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Lighting upβ-cell function:Noninvasive MRI of glucose-stimulated Zn2+secretion 认领 引用
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作者 Lixiong Dai Mauro Botta Shiyuan Liu 《Magnetic Resonance Letters》 EI CAS 2026年第3期82-83,共2页
Deep-tissue visualization of Zn2+flux represents a significant yet challenging objective in molecular diagnostics[1].Since Zn2+is co-released with insulin during glucose-stimulated secretion,real-time imaging of... Deep-tissue visualization of Zn2+flux represents a significant yet challenging objective in molecular diagnostics[1].Since Zn2+is co-released with insulin during glucose-stimulated secretion,real-time imaging of its dynamics could provide a non-invasive window intoβ-cell function and the progression of diabetes[2].However,achieving this goal requires overcoming two major hurdles:sufficient tissue penetration and high detection sensitivity[3].In this context,the recent work by Bingbo Zhang and colleagues represents an important advance.They report a rationally designed Fe3+-based probe,FeL2,which integrates a structurally reinforced Zn2+-responsive motif that effectively enhances relaxivity in deep-seated tissues such as the pancreas,offering a promising new tool for diabetes management and advancing the field of metabolic imaging[4]. 展开更多
关键词 noninvasive MRI real time imaging Zn flux glucose stimulated Zn secretion tissue penetration lighting up cell function molecular diagnostics deep tissue visualization
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Human congenital cataract mutation in MYH9 alters F-actin organization and cell functions 认领 引用
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作者 Hao Yuan Zhen-Yu Wang +3 位作者 Jia-Rui Yang Chen Huang Liang Zhu Xue-Min Li 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2025年第6期969-977,共9页
AIM:To explore the role of a previously-found MYH9 tail domain mutation(p.E1384Q)in the pathogenesis of congenital cataract.METHODS:The cell experiments were conducted in vitro.Wild-type(WT)MYH9 and p.E1384Q mutant fr... AIM:To explore the role of a previously-found MYH9 tail domain mutation(p.E1384Q)in the pathogenesis of congenital cataract.METHODS:The cell experiments were conducted in vitro.Wild-type(WT)MYH9 and p.E1384Q mutant fragments were constructed,which was then transiently transfected into Hek293T cell lines.Western blotting and quantitative real time polymerase chain reaction(qRT-PCR)were used to analyze the protein and mRNA level of non-muscle myosin IIA(NM IIA)and F-actin in transfected cells,and fluorescence microscopy was applied to explore the subcellular localization of NM IIA and F-actin.Cell counting kit-8(CCK8),woundhealing and double staining flow cytometry assays were performed to evaluate the proliferation,migration and apoptosis function of transfected cells,respectively.Transmission electron microscope was conducted to observe the alteration of organelle structure.RESULTS:The transiently-transfected WT and p.E1384Q mutant Hek293T cell lines was constructed.Western blot demonstrated that,comparing with MYH9WT group,the relative protein amount of NM IIA and F-actin significantly decreased in MYH9E1384Q cells(P<0.001).qRT-PCR analysis revealed that the relative mRNA amount of NM IIA and F-actin also significantly reduced in MYH9E1384Q cells when compared with MYH9WT.The immunofluorescence microscopy showed that the fluorescence signal of NM IIA and F-actin significantly decreased in E1384Q cells.The diffuse cytoplasmic distribution of NM IIA in MYH9WT was changed to be clumped distribution,presenting a“speckled”pattern characterized by aggregates of small size in MYH9E1384Q.Functional study revealed that the E1384Q mutation significantly inhibited cell proliferation(P=0.003)and migration(P<0.001),and promoted apoptosis(P<0.001).Electron microscope showed that the mutation remarkably decreased the number of mitochondria(P<0.001)and changed the phenotype of mitochondria.CONCLUSION:The missense gene mutation in MYH9(p.E1384Q)causing congenital cataract results in decreased amount and altered subcellular distribution of NM IIA and F-actin,accompanied by decreased cell proliferation and migration,promotes apoptosis and mitochondrial alteration. 展开更多
关键词 congenital cataract MYH9 F-actin cell function mitochondria
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The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice 认领 引用 被引量：5
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作者 LIU Shuai-Nan LIU Quan +5 位作者 LEI Lei SUN Su-Juan LI Cai-Na HUAN Yi HOU Shao-Cong SHEN Zhu-Fang 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2020年第11期827-836,共10页
Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recen... Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT) to T2 DM. In this study, we evaluated the effect of JTN on the progression of T2 DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp.Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase(GCK), pyruvate carboxylase(PCB) and pancreas duodenum homeobox-1(PDX-1), while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum(ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2 DM. 展开更多
关键词 Jin-tang-ning(JTN) Pre-diabetes βCell function Type 2 diabetes ER stress
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Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes 认领 引用 被引量：7
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作者 LinYang Zhi-GuangZhou +3 位作者 GanHuang Ling-LiOuyang XiaLi XiangYan 《World Journal of Gastroenterology》 SCIE CAS 2005年第19期2900-2905,共6页
AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to... AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with thebaseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±71.5 vs 572.8±72.3 pmol/L, P＜0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P= 0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs= -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P＜0.05). Moreover, GAD-Ab wasthe only risk factor for predicting βcell failure in LADA patients (B = 1.455, EXP (B) = 4.283, P = 0.023). CONCLUSION: The decreasing rate of islet β cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet β cell function, and age at onset and BMI could also act as the predictors. 展开更多
关键词 Latent autoimmune diabetes in adults Type 2 diabetes Islet β cell function Glutamic acid decarboxylase antibody
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MicroRNA-34c regulates porcine granulosa cell function by targeting forkhead box O3a 认领 引用 被引量：3
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作者 XU Yuan ZHANG Ai-ling +4 位作者 ZHANG Zhe YUAN Xiao-long CHEN Zan-mou ZHANG Hao LI Jia-qi 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2017年第9期2019-2028,共10页
Granulosa cells（GCs） are somatic cells of ovary, the behaviors of GCs are important for ovarian function. MicroRNAs（miRNAs） are a class of endogenous 18–24 nucleotide（nt） non-coding RNAs, some of which have bee... Granulosa cells（GCs） are somatic cells of ovary, the behaviors of GCs are important for ovarian function. MicroRNAs（miRNAs） are a class of endogenous 18–24 nucleotide（nt） non-coding RNAs, some of which have been shown to be important regulators of GCs function. miR-34c involved in the regulation of various biological processes and was identified to be a pro-apoptotic and anti-proliferative factor in many cell types. However, the roles of miR-34c in GCs function remain unknown. In this study, we used Annexin V-FITC and Ed U assays to demonstrate that miR-34c exerted pro-apoptotic and anti-proliferative effects in porcine GCs. Dual-luciferase reporter assays, quantitative real-time PCR（q RT-PCR） and Western blotting identified Forkhead box O3a（Fox O3a） as a direct target gene of miR-34c. The overexpression of FoxO3a rescued the phenotypic change caused by miR-34c in porcine GCs. In conclusion, miR-34c regulate the function of porcine GCs by targeting FoxO3a. 展开更多
关键词 porcine microRNA-34c FoxO3a granulosa cell function
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EFFECTS OF GLUCAGON ON ISLET β CELL FUNCTION IN PATIENTS WITH DIABETES MELLITUS 认领 引用 被引量：7
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作者 Tong Wang Xin-hua Xiao Wen-hui Li Heng Wang Qi Sun Tao Yuan Guo-hua Yang 《Chinese Medical Sciences Journal》 CAS 2008年第2期117-120,共4页
Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type... Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus. 展开更多
关键词 glucagon diabetes mellitus C-peptide islet β cell function
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Regulation of neural stem/progenitor cell functions by P2X and P2Y receptors 认领 引用
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作者 Peter Illes Patrizia Rubini 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第3期395-396,共2页
Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belong... Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）. 展开更多
关键词 NSCs cell Regulation of neural stem/progenitor cell functions by P2X and P2Y receptors stem
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Bilayer nicorandil-loaded small-diameter vascular grafts improve endothelial cell function via PI3K/AKT/eNOS pathway 认领 引用 被引量：1
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作者 Zheng Xing Chen Zhao +2 位作者 Chunchen Zhang Yubo Fan Haifeng Liu 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2021年第1期72-86,共15页
For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fa... For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft. 展开更多
关键词 Bilayer vascular grafts Nicorandil Sulfated silk fibroin Endothelial cell function PI3K/AKT/eNOS pathway
