Breast cancer is the most common cancer type in women globally. Although survival rates have improved, treatments cause lasting issues, including impaired cardiorespiratory fitness, chronic inflammation, and reduced quality of life (QOL). Exercise is recommended to alleviate these burdens, but evidence remains inconsistent regarding its effects on cardiorespiratory function, inflammatory markers, and QOL, with limited integrated evaluation.

A systematic search was conducted in the Cochrane Central Register of Controlled Trials, Embase®, PubMed®, and Web of Science for articles published from database inception to April 15, 2025.

The systematic review contained 32 studies involving 1,754 survivors. Literature quality was assessed using the Cochrane Risk of bias assessment tool 2, with analyses performed using RevMan, version 5.4, and Stata, version 18.0.

Exercise significantly improved peak oxygen consumption (weighted mean difference [WMD] = 1.22, p < 0.001) and QOL (general: WMD = 6.05, p < 0.001; breast cancer-specific: WMD = 5.13, p = 0.045). No significant effects were found on maximum oxygen consumption, C-reactive protein, interleukin-6, or tumor necrosis factor-alpha (p > 0.05).

Clinical practice should routinely recommend exercise to improve cardiopulmonary fitness and QOL in breast cancer survivors. Clinicians should incorporate exercise into rehabilitation plans and encourage participation, and future research should explore its specific effects on inflammatory markers.

To explore the dynamic nature of family resilience among patients with lung cancer and the interactions among its core themes during adaptation.

15 patients with lung cancer were purposively recruited from the Lung Cancer Center at the West China Hospital of Sichuan University from June to October 2023.

A descriptive phenomenologic approach was used. Face-to-face semistructured interviews were informed by Walsh's family resilience framework. Interviews were audio recorded, transcribed verbatim, and analyzed in Chinese using Colaizzi's seven-step method with NVivo, version 11.0. Data saturation was reached after 15 interviews.

Three interrelated themes of family resilience were identified-family belief system, organizational patterns, and communication and problem-solving-comprising 10 subthemes. Family attachment, family cohesion, and open expression contributed to the dynamic interactions among these domains and supported family adaptation.

Nurses can assess family strengths and vulnerabilities across these themes and provide tailored family-oriented interventions that promote psychological recovery, mobilize family and social resources, and facilitate open, patient-centered communication.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with a rising incidence largely driven by chronic liver disease. Accurate diagnosis and appropriate clinical assessment at the time of presentation are essential, as therapeutic strategies and prognosis depend on tumor burden, liver function, portal hypertension, and patient performance status.

To develop evidence-based, multidisciplinary recommendations to guide the diagnosis, clinical assessment, and staging of patients with HCC.

This consensus was developed by 43 experts from surgical oncology, hepatology, clinical oncology, radiology, interventional radiology, pathology, liver transplantation, gastroenterology, radiation oncology, and palliative care, under the coordination of the Brazilian Society of Surgical Oncology and 13 collaborating national medical societies. A scientific steering committee predefined clinically relevant questions addressing radiological and histopathological diagnosis, clinical assessment, diagnostic work-up, management of patients at the time of HCC diagnosis, and staging. These questions were discussed and refined in multidisciplinary meetings and submitted to structured voting rounds.

The panel formulated 18 recommendations covering key aspects of HCC evaluation, including standardized application of Liver Imaging Reporting and Data System (LI-RADS®) for imaging-based diagnosis, management of indeterminate lesions, indications for biopsy, histopathological classification and reporting, immunohistochemical markers, assessment of hepatic function and portal hypertension, staging systems, diagnostic work-up, and the role of multidisciplinary care. The recommendations emphasize integration of imaging findings with liver-related factors and clinical context to support individualized decision-making.

This multidisciplinary consensus provides practical, evidence-based recommendations for the diagnosis, clinical assessment, and staging of HCC. By promoting standardized diagnostic practices while reinforcing comprehensive patient evaluation and multidisciplinary management, this document aims to improve diagnostic accuracy, optimize treatment selection, and support safe care.

