Cornin protects against cerebral ischemia/reperfusion injury by preventing autophagy via the PI3K/Akt/mTOR pathway.

BACKGROUND: Ischemia stroke is the leading cause of disability, which is a consequence of vascular occlusion. The purpose of this study is to investigate the effect of cornin which is isolated from the fruit of Verbena officinalis L, against astrocytes autophagy induced by cerebral ischemia/reperfusion (CI/R) injury in vitro and in vivo and its potential mechanism. METHODS: Cornin at dose of 2.5, 5 and 10 mg/kg were intravenously injected to MCAO rats at 15 min after reperfusion. The infarction volume, blood-brain barrier (BBB), neurological severity score (mNSS), and autophagy related protein were used to evaluated the protective effects and potential mechanism of cornin in autophagy with or without phosphoinositide-3 kinase (PI3K)inhibitor LY294002 and mammalian target of rapamycin (mTOR) small interfering RNA (siRNA) at 24 h after CI/R injury. The potential protective effects and mechanism of cornin at concention of 10 ~ 1000 nM were also evaluated in oxygen glucose deprivation/reperfusion (OGD/R) in U87 cells. RESULTS: The results suggest that cornin at dose of 5 or 10 mg/kg significantly reduce the cerebral infarction volume and blood-brain barrier (BBB) leakage, and improve neurological recovery in MCAO rats. Cleaved caspase-3 and Bax levels were significantly decreased, while B-cell lymphoma-2 (Bcl-2) and the apoptosis regulator ratio (Bcl-2/Bax) were markedly increased when treated with 2.5-10 mg/kg cornin. The obvious decreased expressions of glial fibrillary acidic protein (GFAP), myosin-like BCL2 interacting protein (Beclin-1) and microtubule-associated protein light chain 3 II (LC3-II) and increased of neuronal nuclei (NeuN), sequestosome-1 (p62), phosphorylated mTOR (p-mTOR), and phosphorylated Akt (p-Akt) were observed in MCAO rats treated with 10 mg/kg cornin, which was counteracted by LY294002. The expression of autophagy-related proteins with or without LY294002 and mTOR siRNA presented the similar results as in vitro in OGD/R in U87 cells. CONCLUSIONS: These results indicate that cornin improved neurological recovery after cerebral ischemia injury by preventing astrocytes autophagy induced by CI/R via the PI3K/Akt/mTOR signaling pathway.

A Statistical Prediction Model for Survival After Kidney Transplantation from Deceased Donors.

BACKGROUND In an environment of limited kidney donation resources, patient recovery and survival after kidney transplantation (KT) are highly important. We used pre-operative data of kidney recipients to build a statistical model for predicting survivability after kidney transplantation. MATERIAL AND METHODS A dataset was constructed from a pool of patients who received a first KT in our hospital. For allogeneic transplantation, all donated kidneys were collected from deceased donors. Logistic regression analysis was used to change continuous variables into dichotomous ones through the creation of appropriate cut-off values. A regression model based on the least absolute shrinkage and selection operator (LASSO) algorithm was used for dimensionality reduction, feature selection, and survivability prediction. We used receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis (DCA) to evaluate the performance and clinical impact of the proposed model. Finally, a 10-fold cross-validation scheme was implemented to verify the model robustness. RESULTS We identified 22 potential variables from which 30 features were selected as survivability predictors. The model established based on the LASSO regression algorithm had shown discrimination with an area under curve (AUC) value of 0.690 (95% confidence interval: 0.557-0.823) and good calibration result. DCA demonstrated clinical applicability of the prognostic model when the intervention progressed to the possibility threshold of 2%. An average AUC value of 0.691 was obtained on the validation data. CONCLUSIONS Our results suggest that the proposed model can predict the mortality risk for patients after kidney transplants and could help kidney specialists choose kidney recipients with better prognosis.

Analysis of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Effect on the Outcome of Early Infection After Kidney Transplantation.

Background: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections. Methods: We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes. Results: Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients. Conclusions: In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.

Darunavir alleviates irinotecan-induced intestinal toxicity in Vivo.

Irinotecan (CPT-11) is used to treat various cancers but side effects such as delayed diarrhea restrict its use. Darunavir (DRV) is an antiretroviral drug used to treat and prevent human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), but whether DRV is protective against CPT-11-induced intestinal toxicity is unclear. An CPT-11-induced intestinal toxicity model was produced using uninterrupted CPT-11 (ip) for 4 d in mice. Enzyme-linked immuno sorbent assay (ELISA), fecal occult blood test (FOBT), Western blot, histopathological evaluation, and immunohistochemistry staining assays were used to document toxicity. DRV treatment attenuated CPT-11-induced intestinal toxicity via decreasing fecal occult blood and mitigating delayed-onset diarrhea, as well as reducing weight loss, reduced food intake, and pathomorphologic changes without inhibiting ß-glucuronidase (ß-GLU) activity. The high mobility group box-1 protein (HMGB1)-toll-like receptor 4 (TLR4) pathway induced inflammation and tight junction protein (occludin and zonular occluden-1) reduction in the colon was inhibited by DRV. Hepatotoxicity induced by CPT-11 was diminished after treatment with DRV, and activation of the NOD-like receptor 3 inflammasome (NLRP3) was prevented in colon tissue. In addition, DRV didn't reduce the concentration of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38) in plasma at the same dose of irinotecan with DRV. DRV has anti-inflammatory and intestinal-protective properties and may be used to manage CPT-11-induced intestinal toxicity.