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Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV) infection has been regarded as a multi-factorial disorder disease. Previous studies revealed that KIRs were involved in HCV and HIV infection or clearance. The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent HBV infection or HBV clearance. The sequence specific primer polymerase chain reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150 chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls, and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB patients compared with healthy control subjects. The frequency of genotype AH was higher in SR controls than that in both CHB patients and healthy controls. The carriage frequencies of genotype G and AH were higher; while, the frequencies of AF and AJ were lower in SR controls than those in healthy control subjects. The frequency of A haplotype was lower, whereas, the frequency of B haplotype was higher in CHB patients and SR controls than those in healthy controls. In healthy controls, haplotype 4 was found lower compared with that in CHB patients and SR controls and the frequency of haplotype 5 was higher in SR controls than that in other two groups. Based on these findings, it seems that the genotypes M and FZ1 are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that facilitates the clearance of HBV. Cellular & Molecular Immunology. 2008;5(6):457-463.

The blood–brain barrier (BBB) restricts access to the brain of more than 98 % of therapeutic agents and is largely responsible for treatment failure of glioblastoma multiforme (GBM). Therefore, it is of great importance to develop a safe and efficient strategy for more effective drug delivery across the BBB into the brain. Inspired by the extraordinary capability of rabies virus (RABV) to enter the central nervous system, we report the development and evaluation of the metal–organic framework‐based nanocarrier MILB@LR, which closely mimicked both the bullet‐shape structure and surface functions of natural RABV. MILB@LR benefited from a more comprehensive RABV‐mimic strategy than mimicking individual features of RABV and exhibited significantly enhanced BBB penetration and brain tumor targeting. MILB@LR also displayed superior inhibition of tumor growth when loaded with oxaliplatin. The results demonstrated that MILB@LR may be valuable for GBM targeting and treatment.

Intestinal microbiota dysbiosis has been described in inflammatory bowel disease (IBD), but data from China are limited. In this study, we performed molecular analysis of the fecal microbial community from 20 healthy Chinese subjects and 25 patients with Crohn’s disease (CD), and evaluated associations with bacterial and fungal compositions. Decreased richness and diversity of bacterial composition was observed in the CD group compared with healthy (H) subjects. Significant structural differences in bacterial (but not fungal) composition among healthy controls and CD patients were found. A reduction in Firmicutes and Actinobacteria abundance, and overrepresentation of Proteobacteria were observed in the CD patients compared with the H group. The Escherichia-Shigella genus was overrepresented in the CD group, whereas Faecalibacterium, Gemmiger, Bifidobacterium, Romboutsia, Ruminococcus, Roseburia, and Fusicatenibacter abundance were decreased in the CD group compared with H subjects. Differences in fungal microbiota between the H and CD groups were observed at the genus rather than at the phylum level. The Candida genus was overrepresented in the CD (active disease) group compared with the H group, whereas no difference between CD (remission) and H groups was observed. Aspergillus, unclassified_Sordariomycetes, and Penicillium genera had greater representation in the H subjects compared with the CD group. Bacterial and fungal intra- and inter-kingdom correlations were observed between the H and CD groups. Therefore, fecal bacterial and fungal microbiome communities differed considerably between H and CD patients, and between Chinese and Western populations. The role of gut microbiota in homeostasis and in gastrointestinal disorders should be investigated further.

Connexins 43 (Cx43) plays a key role in neointimal formation after vascular injury, but the mechanism still needs to be further explored. We hypothesized that the gap junction-dependent function of Cx43 to mediate intercellular communication has a crucial role in the development and progression of vascular diseases. The effect of intercellular communication mediated by Cx43 hemichannels on neointimal formation after vascular injury was investigated. Cx43 was overexpressed or knockdown in rat vascular smooth muscle cell (SMC) by transfection pcDNA-Cx43 plasmid or small interfering RNA (siRNA) against Cx43 (siCx43). SMC proliferation and marker genes expression after Cx43 alteration and blockade of the Cx43 hemichannel were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and RT-PCR. The effect of carbenoxolone on neointimal formation was investigated in carotid artery injured rat model. We demonstrated that overexpression of Cx43 promoted SMC proliferation, meanwhile, mRNA expression level of smooth muscle alpha-actin and calponin, which were important markers of SMC in a contractile state, were down-regulated in smooth muscle. Knockdown of Cx43 inhibited SMC proliferation but increased SMC marker genes expression level. Carbenoxolone (50 muM) improved SMC contractile differentiation and inhibited its proliferation. Our data showed that carbenoxolone reduced neointimal formation after carotid artery injury. In summary, blockade of intercellular communication via Cx43 hemichannels reduces neointimal formation after vascular injury by inhibiting proliferation and phenotypic modulation of SMCs.

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A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.

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