Biomedicines最新文献

{"title":"Longitudinal Sodium Dynamics After Aneurysmal Subarachnoid Hemorrhage: A Single-Center Cohort Study with a Contemporary Literature Review.","authors":"Adrianna Lebiedzińska, Jarosław Kędziora, Jowita Woźniak, Katarzyna Smarzewska, Waldemar Goździk, Małgorzata Burzyńska","doi":"10.3390/biomedicines14092081","DOIUrl":"10.3390/biomedicines14092081","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Disorders of sodium homeostasis are common after aneurysmal subarachnoid hemorrhage (aSAH), but the prognostic value of longitudinal sodium dynamics remains unclear. We evaluated whether dynamic sodium parameters provide prognostic information beyond admission sodium concentration. <b>Methods:</b> This retrospective cohort study included 232 consecutive patients with angiographically confirmed aSAH admitted between January 2014 and December 2025. Serial serum sodium measurements were used to assess admission sodium, mean sodium, interday sodium variability, and hypernatremia burden. Associations with clinical outcomes were evaluated using multivariable regression, survival analysis, receiver operating characteristic analysis, and linear mixed-effects models. A landmark analysis was performed to assess the prognostic value of sodium variability during the first 5 days after admission. <b>Results:</b> Admission sodium concentration showed limited discrimination for 30-day mortality (area under the curve [AUC] 0.606, 95% confidence interval [CI] 0.509-0.703). Greater interday sodium variability was independently associated with mortality (odds ratio [OR] 1.55, 95% CI 1.29-1.86; <i>p</i> < 0.001) and remained significant after adjustment for severe hypernatremia (OR 1.32, 95% CI 1.09-1.60; <i>p</i> = 0.005). Adding interday variability to the baseline clinical model improved its discriminative performance (AUC 0.845 vs. 0.899; ΔAUC 0.054, 95% CI 0.010-0.099; <i>p</i> = 0.017). The association remained significant in the adjusted landmark analysis (hazard ratio [HR] 1.21, 95% CI 1.13-1.29; <i>p</i> < 0.001). Greater sodium variability was also associated with poorer neurological outcomes. <b>Conclusions:</b> Longitudinal sodium dynamics provide prognostic information beyond admission sodium concentration in patients with aSAH. Greater interday sodium variability was independently associated with 30-day mortality and remained robust after accounting for potential immortal-time bias. Prospective multicenter studies are warranted to validate its prognostic value and the cohort-derived variability threshold.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitoylethanolamide as an Intestinal Gatekeeper: Linking Inflammation, Angiogenesis and Colorectal Cancer Interception.","authors":"Irene Palenca, Giovanni Sarnelli, Giuseppe Esposito","doi":"10.3390/biomedicines14092080","DOIUrl":"10.3390/biomedicines14092080","url":null,"abstract":"<p><p>Angiogenesis is a major determinant of tumor growth, progression and metastatic potential, and its persistent activation is closely intertwined with chronic inflammation. This relationship is particularly relevant in malignancies that arise through a prolonged inflammation-to-carcinogenesis continuum, where pathological vascular remodeling can sustain tissue hypoxia, immune-cell recruitment and the establishment of a tumor-permissive microenvironment. Colorectal cancer (CRC), especially in inflammation-associated settings, represents a paradigmatic example in which the inflammatory-angiogenic axis contributes to disease progression and unfavorable prognosis. Accordingly, identifying well-tolerated strategies capable of restraining pathological angiogenic pressure before overt neoplasia is established may have important preventive and therapeutic implications. This perspective focuses on palmitoylethanolamide (PEA), an endogenous N-acylethanolamine and prototypical autacoid local injury antagonist amide (ALIAmide) generated on demand as part of tissue homeostasis. PEA may act within a proposed multilevel intestinal homeostatic framework by preserving epithelial barrier integrity, limiting inflammatory amplification, modulating PPARα-dependent signaling and mast-cell reactivity, and restraining pro-angiogenic pathways, with context- and compartment-dependent effects on Akt/mTOR-HIF-1α/VEGF signaling. Importantly, direct preclinical evidence now supports PEA-related chemoprevention at two complementary levels: ultramicronized PEA reduced colon cancer cell proliferation and migration and decreased preneoplastic lesions and tumors in the murine azoxymethane model, whereas NAPE-PLD-engineered <i>Lactobacillus paracasei</i> F19 (pNAPE-LP) increased local PEA and reduced tumor burden, epithelial proliferation and angiogenesis in AOM/DSS colitis-associated CRC while modulating Akt/mTOR/p70S6K-HIF-1α signaling. These findings move the PEA-CRC