Gannan Medical University

Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (p < 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (p < 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (p < 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.

Hepatocellular carcinoma (HCC) is a serious concern worldwide. The published reports showed that aberrant CD95 receptor expression plays a critical role in apoptosis in liver cancer. While curcumin has shown promise in inducing apoptosis in liver cancer cells, its direct effects on CD95 expression during this process have not been thoroughly investigated. This study aims to quantitatively assess the expression of the CD95 receptor in HepG2 cells treated with different concentrations of curcumin using techniques such as fluorescence staining, single-molecule force spectroscopy (SMFS), and single-molecule recognition imaging (SMRI). Fluorescence staining results indicate a significant increase in CD95 expression following curcumin treatment. For the first time, SMFS and SMRI techniques were used to directly reveal the binding sites of CD95 on the cell membrane, with the number of binding sites increasing as the curcumin concentration increased. Additionally, the binding force between an antibody-modified probe and CD95 was strengthened with curcumin treatment, suggesting that curcumin enhances both the quantity and affinity of CD95 binding sites. This study provides new insights into curcumin-induced CD95-mediated apoptosis in liver cancer cells and highlights the potential of AFM techniques for investigating drug mechanisms. Overall, these findings may inform innovative therapeutic strategies for liver cancer and improve drug design processes.

Cerebral ischemic injury induces the polarization of astrocytes toward two different phenotypes, i.e., the proinflammatory A1 phenotype and the protective, anti-inflammatory A2 phenotype, affects the prognosis of cerebral ischemia. To explore the neuroprotective effect of phytoestrogens ICT on cerebral ischemic rehabilitation and the preliminary mechanism of regulating astrocyte polarization.

Transient middle cerebral artery occlusion (tMCAO)/reperfusion was performed on rats and then treated with ICT (i.p.) once daily for 28 days. Intervention of GPER specific inhibitor G15 was repeated. The body weight, Garcia JH scale, right/left brain weight ratio, CatWalk gait test and Y maze test to assess overall neural function in rats. Inflammatory factors in ischemic cortical were detected by Western blotting. The number of newborn neurons was observed by BrdU staining, and the double immunofluorescence staining and Western blotting to evaluated the activation and A1 and A2 polarization of astrocytes.

The results showed that ICT treatment markedly perfected functional outcomes on a long-term basis after ischemic stroke, it also improved learning and memory and gait. ICT inhibited the polarization of A1 type astrocytes and promoted the polarization of A2 type astrocytes, promote neuron regeneration in hippocampus DG region. G15 removes some of the protective effects of ICT.

The experimental results show that ICT exerts neuroprotective effects and regulates astrocyte polarization through GPER, suggesting that it may be a potential therapeutic agent for ischemic stroke during the recovery period.