Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

Therapeutic potential of gasotransmitters for cold stress-related cardiovascular disease

Growing evidence has shown that exposure to low ambient temperature poses a huge challenge to human health globally.Actually,cold stress is closely associated with a higher incidence of cardiovascular morbidity and mortality in winter or in cold regions.Cellular and molecular mechanisms underlying cardiovascular complications in response to cold exposure have yet to be fully clarified.Considering that cold exposure is an important risk of cardiovascular complications,it is necessary to clarify the molecular mechanism of cold stress-induced cardiovascular diseases and to develop effective intervention strategies.Hydrogen sulfide(H2S),nitric oxide(NO),and carbon monoxide(CO)are well-known gasotransmitters that are endogenously produced in many biological systems.Accumulating studies have demonstrated that these gasotransmitters play a critical role in a wide spectrum of physiological and/or pathophysiological processes by regulating numerous signaling pathways.These gas signal molecules are emerging as important players in cardiovascular homeostasis,and disruption of these gasotransmitters is critically implicated in cardiovascular anomalies,such as hypertension,atherosclerosis,myocardial ischemia,heart failure,and stroke.Also,evidence is emerging that H2S,NO,and CO may be involved in the pathologies of cold stress-induced cardiovascular ailments.In this review,we aim to highlight and discuss the recent advances towards the development of gasotransmitters-based therapeutics for cold stress-related cardiovascular pathogenesis.We believe that the effects of H2S,NO,and CO on cardiovascular regulation under cold environment will attract tremendous interest in the near future as they serve as novel regulators of cardiovascular biology in cold environment.

Arthroscopic Minimally Invasive Surgery for Knee Joint Gouty Arthritis

Objective:To analyse the efficacy of arthroscopic minimally invasive surgery in patients with knee joint gouty arthritis.Methods:A retrospective analysis method was carried out on randomly selected 56 patients with knee gouty arthritis from early July 2018 to the end of June 2019.All patients underwent arthroscopic minimally invasive surgery.Results:In this study,the patients were followed for 10 months.The Lysholm score of knee function was found to be significantly higher after treatment compared to the scores before treatment(P<0.05).Conclusion:Arthroscopic minimally invasive surgery is a promising method to treat for knee joint gouty arthritis.

APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma(HCC) and APOBEC3B(A3B) remains unknown. It has been confirmed that interleukin-6(IL-6)has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3 B in HepG2 cells. A3 B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3 B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3 B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3 B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.