relationship beyond a purely hypothetical association while remaining preclinical. We therefore propose that reinforcement of PEA signaling, through supplementation, PEA-oriented pharmacological strategies or engineered local biosynthesis, deserves investigation as a cancer-interception approach aimed at maintaining angiogenic and inflammatory homeostasis before autonomous tumor biology becomes established. This concept should not be interpreted as established clinical CRC prevention or as a substitute for conventional anticancer therapy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Admission Serum Sodium as an Early Integrative Marker of Shock Severity in Acute Myocardial Infarction-Complicated Cardiogenic Shock.","authors":"Xi Wang, Qianfeng Xiao, Fangyang Huang, Si Wang, Ying Xu, Mao Chen, Xin Wei","doi":"10.3390/biomedicines14092086","DOIUrl":"10.3390/biomedicines14092086","url":null,"abstract":"<p><p><b>Background</b>: Serum sodium is an important laboratory value in hospitalized patients, but its relationship with mortality in patients with cardiogenic shock complicated by acute myocardial infarction (AMI-CS) has not been evaluated. We assessed the association between admission serum sodium and mortality in AMI-CS. <b>Methods</b>: A total of 312 patients with AMI-CS treated at a single center were retrospectively enrolled in this study. The primary endpoint was all-cause mortality. Patients were divided into three groups by tertiles based on admission serum sodium levels. The prognostic value of admission serum sodium levels was evaluated using Kaplan-Meier survival curves and Cox regression. Restricted cubic splines, subgroup analyses, and sensitivity analyses were also performed. Results: Over a follow-up of 4.5 years, 51.9% of enrolled patients died. In unadjusted analyses, higher admission serum sodium was associated with mortality, as well as rates of sepsis, dialysis, and brain injury during hospitalization, and patients with sodium > 141.2 mmol/L had higher short-term mortality; a J-shaped relationship was observed on unadjusted spline analysis. However, this association did not persist after adjustment for shock severity: the fully adjusted hazard ratio per 1 mmol/L was 1.02 (95% CI 0.98-1.06, <i>p</i> = 0.46) for long-term and 1.03 (95% CI 0.98-1.07, <i>p</i> = 0.28) for 30-day mortality, and the spline association was no longer significant (<i>p</i> for overall association = 0.40; <i>p</i> for nonlinearity = 0.33). Adding severity variables one at a time showed that the association was abolished specifically by arterial lactate. <b>Conclusions</b>: Higher admission serum sodium is associated with mortality in AMI-CS, but this association is largely explained by concurrent shock severity, particularly hyperlactatemia. Admission sodium may serve as an early, readily available integrative marker of shock severity for risk stratification, but whether sodium-directed treatment strategies affect outcomes requires prospective study.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Elalfy et al. ATT-Myc Transgenic Mouse Model and Gene Expression Identify Genotoxic and Non-Genotoxic Chemicals That Accelerating Liver Tumor Growth in Short-Term Toxicity. <i>Biomedicines</i> 2025, <i>13</i>, 743.","authors":"Mahmoud Elalfy, Ahmed Jaafar Aljazzar, Mona G Elhadidy","doi":"10.3390/biomedicines14092085","DOIUrl":"10.3390/biomedicines14092085","url":null,"abstract":"<p><p>The journal retracts and amends the authorship list of the article titled \"ATT-Myc Transgenic Mouse Model and Gene Expression Identify Genotoxic and Non-Genotoxic Chemicals That Accelerating Liver Tumor Growth in Short-Term Toxicity\" [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathogenesis of Immune-Mediated Necrotizing Myopathy: Insights Drawn from Pathological Phenotypes and Mechanistic Elaboration.","authors":"Xiaoke Wu, Junjie Qian, Xin Wang, Na Ji, Yingning Li, Shuying Chen, Qingjie Li, Meirong Liu, Qi Fang","doi":"10.3390/biomedicines14092087","DOIUrl":"10.3390/biomedicines14092087","url":null,"abstract":"<p><p>Immune-mediated necrotizing myopathy (IMNM) is a distinct subtype of idiopathic inflammatory myopathies (IIMs), classified by serum autoantibody status into anti-signal recognition particle (anti-SRP)-positive, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR)-positive, and seronegative subgroups. Its hallmark is a pathological paradox: extensive myofiber necrosis and regeneration accompanied by strikingly sparse inflammatory infiltrates, a feature that distinguishes IMNM from dermatomyositis and inclusion body myositis. In this review, we integrate preclinical and clinical evidence to build an immune-mechanistic pathogenesis model grounded in pathological observations: anti-SRP and anti-HMGCR autoantibodies trigger myofiber injury via both complement-dependent and complement-independent pathways; necrotic myofibers release damage-associated molecular patterns (DAMPs) that activate Toll-like receptor signaling, thereby establishing a complement-independent, self-perpetuating injury-amplification loop; T-cell-dominated adaptive-immune responses, characterized by Th1-M1 pathway activation alongside widespread T-cell exhaustion, may only function as a secondary modulator; and aberrant vascular remodeling coupled with impaired tissue regeneration contributes to long-term prognosis. Variations in macrophage polarization, angiogenic potential, and malignancy risk between anti-SRP-positive and anti-HMGCR-positive IMNM may constitute intrinsic drivers underlying their disparate histopathological features, clinical trajectories, and treatment responses. This model accounts for the limited therapeutic benefit observed with complement-blockade monotherapy and proposes that regimens combining autoantibody suppression with the inhibition of necrosis-driven injury amplification could yield improved clinical outcomes, providing a theoretical basis for pathological subtyping and stratified therapy in IMNM.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Mistargeting During Direct Cardiac Reprogramming: Cardiac-Associated Responses, Polarization, and Cell Death.","authors":"Tingzhen Chen, Shanshan Ding, Zhongwen Zhang, Lin Zhao, Kejun Cao, Guannan Zhang, Changya Weng, Guangyuan Gong, Liang Xu, Min Yang, Tianquan Li, Chengyu Sheng, Yanxiu Li","doi":"10.3390/biomedicines14092089","DOIUrl":"10.3390/biomedicines14092089","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In situ reprogramming of cardiac fibroblasts into induced cardiomyocytes (iCMs) holds great promise for myocardial infarction (MI) therapy by replenishing lost cardiomyocytes. A transcription factor cocktail consisting of Mef2c, Gata4, and Tbx5 (MGT) represents a widely used starting regimen for cardiac reprogramming, with numerous optimization efforts focused primarily on improving reprogramming efficiency. However, the effects of MGT exposure on non-target cardiac cell populations remain largely uncharacterized, and it remains unclear whether such unintended effects could pose safety concerns. <b>Methods</b>: In this study, we introduced the widely used MGT cocktail into primary mouse bone marrow-derived macrophages (BMDMs) and the immortalized mouse macrophage cell line RAW 264.7. We first assessed cardiomyocyte-associated gene and protein expression. We then examined the polarization state of transduced RAW 264.7 cells. In BMDMs, we further assessed apoptosis- and necroptosis-associated markers to determine whether MGT delivery was accompanied by cell death. <b>Results</b>: (a) MGT introduction induced a transient increase in cardiomyocyte-associated Tnnt2/Myh6 transcripts and modest cTnT protein induction in macrophages, with cTnT immunofluorescence remaining elevated after two weeks in BMDMs and a small subset of cells displaying fibroblast-like morphology reminiscent of iCMs. (b) Transduced RAW 264.7 cells displayed elevated Cd206 transcript levels, accompanied by an increased proportion of spindle-like cells and enlarged nuclear area, collectively supporting an M2-like polarization shift. (c) Transduced primary BMDMs, but not RAW 264.7 cells, displayed elevated apoptosis- and necroptosis-associated responses, including increased YP1 fluorescence, PI staining, and p-MLKL immunofluorescence. <b>Conclusions</b>: The classical MGT reprogramming regimen polarized RAW 264.7 cells toward an M2-like state, raising the possibility that, in the TGF-β-rich post-MI environment, this shift could increase the pool of macrophages susceptible to macrophage-to-myofibroblast transition and thereby potentially promote fibrosis. MGT-expressing LV elicited apoptosis-associated and necroptosis-associated changes in transduced BMDMs. These polarization and cell-survival effects highlight potential off-target and safety concerns for in situ direct cardiac reprogramming. Further investigations are warranted to determine whether and how such macrophage perturbations affect tissue remodeling and therapeutic outcomes in the post-MI setting.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-24 Induces Inflammatory Chemokine and Cytokine Responses in Fibroblast-Enriched Synovial Cells from Patients with Knee Osteoarthritis.","authors":"Yui Uekusa, Kentaro Uchida, Makoto Itakura, Naoya Shibata, Manabu Mukai, Dai Iwase, Jun Aikawa, Ayumi Tsukada, Yukie Metoki, Gen Inoue, Masashi Takaso","doi":"10.3390/biomedicines14092084","DOIUrl":"10.3390/biomedicines14092084","url":null,"abstract":"<p><p><b>Background:</b> Interleukin-24 (IL-24) is expressed in synovial myofibroblasts and has been associated with pain severity in female patients with knee osteoarthritis (OA). However, the direct effects of IL-24 on inflammatory responses in synovial fibroblasts and the signaling pathways involved remain unclear. This study investigated IL-24-induced transcriptional and inflammatory responses in fibroblast-enriched synovial cells and examined the effects of STAT3 and p38 mitogen-activated protein kinase (MAPK) inhibition. <b>Methods:</b> Fibroblast-enriched synovial cells isolated from synovial tissue obtained from patients with knee OA undergoing total knee arthroplasty were stimulated with IL-24 for 6 and 24 h. RNA sequencing (RNA-seq) was performed using cells from two patients, and overlapping upregulated genes were subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The concentration- and time-course experiment used samples from nine patients; the HJC0152 and SB203580 experiments used ten specimens from eight patients and ten specimens from nine patients, respectively. Selected inflammatory cytokines and chemokines were subsequently evaluated by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay in concentration- and time-course experiments using nine specimens from nine patients. To investigate signaling involvement, cells were treated with IL-24 in the presence or absence of the STAT3 inhibitor HJC0152 or the p38 MAPK inhibitor SB203580, each at 5 or 10 μM. <b>Results:</b> RNA-seq identified 27 and 34 overlapping upregulated genes that independently met the DEG criteria in both patients at 6 and 24 h, respectively. These genes were enriched in inflammatory pathways, including TNF, IL-17, NF-κB, chemokine, cytokine-cytokine receptor interaction, Toll-like receptor, and NOD-like receptor signaling pathways. IL-24 significantly increased the mRNA expression of <i>CCL2</i>, <i>CXCL1</i>, <i>CXCL3</i>, <i>IL6</i>, and <i>IL8</i>. HJC0152 and SB203580 at 10 μM both significantly reduced IL-24-associated <i>CCL2</i>, <i>CXCL1</i>, and <i>IL6</i> expression. At the protein level, both inhibitors attenuated CCL2, CXCL1, and IL-6 concentrations in IL-24-stimulated cells. HJC0152 also reduced <i>CXCL3</i> expression at the mRNA level, although its protein-level effect was less pronounced. In contrast, the effects of both inhibitors on CXCL3, CXCL10, and IL-8 were limited or inconsistent. <b>Conclusions:</b> IL-24 induces an inflammatory response in fibroblast-enriched synovial cells characterized by increased chemokine and cytokine expression. STAT3 and p38 MAPK inhibition preferentially attenuated IL-24-associated CCL2, CXCL1, and IL-6 responses, suggesting the possible involvement of these pathways in selected IL-24-associated inflammatory responses. These findings provide a basis for further investigation of IL-24-related signaling in OA synovitis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lichen-Derived Bioactive Compounds in Diabetes and Cardiovascular Risk: Experimental Evidence, Mechanisms, and Translational Challenges.","authors":"Alfredo Torres-Benítez, Carlo Acierno, Davide Nilo, Roberta Cutellè, Karla Troncoso-Monsalve, Sebastián Aburto-Urriaga, Francisco Novoa-Sánchez, Ferdinando Carlo Sasso, Vincenzo Russo, Alfredo Caturano","doi":"10.3390/biomedicines14092083","DOIUrl":"10.3390/biomedicines14092083","url":null,"abstract":"<p><p>Cardiometabolic disorders arise from interconnected metabolic, inflammatory, oxidative, mitochondrial, and vascular abnormalities. Lichens produce structurally diverse secondary metabolites, including depsides, depsidones, dibenzofurans, anthraquinones, and other phenolic compounds, whose experimental activities intersect several of these pathways. This narrative review examines the chemical diversity, biological actions, and translational potential of lichen-derived compounds in diabetes and cardiovascular risk modulation. Available studies describe antioxidant, anti-inflammatory, enzyme-inhibitory, antiglycation, cytoprotective, and vasomodulatory effects, but the evidence is predominantly based on chemical assays, molecular docking, in vitro experiments, and heterogeneous preclinical models. Direct demonstrations of improved insulin sensitivity, pancreatic β-cell function, endothelial function, lipid handling, or atherosclerosis remain limited, and human efficacy data are lacking. Translation is further constrained by incomplete chemical standardisation, uncertain bioavailability and target-tissue exposure, limited interaction data, and safety concerns. Usnic acid illustrates the central challenge: broad biological activity coexists with mitochondrial toxicity and clinically relevant hepatotoxic potential. Lichen metabolites therefore currently represent pharmacological probes and medicinal-chemistry scaffolds rather than clinically applicable interventions for diabetes or cardiovascular risk reduction. Future development requires compound-specific target validation, reproducible preparations, pharmacokinetic characterisation, functional disease endpoints, and rigorous safety assessment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effects of Carboplatin, Metformin, and Boric Acid on Cell Viability, Migration, and Oxidative Stress in MCF-7 Breast Cancer and CRL-4010 Normal Mammary Epithelial Cells.","authors":"Nilüfer Ece Süren, Burcu Biltekin, Sevgin Degirmencioglu, Hafize Uzun, Ayhan Bilir","doi":"10.3390/biomedicines14092073","DOIUrl":"10.3390/biomedicines14092073","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Oxidative stress is a key contributor to breast cancer (BC) progression and therapeutic response. Although carboplatin is widely used in BC treatment, the effects of combining carboplatin with metformin and boric acid (BA) on cellular redox homeostasis remain poorly understood. This study investigated the effects of these agents on cell viability, migration, and oxidative stress in BC and normal mammary epithelial cells. <b>Methods:</b> Human BC MCF-7 cells and normal mammary epithelial CRL-4010 cells were treated with carboplatin, metformin, BA, and selected combination regimens. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay following 24, 48, and 72 h of treatment. Cell migration was evaluated using a scratch wound-healing assay, and intracellular oxidative stress responses were assessed by measuring superoxide dismutase (SOD) activity. Statistical analyses were performed using one-way ANOVA followed by Fisher's least significant difference (LSD) post hoc test. <b>Results:</b> Treatment responses were both time- and treatment-dependent in MCF-7 and CRL-4010 cells. Combination regimens significantly reduced cell viability after 48 and 72 h (all <i>p</i> < 0.0001) and generally exhibited greater inhibitory effects than single-agent treatments. Metformin- and BA-containing combinations also produced more pronounced inhibition of cell migration. Significant treatment-related alterations in SOD activity were observed in both cell lines, indicating treatment-associated changes in antioxidant enzyme activity. While several combination regimens decreased SOD activity, others induced increased SOD activity, suggesting differential oxidative stress responses between malignant and non-malignant cells. <b>Conclusions:</b> Carboplatin, metformin, and BA significantly modulated cell viability, migration, and antioxidant responses in both BC and normal mammary epithelial cells. Combination treatments generally produced greater inhibitory effects on cell viability and migration than selected single-agent treatments, particularly in MCF-7 cells. These findings demonstrate treatment-dependent changes in cell viability, migration, and SOD activity and provide a basis for further investigation of the molecular mechanisms underlying carboplatin-based combination treatments.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress Urinary Incontinence as a Chronic Stress Model: Clinical Evidence and Emerging Epigenetic Implications for Mental Disorders.","authors":"Despoina Drivakou, Nikolaos Roussos, Iakovos Theodoulidis, Konstantinos Dinas, Themistoklis Mikos, Mary H Kosmidis","doi":"10.3390/biomedicines14092075","DOIUrl":"10.3390/biomedicines14092075","url":null,"abstract":"<p><p>Stress urinary incontinence (SUI) is conventionally viewed as a peripheral mechanical disorder, yet its psychological burden suggests that a broader biopsychosocial interpretation may be warranted. This perspective considers whether recurrent leakage, anticipatory anxiety, behavioural avoidance, and social evaluative threat may allow SUI to function as a chronic psychosocial stressor. It integrates clinical observations with established concepts in stress physiology, hypothalamic-pituitary-adrenal (HPA) axis regulation, allostatic load, inflammation, and stress-related epigenetic mechanisms, including FKBP5 and NR3C1. Direct molecular evidence in SUI populations remains limited; therefore, the proposed links are presented as a hypothesis-generating framework rather than as established causal pathways. The framework further emphasises the heterogeneity of patient outcomes. Differences in perceived symptom burden, coping, stress responsivity, prior vulnerability, and resilience may help explain why psychological symptoms improve after treatment in some individuals yet persist in others. These interacting psychosocial and biological processes may reinforce a feedback loop between symptom-related threat, sustained stress activation, and affective vulnerability. By moving beyond a solely mechanical model, this perspective supports a more interdisciplinary approach combining urogynecological and psychological assessment. The proposed stress-epigenetic framework is intended to guide future longitudinal and biomarker-informed research and to encourage more integrated approaches to the prevention and management of psychological burden in SUI.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}