ABSTRACT
BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.
ABSTRACT
BACKGROUND@#BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients.@*METHODS@#A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection (TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN.@*RESULTS@#At biopsy, the MUSG of BKPyVAN group (1.008 ± 0.003) was significantly lower than that of isolated BK viruria group (1.013 ± 0.004, P < 0.001), TCMR group (1.011 ± 0.003, P = 0.027), and control group (1.014 ± 0.006, P < 0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (P = 0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012 ± 0.003, P < 0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721-0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687-0.934).@*CONCLUSION@#Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.
ABSTRACT
BACKGROUND@#BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN.@*METHODS@#We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up.@*RESULTS@#After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042).@*CONCLUSION@#Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , BK Virus , Glomerular Filtration Rate , Graft Rejection , Graft Survival , Kidney Diseases , Kidney Transplantation , Polyomavirus Infections , Retrospective Studies , Viral Load , ViremiaABSTRACT
<p><b>OBJECTIVE</b>To evaluate the outcomes of liver transplant recipients who received liver allografts from hepatitis B surface antigen (HBsAg)-positive donors.</p><p><b>METHODS</b>The medical records of 23 male patients (median age, 42.5 years; range: 29-61) who received HBsAg-(+) liver allografts in our organ transplant center were retrospectively analyzed. All patients had confirmed diagnosis of end-stage liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13 HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After transplantation, all patients were administered oral entecavir and intravenous anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along with a steroid-free immune suppression regimen. HBV-related antigen and antibody and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The liver allografts were monitored by ultrasound imaging. After discharge, monthly follow-up recorded liver function, renal function, acute rejection, infections, vascular complications, biliary complications, HBV recurrence, cancer recurrence, and patient survival.</p><p><b>RESULTS</b>Two of the recipients died from severe perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to 38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary ischemia and required a second liver transplantation at five months after the primary transplantation. Three recipients (all primary) died from tumor recurrence at 9, 14, and 18 months post-transplantation, respectively. All other recipients survived and had acceptably low HBV DNA copy levels. Color Doppler imaging showed good graft function and normal texture. The patient and graft survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence rate of HBV infection was 100% (23/23). In surviving patients, no liver function abnormality, graft loss, or death was found to be related to the recurrence of HBV infection.</p><p><b>CONCLUSION</b>Liver transplantation using HBsAg(+) liver grafts was safe for patients with ESLD secondary to HBV infection.</p>