Biomedicine & Pharmacotherapy最新文献

{"title":"Mitigation of biochemical stress response effects in Swiss albino mice via Syzygium cumini and Nigella sativa seed extract dietary supplementation following deltamethrin exposure","authors":"Anupam Kumar ,&nbsp;Joydeep Dutta ,&nbsp;Anand Mohan ,&nbsp;Neeta Raj Sharma ,&nbsp;Gaurav Kumar ,&nbsp;Arun Karnwal ,&nbsp;Tabarak Malik","doi":"10.1016/j.biopha.2025.118585","DOIUrl":"10.1016/j.biopha.2025.118585","url":null,"abstract":"<div><div>Deltamethrin, a synthetic pyrethroid pesticide, is known to induce significant oxidative stress and immunotoxicity upon prolonged exposure. This study investigates the biochemical and physiological impact of deltamethrin on Swiss albino mice and explores the protective potential of <em>Syzygium cumini</em> and <em>Nigella sativa</em> seed extracts. Mice were grouped and administered deltamethrin (18 mg/kg) alone or in combination with seed extracts (100 mg/kg each), and biochemical, hematological, and organ-specific parameters were assessed. Deltamethrin exposure led to marked reductions in body and organ weights, altered hematological indices (e.g., elevated WBC, reduced Hb), and significant changes in serum biomarkers, including elevated ALT, AST, ALKP, cholesterol, and creatinine—indicating hepatic and renal stress. Supplementation with <em>S. cumini</em> and <em>N. sativa</em> extracts ameliorated these effects, as seen by normalized organ weights, improved blood profiles, and reduced enzyme levels. The combined extract treatment exhibited synergistic protective effects. These findings suggest that dietary supplementation with antioxidant-rich seed extracts can effectively mitigate deltamethrin induced biochemical stress, highlighting their potential as natural protective agents in pesticide-exposed systems.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118585"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of bispecific antibody formats targeting PD-1 and LAG-3 for dual checkpoint blockade in cancer immunotherapy","authors":"Jie Wang ,&nbsp;Ning Shi ,&nbsp;Pinnan Zhao ,&nbsp;Yangyihua Zhou ,&nbsp;Juan Tian ,&nbsp;Yaowei Ma ,&nbsp;Xuechen Yang ,&nbsp;Jiannan Feng ,&nbsp;Chunxia Qiao ,&nbsp;Xinying Li ,&nbsp;Yan Zhang ,&nbsp;Xiang Gao ,&nbsp;Longlong Luo","doi":"10.1016/j.biopha.2025.118583","DOIUrl":"10.1016/j.biopha.2025.118583","url":null,"abstract":"<div><div>Bispecific antibodies (BsAbs) targeting PD-1 and LAG-3 offer a promising strategy in cancer immunotherapy by enhancing antitumor immunity and overcoming resistance to PD-1 blockade. Despite the growing interest in PD-1/LAG-3 BsAbs, a systematic comparison of different BsAbs formats remains lacking, leaving a gap in the rational design of optimized therapeutics. In this study, we systematically compared three BsAb formats—YG-003D1 (Ab-ScFv format), YG-003D2 (DVD format), and YG-003D3 (Knob-into-Hole (KIH) format)—to evaluate their structural, functional, and pharmacokinetic properties, providing critical insights into their therapeutic potential.</div><div>YG-003D1 exhibited the strongest binding and blocking activity due to its tetravalent Ab-ScFv structure, which facilitated dual-target engagement with minimal steric hindrance. However, it had relatively low expression yields and a tendency to form aggregates, which could impact manufacturability and long-term stability. YG-003D2, utilizing a DVD format, exhibited mild steric hindrance in dual-target engagement, leading to a moderate reduction in blocking efficiency, particularly in LAG-3 inhibition. Nonetheless, its bivalency for both PD-1 and LAG-3 may provide advantages in specific therapeutic contexts. In contrast, YG-003D3, with its asymmetric KIH format, demonstrated the most favorable balance of manufacturability, stability, and pharmacokinetics. It had high expression yields, minimal aggregation, and a half-life comparable to IgG, making it the most promising candidate for clinical development. However, its monovalent binding per target resulted in slightly reduced blocking potency compared to YG-003D1.