المؤلفون: Huiwen Liu, Li Wang, Hao Xu, Bin Tan, Qin Yi, Hongrong Deng, Yunxia Chen, Bolin He, Jie Tian, Jing Zhu

المصدر: Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-20 (2023)

مصطلحات موضوعية: hiPSC-CMs, PINK1, Proteomic, Phosphoproteomic, Cytoskeleton, Mitochondrial, Medicine

الوصف: Abstract Background Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are seed cells that can be used for alternative treatment of myocardial damage. However, their immaturity limits their clinical application. Mitochondrial development accompanies cardiomyocyte maturation, and PINK1 plays an important role in the regulation of mitochondrial quality. However, the role and mechanism of PINK1 in cardiomyocyte development remain unclear. Methods We used proteomic and phosphoproteomic to identify protein and phosphosite changes in hiPSC-CMs deficient in PINK1. Bioinformatics analysis was performed to identify the potential biological functions and regulatory mechanisms of these differentially expressed proteins and validate potential downstream mechanisms. Results Deletion of PINK1 resulted in mitochondrial structural breakdown and dysfunction, accompanied by disordered myofibrils arrangement. hiPSC-CMs deficient in PINK1 exhibited significantly decreased expression of mitochondrial ATP synthesis proteins and inhibition of the oxidative phosphorylation pathway. In contrast, the expression of proteins related to cardiac pathology was increased, and the phosphoproteins involved in cytoskeleton construction were significantly altered. Mechanistically, PINK1 deletion damaged the mitochondrial cristae of hiPSC-CMs and reduced the efficiency of mitochondrial respiratory chain assembly. Conclusion The significantly differentially expressed proteins identified in this study highlight the important role of PINK1 in regulating mitochondrial quality in hiPSC-CMs. PINK1-mediated mitochondrial respiratory chain assembly is the basis for mitochondrial function. Whereas the cytoskeleton may be adaptively altered in response to mitochondrial dysfunction caused by PINK1 deletion, inadequate energy supply hinders myocardial development. These findings facilitate the exploration of the mechanism of PINK1 in cardiomyocyte development and guide efforts to promote the maturation of hiPSC-CMs.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1479-5876Test

الوصول الحر: https://doaj.org/article/f50fca79db404ec5ab27ae3e6935d67aTest

المؤلفون: Xubin Yang, Hongrong Deng, Jing Lv, Xueyan Chen, Longyi Zeng, Jianping Weng, Hua Liang, Wen Xu

المصدر: Heliyon, Vol 10, Iss 1, Pp e23309- (2024)

مصطلحات موضوعية: Type 2 diabetes, Adipokines, Inflammatory cytokines, Antidiabetic agents, Exenatide, Science (General), Q1-390, Social sciences (General), H1-99

الوصف: Background: Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). Methods: Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results: In total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1β and IFN-γ were significantly decreased with exenatide treatment (P

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2405844023105172Test; https://doaj.org/toc/2405-8440Test

الوصول الحر: https://doaj.org/article/aa371a4f2a4e49f8a829cdd0529c57d6Test

المؤلفون: Xubin Yang, Xueyan Chen, Huan Xu, Junwei Chen, Bin Yao, Qiongyan Lin, Hongrong Deng, Wen Xu

المصدر: BMC Endocrine Disorders, Vol 23, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: pHPT, PTH, Ectopic parathyroid gland, SVS, Case report, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Background As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion’s location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. Case presentation We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient’s symptoms disappeared and serum levels of PTH and calcium normalized. Conclusions SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1472-6823Test

الوصول الحر: https://doaj.org/article/7471e8fcfec64f17ae9e50c1477342a7Test

المؤلفون: Yongwen Zhou, Mao Zheng, Hongrong Deng, Xueying Zheng, Sihui Luo, Daizhi Yang, Xiaodong Mai, Wen Xu, Jinhua Yan, Jianping Weng

المصدر: Journal of Diabetes, Vol 15, Iss 6, Pp 465-473 (2023)

مصطلحات موضوعية: 基础高血糖, 餐后血糖, HbA1C, 1型糖尿病, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Aim Evidence for contribution of basal and postprandial glucose increment, and glycemic variability to glycated hemoglobin (HbA1c) among adults with type 1 diabetes (T1D) is limited. This study aimed to capture glycemic fluctuation patterns and quantify contributions of these factors to HbA1c levels among adults with T1D. Methods HbA1c, continuous glucose monitoring (CGM), and diet diaries were collected and pooled from two clinical trials. Available data sets were divided into HbA1c quartiles: group 1 (≤6.7%), group 2 (6.7%–7.3%), group 3 (7.3%–7.8%), and group 4 (≥7.8%). Area under curve above 110 mg/dL (AUC>110mg/dL) in 24‐h profile was defined as overall hyperglycemia and stratified with postprandial hyperglycemia (PHG, AUC>110mg/dL in 3‐h period after meals) and basal hyperglycemia (BHG, AUC>110mg/dL in remaining period). Linear regression analysis was used to estimate the proportion of variance in HbA1c explained by BHG, preprandial glucose, PHG, glycemic variability, and non‐glycemic factors (age, body mass index, hemoglobin, and duration). Results A total of 169 550 glucose data in 2409 meals recorded from 102 patients (male/female, 34/68) were included. Age and duration were 35.2 ± 12.6 and 8.9 (2.9, 13.0) years, with 51.0% using pumps. Overall, BHG was four times higher than PHG (p all .05). Factors included in analysis explained a total of 74% of the variance in HbA1c, in which BHG accounted for 32.1% of variance whereas PHG accounted for 24.4%. In group with HbA1c >7.3%, BHG accounted for a higher percentage with 33.8% of the variance in HbA1c. Conclusions In our study, basal hyperglycemia better predicts overall glycemic control than postprandial hyperglycemia among adults with T1D. The relative contribution of basal hyperglycemia increased gradually with HbA1c increasing and predominant strategy for insulin titration among T1D is different among different levels of glycemic control.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1753-0393Test; https://doaj.org/toc/1753-0407Test

الوصول الحر: https://doaj.org/article/39a39a127dd44b2497e70df2a731f168Test

المؤلفون: Hongrong Deng, Daizhi Yang, Wen Xu, Jinhua Yan, Ping Ling, Mengyun Lei, Beisi Lin, Zhigu Liu, Xubin Yang, Jing Lv

المصدر: BMJ Open, Vol 13, Iss 8 (2023)

مصطلحات موضوعية: Medicine

الوصف: Introduction Do-it-yourself artificial pancreas system (DIY APS) is built using commercially available insulin pump, continuous glucose monitoring (CGM) and an open-source algorithm. Compared with commercial products, DIY systems are affordable, allow personalised settings and provide updated algorithms, making them a more promising therapy for most patients with type 1 diabetes mellitus (T1DM). Many small and self-reported observational studies have found that their real-world use was associated with potential metabolic and psychological benefits. However, rigorous-designed studies are urgently needed to confirm its efficacy and safety.Methods and analysis In this 26-week randomised, open-label, two-arm, two-phase, crossover trial, participants aged 18–75 years, with T1DM and glycated haemoglobin (HbA1c) 7–11%, will use AndroidAPS during one 12-week period and sensor-augmented pump during another 12-week period. This study will recruit at least 24 randomised participants. AndroidAPS consists of three components: (1) real-time CGM; (2) insulin pump; (3) AndroidAPS algorithm implemented in Android smartphone. The primary endpoint is time in range (3.9–10.0 mmol/L) derived from CGM. The main secondary endpoints include percentage of sensor glucose values below, within and above target range; mean sensor glucose value; measures of glycaemic variability and centralised HbA1c. Safety endpoints mainly include the frequency of hypoglycaemia events, diabetic ketoacidosis and other serious adverse events.Ethics and dissemination This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. There will be verbal and written information regarding the trial given to each participant. The study will be disseminated through peer-reviewed publications and conference presentations.Overall status Recruiting.Study start 11 February 2023.Primary completion 31 July 2024.Trial registration number ClinicalTrials.gov Registry (NCT05726461).

