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Li J, Li J, Sun Y, Fu Y, Shen W, Cai L, Xu F, Gao L, Wang N, Wang B, Lu Y. Association of iodized salt intake with the risk of physical frailty in patients with type 2 diabetes. J Nutr Health Aging 2025; 29:100543. [PMID: 40139023 DOI: 10.1016/j.jnha.2025.100543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 03/06/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025]
Abstract
OBJECTIVES We aimed to investigate the association of the status of iodized salt in terms of consumption of salt type and urinary iodine concentration (UIC) in diabetes, with frailty and examine whether this association could be modified by thyroid function. DESIGN A population-based cohort study. SETTING AND PARTICIPANTS We included 850 patients with type 2 diabetes from 11 communities in Shanghai, who completed five-year follow-up. MEASUREMENTS The type of salt consumed was collected through a standardized questionnaire and UIC was measured by an inductively coupled plasma-mass spectrometer. Frailty was assessed by frailty phenotype. Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured by electrochemiluminescence. Modified Poisson regression model with robust variance was used to estimate the relative risks (RRs) with 95% confidence intervals (CIs) for frailty in relation to iodized salt consumption and UIC. RESULTS In this five-year follow-up study in patients with diabetes, 111 (12.9%) patients progressed to frailty. Patients who consumed non-iodized salt (RR: 1.09, 95% CI: 1.01-1.18) had an increased risk of frailty, compared to patients who consumed iodized salt. Lower UIC was associated with a higher risk of frailty (1.10, 1.01-1.19). In patients with high TSH and low FT4, the RRs of frailty were 1.20 (1.08-1.34) and 1.15 (1.02-1.29) for non-iodized salt, and 1.14 (1.02-1.28) and 1.12 (0.99-1.27) for low UIC. CONCLUSIONS Non-iodized salt consumed and low UIC were associated with an increased risk of frailty in diabetes, particularly in those with high TSH and low FT4. Maintaining adequate iodine intake is critically important for preventing frailty in diabetes, especially for individuals with potential thyroid dysfunction.
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Affiliation(s)
- Jiang Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Jie Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Ying Sun
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Yanqi Fu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Wenqi Shen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Lingli Cai
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Fei Xu
- iHuman Institute, School of Life Science and Technology, Shanghai Tech University, 200011 Shanghai, China
| | - Ling Gao
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, China
| | - Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China
| | - Bin Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China.
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China.
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Zuo X, Meng G, Song L, Dong X. Effects of Adra2α expression of adipose stem cells on the treatment of type 2 diabetic mice. Stem Cell Res Ther 2025; 16:72. [PMID: 39948679 PMCID: PMC11827246 DOI: 10.1186/s13287-025-04192-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Adipose stem cell (ASC) therapy has been tested as a new option for the treatment of type 2 diabetes (T2D). Our previous transcriptome sequencing analysis showed that the adrenergic α2 receptor (Adra2α) was highly expressed in ASCs from T2D mice compared to healthy controls. This study aims to explore the role of Adra2α on the characterization and therapeutic function of ASCs. METHODS Clonidine (an Adra2α agonist) or si-RNA was used to observe Adra2α on ASCs proliferation, migration, growth factors (HGF, TGF-β1 and VEGF) expression and secretion. T2D mice were treated with non-treated control or Adra2α knockdown T2D ASCs (namely NC ASCs or KD ASCs). Mice glucose levels, insulin sensitivity and other metabolic indicators were measured and compared. RESULTS Treatment of ASCs with Clonidine reduced the proliferation, migration, and growth factors expression and secretion of ASCs, while Adra2α knocking down ASCs showed opposite effects. This translated in vivo when T2D + KD ASCs could improve hyperglycemia and insulin resistance, reduce fat content in adipose tissues and livers, suppress body inflammation, and increase pancreatic β cell mass in T2D mice compared to NC ASCs. CONCLUSIONS Adra2α plays a critical role in regulating the proliferation, migration, and expression of growth factors of ASCs. Suppression of Adra2α expression in T2D ASCs restored/improved their therapeutic effects.
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MESH Headings
- Animals
- Diabetes Mellitus, Type 2/therapy
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/pathology
- Mice
- Adipose Tissue/cytology
- Adipose Tissue/metabolism
- Receptors, Adrenergic, alpha-2/metabolism
- Receptors, Adrenergic, alpha-2/genetics
- Stem Cells/metabolism
- Stem Cells/cytology
- Cell Proliferation/drug effects
- Male
- Clonidine/pharmacology
- Cell Movement/drug effects
- Diabetes Mellitus, Experimental/therapy
- Diabetes Mellitus, Experimental/metabolism
- Mice, Inbred C57BL
- Insulin Resistance
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Affiliation(s)
- Xinzhen Zuo
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, People's Republic of China
| | - Gaofan Meng
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, People's Republic of China
| | - Lili Song
- School of Life Science, Shandong University, No. 72, Binhai Road, Qingdao, 266237, Shandong, People's Republic of China
| | - Xiao Dong
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, People's Republic of China.
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Nguyen PBH, Garger D, Lu D, Maalmi H, Prokisch H, Thorand B, Adamski J, Kastenmüller G, Waldenberger M, Gieger C, Peters A, Suhre K, Bönhof GJ, Rathmann W, Roden M, Grallert H, Ziegler D, Herder C, Menden MP. Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy. COMMUNICATIONS MEDICINE 2024; 4:265. [PMID: 39681608 DOI: 10.1038/s43856-024-00637-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 10/09/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet. METHODS Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics. RESULTS Clinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology. CONCLUSIONS These may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.
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Affiliation(s)
- Phong B H Nguyen
- Institute of Computational Biology, Helmholtz Munich, 85764, Neuherberg, Germany
- Faculty of Biology, Ludwig-Maximilians University Munich, 82152, Martinsried, Germany
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
| | - Daniel Garger
- Institute of Computational Biology, Helmholtz Munich, 85764, Neuherberg, Germany
- Faculty of Biology, Ludwig-Maximilians University Munich, 82152, Martinsried, Germany
| | - Diyuan Lu
- Institute of Computational Biology, Helmholtz Munich, 85764, Neuherberg, Germany
| | - Haifa Maalmi
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
| | - Holger Prokisch
- Institute of Neurogenomics, Helmholtz Munich, 85764, Neuherberg, Germany
- Institute of Human Genetics, Technical University Munich, 80333, Munich, Germany
| | - Barbara Thorand
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute of Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
- Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians University Munich, 81377, Munich, Germany
| | - Jerzy Adamski
- Institute of Experimental Genetics, Helmholtz Munich, 85764, Neuherberg, Germany
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia
| | - Gabi Kastenmüller
- Institute of Computational Biology, Helmholtz Munich, 85764, Neuherberg, Germany
- Institute of Bioinformatics and Systems Biology, Helmholtz Munich, 85764, Neuherberg, Germany
| | - Melanie Waldenberger
- Research Unit Molecular Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
| | - Christian Gieger
- Research Unit Molecular Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
- Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians University Munich, 81377, Munich, Germany
| | - Karsten Suhre
- Department of Physiology and Biophysics, Weill Cornell Medicine - Qatar, Education City, Doha, 24144, Qatar
| | - Gidon J Bönhof
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
| | - Wolfgang Rathmann
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
| | - Harald Grallert
- Institute of Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
- Research Unit Molecular Epidemiology, Helmholtz Munich, 85764, Neuherberg, Germany
| | - Dan Ziegler
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany
| | - Christian Herder
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
| | - Michael P Menden
- Institute of Computational Biology, Helmholtz Munich, 85764, Neuherberg, Germany.
- Faculty of Biology, Ludwig-Maximilians University Munich, 82152, Martinsried, Germany.
- German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
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Diaz-Castro J, Toledano JM, Sanchez-Romero J, Aguilar AC, Martín-Alvarez E, Puche-Juarez M, Moreno-Fernandez J, Pinar-Gonzalez M, Prados S, Carrillo MP, Ruiz-Duran S, De Paco Matallana C, Ochoa JJ. COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum. J Clin Med 2024; 13:2124. [PMID: 38610889 PMCID: PMC11012405 DOI: 10.3390/jcm13072124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 04/01/2024] [Accepted: 04/03/2024] [Indexed: 04/14/2024] Open
Abstract
Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.
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Affiliation(s)
- Javier Diaz-Castro
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria (IBS), 18012 Granada, Spain
| | - Juan M. Toledano
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Nutrition and Food Sciences Ph.D. Program, University of Granada, 18071 Granada, Spain
| | - Javier Sanchez-Romero
- Department of Obstetrics and Gynecology, Hospital Clínico Universitario ‘Virgen de la Arrixaca’, El Palmar, 30120 Murcia, Spain; (J.S.-R.); (C.D.P.M.)
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar, 30120 Murcia, Spain
| | - Africa Caño Aguilar
- Department of Obstetrics and Gynaecology, San Cecilio Universitary Hospital, 18071 Granada, Spain
| | - Estefanía Martín-Alvarez
- Unit of Neonatology, Pediatric Service, Hospital Universitario Materno-Infantil Virgen de las Nieves, 18014 Granada, Spain
| | - Maria Puche-Juarez
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Nutrition and Food Sciences Ph.D. Program, University of Granada, 18071 Granada, Spain
| | - Jorge Moreno-Fernandez
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria (IBS), 18012 Granada, Spain
| | - Maria Pinar-Gonzalez
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Nutrition and Food Sciences Ph.D. Program, University of Granada, 18071 Granada, Spain
| | - Sonia Prados
- Department of Obstetrics and Gynaecology, San Cecilio Universitary Hospital, 18071 Granada, Spain
| | - María Paz Carrillo
- Department of Obstetrics & Gynaecology, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (M.P.C.)
| | - Susana Ruiz-Duran
- Department of Obstetrics & Gynaecology, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (M.P.C.)
| | - Catalina De Paco Matallana
- Department of Obstetrics and Gynecology, Hospital Clínico Universitario ‘Virgen de la Arrixaca’, El Palmar, 30120 Murcia, Spain; (J.S.-R.); (C.D.P.M.)
