Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137‐modified ECs (CD137‐Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti‐CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137‐Exo efficiently induced the progression of AS in ApoE^?/? mice. CD137‐Exo increased the proportion of Th17 cells both in vitro and vivo. The IL‐6 contained in CD137‐Exo which is regulated by Akt and NF‐КB pathway was verified to activate Th17 cell differentiation. IL‐17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1) and E‐selectin in the supernatants of ECs after IL‐17 treatment was dramatically increased. CD137‐Exo promoted the progression of AS and Th17 cell differentiation via NF‐КB pathway mediated IL‐6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS.     

The optimum dietary methionine requirement of juvenile humpback grouper (Cromileptes altivelis): effects on growth,micromorphology, protein and lipid metabolism

An 8-week feeding trial was conducted to evaluate optimum dietary methionine (Met) requirement of juvenile humpback grouper (Cromileptes altivelis) and the influence of dietary methionine (Met) supplementations on growth, gut micromorphology, protein and lipid metabolism. Seven isoproteic (48.91%) and isolipidic diets (10%) were made to contain 0.70, 0.88, 1.04, 1.27 1.46, 1.61 and 1.76% of dry matter Met levels. Results showed that lower survival, weight gain (WG%), protein efficiency ratio (PER), protein productive value (PPV) but higher daily feed intake (DFI) and feed conversion ratio (FCR) were observed in the Met deficient groups (0.70 and 0.88%). Optimum dietary Met requirement for humpback grouper was found to be 1.07% through the straight-broken line analysis of WG% against Met. Fish fed Met deficient diets (0.70, 0.88%) exhibited lower mRNA levels of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor-I (IGF-1), target of rapamycin (TOR) as well as S6 kinase 1 (S6K1) than other dietary groups. Whereas, expression of genes related to general control nonderepressible (GCN2) kinase i.e., GCN2 and C/EBPβ enhancer-binding protein β was upregulated in fish fed low Met diets (P < 0.05). The mRNA expression of hepatic fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1) were higher in fish fed 0.70 and 0.88% dietary Met group and the lipolytic genes, hepatic peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase-1 (CPT-1) showed an opposite variation tendency as FAS or SREBP1. Generally, the optimum Met requirement for humpback grouper was predicted to be 1.07% of dry matter.

     

Peptides YYGGEGSSSEQG and SESEM Inhibit TNF-α-Induced Smooth Muscle Cells Proliferation and Migration Through Their Bindings to TNF-α Receptor

International Journal of Peptide Research and Therapeutics - The peptides YYGGEGSSSEQG and SESEM derived from rice α-globulin have been reported to possess anti-atherosclerotic activity, but...     

Species and Population Level Molecular Profiling Reveals Cryptic Recombination and Emergent Asymmetry in the Dimorphic Mating Locus of C. reinhardtii

Heteromorphic sex-determining regions or mating-type loci can contain large regions of non-recombining sequence where selection operates under different constraints than in freely recombining autosomal regions. Detailed studies of these non-recombining regions can provide insights into how genes are gained and lost, and how genetic isolation is maintained between mating haplotypes or sex chromosomes. The Chlamydomonas reinhardtii mating-type locus (MT) is a complex polygenic region characterized by sequence rearrangements and suppressed recombination between its two haplotypes, MT+ and MT−. We used new sequence information to redefine the genetic contents of MT and found repeated translocations from autosomes as well as sexually controlled expression patterns for several newly identified genes. We examined sequence diversity of MT genes from wild isolates of C. reinhardtii to investigate the impacts of recombination suppression. Our population data revealed two previously unreported types of genetic exchange in Chlamydomonas MT—gene conversion in the rearranged domains, and crossover exchanges in flanking domains—both of which contribute to maintenance of genetic homogeneity between haplotypes. To investigate the cause of blocked recombination in MT we assessed recombination rates in crosses where the parents were homozygous at MT. While normal recombination was restored in MT+×MT+ crosses, it was still suppressed in MT−×MT− crosses. These data revealed an underlying asymmetry in the two MT haplotypes and suggest that sequence rearrangements are insufficient to fully account for recombination suppression. Together our findings reveal new evolutionary dynamics for mating loci and have implications for the evolution of heteromorphic sex chromosomes and other non-recombining genomic regions.     

P16 and P53 Play Distinct Roles in Different Subtypes of Breast Cancer

Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16^INK4a and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.