ObjectivesThe radiation-induced bystander effect (RIBE) is a destructive reaction that occurs in non-irradiated cells. Exosomes, as an important intercellular information carrier, are considered potential mediators of RIBE, but their role in B cells remains unclear.MethodsB cell line IM-9 cells were irradiated to obtain exosomes for small RNA sequencing, and cell assays were used to assess the key miRNA’s role in non-irradiated B cell ferroptosis.ResultsExosomes isolated from irradiated and non-irradiated B cells were well characterized, displaying typical cup-shaped morphology (50–150 nm) and expressing exosomal markers ALIX and TSG101. miR-34a-5p was identified to be a key miRNA in regulating ferroptosis, and significantly upregulated in irradiated B cell derived exosomes (IR-exo). IR-exo remarkedly promoted ferroptosis of non-irradiated IM-9 cells, as evident by enhanced lactate dehydrogenase activity and lipid peroxidation, and reduced SLC7A11, GPX4 and FTH1 expression. However, miR-34a-5p silencing in IR-exo reversed IR-exo-induced ferroptosis in non-irradiated B cells. Moreover, CDKN1A inhibition partially counteracted the suppressive effect of miR-34a-5p knockdown on non-irradiated B cell ferroptosis.ConclusionsOur findings suggest that irradiated exosomal miR-34a-5p promotes non-irradiated B cell ferroptosis through CDKN1A, uncovering a novel mechanism for RIBE and offering a new therapeutic target for radioprotection.

ObjectivesUpper respiratory tract infections pose a significant challenge for healthcare systems worldwide. Forming biofilms-complex polymicrobial communities encased in an exopolymer matrix plays a pivotal role in the persistence of these infections, contributing to enhanced resistance against conventional treatments and host immune responses. Consequently, developing innovative strategies to disrupt biofilms has become a therapeutic imperative.This study investigated the in vitro efficacy of a hypertonic solution of salsobromoiodic thermal water, in mitigating biofilm formation by key upper respiratory tract pathogens.MethodsBiofilm formation by Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Candida albicans, Candida parapsilosis, and Candida tropicalis was assessed using the MBEC Assay® system. The effects of the hypertonic salsobromoiodic thermal water solution were compared with standard saline (0.9 % NaCl).ResultsA significant, concentration-dependent reduction in biofilm biomass was observed in all tested microorganisms when treated with the hypertonic solution. This effect was also evident in polymicrobial biofilms, indicating a broad and consistent antibiofilm potential.ConclusionsThe hypertonic solution of salsobromoiodic thermal water demonstrated notable in vitro activity against biofilm formation by major upper respiratory tract pathogens. These findings highlight its potential as novel therapeutic approach for managing biofilm-associated respiratory infections and enhancing conventional antimicrobial treatments effectiveness.

AimThe aim of this study was to assess the prognostic performance of the C-reactive protein-to-albumin ratio (CAR) in predicting mortality and amputation of peripheral artery disease (PAD) patients undergoing endovascular therapy (EVT).MethodsWe conducted a systematic search from the inception date to June 12, 2025, in eight databases and a manual search to cover gray literature. High and low CAR were defined according to the optimal cut-off from each study. Meta-analysis was performed to pool prognostic performance.ResultA total of 1,451 subjects from five observational studies were included. The prevalence of mortality and amputation was 4.7 and 21.4%, respectively. Pre-procedural high CAR was associated with a higher risk of mortality (risk ratio [RR] 3.11; 95% confidence interval [CI] 1.22–8.18; I2 = 40%) and amputation (RR 3.62; 95% CI 1.98–6.63; I2 = 10%). The area under the receiver operating characteristic (ROC) curve of the summary ROC curve of high CAR was 0.75 (sensitivity 77% and specificity 56%) for mortality and 0.85 (sensitivity 85% and specificity 52%) for amputation. The positive predictive value of CAR to predict mortality and amputation was 29.9 and 10.5%, respectively, while the negative predictive value was 90.5 and 97.8%, respectively.ConclusionCAR was a potential prognostic biomarker to predict mortality and amputation in PAD patients undergoing EVT.

BackgroundHypoxia and glycolysis play crucial roles in tumor progression, yet their association with kidney renal clear cell carcinoma (KIRC) remains unclear. Here, a novel prognostic model was developed with hypoxia–glycolysis-related genes (HGRGs) in KIRC, providing insights to elucidate the aforementioned uncertainties.MethodsTranscriptomic information and clinical characteristics of KIRC were acquired from The Cancer Genome Atlas Program, ArrayExpress database, and Gene Expression Omnibus. Significant HGRGs were identified, and a prognostic model was constructed. We performed enrichment analysis, tumor mutational burden (TMB), tumor microenvironment), and drug sensitivity analyses to elucidate potential mechanisms of HGRGs.ResultsThe prognostic model based on five HGRGs (ADORA2B, TGFA, FBP1, HK3, PDHB) effectively predicted the clinical outcome. The nomogram, which integrates a prognostic model and clinical information, demonstrated superior performance. Low-risk patients were enriched in fatty acid metabolism and peroxisome pathways, exhibited higher immunotherapy responsiveness, and showed greater sensitivity to Gefitinib and Afatinib. High-risk patients exhibited activation of inflammatory and profibrotic pathways, an elevated TMB, immunosuppressive microenvironments, and greater sensitivity to Topotecan and Irinotecan. RT-qPCR validated the expression of HGRGs across selected cell lines.ConclusionsThe prognostic model derived from five HGRGs demonstrates excellent clinical value in predicting prognosis and guiding therapeutic strategies in KIRC.

