Yi Cui, Li Wang, Wentao Liang, Li Huang, Shuting Zhuang, Hong Shi, Nuo Xu, Jianzhang Hu
Background. Diabetic keratopathy (DK) poses a significant challenge in diabetes mellitus, yet its molecular pathways and effective treatments remain elusive. The aim of our research was to explore the pyroptosis-related genes in the corneal epithelium of the streptozocin-induced diabetic rats. Methods. After sixteen weeks of streptozocin intraperitoneal injection, corneal epithelium from three diabetic rats and three normal groups underwent whole-transcriptome sequencing. An integrated bioinformatics pipeline, including differentially expressed gene (DEG) identification, enrichment analysis, protein-protein interaction (PPI) network, coexpression, drug prediction, and immune deconvolution analyses, identified hub genes and key drivers in DK pathogenesis. These hub genes were subsequently validated in vivo through RT-qPCR. Results. A total of 459 DEGs were screened out from the diabetic group and nondiabetic controls. Gene Set Enrichment Analysis highlighted significant enrichment of the NOD-like receptor, Toll-like receptor, and NF-kappa B signaling pathways. Intersection of DEGs and pyroptosis-related datasets showed 33 differentially expressed pyroptosis-related genes (DEPRGs) associated with pathways such as IL-17, NOD-like receptor, TNF, and Toll-like receptor signaling. A competing endogenous RNA network comprising 16 DEPRGs, 22 lncRNAs, 13 miRNAs, and 3 circRNAs was constructed. After PPI network, five hub genes (Nfkb1, Casp8, Traf6, Ptgs2, and Il18) were identified as upregulated in the diabetic group, and their expression was validated by RT-qPCR in streptozocin-induced rats. Immune infiltration characterization showed that diabetic corneas owned a higher proportion of resting mast cells, activated NK cells, and memory-resting CD4 T cells. Finally, several small compounds including all-trans-retinoic acid, Chaihu Shugan San, dexamethasone, and resveratrol were suggested as potential therapies targeting these hub genes for DK. Conclusions. The identified and validated hub genes, Nfkb1, Casp8, Traf6, Ptgs2, and Il18, may play crucial roles in DK pathogenesis and serve as therapeutic targets.
{"title":"Identification and Validation of the Pyroptosis-Related Hub Gene Signature and the Associated Regulation Axis in Diabetic Keratopathy","authors":"Yi Cui, Li Wang, Wentao Liang, Li Huang, Shuting Zhuang, Hong Shi, Nuo Xu, Jianzhang Hu","doi":"10.1155/2024/2920694","DOIUrl":"https://doi.org/10.1155/2024/2920694","url":null,"abstract":"<i>Background</i>. Diabetic keratopathy (DK) poses a significant challenge in diabetes mellitus, yet its molecular pathways and effective treatments remain elusive. The aim of our research was to explore the pyroptosis-related genes in the corneal epithelium of the streptozocin-induced diabetic rats. <i>Methods</i>. After sixteen weeks of streptozocin intraperitoneal injection, corneal epithelium from three diabetic rats and three normal groups underwent whole-transcriptome sequencing. An integrated bioinformatics pipeline, including differentially expressed gene (DEG) identification, enrichment analysis, protein-protein interaction (PPI) network, coexpression, drug prediction, and immune deconvolution analyses, identified hub genes and key drivers in DK pathogenesis. These hub genes were subsequently validated in vivo through RT-qPCR. <i>Results</i>. A total of 459 DEGs were screened out from the diabetic group and nondiabetic controls. Gene Set Enrichment Analysis highlighted significant enrichment of the NOD-like receptor, Toll-like receptor, and NF-kappa B signaling pathways. Intersection of DEGs and pyroptosis-related datasets showed 33 differentially expressed pyroptosis-related genes (DEPRGs) associated with pathways such as IL-17, NOD-like receptor, TNF, and Toll-like receptor signaling. A competing endogenous RNA network comprising 16 DEPRGs, 22 lncRNAs, 13 miRNAs, and 3 circRNAs was constructed. After PPI network, five hub