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar, 30120 Murcia, Spain
| | - Julio J. Ochoa
- Department of Physiology, Faculty of Pharmacy, Campus Universitario de Cartuja, University of Granada, 18071 Granada, Spain; (J.D.-C.); (J.J.O.)
- Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, Biomedical Research Centre, Health Sciences Technological Park, Avenida del Conocimiento s/n, Armilla, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria (IBS), 18012 Granada, Spain
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Mahmoud M, Abdel-Rasheed M. Influence of type 2 diabetes and obesity on adipose mesenchymal stem/stromal cell immunoregulation. Cell Tissue Res 2023; 394:33-53. [PMID: 37462786 PMCID: PMC10558386 DOI: 10.1007/s00441-023-03801-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 06/21/2023] [Indexed: 10/07/2023]
Abstract
Type 2 diabetes (T2D), associated with obesity, represents a state of metabolic inflammation and oxidative stress leading to insulin resistance and progressive insulin deficiency. Adipose-derived stem cells (ASCs) are adult mesenchymal stem/stromal cells identified within the stromal vascular fraction of adipose tissue. These cells can regulate the immune system and possess anti-inflammatory properties. ASCs are a potential therapeutic modality for inflammatory diseases including T2D. Patient-derived (autologous) rather than allogeneic ASCs may be a relatively safer approach in clinical perspectives, to avoid occasional anti-donor immune responses. However, patient characteristics such as body mass index (BMI), inflammatory status, and disease duration and severity may limit the therapeutic utility of ASCs. The current review presents human ASC (hASC) immunoregulatory mechanisms with special emphasis on those related to T lymphocytes, hASC implications in T2D treatment, and the impact of T2D and obesity on hASC immunoregulatory potential. hASCs can modulate the proliferation, activation, and functions of diverse innate and adaptive immune cells via direct cell-to-cell contact and secretion of paracrine mediators and extracellular vesicles. Preclinical studies recommend the therapeutic potential of hASCs to improve inflammation and metabolic indices in a high-fat diet (HFD)-induced T2D disease model. Discordant data have been reported to unravel intact or detrimentally affected immunomodulatory functions of ASCs, isolated from patients with obesity and/or T2D patients, in vitro and in vivo. Numerous preconditioning strategies have been introduced to potentiate hASC immunomodulation; they are also discussed here as possible options to potentiate the immunoregulatory functions of hASCs isolated from patients with obesity and T2D.
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Affiliation(s)
- Marwa Mahmoud
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, 33 El Buhouth St, Ad Doqi, Dokki, 12622, Cairo Governorate, Egypt.
- Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
| | - Mazen Abdel-Rasheed
- Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, 33 El Buhouth St, Ad Doqi, Dokki, 12622, Cairo Governorate, Egypt
- Department of Reproductive Health Research, National Research Centre, Cairo, Egypt
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Phoswa WN, Mokgalaboni K. Comprehensive Overview of the Effects of Amaranthus and Abelmoschus esculentus on Markers of Oxidative Stress in Diabetes Mellitus. Life (Basel) 2023; 13:1830. [PMID: 37763234 PMCID: PMC10532493 DOI: 10.3390/life13091830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/29/2023] Open
Abstract
The use of medicinal plants in the management of diabetes mellitus (DM) is extensively reported. However, there is still very limited information on the role of these plants as markers of oxidative stress in DM. This current review evaluated the effect of Amaranthus spinosus, Amaranthus hybridus, and Abelmoschus esculentus on markers of oxidative stress in rodent models of DM. Current findings indicate that these plants have the potential to reduce prominent markers of oxidative stress, such as serum malondialdehyde and thiobarbituric acid-reactive substances, while increasing enzymes that act as antioxidants, such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase. This may reduce reactive oxygen species and further ameliorate oxidative stress in DM. Although the potential benefits of these plants are acknowledged in rodent models, there is still a lack of evidence showing their efficacy against oxidative stress in diabetic patients. Therefore, we recommend future clinical studies in DM populations, particularly in Africa, to evaluate the potential effects of these plants. Such studies would contribute to enhancing our understanding of the significance of incorporating these plants into dietary practices for the prevention and management of DM.
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Affiliation(s)
- Wendy N. Phoswa
- Department of Life and Consumer Sciences, University of South Africa (UNISA), Science Campus, Private Bag X6, Florida, Roodepoort 1710, South Africa;
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Hu Z, Li C, Wu T, Zhou J, Han L, Liu J, Qiang S, Zhao W, Li X, Liu X, Li J, Chen X. Sulfathiazole treats type 2 diabetes by restoring metabolism through activating CYP19A1. Biochim Biophys Acta Gen Subj 2023; 1867:130303. [PMID: 36627088 DOI: 10.1016/j.bbagen.2023.130303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/24/2022] [Accepted: 01/03/2023] [Indexed: 01/09/2023]
Abstract
Globally, diabetes mellitus has been a major epidemic bringing metabolic and endocrine disorders. Currently, 1 in 11 adults suffers from diabetes mellitus, among the patients >90% contract type 2 diabetes mellitus (T2DM). Therefore, it is urgent to develop new drugs that effectively prevent and treat type 2 diabetes through new targets. With high-throughput screening, we found that sulfathiazole decreased the blood glucose and improved glucose metabolism in T2DM mice. Notably, we discovered that sulfathiazole treated T2DM by activating CYP19A1 protein to synthesize estrogen. Collectively, sulfathiazole along with CYP19A1 target bring new promise for the better therapy of T2DM.
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Affiliation(s)
- Zhuozhou Hu
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Chun Li
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Tongyu Wu
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Jing Zhou
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Liang Han
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Jingjing Liu
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Shaojia Qiang
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Wenyang Zhao
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Xiangxiang Li
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Xiaohua Liu
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China
| | - Jiazhong Li
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China.
| | - Xinping Chen
- School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou, Gansu 730000, PR China; Southeast Research Institute of LZU, Putian, Fujian 351152, PR China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, PR China.
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Ganguly R, Singh SV, Jaiswal K, Kumar R, Pandey AK. Modulatory effect of caffeic acid in alleviating diabetes and associated complications. World J Diabetes 2023; 14:62-75. [PMID: 36926656 PMCID: PMC10011896 DOI: 10.4239/wjd.v14.i2.62] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 11/04/2022] [Accepted: 12/14/2022] [Indexed: 02/14/2023] Open
Abstract
Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by elevated blood glucose levels. Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy, nephropathy, retinopathy, cardiovascular disorders, and diabetic foot ulcers. Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications. Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase, heme oxygenase-1, superoxide dismutase, and catalase that are essential in maintaining redox balance, and ameliorate oxidative stress. Caffeic acid (CA) is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties includ-ing antioxidant, anti-inflammatory, anti-atherosclerotic, immune-stimulatory, cardioprotective, antiproliferative, and hepatoprotective activities. CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets. These include various transcription factors such as nuclear factor-B, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor erythroid 2-related factor 2. Therefore, this review summarizes the pharmacological properties, molecular mechanisms, and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications. The bioavailability, drug delivery, and clinical trials of CA have also been discussed.
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Affiliation(s)
- Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
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9
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Lobato TB, Gennari-Felipe M, Pauferro JRB, Correa IS, Santos BF, Dias BB, de Oliveira Borges JC, dos Santos CS, de Sousa Santos ES, de Araújo MJL, Ferreira LA, Pereira SA, Serdan TDA, Levada-Pires AC, Hatanaka E, Borges L, Cury-Boaventura MF, Vinolo MAR, Pithon-Curi TC, Masi LN, Curi R, Hirabara SM, Gorjão R. Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity. Front Microbiol 2022; 13:1037469. [PMID: 36406408 PMCID: PMC9670542 DOI: 10.3389/fmicb.2022.1037469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/12/2022] [Indexed: 03/27/2024] Open
Abstract
Recent studies show that the metabolic characteristics of different leukocytes, such as, lymphocytes, neutrophils, and macrophages, undergo changes both in the face of infection with SARS-CoV-2 and in obesity and type 2 diabetes mellitus (DM2) condition. Thus, the objective of this review is to establish a correlation between the metabolic changes caused in leukocytes in DM2 and obesity that may favor a worse prognosis during SARS-Cov-2 infection. Chronic inflammation and hyperglycemia, specific and usual characteristics of obesity and DM2, contributes for the SARS-CoV-2 replication and metabolic disturbances in different leukocytes, favoring the proinflammatory response of these cells. Thus, obesity and DM2 are important risk factors for pro-inflammatory response and metabolic dysregulation that can favor the occurrence of the cytokine storm, implicated in the severity and high mortality risk of the COVID-19 in these patients.
