Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear.

Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-κB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR).

TLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth in vivo. Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing.

TLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1/NGFR axis represents a novel potential therapeutic target for CRPC.

Cancer remains a leading cause of global mortality, with incidence and mortality rates rising annually. Atorvastatin, a widely used statin, primarily functions by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the mevalonate pathway, thereby lowering cholesterol. Accumulating preclinical and clinical evidence suggests that ATV possesses significant anticancer properties beyond its lipid-lowering effects, positioning it as a promising candidate for adjunctive cancer therapy. The anticancer efficacy of ATV stems fundamentally from its disruption of the mevalonate pathway, which impedes the critical isoprenylation of small GTPases (e.g., Ras, Rho). This inhibition cascades into multifaceted antitumor activities, including the induction of apoptosis and autophagy, dysregulation of the cell cycle, suppression of proliferation, migration, and invasion. ATV further modulates key oncogenic signaling pathways and exhibits potent anti-inflammatory and antioxidant effects within the tumor microenvironment. Crucially, evidence demonstrates that integrating ATV into multimodality regimens-such as alongside immune checkpoint inhibitors and metabolic modulators-significantly improves survival outcomes in patients, substantiating its clinical translational potential. However, a comprehensive and systematic evaluation of its pleiotropic anticancer mechanisms and therapeutic potential is lacking. This review aims to fill this gap by systematically summarizing the efficacy and molecular mechanisms of ATV across various malignancies, alongside its cytoprotective effects on normal tissues. The challenges and future directions for its clinical translation in oncology are also critically discussed.

Good's syndrome (GS) is a rare acquired immunodeficiency defined by the co-occurrence of thymoma and hypogammaglobulinemia. Follicular helper T (Tfh) cells, a specialized CD4+ T cell subset, play a critical role in supporting B-cell antibody production. The status and characteristics of Tfh cells in GS, however, remain largely unexplored.

This study utilized flow cytometry to analyze CD4+CXCR5+ T cells, along with Tfh1 (CXCR3+CCR6-), Tfh2 (CXCR3-CCR6-), and Tfh17 (CXCR3-CCR6+) subsets, in three GS patients compared to twenty healthy controls (HCs). Serum levels of Th1/Th2/Th17 cytokines were also assessed.

The cohort included a 45-year-old female and a 70-year-old female, both with type AB thymoma, and a 47-year-old male with type A thymoma. All patients exhibited markedly reduced serum IgG levels (0.87 g/L, 1.44 g/L, 3.0 g/L) and a profound reduction or absence of peripheral B cells (0%, 0%, 3.7%). The proportions of CD4+CXCR5+ T cells and total Tfh cells in two patients (Cases 1 & 2) were comparable to HCs, while a significant increase was noted in the third patient (Case 3). A key finding was a consistent and drastic reduction in CXCR3+CCR6- Tfh1 cells across all patients, whereas Tfh2 cell frequencies were significantly elevated. Tfh17 cell percentages and Th1/Th2/Th17 cytokine profiles showed no significant alterations.

Our findings reveal, for the first time, a pronounced decrease in circulating CXCR3+ Tfh1 cells in GS patients, suggesting a potential role for this specific immune imbalance in the disease's immunopathogenesis.

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Gut dysbiosis has been implicated in autoimmune pathogenesis, yet integrated microbial and metabolomic profiling in MG remains scarce. To characterize gut microbiota and the fecal metabolome in MG, identify diagnostic biomarkers, and explore associations between microbial taxa, metabolites, and clinical severity.

Fecal samples from 29 MG patients and 10 healthy controls underwent 16S rRNA sequencing and UHPLC-Q-TOF MS metabolomics. LEfSe identified differential taxa; metabolites were screened by VIP > 1.0, P < 0.05, FDR q < 0.05. Random Forest and Spearman correlation assessed biomarker performance and microbiota - metabolite - clinical associations.

MG patients showed significantly reduced alpha- and beta-diversity. LEfSe identified 232 discriminative taxa, with depletion of butanoic acid-producing commensals (Faecalibacterium prausnitzii, Ruminococcus bromii, Bifidobacterium bifidum) and enrichment of Klebsiella. Metabolomics revealed 567 altered metabolites (424 downregulated), including reduced short-chain fatty acids and secondary bile acids (lithocholic, isolithocholic, and allolithocholic acid). The Random Forest metabolite model achieved AUC = 1.0. Spearman analysis revealed that lithocholic acid (P < 0.05) and allocholic acid (P < 0.001) showed positive correlations with the QMGS, while Ruminococcus abundance was positively correlated with butanoic acid (P < 0.01). KEGG analysis implicated cholinergic synapse, bile secretion, sphingolipid signaling, and mTOR pathways.

MG patients exhibit a distinct profile of gut dysbiosis and metabolic disturbances. The specific microbial and metabolic biomarkers identified in this study may offer novel insights for auxiliary diagnosis of MG and guide future microbiota-targeted intervention strategies.

Colorectal cancer (CRC) is a leading malignancy with multifactorial etiology, including genetic, environmental, and microbial factors. Bacteria such as Helicobacter pylori, pks⁺ bacteria, Enterococcus faecalis, and Bifidobacterium bifidum have been linked to CRC, though their roles remain controversial. Some may promote inflammation and genotoxicity, while others may confer protective effects. This study assessed the presence and relative abundance of these bacteria in colorectal FFPE tissue samples.

This case-control study included three groups of FFPE tissue samples: tumor tissues from CRC patients (Tumor, n=50), normal tissues adjacent to tumors (Adjacent, n=50), and normal tissues from non-CRC individuals (Normal, n=30). Sections were prepared with a microtome, and bacterial gene copy numbers were quantified using species-specific primers and quantitative real-time PCR, normalized to human GAPDH. Associations with age, sex, and neoplastic type were analyzed (p < 0.05).

B. bifidum was significantly higher in Adjacent tissues compared to Tumor and Normal (p < 0.0001). H. pylori detection increased progressively from Normal to Adjacent to Tumor tissues (p = 0.002). pks⁺ bacteria were detected only in individuals ≥60 years (p = 0.014). E. faecalis load was higher in Tumor tissues of females and older adults, though overall presence did not differ significantly among groups.

Enrichment of B. bifidum and increased H. pylori detection near tumors suggest the tumor microenvironment favors bacterial persistence. Age- and sex-related patterns in pks⁺ and E. faecalis highlight host influences on microbial distribution in CRC, supporting further mechanistic studies.

To comprehensively review the prevalence and associated factors of kinesiophobia in postoperative patients with breast cancer.

Two reviewers independently screened the literature and extracted the data. Methodological quality assessment of the included studies was performed using the Joanna Briggs Institute critical appraisal checklists. A random-effects model was applied to estimate the pooled prevalence. We used subgroup analyses and narrative synthesis to explore the sources of heterogeneity and identify the associated factors, respectively.

A total of 21 studies comprising 2773 patients met the inclusion criteria. Of these, 14 studies involving 2007 postoperative patients with breast cancer were analyzed, showing a pooled kinesiophobia prevalence of 56.5% (95% CI: 39.5%-72.8%). Subgroup analyses revealed that the prevalence of kinesiophobia, as measured using the Tampa Scale for Kinesiophobia (TSK; 48.4%), was lower than that measured using the Fear-Avoidance Components Scale (FACS; 64.3%). A total of 45 factors associated with kinesiophobia were identified and categorized into biological (n= 20), psychological (n= 17), and social (n= 8) domains based on the biopsychosocial (BPS) model.

The findings indicate a high prevalence of kinesiophobia in postoperative patients with breast cancer, which is associated with multiple factors. This high prevalence underscores the clinical significance of the issue in their postoperative care. Future studies should identify predictors of kinesiophobia in these patients and explore more effective tailored interventions to help them benefit from exercise.

CRD42025641017.

The gut microbiome plays diverse roles in human health. Although Korean red ginseng (KRG) has shown therapeutic potential in animal models, its effects on the human gut microbiome after gastrointestinal (GI) cancer surgery remain underexplored. This prospective randomized controlled study aimed to evaluate postoperative safety of KRG and its impact on the gut microbiome and postoperative outcomes after GI cancer surgery.

Patients were randomly assigned 1:1 to the red ginseng or control groups. Microbiome analysis of preoperative and postoperative fecal samples was performed using 16S rRNA sequencing. The alpha and beta diversities, taxonomic composition changes of microbiome, nutritional index, clinical symptoms, GI symptoms, and quality of life (QOL) were assessed.

A total of 60 patients were enrolled and 16 patients in the red ginseng group and 25 in the control group were included in the final analysis. Postoperative alpha diversity decreased significantly in the control group, but remained relatively stable in the red ginseng group. Postoperative Lactobacillus levels increased significantly in the red ginseng group compared to the control group (18.34 % vs. 0.23 %; p < 0.001), whereas Bifidobacterium levels decreased (p = 0.002). Serum albumin levels were significantly higher in the red ginseng group at 3 months postoperatively (p = 0.003), and global health status/QOL scores were improved in the red ginseng group (p = 0.047).

Red ginseng supplementation may play a protective role in gut microbiome, improving clinical outcomes in patients undergoing GI cancer surgery, as a safe and supportive therapy for enhancing postoperative recovery.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor in children. We previously showed that rotenone suppressed OS cell metastasis. However, its effects on OS cell growth and the underlying mechanisms remain unclear. The purpose of this study was to investigate the role of rotenone in OS and identify its direct target.

Molecular dockingand Biacore assay were used to confirm the interaction between rotenone and USP47. Co-immunoprecipitation, immunofluorescence, and cycloheximide assays were used to verify the relationship betweenUSP47 and FEN1. Cell cycle and apoptosis were examined by flow cytometry. Comet analyses were used to determine DNA damage. Deubiquination and Ub-VME assays were carried out to assess ubiquitination status and properties. Immunohistochemistry and a xenograft mouse model were utilized to validate the effects of various proteins and rotenone in vivo.

Knockdown of FEN1 and USP47 in OS cell lines induced cell cycle arrest and apoptosis through the induction of DNA damage. FEN1 exhibited a direct interaction with USP47. Mechanistically, wild-type USP47 regulated FEN1 protein stability through deubiquitination modification, whereas mutated Cys109Ser USP47 did not. Furthermore, rotenone modulated USP47 protein expression and the combined quantity of Ub-USP47 conjugation through physical interaction. Xenograft studies further confirmed the anti-OS activity of rotenone in vivo.

Rotenone is a potential therapeutic agent for OS due to its direct targeting of USP47 and resultant decrease in FEN1 stability and DNA integrity.

Lung adenocarcinoma (LUAD), the most common subtype of lung cancer and a leading cause of cancer-related deaths, is strongly associated with cigarette smoking and nicotine exposure. However, the molecular mechanisms underlying nicotine-induced LUAD remain unclear. This study employed an integrative approach combining network toxicology, competing endogenous RNA (ceRNA) analysis, molecular docking, and dynamics simulations to investigate nicotine's role in LUAD. Network toxicology identified 81 potential nicotine targets, with 12 core targets showing significant differential expression in LUAD. Functional enrichment suggested involvement of immune escape, inflammation, and cell death. A ceRNA network highlighted microRNA-101 and microRNA-155-5p as key regulators. Molecular docking and dynamics simulations demonstrated stable binding between nicotine and core targets. These findings reveal toxicological mechanisms driving LUAD and offer potential therapeutic targets.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biological behavior and limited therapeutic responsiveness. Identifying genetically and biologically interpretable biomarkers remains critical for improving molecular stratification of this malignancy. Here, we performed an integrative analysis combining bulk transcriptomics, genomic alteration profiling, immune-response modeling, and functional validation to characterize the clinical relevance of voltage-dependent anion channel 1 (VDAC1) in PDAC. Genomic analyses demonstrated that VDAC1 exhibits a low somatic mutation frequency in PDAC and that its dysregulated expression may be partly associated with copy number alterations. Transcriptomic analyses further showed that VDAC1 is significantly upregulated in tumor tissues and associated with unfavorable clinical outcomes. Multiomics characterization indicated that high VDAC1 expression is linked to mitochondrial metabolic programs and reduced cytotoxic immune signatures. Functional validation demonstrated that VDAC1 silencing impaired pancreatic cancer cell proliferation and disrupted mitochondrial homeostasis, including reduced mitochondrial membrane potential, ATP production, and mitochondrial reactive oxygen species levels. In addition, VDAC1 perturbation reduced immunosuppressive cytokine output, suggesting a tumor-intrinsic connection between mitochondrial metabolic regulation and immune-related programs. Collectively, this study provides a genomic alteration-informed multiomics framework supporting VDAC1 as a mitochondrial-associated biomarker in PDAC and highlights its potential relevance for molecular characterization of pancreatic cancer.