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Niri T, Inoue SI, Akazawa S, Nishikido S, Miwa M, Kobayashi M, Yui K, Okita M, Kawakami A, Abiru N. Essential role of interferon-regulatory factor 4 in regulating diabetogenic CD4+ T and innate immune cells in autoimmune diabetes in NOD mice. Clin Exp Immunol 2025; 219:uxae093. [PMID: 39432837 PMCID: PMC11773818 DOI: 10.1093/cei/uxae093] [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: 04/19/2024] [Revised: 09/16/2024] [Accepted: 10/19/2024] [Indexed: 10/23/2024] Open
Abstract
Haploinsufficiency of the transcription factor interferon-regulatory factor 4 (IRF4) prevents the onset of spontaneous diabetes in NOD mice. However, the immunological mechanisms of the IRF4-mediated disease regulation remain unclear. This study aims to investigate the role of IRF4 in the pathogenesis of autoimmune diabetes by conducting adoptive transfer experiments using donor IRF4 gene-deficient CD4+ T cells from BDC2.5-transgenic (Tg) NOD mice and recipient Rag1-knockout NOD mice, respectively. Through this approach, we analyzed both clinical and immunological phenotypes of the recipient mice. Additionally, IRF4-deficient BDC2.5 CD4+ T cells were stimulated to assess their immunological and metabolic phenotypes in vitro. The findings revealed that diabetes was completely prevented in the recipients with Irf4-/- T cells and was approximately 50% lower in those with Irf4+/- T cells than in wild type (WT) controls, whereas Irf4-/- recipients with WT T cells only showed a delayed onset of diabetes. Islet-infiltrating T cells isolated from recipients with Irf4+/- T cells exhibited significantly lower proliferation and IFN-γ/IL-17 double-positive cell fraction rates compared with those in WT controls. Irf4-/- BDC2.5 CD4+ T cells stimulated in vitro showed a reduced number of cell divisions, decreased antigen-specific T-cell markers, and impairment of glycolytic capacity compared with those observed in WT controls. We concluded that IRF4 predominantly regulates the diabetogenic potential in a dose-dependent manner by mediating the proliferation and differentiation of islet-infiltrating T cells while playing an adjunctive role in the innate immune responses toward diabetes progression in NOD mice.
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Affiliation(s)
- Tetsuro Niri
- Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shin-Ichi Inoue
- Division of Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Satoru Akazawa
- Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinpei Nishikido
- Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaki Miwa
- Diabetes Care Support Center, Nagasaki University Hospital, Nagasaki, Japan
| | | | - Katsuyuki Yui
- Shionogi Global Infectious Diseases Division, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Minoru Okita
- Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Atsushi Kawakami
- Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Norio Abiru
- Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Lou Y, Xie Y, Jiang Q, Huang S, Wang X, Wang L, Wang H, Cao S. The effect of sarcopenic obesity on glycaemic status based on fasting plasma glucose and glycated haemoglobin: A prospective cohort study. Diabetes Obes Metab 2025; 27:291-299. [PMID: 39434441 DOI: 10.1111/dom.16016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/28/2024] [Accepted: 10/02/2024] [Indexed: 10/23/2024]
Abstract
AIM To investigate the effect of sarcopenic obesity on the progression of glycaemic status in middle-aged and older adults without diabetes. MATERIALS AND METHODS This research involved 4637 participants without diabetes from the China Health and Retirement Longitudinal Study 2011-2015. Sarcopenic obesity at baseline was evaluated based on the Asian Working Group for Sarcopenia 2019 criteria. According to the American Diabetes Association criteria, we used fasting plasma glucose and glycated haemoglobin to define glycaemic status. Cox proportional hazard models were applied to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS The mean age of included participants was 58.98 ± 8.82 years, and 45.35% were men. During 18,497 person-years of follow-up, 1743 (37.59%) cases with glycaemic status progression were identified. Compared with participants without sarcopenia and obesity, participants with sarcopenic obesity, but not sarcopenia only or obesity only, exhibited a higher risk of progression from normoglycaemia to diabetes (HR = 2.11; 95% CI: 1.10-4.04). Moreover, participants with sarcopenic obesity (HR = 1.65; 95% CI: 1.04-2.63), sarcopenia only (HR = 1.78; 95% CI: 1.11-2.86), or obesity only (HR = 2.00; 95% CI: 1.29-3.12) had increased the risk of progression from prediabetes to diabetes. CONCLUSIONS The effect of sarcopenic obesity on the progression of glycaemic status based on fasting plasma glucose and glycated haemoglobin may be more pronounced than that of sarcopenia only or obesity only.
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Affiliation(s)
- Yiling Lou
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yulin Xie
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingqing Jiang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shen Huang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohan Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linlin Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hengchang Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiyi Cao
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Ansari P, Khan JT, Chowdhury S, Reberio AD, Kumar S, Seidel V, Abdel-Wahab YHA, Flatt PR. Plant-Based Diets and Phytochemicals in the Management of Diabetes Mellitus and Prevention of Its Complications: A Review. Nutrients 2024; 16:3709. [PMID: 39519546 PMCID: PMC11547802 DOI: 10.3390/nu16213709] [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: 08/22/2024] [Revised: 09/27/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs presents limitations in terms of side effects, accessibility, and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function, and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, and retinopathy, which can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, and condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods.
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Affiliation(s)
- Prawej Ansari
- Comprehensive Diabetes Center, Heersink School of Medicine, University of Alabama, Birmingham (UAB), Birmingham, AL 35233, USA
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
| | - Joyeeta T. Khan
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USA
| | - Suraiya Chowdhury
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Alexa D. Reberio
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Sandeep Kumar
- Comprehensive Diabetes Center, Heersink School of Medicine, University of Alabama, Birmingham (UAB), Birmingham, AL 35233, USA
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK;
| | - Yasser H. A. Abdel-Wahab
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
| | - Peter R. Flatt
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
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Chen R, Xie G, Lin Z, Gu G, Yu Y, Yu J, Liu Z. Predicting Microbe-Disease Associations Based on a Linear Neighborhood Label Propagation Method with Multi-order Similarity Fusion Learning. Interdiscip Sci 2024; 16:345-360. [PMID: 38436840 DOI: 10.1007/s12539-024-00607-0] [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: 08/11/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 03/05/2024]
Abstract
Computational approaches employed for predicting potential microbe-disease associations often rely on similarity information between microbes and diseases. Therefore, it is important to obtain reliable similarity information by integrating multiple types of similarity information. However, existing similarity fusion methods do not consider multi-order fusion of similarity networks. To address this problem, a novel method of linear neighborhood label propagation with multi-order similarity fusion learning (MOSFL-LNP) is proposed to predict potential microbe-disease associations. Multi-order fusion learning comprises two parts: low-order global learning and high-order feature learning. Low-order global learning is used to obtain common latent features from multiple similarity sources. High-order feature learning relies on the interactions between neighboring nodes to identify high-order similarities and learn deeper interactive network structures. Coefficients are assigned to different high-order feature learning modules to balance the similarities learned from different orders and enhance the robustness of the fusion network. Overall, by combining low-order global learning with high-order feature learning, multi-order fusion learning can capture both the shared and unique features of different similarity networks, leading to more accurate predictions of microbe-disease associations. In comparison to six other advanced methods, MOSFL-LNP exhibits superior prediction performance in the leave-one-out cross-validation and 5-fold validation frameworks. In the case study, the predicted 10 microbes associated with asthma and type 1 diabetes have an accuracy rate of up to 90% and 100%, respectively.
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Affiliation(s)
- Ruibin Chen
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China
| | - Guobo Xie
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China
| | - Zhiyi Lin
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China.
| | - Guosheng Gu
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China.
| | - Yi Yu
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China
| | - Junrui Yu
- School of Computer, Guangdong University of Technology, Guangzhou, 510000, China
| | - Zhenguo Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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Park SJ, Kim YY, Han JY, Kim SW, Kim H, Ku SY. Advancements in Human Embryonic Stem Cell Research: Clinical Applications and Ethical Issues. Tissue Eng Regen Med 2024; 21:379-394. [PMID: 38502279 PMCID: PMC10987435 DOI: 10.1007/s13770-024-00627-3] [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: 12/12/2023] [Revised: 01/05/2024] [Accepted: 01/08/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos. METHOD This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. RESULTS Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. CONCLUSION The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.
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Affiliation(s)
- Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yoon Young Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Ji Yeon Han
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sung Woo Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hoon Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Seung-Yup Ku
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea.
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea.
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
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Zakarneh S, Khial Y, Tayyem R. Dietary Factors Associated with Glycemic Control in Children and Adolescents with Type 1 Diabetes. Curr Pediatr Rev 2024; 21:29-39. [PMID: 37608667 DOI: 10.2174/1573396320666230822095948] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/26/2023] [Accepted: 06/21/2023] [Indexed: 08/24/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from the autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycemia. It is a common chronic disease in childhood, with a prevalence of 1 in 300 children in the United States and an increasing incidence of 2-5% annually, worldwide. Managing T1DM requires regular insulin administration, adjustment of food intake and exercise, and a comprehensive understanding of nutrition. This review aims to explore the relationship between dietary factors, physical activity, obesity, genetics, and glycemic control in children and adolescents with T1DM. To conduct this review, we conducted a thorough search of publications from December 2004 through April 2022 using PubMed, ScienceDirect, and Embase databases. Key topics included obesity, children, adolescents, nutrients, carbohydrates, proteins, fat, water-soluble vitamins, fat-soluble vitamins, dietary patterns, fruits and vegetables, physical activity, genetics, food habits, carbohydrate count and environmental factors.
