Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"title":"Population pharmacogenomics of CYP1A2, CYP2C19, CYP2D6 and CYP3A4 in a Uruguayan cohort with schizophrenia.","authors":"Sofía Gonzales-Magallanes, Clara Menéndez, Valentina Blanco, José L Badano, Alfonso Cayota, Ismael Olmos, Carina Ricciardi, Mauricio Mato, Natalia Guevara, Sabrina Acuña, Cecilia Maldonado, Marta Vázquez, Mauricio Toledo, Magdalena Cárdenas-Rodríguez, Lucía Spangenberg","doi":"10.1016/j.biopha.2026.119992","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.119992","url":null,"abstract":"<p><p>Latin American populations remain underrepresented in pharmacogenomic research, limiting the applicability of genomic findings to these groups. Uruguay, with its unique admixed demographic history, constitutes a relevant case study for characterizing clinically significant pharmacogene variation. In this work, we characterized haplotypic diversity across four CYP450 genes, CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in a cohort of 47 Uruguayan patients with treatment-resistant schizophrenia (TRS) receiving clozapine. Star-allele frequencies in the TRS cohort were contextualized against the Urugenomes Phase 2 dataset (U2; n = 30), used as the primary Uruguayan population reference, alongside two ancestry-enriched datasets comprising Indigenous-admixed (n = 10) and Afro-Uruguayan (n = 10) individuals. Star-allele and diplotype inference was performed using Aldy v4.8.3, and population-level frequencies were contextualized against global biogeographic references from PharmFreq and gnomAD. CYP1A2*30 predominated across all Uruguayan datasets, while CYP3A4 showed near-complete dominance of the *1 allele. CYP2C19 and CYP2D6 displayed greater inter-dataset heterogeneity, with metabolizer phenotype distributions differing from global reference populations. To assess the clinical relevance of this pharmacogenomic variation, multivariable linear regression models were constructed to predict plasma clozapine concentrations, incorporating clinical, behavioral, and genetic predictors. A model combining HDL, triglycerides, glycemia, cigarette consumption, and CYP1A2*30 allele count explained 41% of the variance in clozapine levels (adjusted R² = 0.41), representing a statistically significant improvement over the clinical-only model (ANOVA p = 0.034). Bootstrap resampling confirmed the stability of all estimated effects, and leave-one-out cross-validation yielded a corrected R² of 0.31. These findings contribute to characterizing the pharmacogenomic landscape of an underrepresented Latin American population and suggest that locally generated CYP haplotype data may complement clinical factors in explaining interindividual variability in clozapine exposure in this population.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"204 ","pages":"119992"},"PeriodicalIF":7.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosmarinic acid- and epigallocatechin gallate-enriched extracts improve insomnia and sleep-wake balance in caffeine-and p-chlorophenylalanine-induced insomnia models.","authors":"Ahjin Kim, Seok Hyun Chung, Taehyeon Park, Huiyun Kim, Hyowon Lee, Ki-Bae Hong, Dong-Woo Lee, Yejin Ahn","doi":"10.1016/j.biopha.2026.119997","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.119997","url":null,"abstract":"<p><p>This study evaluated the effects of a rosmarinic acid- and epigallocatechin gallate-enriched extract mixture (RE-GTE) on insomnia and sleep-wake disturbances induced by excessive caffeine intake or serotonin depletion using p-chlorophenylalanine (PCPA) in mice. RE-GTE was administered in both caffeine- and PCPA-induced insomnia models, and sleep-related behaviors were assessed using pentobarbital-induced sleep tests and behavioral analyses of anxiety-related and locomotor parameters. In addition, sleep-related neurotransmitters and receptor expression were examined using molecular and biochemical approaches. In the caffeine-induced insomnia model, RE-GTE supplementation significantly attenuated caffeine-induced dopaminergic hyperactivity, increased gamma-aminobutyric acid (GABA) levels, and improved anxiety-related and selected locomotor behavioral parameters. RE-GTE also upregulated GABA_A receptor expression while reducing adenosine A1 and A2A receptor expression, accompanied by increased sleep duration. In the PCPA-induced insomnia model, RE-GTE increased