Acute myeloid leukemia (AML) is associated with impaired antitumor immunity and defective activation of protective immune cells. Neem leaf glycoprotein (NLGP), an immunomodulatory component of neem leaf preparation, has demonstrated antitumor activity in several experimental models without apparent toxicity. This study investigated the immunomodulatory and epigenetic effects of NLGP on immune cells involved in tumor protection in AML.

Peripheral immune cells from healthy individuals and AML patients were treated with NLGP. CD33 negative lymphocytes from AML patients were evaluated for lymphocyte proliferation, immune-cell activation, and secretion of the Th1-associated cytokines IFN-γ and TNF-α. Nitric oxide (NO₂⁻) release and reduced glutathione (GSH) content were also measured. The expression of Th1- and tumor-suppression-associated genes was analyzed. Chromatin immunoprecipitation was used to assess enrichment of active histone marks, including H3K4me3 and H3K14Ac, and repressive or regulatory markers, including H3K27me3, HDAC1, p53, Notch1, and c-Myc, at the IFNG and TBX21 loci. Cytotoxic T-lymphocyte (CTL)-mediated killing of AML cells was also examined.

NLGP enhanced lymphocyte proliferation and activated multiple immune-cell populations in normal subjects and AML-derived CD33 negative lymphocytes. It increased IFN-γ, TNF-α, and NO₂⁻ production while reducing GSH content. NLGP upregulated genes associated with Th1 immunity and tumor suppression. At the IFNG and TBX21 loci, it increased enrichment of H3K4me3, H3K14Ac, and p53, while reducing H3K27me3, HDAC1, Notch1, and c-Myc enrichment. NLGP also stimulated CTLs and enhanced their ability to eliminate AML cells.

NLGP promotes tumor-protective immunity in AML through coordinated immune activation and epigenetic regulation, supporting its potential as a novel adjunctive immunotherapeutic strategy.

BackgroundWD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsWe conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays.ResultsWDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities.ConclusionOur study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.

Epithelial ovarian cancer (EOC) is typically diagnosed at an advanced stage and is associated with high mortality due to metastasis and chemoresistance. Cancer stem cells (CSCs) are central to EOC progression, recurrence, and treatment resistance, with their functional behavior shaped by the tumor immune microenvironment. While M1 and M2 macrophages have been well-characterized, the role of interferon-stimulated gene-enriched subpopulations, particularly interferon-induced protein with tetratricopeptide repeats 1 tumor-associated macrophages (IFIT1⁺ TAMs), in regulating CSC properties in EOC remains largely unexplored.

Single-cell RNA sequencing (scRNA-seq) was utilized to map the myeloid landscape and trace transcriptomic evolution in EOC. An in vitro indirect culture model utilizing unpolarized macrophage (M0)-conditioned medium (CM) was established to assess baseline phenotypic alterations. Furthermore, targeted siRNA silencing (si-TNFRSF10B) combined with recombinant human tumor necrosis factor ligand superfamily member 10 (TNFSF10) (rhTRAIL) treatments were employed to evaluate the specific impact of the TNF-related apoptosis-inducing ligand (TRAIL)-Death receptor 5 (DR5) signaling axis on multidrug resistance and CD44 expression.

High-resolution scRNA-seq analysis revealed a stage-dependent decline in IFIT1⁺ TAMs, an interferon-primed subset that robustly expresses the TNFSF10 ligand during early-stage disease. In vitro assays showed that conditioned medium from M0 macrophages suppresses CSC features and enhances expression of the tumor necrosis factor receptor superfamily member 10B (Death receptor 5) (TNFRSF10B/DR5) in EOC cells. Mechanistic studies confirmed that exogenous rhTRAIL treatment markedly diminished CD44⁺ cell populations and enhanced sensitivity to chemotherapeutic agents. Notably, these antitumor effects were largely abrogated following siRNA-mediated silencing of the DR5 receptor in EOC cell lines.

