Biomedicine & Pharmacotherapy最新文献

{"title":"Cognitive dysfunction in chemobrain: Molecular mechanisms and therapeutic implications","authors":"Hyung-Goo Kim ,&nbsp;Mohammad Abdur Rashid ,&nbsp;Michael Poleschuk ,&nbsp;Faheem Ullah ,&nbsp;Sang Hoon Lee ,&nbsp;Sang Hoon Kim ,&nbsp;Bo Qin ,&nbsp;X.F. Steven Zheng ,&nbsp;Mi-Hyeon Jang","doi":"10.1016/j.biopha.2025.118581","DOIUrl":"10.1016/j.biopha.2025.118581","url":null,"abstract":"<div><div>Chemotherapy-induced cognitive impairment (CICI), commonly referred to as chemobrain, is a prevalent side effect of cancer treatment that severely affects survivors' quality of life. Chemotherapeutic agents, including cisplatin, doxorubicin, and paclitaxel, cross the blood-brain barrier (BBB) and induce neurotoxicity, resulting in cognitive dysfunction. These agents trigger reactive oxygen species (ROS) generation, cause mitochondrial dysfunction, and induce DNA damage, all of which impair synaptic plasticity and neurogenesis. Mitochondrial dysfunction is central to chemobrain, as it disrupts ATP production, increases oxidative stress, and leads to neuronal apoptosis. Furthermore, mitochondrial DNA (mtDNA) damage caused by agents like cisplatin impairs oxidative phosphorylation, exacerbating neuronal degeneration. The molecular mechanisms of chemobrain likely involve several key players, including NAMPT-dependent NAD+ depletion and increased levels of Cyclooxygenase-2 (COX-2), which collectively exacerbate oxidative stress and neuroinflammation. Another important molecular target is the Adenosine A2A receptor (A2AR). When activated, it contributes to synaptic dysfunction and cognitive decline, particularly in chemotherapy-related cognitive deficits in the hippocampus. This review explores the complex interplay of these core pathologies in chemobrain and discusses how targeting these pathways could offer a therapeutic strategy to alleviate cognitive impairments in cancer survivors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118581"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152151","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":"Combined haptoglobin and hemopexin therapy for the treatment of cardiopulmonary dysfunction in sickle cell disease","authors":"Melissa J. Lucero ,&nbsp;Christina Lisk ,&nbsp;Delaney Swindle ,&nbsp;Francesca Cendali ,&nbsp;Saini Setua ,&nbsp;Kiruphagaran Thangaraju ,&nbsp;Alamzeb Khan ,&nbsp;David I. Pak ,&nbsp;Quintin O’Boyle ,&nbsp;Shuwei Lu ,&nbsp;Robert Tolson ,&nbsp;Seth Zaeske ,&nbsp;Saqib Khan ,&nbsp;Nishant Rana ,&nbsp;Natalie Westover ,&nbsp;Pavel Davizon-Castillio ,&nbsp;Gemlyn George ,&nbsp;Kathryn Hassell ,&nbsp;Rachelle Nuss ,&nbsp;Nathan Brinkman ,&nbsp;David C. Irwin","doi":"10.1016/j.biopha.2025.118595","DOIUrl":"10.1016/j.biopha.2025.118595","url":null,"abstract":"<div><div>Hemolysis and the downstream consequences of cell-free hemoglobin (Hb) and heme contribute to the development of sickle cell disease pulmonary hypertension (SCD-PH). The plasma concentrations of Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) in sickle cell patients are observed to be significantly lower than healthy donors. The unchecked exposure to Hb and heme contribute to vasculopathy and aberrant cardiac function. This is consistent with vascular remodeling co-localized within iron rich macrophages. Based on these observations in patients, we hypothesize that a joint Hb and heme scavenger approach, combining Hp + Hpx as a therapeutic will attenuate hemolysis driven SCD-PH progression in a SCD mouse model. To test the hypothesis, we utilized our validated Berk-SS mouse model of SCD-PH driven by a 10-week moderate hypoxia exposure and weekly subcutaneous administration of Hp + Hpx. At study termination, we analyzed changes in cardiopulmonary iron deposition, right ventricular and pulmonary functional parameters, and multi-omic indices associated with SCD-PH. Our data demonstrates that Hp+Hpx improves pulmonary vascular resistance and right ventricular function including stiffness, afterload, cardiac output, ventricular to vascular coupling ratio, pulmonary vascular resistance and medial hypertrophy. Histological evaluation of lung and right ventricular tissue demonstrates attenuation of cardiopulmonary pathology. Finally, a multi-omic analysis of whole lung and heart tissue demonstrates a rebalancing of proteins related to PH, iron, inflammation, and