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Liang B, Chen SW, Li YY, Zhang SX, Zhang Y. Comprehensive analysis of endoplasmic reticulum stress-related mechanisms in type 2 diabetes mellitus. World J Diabetes 2023; 14:820-845. [PMID: 37383594 PMCID: PMC10294059 DOI: 10.4239/wjd.v14.i6.820] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 12/27/2022] [Accepted: 04/04/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND The endoplasmic reticulum (ER) is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health. Type 2 diabetes mellitus (T2DM) is a serious threat to human health, but the ER stress (ERS)-related mechanisms in T2DM have not been fully elucidated.
AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.
METHODS We conducted gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in myoblast and myotube form GSE166502, and obtained the differentially expressed genes (DEGs). After intersecting with ERS-related genes, we obtained ERS-related DEGs. Finally, functional analyses, immune infiltration, and several networks were established.
RESULTS Through GSEA and GSVA, we identified several metabolic and immune-related pathways. We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM. Finally, memory CD4+ T cells accounted for the largest proportion of immune cells.
CONCLUSION This study revealed ERS-related mechanisms in T2DM, which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.
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Affiliation(s)
- Bo Liang
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China
| | - Shu-Wen Chen
- Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200000, China
| | - Yuan-Yuan Li
- Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200000, China
| | - Shun-Xiao Zhang
- Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200000, China
| | - Yan Zhang
- Department of Endocrinology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200000, China
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Kazakova P, Abasolo N, de Cripan SM, Marquès E, Cereto-Massagué A, Garcia L, Canela N, Tormo R, Torrell H. Gut Microbiome and Small RNA Integrative-Omic Perspective of Meconium and Milk-FED Infant Stool Samples. Int J Mol Sci 2023; 24:ijms24098069. [PMID: 37175775 PMCID: PMC10179101 DOI: 10.3390/ijms24098069] [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: 03/30/2023] [Revised: 04/24/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023] Open
Abstract
The human gut microbiome plays an important role in health, and its initial development is conditioned by many factors, such as feeding. It has also been claimed that this colonization is guided by bacterial populations, the dynamic virome, and transkingdom interactions between host and microbial cells, partially mediated by epigenetic signaling. In this article, we characterized the bacteriome, virome, and smallRNome and their interaction in the meconium and stool samples from infants. Bacterial and viral DNA and RNA were extracted from the meconium and stool samples of 2- to 4-month-old milk-fed infants. The bacteriome, DNA and RNA virome, and smallRNome were assessed using 16S rRNA V4 sequencing, viral enrichment sequencing, and small RNA sequencing protocols, respectively. Data pathway analysis and integration were performed using the R package mixOmics. Our findings showed that the bacteriome differed among the three groups, while the virome and smallRNome presented significant differences, mainly between the meconium and stool of milk-fed infants. The gut environment is rapidly acquired after birth, and it is highly adaptable due to the interaction of environmental factors. Additionally, transkingdom interactions between viruses and bacteria can influence host and smallRNome profiles. However, virome characterization has several protocol limitations that must be considered.
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Affiliation(s)
- Polina Kazakova
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | - Nerea Abasolo
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | - Sara Martinez de Cripan
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | | | - Adrià Cereto-Massagué
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | - Lorena Garcia
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | - Núria Canela
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
| | - Ramón Tormo
- ESPGHAN, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, 1201 Geneva, Switzerland
- Gastroenterology and Nutrition Pediatric Center, 08006 Barcelona, Spain
| | - Helena Torrell
- Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
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Exosome-Mediated miR-4792 Transfer Promotes Bladder Cancer Cell Proliferation via Enhanced FOXC1/c-Myc Signaling and Warburg Effect. JOURNAL OF ONCOLOGY 2022; 2022:5680353. [PMID: 35096062 PMCID: PMC8791735 DOI: 10.1155/2022/5680353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/30/2021] [Accepted: 12/17/2021] [Indexed: 12/05/2022]
Abstract
Bladder cancer is the second-most common malignancy in the urogenital system and the most common in men. However, our understanding of the driving mechanisms of bladder cancer remains incomplete. The forkhead box (FOX) family of transcription factors is implicated in urogenital development and bladder malignancies. Many exosomal microRNAs have been identified as regulators and mediators of the expression of FOX, including the expression of FOXC1. miR-4792 has been known as a tumor miRNA suppressor. However, the function of miR-4792/FOXC1 signaling in bladder cancer development remains unknown. Here, we studied the role of miR-4792/FOXC1 signaling in bladder cancer by using multiple bladder cancer cell lines and bladder cancer mouse models through in vitro and in vivo approaches. We showed that FOXC1 is highly expressed in multiple bladder cancer cell lines and bladder tumor tissues. The knockdown of FOXC1 expression in bladder cancer cell lines decreases c-Myc expression levels, retards cell growth, and reduces aerobic glycolysis (also known as the Warburg effect) and lactic acid content. By contrast, the overexpression of FOXC1 elicits the opposite effects. FOXC1-downregulated bladder cancer cells form significantly smaller tumors in vivo. The inhibition of c-Myc reverses the effects of FOXC1 overexpression and leads to reduced cell proliferation, aerobic glycolysis, and lactic acid content. miR-4792 expression is downregulated in bladder tumor tissues. miR-4792 exposure to bladder cancer cells reduces the expression levels of FOXC1 and c-Myc, slows down cell growth, and decreases aerobic glycolysis and lactic acid content. However, the enhanced miR-4792 expression elicits opposite effects. These findings provided the first evidence that the exosome-mediated delivery of miR-4792 could play an important role in bladder cancer development through the downregulation of FOXC1 and c-Myc, which further inhibited aerobic glycolysis and lactic acid content.
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Liu Y, Li Y, Chen W, Ye X, Jia R, Yu L, Tang Q, Tu P, Jiang Y, Chu Q, Zheng X. Tetrastigma hemsleyanum flavones exert anti-hepatic carcinoma property both in vitro and in vivo. FOOD QUALITY AND SAFETY 2021. [DOI: 10.1093/fqsafe/fyab025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Abstract:
Tetrastigma hemsleyanum has been regarded as an anticancer food in China. However, its corresponding mechanisms remains unclear. Thus, in this study, the antitumor activity of flavones-rich fraction of root of Tetrastigma hemsleyanum (FRTH) was investigated in vitro and in vivo. The results indicated that FRTH could inhibit the proliferation and migration of HepG2 cells in vitro by PI3K/AKT pathway. FRTH could increase the ROS level and change the mitochondrial membrane potential (MMP) in HepG2 cells. In addition, FRTH treatment (300, 600 mg/kg BW) significantly suppressed tumor growth on HepG2 tumor-bearing nude mice. Besides, immunohistochemistry assays and western blotting revealed that FRTH enhanced the expression level of Bax/Bcl-2, cytochrome C, Caspase-3, caspase-9, Cleaved-caspase-3, and downregulated the expression level of CD31, ki67 and VEGF in HepG2 tumor-bearing mice. Our study suggests Tetrastigma hemsleyanum as a promising candidate medicine for liver cancer treatment.
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Zhang S, Cui T, Duan Y, Zhang H, Wang B, Chen H, Ni J, Shen Y, Xiao-Ai Lv. Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy. Clin Breast Cancer 2021; 22:89-97. [PMID: 34535390 DOI: 10.1016/j.clbc.2021.07.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/13/2021] [Accepted: 07/29/2021] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against drug resistance in triple-negative breast cancer (TNBC). METHODS Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol) cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry, CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively. RESULTS In MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, up-regulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on cell activities were similar to the results of mTOR silencing. After RTEs & Taxol injection, xenograft tumor was smaller, and AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased. CONCLUSION RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy. MICRO RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-468/Taxol cells. We may provide a new potential strategy for TNBC treatment.
