The role of macrophages has transcended the traditional binary framework of M1/M2 polarization, emerging as "tissue microenvironment engineers" that dynamically govern organismal homeostasis and disease progression. Under physiological conditions, they maintain balance through phagocytic clearance, metabolic regulation (e.g., lipid and iron metabolism), and tissue-specific functions (such as hepatic detoxification by Kupffer cells and intestinal microbiota sensing), all meticulously orchestrated by epigenetic mechanisms and neuro-immune crosstalk. In pathological states, their functional aberrations precipitate chronic inflammation, fibrosis, metabolic disorders, and neurodegenerative diseases. Notably, this plasticity is most pronounced within the tumor microenvironment (TME): tumor-associated macrophages (TAMs) polarize toward a protumoral phenotype under conditions of low pH and high reactive oxygen species (ROS). They promote angiogenesis via vascular endothelial growth factor (VEGF), suppress immunity through interleukin-10 (IL-10)/programmed death-ligand 1 (PD-L1), and facilitate tumor invasion by degrading the extracellular matrix, ultimately fostering an immune-evasive niche. Novel intervention strategies targeting TAMs in the TME have shown remarkable efficacy: CRISPR-Cas9 spatiotemporal editing corrects aberrant gene expression; pH/ROS-responsive nanoparticles reprogram TAMs to an antitumoral phenotype; chimeric antigen receptor-macrophage (CAR-M) 2.0 enhances antitumor immunity through programmed death-1 (PD-1) blockade and IL-12 secretion; and microbial metabolites like butyrate induce polarization toward an antitumor phenotype. Despite persisting challenges-including the functional compensation mechanisms between tissue-resident and monocyte-derived macrophages, and obstacles to clinical translation-the macrophage-centered strategy of "microenvironmental regulation via cellular engineering" still holds revolutionary promise for the treatment of tumors and other diseases.

Histone post-translational modifications (HPTMs) have emerged as crucial epigenetic regulators in urological malignancies, including prostate, bladder, and renal cell carcinomas. This review systematically examines four key modifications-lactylation, acetylation, methylation, and phosphorylation-and their roles in carcinogenesis. These dynamic modifications, mediated by "writers", "erasers", and "readers", influence chromatin structure and gene expression, thereby driving oncogenic processes such as metabolic reprogramming, immune evasion, and treatment resistance. The newly discovered lactylation modification links cellular metabolism to epigenetic regulation through lactate-derived histone marks, particularly in clear cell renal cell carcinoma, where it activates oncogenic pathways. Acetylation modifications, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), modulate chromatin accessibility and are implicated in silencing cancer suppressors. Methylation patterns, controlled by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs), demonstrate dual roles in gene regulation, with specific marks either promoting or suppressing carcinogenesis. Finally, phosphorylation dynamics affect critical cellular processes such as cell cycle progression and DNA repair. This review underscores the therapeutic potential of targeting these modifications, as evidenced by promising results with HDAC and Enhancer of zeste homolog 2 (EZH2) inhibitors. However, challenges persist in clinical translation, including off-target effects and the complexity of the cancer microenvironment. Future research should utilize multi-omics approaches to elucidate modification crosstalk and develop precision therapies. Overall, this comprehensive analysis provides valuable insights into the epigenetic mechanisms underlying urological cancers and highlights remaining knowledge gaps and therapeutic opportunities in this rapidly evolving field.

Genes belonging to the adenylate cyclase (ADCY) family regulate various biological processes, including tumor metabolism, metastasis, angiogenesis, and immune escape. However, the functions of these genes in multiple cancers unclear.

This study analyzed the expression, prognostic value, correlation, mutation, and methylation patterns of ten genes belonging to the ADCY family across multiple cancers using multi-omics data. Additionally, the correlation between ADCY5 and immune cells, as well as the function of ADCY5 in multiple cancers were examined using single-cell data and spatial transcriptomic data.

Ten ADCY family genes were differentially expressed in most tumors and normal tissues, and their aberrant expression in multiple cancers significantly reduced patient survival. The expression level of ADCY5 was significantly correlated with the immune microenvironment. We also identified and validated the potential of ADCY5 as a potential biomarker for gastric cancer.

Our pan-cancer analysis nominates the ADCY family as a source of potential cancer biomarkers. We specifically validated ADCY5 in gastric cancer, establishing it as a promising prognostic biomarker with clinical and functional relevance, with significant implications for optimizing immunotherapy strategies and prognostic assessment in this malignancy.

Lung cancer, the leading cause of cancer-related mortality worldwide, poses considerable therapeutic challenges due to the varied responses to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Emerging highlight the pivotal role of host-microbiome interactions in modulating antitumor immunity and influencing clinical outcomes. This review examines how the respiratory and gut microbiota contribute to the immunosuppressive tumor microenvironment through dysbiosis-induced T-cell exhaustion and regulatory cell activation, while certain commensals facilitate dendritic cell-mediated recruitment of cytotoxic T lymphocytes. Additionally, this review explores the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids, influence myeloid-derived suppressor cells. Therapeutically, microbiota-modulation strategies-such as tailored probiotic formulations and precision fecal microbiota transplantation-offer potential to enhance immunotherapy efficacy. This review provides a foundation for microbiome-guided immunotherapy, advocating for biomarker-driven patient stratification and the use of engineered microbial consortia to counteract therapeutic resistance. These findings pave the way for the integration of microbiome science into next-generation precision oncology.

Although epirubicin is used among therapeutic options for multiple myeloma (MM), its clinical use remains limited, in part because the subgroup of patients most likely to benefit has not been clearly defined. Identifying robust biomarkers capable of predicting chemosensitivity is therefore essential to aimed personalized treatment strategies and enhance therapeutic outcomes. This study sought to characterize the molecular effects of epirubicin in MM cells, elucidate its tumor-suppressive mechanisms, and determine potential indicators for patient stratification.

The half-maximal inhibitory concentration (IC50) for epirubicin was quantified using the Cell Counting Kit-8 (CCK-8) viability assay. Gene expression alterations before and after epirubicin exposure were investigated via microarray profiling, followed by bioinformatic interrogation of publicly available datasets to examine the prognostic value of CDC20 expression in MM. Subsequently, functional validation was performed through in vitro assays and in vivo xenograft models to evaluate the impact of epirubicin on cell-cycle progression and tumor growth.

Epirubicin exhibited an IC50 of 23.85 μM in MM.1R cells. Transcriptome analysis revealed 115 genes upregulated and 25 genes downregulated post-treatment. Among the significantly altered genes were CDC20 (log FC = -2.409), KIF20A (log FC = -1.693), FAM72A (log FC = -1.742), CCNB1 (log FC = -1.787), PIF1 (log FC = -2.201), and LMNB1 (log FC = -1.589). Higher CDC20 expression was associated with shorter overall survival (OS), event-free survival (EFS), and post-progression survival (PPS). Mechanistic studies demonstrated that epirubicin triggers G2/M arrest in MM cells by suppressing CDC20, and in vivo experiments corroborated that decreased CDC20 expression contributes to reduced tumor proliferation via cell-cycle blockade.

Epirubicin exerts anti-myeloma effects by downregulating CDC20 and inducing cell-cycle arrest in MM, highlighting CDC20 as a potential biomarker for identifying MM patients likely to benefit from epirubicin.

Hepatocellular carcinoma (HCC) is as the most frequently observed histological subtype among primary liver malignancies. While quercetin (QT) shows potential antitumor activity, its preclinical anti-HCC effects and safety (especially in animals) remain unclear. Most existing studies use single methods (e.g., individual animal or in vitro assays), which compromises the reliability of the conclusions. This study's novelty lies in its use of a combined approach-integrating meta-analysis to quantify efficacy and network pharmacology to explore mechanisms, with experimental validation-to address this research gap. This work explores QT's preclinical anti-HCC effects and adverse effects using this integrated approach.

We collected literature on the treatment of HCC with QT from January 2000 to August 2024. Nine articles meeting the requirements were included in the current study. Subsequent to this, a meta-analysis was conducted, with further validation via network pharmacology approaches and experimental assays.

A meta-analysis found that QT significantly inhibited HCC growth (reduced tumor volume/weight) and reduced mortality in tumor-bearing mice, with no significant effect on body weight. Network pharmacology identified protein kinase B alpha (AKT1) and the phosphoinositide 3-kinase (PI3K)/AKT pathway as potential therapeutic targets. Finally, the aforementioned conclusions were further verified through experimental validation.

Preclinically, QT effectively inhibited HCC growth and reduced mortality in tumor-bearing mice without affecting body weight, likely via the PI3K/AKT pathway (targeting AKT1). Our study results furnish preliminary evidence for QT as a promising candidate for HCC adjuvant treatment, supporting its further evaluation in clinical trials. Limitations include reliance on preclinical data; thus, the translational value needs clinical validation, and the underlying mechanisms require more in-depth investigation.

Cysteine and Glycine Rich Protein 1 (CSRP1) is a member of the cysteine-rich protein family, characterized by a unique double-zinc finger motif. It plays an important role in development and cellular differentiation. Aberrant expression of CSRP1 has been reported in several malignancies, including prostate cancer and acute myeloid leukemia. However, its function in renal cell carcinoma (RCC) remains unexplored. In this study, we investigated the role of CSRP1 in RCC for the first time.

CSRP1 and programmed death-ligand 1 (PD-L1) expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of CSRP1 overexpression on cellular proliferation, migration, and apoptosis were assessed in vitro through CCK-8, wound healing, and flow cytometry assays. To evaluate the role of CSRP1 in immunotherapy, Balb/c mice were treated with anti-PD-L1 antibody, and tumor growth was monitored.

In vitro, overexpression of CSRP1 significantly inhibited proliferation and migration of A498 cells while enhancing their sensitivity to sunitinib treatment. Mechanistically, CSRP1 overexpression downregulated PD-L1 expression in RCC cells. In BALB/c mice inoculated with Renca cells, CSRP1 overexpression led to reduced tumor growth and improved response to anti-PD-L1 therapy.

CSRP1 may play a role in regulating cell viability, migration, drug resistance, and possibly innate immunity in RCC. These findings suggest that CSRP1 could increase the efficacy of targeted drugs and immunotherapy in combination treatment strategies for RCC.