genes (<i>Nfkb1</i>, <i>Casp8</i>, <i>Traf6</i>, <i>Ptgs2</i>, and <i>Il18</i>) were identified as upregulated in the diabetic group, and their expression was validated by RT-qPCR in streptozocin-induced rats. Immune infiltration characterization showed that diabetic corneas owned a higher proportion of resting mast cells, activated NK cells, and memory-resting CD4 T cells. Finally, several small compounds including all-trans-retinoic acid, Chaihu Shugan San, dexamethasone, and resveratrol were suggested as potential therapies targeting these hub genes for DK. <i>Conclusions</i>. The identified and validated hub genes, <i>Nfkb1</i>, <i>Casp8</i>, <i>Traf6</i>, <i>Ptgs2</i>, and <i>Il18</i>, may play crucial roles in DK pathogenesis and serve as therapeutic targets.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"75 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140152247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<i>Background</i>. Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the risk of cardiovascular events. The aim of the present systematic review and meta-analysis is to demonstrate the effects of GLP-1 RA and SGLT2is on intima-media thickness (IMT). <i>Methods</i>. PubMed, EMBASE, Web of Science, SCOPUS, and Google Scholar databases were searched from inception to September 9, 2023. All interventional and observational studies that provided data on the effects of GLP-1 RAs or SGLT2is on IMT were included. Critical appraisal was performed using the Joanna Briggs Institute checklists. IMT changes (preintervention and postintervention) were pooled and meta-analyzed using a random-effects model. Subgroup analyses were based on type of medication (GLP-1 RA: liraglutide and exenatide; SGLT2i: empagliflozin, ipragliflozin, tofogliflozin, and dapagliflozin), randomized clinical trials (RCTs), and diabetic patients. <i>Results</i>. The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA, and eleven examined the effects of SGLT2i. GLP-1 RA and SGLT2i significantly decreased IMT (<span><svg height="8.87491pt" style="vertical-align:-0.3499308pt" version="1.1" viewbox="-0.0498162 -8.52498 32.48 8.87491" width="32.48pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.583,0)"></path></g><g transform="matrix(.013,0,0,-0.013,24.849,0)"></path></g></svg><span></span><span><svg height="8.87491pt" style="vertical-align:-0.3499308pt" version="1.1" viewbox="36.0621838 -8.52498 35.816 8.87491" width="35.816pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,36.112,0)"></path></g><g transform="matrix(.013,0,0,-0.013,43.743,0)"></path></g><g transform="matrix(.013,0,0,-0.013,49.983,0)"></path></g><g transform="matrix(.013,0,0,-0.013,52.947,0)"></path></g><g transform="matrix(.013,0,0,-0.013,59.187,0)"></path></g><g transform="matrix(.013,0,0,-0.013,65.427,0)"></path></g></svg>,</span></span> 95% CI (-0.170, -0.076), <span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.6359 19.289 9.2729" width="19.289pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"></path></g></svg><span></span><span><svg height="9.2729pt" style="vertical-align:-0.6370001pt" version="1.1" viewbox="22.8711838 -8.6359 34.445 9.2729" width="34.445pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,29.161
背景。除了控制血糖外，胰高血糖素样肽-1 受体激动剂（GLP-1 RA）和钠-葡萄糖共转运体 2 抑制剂（SGLT2is）也被认为可以降低心血管事件的风险。本系统综述和荟萃分析旨在证明 GLP-1 RA 和 SGLT2is 对内膜中层厚度（IMT）的影响。研究方法检索了从开始到 2023 年 9 月 9 日的 PubMed、EMBASE、Web of Science、SCOPUS 和 Google Scholar 数据库。纳入了所有提供 GLP-1 RAs 或 SGLT2is 对血管内皮厚度影响数据的干预性和观察性研究。采用乔安娜-布里格斯研究所（Joanna Briggs Institute）的核对表进行严格评估。采用随机效应模型对 IMT 变化（干预前和干预后）进行汇总和元分析。分组分析基于药物类型（GLP-1 RA：利拉鲁肽和艾塞那肽；SGLT2i：empagliflozin、ipragliflozin、tofogliflozin 和 dapagliflozin）、随机临床试验（RCT）和糖尿病患者。结果。文献检索在剔除重复内容后共获得 708 篇相关文章。18 项研究探讨了 GLP-1 RA 的效果，11 项研究探讨了 SGLT2i 的效果。GLP-1 RA和SGLT2i可显著降低IMT（分别为95% CI (-0.170, -0.076), , 和95% CI (-0.092, -0.004), , , ）。元回归显示，IMT变化与基线IMT相关，而与性别、糖尿病病程和治疗时间无关。结论GLP-1 RA和SGLT2i治疗可降低糖尿病患者的IMT，GLP-1 RA可能比SGLT2i更有效。
{"title":"Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis","authors":"Abolfazl Akbari, Shiva Hadizadeh, Leida Heidary","doi":"10.1155/2024/3212795","DOIUrl":"https://doi.org/10.1155/2024/3212795","url":null,"abstract":"<i>Background</i>. Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the risk of cardiovascular events. The aim of the present systematic review and meta-analysis is to demonstrate the effects of GLP-1 RA and SGLT2is on intima-media thickness (IMT). <i>Methods</i>. PubMed, EMBASE, Web of Science, SCOPUS, and Google Scholar databases were searched from inception to September 9, 2023. All interventional and observational studies that provided data on the effects of GLP-1 RAs or SGLT2is on IMT were included. Critical appraisal was performed using the Joanna Briggs Institute checklists. IMT changes (preintervention and postintervention) were pooled and meta-analyzed using a random-effects model. Subgroup analyses were based on type of medication (GLP-1 RA: liraglutide and exenatide; SGLT2i: empagliflozin, ipragliflozin, tofogliflozin, and dapagliflozin), randomized clinical trials (RCTs), and diabetic patients. <i>Results</i>. The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA, and eleven examined the effects of SGLT2i. GLP-1 RA and SGLT2i significantly decreased IMT (<span><svg height=\"8.87491pt\" style=\"vertical-align:-0.3499308pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.52498 32.48 8.87491\" width=\"32.48pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.583,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,24.849,0)\"></path></g></svg><span></span><span><svg height=\"8.87491pt\" style=\"vertical-align:-0.3499308pt\" version=\"1.1\" viewbox=\"36.0621838 -8.52498 35.816 8.87491\" width=\"35.816pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,36.112,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,43.743,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,49.983,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,52.947,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,59.187,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,65.427,0)\"></path></g></svg>,</span></span> 95% CI (-0.170, -0.076), <span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 34.445 9.2729\" width=\"34.445pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,29.161","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140152250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Sun, Qingyin Liu, Xiaona Ye, Ronghua Li, Miaomiao Meng, Xingjun Han
<i>Background and Purpose</i>. There is controversy about the effect of probiotics in regulating glucose homeostasis. This systematic review and meta-analysis is aimed at evaluating the evidence for the efficacy of probiotics in managing blood glucose, blood lipid, and inflammatory factors in adults with prediabetes. <i>Methods</i>. The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as <span><svg height="11.6412pt" style="vertical-align:-0.04979992pt" version="1.1" viewbox="-0.0498162 -11.5914 10.6309 11.6412" width="10.6309pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.0091,0,0,-0.0091,5.567,-5.741)"></path></g></svg>.</span> <i>Results</i>. Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 21.921 11.7782" width="21.921pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"></path></g></svg>;</span></span> <span><svg height="12.0588pt" style="vertical-align:-0.4673996pt" version="1.1" viewbox="-0.0498162 -11.5914 21.776 12.0588" width="21.776pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-74"></use></g><g transform="matrix(.0091,0,0,-0.0091,5.567,-5.741)"><use xlink:href="#g50-51"></use></g><g transform="matrix(.013,0,0,-0.013,14.145,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><svg height="12.0588pt" style="vertical-align:-0.4673996pt" version="1.1" viewbox="25.358183800000003 -11.5914 38.04 12.0588" width="38.04pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlin
{"title":"The Role of Probiotics in Managing Glucose Homeostasis in Adults with Prediabetes: A Systematic Review and Meta-Analysis","authors":"Chao Sun, Qingyin Liu, Xiaona Ye, Ronghua Li, Miaomiao Meng, Xingjun Han","doi":"10.1155/2024/5996218","DOIUrl":"https://doi.org/10.1155/2024/5996218","url":null,"abstract":"<i>Background and Purpose</i>. There is controversy about the effect of probiotics in regulating glucose homeostasis. This systematic review and meta-analysis is aimed at evaluating the evidence for the efficacy of probiotics in managing blood glucose, blood lipid, and inflammatory factors in adults with prediabetes. <i>Methods</i>. The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as <span><svg height=\"11.6412pt\" style=\"vertical-align:-0.04979992pt\" version=\"1.1\" viewbox=\"-0.0498162 -11.5914 10.6309 11.6412\" width=\"10.6309pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.0091,0,0,-0.0091,5.567,-5.741)\"></path></g></svg>.</span> <i>Results</i>. Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g></svg>;</span></span> <span><svg height=\"12.0588pt\" style=\"vertical-align:-0.4673996pt\" version=\"1.1\" viewbox=\"-0.0498162 -11.5914 21.776 12.0588\" width=\"21.776pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-74\"></use></g><g transform=\"matrix(.0091,0,0,-0.0091,5.567,-5.741)\"><use xlink:href=\"#g50-51\"></use></g><g transform=\"matrix(.013,0,0,-0.013,14.145,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"12.0588pt\" style=\"vertical-align:-0.4673996pt\" version=\"1.1\" viewbox=\"25.358183800000003 -11.5914 38.04 12.0588\" width=\"38.04pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlin","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"22 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140152169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuquan Lv, Lirong Fan, Xiaoting Chen, Xiuhai Su, Li Dong, Qinghai Wang, Yuansong Wang, Hui Zhang, Huantian Cui, Shufang Zhang, Lixin Wang
Background. Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. Purpose. The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. Materials and Methods. We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. Results. The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. Conclusion. JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.
{"title":"Jian-Pi-Gu-Shen-Hua-Yu Decoction Alleviated Diabetic Nephropathy in Mice through Reducing Ferroptosis","authors":"Shuquan Lv, Lirong Fan, Xiaoting Chen, Xiuhai Su, Li Dong, Qinghai Wang, Yuansong Wang, Hui Zhang, Huantian Cui, Shufang Zhang, Lixin Wang","doi":"10.1155/2024/9990304","DOIUrl":"https://doi.org/10.1155/2024/9990304","url":null,"abstract":"<i>Background</i>. Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. <i>Purpose</i>. The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. <i>Materials and Methods</i>. We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. <i>Results</i>. The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. <i>Conclusion</i>. JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"22 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140152246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aongus O’Brolchain, Joshua Maletsky, Ibrahim Mian, Serena Edwards
<i>Objective(s)</i>. Diabetic ketoacidosis (DKA) is a rare but well-known complication of sodium-glucose transporter inhibitor (SGLT2i) treatment in patients with type 2 diabetes. The physiological effects of SGLT2i are such that hyperglycaemia and ketonuria are no longer reliable diagnostic tools in patients treated with this class of medication. Diagnostic criteria for DKA varies between major society guidelines. The Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) have recently made changes to their diagnostic criteria to account for the effects of SGTL2i. This study sought to investigate whether treatment with SGLT2i might result in overdiagnosis of DKA and less adherence to the international diagnostic guidelines in hospitalised patients with type 2 diabetes treated with SGLT2i. Additionally, the demographics and clinical characteristics of patients with type 2 diabetes presenting with DKA were compared based on their treatment with SGLT2i at the time of diagnosis. <i>Design</i>. Retrospective observational study. <i>Setting</i>. Inpatients at two teaching hospitals in Queensland, Australia. <i>Primary Outcome Measure(s)</i>. The number of patients meeting the Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) diagnostic criteria for DKA. Patients were divided into two groups by treatment with SGLT2i at the time of diagnosis. <i>Participants</i>. Adult patients (>18 years old) with type 2 diabetes diagnosed with DKA from April 2015 to January 2022. Patients without type 2 diabetes were excluded. <i>Results</i>. One hundred and sixty-five patients were included in this study—comprising 94 patients in the SGLT2i cohort and 70 in the non-SGLT2i cohort. A significantly smaller proportion of patients in the SGLT2i vs. non-SGLT2i cohorts met both JBDS (56% vs. 72%, <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 28.184 11.7782" width="28.184pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"></path></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"></path></g></svg>)</span></span> and AACE/ACE (63% vs. 82%, <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-
{"title":"Does Treatment with Sodium-Glucose Cotransporter-2 Inhibitors Affect Adherence to International Society Criteria for Diabetic Ketoacidosis in Adult Patients with Type 2 Diabetes? A Retrospective Cohort Analysis","authors":"Aongus O’Brolchain, Joshua Maletsky, Ibrahim Mian, Serena Edwards","doi":"10.1155/2024/1849522","DOIUrl":"https://doi.org/10.1155/2024/1849522","url":null,"abstract":"<i>Objective(s)</i>. Diabetic ketoacidosis (DKA) is a rare but well-known complication of sodium-glucose transporter inhibitor (SGLT2i) treatment in patients with type 2 diabetes. The physiological effects of SGLT2i are such that hyperglycaemia and ketonuria are no longer reliable diagnostic tools in patients treated with this class of medication. Diagnostic criteria for DKA varies between major society guidelines. The Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) have recently made changes to their diagnostic criteria to account for the effects of SGTL2i. This study sought to investigate whether treatment with SGLT2i might result in overdiagnosis of DKA and less adherence to the international diagnostic guidelines in hospitalised patients with type 2 diabetes treated with SGLT2i. Additionally, the demographics and clinical characteristics of patients with type 2 diabetes presenting with DKA were compared based on their treatment with SGLT2i at the time of diagnosis. <i>Design</i>. Retrospective observational study. <i>Setting</i>. Inpatients at two teaching hospitals in Queensland, Australia. <i>Primary Outcome Measure(s)</i>. The number of patients meeting the Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) diagnostic criteria for DKA. Patients were divided into two groups by treatment with SGLT2i at the time of diagnosis. <i>Participants</i>. Adult patients (>18 years old) with type 2 diabetes diagnosed with DKA from April 2015 to January 2022. Patients without type 2 diabetes were excluded. <i>Results</i>. One hundred and sixty-five patients were included in this study—comprising 94 patients in the SGLT2i cohort and 70 in the non-SGLT2i cohort. A significantly smaller proportion of patients in the SGLT2i vs. non-SGLT2i cohorts met both JBDS (56% vs. 72%, <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"></path></g></svg>)</span></span> and AACE/ACE (63% vs. 82%, <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"9 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140127310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Zheng, Xin Ji, Qiao qiao Yin, Chensi Wu, Chengan Xu, Hongying Pan, Chun Wu
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation-mediated chronic low-grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome-based therapies for drug delivery vehicles, and targeted therapy for exosomes.