</div><div>While YG-003D3 demonstrated the best overall balance of properties, alternative formats such as YG-003D1 could be refined through Fc engineering or linker optimization to enhance manufacturability and reduce aggregation. Similarly, YG-003D2's steric hindrance could be mitigated by introducing flexible linkers to improve dual-target engagement. Further modifications to YG-003D3, such as affinity tuning or Fc engineering, could enhance its blocking potency while retaining its favorable pharmacokinetics. These insights not only provide a rational framework for PD-1/LAG-3 bispecific inhibitor design but also serve as a reference for broader applications of BsAbs in immunotherapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118583"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normobaric oxygen treatment in a depression-like model in male and female rats – Safety, behavioral benefits, and modulation of serotonin and inflammatory markers","authors":"Sarit Uzzan ,&nbsp;Ira-Sivan Rostevanov ,&nbsp;Ofer Prager ,&nbsp;Haiat Nujedat ,&nbsp;Jacob Kaplanski ,&nbsp;Paul Picton ,&nbsp;Alon Friedman ,&nbsp;Abed N. Azab","doi":"10.1016/j.biopha.2025.118599","DOIUrl":"10.1016/j.biopha.2025.118599","url":null,"abstract":"<div><div>Depression is growingly recognized as a major public health problem. A large body of data supports the notion that alterations in oxygen (O₂) supply to the brain contribute to the pathophysiology of depression. We examined safety and efficacy parameters of chronic normobaric O₂ treatment (NO₂T) in naïve and stress-subjected \"depressed\" rats. Safety parameters – including hematological, biochemical, and respiratory – were tested in naïve rats. Other groups of rats were subjected to a stress protocol and then treated with NO₂T (40 % O₂) for four weeks. Post-stress rats underwent behavioral assessments and evaluations of brain inflammatory mediators and serotonin levels. We found that: i) NO₂T was associated with a high tolerability profile in naïve rats; ii) NO₂T produced a potent antidepressant-like effect as well as other positive behavioral outcomes in post-stress rats; and, iii) NO₂T decreased inflammatory components and kynurenine, and increased serotonin levels in the frontal cortex and hippocampus of post-stress rats. This study provides evidence for the efficacy and safety of NO₂T in a rodent model of depression, highlighting its potential as a novel antidepressant treatment. Further research is needed to explore long-term effects and underlying mechanisms.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118599"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNRF2 integrates ubiquitination-driven ferroptosis and mitochondrial quality control in renal ischemia–reperfusion injury","authors":"Kangyu Wang ,&nbsp;Yun Deng ,&nbsp;Changhong Xu ,&nbsp;Rui Yan ,&nbsp;Hao Wang ,&nbsp;Yalong Zhang ,&nbsp;Jiangwei Man ,&nbsp;Li Yang","doi":"10.1016/j.biopha.2025.118584","DOIUrl":"10.1016/j.biopha.2025.118584","url":null,"abstract":"<div><div>Renal ischemia–reperfusion injury (RIRI) is characterized by a surge of oxidative stress, lipid peroxidation, and mitochondrial dysfunction, leading to ferroptotic tubular cell death and renal impairment. Recent findings implicate ZNRF2, a RING-type E3 ubiquitin ligase localized to the endo‑lysosomal membrane, as a central regulator that integrates ubiquitin-mediated signaling, ferroptosis susceptibility, and mitochondrial quality control (MQC) pathways. In this review, we synthesize current evidence on ZNRF2’s structural features, ubiquitination targets (e.g., GPX4, SLC7A11, NCOA4), and its modulation of key MQC processes—DRP1-driven mitochondrial fission, PINK1–Parkin–mediated mitophagy, and lysosomal clearance via mTORC1/TFEB axis. We propose a temporal model aligning ischemia and reperfusion phases with specific redox and cell-death events, and highlight testable hypotheses such as ZNRF2’s control over GPX4 stability or ferritinophagy dynamics. Moreover, we discuss therapeutic perspectives, including pharmacological modulators of ZNRF2 activity (small‑molecule stabilizers, PROTACs), and timing-based intervention windows. This integrated mechanistic framework advances understanding of RIRI pathogenesis and opens avenues for novel redox-targeted therapeutic strategies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118584"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and