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Affiliation(s)
- Shuo Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Tongxing Cui
- General Surgery department, the affiliated Qingdao Municipal Hospital of Qingdao university, Qingdao 266000, China
| | - Yin Duan
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Hongchen Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Bei Wang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Huiling Chen
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Junjie Ni
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yilin Shen
- The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiao-Ai Lv
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
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Liu P, Guo Y, He Y, Tang Y. Radix Tetrastigma Hemsleyani Flavone Inhibits the Occurrence and Development of Ovarian Cancer Cells by Regulating miRNA-4458 Expression. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Ovarian cancer (OC) has been identified to have the highest mortality rate among gynecological tumors. Most patients are diagnosed at an advanced stage because of its asymptomatic nature and a lack of effective early diagnostic methods. Advanced-stage cancer cells are prone to metastasis
which reduces the efficacy of standard therapies. Thus, we evaluated the effect of different concentrations of radix tetrastigma hemsleyani flavone (RTHF) on SKOV3 OC cells. Our findings indicated a significant inhibition in cell proliferation, migration, and invasion. RTHF treatment resulted
in a significant increase in p21 protein expression, whereas the expression of cyclin D1, MMP-2, and MMP-9 has reportedly decreased. In addition, the expression of miRNA-4458 expression increased significantly in a dose-dependent manner. Co-transfection of miRNA-4458 mimics into SKOV3 cells
revealed that overexpressed miRNA-4458 can increase SKOV3 cell proliferation and p21 protein expression. Reduced cell migration and invasion were also observed along with decreased expression of cyclin D1, MMP-2, and MMP-9. Furthermore, inhibition of miRNA-4458 expression reversed the RTHF
effect on SKOV3 cell proliferation, migration, invasion, and cyclin D1, MMP-2, and MMP-9 expression. These results indicate that RTHF reduces the proliferation, migration, and invasion of OC cells, and the underlying mechanism is associated with the upregulation of miRNA-4458 expression. These
findings provide a new treatment strategy for advanced OC.
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Affiliation(s)
- Ping Liu
- Department of Obstetrics and Gynecology, The Affiliated Hospital North China University of Science and Technology, Tangshan 063000, Hebei, PR China
| | - Yanjuan Guo
- Department of Obstetrics and Gynecology, The Affiliated Hospital North China University of Science and Technology, Tangshan 063000, Hebei, PR China
| | - Yanfang He
- Department of Obstetrics and Gynecology, The Affiliated Hospital North China University of Science and Technology, Tangshan 063000, Hebei, PR China
| | - Yajuan Tang
- Department of Obstetrics and Gynecology, The Affiliated Hospital North China University of Science and Technology, Tangshan 063000, Hebei, PR China
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Tabari D, Scholl C, Steffens M, Weickhardt S, Elgner F, Bender D, Herrlein ML, Sabino C, Semkova V, Peitz M, Till A, Brüstle O, Hildt E, Stingl J. Impact of Zika Virus Infection on Human Neural Stem Cell MicroRNA Signatures. Viruses 2020; 12:E1219. [PMID: 33121145 PMCID: PMC7693339 DOI: 10.3390/v12111219] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/09/2020] [Accepted: 10/23/2020] [Indexed: 12/11/2022] Open
Abstract
Zika virus (ZIKV) is a mosquito-borne virus, which can cause brain abnormalities in newborns, including microcephaly. MicroRNAs (miRNAs) are small non-coding RNAs, which post- transcriptionally regulate gene expression. They are involved in various processes including neurological development and host responses to viral infection, but their potential role in ZIKV pathogenesis remains poorly understood. MiRNAs can be incorporated into extracellular vesicles (EVs) and mediate cell-to-cell communication. While it is well known that in viral infections EVs carrying miRNAs can play a crucial role in disease pathogenesis, ZIKV effects on EV-delivered miRNAs and their contribution to ZIKV pathogenesis have not been elucidated. In the present study, we profiled intracellular and EV-derived miRNAs by next generation sequencing and analyzed the host mRNA transcriptome of neural stem cells during infection with ZIKV Uganda and French Polynesia strains. We identified numerous miRNAs, including miR-4792, which were dysregulated at the intracellular level and had altered levels in EVs during ZIKV infection. Integrated analyses of differentially expressed genes and miRNAs showed that ZIKV infection had an impact on processes associated with neurodevelopment and oxidative stress. Our results provide insights into the roles of intracellular and EV-associated host miRNAs in ZIKV pathogenesis.