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Affiliation(s)
- Tiago Bertola Lobato
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Matheus Gennari-Felipe
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | | | - Ilana Souza Correa
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Beatriz Ferreira Santos
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Beatriz Belmiro Dias
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - João Carlos de Oliveira Borges
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Camila Soares dos Santos
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | | | - Maria Janaína Leite de Araújo
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Liliane Araújo Ferreira
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Sara Araujo Pereira
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | | | - Adriana Cristina Levada-Pires
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Elaine Hatanaka
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Leandro Borges
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Maria Fernanda Cury-Boaventura
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Marco Aurélio Ramirez Vinolo
- Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Tania Cristina Pithon-Curi
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Laureane Nunes Masi
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Rui Curi
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
- Immunobiological Production Section, Bioindustrial Center, Butantan Institute, São Paulo, Brazil
| | - Sandro Massao Hirabara
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
| | - Renata Gorjão
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, São Paulo, Brasil
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10
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Mthiyane FT, Dludla PV, Ziqubu K, Mthembu SXH, Muvhulawa N, Hlengwa N, Nkambule BB, Mazibuko-Mbeje SE. A Review on the Antidiabetic Properties of Moringa oleifera Extracts: Focusing on Oxidative Stress and Inflammation as Main Therapeutic Targets. Front Pharmacol 2022; 13:940572. [PMID: 35899107 PMCID: PMC9310029 DOI: 10.3389/fphar.2022.940572] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/21/2022] [Indexed: 12/02/2022] Open
Abstract
Moringa oleifera is one of the popular plants that have shown significant health benefits. Certainly, preclinical evidence (predominantly from animal models) summarized in the current review supports the beneficial effects of Moringa oleifera leaf extracts in combating the prominent characteristic features of diabetes mellitus. This includes effective control of blood glucose or insulin levels, enhancement of insulin tissue sensitivity, improvement of blood lipid profiles, and protecting against organ damage under sustained conditions of hyperglycemia. Interestingly, as major complications implicated in the progression of diabetes, including organ damage, Moringa oleifera leaf and seed extracts could efficiently block the detrimental effects of oxidative stress and inflammation in these preclinical models. Notably, these extracts (especially leaf extracts) showed enhanced effects in strengthening intracellular antioxidant defences like catalase, superoxide dismutase, and glutathione to lower lipid peroxidation products and reduce prominent pro-inflammatory markers such as tumor necrosis factor-α, interleukin (1L)-β, IL-6, monocyte chemoattractant protein-1 and nitric oxide synthase. From animal models of diabetes, the common and effective dose of leaf extracts of Moringa oleifera was 100-300 mg/kg, within the treatment duration of 2-8 weeks. Whereas supplementation with approximately 20 g leaf powder of Moringa oleifera for at least 2 weeks could improve postprandial blood glucose in subjects with prediabetes or diabetes. Although limited clinical studies have been conducted on the antidiabetic properties of Moringa oleifera, current findings provide an important platform for future research directed at developing this plant as a functional food to manage diabetic complications.
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Affiliation(s)
- Fikile T. Mthiyane
- Department of Biochemistry, North-West University, Mafikeng, South Africa
| | - Phiwayinkosi V. Dludla
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
| | - Khanyisani Ziqubu
- Department of Biochemistry, North-West University, Mafikeng, South Africa
| | - Sinenhlanhla X. H. Mthembu
- Department of Biochemistry, North-West University, Mafikeng, South Africa
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
| | - Ndivhuwo Muvhulawa
- Department of Biochemistry, North-West University, Mafikeng, South Africa
| | - Nokulunga Hlengwa
- Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa
| | - Bongani B. Nkambule
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
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11
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Mokgalaboni K, Nkambule BB, Ntamo Y, Ziqubu K, Nyambuya TM, Mazibuko-Mbeje SE, Gabuza KB, Chellan N, Cirilli I, Tiano L, Dludla PV. Vitamin K: A vital micronutrient with the cardioprotective potential against diabetes-associated complications. Life Sci 2021; 286:120068. [PMID: 34688697 DOI: 10.1016/j.lfs.2021.120068] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/12/2021] [Accepted: 10/17/2021] [Indexed: 12/14/2022]
Abstract
Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes (T2D). The conventional therapies seem to offer minimal long-term cardioprotection against diabetes-related complications in patients living with T2D. There is a growing interest in understanding the therapeutic effects of food-derived bioactive compounds in protecting or managing these metabolic diseases. This includes uncovering the therapeutic potential of fat-soluble micronutrients such as vitamin K, which are abundantly found in green leafy vegetables. We searched the major electronic databases including PubMed, Web of Sciences, Scopus, Google Scholar and Science direct. The search retrieved randomized clinical trials and preclinical studies, reporting on the impact of vitamin K on CVD-related complications in T2D. The current review updates clinical evidence on the therapeutic benefits of vitamin K by attenuating CVD-risk factors such as blood lipid profiles, blood pressure, as well as markers of oxidative stress and inflammation in patients with T2D. Importantly, the summarized preclinical evidence provides a unique perspective into the pathophysiological mechanisms that could be targeted by vitamin K in the primary prevention of T2D-related complications. Lastly, this review further explores the controversies related to the cardioprotective effects of vitamin K, and also provides the basic information such as the source and bioavailability profile of this micronutrient is covered to highlight its therapeutic potential.
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Affiliation(s)
- Kabelo Mokgalaboni
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa
| | - Bongani B Nkambule
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa
| | - Yonela Ntamo
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Khanyisani Ziqubu
- Department of Biochemistry, North West University, Mafikeng Campus, Mmabatho 2735, South Africa
| | - Tawanda M Nyambuya
- Department of Health Sciences, Namibia University of Science and Technology, Windhoek 9000, Namibia
| | | | - Kwazikwakhe B Gabuza
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Nireshni Chellan
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa
| | - Ilenia Cirilli
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, Italy; School of Pharmacy, University of Camerino, Camerino 62032, Italy
| | - Luca Tiano
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, Italy
| | - Phiwayinkosi V Dludla
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa.
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12
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The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint. Cells 2021; 10:cells10113097. [PMID: 34831320 PMCID: PMC8619171 DOI: 10.3390/cells10113097] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/22/2021] [Accepted: 11/02/2021] [Indexed: 02/06/2023] Open
Abstract
microRNAs (miRs) are emerging as attractive therapeutic targets because of their small size, specific targetability, and critical role in disease pathogenesis. However, <20 miR targeting molecules have entered clinical trials, and none progressed to phase III. The difficulties in miR target identification, the moderate efficacy of miR inhibitors, cell type-specific delivery, and adverse outcomes have impeded the development of miR therapeutics. These hurdles are rooted in the functional complexity of miR's role in disease and sequence complementarity-dependent/-independent effects in nontarget tissues. The advances in understanding miR's role in disease, the development of efficient miR inhibitors, and innovative delivery approaches have helped resolve some of these hurdles. In this review, we provide a multidisciplinary viewpoint on the challenges and opportunities in the development of miR therapeutics.
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13
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Refat MS, Hamza RZ, Adam AMA, Saad HA, Gobouri AA, Al-Harbi FS, Al-Salmi FA, Altalhi T, El-Megharbel SM. Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies. PLoS One 2021; 16:e0246265. [PMID: 33661932 PMCID: PMC7932096 DOI: 10.1371/journal.pone.0246265] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open
Abstract
Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.
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Affiliation(s)
- Moamen S. Refat
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
- Department of Chemistry, Faculty of Science, Port Said University, Port Said, Egypt
| | - Reham Z. Hamza
- Biology Department, Faculty of Science, Taif University, Taif, Saudi Arabia
- Zoology Department, Faculty of Science, Zagazig University, Zagazig, Egypt
| | - Abdel Majid A. Adam
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
| | - Hosam A. Saad
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
- Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
| | - Adil A. Gobouri
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
| | | | | | - Tariq Altalhi
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
| | - Samy M. El-Megharbel
- Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia
- Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
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14
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Samadi M, Aziz SGG, Naderi R. The effect of tropisetron on oxidative stress, SIRT1, FOXO3a, and claudin-1 in the renal tissue of STZ-induced diabetic rats. Cell Stress Chaperones 2021; 26:217-227. [PMID: 33047279 PMCID: PMC7736377 DOI: 10.1007/s12192-020-01170-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 12/21/2022] Open
Abstract
Tropisetron is a 5-HT3 receptor antagonist that exerts protective effect against DN. The aim of this study was to investigate the possible molecular mechanisms associated with the renoprotective effects of tropisetron in STZ-induced diabetic rats. Animals were subdivided into 5 equal groups; control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). For induction of type 1 diabetes, a single injection of STZ (55 mg/kg, i.p.) was administered to the animals. Diabetic rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) for 2 weeks. According to the conducted analysis, diabetes led to renal dysfunction (reduction in glomerular filtration rate and urine urea and creatinine as well as elevation in plasma urea and creatinine) and abnormalities in antioxidant defense system (reduction in TAC and elevation in MDA), compared with the control group, which was prevented by tropisetron treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis demonstrated that SIRT1 gene expression decreased while FOXO3a and NF-κB gene expression as well as phosphorylated FOXO3a/total FOXO3a protein ratios and claudin-1 protein level increased in the kidney of diabetic rats compared with the control group. Herein, the results of this research showed that tropisetron treatment reversed these changes. Besides, all these changes were comparable with those produced by glibenclamide as a positive control. Hence, tropisetron ameliorated renal damage due to diabetic nephropathy possibly by suppressing oxidative stress and alteration of SIRT1, FOXO3a, and claudin-1 levels.
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Affiliation(s)
- Mahrokh Samadi
- Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Roya Naderi
- Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran.
