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Tang B, Tan T, Chen Y, Hu Z, Xie Q, Yu X, Chen G. SlJAZ10 and SlJAZ11 mediate dark-induced leaf senescence and regeneration. PLoS Genet 2022; 18:e1010285. [PMID: 35830385 PMCID: PMC9278786 DOI: 10.1371/journal.pgen.1010285] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/07/2022] [Indexed: 11/29/2022] Open
Abstract
During evolutionary adaptation, the mechanisms for self-regulation are established between the normal growth and development of plants and environmental stress. The phytohormone jasmonate (JA) is a key tie of plant defence and development, and JASMONATE-ZIM DOMAIN (JAZ) repressor proteins are key components in JA signalling pathways. Here, we show that JAZ expression was affected by leaf senescence from the transcriptomic data. Further investigation revealed that SlJAZ10 and SlJAZ11 positively regulate leaf senescence and that SlJAZ11 can also promote plant regeneration. Moreover, we reveal that the SlJAV1-SlWRKY51 (JW) complex could suppress JA biosynthesis under normal growth conditions. Immediately after injury, SlJAZ10 and SlJAZ11 can regulate the activity of the JW complex through the effects of electrical signals and Ca2+ waves, which in turn affect JA biosynthesis, causing a difference in the regeneration phenotype between SlJAZ10-OE and SlJAZ11-OE transgenic plants. In addition, SlRbcs-3B could maintain the protein stability of SlJAZ11 to protect it from degradation. Together, SlJAZ10 and SlJAZ11 not only act as repressors of JA signalling to leaf senescence, but also regulate plant regeneration through coordinated electrical signals, Ca2+ waves, hormones and transcriptional regulation. Our study provides critical insights into the mechanisms by which SlJAZ11 can induce regeneration. In plants, senescence is the final stage of development, but regeneration can help them beyond the stage. Plants regeneration is essential for propagation, and in cultivated crops to maintain excellent traits as close as possible. JA signaling can sense environmental signals and integrate various regulatory mechanisms to ensure plants regeneration occurs under optimal conditions. In this work, the JAZ-JAV1-WRKY51 complexes with reported was further optimized, the function of SlJAZ10 and SlJAZ11 was identified to promote inhibitory activity of SlJAV1-SlWRKY51 complex which negatively regulated JA biosynthesis by direct binding of the W-box of the SlAOC promoter. The results of further investigation suggest that the differences in regulation of electrical signals, Ca2+ waves, hormones and transcriptional regulation are responsible for the regeneration between SlJAZ10 and SlJAZ11. In addition, we have found that SlRbcs-3B could maintain the protein stability of SlJAZ11 to protect it from degradation. In summary, despite both SlJAZ10 and SlJAZ11 can function as senescence, only SlJAZ11 has an important promoting function for regeneration.
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Affiliation(s)
- Boyan Tang
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
| | - Tingting Tan
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
| | - Yating Chen
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
| | - Zongli Hu
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
| | - Qiaoli Xie
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
| | - Xiaohui Yu
- Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Tropical Crops, Hainan University, Haikou, People’s Republic of China
- * E-mail: (XY); (GC)
| | - Guoping Chen
- Key Laboratory of Bioengineering Science and Technology, Chongqing University, Ministry of Education, Chongqing, China
- Bioengineering College, Campus B, Chongqing University, Chongqing, People’s Republic of China
- * E-mail: (XY); (GC)
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Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatic Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6042591. [PMID: 35800215 PMCID: PMC9256438 DOI: 10.1155/2022/6042591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/27/2022] [Indexed: 11/17/2022]
Abstract
Muscle atrophy caused by long-term denervation leads to the loss of skeletal muscle mass and strength, resulting in a poor recovery of functional muscles and decreasing quality of life. Increasing differentially expressed microRNAs (DEMs) have been reported to be involved in the pathogenesis of denervated muscle atrophy. However, there is still insufficient evidence to explain the role of miRNAs and their target genes in skeletal muscle atrophy. Therefore, an integrative exploration of the miRNA-mRNA regulatory network in denervated muscle atrophy is necessary. A total of 21 (16 upregulated and 5 downregulated) DEMs were screened out in the GSE81914 dataset. Med1, Myod1, Nfkb1, Rela, and Camta1 were predicted and verified to be significantly upregulated in denervated muscle atrophy, from which 6 key TF-miRNA relationship pairs, including Med1-mir-1949, Med1-mir-146b, Myod1-mir-29b, Nfkb1-mir-21, Rela-mir-21, and Camta1-mir-132, were obtained. 60 target genes were then predicted by submitting candidate DEMs to the miRNet database. GO and KEGG pathway enrichment analysis showed that target genes of DEMs were mainly enriched in the apoptotic process and PI3K/Akt signaling pathway. Through the PPI network construction, key modules and hub genes were obtained and potentially modulated by mir-29b, mir-132, and mir-133a. According to the qRT-PCR results, the expression of COL1A1 and Ctgf is opposite to their related miRNAs in denervated muscle atrophy. In the study, a potential miRNA-mRNA regulatory network was firstly constructed in denervated muscle atrophy, in which the mir-29b-COL1A1 and mir-133a-Ctgf pathways may provide new insights into the pathogenesis and treatment.