ObjectiveTo investigate the role and underlying mechanisms of colony-stimulating factor 2 (CSF2) in the progression of kidney renal clear cell carcinoma (KIRC).MethodsTranscriptomic and clinical data from The Cancer Genome Atlas were analyzed to assess the correlation between CSF2 expression, clinicopathological features, and patient prognosis. A neutrophil–tumor co-culture system was established to examine the effects of CSF2 on neutrophil polarization, tumor cell proliferation, migration, apoptosis, and autophagy. Protein expression was evaluated by flow cytometry, Western blot, and immunofluorescence. PD-L1 knockout and autophagy inhibitors (3-methyladenine and chloroquine) were used to explore regulatory mechanisms.ResultsCSF2 expression was significantly upregulated in KIRC tissues and was positively associated with advanced tumor stage and poor prognosis. In vitro, CSF2 promoted neutrophil polarization toward the tumor-supportive N2 phenotype and enhanced the proliferation and migration of renal cancer cells while inhibiting apoptosis and reactive oxygen species production. Additionally, CSF2 upregulated PD-L1 expression in tumor cells and activated autophagy by increasing LC-3, Beclin1, and ATG7 levels. These effects were reversed by PD-L1 knockout or treatment with the autophagy inhibitor 3-methyladenine.ConclusionCSF2 promotes KIRC progression through PD-L1–mediated neutrophil polarization and autophagy activation, representing a potential therapeutic target.

BackgroundThyroid cancer is the most common malignancy of the endocrine system, and effective treatments for metastatic disease are still lacking. Targeting both glycolysis and oxidative phosphorylation (OXPHOS) simultaneously represents a novel approach to cancer therapy. While polyphyllin has been shown to modulate cellular metabolism in various cancers, its role in thyroid cancer remains unexplored.PurposeThis study aimed to explore the antitumor effects and underlying mechanisms of polyphyllin in thyroid cancer.MethodsThyroid cancer cells were treated with varying concentrations of Polyphyllin I, II, VI, and VII. Cell viability was assessed using the CCK-8 assay to identify the most effective polyphyllin compound and its optimal dosage. Colony formation and EdU incorporation assay were performed to evaluate cell proliferation, while Transwell assays were used to assess cell invasion. Cell migration ability was examined using the wound healing assay. The effect of Polyphyllin II on OXPHOS was evaluated using an extracellular oxygen consumption rate (OCR) assay kit. Glucose uptake, lactate production, glycolysis-related protein expression, and the extracellular acidification rate (ECAR) were measured to assess the effects of Polyphyllin II on glycolysis in thyroid cancer cells. Flow cytometry and western blotting were conducted to detect apoptosis.ResultsPolyphyllin I, II, VI, and VII all inhibit the proliferation of thyroid cancer cells, with Polyphyllin II showing the most potent inhibitory effect. Polyphyllin II suppresses cell proliferation, invasion, and migration of thyroid cancer cells, while also promoting apoptosis. Mechanism studies reveal that Polyphyllin II inhibits extracellular OCR, basal respiration, maximum respiration, ATP-linked respiration, spare respiration capacity, glucose uptake, lactate production, glycolytic rate-limiting enzymes, and the ECAR in thyroid cancer cells.ConclusionPolyphyllin II simultaneously inhibits glycolysis and OXPHOS, thereby suppressing the invasion, migration, and proliferation of thyroid cancer cells, while also promoting apoptosis.

BackgroundPatients with locally advanced breast cancer (LABC) and type 2 diabetes mellitus (T2DM) confront dual challenges: hormone-driven tumor progression and metabolic dysregulation. Although metformin has shown antitumor potential, its effect on estrogen modulation and synergy with nursing care remains unclear in clinical settings.PurposeTo investigate the impact of metformin on estrogen regulation and prognosis-related nursing outcomes in patients with LABC and T2DM.MethodsThis multicenter retrospective cohort study with a prospective randomized intervention component evaluated clinical, metabolic, and care-related indicators during the perioperative period. Serum estradiol (E2) was measured at baseline, post-chemotherapy, and 30 days post-surgery. Glucose metabolism was assessed by fasting blood glucose, HbA1c, and CV%, alongside hypoglycemia monitoring. Care quality metrics included wound healing time, infection rate, chemotherapy adherence, and hospital stay length. Survival outcomes (36-month PFS and OS) were analyzed via Kaplan–Meier curves and Cox models adjusted for age, BMI, and tumor stage. Statistical analysis used SPSS 26.0; continuous variables were expressed as mean ± SD, compared with t-tests; HRs and 95% CIs were reported with P < 0.05 considered significant.ResultsMetformin led to a 19.3% reduction in E2 levels post-chemotherapy, with sustained suppression, outperforming the control group. Glycemic metrics improved: fasting glucose compliance rose to 83.3%, CV% decreased by 38.2%, and hypoglycemia dropped by 66.7%. Wound healing time was shortened by 3.3 days. Chemotherapy adherence reached 92.8% (vs 73.6%) and self-care scores improved by 25.8% (vs 7.2%). Mechanistic analysis indicated enhanced immune microenvironment regulation and reduced pro-inflammatory cytokines.ConclusionMetformin, combined with structured nursing care, significantly improves estrogen control, metabolic stability, and survival in LABC patients with T2DM. These findings support its role in integrated pharmaco-nursing management of tumor-metabolic comorbidities.

Background and objectiveThe World Health Organization (WHO) appeal of January 15, 2024, stated “The current number, size and concurrence of multiple outbreaks, the spread to areas free of cholera for decades and alarmingly high mortality rates present a major threat to global health security.” The current state is extremely worrying, considering the difficulties of countries in dealing with cholera epidemics due to the lack of funding and the difficulty in oral cholera vaccine production and administration. This study aims to analyse the past and current influence of anthropization on cholera onset.MethodsWe analysed the literature, particularly of the last 5 years, on the influence of human actions that impact the spread of cholera.ResultsThe epidemiological data published by WHO and the available literature highlight a strong impact of human actions on the epidemic spread of cholera, the government’s difficulty in making decisions on epidemic prevention or containment, and the fear of the population.ConclusionsCholera should be considered an anthropogenic disaster, considering the historical health analysis of the cholera epidemics in Italy in the last two centuries and in southern Italy and in Naples in 1973.

ObjectiveEndotoxin tolerance (ET) has been demonstrated to attenuate the inflammatory response in murine models of sepsis. This study seeks to elucidate the underlying mechanisms by which ET modulates inflammation in sepsis, with a particular focus on macrophage autophagy.MethodsAn in vivo sepsis model was generated using cecal ligation and perforation, while an in vitro model of inflammatory injury was induced via lipopolysaccharide (LPS) administration. ET was established through pretreatment with low-dose LPS. Subsequent analyses were conducted to assess the presence of the NLRP3 inflammasome, autophagic flux, and the expression levels of TRIM26.ResultsHeightened inflammation was observed in the TNF-α levels and various organs of the sepsis group; conversely, inflammation was reduced in the group receiving ET treatment. Upon stimulation with LPS, primary mouse peritoneal macrophages exhibited activation of the NLRP3 inflammasome and autophagy, accumulation of mitochondrial reactive oxygen species, compromised membrane potential, resulting in cell apoptosis, and decreased expression of TRIM26. ET was found to enhance autophagy, suppress the activation of NLRP3 inflammasomes, and upregulate the expression of TRIM26. Interestingly, modulation of autophagy levels either reversed or intensified the protective effects of ET on macrophages in vitro. Knockdown of TRIM26 using small interfering RNA (siRNA) resulted in increased NLRP3 inflammasome activation and accumulation of P62.ConclusionWe reveal that ET restores the autophagic flux in macrophages, inhibit NLRP3 inflammasome activation, and mitigate inflammatory damage in septic mice, potentially through the regulation of TRIM26.

ObjectiveTo investigate the impact of circASH1L on subcutaneous tumor growth in nude mice with triple-negative breast cancer via the PI3K/AKT pathway.MethodsThe study was conducted using bioinformatics and animal experimental verification methods. circASH1L levels in triple-negative breast cancer (TNBC) were analyzed using a dataset from the gene expression omnibus database. In the animal experiment part, nude mice were divided into shNC group, shcircASH1L-1 group, Oe-NC group, and Oe-circASH1L group. Each group was treated with corresponding circASH1L overexpression or knockdown and transplanted tumor modeling. Immunohistochemistry and western blot experiments were used to verify the effect of circASH1L on the growth of nude mouse transplanted tumors and the PI3K/AKT pathway.ResultsA total of 43 circRNAs were significantly associated with TNBC, among which circASH1L was significantly highly expressed in TNBC. circASH1L-1 negatively regulates tumor volume, mass, expression rate of Ki67 cells, and PI3K/AKT pathway marker proteins.ConclusionsCircASH1L is a tumor promoter in TNBC. The expression level of circASH1L influences both the proliferation of TNBC cells and the growth of TNBC nude mice tumors by modulating the PI3K/AKT pathway.