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The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naive T cells. GAT-2 deficiency had little effect on the metabolic signature in naive T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA–mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA–mTOR signaling.

Type VI secretion system (T6SS) is a secretory system found in Gram-negative bacteria. One of the main structures for T6SS is Hcp (hemolysin co-regulation protein) pipeline. To investigate the role of Hcp major sub-unit genes hcp1 and hcp2 , we deleted hcp1 and hcp2 genes for constructing the in-frame gene deletion mutants. The properties of biofilm formation and the adhesion to chicken embryo fibroblasts cells (DF1 cells) were reduced in the hcp2 mutant. The knockout of hcp1 and hcp2 genes reduced the ability of the avian pathogenic Escherichia coli (APEC) strain CE129 to infect developing chicken embryos. The expression of quorum sensing (QS)-associated genes luxS, lsrR, and pfs were down-regulated in the hcp1 mutant, and the expression of type 1 fimbriae gene fimA and the adhesion-related genes fimC and papC were decreased in the hcp2 mutant, as well as the expression of anti-serum survival factor genes ompA and iss were inhibited in both hcp1 and hcp2 mutants. These results described above from this study help to further elaborate the role of HCP in APEC.

Adherent-invasive Escherichia coli (AIEC) has recently attracted more attention because it is closely related to the pathogenicity of human inflammatory bowel disease (IBD). AIEC possesses a multitude of virulence factors. Considering these virulence factors belonging to various virulence groups, including adhesins, invasins, toxins, protectins, and siderophore-mediated iron acquisition, this review summarizes the current knowledge of how the major virulence factors assisting in AIEC survive in, adhere to, and invade host cells. A comprehensive understanding of the interaction of virulence factors with host cells will provide us a new therapeutic strategy for IBD prevention and treatment.

Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDR1/2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOB1 with NDR1/2 and LATS1, which resulted in increased phosphorylation of LATS1 and MOB1 and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.

Human immediate early response 2 (IER2) has been reported to function as a potential transcriptional factor or transcriptional co‑activator and seems to play a pivotal role in tumor cell motility and metastasis, however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Herein, we demonstrated that overexpression of IER2 in HCC cells increased cell adhesion to fibronectin, migration and invasion, whereas knockdown of IER2 displayed the opposite effects. In agreement with this phenotype, IER2 expression was positively correlated with the metastatic potential and integrin β1 (ITGB1) expression in HCC cell lines. Moreover, we demonstrated a critical role for IER2 in regulation of HCC cell‑extracellular matrix (ECM) adhesion and motility by the transcriptionally promoted ITGB1. Furthermore, we showed that ITGB1‑focal adhesion kinase (FAK)‑Src‑paxillin signal pathway activated by IER2 may contribute to the HCC cell‑ECM adhesion and motility. These results demonstrated that IER2 promoted HCC cell adhesion and motility probably by directly increasing ITGB1 expression and subsequently activating the ITGB1‑FAK‑Src‑paxillin signal pathway.

To measure the amount of physical activity (PA) among obese adults, investigate the association between plasma orexin-A level and PA patterns, and explore the effect of orexin on the prevention and control of obesity. Interviews were conducted in 218 participants (106 obese; 73 overweight; and 39 normal) who ranged in age between 18 and 70 years using a survey that included sociodemographic variables. The International Physical Activity Questionnaire (IPAQ-long version) was used to measure PA. A total of 178 participants agreed to submit blood sample collections, and plasma orexin-A content was measured by ELISA testing. The average level of orexin-A was 85.34 ± 42.85 ng/L in the obese group, 97.38 ± 36.72 ng/L in the overweight group, and 106.56 ± 52.09 ng/L in the control group, which was significantly different (P = 0.03). The concentration of plasma orexin-A correlated with the total PA (P = 0.000), moderate PA (obese = 0.007; overweight: P = 0.000; control: P = 0.000), and walking PA (P = 0.000) in all three groups. Working and domestic PAs were significantly associated with the plasma orexin-A level (P