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Affiliation(s)
- Sara Zakarneh
- Department of Nutrition & Food Technology, Faculty of Agriculture, The University of Jordan, Amman, 11942, Jordan
| | - Yasmin Khial
- Department of Human Nutrition, College of Health Science, Qatar University, Doha, Qatar
| | - Reema Tayyem
- Department of Human Nutrition, College of Health Science, Qatar University, Doha, Qatar
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Tucker TR, Knitter CA, Khoury DM, Eshghi S, Tran S, Sharrock AV, Wiles TJ, Ackerley DF, Mumm JS, Parsons MJ. An inducible model of chronic hyperglycemia. Dis Model Mech 2023; 16:dmm050215. [PMID: 37401381 PMCID: PMC10417516 DOI: 10.1242/dmm.050215] [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: 04/04/2023] [Accepted: 06/28/2023] [Indexed: 07/05/2023] Open
Abstract
Transgene driven expression of Escherichia coli nitroreductase (NTR1.0) renders animal cells susceptible to the antibiotic metronidazole (MTZ). Many NTR1.0/MTZ ablation tools have been reported in zebrafish, which have significantly impacted regeneration studies. However, NTR1.0-based tools are not appropriate for modeling chronic cell loss as prolonged application of the required MTZ dose (10 mM) is deleterious to zebrafish health. We established that this dose corresponds to the median lethal dose (LD50) of MTZ in larval and adult zebrafish and that it induced intestinal pathology. NTR2.0 is a more active nitroreductase engineered from Vibrio vulnificus NfsB that requires substantially less MTZ to induce cell ablation. Here, we report on the generation of two new NTR2.0-based zebrafish lines in which acute β-cell ablation can be achieved without MTZ-associated intestinal pathology. For the first time, we were able to sustain β-cell loss and maintain elevated glucose levels (chronic hyperglycemia) in larvae and adults. Adult fish showed significant weight loss, consistent with the induction of a diabetic state, indicating that this paradigm will allow the modeling of diabetes and associated pathologies.
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Affiliation(s)
- Tori R. Tucker
- Department of Developmental and Cell Biology, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - Courtney A. Knitter
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - Deena M. Khoury
- Department of Developmental and Cell Biology, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - Sheida Eshghi
- Department of Developmental and Cell Biology, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - Sophia Tran
- Department of Developmental and Cell Biology, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - Abigail V. Sharrock
- School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
| | - Travis J. Wiles
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
| | - David F. Ackerley
- School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand
| | - Jeff S. Mumm
- Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA
| | - Michael J. Parsons
- Department of Developmental and Cell Biology, University of California, Irvine, Natural Sciences II, Irvine, CA 92697, USA
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da Silva DR, Gonzalez CF, Lorca G. Internalization of extracellular vesicles from Lactobacillus johnsonii N6.2 elicit an RNA sensory response in human pancreatic cell lines. JOURNAL OF EXTRACELLULAR BIOLOGY 2023; 2:e101. [PMID: 37720361 PMCID: PMC10500552 DOI: 10.1002/jex2.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 06/21/2023] [Accepted: 06/30/2023] [Indexed: 09/19/2023]
Abstract
Cells of all domains of life can secrete extracellular vesicles (EV). These secreted vesicles have been indicated as vehicles carrying molecules that facilitate intra- and inter-species interaction. Lactobacillus johnsonii N6.2, a bacterium used in probiotic preparations, has been shown to produce nano-sized EV. In the present work we used L. johnsonii N6.2 EV, concentrated from exosome depleted MRS supernatant, to identify the uptake mechanisms of EV and the impact of the RNA cargo in the EV on the upregulation of the cellular response of βlox5 human pancreatic cells. Using eukaryotic uptake inhibitors, it was found that EV are internalized by the clathrin/dynamin mediated endocytosis pathway. Further co-localization experiments with the endosome markers RAB5, RAB7 and LAMP1 as well as calcein indicated that EV escape the endosome shortly after RAB7 fusion. Using the expression of the 2',5'-oligoadenylate synthetase (OAS) host pathway, previously identified as targeted by L. johnsonii EV, we found that the host cellular response to the EV are dependent on the integrity of the external components of the EV as well as on the RNA cargo. Global transcriptome analysis was performed on EV and the bacterial whole cell. It was found that the RNA transcripts found within the EV largely represent the most abundantly transcribed genes in the bacterial cells such as those associated with protein synthesis and glycolysis. Further analysis showed an enrichment of smaller size transcripts as well as those encoding for membrane bound or extracellular proteins in L. johnsonii's EV.
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Affiliation(s)
- Danilo R. da Silva
- Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural SciencesUniversity of FloridaGainesvilleFloridaUSA
| | - Claudio F. Gonzalez
- Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural SciencesUniversity of FloridaGainesvilleFloridaUSA
| | - Graciela Lorca
- Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural SciencesUniversity of FloridaGainesvilleFloridaUSA
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Martín-Carro B, Donate-Correa J, Fernández-Villabrille S, Martín-Vírgala J, Panizo S, Carrillo-López N, Martínez-Arias L, Navarro-González JF, Naves-Díaz M, Fernández-Martín JL, Alonso-Montes C, Cannata-Andía JB. Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities. Int J Mol Sci 2023; 24:10309. [PMID: 37373455 DOI: 10.3390/ijms241210309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/14/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Preclinical biomedical models are a fundamental tool to improve the knowledge and management of diseases, particularly in diabetes mellitus (DM) since, currently, the pathophysiological and molecular mechanisms involved in its development are not fully clarified, and there is no treatment to cure DM. This review will focus on the features, advantages and limitations of some of the most used DM models in rats, such as the spontaneous models: Bio-Breeding Diabetes-Prone (BB-DP) and LEW.1AR1-iddm, as representative models of type 1 DM (DM-1); the Zucker diabetic fatty (ZDF) and Goto-kakizaki (GK) rats, as representative models of type 2 DM (DM-2); and other models induced by surgical, dietary and pharmacological-alloxan and streptozotocin-procedures. Given the variety of DM models in rats, as well as the non-uniformity in the protocols and the absence of all the manifestation of the long-term multifactorial complications of DM in humans, the researchers must choose the one that best suits the final objectives of the study. These circumstances, added to the fact that most of the experimental research in the literature is focused on the study of the early phase of DM, makes it necessary to develop long-term studies closer to DM in humans. In this review, a recently published rat DM model induced by streptozotocin injection with chronic exogenous administration of insulin to reduce hyperglycaemia has also been included in an attempt to mimic the chronic phase of DM in humans.
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Affiliation(s)
- Beatriz Martín-Carro
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Javier Donate-Correa
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Research Unit, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Sara Fernández-Villabrille
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Julia Martín-Vírgala
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Sara Panizo
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Natalia Carrillo-López
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Laura Martínez-Arias
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Juan F Navarro-González
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Research Unit, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- Nephrology Service, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Manuel Naves-Díaz
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - José L Fernández-Martín
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cristina Alonso-Montes
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Jorge B Cannata-Andía
- Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040 (Kidney Disease), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Department of Medicine, Universidad de Oviedo, 33006 Oviedo, Spain
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10
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Yuan YG, Wang JL, Zhang YX, Li L, Reza AMMT, Gurunathan S. Biogenesis, Composition and Potential Therapeutic Applications of Mesenchymal Stem Cells Derived Exosomes in Various Diseases. Int J Nanomedicine 2023; 18:3177-3210. [PMID: 37337578 PMCID: PMC10276992 DOI: 10.2147/ijn.s407029] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/31/2023] [Indexed: 06/21/2023] Open
Abstract
Exosomes are nanovesicles with a wide range of chemical compositions used in many different applications. Mesenchymal stem cell-derived exosomes (MSCs-EXOs) are spherical vesicles that have been shown to mediate tissue regeneration in a variety of diseases, including neurological, autoimmune and inflammatory, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells due to the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. MSCs-EXOs exhibit cytokine storm-mitigating properties in response to COVID-19. This review discussed the potential function of MSCs-EXOs in a variety of diseases including neurological, notably epileptic encephalopathy and Parkinson's disease, cancer, angiogenesis, autoimmune and inflammatory diseases. We provided an overview of exosome biogenesis and factors that regulate exosome biogenesis. Additionally, we highlight the functions and potential use of MSCs-EXOs in the treatment of the inflammatory disease COVID-19. Finally, we covered a strategies and challenges of MSCs-EXOs. Finally, we discuss conclusion and future perspectives of MSCs-EXOs.
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Affiliation(s)
- Yu-Guo Yuan
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Jia-Lin Wang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Ya-Xin Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Ling Li
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
- Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Abu Musa Md Talimur Reza
- Department of Molecular Biology and Genetics, Faculty of Science, Gebze Technical University, Gebze, Kocaeli, Türkiye
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11
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Giannoukakis N. Tolerogenic dendritic cells in type 1 diabetes: no longer a concept. Front Immunol 2023; 14:1212641. [PMID: 37388741 PMCID: PMC10303908 DOI: 10.3389/fimmu.2023.1212641] [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: 04/26/2023] [Accepted: 05/31/2023] [Indexed: 07/01/2023] Open
Abstract
Tolerogenic dendritic cells (tDC) arrest the progression of autoimmune-driven dysglycemia into clinical, insulin-requiring type 1 diabetes (T1D) and preserve a critical mass of β cells able to restore some degree of normoglycemia in new-onset clinical disease. The safety of tDC, generated ex vivo from peripheral blood leukocytes, has been demonstrated in phase I clinical studies. Accumulating evidence shows that tDC act via multiple layers of immune regulation arresting the action of pancreatic β cell-targeting effector lymphocytes. tDC share a number of phenotypes and mechanisms of action, independent of the method by which they are generated ex vivo. In the context of safety, this yields confidence that the time has come to test the best characterized tDC in phase II clinical trials in T1D, especially given that tDC are already being tested for other autoimmune conditions. The time is also now to refine purity markers and to "universalize" the methods by which tDC are generated. This review summarizes the current state of tDC therapy for T1D, presents points of intersection of the mechanisms of action that the different embodiments use to induce tolerance, and offers insights into outstanding matters to address as phase II studies are imminent. Finally, we present a proposal for co-administration and serially-alternating administration of tDC and T-regulatory cells (Tregs) as a synergistic and complementary approach to prevent and treat T1D.
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Affiliation(s)
- Nick Giannoukakis
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States
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12
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Neshat SY, Bauer SJ, Rhodes KR, Quiroz VM, Wong VW, Lowmaster SM, Tzeng SY, Green JJ, Doloff JC. Improvement of Islet Engrafts via Treg Induction Using Immunomodulating Polymeric Tolerogenic Microparticles. ACS Biomater Sci Eng 2023; 9:3522-3534. [PMID: 37233985 DOI: 10.1021/acsbiomaterials.3c00329] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Type 1 diabetes (T1D) is a life-threatening condition for which islet transplantation offers a way to extend longevity and vastly improve quality of life, but the degree and duration of success can vary greatly due to the patient's protective immunity against foreign material. The field is in need of cellular engineering modalities to promote a localized, tolerogenic environment to protect transplanted islet tissue. Artificial antigen-presenting cells (aAPCs) can be designed exogenously to mimic immune cells, such as dendritic cells, and administered to patients, allowing greater control over T cell differentiation. As regulatory T cell (Treg) modulation can reduce the activity of cytotoxic T-effector populations, this strategy can be used to promote immune acceptance of both biomaterials and cellular transplants, such as islets. A new class of poly(lactic-co-glycolic acid) (PLGA) and PLGA/PBAE-blend aAPCs containing transforming growth factor beta and conjugated with anti-CD3 and anti-CD28 antibodies, called tolerogenic aAPCs (TolAPCs), are specifically designed to generate a tolerogenic response by inducing Tregs. We characterized TolAPCs' physical and chemical properties via advanced particle imaging and sizing modalities and investigated their impact on the local and systemic immune system across BALB/c and C57BL/6 mouse strains as well as healthy male and female mice via histologic, gene expression, and immunofluorescence staining methods. Strain-specific differences were observed, whereas sex made no difference in the TolAPC response. TolAPCs stimulated the expansion of FOXP3+ Tregs and provided islet cell protection, maintaining improved glucose-stimulated insulin secretion in vitro when co-cultured with cytotoxic CD8+ T cells. We also explored the ability of this TolAPC platform to promote tolerance in a streptozotocin-induced murine T1D C57BL/6 mouse model. We achieved partial islet protection over the first few days following co-injection with PLGA/PBAE TolAPCs; however, grafts failed soon thereafter. Analysis of the local injection site demonstrated that other immune cell types, including APCs and cytotoxic natural killer cells, increased in the islet injection site. While we aimed to promote a localized tolerogenic microenvironment in vivo using biodegradable TolAPCs to induce Tregs and extend islet transplant durability, further TolAPC improvements will be required to both elongate efficacy and control additional immune cell responders.
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Affiliation(s)
- Sarah Y Neshat
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Stuart J Bauer
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Kelly R Rhodes
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Victor M Quiroz
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
| | - Valerie W Wong
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
| | - Shirley M Lowmaster
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
| | - Stephany Y Tzeng
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
| | - Jordan J Green
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Department of Oncology, Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
- Departments of Ophthalmology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
| | - Joshua C Doloff
- Department of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States
- Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States
- Department of Oncology, Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
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Khalil WJ, Akeblersane M, Khan AS, Moin ASM, Butler AE. Environmental Pollution and the Risk of Developing Metabolic Disorders: Obesity and Diabetes. Int J Mol Sci 2023; 24:8870. [PMID: 37240215 PMCID: PMC10219141 DOI: 10.3390/ijms24108870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/25/2023] [Accepted: 05/13/2023] [Indexed: 05/28/2023] Open
Abstract
To meet the increased need for food and energy because of the economic shift brought about by the Industrial Revolution in the 19th century, there has been an increase in persistent organic pollutants (POPs), atmospheric emissions and metals in the environment. Several studies have reported a relationship between these pollutants and obesity, and diabetes (type 1, type 2 and gestational). All of the major pollutants are considered to be endocrine disruptors because of their interactions with various transcription factors, receptors and tissues that result in alterations of metabolic function. POPs impact adipogenesis, thereby increasing the prevalence of obesity in exposed individuals. Metals impact glucose regulation by disrupting pancreatic β-cells, causing hyperglycemia and impaired insulin signaling. Additionally, a positive association has been observed between the concentration of endocrine disrupting chemicals (EDCs) in the 12 weeks prior to conception and fasting glucose levels. Here, we evaluate what is currently known regarding the link between environmental pollutants and metabolic disorders. In addition, we indicate where further research is required to improve our understanding of the specific effects of pollutants on these metabolic disorders which would enable implementation of changes to enable their prevention.
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Affiliation(s)
- William Junior Khalil
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Meriem Akeblersane
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Ana Saad Khan
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Abu Saleh Md Moin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Alexandra E. Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
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14
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Research Progress on the Construction and Application of a Diabetic Zebrafish Model. Int J Mol Sci 2023; 24:ijms24065195. [PMID: 36982274 PMCID: PMC10048833 DOI: 10.3390/ijms24065195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/03/2023] [Accepted: 03/07/2023] [Indexed: 03/11/2023] Open
Abstract
Diabetes is a metabolic disease characterized by high blood glucose levels. With economic development and lifestyle changes, the prevalence of diabetes is increasing yearly. Thus, it has become an increasingly serious public health problem in countries around the world. The etiology of diabetes is complex, and its pathogenic mechanisms are not completely clear. The use of diabetic animal models is helpful in the study of the pathogenesis of diabetes and the development of drugs. The emerging vertebrate model of zebrafish has many advantages, such as its small size, large number of eggs, short growth cycle, simple cultivation of adult fish, and effective improvement of experimental efficiency. Thus, this model is highly suitable for research as an animal model of diabetes. This review not only summarizes the advantages of zebrafish as a diabetes model, but also summarizes the construction methods and challenges of zebrafish models of type 1 diabetes, type 2 diabetes, and diabetes complications. This study provides valuable reference information for further study of the pathological mechanisms of diabetes and the research and development of new related therapeutic drugs.
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15
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Parlar Köprülü RE. How to create an experimental diabetes mellitus model? PHARMACIA 2023. [DOI: 10.3897/pharmacia.70.e96028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Early treatment is very important in terms of preventing diabetes-related late complications with high treatment costs and increasing the patient’s quality of life. In addition to investigating the pathophysiology of the disease studied, animal experiments pave the way for new approaches in treatments. Although there are many methods that can be used when creating a diabetes model, induction of diabetes with alloxan and streptozotocin are the most preferred ones. The aim of this article is to review the available information on diabetes-related methods, common problems and solutions, with known mechanisms of action, dose and time-determined methods.
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Wang W, Wang Y, Chi J, Tan X, Hu J, Ma X, Sun X, Che K, Lv W, Wang Y. hUCMSCs carrying exenatide prevent T1DM by improving intestinal microflora composition and islet tissue damage repair. Mol Med 2022; 28:155. [PMID: 36514009 PMCID: PMC9746121 DOI: 10.1186/s10020-022-00526-0] [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: 02/15/2022] [Accepted: 08/04/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Exenatide is a stable analogue of glucagon-like peptide 1 that can reduce postprandial hyperglycemia and has been utilized as adjunctive therapy for type 1 diabetes mellitus (T1DM). The human umbilical cord is a rich source of MSCs, and human umbilical cord mesenchymal stem cells (hUCMSCs) also show potential to enhance insulin secretion. Here, we aimed to explore the effects of hUCMSCs carrying exenatide in T1DM and further identify the possible mechanisms involved. METHODS hUCMSCs were isolated from human umbilical cord tissues, identified, and transduced with recombinant lentivirus carrying exenatide to obtain exenatide-carrying hUCMSCs (hUCMSCs@Ex-4). RESULTS The results showed that hUCMSCs@Ex-4 restored the blood glucose levels and body weight of NOD mice, and repressed immune cell infiltration and islet tissue changes. Additionally, in T1DM mice, treatment with hUCMSCs@Ex-4 reduced the blood glucose levels and promoted repair of islet tissue damage. Moreover, hUCMSCs@Ex-4 attenuated renal tissue lesions in T1DM mice. Applying bioinformatic analysis, the effects of hUCMSCs@Ex-4 were suggested to correlate with decreased abundance of pro-inflammatory intestinal bacteria and increased abundance of anti-inflammatory intestinal bacteria. CONCLUSION Overall, the study indicated that hUCMSCs carrying exenatide might improve beneficial intestinal microflora abundance and promote islet tissue damage repair, thereby alleviating T1DM.
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Affiliation(s)
- Wei Wang
- grid.412521.10000 0004 1769 1119Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, 266000 People’s Republic of China
| | - Yahao Wang
- grid.410645.20000 0001 0455 0905Medical College, Qingdao University, Qingdao, 266071 People’s Republic of China
| | - Jingwei Chi
- grid.412521.10000 0004 1769 1119Key Laboratory of Thyroid Diseases, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000 People’s Republic of China
| | - Xiaojun Tan
- grid.510325.0Department of Endocrinology, Yidu Central Hospital of Weifang City, Weifang, 261000 People’s Republic of China
| | - Jianxia Hu
- grid.412521.10000 0004 1769 1119The Laboratory of Thyroid Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266000 People’s Republic of China
| | - Xiaolong Ma
- grid.415912.a0000 0004 4903 149XDepartment of Endocrinology, Liaocheng People’s Hospital, Liaocheng, 252000 People’s Republic of China
| | - Xiaofang Sun
- grid.412521.10000 0004 1769 1119Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000 Shandong People’s Republic of China
| | - Kui Che
- grid.412521.10000 0004 1769 1119Key Laboratory of Thyroid Diseases, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000 People’s Republic of China
| | - Wenshan Lv
- grid.412521.10000 0004 1769 1119Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000 Shandong People’s Republic of China
| | - Yangang Wang
- grid.412521.10000 0004 1769 1119Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000 Shandong People’s Republic of China
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Li J, Wang Z, Nan X, Yin M, Fang H. Hotspots and frontier trends of diabetic associated cognitive decline research based on rat and mouse models from 2012 to 2021: A bibliometric study. Front Neurol 2022; 13:1073224. [PMID: 36582609 PMCID: PMC9793002 DOI: 10.3389/fneur.2022.1073224] [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: 10/18/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022] Open
Abstract
Background The establishment of rodent models, such as rat and mouse models, plays a critical role in the study of diabetic associated cognitive decline. With the continuous growth of relevant literature information, it is difficult for researchers to accurately and timely capture the topics in this field. Therefore, this study aims to explore the current status and frontier trends of diabetic associated cognitive decline research based on rat and mouse models through a bibliometric analysis. Methods We collected 701 original articles on this subject from the Science Citation Index Expanded of the Web of Science Core Collection from 2012 to 2021. Then we utilized CiteSpace and VOSviewer for plotting knowledge maps and evaluating hotpots and trends. Results During this decade, except for a slight decline in 2020, the number of annual outputs on diabetes associated cognitive decline research using rat and mouse models increased every year. China (country), China Pharmaceutical University (institution), Gao, Hongchang (the author from the School of Pharmacy of Wenzhou Medical University, China), and Metabolic Brain Disease (journal) published the most papers in this research field. The analysis results of co-cited references and co-occurrence keywords indicated that "mechanisms and prevention and treatment methods", especially "oxidative stress", "potential association with Alzheimer's disease" and "spatial memory" are research focuses in this subject area. The bursts detection of references and keywords implied that "cognitive impairment of type 1 diabetes" and "autophagy and diabetes associated cognitive decline" will be potential directions for future research in this subject area. Conclusion This study systematically assessed general information, current status and emerging trends of diabetic associated cognitive decline research using rat and mouse models in the past decade based on a bibliometric analysis. The number of publications was annually increasing although a slight decline was observed in 2020. Contributions from different countries/regions, institutions, authors, co-cited authors, journals and co-cited journals were evaluated, which may also be used to guide future research. Through the analysis of references and keywords, we predicted the future research hotspots and trends in this field.
