World Journal of Diabetes最新文献

{"title":"Dl-3-n-butylphthalide ameliorates diabetic foot ulcer by inhibiting apoptosis and promoting angiogenesis.","authors":"Wu-Han Wei, Yuan-Ling Bai, Dong Zhu, Jing-Yu Zhang, Qi-Chuan Yin, Qiang Li, Cai-Qi Shen, Pei-Sheng Jin","doi":"10.4239/wjd.v16.i4.101916","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.101916","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFU) are estimated to affect about 18.6 million people worldwide annually. The pathogenesis of DFU is complex, and the available drugs are not effective. Dl-3-n-butylphthalide (NBP) is a synthetic mixture of racemates used in China for the treatment of ischemic stroke. It was initially isolated from the seeds of <i>Apium graveolens</i> Linn, with studies showing its potential role in treating diabetes and its complications.</p><p><strong>Aim: </strong>To predict and validate the mechanism by which NBP treats DFU.</p><p><strong>Methods: </strong>Network pharmacological analysis was performed to identify pharmacological targets and signaling pathways mediating the treatment effect of NBP on DFU. <i>In vivo</i> and <i>in vitro</i> experiments were conducted to validate the therapeutic effects and mechanisms of NBP on DFU.</p><p><strong>Results: </strong>Network pharmacology analysis identified 26 pharmacological targets of NBP and predicted that NBP could treat DFU partially by modulating apoptosis and vascular signaling pathways. Results from animal experiments showed that NBP significantly improved DFU by increasing neovascularization and fibroblast proliferation. <i>In vitro</i> tests demonstrated that NBP treatment promoted the migration and proliferation of human umbilical vein endothelial cells and human dermal fibroblasts, while inhibiting the apoptosis of human umbilical vein endothelial cells, human dermal fibroblasts, and human keratinocytes cells.</p><p><strong>Conclusion: </strong>This study found that NBP could treat DFU by decreasing the rate of apoptosis and increasing angiogenesis <i>via</i> the advanced glycation end products-receptor of advanced glycation end products signaling pathway and binding to the heme oxygenase 1, caspase 3, B cell leukemia/lymphoma 2, brain derived neurotrophic factor, and nuclear factor erythroid 2 L2 genes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"101916"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992102","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}

{"title":"Dysfunctional glucose metabolism triggers oxidative stress to induce kidney injury in diabetes.","authors":"Meng Gao, Meng-Ting Dai, Guo-Hua Gong","doi":"10.4239/wjd.v16.i4.102554","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.102554","url":null,"abstract":"<p><p>In this editorial, we discussed the article published in the recent issue of the <i>World Journal of Diabetes</i>. To understand the effect of mizagliflozin on kidney injury induced by diabetes, we focused on the mechanisms by which high glucose triggers oxidative stress and contributes to kidney injury in diabetes. The high level of unmetabolized glucose reaching the kidney triggers glucose reabsorption by renal tubules, which elevates the cellular glucose level of renal cells. High glucose induces lactate dehydrogenase overexpression and thus shifts glucose metabolism, which causes mitochondrial dysfunction. Mitochondria generate approximately 90% of the reactive oxygen species in cells, whose dysfunction further alters glucose metabolism and enhances reactive oxygen species generation. Oxidative stress stimulates proinflammatory factor production and kidney inflammatory injury. Mizagliflozin decreases glucose reabsorption and thus ameliorates diabetes-induced kidney injury.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"102554"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003717","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}