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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15
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van de Venter M, Didloff J, Reddy S, Swanepoel B, Govender S, Dambuza NS, Williams S, Koekemoer TC, Venables L. Wild-Type Zebrafish ( Danio rerio) Larvae as a Vertebrate Model for Diabetes and Comorbidities: A Review. Animals (Basel) 2020; 11:E54. [PMID: 33396883 PMCID: PMC7824285 DOI: 10.3390/ani11010054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 12/12/2022] Open
Abstract
Zebrafish have become a popular alternative to higher animals in biomedical and pharmaceutical research. The development of stable mutant lines to model target specific aspects of many diseases, including diabetes, is well reported. However, these mutant lines are much more costly and challenging to maintain than wild-type zebrafish and are simply not an option for many research facilities. As an alternative to address the disadvantages of advanced mutant lines, wild-type larvae may represent a suitable option. In this review, we evaluate organ development in zebrafish larvae and discuss established methods that use wild-type zebrafish larvae up to seven days post fertilization to test for potential drug candidates for diabetes and its commonly associated conditions of oxidative stress and inflammation. This provides an up to date overview of the relevance of wild-type zebrafish larvae as a vertebrate antidiabetic model and confidence as an alternative tool for preclinical studies. We highlight the advantages and disadvantages of established methods and suggest recommendations for future developments to promote the use of zebrafish, specifically larvae, rather than higher animals in the early phase of antidiabetic drug discovery.
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Affiliation(s)
- Maryna van de Venter
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Jenske Didloff
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Shanika Reddy
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Bresler Swanepoel
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Sharlene Govender
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Ntokozo Shirley Dambuza
- Department of Pharmacy, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa;
| | - Saralene Williams
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Trevor Craig Koekemoer
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
| | - Luanne Venables
- Department of Biochemistry and Microbiology, Nelson Mandela University, PO Box 77000, Port Elizabeth 6031, South Africa; (J.D.); (S.R.); (B.S.); (S.G.); (S.W.); (T.C.K.); (L.V.)
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16
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Cui L, Yu M, Cui X. MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells. Open Life Sci 2020; 15:959-970. [PMID: 33817282 PMCID: PMC7874585 DOI: 10.1515/biol-2020-0089] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/29/2020] [Accepted: 07/07/2020] [Indexed: 12/14/2022] Open
Abstract
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Increasing evidence suggests that microRNA-30c-5p (miR-30c-5p) participates in the pathogenesis of DN, but the mechanism has not been clearly understood. Therefore, this study aimed to investigate the biological role of miR-30c-5p in human DN progression in vitro. Compared with the controls, DN tissues and high glucose-induced HK-2 cells had significantly reduced miR-30c-5p levels, while ROCK2 expression was prominently elevated. Additionally, the miR-30c-5p mimic distinctly facilitated cell proliferation and blocked cell apoptosis and epithelial–mesenchymal transition (EMT). However, ROCK2 was a target gene of miR-30c-5p, and the effects of miR-30c-5p mimic on cell proliferation, apoptosis and EMT were reversed by ROCK2 upregulation in vitro. Furthermore, the pathogenesis of DN was regulated by the miR-30c-5p/ROCK2 axis via the PI3K/AKT pathway. MiR-30c-5p regulating cell proliferation, apoptosis and EMT through targeting ROCK2 via the PI3K/AKT pathway provides the novel potential target for clinical treatment of DN.
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Affiliation(s)
- Lianshun Cui
- Department of Kidney Disease of Internal, Weihai Central Hospital, No. 3, Mishandong Road West, Wendeng District, 264400, Weihai, China
| | - Meiyan Yu
- Department of Kidney Disease of Internal, Weihai Central Hospital, No. 3, Mishandong Road West, Wendeng District, 264400, Weihai, China
| | - Xinglei Cui
- Department of Kidney Disease of Internal, Weihai Central Hospital, No. 3, Mishandong Road West, Wendeng District, 264400, Weihai, China
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17
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Shi L, Du X, Guo P, Huang L, Qi P, Gong Q. Ascorbic acid supplementation in type 2 diabetes mellitus: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e23125. [PMID: 33157992 PMCID: PMC7647560 DOI: 10.1097/md.0000000000023125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Diabetes is one of the most common chronic diseases in the world. In recent years, with the continuous improvement of people's living standards and changes in dietary structure, the incidence of diabetes is gradually increasing. Studies have shown that ascorbic acid supplementation can reduce blood glucose, increase insulin synthesis and secretion, improve insulin resistance, and reduce the occurrence and development of complications of type 2 diabetes mellitus (T2DM). However, relevant studies have common problems such as the lack of large sample studies and low quality of included studies. Therefore, it is needed that we meta-analyze the clinical trials with high quality to elucidate the efficacy and safety of ascorbic acid supplementation in patients with T2DM. METHODS We will search randomized controlled trials published by PubMed, Embase, the Cochrane Library, Web of Science, and the Clinical Trials.gov website from inception to August 2020 on the effects of ascorbic acid supplementation on blood glucose, glycosylated hemoglobin, serum insulin, insulin resistance and other variables in T2DM patients with no language restrictions. The retrieval adopts the combination of medical subject headings and random words, and traces the references of the included literature to supplement the acquisition of relevant literature. Two researchers will independently screen the retrieved literature, extract the data and cross-check, and the Review Manage software V5.3.0 will be utilized for meta-analysis. RESULTS Our study will provide a high-quality and in-depth comprehensive analysis of the effects of ascorbic acid supplementation on blood glucose control, glycosylated hemoglobin and insulin resistance in type 2 diabetic patients. CONCLUSION This systematic review and meta-analysis concerning randomized controlled trials of ascorbic acid supplementation for type 2 diabetic patients will provide a new direction and strong evidence to evaluate whether ascorbic acid supplementation is of benefit to glucose control and insulin resistance in T2DM. PROSPERO REGISTRATION NUMBER CRD 42019146826.
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Affiliation(s)
- Lipeng Shi
- Clinical Department, Dianjiang Hospital of Traditional Chinese Medicine, Dianjiang, Chongqing
| | - Xuqin Du
- College of Traditional Chinese Medicine, Chongqing Medical University
| | - Pei Guo
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Lumei Huang
- Clinical Department, Dianjiang Hospital of Traditional Chinese Medicine, Dianjiang, Chongqing
| | - Peng Qi
- Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China
| | - Qianhui Gong
- Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China
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18
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Li X, Wei Z, Wu L, Lv H, Zhang Y, Li J, Yao H, Zhang H, Yang B, Xu X, Jiang J. Efficacy of Fe 3O 4@polydopamine nanoparticle-labeled human umbilical cord Wharton's jelly-derived mesenchymal stem cells in the treatment of streptozotocin-induced diabetes in rats. Biomater Sci 2020; 8:5362-5375. [PMID: 32869785 DOI: 10.1039/d0bm01076f] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic β-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe3O4@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.
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Affiliation(s)
- Xiuying Li
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
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Xu E, Hu X, Li X, Jin G, Zhuang L, Wang Q, Pei X. Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells. BMC Endocr Disord 2020; 20:107. [PMID: 32689997 PMCID: PMC7372841 DOI: 10.1186/s12902-020-00593-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 07/13/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor. METHODS We investigated long non-coding RNAs (lncRNAs) and mRNAs that are affected by hyperglycemia-induced damage using human umbilical vein endothelial cells (HUVECs) as a model. HUVECs were cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 6 d, and then lncRNAs and protein-coding transcripts were profiled by RNA-seq. RESULT Among 40,379 lncRNAs screened, 214 were upregulated (log2 [fold-change] > 1, FDR < 0.05) and 197 were downregulated (log2 [fold-change] < - 1, FDR < 0.05) in response to high-glucose. Furthermore, among 28,431 protein-coding genes screened, 778 were upregulated and 998 were downregulated. A total of 945 lncRNA/mRNA pairs were identified, including 126 differentially expressed lncRNAs predicted to target 201 mRNAs, among which 26 were cis-regulatory interactions. The corresponding lncRNA-mRNA network was composed of 354 lncRNA nodes, 1167 mRNA nodes and 9735 edges. Dozens of lncRNAs with high degree may play important roles in high-glucose-induced HUVEC damage, including ENST00000600527, NONHSAT037576.2, NONHSAT135706.2, ENST00000602127, NONHSAT200243.1, NONHSAT217282.1, NONHSAT176260.1, NONHSAT199075.1, NONHSAT067063.2, NONHSAT058417.2. CONCLUSION These observations may provide novel insights into the regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction in diabetes-associated vascular disease.
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Affiliation(s)
- Erqin Xu
- Room of Physical Diagnostics, Clinical College of Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, P.R. China
| | - Xiaolei Hu
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China
| | - Xiaoli Li
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China
| | - Guoxi Jin
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China
| | - Langen Zhuang
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China
| | - Qiong Wang
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China
| | - Xiaoyan Pei
- Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China.
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20
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Sun Y, Song L, Zhang Y, Wang H, Dong X. Adipose stem cells from type 2 diabetic mice exhibit therapeutic potential in wound healing. Stem Cell Res Ther 2020; 11:298. [PMID: 32680569 PMCID: PMC7368682 DOI: 10.1186/s13287-020-01817-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 07/04/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
Background Diabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through the release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose tissue-derived MSCs (ASCs) from type 2 diabetes (T2D) donors are suitable for skin damage repair remains largely unknown. Methods In this study, we compared the phenotype and functionality of ASCs harvested from high-fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D. Results T2D ASCs expressed similar cellular markers as control ASCs but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration. Conclusions From these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.
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Affiliation(s)
- Yongfa Sun
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, Shandong, People's Republic of China
| | - Lili Song
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, Shandong, People's Republic of China
| | - Yong Zhang
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, Shandong, People's Republic of China
| | - Hongjun Wang
- Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Xiao Dong
- College of Life Science, Qingdao Agricultural University, No. 700, Changcheng Road, Chengyang District, Qingdao, 266109, Shandong, People's Republic of China.