oxidative stress. This data provides strong pre-clinical evidence for the clinical study of combined Hb and heme scavenger proteins in the treatment of PH-associated SCD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118595"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119548","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":"Neuroinflammatory suppression with protocatechuic acid attenuates Alzheimer’s disease phenotypes in 5 ×FAD transgenic mice","authors":"Yoonsu Kim ,&nbsp;Minjung Cho ,&nbsp;Chang-Jin Jeon ,&nbsp;Gyuhyeong Goh ,&nbsp;Myungjin Kim","doi":"10.1016/j.biopha.2025.118598","DOIUrl":"10.1016/j.biopha.2025.118598","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a complex pathobiology that includes neuroinflammation, the accumulation of extracellular amyloid-beta (Aβ) plaque, and intracellular neurofibrillary tangles comprising tau. Increasing evidence suggests that the aberrant activation of glial cells, including microglia and astrocytes, is a significant early characteristic that accelerates neuroinflammatory processes in the development of AD. Protocatechuic acid (PCA), a natural phenolic compound, has been investigated for its anti-inflammatory properties in various pathological conditions. Here, we demonstrated that administration of PCA significantly ameliorated neuroinflammation as well as cognitive deficits in the 5 ×FAD mouse model of AD, which overexpresses human amyloid precursor protein (<em>APP</em>) and presenilin-1 (<em>PSEN1</em>) genes carrying five familial Alzheimer's disease (FAD) mutations, leading to accelerated Aβ deposition. We further confirmed that PCA treatment significantly reduced microglial activation and downregulated the production of pro-inflammatory cytokines, astrogliosis, and tau hyperphosphorylation, thereby preserved the integrity of hippocampal neurons. Our RNA sequencing analysis revealed that PCA treatment restored the transcriptomic profile of hippocampal tissues in 5 ×FAD mice, particularly by downregulating genes associated with innate immune and inflammatory responses. Moreover, PCA alleviated gut dysbiosis and enhanced the integrity of the intestinal barrier. The findings suggest that PCA may serve as a promising therapeutic agent for early intervention in AD to mitigate its progression.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118598"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119549","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":"Visnagin mitigates acute kidney injury caused by lipopolysaccharide administration by inhibiting the NF-κB and pyroptosis pathways","authors":"Sheng-Wen Wu ,&nbsp;Chien-Ying Lee ,&nbsp;Shiuan-Shinn Lee ,&nbsp;Wen-Ying Chen ,&nbsp;Chun-Jung Chen ,&nbsp;Ching-Chi Tseng ,&nbsp;Chen-Yu Chiang ,&nbsp;Yu-Hsiang Kuan","doi":"10.1016/j.biopha.2025.118578","DOIUrl":"10.1016/j.biopha.2025.118578","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Sepsis-associated acute kidney injury (AKI) is a life-threatening complication marked by inflammation-driven renal dysfunction. Although advances have been made in supportive care, pharmacologic therapies targeting the underlying molecular mechanisms of sepsis-associated AKI are lacking. Visnagin, a furanochromone derivative with anti-inflammatory properties, has yet to be explored in treatment for sepsis-associated AKI.</div></div><div><h3>Experimental approach</h3><div>This study used a network pharmacology approach to identify visnagin targets associated with AKI. We conducted gene enrichment and protein-protein interaction analyses and performed molecular docking to predict binding affinities between visnagin and key inflammatory proteins. An in vivo murine model of LPS-induced AKI was established to evaluate the protection of visnagin. Renal function was assessed through serum creatinine and blood urea nitrogen levels. Additionally, histological injury, inflammatory cytokine expression, and molecular pathways were analysed.</div></div><div><h3>Key results</h3><div>Bioinformatics analyses identified MAPK1, MAPK14, NFKB1, and CASP1 as hub genes potentially targeted by visnagin. Molecular docking confirmed strong binding affinities between visnagin and these proteins that exceeded the binding affinity of dexamethasone in key inflammatory targets. In vivo, visnagin substantially reduced LPS-induced renal dysfunction and histopathological damage in a dose-dependent manner. Visnagin suppressed the phosphorylation of p38 MAPK and extracellular signal-related kinase, decreased NF-κB activation, and inhibited the generation of proinflammatory cytokines. Moreover, visnagin attenuated pyroptosis by inhibiting the NLRP3/apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain/caspase-1/Gasdermin-D axis.