The mechanism and treatment strategies of GSDMD-mediated pyroptosis in myocardial infarction

Acute myocardial infarction(MI)is associated with high morbidity and mortality and poses a significant challenge to human health.Despite advances in medicine,effective treatment options for MI are still associated with adverse outcomes,such as heart failure.Consequently,identifying the pathogenesis of MI is a promising avenue for developing practical treatments.The inflammatory response plays a critical role in the pathogenesis of MI.Gasdermin D(GSDMD)-mediated pyroptosis regulates the inflammatory response,which is a pathogenic and potential therapeutic target for MI.Therefore,anti-pyroptosis treatment is emerging as a promising therapeutic approach for MI.Overall,this article reviews the mechanism and treatment strategies for GSDMD-mediated pyroptosis in MI,with the hope of providing insights into pathogenic interventions.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway

AIM:To investigate the effect of electroacupuncture(EA)on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lensinduced myopia(LIM).METHODS:Guinea pigs were randomly divided into normal control(NC)group,LIM group,LIM+SHAM acupoint(LIM+SHAM)group,and LIM+EA group.Animals in the NC group received no intervention,while those in other three groups were covered with-6.0 diopter(D)lenses on right eyes.Meanwhile,animals in the LIM+EA group received EA at Hegu(LI4)combined with Taiyang(EX-HN5)acupoints,while those in the LIM+SHAM group were treated at sham points.After treatments for 1,2,and 4wk,morphological changes in ciliary muscles were observed with hematoxylin and eosin(H&E)staining and nick end labeling(TUNEL),and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction(qPCR)and Western blot.Additionally,the adenosine triphosphate(ATP)contents were also determined in ciliary muscles.RESULTS:Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group.The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups,whereas those in the LIM+EA group improved significantly.TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups,whereas reduced in the LIM+EA group.ATP contents showed a significant decrease in the LIM and LIM+SHAM groups,whereas increased after EA treatment.Compared with the NC group,the dynamin-related protein 1(DRP1),Caspase3,and apoptotic protease activator 1(APAF1)levels were significantly increased in the LIM group and decreased in the LIM+EA group.CONCLUSION:The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).