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21
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Elkholy SE, Elaidy SM, El-Sherbeeny NA, Toraih EA, El-Gawly HW. Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ. Life Sci 2020; 250:117557. [PMID: 32184124 DOI: 10.1016/j.lfs.2020.117557] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 02/22/2020] [Accepted: 03/13/2020] [Indexed: 12/11/2022]
Abstract
Diabetic neuropathy (DN) is a common complication of diabetes mellitus (DM). Pathophysiology of DN includes inflammation and changes in expression and function of voltage-gated sodium channels (Nav) in peripheral nerves; and central reduction of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) expression. AIM This study explored the effect of ranolazine (RN) versus pioglitazone (PIO) in DN induced in rats. The role of sciatic interleukin (IL)-1β, tumor necrosis factor-alpha (TNF)-α, Nav1.7, and spinal PPAR-γ expressions were determined. MATERIALS AND METHODS For induction of Type-2 DM, 40 high fat diet-fed rats were challenged by a single dose of intraperitoneal streptozotocin (30 mg/kg). One week later, oral PIO (10 mg/kg; once daily) or RN (20, 50 and 100 mg/kg; twice daily) were administered for six weeks. Weekly body weight and fasting blood sugar (FBS) were measured. Rats were tested for thermal hyperalgesia and mechanical allodynia. At the end of the experiment, sciatic nerves homogenates were examined for TNF-α and IL-1B levels, and Nav1.7 channel expression. Segments of spinal cords were investigated for the PPAR-γ gene expression. Evaluation of histopathology of sciatic nerves and spinal cords were done. KEY FINDINGS In diabetic rats, PIO and RN individually improved evoked-pain behaviors, reduced sciatic TNF-α and 1L-1B levels; downregulated expressional levels of Nav1.7 channels; and increased the spinal PPAR-γ gene expression. RN in the dose of 100 mg/kg/day showed the most advantageous effects. SIGNIFICANCE RN has neuroprotective effects in Type-2 diabetes-induced DN. Further studies of combined RN-PIO treatment are recommended, especially in diabetic patients with cardiovascular co-morbidity.
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Affiliation(s)
- Shereen E Elkholy
- Department of Clinical Pharmacology, Faculty of Medicine, Port-Said University, Port-Said, Egypt
| | - Samah M Elaidy
- Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Nagla A El-Sherbeeny
- Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Eman A Toraih
- Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Center of Excellence of Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt
| | - Hoda W El-Gawly
- Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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22
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Gray ID, Kross AR, Renfrew ME, Wood P. Precision Medicine in Lifestyle Medicine: The Way of the Future? Am J Lifestyle Med 2020; 14:169-186. [PMID: 32231483 PMCID: PMC7092395 DOI: 10.1177/1559827619834527] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 12/21/2018] [Accepted: 02/08/2019] [Indexed: 02/06/2023] Open
Abstract
Precision medicine has captured the imagination of the medical community with visions of therapies precisely targeted to the specific individual's genetic, biological, social, and environmental profile. However, in practice it has become synonymous with genomic medicine. As such its successes have been limited, with poor predictive or clinical value for the majority of people. It adds little to lifestyle medicine, other than in establishing why a healthy lifestyle is effective in combatting chronic disease. The challenge of lifestyle medicine remains getting people to actually adopt, sustain, and naturalize a healthy lifestyle, and this will require an approach that treats the patient as a person with individual needs and providing them with suitable types of support. The future of lifestyle medicine is holistic and person-centered rather than technological.
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Affiliation(s)
- Ian D. Gray
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Andrea R. Kross
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Melanie E. Renfrew
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
| | - Paul Wood
- Avondale College of Higher Education, Cooranbong,
New South Wales, Australia
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23
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Scoville DK, Li CY, Wang D, Dempsey JL, Raftery D, Mani S, Gu H, Cui JY. Polybrominated Diphenyl Ethers and Gut Microbiome Modulate Metabolic Syndrome-Related Aqueous Metabolites in Mice. Drug Metab Dispos 2019; 47:928-940. [PMID: 31123037 PMCID: PMC6657215 DOI: 10.1124/dmd.119.086538] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 05/07/2019] [Indexed: 12/13/2022] Open
Abstract
Polybrominated diphenyl ethers (PBDEs) are persistent environmental toxicants associated with increased risk for metabolic syndrome. Intermediary metabolism is influenced by the intestinal microbiome. To test the hypothesis that PBDEs reduce host-beneficial intermediary metabolites in an intestinal microbiome-dependent manner, 9-week old male conventional (CV) and germ-free (GF) C57BL/6 mice were orally gavaged once daily with vehicle, BDE-47, or BDE-99 (100 μmol/kg) for 4 days. Intestinal microbiome (16S rDNA sequencing), liver transcriptome (RNA-Seq), and intermediary metabolites in serum, liver, as well as small and large intestinal contents (SIC and LIC; LC-MS) were examined. Changes in intermediary metabolite abundances in serum, liver, and SIC, were observed under basal conditions (CV vs. GF mice) and by PBDE exposure. PBDEs altered the largest number of metabolites in the LIC; most were regulated by PBDEs in GF conditions. Importantly, intestinal microbiome was necessary for PBDE-mediated decreases in branched-chain and aromatic amino acid metabolites, including 3-indolepropionic acid, a tryptophan metabolite recently shown to be protective against inflammation and diabetes. Gene-metabolite networks revealed a positive association between the hepatic glycan synthesis gene α-1,6-mannosyltransferase (Alg12) mRNA and mannose, which are important for protein glycosylation. Glycome changes have been observed in patients with metabolic syndrome. In LIC of CV mice, 23 bacterial taxa were regulated by PBDEs. Correlations of certain taxa with distinct serum metabolites further highlight a modulatory role of the microbiome in mediating PBDE effects. In summary, PBDEs impact intermediary metabolism in an intestinal microbiome-dependent manner, suggesting that dysbiosis may contribute to PBDE-mediated toxicities that include metabolic syndrome.
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Affiliation(s)
- David K Scoville
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Cindy Yanfei Li
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Dongfang Wang
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Joseph L Dempsey
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Daniel Raftery
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Sridhar Mani
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Haiwei Gu
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
| | - Julia Yue Cui
- Department of Environmental and Occupational Health Sciences (D.K.S., C.Y.L., J.L.D., J.Y.C.) and Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine (D.W., D.R.), University of Washington, Seattle, Washington; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, P. R. China (D.W.); Albert Einstein College of Medicine, Bronx, New York (S.M.); and Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Phoenix, Arizona (H.G.)
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24
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Zhu QJ, Zhu M, Xu XX, Meng XM, Wu YG. Exosomes from high glucose-treated macrophages activate glomerular mesangial cells via TGF-β1/Smad3 pathway in vivo and in vitro. FASEB J 2019; 33:9279-9290. [PMID: 31162940 DOI: 10.1096/fj.201802427rrr] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Diabetes nephropathy (DN) is characterized by abnormal interactions between kidney-infiltrating macrophages and glomerular mesangial cells. Recently, a novel cell-cell communication mediated by exosomes has gained attention. Exosomes are membrane-bound vesicles that contain a variety of molecules such as proteins, lipids, DNA, mRNA, and microRNAs. Exosomes play an important role in the pathogenesis of DN. In this study, we show that high glucose (HG) led to increased excretion of exosomes from macrophages. Mesangial cells took up exosomes in vitro, which resulted in the activation and proliferation of mesangial cells and the secretion of extracellular matrix and inflammatory cytokines. In addition, C57BL/6 mice injected with exosomes from HG-treated macrophages showed morphologic and functional changes. We then showed that exosomes from HG-treated TGF-β1 knockdown macrophages induced less extracellular matrix and fewer inflammatory factors in mesangial cells compared with vector control. Our findings suggest that TGF-β1 mRNA in exosomes serves a role between macrophages and mesangial cells by activating the TGF-β1/ mothers against decapentaplegic homolog 3 pathway.-Zhu, Q.-J., Zhu, M., Xu, M.-X., Meng, X.-M., Wu, Y.-G. Exosomes from high glucose-treated macrophages activate glomerular mesangial cells via TGF-β1/Smad3 pathway in vivo and in vitro.
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Affiliation(s)
- Qi-Jin Zhu
- Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Mei Zhu
- Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Xing-Xin Xu
- Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Xiao-Ming Meng
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Yong-Gui Wu
- Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, China
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25
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Oyebode OA, Erukainure OL, Ibeji C, Koorbanally NA, Islam MS. Crassocephalum rubens, a leafy vegetable, suppresses oxidative pancreatic and hepatic injury and inhibits key enzymes linked to type 2 diabetes: An ex vivo and in silico study. J Food Biochem 2019; 43:e12930. [PMID: 31368570 DOI: 10.1111/jfbc.12930] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 04/17/2019] [Accepted: 05/08/2019] [Indexed: 01/14/2023]
Abstract
Crassocephalum rubens falls under the wild edible, under-cultivated traditional leafy vegetables (TLV) in Africa; it is used by locals in managing diabetes mellitus among other diseases. This study investigated the in vitro, ex vivo antioxidant and antidiabetic potentials of different extracts of C. rubens. The ameliorative effects of the extracts on Fe2+ -induced oxidative injury was investigated ex vivo together with the effects of the aqueous extract on intestinal glucose absorption and muscle glucose uptake in freshly harvested tissues from normal rats. The aqueous extract was subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) analysis to identify possible bioactive compounds which were then docked with the tested enzymes through in silico modeling. The extracts exhibited antioxidant activity, inhibited α-glucosidase and lipase enzyme activities, intestinal glucose absorption and enhanced muscle glucose uptake compared to controls. Sanguisorbic acid dilactone identified through LC-MS analysis showed a high binding affinity for catalase and lipase enzymes. PRACTICAL APPLICATIONS: The results of this study suggest that the aqueous extract of C. rubens possesses better antioxidant and possible antidiabetic potentials compared to other extracts which could be associated to the synergistic action of its identified bioactive compounds.