hypothalamic serotonin and melatonin levels, reduced stress-related hormones including adrenocorticotropic hormone and corticosterone, increased serotonin receptor expression, and reduced overexpression of the orexin 2 receptor, indicating selective modulation of serotonergic and stress-related markers. Across both models, high-dose RE-GTE (40 mg/kg) increased sleep duration toward normal levels. Collectively, these findings indicate that RE-GTE ameliorates insomnia-related behavioral and neurochemical disturbances and that this improvement is accompanied by selective changes in adenosinergic, GABAergic, and serotonergic markers. These pathway-level associations support further investigation of RE-GTE as a promising natural candidate for the management of sleep disturbances.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"204 ","pages":"119997"},"PeriodicalIF":7.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virulence mechanisms of Desulfovibrio bacteria: viability-dependent processes promote alpha-synuclein aggregation and toxicity in C. elegans.","authors":"Vy A Huynh, Fang Chi, Sima Talebzadeh, Janetta R Hakovirta, Asko Simojoki, Per Erik Joakim Saris","doi":"10.1016/j.biopha.2026.119995","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.119995","url":null,"abstract":"<p><strong>Objectives: </strong>Desulfovibrio (DSV) species have been linked to Parkinson's disease (PD) and demonstrated to enhance alpha-synuclein (alpha-syn) aggregation, a pathological hallmark of PD, in a Caenorhabditis elegans model. However, the bacterial factors underlying this virulence remain unclear. We investigated whether DSV-induced alpha-syn aggregation and toxicity are more strongly driven by bacterial viability-dependent processes or by bacterial structures retained after paraformaldehyde (PFA) treatment.</p><p><strong>Methods: </strong>Live or paraformaldehyde (PFA)-treated (non-viable) DSV cells, and curli-producing or curli-deficient E. coli as controls were fed to C. elegans. Worm survival, alpha-syn aggregation, hydrogen sulfide production, and expression of genes associated with inflammation, oxidative stress, proteostasis and dopaminergic function were evaluated.</p><p><strong>Results: </strong>Curli-producing E. coli retained its ability to induce alpha-syn aggregation, whereas PFA-treated DSV strains lost this effect, showing reduced aggregate number and volume (P < 0.05). Worm survival improved when fed PFA-treated cells, although the difference was not statistically significant. Expression of pmk-1, skn-1 and hsf-1 did not differ between worms fed live and PFA-treated DSV bacteria, while cat-2 expression increased in worms fed PFA-treated bacteria compared to those fed live cells. Patient-derived DSV strains produced substantially higher levels of H₂S than healthy control strains (1058.11 vs. 710.30 ppm/OD₆₀₀; P = 0.003), and H₂S levels were positively correlated with aggregate volume (Spearman's r_s = 0.886, P = 0.019).</p><p><strong>Conclusions: </strong>DSV-derived viability-dependent processes, including metabolic activity, more strongly promote alpha-syn aggregation and toxicity than structural components. These findings highlight the important contribution of bacterial viability-dependent processes to DSV-mediated pathogenic effects relevant to Parkinson's disease.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"204 ","pages":"119995"},"PeriodicalIF":7.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating emerging preservation strategies in cardiac transplantation: From nanotherapeutic frontiers to clinical translation.","authors":"Han Wang, Junyi Wang, Weimin Deng, Fangfang Jin, Chao Lin","doi":"10.1016/j.biopha.2026.120000","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.120000","url":null,"abstract":"<p><p>Hypothermic preservation remains a critical bottleneck in heart transplantation, primarily due to the exacerbation of ischemia-reperfusion injury (IRI) and tightly restricted organ viability windows. Addressing this global clinical crisis requires a departure from traditional monotherapies. This review critically appraises-rather than merely synthesizes-three multidisciplinary advancements: (1) preservation solutions supplemented with nanotherapeutics, with explicit distinction between proof-of-concept, small-animal, and clinically translatable evidence; (2) technological transitions from static cold