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Affiliation(s)
- Jie Li
- Graduate School of Hebei Medical University, Shijiazhuang, China,Department of Endocrinology, Tangshan Workers' Hospital, Tangshan, China
| | - Zhen Wang
- Department of Orthopedics, Handan First Hospital, Handan, China
| | - Xinyu Nan
- Graduate School of Hebei Medical University, Shijiazhuang, China,Department of Endocrinology, Tangshan Workers' Hospital, Tangshan, China
| | - Mingjie Yin
- Graduate School of Hebei Medical University, Shijiazhuang, China,Department of Endocrinology, Tangshan Workers' Hospital, Tangshan, China
| | - Hui Fang
- Graduate School of Hebei Medical University, Shijiazhuang, China,Department of Endocrinology, Tangshan Workers' Hospital, Tangshan, China,*Correspondence: Hui Fang
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Huang H, Hu D, Chen Z, Xu J, Xu R, Gong Y, Fang Z, Wang T, Chen W. Immunotherapy for type 1 diabetes mellitus by adjuvant-free Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP). J Nanobiotechnology 2022; 20:377. [PMID: 35964125 PMCID: PMC9375265 DOI: 10.1186/s12951-022-01581-9] [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: 03/03/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy of parasitic products. Methods We developed a Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP) system, which serves as a new strategy to combat TIDM. In order to improve retention time and reduce contamination risk, a specific imperfection was introduced on the STAMP (asymmetric structure), which allows the tip to quickly separate from the base layer, improving reaction time and patient’s comfort. After loading Schistosoma japonicum-egg as the immune regulator, the effects of STAMP on blood glucose control and pancreatic pathological progression improvement were evaluated in vivo. Meanwhile, the immunoregulatory mechanism and biosafety of STAMP were confirmed by histopathology, qRT-PCR, ELISA and Flow cytometric analysis. Results Here, the newly developed STAMP was able to significantly reduce blood glucose and attenuate the pancreatic injury in T1DM mice independent of the adjuvants. The isolated Schistosoma japonicum-eggs micron slowly degraded in the skin and continuously released egg antigen for at least 2 weeks, ensuring localization and safety of antigen stimulation. This phenomenon should be attributed to the shift of Th2 immune response to reduce Th1 polarization. Conclusion Our results exhibited that STAMP could significantly regulate the blood glucose level and attenuate pancreatic pathological injury in T1DM mice by balancing the Th1/Th2 immune responses, which is independent of adjuvants. This technology opens a new window for the application of parasite products in clinical immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-022-01581-9.
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Affiliation(s)
- Haoming Huang
- National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Dian Hu
- National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Zhuo Chen
- National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Jiarong Xu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Rengui Xu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yusheng Gong
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Zhengming Fang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Ting Wang
- National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. .,Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
| | - Wei Chen
- National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. .,Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. .,Hubei Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
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Shen Y, Li M, Wang K, Qi G, Liu H, Wang W, Ji Y, Chang M, Deng C, Xu F, Shen M, Sun H. Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies. Front Endocrinol (Lausanne) 2022; 13:917113. [PMID: 35846289 PMCID: PMC9279556 DOI: 10.3389/fendo.2022.917113] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/03/2022] [Indexed: 12/23/2022] Open
Abstract
Diabetes mellitus (DM) is a typical chronic disease that can be divided into 2 types, dependent on insulin deficiency or insulin resistance. Incidences of diabetic complications gradually increase as the disease progresses. Studies in diabetes complications have mostly focused on kidney and cardiovascular diseases, as well as neuropathy. However, DM can also cause skeletal muscle atrophy. Diabetic muscular atrophy is an unrecognized diabetic complication that can lead to quadriplegia in severe cases, seriously impacting patients' quality of life. In this review, we first identify the main molecular mechanisms of muscle atrophy from the aspects of protein degradation and synthesis signaling pathways. Then, we discuss the molecular regulatory mechanisms of diabetic muscular atrophy, and outline potential drugs and treatments in terms of insulin resistance, insulin deficiency, inflammation, oxidative stress, glucocorticoids, and other factors. It is worth noting that inflammation and oxidative stress are closely related to insulin resistance and insulin deficiency in diabetic muscular atrophy. Regulating inflammation and oxidative stress may represent another very important way to treat diabetic muscular atrophy, in addition to controlling insulin signaling. Understanding the molecular regulatory mechanism of diabetic muscular atrophy could help to reveal new treatment strategies.
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Affiliation(s)
- Yuntian Shen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Ming Li
- Department of Laboratory Medicine, Department of Endocrinology, Binhai County People’s Hospital affiliated to Kangda College of Nanjing Medical University, Yancheng, China
| | - Kexin Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Guangdong Qi
- Department of Laboratory Medicine, Department of Endocrinology, Binhai County People’s Hospital affiliated to Kangda College of Nanjing Medical University, Yancheng, China
| | - Hua Liu
- Department of Orthopedics, Haian Hospital of Traditional Chinese Medicine, Nantong, China
| | - Wei Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Yanan Ji
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Mengyuan Chang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Chunyan Deng
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Feng Xu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Mi Shen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
| | - Hualin Sun
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China
- Nanjing Institute of Tissue Engineering and Regenerative Medicine Technology, Nanjing, China
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20
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Wang Y, Chen J, Sang T, Chen C, Peng H, Lin X, Zhao Q, Chen S, Eling T, Wang X. NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets. Mol Cell Endocrinol 2022; 549:111643. [PMID: 35398052 DOI: 10.1016/j.mce.2022.111643] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 03/29/2022] [Accepted: 04/03/2022] [Indexed: 01/01/2023]
Abstract
The loss of functional insulin-producing β-cells is a hallmark of type 1 diabetes mellitus (T1DM). Previously, we reported that the non-steroidal anti-inflammatory drug activated gene-1, or growth differentiation factor-15 (NAG-1/GDF15) inhibits obesity and improves insulin sensitivity in both genetic and dietary-induced obese mice. However, the regulatory role of NAG-1/GDF15 in the structure and function of β-cells and the prevention of T1DM is largely unknown. In the current study, we reported that NAG-1/GDF15 transgenic (Tg) mice are resistant to diabetogenesis induced by multiple low-dose streptozotocin (MLD-STZ) treatment. NAG-1/GDF15 overexpression significantly reduced diabetes incidence, alleviated symptoms of T1DM, and improved MLD-STZ-induced glucose intolerance and insulin resistance. Both the mass and function of pancreatic β cells were preserved in the NAG-1/GDF15 Tg mice as evidenced by significantly increased islet area and insulin production. The mechanistic study revealed that NAG-1/GDF15 significantly inhibited STZ-induced apoptosis and preserved the reduction of proliferation in the islets of the Tg mice as compared to the wild-type (WT) mice upon MLD-STZ treatment. Additionally, NAG-1/GDF15 significantly reduced both the serum and islet levels of the inflammatory cytokines (IL-1β, IL-6, and TNFα), and reduced the expression of NF-κB expression and immune cells infiltration in the islets. Collectively, these results indicate that NAG-1/GDF15 is effective in improving STZ-induced glucose intolerance, probably was mediated via suppressing inflammation, inhibiting apoptosis, and preserving β-cell mass and function.
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Affiliation(s)
- Ying Wang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Jiajun Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Tingting Sang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Chaojie Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - He Peng
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Xiaojian Lin
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Qian Zhao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Shengjia Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China
| | - Thomas Eling
- Scientist Emeritus, National Institute of Environmental Health Science, Research Triangle Park, NC, 27709, USA
| | - Xingya Wang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China.
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21
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Valenzuela-Vallejo L, López-Ramírez SA, Morales-Burton V, Aguilera-Martínez S, Álvarez-Olmos MI, Durán-Ventura P. Pediatric diabetic ketoacidosis as type 1 diabetes debut with concurrent SARS-CoV-2 infection: A case report. SAGE Open Med Case Rep 2022; 10:2050313X221097263. [PMID: 35585855 PMCID: PMC9109166 DOI: 10.1177/2050313x221097263] [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: 01/26/2022] [Accepted: 04/11/2022] [Indexed: 11/22/2022] Open
Abstract
Diabetic ketoacidosis is a life-threatening complication associated with type 1 diabetes (T1D). Recent evidence suggests that SARS-CoV-2 could trigger diabetic ketoacidosis in type 1 diabetes susceptibility and previous insulitis; however, the data on SARS-CoV-2-infected patients with diabetic ketoacidosis as their type 1 diabetes are still limited. We report a 13-year-old Latinamerican male with symptoms and laboratory tests diagnostic of diabetic ketoacidosis and positive SARS-CoV-2 reverse transcription polymerase chain reaction, who required mild COVID-19 care management, fluid resuscitation, and insulin infusion at a regular dose, without further complications after the acute infection. Clinical/biochemical improvement allowed outpatient endocrinology follow-up with insulin therapy and continuous glucose monitoring. To our knowledge, we report the first case of diabetic ketoacidosis as the debut of type 1 diabetes in a Colombian pediatric patient with concurrent SARS-CoV-2 infection. Therefore, this report aims to contribute to the global research on SARS-CoV-2 and diabetic ketoacidosis and discuss the approach to these concomitant pathologies.