future perspectives of drug delivery systems loaded with baicalein and baicalin in cancer therapy","authors":"Amirreza Nazemiyeh ,&nbsp;Samar Mahari ,&nbsp;Nima Nazemiyeh ,&nbsp;Hossein Abdolmohammadzadeh ,&nbsp;Zahra Farshbaf ,&nbsp;Athena Rajabzadeh ,&nbsp;Somayeh Vandghanooni ,&nbsp;Hossein Nazemiyeh ,&nbsp;Morteza Eskandani","doi":"10.1016/j.biopha.2025.118589","DOIUrl":"10.1016/j.biopha.2025.118589","url":null,"abstract":"<div><div>Nano drug delivery systems (NDDSs) have emerged as a transformative approach in cancer therapy, addressing challenges such as drug resistance, poor bioavailability, and off-target toxicity. Baicalein (BA) and baicalin (BI), flavonoids derived from <em>Scutellaria baicalensis</em>, exhibit potent anticancer effects but are limited by low solubility and rapid metabolism. This review classifies BA/BI-loaded NDDS into either organic or inorganic nanoparticles (NPs) and evaluates their current status, focusing on their enhanced pharmacokinetics, targeted delivery, and reduced side effects. We highlight their mechanisms of action, such as induction of apoptosis, inhibition of metastasis, and modulation of signaling pathways (e.g., PI3K/AKT, Wnt/β-catenin), across various cancers, including breast, lung, and colorectal. Preclinical studies demonstrate that BA/BI-loaded NPs significantly improve therapeutic efficacy by leveraging the enhanced permeability and retention (EPR) effect and overcoming multidrug resistance. This review synthesizes these advancements, identifies challenges in clinical translation, such as toxicity and scalability, and proposes future directions for optimizing BA/BI-based NPs for clinical application in oncology.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118589"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors of bias in spheroid-based drug screening: Fabrication method, spheroid size, and cell viability","authors":"Sunghan Lee ,&nbsp;Jiseok Lim ,&nbsp;Bongseop Kwak","doi":"10.1016/j.biopha.2025.118597","DOIUrl":"10.1016/j.biopha.2025.118597","url":null,"abstract":"<div><div>Spheroids have emerged as powerful tools in drug screening by providing a physiologically relevant environment that more closely mimics <em>in vivo</em> conditions compared to 2D cultures. Despite these advantages, experimental outcomes using spheroids are often influenced by considerable variability and bias. This review explores three key factors that affect the evaluation of drug efficacy in spheroids, including fabrication method, spheroid size, and cell viability. First, it compares five commonly used spheroid fabrication platforms, outlining their principles, advantages, and limitations. Second, it examines biological contributors to spheroid size variation, such as cell proliferation, apoptosis, protein expression, and cellular differentiation, and how they affect drug response. Third, it discusses how features such as hypoxic core development and anoikis sensitivity affect cell viability and potentially distort toxicity assessments. This review presents a conceptual framework for minimizing bias and improving reproducibility in spheroid-based drug screening.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118597"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory and inflammasome-modulating effects of Jinmu-Tang, a Korean traditional medicine: Integrated network pharmacology and experimental evaluation in a DSS-induced colitis model","authors":"Jin Ah Ryuk ,&nbsp;Seong Eun Jin ,&nbsp;Ami Lee ,&nbsp;Seol Jang ,&nbsp;Hyunil Ha ,&nbsp;Youn-Hwan Hwang","doi":"10.1016/j.biopha.2025.118587","DOIUrl":"10.1016/j.biopha.2025.118587","url":null,"abstract":"<div><div>Jinmu-tang (JMT) is a traditional Korean medicine that is clinically used to treat inflammatory bowel conditions. Despite its long-standing use, the pharmacological mechanism of action remains unclear. This study investigated the potential therapeutic effects and underlying signaling pathways of JMT in dextran sulfate sodium (DSS)-induced ulcerative colitis using an integrated approach combining network pharmacology with <em>in vitro</em> and <em>in vivo</em> experimental validation. We analyzed 23 active compounds