storage (SCS) to ex vivo heart perfusion (EVHP) and nanowarming-assisted cryopreservation; and (3) bioactive compounds derived from Traditional Chinese Medicine (TCM), evaluated through a SWOT framework that acknowledges phytochemical variability and the paucity of clinical transplantation data. We further examine the emerging-but currently nascent and largely speculative---role of artificial intelligence in perfusion decision support. We emphasize that these three domains are not evidentially equivalent: perfusion technology is clinically implemented, pharmacological and nanotherapeutic adjuncts remain predominantly preclinical, and AI applications in cardiac preservation are currently confined to retrospective outcome modelling, with no published closed-loop perfusion control in clinical practice.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"204 ","pages":"120000"},"PeriodicalIF":7.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: A possible mechanism for a protective effect against ulcerative colitis\" [Biomedicine & Pharmacotherapy 154 (2022) 113651].","authors":"Mona H Zohny, Mohammed Alrouji, Sharif Alhajlah, Othman AlOmeir, Mohamed Gamal El-Din Ewees, Dalia M Abdel Ghaffar, Noura El Adle Khalaf, Osama A Mohammed, Mahmoud Said Ibrahim Abdeldaiem, Waleed Barakat El-Bahouty, Amr Elrabat, Sahar Zakaria, Zeinab M Abdel-Nasser, Amira A Haleem, Doaa M El-Gharbawy, Rasha Abdelhady, Mohamed M Y Kaddah, Ahmed Shata, Sameh Saber","doi":"10.1016/j.biopha.2026.119982","DOIUrl":"10.1016/j.biopha.2026.119982","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119982"},"PeriodicalIF":7.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Three-dimensional cell cultures as an in vitro tool for ovarian cancer modeling and natural product discovery\" [Biomed. Pharmacother. 2026 (202) 119823].","authors":"Mirian Carolini Esgoti Aal, Matheus Naia Fioretto, Tainá Dorte da Silva, Isabella Cena Guimaraes, Ana Clara Silveira Goldoni, Vitoria Luíza Alves de Souza Rios, Luiz Gustavo de Almeida Chuffa, Flavia Karina Delella","doi":"10.1016/j.biopha.2026.119967","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.119967","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119967"},"PeriodicalIF":7.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Immunotherapeutic advances in pediatric neuroblastoma: Overcoming resistance through biomarker-guided combinations\", [Biomed. Pharmacother. 196 (2026) 119020].","authors":"Mahla Shokouhfar, Ali Darzi, Fatemeh Ameli, Mohammad Taha Nami, Saeed Khavari Khorasani, Pooya Eini, Ahmad Ghorbani Vanan, Nastaran Bahrami","doi":"10.1016/j.biopha.2026.119939","DOIUrl":"https://doi.org/10.1016/j.biopha.2026.119939","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119939"},"PeriodicalIF":7.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications\" [Biomedicine & Pharmacotherapy 162 (2023) 114687].","authors":"Shumaila Ijaz, Javed Iqbal, Banzeer Ahsan Abbasi, Zakir Ullah, Tabassum Yaseen, Sobia Kanwal, Tariq Mahmood, Sandugash Sydykbayeva, Alibek Ydyrys, Zainab M Almarhoon, Javad Sharifi-Rad, Christophe Hano, Daniela Calina, William C Cho","doi":"10.1016/j.biopha.2026.119513","DOIUrl":"10.1016/j.biopha.2026.119513","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119513"},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Recent advances in glioblastoma multiforme therapy: A focus on autophagy regulation\" [Biomedicine & Pharmacotherapy 155 (2022) 113740].","authors":"Mehdi Sanati, Maryam Moradi Binabaj, Seyed Sajad Ahmadi, Samaneh Aminyavari, Hossein Javid, Hamid Mollazadeh, Bahram Bibak, Elmira Mohtashami, Tannaz Jamialahmadi, Amir R Afshari, Amirhossein Sahebkar","doi":"10.1016/j.biopha.2026.119688","DOIUrl":"10.1016/j.biopha.2026.119688","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119688"},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Decoding tumor microenvironment: EMT modulation in breast cancer metastasis and therapeutic resistance, and implications of novel immune checkpoint blockers\" [Biomedicine & Pharmacotherapy 181 (2024) 117714].","authors":"Jie Yuan, Li Yang, Hua Zhang, Narasimha M Beeraka, Danfeng Zhang, Qun Wang, Minghua Wang, P R Hemanth Vikram, Gautam Sethi, Geng Wang","doi":"10.1016/j.biopha.2026.119655","DOIUrl":"10.1016/j.biopha.2026.119655","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"119655"},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}