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One aim of the United Nations Children's Fund Sustainable Development Goals is to end preventable deaths among newborns and children In 2015, China had 12.4% (17.8 million) of the 143 [...]

Abstract Background Nm23 gene was isolated as a metastatic suppressor gene. The antimetastatic effect of Nm23 has been an enigma for more than 10 years. Little is known about its molecular mechanisms. In this study we overexpressed Nm23-H1 in H7721 cells and observed reduction of cell adhesion, migration and extension of actin stress fibers in cells stimulated by fibronectin (Fn). Methods pcDNA3/Nm23-H1 was introduced into H7721 cells, and expression of Nm23-H1 was monitored by RT-PCR and western blot. Cell adhesion, actin extension and wound-induced migration assays were done on dishes coated with fibronectin. Phosphorylation of focal adhesion kinase (FAK) and total amount of integrin alpha5 and beta1 in Nm23-H1 transfected cells and control cells were measured by western blot. Flow cytometry was used to detect expression of surface alpha5 and beta1 integrin. N-glycosylation inhibitor tunicamycin was used to deglycosylate the integrin beta1 subunit. Results Overexpression of nm23-H1 in H7721 cells reduced cell adhesion, migration and extension of actin stress fibers on dishes coated with Fn. Phosphorylation of FAK in Nm23-H1 transfected cells was also attenuated. Integrin alpha5 and beta1 gene messages were unaltered in nm23-H1 overexpressed cells as detected by RT-PCR. However, while cell surface integrin alpha5 was unchanged, surface expression of beta1 integrin was downregulated. Western blot also showed that the total amounts of integrin alpha5 and beta1 were unaltered, but the level of mature integrin beta1 isoform was decreased significantly. Furthermore, partially glycosylated precursor beta1 was increased, which indicated that the impaired glycosylation of integrin beta1 precursor might contribute to the loss of cell surface integrin beta1 in nm23-H1 overexpressed cells. Conclusion These results suggest that by modulating glycosylation of integrin beta1, nm23-H1 down-regulates integrin beta1 subunit on cell surface and mediates intracellular signaling and subsequent suppression of the invasive process, including cell adhesion and migration.

Associations of regulated on activation, normal T cell expressed and secreted (RANTES) −403G/A, −28C/G, and In1.1T/C polymorphisms with HIV-1 infection and the progression of HIV-1 disease have been widely reported with inconsistent results. To clarify this situation, we performed an updated meta-analysis of all available studies from PubMed, EMBASE, and the China National Knowledge Infrastructure. A total of 24 eligible studies involving more than 10,000 subjects were included. By using the healthy controls, we found that −403G/A polymorphism was significantly associated with reduced susceptibility to HIV-1 infection in G/A+A/A versus GG (odds ratio [OR] = 0.755, 95% confidence interval [CI] = 0.581-0.982); and a significantly decreased risk was also found for −28C/G polymorphisms (G vs. C, OR = 0.804, 95% CI = 0.696-0.927; G/G+C/G vs. C/C, OR = 0.826, 95% CI = 0.704-0.969). Whereas for In1.1T/C polymorphism, increased risk of HIV-1 infection was revealed (C vs. T, OR = 1.216, 95% CI = 1.047-1.430; T/C vs. T/T, OR = 1.68, 95% CI = 1.263-2.234; T/C+T/T vs. C/C, OR = 1.466, 95% CI = 1.147-1.875). Subgroup analyses by ethnicity showed significant association among Asians, but not among Caucasians. When HIV-1-exposed seronegative (HESN) controls were used, no significant association was detected. Moreover, −403G/A and −28C/G polymorphisms were also not associated with long-term nonprogressive HIV-1 infection (all p > .05). This meta-analysis suggests that RANTES −403G/A and −28C/G polymorphisms confer possible protection against HIV-1 infection, whereas In1.1T/C polymorphism may increase risk of HIV-1 infection, especially in Asians. These results may contribute to finding a theoretical basis for effective control strategies against HIV/AIDS. Further investigations are needed to validate our conclusions. [ABSTRACT FROM AUTHOR]

Management of prostate cancer, especially advanced prostate cancer, remains clinically challenging and requires the identification of new biomarkers and therapeutic targets that can be exploited to improve patient outcome. Galectin-3 (gal-3) is a carbohydrate-binding protein involved in cancer progression and metastasis, including prostate tissues. Gal-3 function is regulated by proteolytic cleavage and the cleaved gal-3 is implicated in tumor progression. This study is the first to determine gal-3 expressions with two monoclonal anti-gal-3 antibodies in prostate tissues to distinguish expression patterns between intact and cleaved gal-3 and analyze their clinical relevance. Our results showed gal-3 cleavage occurred in prostate cancer but not normal prostate. Gal-3 presented in tumor tissues was mainly the cleaved form that can be detected by the anti-gal-3 antibody targeting C terminal. The cleaved gal-3, but not the intact gal-3, was increased in prostate cancer compared to normal prostate tissues and positively associated with malignance, tumor progression and metastasis. In addition, the expression of cleaved gal-3 was closely related to PSA level, indicating a PSA-mediated degradation of intact gal-3 in prostate cancer. In summary, our findings suggested the cleaved gal-3 could be a valuable diagnostic biomarker and a therapeutic target for the treatment of prostate cancer, especially advanced metastatic prostate cancer., Competing Interests: None., (IJCEP Copyright © 2018.)