NANOG Alleviates the Damage of Human Hair Follicle Mesenchymal Stem Cells Caused by H_2O_2 through Activation of AKT Pathway

Objective To explore the protective effect of NANOG against hydrogen peroxide(H_2O_2)-induced cell damage in the human hair follicle mesenchymal stem cells(hHF-MSCs). Methods NANOG was expressed from a lentiviral vector, pLVX-IRES-ZsGreen. NANOG hHF-MSCs and vector hHF-MSCs were treated with 400 μmol/L hydrogen peroxide(H_2O_2) for 2 h, the cell survival rate, cell morphology, ROS production, apoptosis and expression of AKT, ERK, and p21 were determined and compared. Results Our results showed that NANOG could activate AKT and upregulate the expression of p-AKT, but not p-ERK. When treated with 400 μmol/L H_2O_2, NANOG hHF-MSCs showed higher cell survival rate, lower ROS production and apoptosis, higher expression of p-AKT, higher ratio of p-AKT/AKT. Conclusion Our results suggest that NANOG could protect hHF-MSCs against cell damage caused by H_2O_2 through activating AKT signaling pathway.     

提高毛发移植的覆盖率

目的探讨显微外科技术自体毛发移植的特点和方法,提高毛发移植成活的覆盖率。方法在较低温度(20°C)环境下,采用边切边缝方法取耳后或枕后毛发,在显微镜下分离成保留周围少量脂肪组织的毛囊族或单株,按需要移植部位不同进行不同的毛囊族或单株并套插的显微外科技术移植共31例。结果31例移植毛发后随访21例,随访时间6~38个月,移植后的毛发能基本覆盖无毛发区的皮肤和瘢痕,移植覆盖率较原来的移植方法提高33%,且外形自然,效果稳定。结论显微外科技术自体毛囊族状(微株小株)或单株移植,具有操作快、损伤小、低温保湿等特点,能较好地保留毛囊周围少量脂肪,在孔与孔的皮肤间隙内再用毛发移植针植入单株毛坯的“套插”移植,更有助于增加毛发覆盖率。     

Rat Cytomegalovirus-Accelerated Transplant Vascular Sclerosis Is Reduced with Mutation of the Chemokine-Receptor R33

Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Deltar33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 x 10(5) pfu RCMV or RCMV-Deltar33 on postoperative day (POD) 1. Grafts from RCMV-Deltar33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Deltar33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Deltar33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-receptor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.     

Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.     

Expression of adhesion molecules and RANTES in kidney transplant from nonheart-beating donors

The main difference between cadaveric kidneys from donors with a heartbeat (HBD) and kidneys from nonheart-beating donors (NHBD) is related to warm ischemia/reperfusion time which constitutes an acute inflammatory process. On the contrary, brain death induces in HBD expression of pro-inflammatory adhesion molecules, making it important to evaluate this kind of molecules in both types of donors. Human renal biopsies from NHBD, HBD and normal kidneys (ischemia time = 0) were taken and frozen just before transplant. A semi-quantitative RT-PCR method was used to determine intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), lymphocyte function associated antigen (LFA-1), LFA-3, CD40, CD40 ligand (CD40L) and RANTES (regulated upon activation, normal T-cell expressed and secreted) gene expression. We have detected an elevated relative gene expression of ICAM-1, VCAM-1 and RANTES in NHBD biopsies compared with normal kidneys. In the case of RANTES, the gene expression from NHBD biopsies was higher than observed in HBD biopsies. The rest of genes were not augmented in any group. Preliminary data about early outcome of transplants indicates a correlation between pretransplant RANTES high gene expression levels and early post-transplant acute rejection. The gene expression of pro-inflammatory molecules like adhesion molecules and RANTES is augmented in kidneys from cadaveric NBD just before transplant. The expression is higher probably because of the prolonged warm ischemia period. A larger clinical study is necessary to clarify the effects of these variable expressions on the transplant outcome.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

器官移植免疫治疗的相关研究进展

通过近十年来的发展，同种异体器官移植在免疫机理、免疫抑制治疗和免疫耐受等方面的研究取得了很大的进步，为人类同种异体器官移植展示了光辉的前景。本文通过丈献回顾，综述其相关进展。     

Hip Arthroplasty Outcomes in the Presence of Kidney Failure: A National Data Linkage Study

BackgroundPatients who have kidney failure are at higher risk of requiring total hip arthroplasty (THA) and are at higher risk of complications. This study compared the rate of revision surgery and mortality following THA between patients who have kidney failure receiving long term dialysis or who had a kidney transplant and those who did not have kidney failure.MethodsA data linkage study was performed using data from 2 national registries: a registry of dialysis and kidney transplant patients and a registry of THA procedures. Both registries had coverage of almost all procedures or treatments in Australia. Data from September 1999 to December 2016 were used. Mortality and revision surgery were compared between patients receiving dialysis, those who had a functioning kidney transplant, and patients who did not have kidney failure using Cox and Fine-Gray (competing risk) regression models. A total of 383,478 primary THA procedures were identified as people receiving dialysis (n = 490), who had a functioning kidney transplant (n = 459), or who did not have kidney failure (n = 382,529).ResultsThere was no significant difference in the overall rate of revision surgery between the groups (dialysis versus no kidney failure HR = 1.20; 95% CI 0.76, 1.88, transplant versus no kidney failure (hazard ratio) HR = 1.01; 95% (confidence interval) CI 0.66, 1.53). The risk for death after surgery was significantly higher in the dialysis group compared to both the functioning transplant group (HR = 3.44; 95%CI 1.58, 7.5), and in those without kidney failure (HR = 4.13; 95%CI 3.25, 5.25).ConclusionThe rate of mortality after THA in patients on dialysis is higher than in patients who have a functioning transplant or those who do not have kidney failure, but there is no early excess mortality to suggest a difference in this metric due to the surgery.     

Recrudescent Tobacco Exposure Following Heart Transplantation: Clinical Profiles and Relationship with Athero-Thrombosis Risk Markers

To identify tobacco recidivism among 86 heart transplant recipients who were smokers but demonstrated compliance with a smoking cessation program pre-transplant, we used a questionnaire and randomly tested urine for nicotine and its by-products. In 36 patients, we also evaluated circulating levels of HS-CRP, homocysteine and MPV. Twenty-eight (32.5%) of 86 patients met our definition for tobacco exposure. In this cohort, 28 (32.5%) of 86 patients met our definition for tobacco exposure. Of these 28, 12 patients self-reported tobacco use and demonstrated biochemical verification; 14 patients demonstrated only biochemical evidence of significant tobacco exposure; 2 patients self-reported tobacco use but did not demonstrate biochemical positivity. Smoking cessation within 6 months of transplantation (r = 0.52) and time post-transplantation (r = 0.43) were independent predictors for recidivism of tobacco use, p < 0.01. No differences in HS-CRP, homocysteine and MPV levels were noted among the groups. Our investigation demonstrates a high rate of tobacco recidivism among heart transplant recipients, yet few admit to it. The adverse effects of tobacco do not appear to be directly modulated by an effect on athero-thrombotic risk markers.     

Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the leading cause of graft loss following kidney transplantation. One factor contributing to CAN is chronic alloimmune injury. However, the involvement of alloantigen-dependent and -independent factors in CAN is unclear. The pathomechanism of CAN has been extensively studied by utilizing the Fischer-to-Lewis (F344-to-LEW) rat model. Transplant capillaropathy (circumferential multiplication of the peritubular capillary basement membrane) and transplant glomerulopathy (reduplication of the glomerular basement membrane) have recently been validated clinicopathologically as ultrastructural indicators of chronic alloimmune injury. To investigate the presence of these markers, F344-to-LEW kidneys were examined by electron and light microscopy 32, 40 and 52 weeks after implantation. F344 rats with or without 30-min ischemia of the left kidney following right nephrectomy served as controls. All transplanted rats displayed marked proteinuria. On electron microscopy, transplant capillaropathy, transplant glomerulopathy, and T-cell cytotoxicity (indicator of ongoing cellular rejection) were absent. On light microscopy, the arteries were devoid of intimal fibrosis. Focal-segmental glomerulopathy resembling hyperfiltration injury was encountered, with mild interstitial infiltration, fibrosis, and tubular atrophy. The proteinuria and kidney pathology were more severe in transplanted than in ischemic or uninephrectomized rats. Because chronic-active rejection could not be detected between weeks 32 and 52, we propose that the alloantigen-dependent initial graft injury subsides, but induces the late events: glomerular hyperfiltration, proteinuria, and glomerulosclerosis. Accordingly, the model - in the late phase - is suitable to investigate alloantigen-independent factors of CAN and lacks markers of alloantigen-dependent processes.