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/13/8/e073263.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/a9ec9f62cab34489b9c048474f0ca2d4Test

المؤلفون: Yongwen Zhou, Xiaodong Mai, Hongrong Deng, Daizhi Yang, Mao Zheng, Bin Huang, Linlin Xu, Jianping Weng, Wen Xu, Jinhua Yan

المصدر: Journal of Diabetes, Vol 14, Iss 7, Pp 476-484 (2022)

مصطلحات موضوعية: 1型糖尿病, 血糖, 血糖控制, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Background Continuous glucose monitoring systems have been widely used but discrepancies among various brands of devices are rarely discussed. This study aimed to explore differences in glycemic metrics between FreeStyle Libre (FSL) and iPro2 among adults with type 1 diabetes mellitus (T1DM). Methods Participants with T1DM and glycosylated hemoglobin of 7%–10% were included and wore FSL and iPro2 for 2 weeks simultaneously. Datasets collected on the insertion and detachment day, and those with insufficient quantity (

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1753-0393Test; https://doaj.org/toc/1753-0407Test

الوصول الحر: https://doaj.org/article/e971285aa5da4b1bbec8705ffaf65ceaTest

المؤلفون: Yunzhi Chen, Xuemei Yan, Tian Wang, Hongrong Deng, Xiaojie Deng, Fen Xu, Hua Liang

المصدر: International Journal of Endocrinology, Vol 2023 (2023)

مصطلحات موضوعية: Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Background. Patatin-like phospholipase domain-containing 3 (PNPLA3) is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD), and its rs738409 (I148M) polymorphism is associated with the occurrence and progression of NAFLD. Endoplasmic reticulum (ER) stress-related hepatocyte lipoapoptosis contributes to the progress of NAFLD. PNPLA3 is also known as a member of the calcium-independent phospholipase A2ε family, which can hydrolyze fatty acids to generate lysophosphatidylcholine (LPC) that induces ER stress-related hepatocyte lipoapoptosis. Whether the PNPLA3 risk genotype 148M/M is involved in more severe ER stress-associated lipoapoptosis is unclear. Methods. A PNPLA3148I knock-in HepG2 cell model was constructed based on HepG2 expressing PNPLA3 148M/M using the Cas9/sgRNA system. PNPLA3 148M/M, I/M, and I/I cells were treated with 0.3 mM palmitic acid (PA) for 24 h to induce lipid deposition. Cellular lipid deposition was detected by oil red staining. Apoptosis was observed by TUNEL. LPC was determined by ELISA, and the expression of PNPLA3, the ER stress marker Bip, molecules involved in the ER stress PERK/elF-2a pathway, and its downstream C/EBP homologous protein (CHOP)-mediated apoptotic pathway were detected by western blot. Results. The results showed no difference in PNPLA3 basal expression and basal hepatocyte lipid content between the three genotypes of cells. Lipid deposition and apoptosis were more severe in PNPLA3 148M/M and 148I/M cells than in I/I cells after PA treatment. PA-induced upregulation of protein expression of Bip, ER stress-responsive PERK pathway molecules p-PERK, p-eIF2α, CHOP, and CHOP-associated apoptotic molecules PUMA and Bax were more pronounced in PNPLA3 148M/M cells than in PNPLA3 148I/I cells. The basal LPC levels and the PA-treated increase of LPC levels in the cell culture supernatants did not differ between the three genotypic cells. Conclusion. PNPLA3 148M/M cells were more susceptible to PA-induced lipid deposition and ER stress-related apoptosis than 148I/I cells, and the proapoptotic susceptibility of PNPLA3 148M/M is independent of LPC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1687-8345Test

