Biomedicine & Pharmacotherapy最新文献

{"title":"Corrigendum to “Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines” [Biomed. Pharmacother. 151 (2022) 113137]","authors":"Elisabetta Panza , Ivana Bello , Martina Smimmo , Vincenzo Brancaleone , Emma Mitidieri , Mariarosaria Bucci , Giuseppe Cirino , Raffaella Sorrentino , Roberta d'Emmanuele di Villa Bianca","doi":"10.1016/j.biopha.2026.119135","DOIUrl":"10.1016/j.biopha.2026.119135","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119135"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230069","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":"Modulation of the gastrointestinal immune environment by chitosan microparticles loaded with Mycobacterium bovis BCG in a Cavia porcellus model in vivo, leading to reduced experimental H. pylori gastric colonization","authors":"Weronika Gonciarz ,&nbsp;Agnieszka Wosiak ,&nbsp;Agnieszka Jeleń ,&nbsp;Ewa Balcerczak ,&nbsp;Marek Brzeziński ,&nbsp;Katarzyna Węgrzyn ,&nbsp;Olga Stasikowska-Kanicka ,&nbsp;Magdalena Chmiela","doi":"10.1016/j.biopha.2026.119126","DOIUrl":"10.1016/j.biopha.2026.119126","url":null,"abstract":"<div><div>The increasing antibiotic resistance of the gastric pathogen <em>Helicobacter pylori</em> (Hp), which can escape the host immune mechanisms, underscores the need for new therapeutics that will allow them to bypass these obstacles. This study aimed to design chitosan (CHI) microparticles (MPs) loaded with <em>Mycobacterium bovis</em> (<em>M. bovis</em>) Bacillus Calmette-Guérin (BCG) with immunomodulating properties and assess their efficacy against Hp infection in <em>Cavia porcellus</em>. Chitosan has been selected due to its mucoadhesive and antibacterial properties. MPs have been modified with N-Acetyl-<span>D</span>-Glucosamine (Glc-NAc) (G MPs) or with Pluronic F127 (P MPs) to deliver mycobacteria to the stomach or the gut, being a center of mucosal immune system. Animals were inoculated orally only with G MPs or P MPs loaded with <em>M. bovis</em> BCG, with both types of MPs, with Hp alone or first with tested MPs and then with Hp. Oral inoculation of animals with MPs resulted in release of mycobacteria in the stomach or the gut, which was followed by the reduction of Hp colonization as shown by quantitative polymerase chain reaction (qPCR) in conjunction with diminishing the amount of mucin involved in Hp attachment as shown by immunofluorescence. Infiltration of gastric mucosa of animals pre-exposed to MPs and then inoculated with Hp with different T lymphocyte subpopulations CD4 + , CD8 + , Foxp3 + (regulatory cells), naïve or memory lymphocytes and eosinophils indicates that all these cells and cytokine profiles may develop environment reflecting immune tolerance or immune regulation rather than protection. The anti-Hp effect of the MPs studied may partly result from chitosan's mucoadhesive, antibacterial and immunomodulatory properties. In conclusion, chitosan MPs (G and P variants) loaded with <em>M. bovis</em> BCG are candidates for further study on a new anti-Hp formula, based on the immunomodulatory and antibacterial properties of mycobacteria and chitosan.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119126"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260293","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":"The calcimimetic etelcalcetide attenuates pressure overload–induced cardiac hypertrophy in rats with and without chronic kidney disease","authors":"Hidehisa Okamoto,&nbsp;Shunsuke Goto,&nbsp;Yuma Nose,&nbsp;Hayaki Okamoto,&nbsp;Hideki Fujii","doi":"10.1016/j.biopha.2026.119054","DOIUrl":"10.1016/j.biopha.2026.119054","url":null,"abstract":"<div><h3>Introduction</h3><div>Calcimimetics such as etelcalcetide (ET) are used to manage secondary hyperparathyroidism patients with chronic kidney disease (CKD) on dialysis. While their cardiovascular benefits—including left ventricular hypertrophy (LVH) suppression—are recognized, the underlying mechanisms remain unclear. This study investigated how ET suppresses LVH using rat models.</div></div><div><h3>Methods</h3><div>LVH was induced via transverse aortic coarctation, and CKD by 5/6 nephrectomy. Rats were assigned to the sham, CKD, LVH, or CKD/LVH groups, with each pathological group further divided into vehicle- or ET-treated subgroups. After eight weeks of treatment, echocardiography, histological, biochemical, and molecular analyses were conducted.