PIEZO2 expression is an independent biomarker prognostic for gastric cancer and represents a potential therapeutic target.

Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC.

What role does PDL1 play in EMT changes in tumors and fibrosis?

Epithelial-mesenchymal transformation (EMT) plays a pivotal role in embryonic development, tissue fibrosis, repair, and tumor invasiveness. Emerging studies have highlighted the close association between EMT and immune checkpoint molecules, particularly programmed cell death ligand 1 (PDL1). PDL1 exerts its influence on EMT through bidirectional regulation. EMT-associated factors, such as YB1, enhance PDL1 expression by directly binding to its promoter. Conversely, PDL1 signaling triggers downstream pathways like PI3K/AKT and MAPK, promoting EMT and facilitating cancer cell migration and invasion. Targeting PDL1 holds promise as a therapeutic strategy for EMT-related diseases, including cancer and fibrosis. Indeed, PDL1 inhibitors, such as pembrolizumab and nivolumab, have shown promising results in clinical trials for various cancers. Recent research has also indicated their potential benefit in fibrosis treatment in reducing fibroblast activation and extracellular matrix deposition, thereby addressing fibrosis. In this review, we examine the multifaceted role of PDL1 in immunomodulation, growth, and fibrosis promotion. We discuss the challenges, mechanisms, and clinical observations related to PDL1, including the limitations of the PD1/PDL1 axis in treatment and PD1-independent intrinsic PDL1 signaling. Our study highlights the dynamic changes in PDL1 expression during the EMT process across various tumor types. Through interplay between PDL1 and EMT, we uncover co-directional alterations, regulatory pathways, and diverse changes resulting from PDL1 intervention in oncology. Additionally, our findings emphasize the dual role of PDL1 in promoting fibrosis and modulating immune responses across multiple diseases, with potential implications for therapeutic approaches. We particularly investigate the therapeutic potential of targeting PDL1 in type II EMT fibrosis: strike balance between fibrosis modulation and immune response regulation. This analysis provides valuable insights into the multifaceted functions of PDL1 and contributes to our understanding of its complex mechanisms and therapeutic implications.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Association between glycemic traits and melanoma: a mendelian randomization analysis.

Background: The causation of Glycemic Traits and risks of Melanoma remains unknown. We used Mendelian Randomization (MR) to assess the links between Glycemic Traits and Melanoma. Method: Pooled data from Genome-Wide Association Studies (GWAS) were utilized to examine the relationships that exist between Fasting Insulin (n = 26), 2-h Glucose (n = 10), Fasting Glucose (n = 47), HbA1c (n = 68), and Type-2 Diabetes (n = 105) and Melanoma. We evaluated the correlation of these variations with melanoma risk using Two-Samples MR. Result: In the IVW model, Fasting Glucose (OR = 0.99, 95%CI = 0.993-0.998, p < 0.05, IVW), Type-2 Diabetes (OR = 0.998, 95%CI = 0.998-0.999, p < 0.01, IVW) and HbA1c (OR = 0.19, 95%CI = 0.0415-0.8788, p < 0.05, IVW) was causally associated with a lower risk of Melanoma. In all models analyzed, there was no apparent causal relationship between Fasting Insulin and Melanoma risk. There was no obvious causal difference in the IVW analysis of 2-h Glucose and Melanoma, but its p < 0.05 in MR Egger (OR = 0.99, 95%CI = 0.9883-0.9984, p < 0.05, MR Egger), and the direction was consistent in other MR analyses, suggesting that there may be a causal relationship. Conclusion: The results of this study suggest that a higher risk of Fasting Glucose, Type-2 Diabetes, 2-h Glucose, and HbA1c may be associated with a lower risk of Melanoma. However, no causal relationship between fasting insulin and melanoma was found. These results suggest that pharmacological or lifestyle interventions that regulate plasma glucose levels in the body may be beneficial in the prevention of melanoma.

[Mechanism study on leptin resistance in lung cancer cachexia rats treated by Xiaoyan Decoction].

OBJECTIVE: To study the leptin resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats. METHODS: An LCC rat model was established. Totally 40 rats were randomly divided into the normal control group, the LCC model group, the XD group, and the positive control group, 10 in each group. After LCC model was set up, rats in the LCC model group were administered with normal saline, 2 mL each time. Rats in the XD group were administered with XD at the daily dose of 2 mL. Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL. All medication lasted for 14 days. The general condition and tumor growth were observed. Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay. Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique. RESULTS: Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P < 0.05). Compared with the LCC model groups, serum leptin levels significantly increased in the XD group (P < 0.01). Leptin receptor levels in the hypothalamus increased significantly in the LCC model group (P < 0.01). Increased receptor levels in the LCC model group indicated that either XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P < 0.01). There was also statistical difference between the XD group and the positive control group (P < 0.05). Contents of NPY was higher in the LCC model group than in the other groups with statistical difference (P < 0.05). There was no statistical difference in NPY between the normal control group and the rest 2 treatment groups (P > 0.05). There was statistical difference in POMC between the normal control group and the LCC model group (P < 0.05). POMC could be decreased in the XD group and the positive control group with statistical significance (P < 0.05), and it was more obviously decreased in the XD group (P < 0.05). CONCLUSIONS: Leptin resistance existed in LCC rats. XD could increase serum leptin levels and reduce leptin receptor levels in the hypothalamus. LCC could be improved by elevating NPY contents in the hypothalamus and reducing POMC contents, promoting the appetite, and increasing food intake from the periphery pathway and the central pathway.