</div></div><div><h3>Conclusion and implications</h3><div>Visnagin mitigates LPS-induced AKI by targeting multiple signalling pathways, particularly NF-κB-mediated inflammation and NLRP3 inflammasome-mediated pyroptosis. These findings suggest that visnagin is a promising multitarget candidate for treating sepsis-associated AKI.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118578"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109363","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":"Proteasome-mediated ubiquitination in neural regeneration","authors":"Huanyi Li ,&nbsp;Yiwen Hu ,&nbsp;Meili Cheng ,&nbsp;Jialin Wang ,&nbsp;Mingxia Zhao ,&nbsp;Bolun Cao ,&nbsp;Yulu Zhao ,&nbsp;Jingjing Jiang","doi":"10.1016/j.biopha.2025.118563","DOIUrl":"10.1016/j.biopha.2025.118563","url":null,"abstract":"<div><div>The proteasome, the principal intracellular protein-degradation system, is essential for nerve regeneration after injury.This review summarizes recent evidence that the proteasome orchestrates axonal regeneration by modulating growth-cone formation, microtubule dynamics, reactive oxygen species (ROS) levels, and neuroinflammation. Proteasomes are delivered to growth cones via retrograde axonal transport, and their localization and activity depend on neuronal maturation and axon length.They further promote growth-cone assembly and axonal extension by regulating tubulin expression and polymerization.As key signaling molecules, ROS levels are tightly coupled to proteasome activity; their reciprocal interactions fine-tune axonal regrowth. Notably, immunoproteasome subunits such as PSMB5i contribute to neurodegeneration via inflammatory pathways. In a cohort of 316 ischemic stroke patients, plasma levels of LMP2, MECL-1, and LMP7 were markedly elevated in the 13.3 % who developed hemorrhagic transformation (P &lt; 0.05), suggesting their utility as early biomarkers of stroke complications. Elucidating these proteasome-driven mechanisms in both regeneration and pathology will inform novel therapeutic strategies for neural repair and related disorders.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118563"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109953","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":"Precision targeting of CXCR4+ leukemia cells by a humanized MMAE-nanoconjugate in an AML mouse model","authors":"Annabel Garcia-León ,&nbsp;Julián I. Mendoza ,&nbsp;Ariana Rueda ,&nbsp;Lorena Alba-Castellon ,&nbsp;Josep F. Nomdedéu ,&nbsp;Alberto Gallardo ,&nbsp;Jorge Sierra ,&nbsp;Ana Garrido ,&nbsp;Esther Vázquez ,&nbsp;Antonio Villaverde ,&nbsp;Ramon Mangues ,&nbsp;Ugutz Unzueta ,&nbsp;Isolda Casanova","doi":"10.1016/j.biopha.2025.118573","DOIUrl":"10.1016/j.biopha.2025.118573","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) presents major clinical challenges due to chemoresistance and high relapse rates, primarily driven by therapy-resistant leukemic stem cells (LSCs) within the bone marrow. To address this issue, we developed T22-HSNBT-H6-MMAE, a novel humanized nanoconjugate designed to target CXCR4^⁺ cells while delivering the cytotoxic payload monomethyl auristatin E (MMAE). CXCR4 signaling pathway plays a critical role in LSC survival by preserving stem-like properties and activating protective mechanisms that promote treatment resistance. Moreover, CXCR4 is overexpressed in approximately 50 % of AML patients and is associated with poor prognosis and high relapse rates. We evaluated the therapeutic potential of T22-HSNBT-H6-MMAE using <em>in vitro</em> assays with AML cell lines and primary patient samples, as well as <em>in vivo</em> studies in a disseminated AML mouse model. Our results demonstrated that T22-HSNBT-H6-MMAE exerts a CXCR4-dependent cytotoxic effect through mitotic catastrophe and apoptosis induction in CXCR4^⁺ AML cell lines. <em>In vivo</em> evaluation in a disseminated CXCR4^⁺ AML mouse model showed potent antineoplastic activity, with complete suppression of leukemic dissemination and significantly