{"title":"NET-Related Gene as Potential Diagnostic Biomarkers for Diabetic Tubulointerstitial Injury","authors":"Yufeng Liang, Jiaqun Lin, Binsan Huang, Mengjie Weng, Tingting Zhen, Liyan Yang, Yongping Chen, Qiu Li, Jianxin Wan","doi":"10.1155/2024/4815488","DOIUrl":"https://doi.org/10.1155/2024/4815488","url":null,"abstract":"<b>Background:</b> Tubulointerstitial injury plays a pivotal role in the progression of diabetic kidney disease (DKD), yet the link between neutrophil extracellular traps (NETs) and diabetic tubulointerstitial injury is still unclear.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"33 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140934704","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}
{"title":"A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study","authors":"Hailin Qin, Kui Yang, Hufei Wang, Wenyong Jiao","doi":"10.1155/2024/1610688","DOIUrl":"https://doi.org/10.1155/2024/1610688","url":null,"abstract":"<b>Objective:</b> This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP).","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"38 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140934835","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}
{"title":"SLC25A28 Overexpression Promotes Adipogenesis by Reducing ATGL","authors":"Hua Guan, Lin Xiao, Kaikai Hao, Qiang Zhang, Dongliang Wu, Zhanyi Geng, Bowen Duan, Hui Dai, Ruifen Xu, Xuyang Feng","doi":"10.1155/2024/5511454","DOIUrl":"https://doi.org/10.1155/2024/5511454","url":null,"abstract":"Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1<i>α</i>. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"35 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834847","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}
Jiayuan He, Xiang Li, Man Yan, Xinsheng Chen, Chang Sun, Jiajun Tan, Yinsheng Song, Hong Xu, Liang Wu, Zhengnan Yang
{"title":"Inulin Reduces Kidney Damage in Type 2 Diabetic Mice by Decreasing Inflammation and Serum Metabolomics","authors":"Jiayuan He, Xiang Li, Man Yan, Xinsheng Chen, Chang Sun, Jiajun Tan, Yinsheng Song, Hong Xu, Liang Wu, Zhengnan Yang","doi":"10.1155/2024/1222395","DOIUrl":"https://doi.org/10.1155/2024/1222395","url":null,"abstract":"This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"10 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835078","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}
Daniel Miezah, Mustapha Amoadu, Priscilla Nyamekye Opoku, Enoch Mensah Junior, Jethro Zutah, Paul Obeng, Jacob Owusu Sarfo
{"title":"Transtheoretical-Based Model of Intervention for Diabetes and Prediabetes: A Scoping Review","authors":"Daniel Miezah, Mustapha Amoadu, Priscilla Nyamekye Opoku, Enoch Mensah Junior, Jethro Zutah, Paul Obeng, Jacob Owusu Sarfo","doi":"10.1155/2024/2935795","DOIUrl":"https://doi.org/10.1155/2024/2935795","url":null,"abstract":"Diabetes is considered a public health problem worldwide, fostered by population growth, an increase in the overall quality of life, changes in dietary patterns, modifications in lifestyle habits, and the natural process of getting older. To properly control diabetes, the transtheoretical model (TTM) may be useful. This scoping review is aimed at identifying TTM interventions for diabetes. The study followed Arksey and O’Malley’s six steps in conducting the scoping review. Four main databases (PubMed, Central, JSTOR, and ScienceDirect), Google Scholar, Google, and a reference list of identified articles were searched for literature. The study included peer-reviewed articles published online from 2000 to 2023 and published in the English language. At the end of the search, 3,514 entries were found in the four main databases, and 23 records were identified through Google, Google Scholar searches, and reference lists. After a thorough screening, 22 records were used for this review. The study found that the primary interventions based on the TTM for managing diabetes and prediabetes were educational materials to promote physical activity among diabetes and prediabetes individuals, health education, exercise, motivational interviews, self-tracking, and dietary changes. Further interventions on diabetes and prediabetes management could adopt the identified transtheoretical interventions to improve the health of their patients.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"1 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811064","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}
{"title":"Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study","authors":"Bin Cao, Kun Li, Jing Ke, Dong Zhao","doi":"10.1155/2024/8462987","DOIUrl":"https://doi.org/10.1155/2024/8462987","url":null,"abstract":"<b>Background and Aims:</b> This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"6 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811088","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}