{"title":"Exosomes as Emerging Regulators of Immune Responses in Type 2 Diabetes Mellitus","authors":"Wei Zheng, Xin Ji, Qiao qiao Yin, Chensi Wu, Chengan Xu, Hongying Pan, Chun Wu","doi":"10.1155/2024/3759339","DOIUrl":"https://doi.org/10.1155/2024/3759339","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation-mediated chronic low-grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome-based therapies for drug delivery vehicles, and targeted therapy for exosomes.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"171 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<i>Background</i>. Oxidative stress and inflammation are closely related pathophysiological processes, both occurring in type 2 diabetes mellitus (T2DM). In addition to the standard treatment of T2DM, a potential strategy has been focused on the use of bile acids (BAs) as an additional treatment. Ursodeoxycholic acid (UDCA), as the first BA used in humans, improves glucose and lipid metabolism and attenuates oxidative stress. The aim of this study was to evaluate the potential metabolic, anti-inflammatory, and antioxidative effects of UDCA in patients with T2DM. <i>Methods</i>. This prospective, double-blind, placebo-controlled clinical study included 60 patients with T2DM, randomly allocated to receive UDCA or placebo. Subjects were treated with 500 mg tablets of UDCA or placebo administered three times per day (total dose of 1500 mg/day) for eight weeks. Two study visits, at the beginning (F0) and at the end (F1) of the study, included the interview, anthropometric and clinical measurements, and biochemical analyses. <i>Results</i>. UDCA treatment showed a significant reduction in body mass index (<span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 28.184 11.7782" width="28.184pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"></path></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"></path></g></svg>)</span></span> and in diastolic blood pressure (<span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"></use></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 28.184 11.7782" width="28.184pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"></use></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"
{"title":"Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, Placebo-Controlled Clinical Study","authors":"Biljana Lakić, Ranko Škrbić, Snežana Uletilović, Nebojša Mandić-Kovačević, Milkica Grabež, Mirna Popović Šarić, Miloš P. Stojiljković, Ivan Soldatović, Zorica Janjetović, Anastasija Stokanović, Nataša Stojaković, Momir Mikov","doi":"10.1155/2024/4187796","DOIUrl":"https://doi.org/10.1155/2024/4187796","url":null,"abstract":"<i>Background</i>. Oxidative stress and inflammation are closely related pathophysiological processes, both occurring in type 2 diabetes mellitus (T2DM). In addition to the standard treatment of T2DM, a potential strategy has been focused on the use of bile acids (BAs) as an additional treatment. Ursodeoxycholic acid (UDCA), as the first BA used in humans, improves glucose and lipid metabolism and attenuates oxidative stress. The aim of this study was to evaluate the potential metabolic, anti-inflammatory, and antioxidative effects of UDCA in patients with T2DM. <i>Methods</i>. This prospective, double-blind, placebo-controlled clinical study included 60 patients with T2DM, randomly allocated to receive UDCA or placebo. Subjects were treated with 500 mg tablets of UDCA or placebo administered three times per day (total dose of 1500 mg/day) for eight weeks. Two study visits, at the beginning (F0) and at the end (F1) of the study, included the interview, anthropometric and clinical measurements, and biochemical analyses. <i>Results</i>. UDCA treatment showed a significant reduction in body mass index (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"></path></g></svg>)</span></span> and in diastolic blood pressure (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-113\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"5 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitchell J. Sammut, David P. McBey, Amit P. Sayal, C. W. James Melling
