Selenium nanoparticles reduce oxidative stress-induced cardiomyocyte apoptosis in ascites syndrome in broiler chickens via the ATF6-DR5 signaling pathway

Broiler ascites syndrome(AS)is one of the main diseases threatening the health of broilers.It is well documented that myocardial hypertrophy and failure is one of the key mechanisms of broiler ascites syndrome.Therefore,prevention of cardiac hypertrophy and failure would be one goal to reduce broiler ascites syndrome incidence.Myocardial hyper-trophy and failure are closely related to endoplasmic reticulum stress(ERS)in cardiac myocytes,and the endoplasmic reticulum stress signaling system(ATF6-DR5)is one of the important pathways of myocardial apoptosis.Excessive hyper-trophy will affect the heart muscle's normal contraction and diastole function,and the heart will turn from compen-sated to decompensate thus causing myocardial injury.Myocardial apoptosis is a core component of the pathological changes of this myocardial injury.Nano-selenium is a kind of red elemental selenium nanoparticle.Due to its excellent physical,chemical and biological properties,it has attracted extensive academic attention in recent years.It has been proven to have excellent antioxidant,antibacterial,antitumor,antihypertrophic,and antiapoptotic abilties.Herein,nano-selenium(1μmol/L)can inhibit hydrogen peroxide(H_(2)O_(2))-induced oxidative stress in broiler primary cardiomyocytes,and at the same time reduce cardiomyocyte apoptosis.In vivo,nano-selenium can reduce broiler myocardial injury-related enzyme indicators(AST,CK and LDH),and alleviate myocardial injury.It can also activate the antioxidant enzyme system(SOD,GSH-Px and CAT)and reduce MDA,and make the recovery ofT-AOC ability in the organization.Meanwhile,nano-selenium can down-regulate the genes and proteins expression of ATF-6,GRP-78,CHOP and caspase 12 in the ERS-related signaling pathway,and inhibit that of downstream-related caspase 3,Bax and caspase 9,and increase that of the downstream anti-apoptotic Bcl-2,thereby maintaining the homeostasis of the endoplasmic reticulum and alleviating cardiomyocyte apoptosis.It can be seen that nano-selenium can protect the damaged myocardium in the broiler ascites caused by high-salt drinking by regulating the ATF6-DR5 signaling pathway.This study was performed in chickens and cardiomyocyte cells and attempted to demonstrate that selenium nanoparticles can protect the damaged myocar-dium in broiler ascites.This paper provides a new idea for preventing and treating broiler ascites syndrome.

CircRNA ATF6 promotes ovarian cancer cell progression by activating PTEN/mTOR signaling pathway

Ovarian cancer is a malignant cancer type and affects women’s lives in the world.Circular RNAs(circRNAs)have been involved with the progression of cancers.In our study,we are going to explore the functions of circATF6 in ovarian cancer.The qRT-PCR assay was used to detect expressions of genes.Actinomycin D and RNase R treatment were implemented to verify the circular RNA character of circATF6.Besides,Cell proliferation was assessed by colony formation assay and EdU assay.Silenced circATF6 could reduce the proliferation of ovarian cancer cells.In addition,inhibited circATF6 could promote the cell apoptosis and inhibit related proteins in PTEN/mTOR signaling pathway in ovarian cancer.In conclusion,CircRNA ATF6 promotes ovarian cancer cell progression by activating PTEN/mTOR signaling pathway.

Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB/IL-6/STAT3 and JNK/PTX3 pathways

Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.