This study investigated necroptosis-related molecular alterations in the endometrium of patients with polycystic ovary syndrome (PCOS) using quantitative proteomic analysis and developed a predictive model for pregnancy outcomes based on these findings.

Liquid chromatography-tandem mass spectrometry was used to identify and quantify endometrial proteins. Differentially expressed proteins (DEPs) were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify key pathways. Candidate prognostic necroptosis-related proteins were obtained by intersecting DEPs with the necroptosis gene set, followed by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses to select those associated with pregnancy outcomes and construct a predictive model.

A total of 611 DEPs were identified (132 upregulated and 479 downregulated). KEGG enrichment revealed significant involvement of the necroptosis pathway. Six necroptosis-related proteins were identified using Cox and LASSO regression analyses and used to construct the predictive model. Kaplan-Meier analysis showed that the low-risk group had significantly better pregnancy outcomes than the high-risk group. The model achieved an area under the receiver operating characteristic curve of 0.903 for predicting live birth at 37 weeks, and decision curve analysis demonstrated superior clinical benefit compared to conventional clinical indicators. Furthermore, correlation analysis revealed significant associations between necroptosis-related proteins and classical endometrial receptivity markers, suggesting potential molecular crosstalk.

Proteomic profiling revealed enrichment of the necroptosis pathway in the endometrium of patients with PCOS. The constructed model indicated preliminary predictive potential for pregnancy outcomes, suggesting that necroptosis may contribute to impaired endometrial receptivity.

This study aimed to explore the functional dynamics between microRNA-200b-3p (miR-200b-3p) and DNA damage-induced transcript 4 (DDIT4) in colorectal cancer (CRC) and their potential as therapeutic targets. Pan-cancer analysis was conducted to evaluate DDIT4 expression across multiple cancer types. Immunohistochemical staining of CRC clinical samples was performed to confirm DDIT4 protein levels. Functional assays, including cell proliferation, migration, and invasion analyses, were used to assess the effects of DDIT4 silencing in CRC cells. Bioinformatics and experimental validation identified microRNAs targeting DDIT4 and their prognostic significance using GEPIA, HPA and ENCORI databases. Pan-cancer analysis showed DDIT4 was highly expressed in CRC compared to other cancers. Immunohistochemistry confirmed moderate to high DDIT4 expression in CRC patient samples. Knockdown of DDIT4 significantly reduced proliferation, migration, and invasion of SW480 CRC cells. miRNA analysis identified miR-200b-3p as a potential regulator of DDIT4. Low expression of miR-200b-3p correlated with poor prognosis in CRC patients. Luciferase reporter assays confirmed direct binding of miR-200b-3p to DDIT4 mRNA. Furthermore, overexpression of DDIT4 was shown to mitigate the tumor-suppressive effects of miR-200b-3p, restoring proliferation, migration, and invasion. DDIT4 promotes CRC progression and is regulated by miR-200b-3p. Targeting the miR-200b-3p/DDIT4 axis may represent a novel therapeutic approach for CRC treatment.

Glioma, a prevalent malignancy globally, presents a serious threat to human health. Recent research has highlighted the significant anti-tumor properties of 6-gingerol (6-G), an active component of the traditional Chinese medicine ginger, though its precise mechanisms in glioma remain to be fully elucidated. This study employed network pharmacology, molecular docking, and dynamic simulation to explore the targets and underlying mechanisms of 6-G's anti-glioma effects, followed by in vitro validation of the key pathways. Drug-related targets were identified via PharmMapper and Swiss target prediction databases, while disease-related targets were sourced from GeneCards, OMIM, and TTD. The intersection of these datasets yielded potential therapeutic targets. Subsequent PPI network analysis using STRING11.5 and core gene screening with Cytoscape 3.9.1 led to the construction of a "drug-target network" and the identification of central genes. GO and KEGG enrichment analyses were conducted on potential therapeutic targets. Molecular docking and dynamic simulations were utilized to analyze the interactions between core genes and 6-G. Ultimately, the primary mechanism underlying 6-G's anti-GC effects was validated through in vitro experiments. A total of 183 potential targets for 6-G treatment of glioma were identified, with PPI analysis and core target screening revealing 10 critical targets. Enrichment analyses underscored the PI3K/AKT pathway as the primary signaling mechanism through which 6-G exerts its therapeutic effects. Molecular docking results showed that AKT1, HSP90AA1, EGFR, and MAPK3 were the key targets of 6-G in the treatment of glioma, and dynamic simulations further verified these findings. In vitro findings demonstrated that 6-G effectively inhibits the proliferation of U87 and U251 glioma cells, induces apoptosis, arrests the G1 phase of the cell cycle, and suppresses migration and invasion. Western blot analysis confirmed a significant downregulation of p-AKT in the PI3K/AKT pathway. In conclusion, 6-G impairs glioma cell proliferation, promotes apoptosis, induces G1 phase arrest, and inhibits migration and invasion, primarily through the suppression of the PI3K-AKT pathway. This finding provides a robust foundation for further research and clinical application.