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The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus 认领 引用
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作者 Mengdan Kong Ailin Zhong +1 位作者 Shilin Qu Junli Xue 《Advances in Bioscience and Biotechnology》 CAS 2024年第2期129-139,共11页
Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The st... Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious. 展开更多
关键词 Tuberculosis Infection Type 2 Diabetes Mellitus Pancreatic β-Cell Function Insulin Resistance
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THE CHANGES OF PANCREATIC ACINAR CELL FUNCTION IN ACUTE NECROTIZING PANCREATITIS OF RATS 认领 引用
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作者 余枭 张圣道 +3 位作者 韩天权 汤耀卿 雷若庆 夏宗勤 《Medical Bulletin of Shanghai Jiaotong University》 2000年第1期18-21,共4页
ObjectiFe To evaluate the changes of pancreatic acinar cell functions in the rats with acutenecrotizing pancreatitis (ANP). methods Seventy SD rats were randomized into two groups: experimental group(n=35) and control... ObjectiFe To evaluate the changes of pancreatic acinar cell functions in the rats with acutenecrotizing pancreatitis (ANP). methods Seventy SD rats were randomized into two groups: experimental group(n=35) and control group (n=35). To prepare the experimental model, the retrograde injection of 5% sodiumtaurocholate into the pancreatic duct was used for inducing ANP. Radioactive tracing by L -3H-phenylalanineand autoradiography were performed for scoring the differences of changes of amino acid uptake, enzyme-proteinsynthesis and output from acinar cells in rats between both groups. Results No changes were observed in aminoacid uptake and enzyme -protein synthesis in rats with dotted and haemorrhagic necrotizing foci as compared withcontrol group. However, accumulated zymogen granules in the interstitial of acinar cells were seen in theexperimental group. Conclusion It indicates that in experimental ANP rats, the functions of acinar cells in bothamino acid uptake and protein synthesis were essentially normal, but the pathway of enzyme output was affectedinto ectopic secretion through the bottom or lateral cellular membrane of pancreatic acinar cell. 展开更多
关键词 acute necrotizing pancreatitis cell functions radioactive trace autoradiography
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Preventing trogocytosis by cathepsin B inhibition augments CAR T-cell function 认领 引用
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作者 Kenneth A.Dietze Kiet Nguyen +16 位作者 Aashli Pathni Frank Fazekas Wenxiang Sun Ethan Rosati Jillian M.Baker Maday Galeana Figueroa Etse Gebru Daniel Yamoah Rediet Mulatu Alexander Wang Aaron P.Rapoport David H.Lum Xiaoxuan Fan Sabarinath V.Radhakrishnan Djordje Atanackovic Arpita Upadhyaya Tim Luetkens 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2026年第5期3075-3089,共15页
Chimeric antigen receptor(CAR)T-cell therapy has shown remarkable efficacy in cancer treatment.Nevertheless,most patients receiving CAR T cells relapse within 5 years of treatment.CAR-mediated trogocytosis(CMT)is a po... Chimeric antigen receptor(CAR)T-cell therapy has shown remarkable efficacy in cancer treatment.Nevertheless,most patients receiving CAR T cells relapse within 5 years of treatment.CAR-mediated trogocytosis(CMT)is a potential tumor escape mechanism in which cell surface proteins transfer from tumor cells to CAR T cells.CMT results in the emergence of antigen-negative tumor cells,which can evade future CAR detection,and antigen-positive CAR T cells,which have been suggested to cause CAR T-cell fratricide and exhaustion.Whether CMT indeed causes CAR T-cell dysfunction and the molecular mechanisms conferring CMT remain unknown.Using a selective degrader of trogocytosed antigen in CAR T cells,we show that the presence of trogocytosed antigen on the CAR T-cell surface directly causes CAR T-cell fratricide and exhaustion.By performing small molecule screening using a custom high-throughput CMT screening assay,we found that the cysteine protease cathepsin B is essential for CMT and that inhibition of cathepsin B is sufficient to prevent CAR T-cell fratricide and exhaustion,leading to improved long-term in vitro and in vivo CAR T-cell persistence and in vitro antitumor activity.Our data demonstrate that it is feasible to separate CMT from cytotoxic activity,that CAR T-cell persistence,a key factor associated with clinical CAR T-cell efficacy,is directly linked to cathepsin B activity in CAR T cells,and that it is possible to improve CAR T-cell function through selective inhibition of CMT. 展开更多
关键词 trogocytosis tumor escape mechanism CAR T cell function car t cellswhich cell surface proteins transfer tumor cells car t cells cathepsin B inhibition
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Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes 认领 引用
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作者 Fan Yu Yinfang Tu +22 位作者 Yanfang Zhang Tianwei Gu Haoyong Yu Xiangyu Meng Si Chen Fengjing Liu Ke Huang Tianhao Ba Siqian Gong Danfeng Peng Dandan Yan Xiangnan Fang Tongyu Wang Yang Hua Xianghui Chen Hongli Chen Jie Xu Rong Zhang Linong Ji Yan Bi Xueyao Han Hong Zhang Cheng Hu 《Chinese Medical Journal》 SCIE CAS CSCD 2025年第9期1129-1131,共3页
To the Editor:Maturity-onset diabetes of the young(MODY)is characterized as a non-autoimmune form of diabetes with an autosomal dominant inheritance pattern.Due to the overlapping clinical phenotypes among MODY,such a... To the Editor:Maturity-onset diabetes of the young(MODY)is characterized as a non-autoimmune form of diabetes with an autosomal dominant inheritance pattern.Due to the overlapping clinical phenotypes among MODY,such as type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM),over 80%of MODY patients are initially misdiagnosed.[1]In recent decades,the advent and development of next-generation sequencing technology have facilitated a deeper understanding of MODY.High-throughput sequencing has remarkably expanded our knowledge of the pathogenic patterns of MODY across diverse populations. 展开更多
关键词 high throughput sequencing multi center study pancreatic cell function next generation sequencing clinical phenotypes type diabetes mellitus t dm maturity onset diabetes young pathogenic variants
Comments on‘BAF60a-dependent chromatin remodeling preservesβ-cell function and contributes to the therapeutic benefits of GLP-1R agonists’ 认领 引用
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作者 Qingqian Wu Yue Gao Zhuo-Xian Meng 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2025年第10期57-59,共3页
Type 2 diabetes(T2D)is a highly prevalent metabolic disease characterized by impaired glucose-stimulated insulin secretion(GSIS)and progressive failure of pancreaticβ-cell.However,the underlying molecular mechanisms ... Type 2 diabetes(T2D)is a highly prevalent metabolic disease characterized by impaired glucose-stimulated insulin secretion(GSIS)and progressive failure of pancreaticβ-cell.However,the underlying molecular mechanisms governingβ-cell dysfunction during the course of T2D remain incompletely understood,and current therapeutic strategies show limited and heterogeneous benefits.Maintainingβ-cell identity and functional plasticity under metabolic stress is essential for glucose homeostasis.Accumulating evidence indicates that epigenetic remodeling is a central driver ofβ-cell adaptation and deterioration(Kim and Kulkarni,2020;Wang et al.,2022).Among epigenetic regulators,ATP-dependent switch/sucrose non-fermentable(SWI/SNF)complexes have emerged as key determinants ofβ-cell transcriptional competence.However,whether individual SWI/SNF subunits act as metabolic sensors inβ-cells is still unclear. 展开更多
关键词 baf chromatin remodeling cell function type diabetes type diabetes t d glucose stimulated insulin secretion GLP R agonists metabolic disease
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Expansion of functional human salivary acinar cell spheroids with reversible thermo-ionically crosslinked 3D hydrogels 认领 引用
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作者 Jose G.Munguia-Lopez Sangeeth Pillai +5 位作者 Yuli Zhang Amatzia Gantz Dimitria B.Camasao Showan N.Nazhat Joseph M.Kinsella Simon D.Tran 《International Journal of Oral Science》 SCIE CAS CSCD 2025年第3期368-378,共11页
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e... Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids. 展开更多
关键词 secretory cellsthe xerostomia vitro platforms head neck cancers test therapies functional human salivary acinar cell spheroids reversible thermo ionically crosslinked D hydrogels Sjogren's syndrome
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Effect of Dapagliflozin combined1with insulin treatment on blood glucose index and pancreaticβ-cell function in overweight/obese type 2 diabetes mellitus patients with different disease durations 认领 引用
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作者 ZHANG Yan 《China Medical Abstracts(Internal Medicine)》 2025年第1期24-25,共2页
Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreaticβ-cell function in overweight/obese type 2 diabetes mellitus(T2DM)patients with different dis... Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreaticβ-cell function in overweight/obese type 2 diabetes mellitus(T2DM)patients with different disease durations.Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected.They were divided into three groups,short duration group(≤10 years group,n=95),medium duration group(10-20 years group,n=96)and long duration group(≥20 years group,n=97).Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months.Clinical efficacy,blood glucose indices,pancreaticβ-cell function and complications during the treatment period were compared among the three groups.Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA,c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<O.05).Meanwhile,HDL-C,C-P,HOMA-βand HOMA-IS values showed a significant increase(P<0.05).After treatment,WC,FPG,2 hPG,HbA,c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<O.05),while HDL-C,C-P,HOMA-βand HOMA-IS decreased in turn in≤1O years group,10-20 years group,≥20 years group(P<0.05).The BMI of 10-20 years group was lower than that of≤10 years group and≥20 years group(P<0.05),while the BMI of≥20 years group was higher than that of≤10 years group(P<0.05).Conclusion In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreaticβ-cell function,especially for patients with a shorter disease duration. 展开更多
关键词 impaired pancreatic function blood glucose index insulin treatment dapagliflozin disease duration overweight obese type diabetes mellitus pancreatic cell function
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A review on cell damage,viability,and functionality during 3D bioprinting 认领 引用 被引量：10
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作者 He-Qi Xu Jia-Chen Liu +1 位作者 Zheng-Yi Zhang Chang-Xue Xu 《Military Medical Research》 SCIE CAS CSCD 2023年第5期620-635,共16页
Three-dimensional(3D)bioprinting fabricates 3D functional tissues/organs by accurately depositing the bioink composed of the biological materials and living cells.Even though 3D bioprinting techniques have experienced... Three-dimensional(3D)bioprinting fabricates 3D functional tissues/organs by accurately depositing the bioink composed of the biological materials and living cells.Even though 3D bioprinting techniques have experienced significant advancement over the past decades,it remains challenging for 3D bioprinting to artificially fabricate functional tissues/organs with high post-printing cell viability and functionality since cells endure various types of stress during the bioprinting process.Generally,cell viability which is affected by several factors including the stress and the environmental factors,such as pH and temperature,is mainly determined by the magnitude and duration of the stress imposed on the cells with poorer cell viability under a higher stress and a longer duration condition.The maintenance of high cell viability especially for those vulnerable cells,such as stem cells which are more sensitive to multiple stresses,is a key initial step to ensure the functionality of the artificial tissues/organs.In addition,maintaining the pluripotency of the cells such as proliferation and differentiation abilities is also essential for the 3D-bioprinted tissues/organs to be similar to native tissues/organs.This review discusses various pathways triggering cell damage and the major factors affecting cell viability during different bioprinting processes,summarizes the studies on cell viabilities and functionalities in different bioprinting processes,and presents several potential approaches to protect cells from injuries to ensure high cell viability and functionality. 展开更多
关键词 Three-dimensional bioprinting Cell damage Shear stress Cell viability Cell functionality
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Insulin sensitivity,βcell function,and adverse pregnancy outcomes in women with gestational diabetes 认领 引用 被引量：6
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作者 Yun Shen Yanwei Zheng +9 位作者 Yingying Su Susu Jiang Xiaojing Ma Jiangshan Hu Changbin Li Yajuan Huang Yincheng Teng Yuqian Bao Minfang Tao Jian Zhou 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第21期2541-2546,共6页
Background: The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association b... Background: The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.Methods: This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.Results: Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes.Conclusions: We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values. 展开更多
关键词 βcell function Insulin sensitivity Adverse pregnancy outcomes
The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study 认领 引用 被引量：23
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作者 Yun-Yun Li Xiu-Fen Yang +3 位作者 Hong Gu Torkel Snellingen Xi-Pu Liu Ning-Pu Liu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第3期493-500,共8页
AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether th... AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI. 展开更多
关键词 type 2 diabetes mellitus diabetic retinopathy insulin resistance β-cell function body mass index
