Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model

Objective(s): The main goal of the current research was to examine the effects of Berberine (BBR) on apoptotic signaling and hippocampal oxidative stress induced by common carotid artery occlusion. Materials and Methods: Chronic cerebral hypoperfusion (CCH) model was created by occluding the two common carotid arteries (two-vessel occlusion 2VO) permanently. BBR (50 and 100 mg/kg/daily) was intra-gastrically administered to ischemic rats. Neuronal survival was evaluated by Nissl staining. The levels of malondialdehyde (MDA) and antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD), along with the activities of caspase 3 were estimated in the hippocampus 2 month after treating the rats with 2VO. Results: According to findings of the present research, the BBR therapy inhibited the neurodegeneration of hippocampus. BBR also significantly decreased the amount of MDA and activity of caspase 3 in the hippocampus. Furthermore, the administration of BBR alleviated the lowered activities of SOD and CAT after 2VO surgery. Conclusion: The antioxidant and antiapoptotic properties of BBR might play important roles in improving functional outcomes and might have significant neuroprotective effects on the CCH damage. © 2019, Mashhad University of Medical Sciences. All rights reserved

Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model

Objective(s): The main goal of the current research was to examine the effects of Berberine (BBR) on apoptotic signaling and hippocampal oxidative stress induced by common carotid artery occlusion. Materials and Methods: Chronic cerebral hypoperfusion (CCH) model was created by occluding the two common carotid arteries (two-vessel occlusion 2VO) permanently. BBR (50 and 100 mg/kg/daily) was intra-gastrically administered to ischemic rats. Neuronal survival was evaluated by Nissl staining. The levels of malondialdehyde (MDA) and antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD), along with the activities of caspase 3 were estimated in the hippocampus 2 month after treating the rats with 2VO. Results: According to findings of the present research, the BBR therapy inhibited the neurodegeneration of hippocampus. BBR also significantly decreased the amount of MDA and activity of caspase 3 in the hippocampus. Furthermore, the administration of BBR alleviated the lowered activities of SOD and CAT after 2VO surgery. Conclusion: The antioxidant and antiapoptotic properties of BBR might play important roles in improving functional outcomes and might have significant neuroprotective effects on the CCH damage. © 2019, Mashhad University of Medical Sciences. All rights reserved

New fixed point theorem under R-contractions

In this manuscript we introduce the notions of R-function and R-contractions, and we show an ad hoc fixed point theorem. We prove that this new kind of contractions properly includes the family of all Meir-Keeler contractions and other well-known classes of contractions that have been given very recently (for instance, those using simulation functions and manageable functions). As a consequence, our approach turns out to be appropriate to unify the treatment of different kinds of contractive nonlinear operators.This article was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah. The second author, therefore, acknowledges with thanks DSR for technical and financial support. The authors are grateful to three anonymous referees for their useful suggestions and comments. AF Roldán López de Hierro is grateful to the Department of Quantitative Methods for Economics and Business of the University of Granada. The same author has been partially supported by Junta de Andalucía by project FQM-268 of the Andalusian CICYE

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting