Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown limited efficacy in gastric cancer, primarily due to the rarity of inherent homologous recombination (HR) deficiency. The nuclear Arp2/3 complex was recently implicated in DNA double-strand break repair via HR. Here, we investigate whether pharmacological inhibition of Arp2/3 can induce a functional HR-deficient state to synergize with PARPi in gastric cancer cells.

HR repair efficiency was assessed using a direct repeat green fluorescent protein (DR-GFP) reporter assay in HEK-293T cells following Arp2/3 inhibition with CK666, siRNA-mediated knockdown, or CRISPR/Cas9-mediated knockout of ACTR2/ACTR3. HGC-27 and AGS gastric cancer cells were treated with CK666 alone and in combination with olaparib or niraparib. Cell viability and synergy were evaluated by Cell Counting Kit-8 (CCK-8) and clonogenic assays (n = 3 independent experiments). DNA damage and apoptosis were assessed by immunofluorescence for gamma H2A histone family member X (γH2AX) foci (≥100 cells per condition) and Western blot analysis for cleaved PARP.

Arp2/3 inhibition with CK666 significantly impaired HR repair efficiency in the DR-GFP assay (p < 0.01). This effect was recapitulated by genetic knockdown or knockout of ACTR2/ACTR3. CK666 alone exerted minimal cytotoxicity, but synergized with both olaparib and niraparib to suppress proliferation (Combination Index <1), reducing the half-maximal inhibitory concentration (IC₅₀) of PARPi by approximately threefold. Combination treatment markedly enhanced γH2AX foci formation (p < 0.0001) and increased the level of cleaved PARP compared with either monotherapy.

Inhibition of Arp2/3 compromises HR repair capacity, thereby creating a synthetic lethal interaction with PARP inhibition in gastric cancer cells. This combination strategy represents a promising therapeutic approach to broaden the clinical utility of PARPi in HR-proficient tumors and may also enable dose reduction to mitigate associated toxicities.

This review examines recent advances in the use of probiotics combined with immune modulation for the prevention and treatment of gastric cancer. It highlights the interactions between gastrointestinal probiotics, including Lactobacillus, and Helicobacter pylori infection, emphasizing their roles in gastric cancer initiation and progression. The article evaluates how probiotics exert anticancer effects by restoring intestinal microecological balance, enhancing mucosal immunity, and suppressing H. pylori. It also discusses preliminary findings on Lactobacillus in colorectal cancer and their potential relevance to gastric cancer research. Finally, the clinical potential of combining probiotics with immunotherapy for gastric cancer is assessed, and future research directions in this rapidly evolving field are proposed.

Cervical cancer (CC) is a prevalent malignancy in women. RNA-binding motif single-stranded interacting protein 3 (RBMS3) acts as a tumor suppressor in many cancer types, but its role and underlying regulatory mechanisms in CC remain unclear.

The expression levels of RBMS3 and heat shock protein family A member 6 (HSPA6) were evaluated in clinical CC tissues. Gain- and loss-of-function assays, transcriptome sequencing, and rescue experiments were performed in CC cell lines and nude mouse xenograft models.

RBMS3 expression was notably lower in CC tissues (n = 306) than in normal cervical tissues (n = 22), with reduced levels linked to shorter overall patient survival (p < 0.05). Overexpression of RBMS3 reduced cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo (p < 0.001). HSPA6 was identified as a key target of RBMS3 and was also downregulated in CC tissues. RBMS3 potentially binds to HSPA6 mRNA and enhances its stability. Knockdown of HSPA6 reversed the tumor-suppressive effects of RBMS3 (p < 0.001).

RBMS3 inhibits CC progression by stabilizing HSPA6 mRNA. The RBMS3-HSPA6 axis may represent a prognostic biomarker and therapeutic target in CC.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder characterized by dysregulated ovarian signaling, metabolic inflammation, insulin resistance, and aberrant angiogenesis, for which effective disease-modifying therapies remain limited. Resveratrol (RES), a pleiotropic polyphenol, has attracted increasing attention for its ability to modulate multiple molecular and cellular pathways implicated in PCOS pathophysiology. In this review, we synthesize current evidence to clarify how RES regulates key pathological signaling networks in PCOS, including ovarian follicular dysfunction, impaired insulin signaling, hyperandrogenism, oxidative stress, and vascular remodeling. Rather than merely cataloguing isolated mechanisms, we integrate findings from experimental models to highlight major convergent nodes-such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR), sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and vascular endothelial growth factor (VEGF)-related pathways-through which RES may exert coordinated regulatory effects at the cellular and tissue levels. We further examine the available clinical studies to assess the translational relevance of these mechanistic insights, with particular emphasis on phenotypic heterogeneity, dose dependence, and the treatment window. Although clinical outcomes remain modest and variable, the available evidence suggests that RES may provide context-dependent benefits in selected PCOS subtypes. Collectively, this review offers a network-based framework linking the molecular actions of RES to the complex pathophysiology of PCOS and identifies key knowledge gaps that must be addressed to improve translational precision and therapeutic applicability.

Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases. Although Prohibitin 1 (PHB1) has been implicated in tumorigenesis, its role in KIRC remains unclear. This study aimed to investigate the expression, function, and underlying mechanisms of PHB1 in KIRC.

PHB1 expression and clinical relevance were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus database (GEO), and TIMER3.0 datasets. Single-cell RNA sequencing (scRNA-seq) data from 19 KIRC patients and normal kidney samples were used to assess cell-type-specific expression. Functional experiments, including CCK-8, EdU incorporation, colony formation, and Transwell assays, were performed to evaluate the effects of PHB1 on cell proliferation, migration, and invasion. A xenograft model was used to evaluate the effects of PHB1 in vivo. Western blotting and correlation analyses were conducted to assess the potential regulatory interplay between VHL, SKP2, PHB1, and p53.

PHB1 was significantly downregulated in KIRC tissues. Single-cell analysis showed reduced PHB1 expression in tumor-derived epithelial cells, fibroblasts, endothelial cells, and immune cells. Lower PHB1 levels were associated with poorer overall survival. PHB1 overexpression inhibited proliferation and migration, whereas knockdown promoted these effects. In vivo, PHB1 overexpression reduced tumor growth. Moreover, VHL knockout altered the protein levels of SKP2 and PHB1. Cellular manipulation of PHB1 moderately altered endogenous p53 protein expression. Based on TCGA data analysis, PHB1 expression showed a positive correlation with VHL and a negative correlation with SKP2.

Collectively, PHB1 acts as a potential tumor suppressor in KIRC. Its expression pattern is associated with the VHL-SKP2 signaling axis, and the tumor-suppressive effects of PHB1 may be partially associated with the modulation of p53 expression. These findings suggest that PHB1 has the potential to serve as a reliable biomarker and therapeutic candidate for KIRC treatment.

G protein-coupled receptor 19 (GPR19) is an orphan G protein-coupled receptor with emerging relevance in cancer; however, its role in breast cancer remains poorly understood. Given the high frequency of tumor protein p53 (TP53) alterations in aggressive breast cancer, particularly triple-negative breast cancer (TNBC), we investigated the clinical significance, biological function, and molecular mechanism of GPR19 in TP53-mutant breast cancer.

Public datasets (Gene Expression Omnibus and The Cancer Genome Atlas) were analyzed to assess GPR19 expression in relation to TP53 status, molecular subtype, and prognosis. Expression was validated in breast cancer cell lines, paired clinical tissues, and tissue microarrays by quantitative PCR, Western blotting, immunofluorescence, and immunohistochemistry. Stable GPR19 knockdown models in MDA-MB-231 and BT-549 cells were used to evaluate proliferation, cell cycle distribution, and apoptosis. RNA sequencing, rescue experiments with the extracellular signal-regulated kinase (ERK) activator Ro 67-7476, and a nude mouse xenograft model were employed to investigate the underlying mechanism.

GPR19 was significantly upregulated in TP53-mutant breast cancer, primary tumors, and especially TNBC, and its high expression was associated with poor survival. Functionally, GPR19 depletion markedly suppressed cell proliferation, colony formation, and DNA synthesis, while inducing G2/M arrest and apoptosis in TP53-mutant breast cancer cells. Mechanistically, GPR19 knockdown reduced ERK phosphorylation and downregulated forkhead box protein M1 (FOXM1) and its downstream G2/M regulators cyclin B1 (CCNB1) and polo-like kinase 1 (PLK1), whereas total ERK levels remained largely unchanged. Pharmacological activation of ERK partially restored FOXM1 expression, alleviated cell cycle disturbance and apoptosis, and reversed the growth-inhibitory effects of GPR19 depletion. In vivo, GPR19 knockdown suppressed xenograft growth, reduced Ki-67 staining, increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positivity, and inhibited the ERK-FOXM1-CCNB1/PLK1 signaling cascade, all of which were partially rescued by ERK activation.

GPR19 functions as a novel oncogenic driver and clinically relevant biomarker in breast cancer, particularly in TP53-mutant and TNBC subsets. By activating the ERK-FOXM1 axis, GPR19 sustains cell cycle progression and suppresses apoptosis, highlighting this pathway as a potential therapeutic vulnerability in aggressive breast cancer.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a major cause of cancer-related mortality. Despite advances in targeted therapies, tumor heterogeneity and acquired resistance frequently undermine clinical outcomes. This study aimed to identify novel oncogenic drivers and underlying mechanisms in LUAD.

We examined cellular retinoic acid-binding protein 2 (CRABP2) expression in human LUAD specimens and evaluated its functional role through in vitro assays (cell proliferation, migration, invasion, and apoptosis) and in vivo xenograft tumor growth. Mechanistic exploration involved RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and immunoblotting for the nuclear factor kappa B (NF-κB) signaling components, along with rescue experiments to dissect the pathway dependency.

CRABP2 was identified as a candidate oncogene in LUAD. Functional assays confirmed that CRABP2 promoted proliferation, migration, and invasion, suppressed apoptosis, and accelerated xenograft tumor growth. Mechanistically, CRABP2 potentiated retinoic acid (RA) signaling and activated the NF-κB pathway, as evidenced by enhanced inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) phosphorylation, subsequent NF-κB inhibitor alpha (IκBα) phosphorylation, and nuclear translocation of total and phosphorylated p65. Rescue experiments revealed that CRABP2‑induced NF-κB activation is RA-dependent and that this activation mediates the oncogenic effects of CRABP2.

Our findings establish a CRABP2/RA/NF‑κB axis that drives LUAD progression, highlighting this pathway as a potential therapeutic target for intervention in LUAD.

While mitochondrial dysfunction and immune cell dysregulation have been established as important contributors to the pathogenesis of osteosarcoma (OS), the prognostic value of mitochondria-related genes (MRGs) and immune-related genes (IRGs) in OS remains poorly understood.

Data were obtained from public databases. Differentially expressed genes (DEGs) and key module genes were identified viadifferential expression analysis and weighted gene co-expression network analysis, respectively. Candidate genes of interest were identified by intersecting key module genes, DEGs, MRGs, and IRGs. Then, candidate genes were screened using regression analysis and proportional hazards assumption testing to identify prognostic genes. A risk model was then constructed in the TARGET-OS dataset and validated in GSE16091. Independent prognostic, immune infiltration, and gene expression analyses were conducted. In addition, single-cell analysis was performed to identify key cell populations, and pseudotime analysis as well as cell communication network construction were carried out. Finally, the expression patterns of selected prognostic genes were additionally validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the functional role of protein kinase Cα (PRKCA) in osteosarcoma cell proliferation, migration, and invasion was evaluated in vitro.

Glutathione S-transferase Pi-1 (GSTP1), catalase (CAT), TNFSF10, and PRKCA were identified as mitochondria- and immunity-related prognostic genes in OS and were used to construct a risk model. The risk model was able to effectively predict the survival of patients with OS. A nomogram based on the identified prognostic genes additionally exhibited excellent performance when predicting OS patient survival. Significant differences in the abundance of 14 immune cell types and 8 immune checkpoint molecules were noted between the high-risk and low-risk groups. Single-cell analyses were then conducted to annotate 10 cell types, and M1 macrophages were identified as a potentially relevant cell population in the OS microenvironment. During M1 macrophage differentiation, initial reductions in CAT and PRKCA expression were noted, followed by subsequent increases and final decreases. In contrast, the expression of GSTP1 and TNFSF10 in these cells first rose and then declined. Furthermore, PRKCA was selected for further in vitro analyses, which revealed that it can enhance the invasion, migration, and proliferation of OS cells.

