Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress.Method:LO2 hepatocytes was cultured in vitro,hepatocytes were randomly divided into blank control group,25 mmol/L glucose solution,27 mmol/L glucose solution,29 mmol/L glucose solution,31 mmol/L glucose solution,33 mmol/L glucose solution,35 mmol/L glucose solution treatment group,after determining the optimal concentration as 31 mmol/L,use 30 mmol/L metformin solution,and then divided into blank control group,normal hepatocytes+the optimal concentration of glucose solution,normal hepatocytes+metformin solution,normal hepatocytes+.The optimal concentration of glucose solution normal hepatocytes+metformin solution,calculate the number of hepatocytes on cell count plate respectively in the 12 h,24 h,48 h,and use the lactic acid kit to determine the lactic acid value of the cell culture medium of normal liver cells+optimal concentration glucose solution and normal liver cells+optimal concentration glucose solution+metformin solution at 12 h,24 h,and 48 h,respectively.Results:There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the high-glycemic control group compared with that in the high-glycemic control group without metformin.Conclusions:Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro,and has a protective effect on hepatocytes under high glucose stress.Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis.

Unlocking the potential of transdermal drug delivery

Transdermal drug delivery(TDD)has gained clinical approval over several decades,with extensive research dedicated to novel drug and device development.Despite notable research progress,the mar-ket adoption of TDD devices has not met anticipated levels,with oral administration and injection remaining predominant delivery meth-ods.To maximize the potential of TDD,we identify bottlenecks hinder-ing its widespread clinical application and propose promising research avenues.We begin by analyzing stringent demands necessary to truly benefit patients,addressing significant challenges in biomechanics,nanomedicine,and flexible electronics.Subsequently,we delve into skin anatomy,enhancement strategies,nano-carriers,and their under-lining mechanisms,highlighting the importance and framework of quantitative modeling.Based on these discussions,we highlight the core strength of TDD,such as automatic precise administration based on feedback and high delivery efficiencies,especially applicable to localized conditions(e.g.,central nervous system diseases,tumors).Finally,we envision the future of intelligent TDD device and its opera-tion scenario,aiming to steer research efforts toward faster translation of laboratory innovations into widely used products for sufferers.

Generation of inactivated IL2RG and RAG1 monkeys with severe combined immunodeficiency using base editing

Severe combined immunodeficiency(SCiD)encompasses a range of inherited disorders that lead to a profound deterioration of the immune system.Among the pivotal genes associated with SCID,RAG1 and IL2RG play crucial roles.IL2RG is essential for the development,differentiation,and functioning of T,B,and NK cells,while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes.Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems.