Evaluation of the possible association of PDCD-1 and LAG3 gene polymorphisms with hepatocellular carcinoma risk.

PURPOSE: Programmed death-1 (PDCD-1) and lymphocyte activating 3 (LAG3), two important immunosuppressive molecules, play crucial roles in immune escape of tumor cells. This study evaluated the effects of PDCD-1 (rs10204525 and rs36084323), and LAG3 (rs870849 and rs1882545) gene polymorphisms on hepatocellular carcinoma (HCC) risk. METHODS: 341 patients with HCC and 350 cancer-free controls in the South Chinese population were included in a population-based case-control study. DNAs were extracted from peripheral blood samples. Genotypes were analyzed using multiplex PCR and sequencing. SNPs were analyzed using multiple inheritance models (co-dominant, dominant, recessive, and over-dominant). RESULTS: The allele and genotype frequencies of neither of the four polymorphisms, adjusted for age and gender, differed between HCC patients and controls. The differences were also not significant after stratifying by gender and age. According to our results, HCC patients with rs10204525 TC genotype had significantly lower AFP levels than HCC patients with rs10204525 TT genotype (P = 0.004). Moreover, the frequency of PDCD-1 rs36084323 CT genotype reduced the risk of TNM grade (CT vs. C/C-T/T: OR = 0.57, 95%CI = 0.37-0.87, P = 0.049). CONCLUSION: Our results demonstrated that the PDCD-1 (rs10204525 and rs36084323), and LAG3 (rs870849 and rs1882545) polymorphism did not influence the risk of HCC, PDCD-1 rs10204525 TC genotype was associated with the lower AFP levels and rs36084323 CT genotypes were related to HCC tumor grades in the South Chinese samples.

Dual-Site Chemosensor for Monitoring ·OH-Cysteine Redox in Cells and In Vivo.

The reaction between hydroxyl radical (·OH) and cysteine (Cys) plays an important role in the redox balance of living cells. A deeper insight into this intracellular reaction modulation and process is necessary and draws great interest. A highly effective technique consists of the real-time visualization of the two bioactive species and the perception of their respective changes by using a fluorescent probe. In this study, a dual-site chemosensor SPI based on phenothiazine-cyanine was developed, which realized quantitative detection and real-time imaging of ·OH and Cys at their own fluorescence channels (·OH: λex = 485 nm, λem = 608 nm; Cys: λex = 426 nm, λem = 538 nm) without spectral crosstalk. The fluorescent sensor showed excellent anti-interference and selectivity for common biological substances, apart from the successful imaging of exogenous and endogenous ·OH and Cys. We further visualized the redox dynamic reaction and explored the correlation of ·OH and Cys generated by different inhibitors (sulfasalazine and (1S, 3R)-RSL3). Notably, the chemosensor also possesses the capacity to clearly monitor ·OH and Cys in living mice and zebrafish. This study reports on the first chemosensor to investigate the process of intracellular redox modulation and control between ·OH and Cys, which show potential to further explore some metabolic and physiological mechanisms.

Functional Heterogeneity of Bone Marrow Mesenchymal Stem Cell Subpopulations in Physiology and Pathology.

Bone marrow mesenchymal stem cells (BMSCs) are multi-potent cell populations and are capable of maintaining bone and body homeostasis. The stemness and potential therapeutic effect of BMSCs have been explored extensively in recent years. However, diverse cell surface antigens and complex gene expression of BMSCs have indicated that BMSCs represent heterogeneous populations, and the natural characteristics of BMSCs make it difficult to identify the specific subpopulations in pathological processes which are often obscured by bulk analysis of the total BMSCs. Meanwhile, the therapeutic effect of total BMSCs is often less effective partly due to their heterogeneity. Therefore, understanding the functional heterogeneity of the BMSC subpopulations under different physiological and pathological conditions could have major ramifications for global health. Here, we summarize the recent progress of functional heterogeneity of BMSC subpopulations in physiology and pathology. Targeting tissue-resident single BMSC subpopulation offers a potentially innovative therapeutic strategy and improves BMSC effectiveness in clinical application.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice.

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.