</div></div><div><h3>Results</h3><div>ET reduced serum parathyroid hormone and fibroblast growth factor 23 (FGF23) levels in the CKD and CKD/LVH groups but not in the LVH group, where these levels were not increased. ET did not affect serum calcium, phosphorus, or vitamin D levels in the LVH and CKD/LVH groups. Nonetheless, ET suppressed cardiac hypertrophy and cardiomyocyte enlargement in the LVH and CKD/LVH groups despite no changes in systemic mineral metabolism parameters. Mechanistically, ET attenuated cardiac hypertrophy, serum aldosterone levels, and cardiac renin-angiotensin-aldosterone system (RAAS) components in the LVH and CKD/LVH groups. Cardiac FGF23 expression, elevated in the LVH and CKD/LVH groups, was also decreased by ET. The calcineurin/nuclear factor of the activated T-cell signaling pathway was unaffected.</div></div><div><h3>Conclusion</h3><div>ET effectively suppressed LVH in the LVH and CKD/LVH groups. These findings suggest that ET’s cardioprotective effects are mediated via the modulation of the RAAS and cardiac FGF23 expression rather than solely through the correction of CKD-mineral bone disorder abnormalities.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119054"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071122","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":"Oral submucous fibrosis: Regulatory mechanism of collagen metabolism and management","authors":"Zhao-Yong Hu ,&nbsp;Yan-Li Liu ,&nbsp;Jia-Kang Qiu ,&nbsp;Qiao-Juan Zuo ,&nbsp;Qun Li ,&nbsp;Jin Tan","doi":"10.1016/j.biopha.2026.119053","DOIUrl":"10.1016/j.biopha.2026.119053","url":null,"abstract":"<div><div>Oral submucous fibrosis (OSF) is a chronic and insidious potentially malignant disorder characterized by progressive fibrosis of the oral submucosa. It is recognized to be an irreversible disease of multifactorial origin, with limited therapeutic options due to incomplete understanding of its pathogenesis. Increased collagen synthesis or decreased collagen degradation is vital for the development of OSF. This review mainly introduces the key regulatory mechanism of collagen metabolism. Prolonged use of areca nut is arguably the major causative agents for OSF, which is vital for the myofibroblast transdifferentiation, fibroblastic proliferation, collagen synthesis, and resistance to collagenases. Chemical constituents of areca nut, and these components induced changes in epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodelling, inflammatory cytokines and growth factors, autoimmunity, and aberrant non-coding RNAs, are pivotal regulating factors for the myofibroblast activity and collagen metabolism in OSF. Oxidative stress following cell injury by areca nut extract, represented by reactive oxygen species (ROS) production, regulates ECM, EMT and cell cycle in OSF. Other factors such as nutrition, local stimulating factors and genetic susceptibility are also involved in the disease onset and progression. This paper summarizes both etiological factors and pathogenetic mechanisms underlying the collagen metabolism dysregulation in OSF, which provides new molecular targets and further research directions for the management of OSF.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119053"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168547","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":"Involvement of Keap1/Nrf2 and the antioxidant defence in cytoprotective effects induced by cannabis polyphenols in SH-SY5Y neuronal cells","authors":"Guillermo Cásedas ,&nbsp;Henar Rojas-Márquez ,&nbsp;Lucía Ventura ,&nbsp;Cristina Moliner ,&nbsp;Filippo Maggi ,&nbsp;Ainara Rubio-Castellanos ,&nbsp;Víctor López","doi":"10.1016/j.biopha.2026.119048","DOIUrl":"10.1016/j.biopha.2026.119048","url":null,"abstract":"<div><div>Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). <em>Cannabis sativa</em> L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant’s antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from <em>Cannabis sativa L.</em> in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 µM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed <em>in silico</em>. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. <em>In silico</em> docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that <em>Cannabis sativa</em> L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119048"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127895","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":"The influence of Borrelia burgdorferi and Anaplasma phagocytophilum bacteria on phospholipid metabolism in the blood of patients","authors":"Marta Dobrzyńska ,&nbsp;Elżbieta Skrzydlewska ,&nbsp;Iwona Jarocka-Karpowicz ,&nbsp;Monika Groth ,&nbsp;Ewelina Kruszewska ,&nbsp;Anna Moniuszko-Malinowska","doi":"10.1016/j.biopha.2026.118995","DOIUrl":"10.1016/j.biopha.2026.118995","url":null,"abstract":"<div><div>Ticks carry various pathogens, including the spirochete <em>Borrelia burgdorferi</em>, which causes Lyme disease (LD) in humans, and the Gram-negative bacterium <em>Anaplasma phagocytophilum</em>, which causes human granulocytic anaplasmosis (HGA). These diseases pose both diagnostic and therapeutic challenges. It is known that tick-borne diseases are typically accompanied by oxidative stress and inflammation, and consequently, other metabolic changes. Therefore, the aim of the study was to evaluate the modification of ROS- and enzyme-dependent metabolism of phospholipids and free polyunsaturated fatty acids (PUFAs), by assessing the level of ROS-dependent lipid peroxidation products and enzyme-dependent endocannabinoids and eicosanoids in the blood serum of patients with LD, HGA, and co-infections (LD+HGA) before and after pharmacotherapy, and thus to determine the effectiveness of pharmacotherapy based on doxycycline and amoxicillin. In the course of LD, HGA, and LD+HGA, systemic oxidative stress (increased 4-HNE level) occurs, which is accompanied by increased enzymatic metabolism of PUFAs with a tendency for free PUFAs to increase before and decrease after treatment, especially in LD, endocannabinoids (increased, especially 2-AG in HGA and LD+HGA), and all examined eicosanoid levels. Pharmacotherapy, especially in patients with LD, resulted in a decrease in all free PUFAs and a reduction in thromboxane B2 (TXB2) level. On the other hand, treatment with doxycycline in the HGA significantly increased PGE2 levels and decreased TXB2. Metabolic changes resulting from the infection, along with the incomplete return of the assessed parameters to physiological conditions, suggest that patients could benefit from additional supplementation, such as drugs or natural antioxidants that regulate lipid metabolism.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 118995"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183752","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":"Corrigendum: “Inhibition of oxidative stress, IL-13, and WNT/-catenin in ovalbumin-sensitized rats by a novel organogel of Punica granatum seed oil saponifiable fraction” [Biomed. Pharmacother. 154 (2022) 113667]","authors":"Nadia Z. Shaban ,&nbsp;Alaa S. Mohammed ,&nbsp;Marwa M. Abu-Serie ,&nbsp;Adham M. Maher ,&nbsp;Noha H. Habashy","doi":"10.1016/j.biopha.2026.119145","DOIUrl":"10.1016/j.biopha.2026.119145","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119145"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272876","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":"Corrigendum to \"Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice\" [Biomed. Pharmacother. 167 (2023) 115503]","authors":"Serenella Anzilotti ,&nbsp;Valeria Valente ,&nbsp;Paola Brancaccio ,&nbsp;Cristina Franco ,&nbsp;Antonella Casamassa ,&nbsp;Giovanna Lombardi ,&nbsp;Alessandra Palazzi ,&nbsp;Andrea Conte ,&nbsp;Simona Paladino ,&nbsp;Lorella Maria Teresa Canzoniero ,&nbsp;Lucio Annunziato ,&nbsp;Giovanna Maria Pierantoni ,&nbsp;Giuseppe Pignataro","doi":"10.1016/j.biopha.2026.119161","DOIUrl":"10.1016/j.biopha.2026.119161","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119161"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313452","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":"Discovery of first-in-class melanostatin-based ago-allosteric modulators of the dopamine D2 receptors","authors":"Hugo F. Costa-Almeida ,&nbsp;Xavier C. Correia ,&nbsp;Sara C. Silva-Reis ,&nbsp;Beatriz L. Pires-Lima ,&nbsp;Vera M. Costa ,&nbsp;Xerardo García-Mera ,&nbsp;Eddy Sotelo ,&nbsp;José Brea ,&nbsp;María I. Loza ,&nbsp;Félix Carvalho ,&nbsp;José E. Rodríguez-Borges ,&nbsp;Ivo E. Sampaio-Dias","doi":"10.1016/j.biopha.2026.119091","DOIUrl":"10.1016/j.biopha.2026.119091","url":null,"abstract":"<div><div>Melanostatin (MIF-1) is an endogenous tripeptide that acts as a positive allosteric modulator (PAM) of the dopamine D₂ receptors (D₂R), making it a valuable pharmacological lead for the treatment of dopamine-related disorders of the central nervous system (CNS). In this study, a novel series of MIF-1 derivatives was synthesized and pharmacologically evaluated to investigate the influence of ring flexibility and stereochemistry on PAM activity. For this purpose, the alicyclic β-amino acids (1<em>R</em>,2<em>S</em>)-2-aminocyclopentane-1-carboxylic acid (cispentacin) and its unsaturated precursor, (1<em>R</em>,2<em>S</em>)-2-aminocyclopent-3-ene-1-carboxylic acid, were used as proline surrogates. The results obtained showed that cispentacin-based derivatives <strong>8b</strong> and <strong>9b</strong> displayed PAM activity at 10 pM, significantly reducing the EC₅₀ of dopamine by 4.34- and 4.22-fold, respectively (<strong>8b</strong>: EC₅₀ = 20.08 ± 3.95 nM; <strong>9b</strong>: EC₅₀ = 20.61 ± 4.60 nM). At 1 nM, <strong>8b</strong> further decreased the EC₅₀ of dopamine by 9.20-fold (EC₅₀ = 9.47 ± 5.02 nM) and, at higher concentrations (10 and 100 μM), it activated the D₂R in the absence of dopamine, representing the first-in-class MIF-1-based ago-allosteric modulator of the D₂R. Cytotoxicity assays in human dopaminergic-differentiated SH-SY5Y cells showed that neither <strong>8b</strong> nor <strong>9b</strong> exhibited cytotoxic effects at 100 μM, as assessed by both the MTT reduction and neutral red uptake assays, supporting their favorable toxicological profiles. Overall, these findings demonstrate that a fine-tuned interplay between ring flexibility and stereochemistry is a key determinant in generating effective PAM of the D₂R, providing a framework for the future design of MIF-1-based modulators targeting Parkinson’s disease and other dopamine-related CNS disorders.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119091"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185962","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":"Placental transfer characteristics and functional impact of SGLT2 inhibitors in human experimental models","authors":"Sabrina Kuoni ,&nbsp;Alexandra Dolder ,&nbsp;Roger Lehmann ,&nbsp;Regula Steiner ,&nbsp;Nicole Ochsenbein-Kölble ,&nbsp;Ana Paula Simões-Wüst","doi":"10.1016/j.biopha.2026.119097","DOIUrl":"10.1016/j.biopha.2026.119097","url":null,"abstract":"<div><div>Understanding the mechanisms of drug transfer across the human placenta is critical for evaluating foetal exposure and developmental safety. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), a novel class of antidiabetics, remain poorly characterized with respect to their placental transfer and potential effect on placental function. Here, we address this knowledge gap. We investigated placental transfer mechanisms of dapagliflozin (DAPA), empagliflozin (EMPA), ertugliflozin (ERTU) and canagliflozin (CANA) using term placentas and complementary <em>in vitro</em> assays. All SGLT2i crossed the barrier within four hours of perfusion at clinically relevant concentrations. DAPA, the smallest compound, showed the fastest transfer, whereas EMPA, the largest, was the slowest. The more lipophilic compounds, CANA and ERTU, accumulated strongly in placental tissue. Transport of all SGLT2i – especially EMPA and ERTU – increased with the addition of an ATP-synthesis inhibitor, indicating the influence of active efflux transporters. Additionally, transport was significantly enhanced under low-bovine serum albumin conditions, implicating protein binding as a key rate-limiting factor. During Transwell® permeability assays, all SGLT2i crossed the BeWo b30 cell layer that mimics early gestational cytotrophoblasts. BeWo cells exposed to SGLT2i showed no impairment in forskolin-induced differentiation, viability, or secretion of pregnancy-related hormones, but revealed increased glycolytic activity. Our findings indicate that at clinically relevant concentrations, SGLT2i cross the placenta by passive diffusion, modulated by efflux transporters and protein binding, and might alter placental glycolytic activity without impairing viability, differentiation, or hormone secretion. Their use during pregnancy should remain contraindicated, but if attempted, monitoring unbound drug concentrations is advised.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119097"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185964","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}