The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. The purpose of this study was to investigate the effects of RT on IR development in female T1DM rodents. Forty Sprague Dawley eight-week-old female rats were divided into four groups: control sedentary (CS; <span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 17.789 8.55521" width="17.789pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"></path></g></svg><span></span><span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="21.3711838 -8.34882 12.679 8.55521" width="12.679pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,21.421,0)"></path></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"></path></g></svg>),</span></span> control trained (CT; <span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 17.789 8.55521" width="17.789pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"></use></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="21.3711838 -8.34882 12.679 8.55521" width="12.679pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,21.421,0)"><use xlink:href="#g113-50"></use></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><use xlink:href="#g113-49"></use></g></svg>),</span></span> T1DM sedentary (DS; <span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 17.789 8.55521" width="17.789pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"></use></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><svg height="8.55521pt" style="vertical-align:-0.2063904pt" version="1.1" viewbox="21.3711838 -8.34882 12.679 8.55521" width="12.679pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,21.421,0)"><use xlink:href="#g113-50"></use></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><use xlink:href="#
{"title":"The Effects of Resistance Exercise Training on Skeletal Muscle Metabolism and Insulin Resistance Development in Female Rodents with Type 1 Diabetes","authors":"Mitchell J. Sammut, David P. McBey, Amit P. Sayal, C. W. James Melling","doi":"10.1155/2024/5549762","DOIUrl":"https://doi.org/10.1155/2024/5549762","url":null,"abstract":"The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. The purpose of this study was to investigate the effects of RT on IR development in female T1DM rodents. Forty Sprague Dawley eight-week-old female rats were divided into four groups: control sedentary (CS; <span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"></path></g></svg><span></span><span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"></path></g></svg>),</span></span> control trained (CT; <span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-111\"></use></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"><use xlink:href=\"#g113-50\"></use></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"><use xlink:href=\"#g113-49\"></use></g></svg>),</span></span> T1DM sedentary (DS; <span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-111\"></use></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"><use xlink:href=\"#g113-50\"></use></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"><use xlink:href=\"#","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"42 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.
糖尿病视网膜病变（DR）是糖尿病的一种严重微血管并发症，也是欧洲和美国劳动适龄人口失明的主要原因之一。目前，糖尿病视网膜病变尚无根治方法，但早期发现和及时干预可以防止病情迅速恶化。目前已知的几种 DR 治疗方法主要是基于血糖、血压和血脂控制的眼科治疗，包括激光光凝、糖皮质激素、玻璃体切除术和抗血管内皮生长因子（anti-VEGF）药物。尽管上述疗法具有临床疗效，但它们都不能完全缩短 DR 的临床病程或逆转视网膜病变。微RNA（miRNA）是基因表达的重要调节因子，参与细胞的生长、分化、发育和凋亡。研究表明，microRNA 在 DR 中发挥着重要作用，尤其是在炎症、氧化应激和神经变性的分子机制中。本综述旨在系统地总结 miRNAs 参与 DR 发生和发展的信号通路和分子机制，主要从氧化应激、炎症和新生血管的发病机理入手。同时，本文还探讨了针对DR的miRNA特异性疗法的研究进展和应用。
{"title":"Advances in Research Related to MicroRNA for Diabetic Retinopathy","authors":"Yahan Luo, Chunxia Li","doi":"10.1155/2024/8520489","DOIUrl":"https://doi.org/10.1155/2024/8520489","url":null,"abstract":"Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"59 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139760528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08eCollection Date: 2024-01-01DOI: 10.1155/2024/2350551
Ritesh Chimoriya, Kimberly Mitlehner, Chee L Khoo, Uchechukwu Levi Osuagwu, Russell Thomson, Lei Si, Michael Lean, David Simmons, Milan K Piya
Background: The Diabetes Remission Clinical Trial (DiRECT) study demonstrated that an intensive and structured weight management program in UK primary care resulted in high rates of diabetes remission in adults with recent onset type 2 diabetes mellitus (T2DM). This study was aimed at evaluating the translation of the DiRECT intervention into an Australian primary care setting.
Methods: All patients enrolled in the DiRECT-Australia Type 2 Diabetes Remission Service in a region of Sydney (Macarthur region, South Western Sydney, Australia) were included. Eligible participants were aged 20-70 years, noninsulin treated, with T2DM of ≤6 years' duration, and body mass index (BMI) ≥ 27 kg/m2. Total diet replacement of 825-853 kcal/day using meal replacements was implemented for 12 weeks, followed by an ongoing structured program until 52 weeks, with regular follow-up with a general practitioner, dietitian, and/or practice nurse.
Results: Of 39 recruited participants, 32 (82.1%) and 27 (69.2%) completed 12 weeks and 52 weeks of the structured program, respectively. Decrease in weight by -12.0 kg (95% CI: -9.6, -14.4; p < 0.001) and -9.1 kg (95% CI: -5.2, -12.9; p < 0.001) and decrease in glycated haemoglobin (HbA1c) by -1.1% (95% CI: -0.6, -1.6; p < 0.001) and -0.6% (95% CI: -0.1, -1.1; p = 0.013) were observed at 12 and 52 weeks, respectively. At the end of 12 and 52 weeks, 93.8% (30/32) and 55.6% (15/27) of those with follow-up data met the criteria for diabetes remission, respectively. Quality of life and wellbeing scores increased over the course of 12 weeks, remaining significantly higher at 52 weeks. Participants reported they would be willing to pay A$92.50 (95% CI: A$75.80, A$109.30) per fortnight for the low-calorie meal replacement shakes.
Conclusions: These findings support the feasibility of a structured diabetes remission service in an Australian primary care setting to achieve improvements in glycaemia, weight, and quality of life and wellbeing, and suggest a substantial willingness to pay for diet replacement products among participants.
{"title":"Translation of a Diabetes Remission Service into Australian Primary Care: Findings from the Evaluation of DiRECT-Australia.","authors":"Ritesh Chimoriya, Kimberly Mitlehner, Chee L Khoo, Uchechukwu Levi Osuagwu, Russell Thomson, Lei Si, Michael Lean, David Simmons, Milan K Piya","doi":"10.1155/2024/2350551","DOIUrl":"10.1155/2024/2350551","url":null,"abstract":"<p><strong>Background: </strong>The Diabetes Remission Clinical Trial (DiRECT) study demonstrated that an intensive and structured weight management program in UK primary care resulted in high rates of diabetes remission in adults with recent onset type 2 diabetes mellitus (T2DM). This study was aimed at evaluating the translation of the DiRECT intervention into an Australian primary care setting.</p><p><strong>Methods: </strong>All patients enrolled in the DiRECT-Australia Type 2 Diabetes Remission Service in a region of Sydney (Macarthur region, South Western Sydney, Australia) were included. Eligible participants were aged 20-70 years, noninsulin treated, with T2DM of ≤6 years' duration, and body mass index (BMI) ≥ 27 kg/m<sup>2</sup>. Total diet replacement of 825-853 kcal/day using meal replacements was implemented for 12 weeks, followed by an ongoing structured program until 52 weeks, with regular follow-up with a general practitioner, dietitian, and/or practice nurse.</p><p><strong>Results: </strong>Of 39 recruited participants, 32 (82.1%) and 27 (69.2%) completed 12 weeks and 52 weeks of the structured program, respectively. Decrease in weight by -12.0 kg (95% CI: -9.6, -14.4; <i>p</i> < 0.001) and -9.1 kg (95% CI: -5.2, -12.9; <i>p</i> < 0.001) and decrease in glycated haemoglobin (HbA1c) by -1.1% (95% CI: -0.6, -1.6; <i>p</i> < 0.001) and -0.6% (95% CI: -0.1, -1.1; <i>p</i> = 0.013) were observed at 12 and 52 weeks, respectively. At the end of 12 and 52 weeks, 93.8% (30/32) and 55.6% (15/27) of those with follow-up data met the criteria for diabetes remission, respectively. Quality of life and wellbeing scores increased over the course of 12 weeks, remaining significantly higher at 52 weeks. Participants reported they would be willing to pay A$92.50 (95% CI: A$75.80, A$109.30) per fortnight for the low-calorie meal replacement shakes.</p><p><strong>Conclusions: </strong>These findings support the feasibility of a structured diabetes remission service in an Australian primary care setting to achieve improvements in glycaemia, weight, and quality of life and wellbeing, and suggest a substantial willingness to pay for diet replacement products among participants.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2024 ","pages":"2350551"},"PeriodicalIF":4.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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