Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

Critical care practice in India:Results of the intensive care unit need assessment survey(ININ2018)

BACKGROUND A diverse country like India may have variable intensive care units(ICUs)practices at state and city levels.AIM To gain insight into clinical services and processes of care in ICUs in India,this would help plan for potential educational and quality improvement interventions.METHODS The Indian ICU needs assessment research group of diverse-skilled individuals was formed.A pan-India survey"Indian National ICU Needs"assessment(ININ 2018-I)was designed on google forms and deployed from July 23rd-August 25th,2018.The survey was sent to select distribution lists of ICU providers from all 29 states and 7 union territories(UTs).In addition to emails and phone calls,social medial applications-WhatsApp™,Facebook™and LinkedIn™were used to remind and motivate providers.By completing and submitting the survey,providers gave their consent for research purposes.This study was deemed eligible for category-2 Institutional Review Board exempt status.RESULTS There were total 134 adult/adult-pediatrics ICU responses from 24(83%out of 29)states,and two(28%out of 7)UTs in 61 cities.They had median(IQR)16(10-25)beds and most,were mixed medical-surgical,111(83%),with 108(81%)being adult-only ICUs.Representative responders were young,median(IQR),38(32-44)years age and majority,n=108(81%)were males.The consultants were,n=101(75%).A total of 77(57%)reported to have 24 h in-house intensivist.A total of 68(51%)ICUs reported to have either 2:1 or 2≥:1 patient:nurse ratio.More than 80%of the ICUs were open,and mixed type.Protocols followed regularly by the ICUs included sepsis care,ventilator-associated pneumonia(83%each);nutrition(82%),deep vein thrombosis prophylaxis(87%),stress ulcer prophylaxis(88%)and glycemic control(92%).Digital infrastructure was found to be poor,with only 46%of the ICUs reporting high-speed internet availability.CONCLUSION In this large,national,semi-structured,need-assessment survey,the need for improved manpower including;in-house intensivists,and decreasing patient-tonurse ratios was evident.Sepsis was the most common diagnosis and quality and research initiatives to decrease sepsis mortality and ICU length of stay could be prioritized.Additionally,subsequent surveys can focus on digital infrastructure for standardized care and efficient resource utilization and enhancing compliance with existing protocols.