of JMT and predicted their molecular targets using public datasets. The therapeutic efficacy of JMT was evaluated using a DSS-induced colitis mouse model. Colonic tissues were examined using histopathology, immunohistochemistry, and mRNA expression analysis of inflammatory markers. Gut microbiota modulation was assessed using 16S rRNA sequencing and linear discriminant analysis Effect size. The barrier-protective effects of JMT and its major compounds, along with their ability to inhibit inflammasome activation, were investigated using Caco-2 and J774A.1 cells. Network pharmacology analysis of the 23 active compounds revealed the enrichment of inflammation-related biological processes, suggesting potential anti-inflammatory mechanisms. JMT significantly alleviated disease symptoms, reduced inflammatory cytokine expression, and improved intestinal barrier integrity in a DSS-induced colitis mouse model, as confirmed by histological, molecular, and microbiome analyses. <em>In vitro</em> experiments using J774A.1 macrophages demonstrated that treatment with JMT extract and representative compounds suppressed inflammasome activation, as evidenced by reduced IL-1β production, LDH release, and expression of inflammasome-related proteins. JMT exhibited anti-inflammatory effects against ulcerative colitis by targeting inflammation-related pathways and suppressing inflammasome activation, demonstrating its potential as a multi-target therapeutic agent for inflammatory bowel diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118587"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphiregulin reflects brain metastasis progression and leads to PD-L1 expression in non-small cell lung cancer cells","authors":"Dimitri Leite Ferreira ,&nbsp;Tiphaine Biojout ,&nbsp;Céline Bazille ,&nbsp;Maelle Guyot ,&nbsp;Lucie Malandain ,&nbsp;Laureline Charrier ,&nbsp;Jérôme Toutain ,&nbsp;Elodie Peres ,&nbsp;Samuel Valable ,&nbsp;Jeannick Madelaine ,&nbsp;Jérôme Levallet ,&nbsp;Guénaëlle Levallet ,&nbsp;Emmanuel Bergot","doi":"10.1016/j.biopha.2025.118600","DOIUrl":"10.1016/j.biopha.2025.118600","url":null,"abstract":"<div><h3>Background</h3><div>The Hippo kinase Nuclear Dbf2-related kinase 2 (NDR2) promotes brain metastasis (BM) in non-small cell lung cancer (NSCLC) by the disrupting Yes-associated protein 1 (YAP-1), suggesting a role in circulating tumor cells and/or brain colonization. The underlying mechanism remains to be clarified.</div></div><div><h3>Methods</h3><div>Human bronchial epithelial tumor cells (A549, H1975, H2030 and the brain-tropic H2030-BrM3 line) with or without NDR2 depletion (<em>via</em> siRNA or shRNA), were exposed to shear stress (up to 40 dyn/cm² for 3 h) using an Ibidi® pump system, in the presence or absence of exogenous Amphiregulin (AREG), and subsequently reseeded or not. Viability, apoptosis, proliferation, and YAP-1-dependent gene expression were analyzed. H2030-BrM3 cells (shControl or shNDR2) were injected intracardially into nude athymic mice (n = 10/group) to evaluate plasma AREG levels correlation with BM. AREG expression was assessed in human NSCLC tumor samples from primary and/or brain metastatic sites.</div></div><div><h3>Results</h3><div>NSCLC cells tolerated shear stress and showed reduced apoptosis after reseeding when expressing NDR2. Shear stress induced a dedifferentiation (<em>via</em> Sox2/9 variation) and increased AREG expression in most NSCLC cell lines. AREG enhanced NSCLC cells survival and proliferation under shear stress. In mice, plasma AREG levels correlated with BM volume. In human NSCLC samples, AREG-positive tumors displayed elevated Programmed Death-Ligand 1 (PD-L1), suggesting immune escape. Exogenous AREG treatment in H2030-BrM3 cells induced PD-L1 expression <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>AREG supports tumor adaptation to mechanical stress and may drive immune tolerance via PD-L1. Its correlation with BM burden highlights its potential as a biomarker and therapeutic target in NSCLC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118600"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-targeted delivery of CXCL10 by mesenchymal stromal cells potentiates adoptive T cell therapy to