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Affiliation(s)
- Olajumoke Arinola Oyebode
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal (Westville Campus), Durban, South Africa
| | - Ochuko Lucky Erukainure
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal (Westville Campus), Durban, South Africa
| | - Collins Ibeji
- Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, University of Nigeria, Nsukka, Nigeria
| | - Neil Anthony Koorbanally
- School of Chemistry and Physics, University of KwaZulu-Natal (Westville Campus), Durban, South Africa
| | - Md Shahidul Islam
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal (Westville Campus), Durban, South Africa
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26
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Mehta BK, Banerjee S. Minocycline reverses diabetes-associated cognitive impairment in rats. Pharmacol Rep 2019; 71:713-720. [PMID: 31207433 DOI: 10.1016/j.pharep.2019.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Revised: 02/12/2019] [Accepted: 03/19/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Minocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats. METHODS High fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment. RESULTS We induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment. CONCLUSIONS Minocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.
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Affiliation(s)
- Bina K Mehta
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
| | - Sugato Banerjee
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
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Lv P, Yu J, Xu X, Lu T, Xu F. Eriodictyol inhibits high glucose-induced oxidative stress and inflammation in retinal ganglial cells. J Cell Biochem 2018; 120:5644-5651. [PMID: 30317656 DOI: 10.1002/jcb.27848] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 09/17/2018] [Indexed: 12/31/2022]
Abstract
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and is considered as a leading cause of blindness. Oxidative stress and inflammation are significant drivers for the development of DR. Eriodictyol, a flavonoid compound, was proved to possess anti-inflammatory, antioxidative, and antidiabetic activities. However, the role of eriodictyol in DR has not been unveiled. In the current study, we explored the protective effects of eriodictyol on high glucose (HG)-induced rat retinal ganglial cells (RGCs). The results suggested that eriodictyol improved cell viability of HG-induced rat RGC-5 cells in a dose-dependent manner. Eriodictyol reduced the reactive oxygen species production and increased the activities of superoxide dismutase, glutathione peroxidase and catalase in rat RGC-5 cells in response to HG stimulation. The production of proinflammatory cytokines including tumor necrosis factor alpha and interleukin-8 was diminished after eriodictyol treatment. Eriodictyol also suppressed cell apoptosis induced HG in rat RGC-5 cells. Furthermore, eriodictyol enhanced the nuclear translocation of nuclear factor erythroid-2 (E2)-related factor 2 (Nrf2) and elevated the expression of antioxidant enzyme heme-oxygenase-1 (HO-1). These findings suggested that eriodictyol protects the RGC-5 cells from HG-induced oxidative stress, inflammation, and cell apoptosis through regulating the activation of Nrf2/HO-1 pathway.
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Affiliation(s)
- Peilin Lv
- Bioinspired Engineering and Biomechanics Center (BEBC), MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.,Department of Ophthalmology, The First hospital in Xi'an, Xi'an, China
| | - Jingni Yu
- Department of Ophthalmology, The Fourth hospital in Xi'an, Xi'an, China
| | - Xiayu Xu
- Bioinspired Engineering and Biomechanics Center (BEBC), MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Tianjian Lu
- MOE Key Laboratory of Multifunctional Materials and Structures, Xi'an Jiaotong University, Xi'an, China
| | - Feng Xu
- Bioinspired Engineering and Biomechanics Center (BEBC), MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
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Mayyas F, Alzoubi KH. Cardiac effects of cigarette tobacco smoking in rat model of diabetes. Life Sci 2018; 211:279-285. [PMID: 30244088 DOI: 10.1016/j.lfs.2018.09.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 09/19/2018] [Accepted: 09/19/2018] [Indexed: 01/08/2023]
Abstract
AIMS Tobacco smoking is considered a global health issue, contributing to increased risk of cardiovascular disease (CVD) and diabetes (DM). We aimed to assess effects of cigarette smoking on cardiac inflammation, oxidative stress and fibrosis in rat model of streptozotocin (STZ)-induced diabetes. MAIN METHODS Adults Wistar rats were assigned into control (fresh air, intraperitoneal injection (i.p) of citrate buffer), cigarette smoking (1 h daily for 4 weeks, i.p citrate buffer), DM (35 STZ mg/kg single i.p, fresh air), and DM + Smoking groups for 4 weeks. Cardiac biomarkers of oxidative stress, inflammation, and fibrosis were evaluated. KEY FINDINGS STZ-induced diabetes as documented by the persistent increase in blood glucose. Relative to control, a significant decrease in body weight was observed in diabetic groups paralleled with increased heart to body weight ratio and systolic blood pressure in all groups. Levels of total nitrite, thiobarbituric acid substances, endothelin -1, interleukin-6 and myeloperoxidase were increased in the DM, Smoking and DM + Smoking groups without changes in C-reactive protein. Cardiac levels of GSH were increased in Smoking groups whereas activities of catalase and superoxide dismutase increased in DM, Smoking and DM + Smoking groups. DM but not smoking increased cardiac fibrosis with a parallel increase in transforming growth factor beta. Cardiac levels of matrix metalloproteinase-2 were elevated in Smoking groups and decreased in DM. SIGNIFICANCE Exposure to cigarette smoke may increase risk of CVD in DM by increased cardiac oxidative stress and inflammation. Smoking was associated with increased oxidant enzymes and metalloproteinase-2 probably to prevent cardiac fibrosis.
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Affiliation(s)
- F Mayyas
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
| | - K H Alzoubi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
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29
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An HJ, Lee B, Kim SM, Kim DH, Chung KW, Ha SG, Park KC, Park YJ, Kim SJ, Yun HY, Chun P, Yu BP, Moon HR, Chung HY. A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation. Biol Pharm Bull 2018; 41:29-35. [PMID: 29311481 DOI: 10.1248/bpb.b17-00371] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating β-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.
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Affiliation(s)
- Hye Jin An
- College of Pharmacy, Pusan National University
| | - Bonggi Lee
- College of Pharmacy, Pusan National University.,Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM)
| | | | | | | | | | | | | | | | | | | | - Byung Pal Yu
- Department of Physiology, The University of Texas Health Science Center at San Antonio
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30
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Wang M, Song L, Strange C, Dong X, Wang H. Therapeutic Effects of Adipose Stem Cells from Diabetic Mice for the Treatment of Type 2 Diabetes. Mol Ther 2018; 26:1921-1930. [PMID: 30005867 DOI: 10.1016/j.ymthe.2018.06.013] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 05/30/2018] [Accepted: 06/12/2018] [Indexed: 02/07/2023] Open
Abstract
To assess the potential therapeutic effects of adipose tissue-derived mesenchymal stem cells (ASCs) for the treatment of type 2 diabetes (T2D), we compared the phenotype and functionality of ASCs isolated from high-fat diet and streptozotocin (STZ)-induced T2D and the leptin receptor-deficient (db/db) mice with cells from healthy C57BL/6 mice. ASCs from T2D or db/db mice showed similar expression patterns of cellular markers and abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. However, the rate of proliferation was reduced. ASCs from db/db mice secreted less hepatocyte growth factor (HGF). T2D mice receiving a single intravenous injection of T2D or db/db ASCs showed increased insulin sensitivity, reduced inflammation and fat content in adipose tissue and the liver and increased pancreatic β cell mass through 5 weeks post-infusion. Our data show that, although ASCs from T2D or db/db mice had inferior proliferative capacity compared to cells from healthy controls, improved insulin sensitivity and less β cell death was seen in T2D mice receiving mesenchymal stem cell (MSC) therapy. This study offers evidence that ASCs from diabetic donors have the potential to be used for cell therapy in the treatment of insulin resistance and T2D.
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Affiliation(s)
- Mengmeng Wang
- College of Life Science, Qingdao Agricultural University, Qingdao, Shandong 266109, China
| | - Lili Song
- China Agricultural University, Beijng 100094, China
| | - Charlie Strange
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Xiao Dong
- College of Life Science, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
| | - Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
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Abstract
PURPOSE OF REVIEW Diabetic kidney disease (DKD) is one of the most common complications in diabetes mellitus and accounts for a large proportion of clinical nephrology practice. Studies have shown that the kallikrein-kinin system (KKS) may be involved in several pathogenic mechanisms that contribute to DKD, including oxidative stress, inflammatory cytokines, and profibrotic autacoids. This review focuses on recent research advance on the potential role of the KKS in the development of DKD and its clinical relevance. RECENT FINDINGS A number of recent studies support the idea that there is a protective role of the KKS in diabetes. For example, agents that activate the KKS have shown strong renal protective effects that might highlight its potential to change the clinical practice. In addition, diabetic mice lacking both bradykinin B2 and B1 receptors have worse kidney lesions as compared with wild-type diabetic mice. SUMMARY Current basic research has demonstrated that pharmacological activation of the KKS improves renal outcomes in diabetes. These findings suggest that this system may be a therapeutic target in preventing and treating DKD.
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Chaudhary K, Promsote W, Ananth S, Veeranan-Karmegam R, Tawfik A, Arjunan P, Martin P, Smith SB, Thangaraju M, Kisselev O, Ganapathy V, Gnana-Prakasam JP. Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression. Sci Rep 2018; 8:3025. [PMID: 29445185 PMCID: PMC5813018 DOI: 10.1038/s41598-018-21276-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 01/31/2018] [Indexed: 12/31/2022] Open
Abstract
Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.