الوصول الحر: https://doaj.org/article/505aa736132643dda52e9d9c95156252Test

المؤلفون: Li Wang, Hao Xu, Bin Tan, Qin Yi, Huiwen Liu, Hongrong Deng, Yunxia Chen, Rui Wang, Jie Tian, Jing Zhu

المصدر: Frontiers in Endocrinology, Vol 13 (2022)

مصطلحات موضوعية: obesity, puberty, microbiota, short chain fatty acids (SCFAs), high-fat diet, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: The intestinal microbiota and its derived short-chain fatty acids (SCFAs) can reverse obesity and obesity-related metabolic diseases, but whether it has an effect on obesity complicated by precocious puberty and its potential mechanism need to be further understood. The purpose of this study was to investigate the effect of the gut microbiota and its derived short-chain fatty acids (SCFAs) on obesity-induced precocious puberty rats and their regulatory mechanisms. We constructed obesity-induced precocious puberty rats using a high-fat diet (HFD) had notable similarity to precocious puberty caused by obesity due to overeating in children. We then added acetate, propionate, butyrate or their mixture to the HFD, and investigated the effect of intestinal microbiota and its derived SCFAs on the hypothalamic-pituitary-gonadal axis (HPGA) in rats with obesity-induced precocious puberty. We found that obesity-induced precocious puberty rats had an early first estrous cycle, increased hypothalamic mRNA expression of Kiss1, GPR54 and GnRH, and early gonadal maturation. Meanwhile, the intestinal microbiota imbalance and the main SCFAs production decreased in the colon. The addition of acetate, propionate, butyrate or their mixture to the HFD could significantly reverse the precocious puberty of rats, reduce GnRH release from the hypothalamus and delay the development of the gonadal axis through the Kiss1–GPR54–PKC–ERK1/2 pathway. Our findings suggest that gut microbiota-derived SCFAs are promising therapeutic means for the prevention of obesity-induced precocious puberty and provide new therapeutic strategies with clinical value.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2022.1051797/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/8a2d5f87f38f4d89a7d14c39172be655Test

المؤلفون: Qianwen Huang, Daizhi Yang, Hongrong Deng, Hua Liang, Xueying Zheng, Jinhua Yan, Wen Xu, Xiangwen Liu, Bin Yao, Sihui Luo, Jianping Weng

المصدر: Diabetes & Metabolism Journal, Vol 46, Iss 1, Pp 93-103 (2022)

مصطلحات موضوعية: adult, diabetes mellitus, type 1, diabetic nephropathies, diabetic retinopathy, metabolic syndrome, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Background Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. Methods We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). Results Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P

وصف الملف: electronic resource

العلاقة: http://www.e-dmj.org/upload/pdf/dmj-2020-0240.pdfTest; https://doaj.org/toc/2233-6079Test; https://doaj.org/toc/2233-6087Test

الوصول الحر: https://doaj.org/article/2042062122c34cd59b8b117140ec407bTest

المؤلفون: Riying Liang, Meijun Wang, Chang Fu, Hua Liang, Hongrong Deng, Ying Tan, Fen Xu, Mengyin Cai

المصدر: Endocrine Connections, Vol 9, Iss 9, Pp 946-954 (2020)

مصطلحات موضوعية: chronic kidney disease, glucagon-like peptide-1, apoptosis, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Background: Obesity is associated with the development and progression of c hronic kidney disease. Emerging evidence suggests that glucagon-like p eptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (S IRT1) was considered as a crucial regulator in metabolism-related kidney disease. He rein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated. Methods: Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its prote ctive effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mes angial cells was elucidated. Results: Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregula ted, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxid ative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV4 0 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the dow nregulation of TXNIP by liraglutide was blocked. Conclusions: Liraglutide might have a beneficial effect on metabolism-relate d kidney damage by inhibiting apoptosis via activation of SIRT1 and supp ression of TXNIP pathway.

وصف الملف: electronic resource

العلاقة: https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0294.xmlTest; https://doaj.org/toc/2049-3614Test

الوصول الحر: https://doaj.org/article/8ab9070512dc4b0eaf34436c4a38cdbdTest