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Affiliation(s)
- Laura Valenzuela-Vallejo
- School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
- Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Sofía A López-Ramírez
- School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
- Pediatrics Department, Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Verónica Morales-Burton
- Pediatrics Department, Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
- Pediatrics, MSc Health Economics, Policy & Management, Instituto de Cardiología, Bogotá, Colombia
| | - Sara Aguilera-Martínez
- Pediatrics, Pediatrics Department, Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Martha I Álvarez-Olmos
- Pediatric Infectious Diseases, Pediatrics Department, Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
- Pediatrics Infectious Diseases Fellowship Program, Universidad El Bosque, Bogotá, Colombia
| | - Paola Durán-Ventura
- Pediatric Endocrinology, Pediatrics Department, Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
- Endociencia, Bogotá, Colombia
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22
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Gupta S, Burman S, Nair AB, Chauhan S, Sircar D, Roy P, Dhanwat M, Lahiri D, Mehta D, Das R, Khalil HE. Brassica oleracea Extracts Prevent Hyperglycemia in Type 2 Diabetes Mellitus. Prev Nutr Food Sci 2022; 27:50-62. [PMID: 35465108 PMCID: PMC9007711 DOI: 10.3746/pnf.2022.27.1.50] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/07/2022] [Accepted: 01/16/2022] [Indexed: 11/25/2022] Open
Abstract
This study investigated the protective effect of extracts from flowers of Brassica oleracea L. var. italica Plenck on type 2 diabetes mellitus and its associated disorders. Three different doses of each extract (petroleum ether, ethanol, and aqueous) were administered orally for 42 days. Biochemical parameters, behavioral studies, and histological studies were measured at different periods. Mortality was found to be nil up to 2,000 mg/kg. Statistically significant (P<0.001) improvement in serum glucose level was observed in the groups receiving 400 mg/kg of petroleum ether, aqueous, or ethanol extracts compared with the negative control group. Insulin level was decreased by aqueous extracts, whereas lipid profiles were improved by aqueous and ethanol extracts. A reduction in transfer latency was observed in treatments of all three extract types. Ethanol extract treatment (400 mg/kg) showed maximum percentage inhibition in a lipid peroxidation assay. Additionally, the aqueous and ethanol extract treatments markedly reduced tumor necrosis factor-α, interleukin-6, and glycosylated hemoglobin levels. Histological results showed that high doses of extracts alleviated the damages induced by type 2 diabetes mellitus in various organs and bones. Based on the results of this study, it can be concluded that B. oleracea has the potential to alleviate type 2 diabetes mellitus.
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Affiliation(s)
- Sumeet Gupta
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Satish Burman
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Anroop B. Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Samrat Chauhan
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Debabrata Sircar
- Department of Biotechnology, Indian Institute of Technology-Roorkee, Uttarakhand 247667, India
| | - Partha Roy
- Department of Biotechnology, Indian Institute of Technology-Roorkee, Uttarakhand 247667, India
| | - Meenakshi Dhanwat
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Debrupa Lahiri
- Department of Metallurgical and Materials Engineering and Centre of Nanotechnology, Indian Institute of Technology-Roorkee, Uttarakhand 247667, India
| | - Dinesh Mehta
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Rina Das
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana 133207, India
| | - Hany Ezzat Khalil
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
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23
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The Purinergic Landscape of Type 2 Diabetes Mellitus. Molecules 2022; 27:molecules27061838. [PMID: 35335211 PMCID: PMC8951306 DOI: 10.3390/molecules27061838] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/08/2022] [Accepted: 03/08/2022] [Indexed: 12/20/2022] Open
Abstract
Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP acts at plasma membrane P2 receptors (P2Rs). The levels of extracellular ATP (eATP) are set by both passive and active release mechanisms and degradation processes. Under physiological conditions, eATP concentration is in the low nanomolar range but can rise to tens or even hundreds of micromoles/L at inflammatory sites. A dysregulated eATP homeostasis is a pathogenic factor in several chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance and impairment of insulin production from pancreatic β-cells in a landscape of systemic inflammation. Although various hypoglycemic drugs are currently available, an effective treatment for T2DM and its complications is not available. However, counteracting systemic inflammation is anticipated to be beneficial. The postulated eATP increase in T2DM is understood to be a driver of inflammation via P2X7 receptor (P2X7R) activation and the release of inflammatory cytokines. Furthermore, P2X7R stimulation is thought to trigger apoptosis of pancreatic β-cells, thus further aggravating hyperglycemia. Targeting eATP and the P2X7R might be an appealing novel approach to T2DM therapy.
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24
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Evidence and possible mechanisms of probiotics in the management of type 1 diabetes mellitus. J Diabetes Metab Disord 2022; 21:1081-1094. [PMID: 35673472 PMCID: PMC9167374 DOI: 10.1007/s40200-022-01006-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 02/12/2022] [Indexed: 10/19/2022]
Abstract
Abstract Type 1 diabetes mellitus (T1DM) is one of the most common chronic immune-mediated diseases. The prevalence is worldwide especially among children and young adults. The destruction of the pancreatic β-cells due to some abnormalities in the immune system characterizes T1DM. Considering the high burden of the disease and its impact on human health, researchers have made great efforts during the last decades; investigating the disease pathogenesis and discovering new strategies for its management. Fortunately, probiotics have been found as potential remedies for T1DM. This review aims to explore the potentialities of probiotics in managing T1DM and its complications. Based on the outcomes of human and animal studies carried out from 2016 to 2021, the review hopes to assess the effectiveness of probiotics in the prevention and treatment of T1DM and its complications. We first tried to explain the disease's pathogenesis, and highlighted the possible mechanisms involved in these potentialities of probiotics. We concluded that, probiotics can be used as possible therapeutic tools for the management of T1DM. Possible mechanisms of action of probiotics include; the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of short chain fatty acids (SCFAs), and the regulation of GLP-1. However, we recommend further studies especially human trials should be carried out to investigate these potentialities of probiotics. Highlights • T1DM is highly prevalent worldwide, causing high morbidity and mortality especially among children and young adults• Gut microbiota plays a significant role in the pathogenesis of T1DM via an interconnection with the immune system• Probiotics can be used as possible therapeutic tools for the management of T1DM• Possible mechanisms of action of probiotics include the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of SCFAs, and the regulation of GLP-1.
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25
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Bastos TSB, Braga TT, Davanso MR. Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation. Endocr Metab Immune Disord Drug Targets 2022; 22:815-833. [PMID: 34979894 DOI: 10.2174/1871530322666220103114450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/15/2021] [Accepted: 12/10/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. OBJECTIVE The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. METHOD Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. CONCLUSION The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.
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Affiliation(s)
| | - Tárcio Teodoro Braga
- Department of Pathology, Federal University of Parana, Curitiba; Brazil
- Graduate Program in Biosciences and Biotechnology, Institute Carlos Chagas, Fiocruz-Parana, Curitiba, Brazil
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26
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Shen Z, Huang W, Liu J, Tian J, Wang S, Rui K. Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases. Front Immunol 2021; 12:749192. [PMID: 34646275 PMCID: PMC8503317 DOI: 10.3389/fimmu.2021.749192] [Citation(s) in RCA: 140] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/13/2021] [Indexed: 12/15/2022] Open
Abstract
Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials of inflammatory and autoimmune diseases. Emerging evidence indicates that the immunomodulatory effect of MSCs is primarily attributed to the paracrine pathway. As one of the key paracrine effectors, mesenchymal stem cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm in diameter that play an important role in cell-to-cell communication by carrying bioactive substances from parental cells. Recent studies support the finding that MSC-EXOs have an obvious inhibitory effect toward different effector cells involved in the innate and adaptive immune response. Moreover, substantial progress has been made in the treatment of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSC-EXOs are capable of reproducing MSC function and overcoming the limitations of traditional cell therapy. Therefore, using MSC-EXOs instead of MSCs to treat autoimmune diseases appears to be a promising cell-free treatment strategy. In this review, we review the current understanding of MSC-EXOs and discuss the regulatory role of MSC-EXOs on immune cells and its potential application in autoimmune diseases.
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Affiliation(s)
- Ziwei Shen
- Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.,Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Wei Huang
- Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.,Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jun Liu
- Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.,Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jie Tian
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Shengjun Wang
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Ke Rui
- Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.,Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
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27
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Chakraborty T, Gupta S, Nair A, Chauhan S, Saini V. Wound healing potential of insulin-loaded nanoemulsion with Aloe vera gel in diabetic rats. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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28
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Alsalahi A, Chik Z, Mohamed Z, Giribabu N, Alshawsh MA. Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats. Saudi J Biol Sci 2021; 28:4633-4643. [PMID: 34354450 PMCID: PMC8325054 DOI: 10.1016/j.sjbs.2021.04.072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 04/22/2021] [Accepted: 04/22/2021] [Indexed: 11/19/2022] Open
Abstract
Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.
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Affiliation(s)
- Abdulsamad Alsalahi
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
- Department of Pharmacology, Faculty of Pharmacy, Sana’a University, Mazbah District, 1247 Sana’a Secretariat, Yemen
| | - Zamri Chik
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Zahurin Mohamed
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Nelli Giribabu
- Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
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29
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Al-Anbari HSN, Ismail DK, Hasan MK, Aga QAAK, Shinu P, Nair AB. High Blood Lead Levels: An Increased Risk for Development of Brain Hyperintensities among Type 2 Diabetes Mellitus Patients. Biol Trace Elem Res 2021; 199:2149-2157. [PMID: 32865724 DOI: 10.1007/s12011-020-02359-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/25/2020] [Indexed: 01/21/2023]
Abstract
The current study was aimed to ascertain the effect of blood lead level on brain tissues in patients with type 2 diabetes. A total of 300 human participants ages 27 to 60 years with type 2 diabetes (n = 150) and healthy individuals (n = 150) were included in this study. The serum samples were used for measuring HbA1c and fasting blood glucose. Blood lead level was measured using flame atomic absorption spectrophotometer. Magnetic resonance imaging sub-analysis was used to assess the brain hyperintensities. Brain hyperintensities were found in 55% of patients with diabetes and 6% of non-diabetic control group subjects. The deep white matter hyperintensities were observed in 45% of diabetic patients, while the subcortical hyperintensities were noted in 10% of cases. Entorhinal cortex changes (31%) and hippocampus changes (42%) were noted in diabetic patients with brain hyperintensities. Diabetic patients with brain hyperintensities showed higher blood lead levels, HbA1c, and fasting blood sugar (p < 0.0001) as compared with healthy volunteers. A higher correlation (R2 = 0.8922) was found between deep white matter hyperintensities' size and blood lead levels. In nutshell, persistence of high blood lead level in diabetic patients may progress to brain hyperintensities which may consequently lead to cognitive, behavioral changes and Alzheimer's disease.
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Affiliation(s)
| | - Dawser K Ismail
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al Esraa University College, Baghdad, 10069, Iraq
| | - Mohammed Khudair Hasan
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al Esraa University College, Baghdad, 10069, Iraq
| | - Qutaiba Ahmed Al Khames Aga
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman, 19392, Jordan.
| | - Pottathil Shinu
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
| | - Anroop B Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
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30
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Nadia Ahmad NF, Nik Ghazali NN, Wong YH. Wearable patch delivery system for artificial pancreas health diagnostic-therapeutic application: A review. Biosens Bioelectron 2021; 189:113384. [PMID: 34090154 DOI: 10.1016/j.bios.2021.113384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 12/13/2022]
Abstract
The advanced stimuli-responsive approaches for on-demand drug delivery systems have received tremendous attention as they have great potential to be integrated with sensing and multi-functional electronics on a flexible and stretchable single platform (all-in-one concept) in order to develop skin-integration with close-loop sensation for personalized diagnostic and therapeutic application. The wearable patch pumps have evolved from reservoir-based to matrix patch and drug-in-adhesive (single-layer or multi-layer) type. In this review, we presented the basic requirements of an artificial pancreas, surveyed the design and technologies used in commercial patch pumps available on the market and provided general information about the latest wearable patch pump. We summarized the various advanced delivery strategies with their mechanisms that have been developed to date and representative examples. Mechanical, electrical, light, thermal, acoustic and glucose-responsive approaches on patch form have been successfully utilized in the controllable transdermal drug delivery manner. We highlighted key challenges associated with wearable transdermal delivery systems, their research direction and future development trends.
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Affiliation(s)
- Nur Farrahain Nadia Ahmad
- Department of Mechanical Engineering, Faculty of Engineering, Universiti Malaya, 50603, Kuala Lumpur, Malaysia; School of Mechanical Engineering, Faculty of Engineering, Universiti Teknologi Malaysia, 81310, Johor Bahru, Johor, Malaysia
| | - Nik Nazri Nik Ghazali
- Department of Mechanical Engineering, Faculty of Engineering, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Yew Hoong Wong
- Department of Mechanical Engineering, Faculty of Engineering, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
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Ríos-Ríos WDJ, Sosa-Luis SA, Torres-Aguilar H. Current advances in using tolerogenic dendritic cells as a therapeutic alternative in the treatment of type 1 diabetes. World J Diabetes 2021; 12:603-615. [PMID: 33995848 PMCID: PMC8107985 DOI: 10.4239/wjd.v12.i5.603] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/26/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells of the pancreatic islets by autoreactive T cells, leading to high blood glucose levels and severe long-term complications. The typical treatment indicated in T1D is exogenous insulin administration, which controls glucose levels; however, it does not stop the autoimmune process. Various strategies have been implemented aimed at stopping β-cell destruction, such as cellular therapy. Dendritic cells (DCs) as an alternative in cellular therapy have gained great interest for autoimmune disease therapy due to their plasticity to acquire immunoregulatory properties both in vivo and in vitro, performing functions such as anti-inflammatory cytokine secretion and suppression of autoreactive lymphocytes, which are dependent of their tolerogenic phenotype, displayed by features such as semimature phenotype, low surface expression of stimulatory molecules to prime T cells, as well as the elevated expression of inhibitory markers. DCs may be obtained and propagated easily in optimal amounts from peripheral blood or bone marrow precursors, such as monocytes or hematopoietic stem cells, respectively; therefore, various protocols have been established for tolerogenic (tol)DCs manufacturing for therapeutic research in the treatment of T1D. In this review, we address the current advances in the use of tolDCs for T1D therapy, encompassing protocols for their manufacturing, the data obtained from preclinical studies carried out, and the status of clinical research evaluating the safety, feasibility, and effectiveness of tolDCs.
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Affiliation(s)
- William de Jesús Ríos-Ríos
- Department of Biochemical Sciences Faculty, Universidad Autónoma “Benito Juárez” de Oaxaca, Oaxaca 68120, Mexico
| | - Sorely Adelina Sosa-Luis
- Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico
| | - Honorio Torres-Aguilar
- Department of Biochemical Sciences Faculty, Universidad Autónoma “Benito Juárez” de Oaxaca, Oaxaca 68120, Mexico
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Shi D, Ao L, Yu H, Li J, Xia Y, Wu X, He D, Zhong W, Xia H. Diabetes increases the risk of meningioma: A systematic review and meta-analysis of observational studies. Cancer Epidemiol 2021; 73:101946. [PMID: 33965653 DOI: 10.1016/j.canep.2021.101946] [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: 01/26/2021] [Revised: 04/22/2021] [Accepted: 05/02/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Increasing epidemiological evidence suggests that diabetes may be associated with meningioma risk, but the evidence supporting this association is still inconclusive. Therefore, we performed a meta-analysis of all eligible observational studies to evaluate the potential association of diabetes with meningioma risk. METHODS A comprehensive literature search was performed in the PubMed, Web of Science and Cochrane Library databases up to November 30, 2020. A random-effects model was applied to calculate the pooled effect size (ES) and its 95 % confidence interval (CI). RESULTS Eight studies were included in this study. In a random-effects pooled analysis, the results showed that DM (diabetes mellitus) increased the risk of meningioma (ES 1.17, 95 % CI: 1.02-1.35, P = 0.027). In subgroup analyses, DM increased the risk of meningioma in women (ES: 1.19, 95 % CI: 1.02-1.40, P = 0.027) and men (ES: 1.53, 95 % CI: 1.25-1.88, P = 0.000). This effect was not observed in the postmenopausal group (ES: 1.18, 95 % CI: 0.64-2.18, P = 0.597). CONCLUSION Our meta-analysis showed that DM increases the risk of meningioma, but the association was only present in some subgroups. This conclusion should be further confirmed.
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Affiliation(s)
- Dongjie Shi
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Lei Ao
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hua Yu
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Juan Li
- Clinical Skill Training Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yongzhi Xia
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Xuedong Wu
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Dahai He
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Wenjie Zhong
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Haijian Xia
- Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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Wang X, Kang J, Liu Q, Tong T, Quan H. Fighting Diabetes Mellitus: Pharmacological and Non-pharmacological Approaches. Curr Pharm Des 2021; 26:4992-5001. [PMID: 32723251 DOI: 10.2174/1381612826666200728144200] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 06/29/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges. OBJECTIVES This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus. METHODS Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc. Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5'-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed. CONCLUSION Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.
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Affiliation(s)
- Xin Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jinhong Kang
- College of Pharmacy, Korea University, Sejong 30019, Korea
| | - Qing Liu
- Jilin Green Food Engineering Research Institute, Changchun, 130022, China
| | - Tao Tong
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Helong Quan
- Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang Province, 321004, China
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Batra M, Gupta S, Nair AB, Dhanawat M, Sandal S, Morsy MA. Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension. Eur J Ophthalmol 2021; 31:2237-2244. [PMID: 33843288 DOI: 10.1177/11206721211008783] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Vision impairment remains a major health problem worldwide. Elevated intraocular pressure is a prime risk factor for blindness in the elderly. Netarsudil is a Rho-associated protein kinase (ROCK) inhibitor, which also inhibits norepinephrine transport. This narrative review summarizes the properties and clinical significance of netarsudil, a promising drug in topical glaucoma therapy. METHODS We searched PubMed, Medline and Scopus databases using relevant keywords to retrieve information on the physicochemical properties, formulation, mechanism of action, clinical pharmacokinetics, dose and toxicity of netarsudil. RESULTS Netarsudil showed promising effects in lowering the elevated intraocular pressure by two mechanisms. The US FDA approved netarsudil for clinical use in 2017 under the trademark of Rhopressa® while European Medicines Agency approved Rhokiinsa® in 2019. This drug is available as a 0.02% ophthalmic solution for once-daily topical application. CONCLUSION The discovery of netarsudil is a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and is well tolerated in cases with ocular hypertension and chronic glaucoma.
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Affiliation(s)
- Mansi Batra
- Department of Clinical Practice, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana (Ambala), Haryana, India
| | - Sumeet Gupta
- Department of Pharmacology, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana (Ambala), Haryana, India
| | - Anroop B Nair
- College of Clinical Pharmacy, Department of Pharmaceutical Sciences, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Meenakshi Dhanawat
- Department of Pharmaceutical Chemistry, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana (Ambala), Haryana, India
| | - Suraj Sandal
- Department of Pharmacology, M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana (Ambala), Haryana, India
| | - Mohamed Aly Morsy
- College of Clinical Pharmacy, Department of Pharmaceutical Sciences, King Faisal University, Al-Ahsa, Saudi Arabia.,Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt
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Prashanth G, Vastrad B, Tengli A, Vastrad C, Kotturshetti I. Identification of hub genes related to the progression of type 1 diabetes by computational analysis. BMC Endocr Disord 2021; 21:61. [PMID: 33827531 PMCID: PMC8028841 DOI: 10.1186/s12902-021-00709-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 02/22/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) is a serious threat to childhood life and has fairly complicated pathogenesis. Profound attempts have been made to enlighten the pathogenesis, but the molecular mechanisms of T1D are still not well known. METHODS To identify the candidate genes in the progression of T1D, expression profiling by high throughput sequencing dataset GSE123658 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and gene ontology (GO) and pathway enrichment analyses were performed. The protein-protein interaction network (PPI), modules, target gene - miRNA regulatory network and target gene - TF regulatory network analysis were constructed and analyzed using HIPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, validation of hub genes was conducted by using ROC (Receiver operating characteristic) curve and RT-PCR analysis. A molecular docking study was performed. RESULTS A total of 284 DEGs were identified, consisting of 142 up regulated genes and 142 down regulated genes. The gene ontology (GO) and pathways of the DEGs include cell-cell signaling, vesicle fusion, plasma membrane, signaling receptor activity, lipid binding, signaling by GPCR and innate immune system. Four hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell-cell signaling, cytokine signaling in immune system, signaling by GPCR and innate immune system. ROC curve and RT-PCR analysis showed that EGFR, GRIN2B, GJA1, CAP2, MIF, POLR2A, PRKACA, GABARAP, TLN1 and PXN might be involved in the advancement of T1D. Molecular docking studies showed high docking score. CONCLUSIONS DEGs and hub genes identified in the present investigation help us understand the molecular mechanisms underlying the advancement of T1D, and provide candidate targets for diagnosis and treatment of T1D.