{"title":"Prevalence and associated factors of depressive symptoms in Chinese diabetic patients: A study based on Andersen's behavioral model.","authors":"Wen-Hui Xiao, Xiao-Cong Yang, Si-Jie Xu, Ying Bian, Guan-Yang Zou","doi":"10.4239/wjd.v16.i4.100638","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.100638","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a rapidly growing global health emergency of the 21^st century. Comorbidities, such as DM and depression, are common, presenting challenges to the healthcare system.</p><p><strong>Aim: </strong>To investigate the prevalence of depression and its associated factors in patients with DM and to strengthen the management of depression in this patient group.</p><p><strong>Methods: </strong>Participants were selected from the 2018 China Health and Retirement Longitudinal Study. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale, with a score of 10 or more indicating depression. Group differences were compared using analysis of variance and <i>χ</i> ² tests. Binary logistic regression was conducted to explore the odds ratios (ORs) of independent variables. Following Andersen's behavioral model, predisposing, enabling, health need, and health behavior variables were introduced stepwise into the logistic model.</p><p><strong>Results: </strong>Of the 1673 patients with diabetes, 41.4% had depressive symptoms. Regarding the predisposing characteristics, patients who were male (OR 0.426, <i>P</i> < 0.05), married (OR 0.634, <i>P</i> < 0.05), and received a high school education or higher (OR 0.432, <i>P</i> < 0.05) reported fewer depressive symptoms. Healthcare needs, including better self-rated health (OR 0.458 for fair and OR 0.247 for good, <i>P</i> < 0.05) and more sleep (OR 0.642, <i>P</i> < 0.05), were associated with a lower likelihood of depressive symptoms. In contrast, pain (OR 1.440 for mild and OR 2.644 for severe, <i>P</i> < 0.05) and impairment in the basic activities of daily living (OR 1.886, <i>P</i> < 0.05) were inversely associated. Additionally, patients highly satisfied with healthcare services (OR 0.579, <i>P</i> < 0.05) were less likely to have depressive symptoms.</p><p><strong>Conclusion: </strong>Nearly half of the patients with DM reported depressive symptoms, which were strongly associated with predisposing characteristics and healthcare needs, particularly physical pain and impairment in basic activities of daily living. Our study emphasizes the significance of enhanced screening and intervention for depression in diabetes care along with improved management of functional impairments.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"100638"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043486","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}

{"title":"Role and mechanism of Roux-en-Y gastric bypass in the treatment of diabetic urinary bladder hyperactivity by reducing TRPV1 and P2X3.","authors":"Guang-Yong Li, Shuai Ren, Bin-Cheng Huang, Jia-Jin Feng, Qiang-Qiang Wang, Qing-Jie Peng, Hai-Fu Tian, Le-Yi Yu, Cun-Ling Ma, Shu-Zhe Fan, Xiao-Jiang Chen, Mohammed Abdulkarem Al-Qaisi, Rui He","doi":"10.4239/wjd.v16.i4.96176","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.96176","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is linked to an earlier onset and heightened severity of urinary complications, particularly bladder dysfunction, which profoundly impacts patient quality of life. Overactive bladder (OAB) is a common storage disorder of the lower urinary tract and is characterized by urgency, frequency, and nocturia. Several factors contribute to bladder dysfunction in diabetic individuals, including changes in urothelial signaling, detrusor morphology, and central nervous system regulation. The transient receptor potential vanilloid type 1 channel, expressed by bladder urothelial cells, is upregulated in OAB and plays a crucial role in ATP release during bladder filling. This ATP release subsequently activates purinergic receptor P2X3, further exacerbating OAB symptoms.</p><p><strong>Aim: </strong>To clarify the mechanism of Roux-en-Y gastric bypass (RYGB) metabolic surgery to improve OAB in type 2 DM (T2DM).</p><p><strong>Methods: </strong>The model of T2DM was induced by feeding a high-fat diet to mice for 16 weeks. After 16 weeks, sham operation and RYGB operation were performed. The related indexes of glucose metabolism were also detected to evaluate the therapeutic effect, and the recovery degree of bladder function and micturition behavior of mice was assessed by urodynamics and micturition spot analysis.</p><p><strong>Results: </strong>Compared with the normal mice in the sham group, T2DM mice had increased urine spot count, uncontrolled urination behavior, shortened urination interval, and reduced bladder capacity. Immunohistochemistry and immunofluorescence costaining showed that Transient receptor potential vanilloid type 1 (TRPV1) and purinergic receptor P2X3 were both expressed in mouse bladder epithelial layer, and they had the same localization. In the bladder of T2DM mice, the mRNA and protein expression of TRPV1 and P2X3 were significantly increased. The ATP content in urine of T2DM mice was significantly higher than that of the sham group. After RYGB operation, the glucose metabolism index of the RYGB group was significantly improved compared with the OAB group. Comparing the results of urine spots, urodynamics, and histology, it was found that the function and morphological structure of the bladder in the RYGB group also recovered obviously. Compared with the OAB group, the expression of TRPV1 and P2X3 in the RYGB group was downregulated, and the level of inflammatory factors was significantly decreased. RYGB significantly decreased the content of ATP in urine and activated AMPK signaling.</p><p><strong>Conclusion: </strong>RYGB downregulated the expression of TRPV1 by inhibiting inflammatory factors, thus inhibiting the enhancement of P2X3 by TRPV1. RYGB directly inhibited the activity of P2X3 by inhibiting ATP synthesis in the bladder epithelium to improve OAB.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"96176"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032500","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}

