1.Up-regulation of leptin in adipocytes exposed to high glucose and its effect in peritoneal angiogenesis
Ran JING ; Jiangzi YUAN ; Xinghua SHAO ; Wei FANG ; Zhaohui NI
Chinese Journal of Nephrology 2016;32(9):673-677
Objective By simulating a high-glucose condition of peritoneal dialysis (PD)fluid,to explore the effect of high glucose on the expression of leptin and its relationship with peritoneal angiogenesis.Methods Adipocytes differentiated from 3T3-L1 were divided into high glucose group (139 mmol/l glucose) and high mannitol group.Leptin levels in supernatant collected at 0 h,12 h,24 h and 48 h were measured by ELISA.Endothelial cells (ECs) were respectively cultured with normal glouse,high glucose,high mannitol condition,supernatants of adipocyte induced by normal glouse,high glucose and high mannitol,high glucose supernatants+leptin antibody,and high mannitol supernatants + leptin antibody.Tubular structure formation and migration of ECs were detected.Results Adipocytes exposed to high glucose for 48 h produced more leptin as compared with control group,high mannitol group,12 h-high glucose group and 24 h-high glucose group (all P < 0.05).Compared with ECs in normal group,ECs in high glucose had less tubular structure formation and increased migration (all P < 0.01).Compared with those of ECs in high glucose,the tubular structure formation and the migration of ECs in adipocyte supernatants induced by high glucose had increased (all P < 0.01),and these effects were reduced by leptin antibody (all P < 0.01).Conclusion There is an up-regulation of leptin in adipocytes exposed to high glucose,which may be an alternative way to prevent peritoneal angiogenesis.
2.Meta analysis for the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy
Lei TIAN ; Xinghua SHAO ; Yuanyuan XIE ; Qin WANG ; Ling WANG ; Zhaohui NI ; Shan MOU
Chinese Journal of Nephrology 2014;30(11):833-840
Objective To access the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy (IgAN) by Meta analysis.Methods Databases EMBASE,Pubmed,Elsevier Science Direct,Scopus,Web of Science,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,WanFang and VIP Data were retrieved to collect the randomized controlled trials (RCTs) at least 3 years follow-up on immunosuppression for IgAN published before May 2014.The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria,and the methodological quality was assessed.Statistic software Stata 12.0 was used to conduct analysis.Results Nine articles were included in this study with a total of 568 patients.Immurnosuppression could lowered the risk for the progression to ESRD (RR=0.32,95%CI:0.20-0.49,P < 0.01).As far as the efficacy of immunosuppression,subgroup analysis indicated that three studies with more than 7 year follow-up (RR=0.28,95%CI:0.13-0.59,P < 0.01) were similar with 7 studies followed by for less than 7 years (RR=0.34,95% CI:0.19-0.59,P<0.01); six adopted immunosuppressor monotherapy (RR=0.29,95% CI:0.15-0.58,P< 0.01) were similar to two used corticosteroids plus other immunosuppression (RR=0.33,95%CI:0.18-0.59,P < 0.01); There were no significant differences between four studies from Europe (RR=0.27,95%CI:0.14-0.53,P < 0.01) and five from Asia (RR=0.35,95% CI:0.19-0.65,P<0.01).Immunosuppression was associated with an increased risk for adverse events (RR=2.33,95% CI:1.33-4.09,P<0.01).Conclusion Immunosuppression for IgAN may reduce long-term risk of progression to ESRD,but increase the risk of adverse events to some extent.
3.The effect of recipient kidney function by Ber coadministration CsA used to induce immune tolerance in rats of allogenic cardiac transplantation
Xinghua NI ; Yaoying ZENG ; Jingfang DI ; Xianhui HE ; Tongcheng LIU ; Yi LIN ; Wenyue XIE ; Shan ZENG ; Zheng FENG ;
Chinese Pharmacological Bulletin 2003;0(10):-
AIM To investigate the effect of recipient kidney function by CsA coadministration Ber used to induce immune tolerance in rats of allogenic cardiac transplantation. METHODS The authors established the SD to Wistar rats heterotopic cardiac transplantation model by Onos methods.Observe the cardiac allograft survival and levels of BUN and Cr in the recipients plasma. The recipients were classified into 5 groups randomly after heterotopic cardiac transplantation were performed. Group A (Wistar to Wistar)): Received placebo intraperitoneal injected for 21 days; Group B (SD to Wistar): Saline intraperitoneal injected for 21 days; Group C (SD to Wistar):CsA 2 mg?kg -1 ?d -1 intraperitoneal injected for 21 days; Group D(SD to Wistar):Ber 16 mg?kg -1 ?d -1 gastrointubation for 21 days; Group E(SD to Wistar): Ber 16 mg?kg -1 ?d -1 gastrointubation coadministration CsA 2 mg?kg -1 ?d -1 ip for 21 days. RESULTS The levels of BUN and Cr in recipint plasma is lower evidently compare with the group with CsA ip simply. CONCLUSION Ber can reduce the renal toxicity in recipients by CsA which was intraperitoneal injected (ip) over a long period time.