prolonged survival, all without systemic toxicity. Notably, the nanoconjugate remained effective even in models with extensive bone marrow involvement and exhibited activity against diverse patient-derived CXCR4^⁺ AML blasts, while sparing healthy donor bone marrow and peripheral blood mononuclear cells (PBMCs) from significant toxicity. Collectively, these findings highlight T22-HSNBT-H6-MMAE as a promising therapeutic candidate for a broad range of AML patients, offering selective antineoplastic activity against CXCR4^⁺ leukemic cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118573"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119550","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":"Bridging predictions with experimental reality: In vitro evaluation of phenolic natural products as SARS-CoV-2 exoribonuclease inhibitors","authors":"Matěj Danda ,&nbsp;Barbora Chvátalová ,&nbsp;Daniela Nečasová ,&nbsp;Ivana Křížová ,&nbsp;Tomáš Ruml ,&nbsp;Michaela Rumlová","doi":"10.1016/j.biopha.2025.118588","DOIUrl":"10.1016/j.biopha.2025.118588","url":null,"abstract":"<div><div>SARS-CoV-2 exoribonuclease (ExoN) is essential for viral replication, contributing to proofreading, RNA synthesis, and genomic RNA recombination. As such, it represents a promising target for antiviral drugs. Several low-molecular-weight inhibitors, including disulfiram and aurintricarboxylic acid (ATA), have been reported to inhibit ExoN activity. Computational studies have also suggested that various natural phenolic compounds may inhibit ExoN; however, their inhibitory potency remains largely unknown. In this study, we systematically evaluated the inhibitory potency of 60 phenolic phytochemicals, including flavonoids, phenolic acids, coumarins, and other related compounds, using a dual-assay approach, with ATA as the reference inhibitor. Initially, we used nano-differential scanning fluorimetry to assess the thermal stabilization or destabilization of the enzyme induced by compound binding. Subsequently, we performed a TBE-PAGE-based enzymatic activity assay to examine ExoN activity inhibition. Selected compounds were then validated using a FRET-based enzymatic assay. While none of the compounds achieved the ATA’s inhibitory efficacy, three compounds demonstrated measurable inhibitory activity: myricetin (IC₅₀ = 142 µM), ellagic acid (IC₅₀ = 44.4 µM), and shikonin (IC₅₀ = 7.92 µM). Our dual assay approach, complemented by crosslinking experiments, revealed that shikonin exhibits a distinct inhibitory mechanism, possibly involving the disruption of ExoN subunit interactions. These findings emphasize the necessity of experimental validation following <em>in silico</em> screening, particularly for promiscuous chemicals such as phenolic natural products. This approach may help to narrow down rationally designed compounds for further optimization.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118588"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109364","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":"Recent advances and clinical potential of hyaluronic acid methacrylate (HAMA)/ceramic composites in oral and dental regenerative therapies: A comprehensive review","authors":"Mohammad Golrokhian ,&nbsp;Haleh Fakhimi Rezaei ,&nbsp;Maryam Rezaeianjam ,&nbsp;Bita Moslem ,&nbsp;Kimia Naderpour ,&nbsp;Amir Abbas Seraji","doi":"10.1016/j.biopha.2025.118590","DOIUrl":"10.1016/j.biopha.2025.118590","url":null,"abstract":"<div><div>Hyaluronic acid methacrylate (HAMA) has emerged as a promising biomaterial for oral and dental applications due to its inherent biocompatibility, controllable biodegradability, and tunable mechanical properties. The incorporation of ceramic components (e.g., hydroxyapatite, tricalcium phosphate, bioactive glass) into HAMA-based composites synergistically enhances their mechanical robustness, bioactivity, and osteogenic capacity, thereby expanding their utility in dental tissue engineering, periodontal regeneration, and implant surface functionalization. This review provides a comprehensive analysis of recent advancements in the design, fabrication, and application of HAMA/ceramic composites. Our analysis of the literature reveals that these composites demonstrate significant promise: they enhance compressive modulus, support high cell viability in 3D-bioprinted constructs, and achieve sustained release of