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Affiliation(s)
- Denna Tabari
- Research Division, Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany; (D.T.); (M.S.); (S.W.)
| | - Catharina Scholl
- Research Division, Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany; (D.T.); (M.S.); (S.W.)
| | - Michael Steffens
- Research Division, Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany; (D.T.); (M.S.); (S.W.)
| | - Sandra Weickhardt
- Research Division, Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany; (D.T.); (M.S.); (S.W.)
| | - Fabian Elgner
- Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany; (F.E.); (D.B.); (M.-L.H.); (C.S.); (E.H.)
| | - Daniela Bender
- Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany; (F.E.); (D.B.); (M.-L.H.); (C.S.); (E.H.)
| | - Marie-Luise Herrlein
- Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany; (F.E.); (D.B.); (M.-L.H.); (C.S.); (E.H.)
| | - Catarina Sabino
- Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany; (F.E.); (D.B.); (M.-L.H.); (C.S.); (E.H.)
| | - Vesselina Semkova
- Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn Medical Faculty & University Hospital Bonn, 53127 Bonn, Germany; (V.S.); (M.P.); (A.T.); (O.B.)
| | - Michael Peitz
- Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn Medical Faculty & University Hospital Bonn, 53127 Bonn, Germany; (V.S.); (M.P.); (A.T.); (O.B.)
- Cell Programming Core Facility, Medical Faculty, University of Bonn, 53172 Bonn, Germany
| | - Andreas Till
- Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn Medical Faculty & University Hospital Bonn, 53127 Bonn, Germany; (V.S.); (M.P.); (A.T.); (O.B.)
| | - Oliver Brüstle
- Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn Medical Faculty & University Hospital Bonn, 53127 Bonn, Germany; (V.S.); (M.P.); (A.T.); (O.B.)
| | - Eberhard Hildt
- Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany; (F.E.); (D.B.); (M.-L.H.); (C.S.); (E.H.)
| | - Julia Stingl
- Department of Clinical Pharmacology, University Hospital, RWTH Aachen University, 52074 Aachen, Germany;
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Zhu R, Xu X, Ying J, Cao G, Wu X. The Phytochemistry, Pharmacology, and Quality Control of Tetrastigma hemsleyanum Diels & Gilg in China: A Review. Front Pharmacol 2020; 11:550497. [PMID: 33101019 PMCID: PMC7546407 DOI: 10.3389/fphar.2020.550497] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 09/04/2020] [Indexed: 12/18/2022] Open
Abstract
Tetrastigma hemsleyanum Diels & Gilg (TDG), the family member of Vitaceae, is a traditional herbal medicine in China. The root of TDG can be immediately used after cleaning the muddy soil, and can be dehydrated for dry use. TDG is able to be collected all year round, which is commonly used in the treatment of hepatitis, infantile high fever, snake bite, etc. Based on phytochemistry, the chemical components of TDG are divided into flavonoids, phenolic acids, terpenes, steroids, polysaccharide, and other compounds, showing many pharmacological effects which include anti-tumor, anti-oxidation, anti-inflammatory, antipyretic, analgesic, and immunomodulatory activity, as well as other activities. Currently, TDG involves some problems of the reduction of wild resources, the backward processing methods, and storage difficulties as well as the imperfection of detection methods. Therefore, this review summarizes the literature of the past 20 years, and the purpose of this review is to summarize the recent researches on the phytochemistry, pharmacology, quality control, and clinical application of TDG. The above discussions provide new insights for the future research on TDG.