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Affiliation(s)
- G Prashanth
- Department of General Medicine, Basaveshwara Medical College, Chitradurga, Karnataka, 577501, India
| | - Basavaraj Vastrad
- Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka, 582103, India
| | - Anandkumar Tengli
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru and JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570015, India
| | - Chanabasayya Vastrad
- Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad, Karanataka, 580001, India.
| | - Iranna Kotturshetti
- Department of Ayurveda, Rajiv Gandhi Education Society's Ayurvedic Medical College, Ron, Karanataka, 582209, India
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Kiersztan A, Gaanga K, Witecka A, Jagielski AK. DHEA-pretreatment attenuates oxidative stress in kidney-cortex and liver of diabetic rabbits and delays development of the disease. Biochimie 2021; 185:135-145. [PMID: 33771656 DOI: 10.1016/j.biochi.2021.03.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 02/15/2021] [Accepted: 03/17/2021] [Indexed: 02/02/2023]
Abstract
In view of reported discrepancies concerning antioxidant activity of dehydroepiandrosterone (DHEA), a widely used dietary supplement, the current investigation was undertaken to evaluate the antioxidant properties of DHEA in both kidney-cortex and liver of alloxan (ALX)-induced diabetic rabbits, as this diabetogenic compound exhibits the ROS-dependent action. ALX was injected to animals following 7 days of DHEA administration. Four groups of rabbits were used in the experiments: control, DHEA-treated control, diabetic and DHEA-treated diabetic. Our results show for the first time, that in kidney-cortex DHEA resulted in normalization of hydroxyl free radicals (HFR) levels and restoration of catalase (CAT) and glutathione peroxidase (GPx) activities to near the control values, while in liver DHEA prevented the malondialdehyde (MDA) accumulation and normalized glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH) activities. Moreover, in both kidney-cortex and liver DHEA supplementation prevented GSSG elevation accompanied by a decrease in GSH/GSSG ratio. Although DHEA attenuated oxidative stress in both kidney-cortex and liver of ALX-induced diabetic rabbits and significantly delayed the onset of diabetes in time, it did not protect against the final development of diabetes. In conclusion, the current investigation underscores the complexity of the antioxidant action of DHEA. The data are of clinical interest since DHEA supplementation could prevent the deleterious effects of ROS and delay, or even prevent the onset of many diseases. However, in view of the reported pro-oxidant effects of high DHEA doses, the potential use of this agent as a supplement needs a careful evaluation.
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Affiliation(s)
- Anna Kiersztan
- Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
| | - Kongorzul Gaanga
- Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland
| | - Apolonia Witecka
- Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland
| | - Adam K Jagielski
- Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland
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Calabrese CM, Valentini A, Calabrese G. Gut Microbiota and Type 1 Diabetes Mellitus: The Effect of Mediterranean Diet. Front Nutr 2021; 7:612773. [PMID: 33521039 PMCID: PMC7838384 DOI: 10.3389/fnut.2020.612773] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 12/02/2020] [Indexed: 12/15/2022] Open
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting from a complex interplay between genetic susceptibility and environmental factors. Regarding the latter, gut microbiota has a pivotal role in the pathogenesis of T1DM, by affecting intestinal permeability, molecular mimicry, and modulating innate and adaptive immune system, as described in several previous studies. The composition of the gut microbiota is largely influenced by diet. Some observational studies have shown that a low fiber intake is associated with the development of many inflammatory and immune-mediated diseases. In this context, the Mediterranean diet (MD), which is based on high consumption of cereals (preferably as whole grains), legumes, nuts, vegetables, fruits, olive oil, and fish, could play a protective role. Many of the characteristic components of MD have functional characteristics with positive effects on health and well-being. Eating habits are the main significant determinants of the microbial multiplicity of the intestine and the food components influence both microbial populations and their metabolic activities from the early stages of life. Moreover, food metabolites influence the immune response. The intestine is considered the primary site where food metabolites mediate their effects, through epithelial integrity or mucosal immunity. The compromised epithelial integrity allows the translocation of bacteria and/or the diffusion of their products, such as food antigens and lipopolysaccharides, from the intestinal lumen to the tissues, which could enhance the stimulation of immune cells, contributing to the pathogenesis of autoimmune diseases, such as T1DM. The intake of a high amount of fiber and therefore of prebiotics with MD allows the microbiota to have a good microbial balance. Moreover, as more dietary fibers are ingested, a higher amount of short-chain fatty acids (SCFAs) is produced by anaerobic gut microbiota, promoting gut homeostasis, to which also contribute tryptophan metabolites and omega-3-fatty acids. Furthermore, the higher intake of polyunsaturated fatty acids and omega-3-fatty-acids contribute to a better metabolic control. In this review we report the relationship between gut microbiota and T1DM and we explore the effects of Mediterranean diet on microbiota as a potential therapeutic strategy, aimed at preventing or delaying progression of T1DM and its complications.
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Affiliation(s)
| | - Alessia Valentini
- Dipartimento di Medicina Interna, Ospedale Madre Giuseppina Vannini, Rome, Italy
| | - Giorgio Calabrese
- Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Alessandria, Italy
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Mechanisms of Antidiabetic Activity of Methanolic Extract of Punica granatum Leaves in Nicotinamide/Streptozotocin-Induced Type 2 Diabetes in Rats. PLANTS 2020; 9:plants9111609. [PMID: 33228177 PMCID: PMC7699557 DOI: 10.3390/plants9111609] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 12/23/2022]
Abstract
The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL.
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Song WY, Jiang XH, Ding Y, Wang Y, Zhou MX, Xia Y, Zhang CY, Yin CC, Qiu C, Li K, Sun P, Han X. Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration. Br J Pharmacol 2020; 177:4433-4447. [PMID: 32608014 DOI: 10.1111/bph.15183] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 06/18/2020] [Accepted: 06/22/2020] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND AND PURPOSE Intra-islet heparan sulfate (HS) plays an important role in the maintenance of pancreatic islet function. The aim of this study was to investigate the effect mechanism of HS loss on the functioning of islets in diabetic mice. EXPERIMENTAL APPROACH The hypoglycaemic effect of a heparanase inhibitor, OGT2115, was tested in a streptozotocin-induced diabetic mouse model. The islets in pancreatic sections were also stained to reveal their morphology. An insulinoma cell line (MIN6) and primary isolated murine islets were used to investigate the effect of OGT2115 in vitro. KEY RESULTS Intra-islet HS was clearly lost in streptozotocin-induced diabetic mice due to the increased heparanase expression in damaged islets. OGT2115 prevented intra-islet HS loss and improved the glucose profile and insulin secretion in streptozotocin-treated mice. The apoptosis of pancreatic beta cells and the infiltration of mononuclear macrophages, CD4- and CD8-positive T-cells in islets was reduced by OGT2115 in streptozotocin-treated mice, but OGT2115 did not alter the direct streptozotocin-induced damage in vitro. The expression of heparanase was increased in high glucose-treated isolated islets but not in response to direct streptozotocin stimulation. Further experiments showed that high glucose stimuli could decreased expression of PPARγ in cultured islets, thereby relieving the PPARγ-induced inhibition of heparanase gene expression. CONCLUSION AND IMPLICATIONS Hyperglycaemia could cause intra-islet HS loss by elevating the expression of heparanase, thereby aggravating inflammatory cell infiltration and islet damage. Inhibition of heparanase might provide benefit for pancreatic beta cell protection in Type 1 diabetes.
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Affiliation(s)
- Wen-Yu Song
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Xiao-Han Jiang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Ying Ding
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan Wang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Ming-Xuan Zhou
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Yun Xia
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Chen-Yu Zhang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Chong-Chong Yin
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Chen Qiu
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Kai Li
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Peng Sun
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Xiao Han
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
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Serralha RS, Rodrigues IF, Bertolini A, Lima DY, Nascimento M, Mouro MG, Punaro GR, Visoná I, Rodrigues AM, Higa EMS. Esculin reduces P2X7 and reverses mitochondrial dysfunction in the renal cortex of diabetic rats. Life Sci 2020; 254:117787. [PMID: 32417372 DOI: 10.1016/j.lfs.2020.117787] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 05/09/2020] [Accepted: 05/11/2020] [Indexed: 02/07/2023]
Abstract
AIMS To evaluate the effects of esculin treatment on P2X7 receptor and mitochondrial dysfunction in the renal cortex of diabetic rats. MAIN METHODS Male Wistar rats, 7 weeks old, were unilaterally nephrectomized. Part of these animals were induced to diabetes using streptozotocin (60 mg/kg). Diabetes was confirmed 48 h after induction, with blood glucose levels ≥200 mg/dL. Part of control and diabetic animals were selected to receive daily doses of esculin (50 mg/kg), during 8 weeks. The animals were placed in metabolic cages at the eighth week of protocol for 24 h urine collection and a small aliquot of blood was collected for biochemical analysis. After this procedure, the animals were euthanized and the remaining kidney was stored for histopathological analysis, Western blotting and mitochondrial high-resolution respirometry. KEY FINDINGS Although esculin did not change metabolic parameters, renal biochemical function, neither TBARS in DM rats, esculin reduced P2X7 levels in these animals and restored mitochondrial function via glycolysis substrates and β-oxidation. Besides, at the histological analysis, we observed that esculin reduced inflammatory infiltrates and collagen IV deposits as compared to diabetic group. SIGNIFICANCE Esculin attenuated the development of renal injuries caused by hyperglycemia, proinflammatory and oxidative mechanisms mediated by P2X7 receptor, as seen by histological findings and improved mitochondrial function in diabetic animals. This suggests that esculin could be used as an adjuvant therapy to prevent the diabetic nephropathy.
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Affiliation(s)
- R S Serralha
- Translational Medicine, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil.
| | - I F Rodrigues
- Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - A Bertolini
- Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - D Y Lima
- Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - M Nascimento
- Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology, Universidade Federal de Sao Paulo, Brazil
| | - M G Mouro
- Translational Medicine, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - G R Punaro
- Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - I Visoná
- Pathology Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - A M Rodrigues
- Translational Medicine, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
| | - E M S Higa
- Translational Medicine, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Nephrology Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil; Emergency Division, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil
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Wang M, Tan Y, Shi Y, Wang X, Liao Z, Wei P. Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments. Front Endocrinol (Lausanne) 2020; 11:568. [PMID: 32982969 PMCID: PMC7477770 DOI: 10.3389/fendo.2020.00568] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 07/13/2020] [Indexed: 12/11/2022] Open
Abstract
Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity.