antimicrobials and ions to concurrently combat infection and promote osteogenesis. Key findings indicate their efficacy in guided bone regeneration, periodontal defect repair, where they reduce inflammatory markers and inhibit periodontal pathogens, and as bioactive implant coatings that improve osseointegration. Despite these advancements, significant challenges persist in scalability, long-term structural stability, and clinical translation. By integrating insights from materials science, cellular biology, and clinical dentistry, this review concludes that HAMA/ceramic composites represent a paradigm-shifting platform for next-generation dental therapies. Their unique combination of properties positions them to overcome the limitations of conventional biomaterials, though future efforts must focus on standardizing fabrication protocols and validating their efficacy in controlled human trials.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118590"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109432","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":"Recent developments in bioconjugation: From strategies to design and clinical applications","authors":"Faezeh Samieipour ,&nbsp;Hassan Dianat-Moghadam ,&nbsp;Hossein Khanahmad","doi":"10.1016/j.biopha.2025.118593","DOIUrl":"10.1016/j.biopha.2025.118593","url":null,"abstract":"<div><div>Bioconjugation is defined as the covalent attachment of biomolecules, such as proteins, carbohydrates, nucleic acids, or lipids, to another biomolecule or functional entity such as synthetic polymers, fluorescent probes, drugs, dyes, and targeting ligands. Bioconjugation plays a key role in modern biotechnology and medicine, enabling precise control over molecular recognition, stability, and biodistribution. This review provides a comprehensive and integrative perspective on bioconjugation, encompassing both traditional and emerging strategies while critically comparing their efficiency, stability, and clinical applicability. It evaluates the strengths and limitations of various approaches, from classical amide and thiol couplings to advanced bioorthogonal click chemistry. Furthermore, the review highlights innovative directions in optimizing bioconjugation, including linker design, enhanced stability profiles, stimuli-responsive release mechanisms, and predictive release kinetics. The work integrates recent advances into a framework that addresses key challenges, such as site-specificity, immunogenicity, and scalability and offers a practical guide for next-generation diagnostics and therapeutics.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118593"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109954","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":"Trimethylamine N-Oxide (TMAO) and cancer risk: Insights into a possible link","authors":"Biki Saha ,&nbsp;Antara Banerjee ,&nbsp;Rupak Pathak ,&nbsp;Asim K. Duttaroy ,&nbsp;Surajit Pathak","doi":"10.1016/j.biopha.2025.118592","DOIUrl":"10.1016/j.biopha.2025.118592","url":null,"abstract":"<div><div>The gut microbiota play a crucial role in cancer pathogenesis, partly through metabolites derived from dietary components or host compounds. Among these, trimethylamine N-oxide (TMAO), a secondary gut microbiota-derived metabolite has gained attention for its potential link to cancer. TMAO is formed when gut microbes convert dietary choline, carnitine, and betaine into trimethylamine (TMA), which is then oxidized in the liver by FMO3. While TMAO has been well studied in cardiovascular, kidney, and metabolic diseases, growing evidence links elevated TMAO levels to increased risks of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Although the exact mechanisms remain unclear, TMAO appears to contribute to cancer progression by promoting inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance. This review discusses the dietary and microbial pathways involved in TMAO synthesis, its role in cancer progression, and critically evaluates the current literature on its potential contribution to cancer. Understanding the role of TMAO could offer new strategies for cancer prevention and therapy that target the gut microbiota and their metabolites.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118592"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109976","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}