Our findings reveal that IFIT1⁺ tumor-associated macrophages intrinsically harbor anti-cancer stem cell potential through the TNFSF10 ligand. Activation of the TNFSF10-TNFRSF10B pathway suppresses cancer stemness and may enhance chemosensitivity. These insights shed light on the functional diversity of macrophages, highlighting that driving tumor-associated macrophages toward a sustained, interferon-primed IFIT1⁺ phenotype represents a promising therapeutic approach to target cancer stem cell populations in epithelial ovarian cancer.

PDE4DIP encodes a scaffold protein that has been implicated in compartmentalized signaling and cytoskeletal organization, but the role of its myomegalin variant 8 (MMG8) isoform in hepatocellular carcinoma (HCC) remains unclear. To address this gap, we examined PDE4DIP expression in public HCC datasets and investigated the functional role of MMG8 in HCC models.

PDE4DIP expression was analyzed in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and two Gene Expression Omnibus (GEO) cohorts (GSE14520, GSE36376). MMG8 function was assessed in Huh7 cells using siRNA-mediated knockdown and in Hepa1-6 cells using lentiviral Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9)-mediated knockout. Cell proliferation in MMG8-KD Huh7 cells and MMG8-KO Hepa1-6 cells was assessed using Cell Counting Kit-8 (CCK-8) assays, while Huh7 cell migration was evaluated using Transwell assays. Tumor growth was assessed using a murine subcutaneous tumor model. Immunohistochemical staining for Ki67 and cleaved caspase-3 was employed to assess tumor cell proliferation and apoptosis-associated changes, respectively. Gene set enrichment analysis was performed in TCGA-LIHC tumors stratified based on PDE4DIP expression.

PDE4DIP expression differed between tumor and non-tumor tissues across HCC cohorts, although the directionality of this difference was not uniform. MMG8 knockdown in Huh7 cells reduced proliferation and migratory activity. A single-cell-derived MMG8-KO Hepa1-6 clone exhibited reduced proliferation in vitro and formed smaller tumors in vivo, with lower Ki67 positivity but no significant difference in cleaved caspase-3 positivity between groups. In tumors from the TCGA-LIHC cohort, PDE4DIP expression was associated with distinct transcriptional programs. Specifically, PDE4DIP-high tumors presented with positive normalized enrichment score (NES) values for several metabolic pathways, whereas adhesion/extracellular matrix (ECM), cell cycle/proliferation, and translation/ribosome-related pathways exhibited negative NES values.

These findings support a functional contribution of MMG8 to proliferative, migratory, and tumor-growth phenotypes in the tested HCC models. Bulk gene-level PDE4DIP expression in human tumors was associated with context-dependent transcriptional states and should not be interpreted as a direct surrogate for MMG8 function.

Cysteinyl-tRNA synthetase 1 (CARS1) has been included in ferroptosis-related prognostic signatures, but its clinicopathological relevance, cellular functions, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized.

Transcriptomic and clinical data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were integrated with corresponding data from an institutional HCC tissue cohort of 60 patients. CARS1 expression was evaluated by immunohistochemistry, and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA) and multiplex immunofluorescence, as well as by analyzing public single-cell datasets. The effects of CARS1 depletion were evaluated in MHCC97H and Hep3B cells using Cell Counting Kit-8 (CCK-8) assays, cell-cycle profiling, wound-healing assays, Transwell migration assays, western blotting, and erlotinib-sensitivity assays.

CARS1 expression was elevated in HCC and was associated with adverse clinicopathological features and poor overall survival. Quantitative immunohistochemistry confirmed elevated CARS1 protein expression in tumor tissues. CARS1 depletion inhibited cell proliferation, altered cell-cycle distribution, impaired migration, and enhanced in vitro sensitivity to erlotinib. High CARS1 expression was also associated with increased infiltration of Th2-like immune cells.

