Crocetin protects cardiomyocytes against hypoxia/reoxygenation injury by attenuating Drp1-mediated mitochondrial fission via PGC-1α

BACKGROUND Saffron(Crocus sativus L.)has been traditionally used as food,spice,and medicine.Crocetin(CRT),as main bioactive component of saffron,has accumulated pieces of beneficial evidence on myocardial ischemia/reperfusion(I/R)injury.However,the mechanisms are poorly explored.This study aims to investigate the effects of CRT on H9c2 cells under hypoxia/reoxygenation(H/R)and elucidated the possible underlying mechanism.METHODS H/R attack was performed on H9c2 cells.Cell counting kit-8 was used to detect the cell viability.Cell samples and culture supernatants were evaluated via commercial kits to measure the superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,and cellular adenosine triphosphate(ATP)content.Various fluorescent probes were used to detect cell apoptosis,intracellular and mitochondrial reactive oxygen species(ROS)content,mitochondrial morphology,mitochondrial membrane potential(MMP),and mitochondrial permeability transition pore(mPTP)opening.Proteins were evaluated via Western Blot.RESULTS H/R exposure severely reduced cell viability and increased LDH leakage.Peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)suppression and dynamin-related protein 1(Drp1)activation were coincided with excessive mitochondrial fission,mitochondrial permeability transition pore(mPTP)opening and mitochondrial membrane potential(MMP)collapse in H9c2 cells treated with H/R.Mitochondria fragmentation under H/R injury induced ROS over-production,oxidative stress,and cell apoptosis.Notably,CRT treatment significantly prevented mitochondrial fission,mPTP opening,MMP loss,and cell apoptosis.Moreover,CRT sufficiently activated PGC-1α and inactivated Drp1.Interestingly,mitochondrial fission inhibition with mdivi-1 similarly suppressed mitochondrial dysfunction,oxidative stress and cell apoptosis.However,silencing PGC-1α with small interfering RNA(siRNA)abolished the beneficial effects of CRT on H9c2 cells under H/R injury,accompanied with increased Drp1 and p-Drp1ser616 levels.Furthermore,over-expression of PGC-1αwith adenovirus transfection replicated the beneficial effects of CRT on H9c2 cells.CONCLUSIONS Our study identified PGC-1α as a master regulator in H/R-injured H9c2 cells via Drp1-mediated mitochondrial fission.We also presented the evidence that PGC-1α might be a novel target against cardiomyocyte H/R injury.Our data revealed the role of CRT in regulating PGC-1α/Drp1/mitochondrial fission process in H9c2 cells under the burden of H/R attack,and we suggested that modulation of PGC-1α level may provide a therapeutic target for treating cardiac I/R injury.

Role of mitochondrial quality control in exercise-induced health adaptation

Long-term endurance training or physical activity has been confirmed not only to improve physical performance, but to bring about an obvious beneficial effect on human health; however, the mechanism of this effect is not clear. The most studied health adaptations in skeletal muscle response to endurance exercise are increased muscle glycogen level and insulin sensitivity, fiber type transformation toward oxidative myofibers, and increased mitochondrial content/function. Mitochondria are dynamic organelles in eukaryotic cells critical in physical performance and disease occurrence. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes and confer positive impacts on skeletal muscle contractile and metabolic functions. This review focused on the regulation of these processes by endurance exercise and discussed its potential benefits in health and disease. We presented evidence suggesting that exercise training potentiates not only the biogenesis of mitochondria but also the removal of old and unhealthy mitochondria through mitochondrial quality control.

The relationship between the lymphatic system and Alzheimer's disease wasdiscussed based on the tri-jiao theory

Type of the lymphatic system is a new concept put forward by foreign scholars in recent years.It is similar to the lymphatic system,is the brain of the internal fluid metabolism channel and its metabolites in the brain plays a major role in the process of removal,sleep disorders in alzheimer's disease brain stroke,traumatic brain injury and other central nervous system diseases.The Tri-jiao theory is a very important in traditional Chinese medicine plate structure,it is from the function to traffic from running water channel,but still no definite conclusion on structure.This paper attempts to explore the relationship between trioke and the lymphatic system and their influence on Alzheimer's disease through modern medical research on the lymphatic system,so as to provide new inspirations for the treatment of Alzheimer's disease.

Periarthritis of shoulder treated with Fu’s subcutaneous needling and electroacupuncture:A controlled trail

Objective:To observe and compare the therapeutic effect on shoulder periarthritis between Fu’s subcutaneous needling(FSN)and electroacupuncture(EA).Methods:A total of 68 patients with periarthritis of shoulder were divided into a FSN group and an EA group according to the random number table,34 cases in each one.In the FSN group,FSN was adopted,once every two days,totally for 10 times.In the EA group,EA was used once daily,consecutively for 20 times.Shoulder pain score and shoulder function score(Constant-Murley score)before and after treatment were compared between the two groups.The clinical therapeutic effect was analyzed and evaluated statistically.Results:After 20-day treatment,shoulder pain score was reduced obviously as compared with that before treatment in the patients of either group(both P<0.01).After treatment,shoulder pain score in the FSN group was lower significantly than that in the EA group(P<0.01).In 20 days of treatment,CMS was improved obviously as compared with that before treatment in the patients of both groups(both P<0.01)and CMS in the FSN group was higher significantly than that in the EA group after treatment(P<0.01).The effective rate was 94.11%in the FSN group and was 91.17%in the EA group.The remarkably effective rate was 73.52%in the FSN group,significantly higher than 20.58%in the EA group(P<0.01).Conclusion:Both FSN and EA are effective in treatment of periarthritis of shoulder,but FSN obtains a much higher remarkably effective rate in treatment of periarthritis of shoulder and its effects for relieving shoulder pain and improving shoulder function are superior to EA.Because of its effective treatment and simple operation,FSN deserves to be promoted in clinical practice for periarthritis of shoulder.

Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease:Current Progresses and Challenges

The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an updated literature review detailing epidemiology,risk factors,pathogenic pathways,and treatment strategies linked to NAFLD-related HCC,we conducted a literature search on PubMed from its inception to December 31,2021.About 25%of the global population suffers from NAFLD.The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years.Older age,male sex,metabolic comorbidities,unhealthy lifestyle habits(such as smoking and alcohol consumption),physical inactivity,genetic susceptibility,liver fibrosis,and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC.Therefore,low-calorie diet,moderate-intensity exercise,treatment of metabolic comorbidities,and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC.In addition,all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC.Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC.Hepatic resection,liver transplantation,ablation,transarterial chemoembolization,radiotherapy,targeted drugs,and immune checkpoint inhibitors are used to treat NAFLD-related HCC.Lenvatinib treatment may lead to better overall survival,while immune checkpoint inhibitors may lead to worse overall survival.Given the specific risk factors for NAFLD-related HCC,primary prevention is key.Moreover,the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.