{"title":"Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis.","authors":"Abul Bashar Mohammad Kamrul-Hasan, Joseph M Pappachan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Nitin Kapoor","doi":"10.4239/wjd.v16.i4.101731","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.101731","url":null,"abstract":"<p><strong>Background: </strong>Despite therapeutic benefits, discontinuation of tirzepatide is common in randomized controlled trials (RCTs) due to adverse events (AEs) and other causes. No previous systematic reviews have explored the reasons for discontinuing tirzepatide in the RCTs.</p><p><strong>Aim: </strong>To explore the reasons for permanent discontinuation of tirzepatide <i>vs</i> controls [placebo, insulin, and glucagon-like peptide-1 receptor agonists (GLP-1Ras)] in RCTs.</p><p><strong>Methods: </strong>Relevant RCTs were systematically searched using related terms through multiple databases such as MEDLINE (<i>via</i> PubMed), Scopus, Cochrane Central Register, and ClinicalTrials.gov from their inception until June 20, 2024. RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Seventeen RCTs (<i>n</i> = 14645), mostly having low risks of bias, were analyzed. Compared to placebo, the risk of permanent discontinuation of the study drug was substantially lower with tirzepatide 10 mg (RR: 0.69, 95%CI: 0.51-0.93, <i>P</i> = 0.02) and similar with tirzepatide 5 mg (RR: 0.74, 95%CI: 0.47-1.17, <i>P</i> = 0.20) and 15 mg (RR: 0.94, 95%CI: 0.68-1.31, <i>P</i> = 0.71). Tirzepatide had identical discontinuation risks when compared to insulin at 5 mg (RR: 0.96, 95%CI: 0.75-1.24, <i>P</i> = 0.77) and 10 mg (RR: 1.19, 95%CI: 0.77-1.82, <i>P</i> = 0.44) doses, whereas such risk was higher with tirzepatide 15 mg than insulin (RR: 1.31, 95%CI: 1.03-1.67, <i>P</i> = 0.03). Compared to GLP-1RA, the permanent discontinuation risk was similar with tirzepatide 5 mg (RR: 0.98, 95%CI: 0.70-1.37, <i>P</i> = 0.90) but was higher with tirzepatide 10 mg (RR: 1.40, 95%CI: 1.03-1.90, <i>P</i> = 0.03) and 15 mg (RR: 1.70, 95%CI: 1.27-2.27, <i>P</i> = 0.0004). Tirzepatide, at all doses, had higher risks of AE-related discontinuation than insulin; such risks were only greater with higher doses of tirzepatide than with placebo or GLP-1RA. Discontinuation risk due to withdrawal by the study subjects was lower with tirzepatide than with placebo or insulin. Compared to the placebo, tirzepatide (all doses) conferred a lower risk of study drug discontinuation due to other causes not specifically mentioned.</p><p><strong>Conclusion: </strong>The discontinuation risk is not higher in tirzepatide group than in the placebo arm. Many factors other than AEs led to drug discontinuation in the included RCTs.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"101731"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992785","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}

{"title":"Digital health technologies/interventions in smart ward development for elderly patients with diabetes: A perspective from China and beyond.","authors":"Wei Yang, Juan Lu, Si-Cong Si, Wei-Hua Wang, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu","doi":"10.4239/wjd.v16.i4.103002","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.103002","url":null,"abstract":"<p><p>Diabetes is highly prevalent among the elderly worldwide, with the highest number of diabetes cases in China. Yet, the management of diabetes remains unsatisfactory. Recent advances in digital health technologies have facilitated the establishment of smart wards for diabetes patients. There is a lack of smart wards tailored specifically for older diabetes patients who encounter unique challenges in glycemic control and diabetes management, including an increased vulnerability to hypoglycemia, the presence of multiple chronic diseases, and cognitive decline. In this review, studies on digital health technologies for diabetes in China and beyond were summarized to elucidate how the adoption of digital health technologies, such as real-time continuous glucose monitoring, sensor-augmented pump technology, and their integration with 5^th generation networks, big data cloud storage, and hospital information systems, can address issues specifically related to elderly diabetes patients in hospital wards. Furthermore, the challenges and future directions for establishing and implementing smart wards for elderly diabetes patients are discussed, and these challenges may also be applicable to other countries worldwide, not just in China. Taken together, the smart wards may enhance clinical outcomes, address specific issues, and eventually improve patient-centered hospital care for elderly patients with diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"103002"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051299","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}

{"title":"Characteristic dysbiosis in patients with type 2 diabetes and hyperuricemia, and the effect of empagliflozin on gut microbiota.","authors":"Xin-Ru Deng, Yu-Jia Zhai, Xiao-Yang Shi, Sha-Sha Tang, Yuan-Yuan Fang, Hong-Yan Heng, Ling-Yun Zhao, Hui-Juan Yuan","doi":"10.4239/wjd.v16.i4.102970","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.102970","url":null,"abstract":"<p><strong>Background: </strong>Gut microbiota play a crucial role in metabolic diseases, including type 2 diabetes (T2DM) and hyperuricemia (HUA). One-third of uric acid is excreted into the intestinal tract and further metabolized by gut microbiota. Thus, the gut microbiota might be a new therapeutic target for HUA. Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota. We hypothesize that gut dysbiosis in patients with diabetes and HUA, and the reduction of uric acid by empagliflozin, may be mediated by gut microbiota.</p><p><strong>Aim: </strong>To investigate dysbiosis in patients with T2DM and HUA, and the effect of empagliflozin on gut microbiota associated with purine metabolism.</p><p><strong>Methods: </strong>In this age and sex-matched, case-control study, we recruited 30 patients with T2DM and HUA; 30 with T2DM; and 30 healthy controls at the Henan Provincial People's Hospital between February 2019 and August 2023. Nine patients with T2DM and HUA were treated with empagliflozin for three months. Gut microbiota profiles were assessed using the 16S rRNA gene.</p><p><strong>Results: </strong>Patients with T2DM and HUA had the highest total triglycerides (1.09 mmol/L in heathy control <i>vs</i> 1.56 mmol/L in T2DM <i>vs</i> 2.82 mmol/L in T2DM + HUA) and uric acid levels (302.50 μmol/L in heathy control <i>vs</i> 288.50 μmol/L in T2DM <i>vs</i> 466.50 μmol/L in T2DM + HUA) among the three groups. The composition of the gut microbiota differed significantly between patients with T2DM and HUA, and those with T2DM/healthy controls (<i>P</i> < 0.05). Notably, patients with T2DM and HUA demonstrated a deficiency of uric acid-degrading bacteria such as <i>Romboutsia</i>, <i>Blautia</i>, <i>Clostridium sensu stricto 1</i> (<i>P</i> < 0.05). Empagliflozin treatment was associated with significantly reduced serum uric acid levels and purine metabolism-related pathways and genes in patients with T2DM and HUA (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Gut dysbiosis may contribute to the pathogenesis of HUA in T2DM, and empagliflozin may partly restore the gut microbiota related to uric acid metabolism.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"102970"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046612","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}

{"title":"MicroRNA-122-5p is upregulated in diabetic foot ulcers and decelerates the transition from the inflammatory to the proliferative stage.","authors":"Mei-Jie Yuan, He-Chen Huang, Hong-Shuo Shi, Xiao-Ming Hu, Zhuo Zhao, Yu-Qi Chen, Wei-Jing Fan, Jian Sun, Guo-Bin Liu","doi":"10.4239/wjd.v16.i4.100113","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.100113","url":null,"abstract":"<p><strong>Background: </strong>Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers (DFUs); however, existing medical interventions remain insufficient. MicroRNAs (miRs) highlight notable capacity for accelerating the repair process of DFUs. Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions, thereby influencing extracellular matrix dynamics.</p><p><strong>Aim: </strong>To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.</p><p><strong>Methods: </strong>Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). A diabetic wound healing model induced by streptozotocin was used, with mice receiving intradermal injections of adeno-associated virus -DJ encoding empty vector or miR-122. Skin tissues were retrieved at 3, 7, and 14 days after injury for gene expression analysis, histology, immunohistochemistry, and network studies. The study explored miR-122-5p's role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.</p><p><strong>Results: </strong>High-throughput sequencing revealed miR-122-5p as crucial for DFU healing. qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice. Western blot, along with immunohistochemical and enzyme-linked immunosorbent assay, demonstrating the upregulation of inflammatory mediators (hypoxia inducible factor-1α, matrix metalloproteinase 9, tumor necrosis factor-α) and reduced fibrosis markers (fibronectin 1, α-smooth muscle actin) by targeting vascular endothelial growth factor. Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice. Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization, highlighting its role in inflammation. MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media, highlighting its pivotal role in regulating DFU healing.</p><p><strong>Conclusion: </strong>MiR-122-5p impedes cutaneous healing of diabetic mice <i>via</i> enhancing inflammation and inhibiting fibrosis, offering insights into miR roles in human skin wound repair.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"100113"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064977","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}