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Glutamine deprivation impairs function of infiltrating CD8+T cells in hepatocellular carcinoma by inducing mitochondrial damage and apoptosis 认领 引用 被引量：3
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作者 Wei Wang Meng-Nan Guo +2 位作者 Ning Li De-Quan Pang Jing-Hua Wu 《World Journal of Gastrointestinal Oncology》 SCIE 2022年第6期1124-1140,共17页
BACKGROUND The functions of infiltrating CD8+T cells are often impaired due to tumor cells causing nutrient deprivation in the tumor microenvironment.Thus,the mechanisms of CD8+T cell dysfunction have become a h... BACKGROUND The functions of infiltrating CD8+T cells are often impaired due to tumor cells causing nutrient deprivation in the tumor microenvironment.Thus,the mechanisms of CD8+T cell dysfunction have become a hot research topic,and there is increased interest on how changes in metabolomics correlate with CD8+T cell dysfunction.AIM To investigate whether and how glutamine metabolism affects the function of infiltrating CD8+T cells in hepatocellular carcinoma.METHODS Immunohistochemical staining and immunofluorescence were performed on surgically resected liver tissues from patients.Differentially expressed genes in infiltrating CD8+T cells in hepatocellular carcinoma were detected using RNA sequencing.Activated CD8+T cells were co-cultured with Huh-7 cells for 3 d.The function and mitochondrial status of CD8+T cells were analyzed by flow cytometry,quantitative real-time polymerase chain reaction,and transmission electron microscopy.Next,CD8+T cells were treated with the mitochondrial protective and damaging agents.Functional alterations in CD8+T cells were detected by flow cytometry.Then,complete medium without glutamine was used to culture cells and their functional changes and mitochondrial status were detected.RESULTS There were a large number of infiltrating PD-1+CD8+T cells in liver cancer tissues.Next,we cocultured CD8+T cells and Huh-7 cells to explore the regulatory effect of hepatoma cells on CD8+T cells.Flow cytometry results revealed increased PD-1 expression and decreased secretion of perforin(PRF1)and granzyme B(GZMB)by CD8+T cells in the co-culture group.Meanwhile,JC-1 staining was decreased and the levels of reactive oxygen species and apoptosis were increased in CD8+T cells of the co-culture group;additionally,the mitochondria of these cells were swollen.When CD8+T cells were treated with the mitochondrial protective and damaging agents,their function was restored and inhibited,respectively,through the mitochondrial damage and apoptotic pathways.Subsequently,complete medium without glutamine was used to culture cells.As expected,CD8+T cells showed functional downregulation,mitochondrial damage,and apoptosis.CONCLUSION Glutamine deprivation impairs the function of infiltrating CD8+T cells in hepatocellular carcinoma through the mitochondrial damage and apoptotic pathways. 展开更多
关键词 Glutamine Mitochondrial damage CD8+T cells T cell function Hepatocellular carcinoma
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Long-term exposure to decabrominated diphenyl ether mpairs CD8 T-cell function in adult mice 认领 引用 被引量：2
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作者 Weihong Zeng Ying Wang +9 位作者 Zhicui Liu Asma Khanniche Qingliang Hu Yan Feng Weiyi Ye Jianglong Yang Shujun Wang Lin Zhou Hao Shen Yan Wang 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2014年第4期367-376,共10页
Polybrominated diphenyl ethers （PBDEs） are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been show... Polybrominated diphenyl ethers （PBDEs） are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been shown to affect human neuronal, endocrine and reproductive systems, but their effect on the immune system is not well understood. In this study, experimental adult mice were intragastrically administered 2,2＇,3,3＇,4,4＇,5,5＇,6,6＇-decabromodiphenyl ether （BDE-209） at doses of 8, 80 or 800 mg/kg of body weight （bw） at 2-day intervals. Our results showed that continuous exposure to BDE-209 resulted in high levels of BDE-209 in the plasma that approached the levels found in people who work in professions with high risks of PDBE exposure. Reduced leukocytes, decreased cytokine （IFN-7, IL-2 and TNF-a） production and lower CD8 T-cell proliferation were observed in the mice exposed to BDE-209. Additionally, mice with long-term BDE-209 exposure had lower numbers of antigen-specific CD8 T cells after immunization with recombinant Listeria monocytogenesexpressing ovalbumin （rLm-OVA） and the OVA-specific CD8 T cells had reduced functionality. Taken together, our study demonstrates that continuous BDE-209 exposure causes adverse effects on the number and functionality of immune cells in adult mice. 展开更多
关键词 BDE-209 CD8 T cells continuous exposure immunotoxicity T-cell functions
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