One of the most common tumors in the world is hepatocellular carcinoma (HCC), and its mortality rates are still on the rise, so addressing it is considered an important challenge for universal health. Despite the various treatments that have been developed over the past decades, the prognosis for advanced liver cancer is still poor. Recently, tumor immunotherapy has opened new opportunities for suppression of tumor progression, recurrence, and metastasis. Besides this, investigation into this malignancy due to high immune checkpoint expression and the change of immunometabolic programming in immune cells and tumor cells is highly considered. Because anti-cytotoxic T lymphocyte–associated protein (CTLA)-4 antibodies and anti-programmed cell death protein (PD)-1 antibodies have shown therapeutic effects in various cancers, studies have shown that T cell immunoglobulin mucin-3 (TIM-3), a new immune checkpoint molecule, plays an important role in the development of HCC. In this review, we summarize the recent findings on signal transduction events of TIM-3, its role as a checkpoint target for HCC therapy, and the immunometabolic situation in the progression of HCC.
Background:One of the consequences of toxoplasmosis is the risk of passing it from mother to fetus and the onset of congenital toxoplasmosis during pregnancy. The purpose of this study was to evaluate the B1 gene of Toxoplasma gondii in the placental tissues of pregnant women with acute toxoplasmosis.Materials and Methods:The study was a cross-sectional study. Serum samples of pregnant women who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were tested for immunoglobulin G (IgG) antibodies against T. gondii by enzyme-linked immunosorbent assay. Then, polymerase chain reaction was used to identify the specific B1 gene of T. gondii in IgG seropositive women. The placental tissues of the pregnant women with positive serum B1 gene examined for this gene. Anti-Toxoplasma immunoglobulin M (IgM) was performed on the umbilical cord and neonate blood.Results:Anti-Toxoplasma IgG was detected in 167 out of 653 (25.6%) pregnant women. T. gondii B1 gene was identified in 36 out of 167 (21.6%) of IgG seropositive women. After delivery, the B1 gene was evaluated in 15 out of 36 (41.7%) patients’ placental tissues, 13 of which were positive for this gene (86.7%). Anti-Toxoplasma IgM was detected neither in any umbilical cord nor in neonatal blood samples. All newborns, with the exception of one case, were born with normal birth weight and in term birth.Conclusion:The B1 gene was detected in 86.7% of the placental tissue of women who were involved in acute toxoplasmosis during pregnancy.
Valporic acid (VPA) has been implicated to have anti-inflammatory and anti-oxidant activities in several ischemic/reperfusion (I/R) injury models. This study intended to evaluate whether VPA could affect the inflammatory/anti-inflammatory cytokines balance and severity of renal I/R injury in rat. I/R injury was induced in two groups of animals, vehicle normal saline and VPA-treated (IP injection, 150 mg/kg) rats, by 45 min occlusion of both left and right renal arteries followed by 3, 24 and 120 h reperfusion in separate groups. After each time point, kidneys and blood samples were collected for cytokine genes (TNF-α, IL-1β, IL-10 and TGF-β) expression analysis and histological examinations in the kidney tissues. Serum creatinine levels were measured for evaluation of renal function. We observed significantly downregulated mRNA expressions for IL-1β and TNF-α in blood and tissue samples 24 and 120 h post I/R injury in VPA-treated animals compared to control groups (P < 0.0001). On the other hand, mRNA expression levels for IL-10 and TGF-β were significantly increased in the blood samples from VPA-treated animals at two time points after I/R injury (P < 0.0001) and at 120 h in tissue samples (P < 0.001). Histopathology analysis showed downgraded ischemic changes in VPA group compared to sham control. Also, decreased serum creatinine levels were observed in VPA-treated animals particularly 120 h post I/R injury (P < 0.0001) that was correlated with less pathological changes in this group. Our results indicate that VPA can attenuate pro-inflammatory responses and augment the anti-inflammatory condition in favor of faster renal recovery from ischemic changes and improved renal function after renal I/R injury.
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