{"title":"MiR-29a-3p inhibits fibrosis of diabetic kidney disease in diabetic mice <i>via</i> downregulation of DNA methyl transferase 3A and 3B.","authors":"Ying Yang, Yi Chen, Jian-Ying Tang, Jian Chen, Gui-Qing Li, Bing Feng, Jiao Mu","doi":"10.4239/wjd.v16.i4.93630","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.93630","url":null,"abstract":"<p><strong>Background: </strong>At present, the incidence of diabetic nephropathy is increasing year by year, and there are many studies on the pathogenesis of diabetic nephropathy, but it is still not completely clear. The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis, and the roles of micro-RNA (miRNA)-29 and DNA methyl transferase (DNMTs) in cell fibrosis have been confirmed in other studies, but there is a lack of relevant research in the kidney at present.</p><p><strong>Aim: </strong>To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>The expression of miR-29a-3p, DNMT3A/3B, fibrosis-related molecules, Wnt3a, β-catenin, Janus kinase 2, and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting. Furthermore, the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting. The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining.</p><p><strong>Results: </strong>In both the <i>in vivo</i> and <i>in vitro</i> experiments, it was observed that high glucose induction significantly decreased miR-29a-3p expression. As a result of this downregulation, DKD-related fibrosis was found to be promoted, as confirmed by elevated expression levels of α-smooth muscle actin, collagen type I, and fibronectin. MiR-29a-3p targets the 3' non-coding regions of <i>DNMT3A</i> and <i>DNMT3B</i> and inhibits their expression. Inhibition of <i>DNMT3A</i> and <i>DNMT3B</i> can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis.</p><p><strong>Conclusion: </strong>MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"93630"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988716","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}

{"title":"Increased blood urea nitrogen levels and compromised peripheral nerve function in patients with type 2 diabetes.","authors":"Rui Wang, Yu-Xian Xu, Feng Xu, Chun-Hua Wang, Li-Hua Zhao, Li-Hua Wang, Wei-Guan Chen, Xue-Qin Wang, Cheng-Wei Duan, Jian-Bin Su","doi":"10.4239/wjd.v16.i4.101966","DOIUrl":"https://doi.org/10.4239/wjd.v16.i4.101966","url":null,"abstract":"<p><strong>Background: </strong>Increased blood urea nitrogen (BUN) levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes (T2D), potentially playing a role in the development of diabetic complications, including diabetic peripheral neuropathy.</p><p><strong>Aim: </strong>To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.</p><p><strong>Methods: </strong>This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured. Electromyography was used to assess peripheral motor and sensory nerve function in all patients, and overall composite <i>Z</i>-scores were subsequently calculated for nerve latency, amplitude, and conduction velocity (NCV) across the median, ulnar, common peroneal, posterior tibial, superficial peroneal, and sural nerves.</p><p><strong>Results: </strong>Across the quartiles of BUN levels, the overall composite <i>Z</i>-score for latency (<i>F</i> = 38.996, <i>P</i> for trend < 0.001) showed a significant increasing trend, whereas the overall composite <i>Z</i>-scores for amplitude (<i>F</i> = 50.972, <i>P</i> for trend < 0.001) and NCV (<i>F</i> = 30.636, <i>P</i> for trend < 0.001) exhibited a significant decreasing trend. Moreover, the BUN levels were closely correlated with the latency, amplitude, and NCV of each peripheral nerve. Furthermore, multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite <i>Z</i>-score for latency (β = 0.166, <i>t</i> = 3.864, <i>P</i> < 0.001) and lower overall composite Z-scores for amplitude (β = -0.184, <i>t</i> = -4.577, <i>P</i> < 0.001) and NCV (β = -0.117, <i>t</i> = -2.787, <i>P</i> = 0.006) independent of the estimated glomerular filtration rate and other clinical covariates. Additionally, when the analysis was restricted to sensory or motor nerves, elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction.</p><p><strong>Conclusion: </strong>Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 4","pages":"101966"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053283","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}