treat solid tumors","authors":"Jeong Ho Yoon ,&nbsp;Gyu-Bum Yeon ,&nbsp;Hojae Lee ,&nbsp;Hyunseo An ,&nbsp;Jiwon Oh ,&nbsp;Seok-Jin Kang ,&nbsp;In-Byung Park ,&nbsp;Seon Ah Lim ,&nbsp;Soo Seok Hwang ,&nbsp;Dae-Sung Kim ,&nbsp;Ji Hyung Kim ,&nbsp;Taehoon Chun ,&nbsp;Yang-Xin Fu ,&nbsp;Joonbeom Bae","doi":"10.1016/j.biopha.2025.118579","DOIUrl":"10.1016/j.biopha.2025.118579","url":null,"abstract":"<div><div>Limited T cell infiltration into solid tumors remains one of the major obstacles to successful cancer immunotherapy, particularly for adoptive cell therapy (ACT). Although the chemokine CXCL10 recruits T cells, its direct therapeutic application is hampered by poor pharmacokinetics, systemic leakage, and failure to establish stable concentration gradients required for effective cell migration. To overcome these challenges, we engineered mesenchymal stromal cells (MSCs) to co-express NAD(P)H quinone oxidoreductase 1 (NQO1) for enhanced survival and CXCL10-Fc fusion protein for sustained chemokine delivery (NIP-MSCs). The engineered MSCs exhibited resilience to tumor microenvironment conditions through improved redox homeostasis, resulting in enhanced persistence and sustained IP10-Fc production <em>in vivo</em>. Crucially, tumor-targeted delivery of CXCL10-Fc established potent chemotactic gradients with minimal systemic leakage, dramatically increasing both endogenous and adoptively transferred T cell recruitment to tumor site. In syngeneic mouse models, NIP-MSC treatment significantly suppressed tumor growth through enhanced CD8⁺ T cell infiltration. When combined with ACT in melanoma models, NIP-MSCs resulted in superior tumor control and significantly prolonged survival compared to conventional approaches. This work validates NIP-MSCs as a promising platform to overcome T cell exclusion and potentiate immunotherapy efficacy in solid tumors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118579"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing mood post-bariatric surgery: Associations of rosuvastatin with vitamin D, oxidative stress, and neurotransmitter-related outcomes in rats","authors":"Sally A. Fahim ,&nbsp;Muhammad Y. Al-Shorbagy ,&nbsp;Rabab H. Sayed ,&nbsp;Albeir Messiha ,&nbsp;Muhammed A. Saad","doi":"10.1016/j.biopha.2025.118582","DOIUrl":"10.1016/j.biopha.2025.118582","url":null,"abstract":"<div><div>Bariatric surgery is effective for severe obesity, yet post-surgical depression poses challenges to weight loss outcomes. Beyond lipid-lowering, statins reduce diabetes recurrence and cardiac risks. Statin use has been linked with higher vitamin D levels, which decline after surgery. Rosuvastatin shows neuroprotective associations and potential benefits in reducing depression. Therefore, the aim of our study is to investigate the role of rosuvastatin in post-bariatric surgery depression. Twenty-four male Wistar rats were divided into four groups: Sham, which underwent a sham operation and received normal saline for 4 months, Sham + Rosuvastatin (2 mg/kg, orally), Gastric Banding, and Gastric Banding + Rosuvastatin, which received rosuvastatin post-surgery for 4 months. Body weight, lipid profile, and depressive-like behavior were assessed. Hippocampal levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT), dopamine (DA), and noradrenaline (NA) were measured, along with antioxidant markers including catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Serum levels of 1,25-dihydroxyvitamin D and its transporter SR-B1 were analyzed, as well as gene expression levels of the vitamin D catabolic enzyme CYP24A1 and activating enzyme CYP27B1 were also examined. Rosuvastatin treatment was associated with improvements in depressive-like behavior, reductions in oxidative stress, and normalization of neurotransmitter levels. Rosuvastatin treatment was associated with higher levels of vitamin D, CYP27B1, and SR-B1, along with lower levels of CYP24A1. The findings represent a preliminary study suggesting that rosuvastatin may be a potential therapeutic option for post-gastric banding–associated depressive-like behavior.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118582"},"PeriodicalIF":7.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}