MiR-219-5p inhibits hepatocellular carcinoma cell proliferation by targeting glypican-3

MicroRNAs (miRNAs) have been linked to the molecular pathogenesis of many cancers. In this study, we found that miR-219-5p was significantly downregulated in 83 HCC tissues and three HCC cell lines, compared to their non-tumor counterparts. MiR-219-5p expression correlated with tumor size, histological differentiation, and overall survival time in HCC patients. We also found that miR-219-5p could inhibit cell proliferation in vitro and arrest cell cycle at the G1 to S transition. Further studies identified that miR-219-5p reduced both the mRNA and protein levels of glypican-3 (GPC3). These findings indicate that miR-219-5p exerts tumor-suppressive effects in hepatic carcinogenesis through negative regulation of GPC3 expression.     

Structural analysis of Shu proteins reveals a DNA binding role essential for resisting damage

The yeast Shu complex, consisting of the proteins Shu1, Shu2, Psy3, and Csm2, maintains genomic stability by coupling post-replication repair to homologous recombination. However, a lack of biochemical and structural information on the Shu proteins precludes revealing their precise roles within the pathway. Here, we report on the 1.9-Å crystal structure of the Psy3-Csm2 complex. The crystal structure shows that Psy3 forms a heterodimer with Csm2 mainly through a hydrophobic core. Unexpectedly, Psy3 and Csm2 share a similar architecture that closely resembles the ATPase core domain of Rad51. The L2 loop present in Psy3 and Csm2 is similar to that of Rad51 and confers the DNA binding activity of the Shu complex. As with Rad51, the Shu complex appears to form a nucleoprotein filament by binding nonspecifically to DNA. Structure-based mutagenesis studies have demonstrated that the DNA binding activity of the Shu complex is essential for repair of the methyl methanesulfonate-induced DNA damage. Our findings provide good foundations for the understanding of the Srs2 regulation by the Shu complex.     

Elevated serum IL-16 and RANTES levels in patients with autoimmune thyroid diseases and modulation by methimazole therapy

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.     

Linear chromosome-generating system of Agrobacterium tumefaciens C58: protelomerase generates and protects hairpin ends

Agrobacterium tumefaciens C58, the pathogenic bacteria that causes crown gall disease in plants, harbors one circular and one linear chromosome and two circular plasmids. The telomeres of its unusual linear chromosome are covalently closed hairpins. The circular and linear chromosomes co-segregate and are stably maintained in the organism. We have determined the sequence of the two ends of the linear chromosome thus completing the previously published genome sequence of A. tumefaciens C58. We found that the telomeres carry nearly identical 25-bp sequences at the hairpin ends that are related by dyad symmetry. We further showed that its Atu2523 gene encodes a protelomerase (resolvase) and that the purified enzyme can generate the linear chromosomal closed hairpin ends in a sequence-specific manner. Agrobacterium protelomerase, whose presence is apparently limited to biovar 1 strains, acts via a cleavage-and-religation mechanism by making a pair of transient staggered nicks invariably at 6-bp spacing as the reaction intermediate. The enzyme can be significantly shortened at both the N and C termini and still maintain its enzymatic activity. Although the full-length enzyme can uniquely bind to its product telomeres, the N-terminal truncations cannot. The target site can also be shortened from the native 50-bp inverted repeat to 26 bp; thus, the Agrobacterium hairpin-generating system represents the most compact activity of all hairpin linear chromosome- and plasmid-generating systems to date. The biochemical analyses of the protelomerase reactions further revealed that the tip of the hairpin telomere may be unusually polymorphically capable of accommodating any nucleotide.     

Anal HPV infection in HIV-positive men who have sex with men from China

Background

Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM), especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China.

Methods

A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping.

Results

A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%). HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3%) were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%), HPV16 (13.0%), HPV52 (8.5%) and HPV11 (7.6%). Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001), which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection.

Conclusions

A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV.