Sequence and Bioinformatics Analysis on MSTN Gene of the Hybrid Grouper Derived from(Epinephelus fuscoguttatus×Epinephelus polyphekadion)

[Objectives]This study aimed to investigate the sequence structure and function of Myostatin(MSTN)gene in the hybrid grouper(Epinephelus fuscoguttatus,♀×Epinephelus polyphekadion,♂).[Methods]Genetic DNA samples were extracted from the caudal fins of the hybrid grouper and its parents to amplify their MSTN genes.Then,MSTN gene sequences were analyzed using bioinformatics tools to predict their protein structures and functions.[Results]The hybrid grouper and its parents shared the same MSTN gene structure,consisting of three exons and two introns.Nucleotide sequence of the gene could be translated into 376 amino acids,including an N-terminal signal peptide,a proteolytic processing site(RXXR motif),and nine conserved cysteine residues at C-terminal,which were the typical features of transforming growth factor beta(TGF-β)superfamily proteins.Alignment of protein sequence showed that MSTN was highly conserved between the hybrid grouper and its parents.Especially,exon 3,an important functional domain,exhibited a sequence similarity of 100%among them.In addition,four variable amino acid residues were detected in exon 2 at positions 141,153,185 and 186 in the hybrid grouper,but they did not affect the secondary structure of the protein.[Conclusion]These results will provide molecular information for future investigation on the growth and heterosis of hybrid grouper species,and on the roles of MSTN gene in regulating the growth traits of the hybrid grouper.

Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy(ICP)is a cholestatic disorder with potentially deleterious consequences for fetuses.Although a clear correlation between the elevated levels of maternal serum bile acids and deficient fetal outcome has been established in clinical practice,the underlying mechanisms remain elusive.Herein,we report that bile acids induce NF-κB pathway activation via G protein-coupled bile acid receptor 1(Gpbar1),with consequent upregulation of inflammatory genes in trophoblasts,leading to aberrant leukocyte infiltration and inflammation in placenta.Ursodeoxycholic acid(UDCA),a drug used clinically to treat ICP,competes with other bile acids for binding with Gpbar1 and thus inhibits bile acid-induced inflammatory response in trophoblasts and improves fetal survival in pregnant rats with obstructive cholestasis.Notably,inhibition of NF-κB by andrographolide is more effective than UDCA in benefiting placentas and fetuses.Thus,anti-inflammation therapy targeting Gpbar1/NF-κB pathway could be effective in suppressing bile acid-induced inflammation and alleviating ICP-associated fetal disorders.

Ketogenic diet for human diseases:the underlying mechanisms and potential for clinical implementations

The ketogenic diet(KD)is a high-fat,adequate-protein,and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies.The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade,subject to emerging evidence of the promising therapeutic potential of the KD for various diseases,besides epilepsy,from obesity to malignancies.In this review,we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases,and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels.We emphasize that the KD may function through multiple mechanisms,which remain to be further elucidated.The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed.We suggest that,with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action,randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

Distinct chemokines selectively induce HIV-1 gp120-integrinα4β7 binding via triggering conformer-specific activation ofα4β7

Dear Editor,Gut associated lymphoid tissue(GALT)is the principal site where human immunodeficiency virus 1(HIV-1)replicates.CD4^(+) T cells residing in GALT are predominant targets of HIV-1 during the acute phase of infection.CD4^(+) T cells expressing a high level of gut-homing receptor integrin α4β7 are more susceptible to productive infection by HIV-1.