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Affiliation(s)
- Ruyi Zhu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaofen Xu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jialiang Ying
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Gang Cao
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Wu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Hadj-Moussa H, Zhang J, Pifferi F, Perret M, Storey KB. Profiling torpor-responsive microRNAs in muscles of the hibernating primate Microcebus murinus. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 2020; 1863:194473. [DOI: 10.1016/j.bbagrm.2019.194473] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 12/09/2019] [Accepted: 12/09/2019] [Indexed: 12/25/2022]
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Zhou W, Wang X, Yin D, Xue L, Ma Z, Wang Z, Zhang Q, Zhao Z, Wang H, Sun Y, Yang Y. Effect of miR-140-5p on the regulation of proliferation and apoptosis in NSCLC and its underlying mechanism. Exp Ther Med 2019; 18:1350-1356. [PMID: 31363375 DOI: 10.3892/etm.2019.7701] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 01/11/2019] [Indexed: 12/18/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for ~80% of lung cancer cases. According to novel research, numerous microRNAs (miRs) have been suggested to function as important regulators of cancer. In addition, the expression of miR-140-5p is decreased in patients with NSCLC. Therefore, it is important to further elucidate the role of miR-140-5p in NSCLC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used in order to investigate the expression of miR-140-5p in NSCLC tissues and matched normal tissues and to determine miR-140-5p levels following transfection with mimics into A549 lung cancer cells. Targetscan software was used to predict the oncogene target of miR-140-5p. This analysis revealed that YES proto-oncogene 1 (YES1) includes a target site for miR-140-5p binding. The results revealed that YES1 is a potential target gene of miR-140-5p, and this was further confirmed by the results of luciferase reporter assays, which demonstrated that miR-140-5p directly targeted the predicted binding site in the 3'-untranslated region of YES1. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to determine the levels of cell viability and apoptosis. Western blot assays was performed to investigate the expression levels of YES1 and proteins associated with apoptosis in A549 cells following transfection. The results revealed that miR-140-5p expression was significantly downregulated in NSCLC tissues compared with matched normal tissues. The expression of miR-140-5p was significantly increased following transfection with miR-140-5p mimics. The results of CCK-8 and flow cytometry assays indicated that miR-140-5p inhibited proliferation and induced apoptosis of tumor cells. Western blot analysis and RT-qPCR revealed that YES1 and B-cell lymphoma 2 (Bcl-2) mRNA and protein expression levels were markedly decreased in A549 cells, while Bcl-2 associated X (Bax) and caspase-3 expression levels increased significantly following transfection with miR-140-5p mimics compared with the negative control group. In conclusion, miR-140-5p may induce apoptosis in A549 cells by targeting YES1 and regulating the expression of apoptosis-associated proteins Bcl-2, Bax and caspase-3.
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Affiliation(s)
- Wenwen Zhou
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Xiaoyu Wang
- Foundation and Clinic of Malignant Tumor, Postgraduate College, Chengde Medical University, Chengde, Hebei 067000, P.R. China
| | - Duanduan Yin
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Lei Xue
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Zhongfeng Ma
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Zhenzhen Wang
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Qianyi Zhang
- Division of Pharmacy, University of Tasmania, Hobart, Tasmania 7005, Australia
| | - Zishu Zhao
- Foundation and Clinic of Malignant Tumor, Postgraduate College, Chengde Medical University, Chengde, Hebei 067000, P.R. China
| | - Haixia Wang
- Foundation and Clinic of Malignant Tumor, Postgraduate College, Hebei Medical University, Shijiazhuang, Hebei 051117, P.R. China
| | - Yan Sun
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Yanhong Yang
- Department of Oncology, Qinhuangdao First People's Hospital, Qinhuangdao, Hebei 066000, P.R. China
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