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Wu ZH, Li C, Zhang YJ, Zhou W. Identification of a Cancer Stem Cells Signature of Head and Neck Squamous Cell Carcinoma. Front Genet 2022; 13:814777. [PMID: 35646104 PMCID: PMC9132479 DOI: 10.3389/fgene.2022.814777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most widespread and deadly cancer. In recent times, it has been determined that undifferentiated cell populations with stem cell-like properties in HNSCC are major factors influencing recurrence and progression. Method: In this study, we determine key genes related to stemness by merging WGCNA with HNSCC mRNAsi based on the online database. Results: We first download the mRNA expression-based stemness index (mRNAsi) data and contrast the expression levels of mRNAsi in cancers and control samples; we found significantly elevated mRNAsi expressions in HNSCC tissues (p = 0.002). Moreover, the brown module showed a relatively high negative correlation with mRNAsi (cor = -0.8). Thus, we selected the brown module as the interesting module and used it for following analysis. We screened 20 key genes (PDGFRB, PLPP4, CALU, ADAMTS14, COL5A3, KCNE4, LOXL1, CLEC11A, PODN,BGN, AEBP1, COL1A2, LAMA4, LOXL2, LRRC15, THY1, SPON2, COL1A1, NID2, and AC134312.5) including and as to decide the neighbor genes biological interaction network of these 20 stemness-related genes in HNSCC. The top 10 frequent alterations were PIK3CA, FGF3, FGF19, FGF4, DVL3, P3H2, GNB4, COL22A1, COL14A1, and PLOD2. Conclusion: This study showed the critical role of stemness-related genes in HNSCC. However, more related studies are needed to confirm these results.
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Affiliation(s)
- Zeng-Hong Wu
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cheng Li
- Department of Otolaryngology Head and Neck Surgery, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
| | - You-Jing Zhang
- Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhou
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Qi P, Huang M, Li T. Screening the Potential Biomarkers of COVID-19-Related Thrombosis Through Bioinformatics Analysis. Front Genet 2022; 13:889348. [PMID: 35692833 PMCID: PMC9174658 DOI: 10.3389/fgene.2022.889348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 05/09/2022] [Indexed: 11/30/2022] Open
Abstract
A high proportion of critically ill patients with coronavirus disease 2019 (COVID-19) experience thrombosis, and there is a strong correlation between anticoagulant therapy and the COVID-19 survival rate, indicating that common COVID-19 and thrombosis targets have potential therapeutic value for severe COVID-19.Gene expression profiling data were downloaded from Gene Expression Omnibus (GEO), and common differentially expressed genes (co-DEGs) were identified. The potential biological functions of these co-DEGs were explored by functional enrichment analysis, and protein–protein interaction (PPI) networks were constructed to elucidate the molecular mechanisms of the co-DEGs. Finally, hub genes in the co-DEG network were identified, and correlation analysis was performed.We identified 8320 upregulated genes and 7651 downregulated genes from blood samples of COVID-19 patients and 368 upregulated genes and 240 downregulated genes from blood samples of thrombosis patients. The enriched cellular component terms were mainly related to cytosolic ribosomes and ribosomal subunits. The enriched molecular function terms were mainly related to structural constituents of ribosomes and electron transfer activity. Construction of the PPI network and identification of hub genes ultimately confirmed that RPS7, IGF1R, DICER1, ERH, MCTS1, and TNPO1 were jointly upregulated hub genes, and FLNA and PXN were jointly downregulated hub genes.The identification of novel potential biomarkers provides new options for treating COVID-19-related thrombosis and reducing the rate of severe COVID-19.