4.Contrast-enhanced ultrasound predicts the long-term prognosis of chronic kidney disease patients
Qing MA ; Yao XU ; Hongli LI ; Minfang ZHANG ; Qin WANG ; Yuanyuan XIE ; Xinghua SHAO ; Chunlin WANG ; Lei TIAN ; Yanhong YUAN ; Zhaohui NI ; Shan MOU
Chinese Journal of Nephrology 2017;33(3):180-186
Objective To evaluate the ability of contrast-enhanced ultrasound (CEUS) as a prognostic indicator of renal function in chronic kidney disease (CKD) patients.Methods A total of 122 patients with CKD were collected,and patients with allergies to sulfur hexafluoride,pregnancy,cardiopulmonary insufficiency,urinary calculus and tumour were excluded.These patients were divided into estimated glomerular filtration rate [eGFR,ml·min1· (1.73 m2)-1] ≥60 group,eGFR 30-59 group and eGFR < 30 group.CEUS was performed after an intravenous bolus injection of 1.5 ml SonoVue (BR1;Bracco Milan,Italy).Time-intensity curves (TICs) and quantitative indexes were created using QLAB quantification software.Followed up for 2 years,and patients with eGFR dropped 50%,double serum creatinine and end-stage renal disease (ESRD) were regarded as having kidney failure events.Risk factors related to kidney survival were investigated using a multivariate Cox regression model.Results One hundred patients were enrolled in the study,with 78% patients in CKD 1-2 stages,16% in CKD 3 stage and 6% in CKD 4-5 stages.Patients were followed for a mean period of 14.1 months,ten (10%) patients exhibited composite kidney failure events.Among 3 groups,significant differences in the left kidney length derived peak intensity (DPI) were noted (P=0.014,P=0.010).Multivariate Cox regression analysis revealed that the DPI was an independent factor of progression of kidney disease.Multiple linear regression showed that age,basic eGFR,peak intensity were associated with eGFR decline rate.Patients with DPI < 12.27 db were less to recover from kidney disease progression as compared with patients with DPI≥ 12.27 db (P=0.008).The area under the curve (AUC) for DPI was 0.778(95% CI 0.612-0.944,P< 0.05),with a sensitivity of 64% and a specificity of 88%.Conclusions The DPI might be the most valuable CEUS parameter for the evaluation of renal function.The DPI could serve as an independent predictor of the long-term prognosis of CKD patients.
5.Episodic Neurological Dysfunction in X-Linked Charcot-Marie-Tooth Disease: Expansion of the Phenotypic and Genetic Spectrum
Feixia ZHAN ; Wotu TIAN ; Yuwen CAO ; Jingying WU ; Ruilong NI ; Taotao LIU ; Yun YUAN ; Xinghua LUAN ; Li CAO
Journal of Clinical Neurology 2024;20(1):59-66
Background:
and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1.
Methods:
Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1.
Results:
We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel.
Conclusions
These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.
6.Contrast induces kidney epithelial cell apoptosis through NRLP3 inflammasome pathway
Jianxiao SHEN ; Ling WANG ; Na JIANG ; Xinghua SHAO ; Chaojun QI ; Zhen ZHANG ; Yijun ZHOU ; Shu LI ; Shan MOU ; Leyi GU ; Zhaohui NI
Chinese Journal of Nephrology 2018;34(1):36-43
Objective To investigate the effect of pyrin domain 3 (NLRP3) inflammasome in the process of contrast induced human kidney cell apoptosis.Methods Human kidney 2 (HK-2) cells were cultured in DMEM-F12 medium with 5% FBS.Cells were divided into control group,Contrast group (O group),NLRP3-siRNA+Iohexol group (si-NLRP3+O group),ASC-siRNA+Iohexol group (si-ASC+O group),and mannitol group (M group).Different concentrations of hypotonic contrast agent were added to HK-2 cell culture plates for 24,48 and 72 h.Flow cytometry was used to detect apoptosis.NLRP3 and ASC mRNA expressions were detected by RT-PCR.The expressions of NLRP3,ASC,caspase-8/cleaved caspase-8,Bcl-2/Bax,caspase-1/cleaved caspase-1,and caspase-3/cleaved caspase-3 protein were detected by Western blot.The levels of interleukin (IL) 1β and IL-18 in supernatant were detected by ELISA.Results Compared with the control group,the rate of apoptotic cells,as well as the expressions of NLRP3,ASC and cleaved caspase-1 proteins were increased in HK-2 cells of contrast group.The expressions of NLRP3 and ASC mRNA in the contrast group also increased,so did IL-1β and IL-18 levels (all P<0.05),suggesting that NLRP3 inflammasome in HK-2 cells was activated by contrast.Compared with the control group,the expressions of cleaved caspase-8,Bax and cleaved caspase-3 protein were increased,and the expression of anti-apoptotic protein Bcl-2 was decreased (all P < 0.05).Compared with the contrast group,the rate of apoptotic cells in the si-NLRP3 + contrast group and si-ASC + contrast group was significantly decreased;the expression of cleaved caspase-1 was decreased;the expressions of Bax and cleaved caspase-3 were decreased,and Bcl-2 level was increased.The expressions of IL-1β and IL-18 in the supernatant of cells were decreased (all P < 0.05).Conclusion Contrast agent can activate the NLRP3 pathway in HK-2 cells and induce apoptosis,which could be reduced by blocking the NLRP3 pathway.