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Affiliation(s)
- Kapil Chaudhary
- Department of Medicine, Washington University, St. Louis, Missouri, USA
| | | | - Sudha Ananth
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Rajalakshmi Veeranan-Karmegam
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Amany Tawfik
- Dental College of Georgia, Augusta University, Augusta, Georgia, USA
| | | | - Pamela Martin
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Sylvia B Smith
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Muthusamy Thangaraju
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | - Oleg Kisselev
- Department of Ophthalmology and Department of Biochemistry & Molecular Biology, Saint Louis University, St. Louis, Missouri, USA
| | - Vadivel Ganapathy
- Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Jaya P Gnana-Prakasam
- Department of Ophthalmology and Department of Biochemistry & Molecular Biology, Saint Louis University, St. Louis, Missouri, USA.
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Du YG, Zhang KN, Gao ZL, Dai F, Wu XX, Chai KF. Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway. Exp Ther Med 2017; 15:2156-2164. [PMID: 29434819 DOI: 10.3892/etm.2017.5621] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 02/24/2017] [Indexed: 12/28/2022] Open
Abstract
The present study investigated the mechanism underlying the anti-inflammatory effects of Tangshen formula (TS) in Sprague Dawley (SD) rats with diabetic nephropathy (DN). A rat model of DN was established by intraperitoneal injection of 1% (40 mg/kg) streptozotocin and administration of a high fat and glucose diet. Subsequently, SD rats were randomly divided into six groups (n=8): A DN group, a valsartan group, a high-dose TS group, a middle-dose TS group, a low-dose TS group and a control group with normal SD rats. Once rats received their allocated treatment for 12 weeks, body weight and kidney weight were recorded, and fasting blood glucose, ratio of urinary protein, β2-MG and creatinine clearance rate were determined. Furthermore, hemodynamic indices, including plasma viscosity and whole blood reduction viscosity were detected. Immunohistochemistry was used to detect the infiltration of macrophages in the kidneys of rats. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to investigate the activation; mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), nuclear factor-κB (NF-κB) and sirtuin-1 (SIRT1) in each group. In comparison with the DN group, each biochemical indicator of rats in the high-dose TS group was significantly decreased (P<0.05). Blood viscosity in each treatment group was significantly decreased when compared with the DN group (P<0.01). Hematoxylin and eosin staining indicated that the infiltration of macrophages was significantly decreased in the high-dose TS group when compared with the DN group (P<0.01). mRNA and protein expression levels of MCP-1 and MIF in the high-dose TS group were significantly decreased when compared with the DN group (P<0.05). In the treatment groups, SITR1 mRNA expression levels were significantly increased, whereas the mRNA expression levels of NF-κB were significantly decreased (P<0.01). Western blotting results indicated a significant decrease in the protein expression levels of acetylated NF-κB in the treatment groups when compared with the DN group (P<0.01) and the propensity of protein expression of the other inflammatory factors were consistent with the mRNA findings. The results of the high-dose TS group were similar to those of the valsartan group. The present study indicates that TS was able to activate SITR1, which lead to NF-κB deacetylation, thus reducing the release of inflammatory factors and decreasing the severity of diabetic nephropathy.
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Affiliation(s)
- Yue-Guang Du
- Department of Pathology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Ke-Na Zhang
- Department of Pathology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Zong-Lei Gao
- National Traditional Chinese Medicine Clinical Research Center, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Fengjiao Dai
- National Traditional Chinese Medicine Clinical Research Center, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Xi-Xi Wu
- National Traditional Chinese Medicine Clinical Research Center, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Ke-Fu Chai
- National Traditional Chinese Medicine Clinical Research Center, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
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Rodrigues MJ, Custódio L, Lopes A, Oliveira M, Neng NR, Nogueira JMF, Martins A, Rauter AP, Varela J, Barreira L. Unlocking the in vitro anti-inflammatory and antidiabetic potential of Polygonum maritimum. PHARMACEUTICAL BIOLOGY 2017; 55:1348-1357. [PMID: 28301958 PMCID: PMC6130642 DOI: 10.1080/13880209.2017.1301493] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
CONTEXT Several Polygonum species (Polygonaceae) are used in traditional medicine in Asia, Europe and Africa to treat inflammation and diabetes. OBJECTIVE Evaluate the in vitro antioxidant, anti-inflammatory and antidiabetic potential of methanol and dichloromethane extracts of leaves and roots of the halophyte Polygonum maritimum L. MATERIAL AND METHODS Antioxidant activity was determined (up to 1 mg/mL) as radical-scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), copper (CCA) and iron (ICA) chelating activities and iron reducing power (FRAP). NO production was measured in lipopolysaccharide (LPS)-stimulated macrophages for 24 h at concentrations up to 100 μg/mL and antidiabetic potential was assessed by α-amylase and α-glucosidase inhibition (up to 10 mg/mL) assays. The phytochemical composition of the extracts was determined by gas chromatography-mass spectrometry (GC-MS). RESULTS The methanol leaf extract had the highest activity against DPPH• (IC50 = 26 μg/mL) and ABTS+• (IC50 = 140 μg/mL), FRAP (IC50 = 48 μg/mL) and CCA (IC50 = 770 μg/mL). Only the dichloromethane leaf extract (LDCM) showed anti-inflammatory activity (IC50 = 48 μg/mL). The methanol root (IC50 = 19 μg/mL) and leaf (IC50 = 29 μg/mL) extracts strongly inhibited baker's yeast α-glucosidase, but LDCM had higher rat's α-glucosidase inhibition (IC50 = 2527 μg/mL) than acarbose (IC50 = 4638 μg/mL). GC-MS analysis identified β-sitosterol, stigmasterol, 1-octacosanol and linolenic acid as possible molecules responsible for the observed bioactivities. CONCLUSIONS Our findings suggest P. maritimum as a source of high-value health promoting commodities for alleviating symptoms associated with oxidative and inflammatory diseases, including diabetes.
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Affiliation(s)
| | - Luísa Custódio
- CCMAR, Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal
| | - Andreia Lopes
- CCMAR, Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal
| | - Marta Oliveira
- CCMAR, Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal
| | - Nuno R. Neng
- Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - José M. F. Nogueira
- Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - Alice Martins
- Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - Amélia P. Rauter
- Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - João Varela
- CCMAR, Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal
| | - Luísa Barreira
- CCMAR, Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal
- CONTACT Luísa BarreiraCCMAR Centro de Ciências do Mar, Universidade do Algarve, Campus de Gambelas, 8005-139Faro, Portugal
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Onphachanh X, Lee HJ, Lim JR, Jung YH, Kim JS, Chae CW, Lee SJ, Gabr AA, Han HJ. Enhancement of high glucose-induced PINK1 expression by melatonin stimulates neuronal cell survival: Involvement of MT 2 /Akt/NF-κB pathway. J Pineal Res 2017; 63. [PMID: 28580603 DOI: 10.1111/jpi.12427] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 05/31/2017] [Indexed: 12/11/2022]
Abstract
Hyperglycemia is a representative hallmark and risk factor for diabetes mellitus (DM) and is closely linked to DM-associated neuronal cell death. Previous investigators reported on a genome-wide association study and showed relationships between DM and melatonin receptor (MT), highlighting the role of MT signaling by assessing melatonin in DM. However, the role of MT signaling in DM pathogenesis is unclear. Therefore, we investigated the role of mitophagy regulators in high glucose-induced neuronal cell death and the effect of melatonin against high glucose-induced mitophagy regulators in neuronal cells. In our results, high glucose significantly increased PTEN-induced putative kinase 1 (PINK1) and LC-3B expressions; as well it decreased cytochrome c oxidase subunit 4 expression and Mitotracker™ fluorescence intensity. Silencing of PINK1 induced mitochondrial reactive oxygen species (ROS) accumulation and mitochondrial membrane potential impairment, increased expressions of cleaved caspases, and increased the number of annexin V-positive cells. In addition, high glucose-stimulated melatonin receptor 1B (MTNR1B) mRNA and PINK1 expressions were reversed by ROS scavenger N-acetyl cysteine pretreatment. Upregulation of PINK1 expression in neuronal cells is suppressed by pretreatment with MT2 receptor-specific inhibitor 4-P-PDOT. We further showed melatonin stimulated Akt phosphorylation, which was followed by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and nuclear translocation. Silencing of PINK1 expression abolished melatonin-regulated mitochondrial ROS production, cleaved caspase-3 and caspase-9 expressions, and the number of annexin V-positive cells. In conclusion, we have demonstrated the melatonin stimulates PINK1 expression via an MT2 /Akt/NF-κB pathway, and such stimulation is important for the prevention of neuronal cell apoptosis under high glucose conditions.
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Affiliation(s)
- Xaykham Onphachanh
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- Animal Science Department, Faculty of Agriculture and Forest Resource, Souphanouvong University, Luang Prabang, Lao PDR
| | - Hyun Jik Lee
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
| | - Jae Ryong Lim
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
| | - Young Hyun Jung
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
| | - Jun Sung Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
| | - Chang Woo Chae
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
| | - Sei-Jung Lee
- Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, South Korea
| | - Amr Ahmed Gabr
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ho Jae Han
- Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Korea
- BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, Seoul, Korea
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Guo X, Sun W, Huang L, Wu L, Hou Y, Qin L, Liu T. Effect of Cinnamaldehyde on Glucose Metabolism and Vessel Function. Med Sci Monit 2017; 23:3844-3853. [PMID: 28790298 PMCID: PMC5562185 DOI: 10.12659/msm.906027] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background Material/Methods Results Conclusions
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Affiliation(s)
- Xuan Guo
- Department of Endocrinology, Beijing University of Chinese Medicine, Beijing, China (mainland)
| | - Wen Sun
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China (mainland)
| | - Liansha Huang
- Preventive Treatment of Disease Centre, Chinese Medicine Hospital of Baoan, Shenzhen, Guangdong, China (mainland)
| | - Lili Wu
- Beijing key Laboratory of Health Cultivation, Beijing University of Chinese Medicine, Beijing, China (mainland)
| | - Yi Hou
- Department of Endocrinology, Beijing University of Chinese Medicine, Beijing, China (mainland)
| | - Lingling Qin
- Department of Science and Technology, Beijing University of Chinese Medicine, Beijing, China (mainland)
| | - Tonghua Liu
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China (mainland)
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Sun WW, Zhu P, Shi YC, Zhang CL, Huang XF, Liang SY, Song ZY, Lin S. Current views on neuropeptide Y and diabetes-related atherosclerosis. Diab Vasc Dis Res 2017; 14:277-284. [PMID: 28423914 DOI: 10.1177/1479164117704380] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Diabetes-induced atherosclerotic cardiovascular disease is the leading cause of death of diabetic patients. Neuronal regulation plays a critical role in glucose metabolism and cardiovascular function under physiological and pathological conditions, among which, neurotransmitter neuropeptide Y has been shown to be closely involved in these two processes. Elevated central neuropeptide Y level promotes food intake and reduces energy expenditure, thereby increasing adiposity. Neuropeptide Y is co-localized with noradrenaline in central and sympathetic nervous systems. As a major peripheral vascular contractive neurotransmitter, through interactions with its receptors, neuropeptide Y has been implicated in the pathology and progression of diabetes, by promoting the proliferation of endothelial cells and vascular fibrosis, which may contribute to diabetes-induced cardiovascular disease. Neuropeptide Y also participates in the pathogenesis of atherosclerosis, the major form of cardiovascular disease, via aggravating endothelial dysfunction, growth of vascular smooth muscle cells, formation of foam cells and platelets aggregation. This review highlights the causal role of neuropeptide Y and its receptor system in the development of diabetes mellitus and one of its complications: atherosclerotic cardiovascular disease. The information from this review provides both critical insights onto the mechanisms underlying the pathogenesis of atherosclerosis and evidence for the development of therapeutic strategies.
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Affiliation(s)
- Wei-Wei Sun
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Ping Zhu
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Yan-Chuan Shi
- 2 Neuroscience Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Chen-Liang Zhang
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xu-Feng Huang
- 3 School of Health Sciences and Illawarra Health and Medical Research Institute, University of Wollongong Australia, Wollongong, NSW, Australia
| | - Shi-Yu Liang
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Zhi-Yuan Song
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Shu Lin
- 1 Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China
- 3 School of Health Sciences and Illawarra Health and Medical Research Institute, University of Wollongong Australia, Wollongong, NSW, Australia
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Zhang D, Zhu B, Zhang W, Wang W, Guo D, Yang L, Wang L. Total bilirubin level may be a biomarker of nephropathy in type 2 diabetes mellitus: A meta-analysis of observational studies based on MOOSE compliant. Medicine (Baltimore) 2017; 96:e5765. [PMID: 28072721 PMCID: PMC5228681 DOI: 10.1097/md.0000000000005765] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Recently, the number of the studies on the relationship between the total bilirubin level (TBL) and diabetic nephropathy (DN) is increasing, but their results were not consistent. Therefore, we performed a meta-analysis to analyze the relationship between TBL and the risk of DN.We searched 5 databases before October 31, 2016, and reviewed the reference list of relevant articles. The fixed or random-effects model was used to pool risk estimates. We conducted the dose-response meta-analysis to evaluate the relationship between TBL and the risk of DN.Our meta-analysis showed that TBL in the DN group was lower than that in diabetes without the kidney disease (NDN) group (standard mean difference [SMD]: -0.63, 95% CI: -0.80, -0.46). The result of each subgroup also showed that TBL in the DN group was lower than that in the NDN group. The result of meta-regression indicated that duration of diabetes mellitus might be the source of heterogeneity. Our meta-analysis also showed that there was a significant negative relationship between TBL and the risk of DN (OR: 0.86, 95%CI: 0.82, 0.90). The results of subgroup analysis were similar to those of SMD; no sources of heterogeneity were detected by meta-regression. Sensitivity analysis indicated that the results were robust. We observed a linear association between TBL and the risk of DN, and there was a negative dose-response association between TBL and the risk of DN.In conclusion, bilirubin may be used as a biomarker of DN. It helps early diagnosis and effective therapeutic strategies on DN.
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Affiliation(s)
- Dan Zhang
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
| | - Bo Zhu
- Department of Cancer Prevention and Treatment, Cancer Hospital of China Medical University/ Liaoning Cancer Hospital & Institute Shenyang, People's Republic of China
| | - Wei Zhang
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
| | - Wei Wang
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
| | - Dan Guo
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
| | - Ligang Yang
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
| | - Lu Wang
- Department of Endocrinology, Fourth Hospital of China Medical University, Shenyang
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Dong N, Xie Z, Dai J, Wang W, Sun R, Zhan Y, Sun M, Tian J, Yu B. Statin-induced improvements in vulnerable plaques are attenuated in poorly controlled diabetic patients with coronary atherosclerosis disease: a serial optical coherence tomography analysis. Acta Diabetol 2016; 53:999-1008. [PMID: 27590661 DOI: 10.1007/s00592-016-0902-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 08/17/2016] [Indexed: 11/30/2022]
Abstract
AIMS The incidence of cardiac events is increased in diabetic patients even after lipid-lowering therapy. This study aimed to compare the statin-induced changes in the characteristics of vulnerable plaques in patients without diabetes mellitus (DM) and in those with better- or poorly controlled DM, measured by optical coherence tomography (OCT). METHODS This was a retrospective study of 99 non-culprit lipid-rich plaques from 75 patients who underwent intensive OCT imaging examination. Thirty-four non-diabetic patients were assigned to Group A. According to the average HbA1c level, 22 diabetic patients were assigned to Group B, and 19, to Group C (average HbA1c < 8 and ≥8 %, respectively). RESULTS Following 12 months of statin therapy, similar improvements in serum lipid levels were observed in the three groups. However, the increase in fibrous-cap thickness of plaques was the highest in Group A (Group A, 183 %; Group B, 104 %; and Group C, 53 %). Significant reductions in lipid volume index were observed in Groups A and B (Group A: -12 %, P < 0.001; Group B: -13 %, P = 0.038; Group C: 7 %, P = 0.948). Percent changes in OCT measurements were significantly correlated with average HbA1c in patients. CONCLUSIONS Improved glucose control may enhance the statin-induced reduction in characteristics of vulnerable plaque in diabetic patients.
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Affiliation(s)
- Nana Dong
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Zulong Xie
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Jiannan Dai
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Wei Wang
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Rong Sun
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Yefei Zhan
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Meng Sun
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Jinwei Tian
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
| | - Bo Yu
- Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
- The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
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40
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Wu P, Yan Y, Ma LL, Hou BY, He YY, Zhang L, Niu ZR, Song JK, Pang XC, Yang XY, Du GH. Effects of the Nrf2 Protein Modulator Salvianolic Acid A Alone or Combined with Metformin on Diabetes-associated Macrovascular and Renal Injury. J Biol Chem 2016; 291:22288-22301. [PMID: 27417135 DOI: 10.1074/jbc.m115.712703] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Indexed: 11/06/2022] Open
Abstract
Nuclear factor E2-related factor 2 (Nrf2) is considered a promising target against diabetic complications such as cardiovascular diseases and diabetic nephropathy. Herein, we investigated the effects of a potential Nrf2 modulator, salvianolic acid A (SAA), which is a natural polyphenol, on diabetes-associated macrovascular and renal injuries in streptozotocin-induced diabetic mice. Given that lowering glucose is the first objective of diabetic patients, we also examined the effects of SAA combined with metformin (MET) on both complications. Our results showed that SAA significantly increased the macrovascular relaxation response to acetylcholine and sodium nitroprusside in diabetic mice. Interestingly, treatment with SAA alone only provided minor protection against renal injury, as reflected by minor improvements in impaired renal function and structure, despite significantly reduced oxidative stress observed in the diabetic kidney. We demonstrated that decreased oxidative stress and NF-κB p65 expression were associated with SAA-induced expression of Nrf2-responsive antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (quinone) 1 (NQO-1), and glutathione peroxidase-1 (GPx-1) in vivo or in vitro, which suggested that SAA was a potential Nrf2 modulator. More significantly, compared with treatment with either SAA or MET alone, we found that their combination provided further protection against the macrovascular and renal injury, which was at least partly due to therapeutic activation of both MET-mediated AMP-activated protein kinase and SAA-mediated Nrf2/antioxidant-response element pathways. These findings suggested that polyphenol Nrf2 modulators, especially combined with drugs activating AMP-activated protein kinase, including hypoglycemic drugs, are worthy of further investigation to combat diabetic complications.
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Affiliation(s)
- Ping Wu
- From the Institute of Materia Medica and
| | - Yu Yan
- From the Institute of Materia Medica and
| | - Lin-Lin Ma
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050 and
| | - Bi-Yu Hou
- From the Institute of Materia Medica and
| | - Yang-Yang He
- From the Institute of Materia Medica and the State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China
| | - Li Zhang
- From the Institute of Materia Medica and
| | - Zi-Ran Niu
- From the Institute of Materia Medica and
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