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Affiliation(s)
- Peng Qi
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mengjie Huang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Tanshi Li
- Department of Emergency, First Medical Center of Chinese PLA General Hospital, Beijing, China
- *Correspondence: Tanshi Li,
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Zhang D, Li X, Jing B, Shi H, Chang S, Chen Z, Zheng Y, Pan Y, Qian G, Zhao G. Identification of pathways and key genes in male late‑stage carotid atherosclerosis using bioinformatics analysis. Exp Ther Med 2022; 24:460. [PMID: 35747144 PMCID: PMC9204528 DOI: 10.3892/etm.2022.11387] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/05/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Di Zhang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Xin Li
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Bei Jing
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Huimei Shi
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Shiquan Chang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Zhenni Chen
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Yachun Zheng
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Yuwei Pan
- Department of Preventive Treatment of Disease, Tianhe Traditional Chinese Medicine Hospital, Guangzhou, Guangdong 510665, P.R. China
| | - Guoqiang Qian
- College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
| | - Guoping Zhao
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
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Li Z, Bai H, Zhang R, Chen B, Wang J, Xue B, Ren X, Wang J, Jia Y, Zang W, Wang J, Chen X. Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury. Eur J Neurosci 2022; 56:3991-4008. [PMID: 35560852 DOI: 10.1111/ejn.15693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 03/21/2022] [Accepted: 03/26/2022] [Indexed: 11/28/2022]
Abstract
Spinal cord injury (SCI) damages sensory systems, producing chronic neuropathic pain that is resistant to medical treatment. The specific mechanisms underlying SCI-induced neuropathic pain (SCI-NP) remain unclear, and protein biomarkers have not yet been integrated into diagnostic screening. To better understand the host molecular pathways involved in SCI-NP, we used the bioinformatics method, the PubMed database, and bioinformatics methods to identify target genes and their associated pathways. We reviewed 2504 articles on the regulation of SCI-NP and used the text mining of PubMed database abstracts to determine associations among 12 pathways and networks. Based on this method, we identified two central genes in SCI-NP: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Adult male Sprague-Dawley rats were used to build the SCI-NP models. The threshold for paw withdrawal was significantly reduced in the SCI group and TLR4 was activated in microglia after SCI. ELISA analysis of TNF-α and IL-6 levels was significantly higher in the SCI group than in the sham group. Western blot showed that expressions of the TLR4/MyD88/NF-κB inflammatory pathway protein increased dramatically in the SCI group. Using the TLR4 inhibitor TAK-242, the pain threshold and expressions of inflammatory factors and proteins of the proteins of the inflammatory signal pathway were reversed, TLR4 in microglia was suppressed, suggesting that SCI-NP was related to neuroinflammation mediated by the TLR4 signaling pathway. In conclusion, we found TNF-α and IL-6 were the neuroinflammation-related genes involved in SCI-NP that can be alleviated by inhibiting the inflammatory pathway upstream of the TLR4/MyD88/NF-κB inflammatory pathway.
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Affiliation(s)
- Zefu Li
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Huiying Bai
- Outpatient Surgery, Zhengzhou University Hospital, Zhengzhou, Henan Province, China
| | - Ruoyu Zhang
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Bohan Chen
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Junmin Wang
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Bohan Xue
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xiuhua Ren
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Jiarui Wang
- The Johns Hopkins University, Baltimore, Maryland, USA
| | - Yanjie Jia
- Department of Neurology, the first affiliated Hospital Zhengzhou University, Zhengzhou, Henan Province, China
| | - Weidong Zang
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Jian Wang
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xuemei Chen
- Department of Basic Medical College of Human Anatomy of Zhengzhou University, Zhengzhou, Henan Province, China
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Wang JD. iTRAQ based characterization of proteomic change in petroleum hydrocarbon-degrading Pseudomonas aeruginosa in different pH conditions. Arch Microbiol 2022; 204:263. [DOI: 10.1007/s00203-022-02880-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 03/25/2022] [Accepted: 03/28/2022] [Indexed: 11/28/2022]
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Zeng M, He S, Hao J, Zhao Y, Zheng C. iTRAQ-based proteomic analysis of heteromorphic leaves reveals eco-adaptability of Populus euphratica Oliv. JOURNAL OF PLANT PHYSIOLOGY 2022; 271:153644. [PMID: 35219031 DOI: 10.1016/j.jplph.2022.153644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 01/28/2022] [Accepted: 02/08/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Heterophylly is regard as adaptation to different environments in plant, and Populus euphratica is an important heterophyllous woody plant. However, information on its molecular mechanism in eco-adaptability remains obscure. RESULTS In this research, proteins were identified by isobaric tags for relative and absolute quantitation (iTRAQ) technology in lanceolate, ovate, and dentate broad-ovate leaves from adult P. euphratica trees, respectively. Besides, chlorophyll content, net photosynthetic rate, stomatal conductance, transpiration rate and peroxidase activity in these heteromorphic leaves were investigated. A total number of 2,689 proteins were detected in the heteromorphic leaves, of which 56, 73, and 222 differential abundance proteins (DAPs) were determined in ovate/lanceolate, dentate broad-ovate/lanceolate, and dentate broad-ovate/ovate comparison groups. Bioinformatics analysis suggested these altered proteins related to photosynthesis, stress tolerance, respiration and primary metabolism accumulated in dentate broad-ovate and ovate leaves, which were consistent with the results of physiological parameters and Real-time Quantitative PCR experiments. CONCLUSION This research demonstrated the mechanism of the differential abundance proteins in providing an optimal strategy of resource utilization and survival for P. euphratica, that could offer clues for further investigations into eco-adaptability of heterophyllous woody plants.
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Affiliation(s)
- Ming Zeng
- College of Biological Sciences and Technology, Beijing Forestry University, No. 35 Qing Hua Dong Lu, Beijing, 100083, China; Guangdong Academy of Forestry, Guangzhou, 510520, China.
| | - Shuhang He
- College of Biological Sciences and Technology, Beijing Forestry University, No. 35 Qing Hua Dong Lu, Beijing, 100083, China.
| | - Jianqing Hao
- School of Basic Medical Sciences, Shanxi Medical University, No. 56 Xinjian Nan Lu, Taiyuan, 030001, China.
| | - Yuanyuan Zhao
- College of Biological Sciences and Technology, Beijing Forestry University, No. 35 Qing Hua Dong Lu, Beijing, 100083, China.
| | - Caixia Zheng
- College of Biological Sciences and Technology, Beijing Forestry University, No. 35 Qing Hua Dong Lu, Beijing, 100083, China.
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Tu S, Zhang H, Qu X. Screening of key methylation-driven genes CDO1 in breast cancer based on WGCNA. Cancer Biomark 2022; 34:571-582. [PMID: 35342080 DOI: 10.3233/cbm-210485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND With the rapid development of genomics and molecular biology, not only have biochemical indicators been used as tumour markers, but many new molecular markers have emerged. Epigenetic abnormalities are a new type of molecular marker, and DNA methylation is an important part of epigenetics. OBJECTIVE This study used weighted gene coexpression network analysis (WGCNA) to analyse key methylation-driven genes in breast cancer. METHODS The RNA-seq transcriptome data, DNA methylation data, and clinical information data of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database, and the MethylMix R package was used to screen methylation-driven genes in breast cancer. The ClusterProfiler package and enrichplot package in R software were used to further analyse the function and signalling pathway of methylation-driven genes. Through univariate and multivariate Cox regression analyses, methylation-driver genes related to prognostic were obtained, a prognostic model was constructed and prognostic characteristics were analysed. RESULTS The 17 methylation-driven genes related to prognosis were obtained by the WGCNA method in breast cancer, and the prognostic significance of these methylation-driven genes was determined by transcriptome and methylation combined survival analysis. Analysis of functions and signalling pathways showed that these genes were mainly enriched in biological processes and signalling pathway. Through univariate and multivariate Cox regression analyses, a prognostic model of 5 methylation-driven genes was constructed. CONCLUSIONS The AUC of the receiver operating characteristic (ROC) curve of this model was 0.784, showing that the model had a good prediction effect. Based on WGCNA screening, it was found that only CDO1 was the key methylation-driven gene for prognosis in breast cancer, indicating that CDO1 may be an important indicator of the prognosis of breast cancer patients.
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Affiliation(s)
- Simei Tu
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, Liaoning, China
| | - Hao Zhang
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, Liaoning, China
| | - Xinjian Qu
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, Liaoning, China
- Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
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48
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Wang J, Li M, Zhuo S, Liu Y, Yu X, Mukhtar S, Ali M, Lu G. Mitogen-activated protein kinase 4 is obligatory for late pollen and early fruit development in tomato. HORTICULTURE RESEARCH 2022; 9:uhac048. [PMID: 35591931 PMCID: PMC9113226 DOI: 10.1093/hr/uhac048] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/14/2022] [Indexed: 06/09/2023]
Abstract
Mitogen-activated protein kinase (MAPK) cascades are universal signal transduction modules regulating vegetative and reproductive development of plants. However, the molecular mechanisms of the SlMPK4 gene in tomato pollen and fruit development remain elusive. SlMPK4 is preferentially and highly expressed in tomato stamens and its mRNA levels increase during early flower development, peaking at the mature pollen stage. Either up- or downregulation of SlMPK4 expression had no significant effect on tomato vegetative growth. However, RNAi-mediated suppression of SlMPK4 caused defects in pollen development, resulting in pollen abortion. The aborted pollen grains were either malformed or collapsed and completely lacked viability, resulting in a predominantly reduced fruit set rate in RNAi lines compared with control and overexpressing transgenic plants. Interestingly, seed development was inhibited in RNAi lines. Moreover, >12% of emasculated RNAi flowers developed seedless fruits without pollination. Anthers can produce typical microspore mother cells as well as uninucleate microspores, according to cytological investigations, while binucleate pollen ceased to produce typical mature pollen. Pollen abortion was further confirmed by transmission electron microscopy analysis at the binucleate stage in RNAi plants. The exine layer in aberrant pollen had a normal structure, while the intine layer appeared thicker. Suppression of SlMPK4 affects the transcript level of genes related to cell wall formation and modification, cell signal transduction, and metabolic and biosynthetic processes. A subset of genes that may be putative substrates of plant MAPKs were also differentially changed in RNAi transgenic flowers. Taken together, these results suggest that SlMPK4 plays a critical role in regulating pollen development and fruit development in tomato plants.