Elevated CARS1 expression is associated with an adverse biological and immune phenotype in HCC. These clinical, histopathological, and loss-of-function findings support further investigation of CARS1 as a prognostic marker and candidate therapeutic target in HCC, although additional mechanistic and in vivo validation is required.

The endophilin protein family comprises a group of evolutionarily highly conserved Bin-Amphiphysin-Rvs (BAR) domain proteins that play key roles in cell membrane morphogenesis, endocytic trafficking, and organelle dynamics. The human endophilin family includes five main members, encoded by the genes SH3GL2 (endophilin A1), SH3GL1 (endophilin A2), SH3GL3 (endophilin A3), SH3GLB1 (endophilin B1), and SH3GLB2 (endophilin B2). Notably, SH3GLB1 gives rise to functionally distinct splice variants, including the ubiquitously expressed B1a and the neuron-enriched B1b/c, which play critical, opposing roles in conditions such as Alzheimer disease (AD). These isoforms perform distinct, often opposing functions in disease pathogenesis via specific molecular mechanisms. For instance, endophilin A1 acts as a tumor suppressor; its gene, SH3GL2, is frequently deleted or downregulated in cancers such as non-small cell lung cancer, and its loss promotes tumor progression by sustaining epidermal growth factor receptor (EGFR) signaling. Conversely, endophilin A2 drives cancer metastasis. In AD, endophilin A1 expression is significantly elevated, exacerbating synaptic dysfunction, while neuron-specific endophilin B1 isoforms are decreased, worsening amyloid pathology. The regulation of endophilins involves intricate networks, including post-transcriptional control by microRNAs (e.g., miR-330 targeting SH3GL2 in glioblastoma) and post-translational modifications. This review provides a comprehensive overview of the structural characteristics and regulation of expression and activity. It delineates the molecular mechanisms by which their dysfunction contributes to disease pathogenesis, aiming to provide new insights into these multifaceted proteins in health and disease.

Beauvericin is a cyclic hexadepsipeptide derived from Bombyx batryticatus. It is known as Jiangcan in traditional Chinese medicine and has diverse pharmacological properties, including antitumor, antiviral, insecticidal, and antibacterial effects. However, its specific mechanisms against multiple myeloma (MM) are not fully understood. The aim of this study was to elucidate the mechanism of beauvericin in MM.

This study utilized the mouse Sp2/0 cell line, the human U266 cell line, and a subcutaneous tumor allograft model in C57BL/6J mice. Flow cytometry was employed to evaluate apoptosis, and the Cell Counting Kit-8 (CCK-8) assay was used to measure cellular viability. Network pharmacology was employed for target prediction, followed by molecular docking analyses to confirm drug-target interactions. The protein expression levels of Ubiquitin-Specific Protease 9X (USP9X) and Bcl-2 were assessed by Western blotting following USP9X knockdown. Additionally, co-immunoprecipitation assays were performed to evaluate whether beauvericin modulates the Bcl-2/USP9X interaction and affects Bcl-2 ubiquitination. The antitumor effects of beauvericin were further evaluated through in vivo experiments.

Network pharmacology analysis identified 82 MM-related target genes for beauvericin. These included key targets such as Caspase-3, Bcl-2, Matrix metallopeptidase 9 (MMP9), and Caspase-8, which may contribute to the anti-MM effects of beauvericin. Molecular docking revealed strong affinity and stability between beauvericin and Bcl-2. In vitro experiments confirmed that beauvericin inhibits MM cell proliferation, promotes apoptosis, and enhances Bcl-2 ubiquitination and degradation by disrupting the interaction between the deubiquitinating enzyme USP9X and Bcl-2. In vivo studies demonstrated that beauvericin treatment suppressed the growth of subcutaneous MM tumors C57BL/6J mice.

Beauvericin may exert its anti-MM effects by disrupting the USP9X-Bcl-2 interaction, thereby promoting Bcl-2 ubiquitination and degradation, and inducing cell apoptosis in MM cells.