This study identified GSTP1, CAT, TNFSF10, and PRKCA as prognostic genes associated with mitochondrial and immune function in OS, with in vitro evidence providing direct support for the potential functional role of PRKCA in OS progression. These findings highlight a new avenue for predicting clinical prognosis in OS and may provide a basis for future studies of putative therapeutic targets.

Methyltransferase-like 9 (METTL9) has been implicated in tumor progression, yet its clinical significance, functional roles, and immunoregulatory functions in lung adenocarcinoma (LUAD) remain unclear. This study aimed to integrate multi-omics datasets and experimental evidence to systematically evaluate the expression profile, prognostic value, molecular mechanisms, and tumor microenvironment (TME)-related functions of METTL9 in LUAD.

Transcriptome and clinical data for LUAD and METTL9 protein expression were obtained from public databases. Survival analysis was performed using Kaplan-Meier analysis and Cox proportional hazards models. METTL9-related differentially expressed genes (DEGs) were screened, followed by functional annotation and pathway enrichment analysis. A protein-protein interaction (PPI) network associated with METTL9 was constructed using STRING. METTL9 gene mutations and promoter methylation levels were analyzed via cBioPortal and UALCAN. Immune infiltration was evaluated through gene set variation analysis (GSVA) and the TIMER platform. The role of METTL9 depletion in regulating transforming growth factor-β (TGF-β)/Smad signaling, epithelial-mesenchymal transition (EMT), as well as the behavior of A549 and H1975 cells was investigated.

METTL9 was markedly elevated in LUAD, which was confirmed in external datasets and immunohistochemistry. Increased METTL9 expression showed a strong association with advanced TNM stage, unfavorable clinicopathological parameters, and poor survival outcomes in univariate analysis. Receiver operating characteristic (ROC) analysis indicated that METTL9 showed moderate diagnostic utility for LUAD, with an Area Under the Curve (AUC) of 0.704 (95% Confidence Interval [CI]: 0.650-0.758) in the The Cancer Genome Atlas (TCGA) dataset and 0.815 (95% CI: 0.758-0.872) in the GSE31210 dataset. Moreover, high METTL9 expression was significantly correlated with poor survival outcomes (Hazard Ratio [HR] = 1.349, 95% CI: 1.010-1.802, p = 0.043). METTL9 interacted with multiple oncogenic proteins in the PPI network and showed significant correlations with cuproptosis-related genes. Immune infiltration analysis further demonstrated that METTL9 expression showed significantly associated with immune cell infiltration and the tumor immune microenvironment in LUAD. METTL9 knockdown suppressed LUAD cell proliferation, migration, invasion, and EMT, while promoting apoptosis and reducing the expression of B-cell lymphoma 2 (Bcl-2), phosphorylated Smad2 (p-smad2), and phosphorylated Smad3 (p-smad3).

METTL9 is upregulated in LUAD and correlates with an unfavorable prognosis. Our results indicate that METTL9 may contribute to LUAD progression and EMT, potentially in relation to the TGF-β/Smad signaling pathway.

Intracranial aspergilloma is a rare fungal infection of the central nervous system, predominantly affecting immunocompromised individuals. However, cases in immunocompetent hosts are increasingly reported, often mimicking meningiomas due to similar radiological features, leading to diagnostic delays and poor outcomes.

We present two cases of isolated intracranial aspergilloma in immunocompetent patients. The first case involved a 55-year-old female with a right parietal scalp swelling mimicking a convexity meningioma, confirmed as aspergilloma on histopathology following surgical excision. The second case was a 63-year-old male with symptoms of raised intracranial pressure and a right planum sphenoidale lesion mimicking skull base meningioma, also diagnosed postoperatively as invasive aspergillosis. Both patients underwent surgical resection and voriconazole therapy, with favorable short-term outcomes. These cases highlight the diagnostic challenges posed by overlapping imaging characteristics of aspergilloma and meningioma.

A high index of suspicion, even in immunocompetent patients, is essential for timely histopathological confirmation and antifungal treatment to mitigate morbidity and mortality. Adding aspergilloma to the differential diagnosis of meningioma-like lesions on radiology may improve outcomes.