Genistein is a multifunctional natural compound.In this study, we demonstrate the activity of genistein on non-small lung cancer A549 and 95D cells.A CCK8 assay was used to detect the cytotoxicity ...

Background: Increasing evidence supports a critical role of chronic inflammation in intracranial aneurysm (IA). Understanding how the immunological alterations in IA provides opportunities for targeted treatment. However, there is a lack of comprehensive and detailed characterization of the changes in circulating immune cells in IA.Objective: To perform a comprehensive and detailed characterization of the changes in circulating immune cells in patients with IA.Methods: Peripheral blood mononuclear cell samples from IA patients (n = 26) and age-and sex-matched healthy controls (HCs, n = 20) were analyzed using high dimensional mass cytometry, and the frequency and phenotype of immune cell subtypes were assessed.Results: We identified 28 cell clusters and found that the immune signature of IA consists of cluster changes. IA patients exhibited dysfunction of immunity, with dysregulation of CD4⁺ T-cell clusters, increased B cells and monocytes, and decreased CD8⁺ T cells, DNT cells, and DPT cells. Moreover, compared with findings in HC, IA was associated with enhanced lymphocyte and monocyte immune activation, with a higher expression of HLA-DR, CXCR3, and CX3CR1. In addition, the expression of TLR4, p-STAT3, and the exhaustion marker PD1 was increased in T cells, B cells, and NK cells in IA patients.Conclusions: Our data provide an overview of the circulating immune cell landscape of IA patients, and reveal that the dysfunction of circulating immunity may play a potential role in the development of IA.

Vorinostat (SAHA) is a histone deacetylase inhibitor that exerts its effects through epigenetic regulation. Specifically, SAHA can inhibit the proliferation of triple-negative breast cancer (TNBC) cells alone or in combination with other chemotherapeutic agents. Doxorubicin (DOX), a traditional chemotherapeutic drug, exhibits a potent cytotoxic effect on cancer cells while also inducing strong toxic effects. In this study, we investigated the synergistic potential of these two drugs in combination against TNBC. Our results suggested that the combination of these two drugs could enhance the inhibitory effect on cancer cell proliferation, resulting in alterations in cell mitotic phase, and suppression of cancer cell stemness. Moreover, our in vivo study unveiled that when SAHA was combined with DOX, it not only exhibited an inhibitory effect on tumor metastasis but also played a role in regulating the immune microenvironment within tumors. Overall, the combination of DOX and SAHA presents a promising avenue for innovative combination chemotherapy in the context of TNBC.

Background: Radiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear.Method: In this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. Results: We observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. Conclusion: In recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells.