Plasma TIGIT Level Is a Possible Marker in HIV-Related Liver Damage.

T cell immunoglobulin and ITIM domain (TIGIT), has a key role in immunopathogenesis of HIV. Previous studies on immune checkpoint receptors had mainly focused on the membrane form. To evaluate clinical significance of soluble form of TIGIT (sTIGIT) in people living with HIV. Blood samples of 61 untreated HIV-infected patients and 24 healthy individuals were collected and TIGIT concentrations in plasma were measured by ELISA method. A decreased level of plasma TIGIT in HIV-infected patients was found to be negatively associated with AST/ALT ratio (r = -0.5358, p = 0.0483) that was indicative of liver damage. Moreover, the proportion of TIGIT on CD3+CD4+ cells in HIV-infected individuals increased (47.12 ± 5.051%) compared with in healthy controls (22.13 ± 4.426%, p < 0.01), which indicated change in plasma TIGIT level was at least partially attributed to CD3+CD4+ T cells. Furthermore, there was a strong positive correlation between TIGIT plasma levels and lymphocyte activation gene-3 (LAG-3) plasma levels in HIV-infected patients with a linear correlation coefficient r = 0.904. Therefore, plasma TIGIT level is a possible marker in HIV-related liver damage and LAG-3 closely related to TIGIT possibly plays a co-ordinated role in HIV-related liver damage.

Toxic effects and foundation of proton radiation on the early-life stage of zebrafish development.

Proton is a major particle of space radiation environment and a prospective radiotherapy beam. However, its risk needs to be fully evaluated for the understanding and to establish the better protective strategy for astronaut and patient. Zebrafish is an ideal model for the toxicity studies on medicines and environmental genetic toxicants. In the current study, embryos of zebrafish at 24 h post-fertilization (hpf) were exposed to proton beam. Some toxic parameters of embryo-larval development were investigated. Microarray combining with qRT-PCR were used to detect the gene expression situation. Generally, fractions of a variety of abnormal phenotypes of embryos and larvae increased in a dose-dependent manner after irradiation. The copy number of mitochondria, the basal respiration rate and the maximum respiration rate of embryos significantly decreased after irradiation. Microarray data demonstrated that MAPK signaling pathway, cell communication, glycolysis and TGF-ß signaling pathway were significantly affected in the irradiated group. The expressions of matrix metallopeptidase 9 (mmp9) and TIMP metallopeptidase inhibitor 2b (timp2b) genes, and enzymatic activity of MMP9 were significantly upregulated in irradiated group. Overall, these results suggest that acute radiation of proton severely affects the development of organism and results in aberration occurrence in the early stage of zebrafish development, which may relates to mitochondrial and glycolytic dysfunction.

Ilomastat, a synthetic inhibitor of MMPs, prevents lung injury induced by γ-ray irradiation in mice.

Lung injury is one of the pathological features in human or animal after radiation and the main side effect for patient after lung cancer radiotherapy. The efficient protective strategy still needs to exploit and the underlying mechanisms remain to be investigated. We found that the expression and activity of matrix metalloproteinases (MMPs) significantly increased at the early stage of radiation-induced lung injury (RILI). Pretreatment with Ilomastat, a synthetic inhibitor of MMPs, decreased the expression and activity of MMPs and significantly alleviated the lung inflammation and fibrosis in the irradiated mice, as well as enhanced the survival of irradiated mice. In addition, the levels of TGF-ß, IL-6, TNF-α and IL-1ß in the tissues dramatically reduced in the irradiated mice pretreated with Ilomastat. Furthermore, our experiments in vitro also showed that radiation significantly increased the MMPs activity, and Ilomastat pretreatment inhibited the activity of MMPs activated by irradiation and increased the cell survival. It is the first report, to our knowledge, to demonstrate that Ilomastat is a potential effective reliever for RILI and MMPs may play important roles in the process of RILI.