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Affiliation(s)
- Mina Wang
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Beijing Key Laboratory of Acupuncture Neuromodulation, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Yan Tan
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yifan Shi
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Xu Wang
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, Stockholm, Sweden
- Zehuan Liao
| | - Peng Wei
- School of Traditional Chinese Medicine, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Peng Wei
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Khursheed R, Singh SK, Wadhwa S, Kapoor B, Gulati M, Kumar R, Ramanunny AK, Awasthi A, Dua K. Treatment strategies against diabetes: Success so far and challenges ahead. Eur J Pharmacol 2019; 862:172625. [DOI: 10.1016/j.ejphar.2019.172625] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 08/11/2019] [Accepted: 08/20/2019] [Indexed: 12/18/2022]
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Laso-García F, Diekhorst L, Gómez-de Frutos MC, Otero-Ortega L, Fuentes B, Ruiz-Ares G, Díez-Tejedor E, Gutiérrez-Fernández M. Cell-Based Therapies for Stroke: Promising Solution or Dead End? Mesenchymal Stem Cells and Comorbidities in Preclinical Stroke Research. Front Neurol 2019; 10:332. [PMID: 31024426 PMCID: PMC6467162 DOI: 10.3389/fneur.2019.00332] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 03/19/2019] [Indexed: 01/11/2023] Open
Abstract
Stroke is a major health problem worldwide. It has been estimated that 90% of the population attributable risk of stroke is due to risk factors such as aging, hypertension, hyperglycemia, diabetes mellitus and obesity, among others. However, most animal models of stroke use predominantly healthy and young animals. These models ignore the main comorbidities associated with cerebrovascular disease, which could be one explanation for the unsuccessful bench-to-bedside translation of protective and regenerative strategies by not taking the patient's situation into account. This lack of success makes it important to incorporate comorbidities into animal models of stroke in order to study the effects of the various therapeutic strategies tested. Regarding cell therapy, the administration of stem cells in the acute and chronic phases has been shown to be safe and effective in experimental animal models of stroke. This review aims to show the results of studies with promising new therapeutic strategies such as mesenchymal stem cells, which are being tested in preclinical models of stroke associated with comorbidities and in elderly animals.
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Affiliation(s)
- Fernando Laso-García
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Luke Diekhorst
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Mari Carmen Gómez-de Frutos
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Laura Otero-Ortega
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Blanca Fuentes
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Gerardo Ruiz-Ares
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - Exuperio Díez-Tejedor
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
| | - María Gutiérrez-Fernández
- Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autonoma University of Madrid, Madrid, Spain
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Jiaojiao Y, Sun C, Wei Y, Wang C, Dave B, Cao F, Liandong H. Applying emerging technologies to improve diabetes treatment. Biomed Pharmacother 2018; 108:1225-1236. [PMID: 30372824 DOI: 10.1016/j.biopha.2018.09.155] [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: 07/30/2018] [Revised: 09/18/2018] [Accepted: 09/26/2018] [Indexed: 10/28/2022] Open
Abstract
Insulin, as the most important drug for the treatment of diabetes, can effectively control the blood glucose concentration in humans. Due to its instability, short half-life, easy denaturation and side effects, the administration way of insulin are limited to subcutaneous injection accompany with poor glucose control and low patient compliance. In recent years, emerging insulin delivery systems have been developed in diabetes research. In this review, a variety of stimuli-responsive insulin delivery systems with their response mechanism and regulation principle are described. Further, the introduction of stem cell transplantation and mobile application based delivery technologies are prudent for the diabetes treatment. This article also discusses the advantages and limitations of current strategies, along with the opportunities and challenges for future insulin therapy.
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Affiliation(s)
- Yu Jiaojiao
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China
| | - Caifeng Sun
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China
| | - Yuli Wei
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China
| | - Chaoying Wang
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China
| | | | - Fei Cao
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China
| | - Hu Liandong
- School of Pharmaceutical Sciences, Hebei University, Baoding, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China.
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Comparative genome-wide survey of single nucleotide variation uncovers the genetic diversity and potential biomedical applications among six Macaca species. Int J Mol Sci 2018; 19:ijms19103123. [PMID: 30314376 PMCID: PMC6212917 DOI: 10.3390/ijms19103123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/21/2018] [Accepted: 10/08/2018] [Indexed: 12/30/2022] Open
Abstract
Macaca is of great importance in evolutionary and biomedical research. Aiming at elucidating genetic diversity patterns and potential biomedical applications of macaques, we characterized single nucleotide variations (SNVs) of six Macaca species based on the reference genome of Macaca mulatta. Using eight whole-genome sequences, representing the most comprehensive genomic SNV study in Macaca to date, we focused on discovery and comparison of nonsynonymous SNVs (nsSNVs) with bioinformatic tools. We observed that SNV distribution patterns were generally congruent among the eight individuals. Outlier tests of nsSNV distribution patterns detected 319 bins with significantly distinct genetic divergence among macaques, including differences in genes associated with taste transduction, homologous recombination, and fat and protein digestion. Genes with specific nsSNVs in various macaques were differentially enriched for metabolism pathways, such as glycolysis, protein digestion and absorption. On average, 24.95% and 11.67% specific nsSNVs were putatively deleterious according to PolyPhen2 and SIFT4G, respectively, among which the shared deleterious SNVs were located in 564–1981 genes. These genes displayed enrichment signals in the ‘obesity-related traits’ disease category for all surveyed macaques, confirming that they were suitable models for obesity related studies. Additional enriched disease categories were observed in some macaques, exhibiting promising potential for biomedical application. Positively selected genes identified by PAML in most tested Macaca species played roles in immune and nervous system, growth and development, and fat metabolism. We propose that metabolism and body size play important roles in the evolutionary adaptation of macaques.
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PBMT and topical diclofenac as single and combined treatment on skeletal muscle injury in diabetic rats: effects on biochemical and functional aspects. Lasers Med Sci 2018; 34:255-262. [PMID: 29992491 DOI: 10.1007/s10103-018-2580-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 07/01/2018] [Indexed: 12/21/2022]
Abstract
Physical exercise generates several benefits in a short time in patients with diabetes mellitus. However, it can increase the chances of muscle damage, a serious problem for diabetic patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat these injuries, despite the serious adverse effects. In this way, photobiomodulation therapy (PBMT) with low-level laser therapy (LLLT) and/or light emitting diode therapy (LEDT) can be used as an alternative in this case. However, its efficacy in tissue repair of trauma injuries in diabetes mellitus until now is unknown, as well as the combination between PBMT and NSAIDs. The objective of the present study was to evaluate the effects of NSAIDs and PBMT applied alone or combined on functional and biochemical aspects, in an experimental model of muscle injury through controlled trauma in diabetic rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm2; 3 J; 107.1 J/cm2, 30 s), diclofenac sodium for topical use (1 g), or combination of them. Our results demonstrated that PBMT + diclofenac, and PBMT alone reduced the gene expression of cyclooxygenase-2 (COX-2) at all assessed times as compared to the injury and diclofenac groups (p < 0.05 and p < 0.01 respectively). The diclofenac alone showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). Prostaglandin E2 levels in blood plasma demonstrated similar results to COX2. In addition, we observed that PBMT + diclofenac and PBMT alone showed significant improvement compared with injury and diclofenac groups in functional analysis at all time points. The results indicate that PBMT alone or in combination with diclofenac reduces levels of inflammatory markers and improves gait of diabetic rats in the acute phase of muscle injury.
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Bahendeka S, Wesonga R, Were TP, Nyangabyaki C. Autoantibodies and HLA class II DR-DQ genotypes in Ugandan children and adolescents with type 1 diabetes mellitus. Int J Diabetes Dev Ctries 2018. [DOI: 10.1007/s13410-018-0622-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Mitutsova V, Yeo WWY, Davaze R, Franckhauser C, Hani EH, Abdullah S, Mollard P, Schaeffer M, Fernandez A, Lamb NJC. Adult muscle-derived stem cells engraft and differentiate into insulin-expressing cells in pancreatic islets of diabetic mice. Stem Cell Res Ther 2017; 8:86. [PMID: 28420418 PMCID: PMC5395782 DOI: 10.1186/s13287-017-0539-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 03/16/2017] [Indexed: 12/12/2022] Open
Abstract
Background Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. Results In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter. Differentiated clusters of beta-like cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1, and MafA, and secreted significant levels of insulin in response to glucose challenges. In vivo, undifferentiated MDSC injected into streptozotocin (STZ)-treated mice engrafted within 48 h specifically to damaged pancreatic islets and were shown to differentiate and express insulin 10–12 days after injection. In addition, injection of MDSC into hyperglycemic diabetic mice reduced their blood glucose levels for 2–4 weeks. Conclusion These data show that MDSC are capable of differentiating into mature pancreatic beta islet-like cells, not only upon culture in vitro, but also in vivo after systemic injection in STZ-induced diabetic mouse models. Being nonteratogenic, MDSC can be used directly by systemic injection, and this potential reveals a promising alternative avenue in stem cell-based treatment of beta-cell deficiencies. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0539-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Violeta Mitutsova
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France
| | - Wendy Wai Yeng Yeo
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France.,Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia
| | - Romain Davaze
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France
| | - Celine Franckhauser
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France
| | - El-Habib Hani
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France
| | - Syahril Abdullah
- Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia
| | - Patrice Mollard
- Networks and Rhythms in Endocrine Glands, IGF, CNRS UMR-5203, Montpellier, France
| | - Marie Schaeffer
- Networks and Rhythms in Endocrine Glands, IGF, CNRS UMR-5203, Montpellier, France
| | - Anne Fernandez
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France.
| | - Ned J C Lamb
- Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille, 34396, Montpellier cedex 05, France.
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Affiliation(s)
- Anne Phillips
- Senior Lecturer in Diabetes Care, University of York
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Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice. PLoS One 2015; 10:e0142688. [PMID: 26606254 PMCID: PMC4659659 DOI: 10.1371/journal.pone.0142688] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 10/26/2015] [Indexed: 01/14/2023] Open
Abstract
In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3+ T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs.
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