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Affiliation(s)
- Jie Wang
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
- Ningbo Academy of Agricultural Sciences, Ningbo 315000, Zhejiang, China
| | - Mengzhuo Li
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
| | - Shibin Zhuo
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
| | - Yue Liu
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
| | - Xiaolin Yu
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
| | - Sidra Mukhtar
- Directorate of Agriculture Research, Agricultural Research Institute Tarnab, Peshawar, Pakistan
| | - Muhammad Ali
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
| | - Gang Lu
- Department of Horticulture, Zhejiang University, Hangzhou 310058, China
- Key Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Ministry of Agricultural, Zhejiang University, Hangzhou 310058, China
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Systems-level analysis of the global regulatory mechanism of CodY in Lactococcus lactis metabolism and nisin immunity modulation. Appl Environ Microbiol 2022; 88:e0184721. [PMID: 35044848 DOI: 10.1128/aem.01847-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Bacteria adapt to the constantly changing environment by regulating their metabolism. The global transcriptional regulator CodY is known to regulate metabolism in low G+C Gram-positive bacteria. Systems-level identification of its direct targets by proteome and ChIP-seq assays was rarely reported. Here, we identified CodY serves as an activator or a repressor of hundreds of genes involved in nitrogen metabolism, carbohydrate metabolism, and transcription through iTRAQ proteome and ChIP-seq. Combined with EMSA experiment, apart from the genes associated with amino acid biosynthesis (ilvD, leuA, optS, ybbD, dtpT, and pepN), genes involved in cell wall synthesis (murD and ftsW) and nisin immunity (nisI) were identified to be regulated by CodY. Moreover, it was demonstrated that CodY activated the transcription of nisI and contributed to the nisin immunity by nisin resistance assay. Intriguingly, CodY showed a self-regulation through binding to the motif 'AAAGGTGTGACAACT'in the CDS region of codY verified by DNase I footprinting assay and MEME analysis. In addition, a novel conserved AT-rich motif 'AATWTTCTGACAATT' was obtained in L. lactis F44. This study provides new insights into the comprehensive CodY regulation in L. lactis by controlling metabolism, nisin immunity and self-expression. Importance Lactococcus lactis, a widely used lactic acid bacteria (LAB) in the food fermentation, has been the model strain in genetic engineering, and its application has extended from food to microbial cell factory. CodY is a global regulator in low G+C Gram-positive bacteria. Its function and direct target genes in genome-level were rarely known in L. lactis. In this study, we described the comprehensive regulation mechanism of CodY. It widely modulated the metabolism of nitrogen and carbohydrate, cell wall synthesis and nisin immunity in L. lactis F44, and its expression level was regulated by feedback control.
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50
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Li H, Zhang L, Zhang K, Huang Y, Liu Y, Lu X, Liao W, Liu X, Zhang Q, Pan W. Gut microbiota associated with cryptococcal meningitis and dysbiosis caused by anti-fungal treatment. Front Microbiol 2022; 13:1086239. [PMID: 36909846 PMCID: PMC9994644 DOI: 10.3389/fmicb.2022.1086239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/05/2022] [Indexed: 02/24/2023] Open
Abstract
The gut microbiota is a dynamic and highly diverse microbial ecosystem that affects many aspects of the host's physiology. An improved understanding of the gut microbiota could lead to better strategies for the diagnosis and therapy of cryptococcal meningitis (CM), but the impact of Cryptococcus infection and anti-fungal treatment on the gut microbiota has rarely been studied. We characterized the diversity and composition of the gut microbiota in CM patients at diagnosis and healthy controls (HCs) using metagenomic sequencing and determined the effects of anti-fungal drugs. We found that CM patients had distinct bacterial and fungal compositions compared with HCs, with eight differentially abundant fungal and 72 differentially abundant bacterial species identified between the two groups. CM patients showed an increased abundance of Enterococcus avium, Leuconostoc mesenteroides, and Weissella cibaria, and a decreased abundance of Prevotella spp. compared with HCs. However, anti-fungal treatment only led to minor changes in the intestinal microbiota. Moreover, both positive and negative correlations existed in fungal, bacterial, and clinical indicators. Our study suggests that the Cryptococcus neoformans infection caused a distinct dysbiosis of the gut microbiota and contributes valuable information implying potential links between the CM and gut microbiota.
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Affiliation(s)
- Hang Li
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lei Zhang
- Department of Dermatology, The Third Affiliated Hospital of Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Xi'an, China
| | - Keming Zhang
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yue Huang
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, The First Naval Hospital of Southern Theater Command, Zhanjiang, China
| | - Yi Liu
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xiaodi Lu
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wanqing Liao
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xiaogang Liu
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Qilong Zhang
- Department of Neurology, Jiangxi Chest Hospital, Jiangxi, China
| | - Weihua Pan
- Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Dermatology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
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