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A small molecule UPR modulator for diabetes identified by high throughput screening

Acta Pharmaceutica Sinica B 2021年第12期11卷 3983-3993页

作者： Valeria Marrocco Tuan Tran Siying Zhu Seung Hyuk Choi Ana M.Gamo Sijia Li Qiangwei Fu Marta Diez Cunado Jason Roland Mitch Hull Van Nguyen-Tran Sean Joseph arnab k.chatterjee Nikki Rogers Matthew S.Tremblay Weijun Shen Calibr at Scripps Research The Scripps Research InstituteLa JollaCA 92037USA

Unfolded protein response(UPR) is a stress response that is specific to the endoplasmic reticulum(ER).UPR is activated upon accumulation of unfolded(or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of *** addition,UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ***,we describe a cell-based ultra-high throughput screening(uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and in vivo disease *** asialoglycoprotein receptor 1(ASGR) fused with Cypridina luciferase(CLuc) as reporter assay for folding capacity,we have screened a million small molecule library and identified APC655 as a potent activator of protein folding,that appears to act by promoting chaperone ***,APC655 improved pancreatic β cell viability and insulin secretion under ER stress conditions induced by thapsigargin or ***655 was also effective in preserving β cell function and decreasing lipid accumulation in the liver of the leptin-deficient(ob/ob) mouse *** results demonstrate a successful uHTS campaign that identified a modulator of UPR,which can provide a novel candidate for potential therapeutic development for a host of metabolic diseases.

关键词： βcells Unfolded protein response Small molecules Protein folding Endoplasmic reticulum Chaperones Cell signaling Diabetes ER stress Liver Pancreas Metabolic diseases

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Development of a Tribofidelic Human Heel Surrogate for Barefoot Slip Testing

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Journal of Bionic Engineering 2022年第2期19卷 429-439页

作者： Subhodip chatterjee arnab Chanda Centre for Biomedical Engineering Indian Institute of Technology DelhiNew Delhi 110016India Department of Biomedical Engineering All India Institute of Medical ScienceNew Delhi 110029India

Barefoot slips contribute to over 37% of recurrent fall-related injuries across all age *** study slip risk across a wide range of flooring conditions,slip meters with barefoot surrogates(i.e.,sensors,as per ASTM standard nomenclature)such as animal skins and rubbers have been used to date,which exhibit biomechanical and frictional properties widely different from the barefoot human *** of a surrogate which can accurately simulate the human heel skin properties would be immensely beneficial for realistic assessment of barefoot slipping risk.A novel surrogate was developed using 3D scanning and printing,and biomimetics,which precisely simulates the biomechanical and frictional properties of the barefoot human heel *** slip testing was conducted with this surrogate on three common bathroom floorings and with six different *** of Friction(COF)results similar to human slipping experiments,high repeatability and reproducibility across wet and oily flooring conditions,were confirmed through experiments with the developed heel skin *** heel skin surrogate would be an indispensable model for accurate estimation of barefoot risk against slips and falls in bathrooms,bathtubs,and swimming pools.

关键词： Barefoot Surrogate Slip Fall Bathroom Bathtub

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