Int J Med Sci
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Antibodies targeting the immune checkpoint inhibitor, programmed cell death 1 (PD-1), have provided a breakthrough in the treatment of lung cancer. However, the function of PD-1 in natural killer (NK) cells of cancer patients remains unclear. Herein, we analyzed the expression of PD-1 on the NK cells in the peripheral blood of patients with lung cancer and found that the level of PD-1+ NK cells in patients was significantly higher than that in healthy individuals. ⋯ In addition, IL-2 could increase the expression of PD-1 on NK cells in vitro, indicating that high IL-2 level in the plasma is largely responsible for the abundance of PD-1+ NK cells in patients with lung cancer. These findings demonstrate intriguing mechanisms for understanding the expression of PD-1 on NK cells and the function of PD-1+ NK cells in lung cancer. This study confirms and extends previous studies demonstrating that PD-1 can negatively regulate the antitumor function of NK cells.
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Objectives: The study was aimed to assess γ‑glutamyltransferase (GGT) activity and concentration as a marker of oxidative stress induced by exposure to tobacco smoke in acute pancreatitis (AP) course. Examination of the relationship between GGT activity/concentration and single-nucleotide polymorphism (SNP rs5751901 and rs2236626) in GGT1 gene was performed. Subjects and methods: We examined SNPs in 38 AP patients and 51 healthy subjects by PCR-RFLP methods. ⋯ Conclusions: SNP rs5751901 and rs2236626 cause changes in GGT activity. Smoking in the AP course contributes to increased GGT activity and excessive GSH use up in patients with TC and CC genotypes for both SNPs. Exposure to smoke xenobiotics enhances (3-fold) the risk of AP occurrence in individuals with TC genotypes for SNP rs5751901.
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Basal-like breast cancer is among the most aggressive cancers and there is still no effective targeted treatment. In order to identify new therapeutic targets, we performed mRNA-Seq on eight breast cancer cell lines. Among the genes overexpressed in basal-like tumors, we focused on the RhoA and RhoB genes, which encode small GTPases known to play a role in the actin cytoskeleton, allowing cells to migrate. qRT-PCR and Western blotting were used for expression studies. ⋯ Rho proteins are involved in the formation of stress fibers, a conformation of the actin cytoskeleton found in migrating cells: inhibition of RhoA expression decreased the formation of these fibers. BRCA1, a gene frequently inactivated in basal-like tumors, appears to play a role in the differential expression of RhoA and RhoB in these tumors, as the restoration of BRCA1 expression in a BRCA1-mutated basal-like cell line decreased expression of RhoA and increased expression of RhoB, resulting in reduced migratory capacity. These results suggest Rho proteins as potential therapeutic targets for basal-like and BRCA1-mutated breast cancer, as migration and acquisition of mesenchymal properties are key functional pathways in these tumors with high metastatic potential.
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Comparative Study
Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.
Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. ⋯ Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.
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Background: Despite significant advances in the materials and methods development used in surgical repair and postoperative rehabilitation, the adhesion formation remains the most common clinical problem in tendon injuries. Therefore, the development of novel therapies is necessary for targeting at preventing tendon adhesion formation and improving tendon strength. Methods: We used rat fibroblasts for in vitro experiments to determine the optimal concentration of TSA in rats, and then set up negative control group, TSA intervention group, mir-29b interference adenovirus intervention group and TSA and mir-29b interference adenovirus co-intervention group. ⋯ Conclusion: We conclude that the use of miR-29b inhibitor at the end of the tendon break could initiate endogenous repair mechanism and subsequently use of TSA should be able to inhibit the exogenous repair mechanism. Therefore, the combination of both treatments could prevent tendon adhesion and ensure tendon strength. Our findings suggested that this approach would be a feasible approach for tendon repair.