{"title":"The Protective Effects of Vanillic Acid and Vanillic Acid-Coated Silver Nanoparticles (AgNPs) in Streptozotocin-Induced Diabetic Rats","authors":"Eman S. Alamri, Haddad A. El Rabey","doi":"10.1155/2024/4873544","DOIUrl":"https://doi.org/10.1155/2024/4873544","url":null,"abstract":"The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (<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 6.416 8.55521\" width=\"6.416pt\" 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></svg>)</span></span> for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at <span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 8.8423\" 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)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"8.8423pt\" style=\"vertical-align:-0.2064009pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 8.8423\" width=\"21.918pt\" 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)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"></path></g></svg>)</span></span> increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, usin","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"43 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140312835","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}
{"title":"The Effect of Canagliflozin on High-Density Lipoprotein Cholesterol and Angiopoietin-Like Protein 3 in Type 2 Diabetes Mellitus","authors":"Simo Liu, Jing Ke, Xiaotong Feng, Zongwei Wang, Xin Wang, Longyan Yang, Dong Zhao","doi":"10.1155/2024/2431441","DOIUrl":"https://doi.org/10.1155/2024/2431441","url":null,"abstract":"<i>Background</i>. Diabetes mellitus is often accompanied by dyslipidemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM), have been reported to exert effects on lipid, while the results remain controversial. This study is aimed at exploring the effect of SGLT2 inhibitor canagliflozin on lipid profile. <i>Methods</i>. This study was a single-center, open-label, nonrandomized, prospective study. Metformin (500 mg three times per day) or canagliflozin (100 mg, once daily) was administered for 12 weeks. Fasting blood samples were collected before and 12 weeks after treatment. Serum lipid profile levels and angiopoietin-like protein 3 (ANGPTL3) were determined. In animal experiment, C57BL/6 J mice were divided into three groups including control, STZ + HFD, and STZ + HFD + canagliflozin. Lipid profile and plasma ANGPTL3 level were measured after 12 week’s treatment. Moreover, the expression of ANGPTL3 was detected in the liver tissues. <i>Results</i>. There was a decreased trend in low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) after canagliflozin treatment, while canagliflozin significantly increased high-density lipoprotein cholesterol (HDL-c) level and decreased plasma ANGPTL3 level. In addition, the expression of ANGPTL3 in liver tissues decreased obviously in diabetic mice with canagliflozin treatment. <i>Conclusions</i>. Canagliflozin increases HDL-c level and suppresses ANGPTL3 expression in patients with T2DM and diabetic mice. The reduction of ANGPTL3 may contribute to the increase of HDL-c. However, the specific mechanism needs further research. This trial is registered with ChiCTR1900021231.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"51 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140312764","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}
Helena Enders-Seidlitz, Klemens Raile, Maolian Gong, Angela Galler, Peter Kuehnen, Susanna Wiegand
{"title":"Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization","authors":"Helena Enders-Seidlitz, Klemens Raile, Maolian Gong, Angela Galler, Peter Kuehnen, Susanna Wiegand","doi":"10.1155/2024/5558634","DOIUrl":"https://doi.org/10.1155/2024/5558634","url":null,"abstract":"<i>Introduction</i>. Childhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort. <i>Methods</i>. We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, <span><svg height=\"12.7112pt\" style=\"vertical-align:-3.403299pt\" version=\"1.1\" viewbox=\"-0.0498162 -9.3079 49.422 12.7112\" width=\"49.422pt\" 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,-0.013,6.175,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,9.308,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,16.211,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,21.71,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.34,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,33.215,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,41.791,0)\"></path></g></svg><span></span><span><svg height=\"12.7112pt\" style=\"vertical-align:-3.403299pt\" version=\"1.1\" viewbox=\"52.277183799999996 -9.3079 36.313 12.7112\" width=\"36.313pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,52.327,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,55.811,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,62.818,0)\"><use xlink:href=\"#g190-116\"></use></g><g transform=\"matrix(.013,0,0,-0.013,67.524,0)\"><use xlink:href=\"#g190-118\"></use></g><g transform=\"matrix(.013,0,0,-0.013,74.492,0)\"><use xlink:href=\"#g190-109\"></use></g><g transform=\"matrix(.013,0,0,-0.013,77.781,0)\"><use xlink:href=\"#g190-106\"></use></g><g transform=\"matrix(.013,0,0,-0.013,81.265,0)\"><use xlink:href=\"#g190-111\"></use></g></svg>)</span></span> in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during <span><svg height=\"9.39034pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.75334 47.029 9.39034\" width=\"47.029pt\" 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,-0.013,9.946,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,19.241,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,27.614,0)\"><use ","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"27 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140172050","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}
Yi Cui, Li Wang, Wentao Liang, Li Huang, Shuting Zhuang, Hong Shi, Nuo Xu, Jianzhang Hu
{"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}