Clinical significance of B7-H3 expression in circulating CD4+CD25high T cells, CD14+ monocytes, and plasma for the progression of HIV infection.

BACKGROUND: B7-H3 is an important immune checkpoint molecule that plays a negative role in immune regulation. This study was aimed to explore B7-H3 expression in HIV-infected patients and its clinical significance. METHODS: To explore the expression and clinical significance of B7-H3 in HIV-infected patients, we investigated the B7-H3 expression pattern and the correlation of B7-H3 expression with clinical parameters of HIV-infected patients with different levels of CD4+ T cells. To assess the role of B7-H3 in regulating the function of T cells in HIV infection, we performed a proliferation assay and T cell function test in vitro. RESULTS: B7-H3 expression in HIV-infected patients was significantly higher than that in healthy controls. mB7-H3 expression on CD4+CD25high T cells and CD14+ monocytes increased with disease progression. mB7-H3 expression on CD4+CD25high T cells and monocytes was negatively correlated with lymphocyte count, CD4+T cell count, and positively correlated with HIV viral load in HIV-infected patients. when the number of CD4+ T cells in HIV-infected patients was ≥ 200/µL, sB7-H3 and mB7-H3 expression levels on CD4+CD25high T cells and monocytes were negatively correlated with lymphocyte count, CD4+T cell count. sB7-H3 and mB7-H3 expression on monocytes were positively correlated with HIV viral load. B7-H3 inhibited the proliferation of lymphocytes and the secretion of IFN-γ in vitro, especially the ability of CD8+ T cells to secrete IFN-γ. CONCLUSIONS: B7-H3 played an important negative regulatory role in anti-HIV infection immunity. It could be used as a potential biomarker for the progression of HIV infection and a novel target for the treatment of HIV infection.

The biological functions of LGR5 in promoting non-small cell lung cancer progression.

BACKGROUND: The Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), which is used as a marker of adult stem cells and colorectal cancer stem cells (CSCs), is closely associated with the progression of non-small cell lung cancer (NSCLC). This study aimed to identify the clinical significance and biological function of LGR5 in NSCLC. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-PCR) was applied to detect the expression of LGR5 and stemness-related genes in 22 NSCLC patients, and the clinical significance of LGR5 in NSCLC progression was estimated by statistical analysis. LGR5 overexpressing A549- and H1299-transfected cells were established, and CCK-8 and clone formation assays were used to test the proliferation ability. A wound-healing assay was utilized to clarify the migration ability. The invasion ability was confirmed via the Transwell assay kit. RESULTS: LGR5 expression was markedly higher in NSCLC tissues than in the matched adjacent normal tissues, and had a trend to associate with tumor size, lymph node metastasis, and TNM stage. The proliferation rates, clone formation rates, wound healing rates, number of invasive cells, and the NOTCH1 expression of the LGR5 overexpressing groups, were significantly higher than those of the control groups. CONCLUSIONS: LGR5 plays an essential role in NSCLC tumorigenesis and is closely associated with the proliferation, metastasis, and invasion of NSCLC cells. LGR5 may promote NSCLC progression via NOTCH1 and could be a new target for gene-targeted therapies for NSCLC.

Clinical Significance of B7-H3 Expression During the Progression of Hepatitis B Virus Infection.

B7-H3, one of the costimulatory members participating in checkpoint pathway, has been shown to be upregulated after hepatitis B virus (HBV) infection. To further explore the clinical significance of dynamic B7-H3 expression during the progression of HBV infection, we systematically investigated the expression pattern of B7-H3 and the correlation of B7-H3 expression with the ratio of T lymphocyte subsets and clinical parameters at different stages in the course of the disease. Flow cytometry and enzyme-linked immunosorbent assay data showed that soluble form of B7-H3 (sB7-H3) was positively correlated with the frequency of Treg cells in acute hepatitis B (AHB), chronic hepatitis B (CHB), and hepatocellular carcinoma patients with HBV infection (HBV-HCC). Membrane form of B7-H3 (mB7-H3) expressed on Treg cells and monocytes was positively correlated with the frequency of Treg cells in CHB. SB7-H3 had relationship with mB7-H3 expressed on Treg cells and monocytes at different stages during HBV infection, except for HBV-HCC. MB7-H3 expressed on Treg cells was positively correlated with that on monocytes in AHB, CHB, HBV-liver cirrhosis, and HBV-HCC. The B7-H3 expression was positively correlated with aspartate aminotransferase and alanine aminotransferase levels in CHB and sB7-H3 level was higher in late tumor/node/metastasis (TNM) stage in HCC. Higher mB7-H3 expression was associated with greater tumor size, later TNM stage, and worse prognosis in HBV-HCC indicated by immunohistochemistry. Taken together, these results suggested that B7-H3 might contribute to the progression of HBV infection by triggering inhibitory signals in effector T cells and it was closely associated with the progression and poor prognosis during HBV infection. B7-H3 could be utilized as a potential clinical indicator and a potential target for therapeutic strategies against HBV infection.

Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair.

The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-ß1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1ß, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.