Duncan A. Sylvestre , Nuanyi Liang , James Guinto Galan , Amber Safar , Felipe de Costa Souza , Mitchell C. Bancks , Vedanth Sundaram , Brian W. Scott , Kasey Schalich , Michael Goodson , Jennifer M. Rutkowsky , Kristopher Galang , Gulustan Ozturk , David A. Mills , Daniela Barile , Ameer Y. Taha
{"title":"Milk fat-globules derived from whey protein phospholipid concentrate prevent high-fat diet induced cognitive impairment in wistar rats in a manner associated with increased brain neuronal connectivity and sphingolipid clearance","authors":"Duncan A. Sylvestre , Nuanyi Liang , James Guinto Galan , Amber Safar , Felipe de Costa Souza , Mitchell C. Bancks , Vedanth Sundaram , Brian W. Scott , Kasey Schalich , Michael Goodson , Jennifer M. Rutkowsky , Kristopher Galang , Gulustan Ozturk , David A. Mills , Daniela Barile , Ameer Y. Taha","doi":"10.1016/j.biopha.2026.119009","DOIUrl":"10.1016/j.biopha.2026.119009","url":null,"abstract":"<div><div>Whey protein phospholipid concentrate (WPPC), a co-product of whey protein processing, is enriched in milk fat globules containing phospholipids, glycoconjugates and sugar monomers (e.g. sialic acid) critical to myelin synthesis in the brain. We hypothesized that WPPC will prevent cognitive impairment induced by a high fat (HF) diet by promoting myelin turnover and improving neuronal connectivity between the entorhinal cortex-hippocampal circuitry involved in encoding memory. Rats were randomized from weaning to ∼6.5 months of age to the following diets: a low-fat (LF) diet containing 10 % fat by weight, a HF diet containing 45 % fat by weight to induce cognitive impairment, and a HF diet containing either 1.6 % (HF1.6) or 10 % (HF10) WPPC by weight (n = 12 per group). Rats received cognitive testing after 1.5 and 4 months of dietary intervention, then implanted with chronic bipolar electrodes to measure axonal evoked responses within the entorhinal cortex-hippocampal circuitry by stimulating the entorhinal cortex, measuring the half-max response in the hippocampus, and comparing the half-max response to a measurement made approximately one hour later (as a marker of memory storage potential). Hippocampal phospholipid and sphingolipid components of myelin were quantified. At 4 months, rats on the HF diet performed significantly worse on cognitive testing than rats on the LF, HF1.6 and HF10 diets. These effects were linked to slight improvements in the evoked response associated with hippocampal-dependent memory storage. Additionally, hippocampus sphingolipids were higher in rats on the HF diet compared to the LF, HF1.6 and HF10 groups. These findings demonstrate that WPPC prevented cognitive impairment induced by a HF diet by regulating entorhinal cortex-hippocampal circuitries associated with memory storage, through modulating myelin turnover.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119009"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215299","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}
Mohammed Alorabi , Simona Cavalu , Hayder M. Al-kuraishy , Ali I. Al-Gareeb , Gomaa Mostafa-Hedeab , Walaa A. Negm , Amal Youssef , Aya H. El-Kadem , Hebatallah M. Saad , Gaber El-Saber Batiha
{"title":"Corrigendum to “Pentoxifylline and berberine mitigate diclofenac-induced acute nephrotoxicity in male rats via modulation of inflammation and oxidative stress” [Biomed. Pharmacother. 152 (2022) 113225]","authors":"Mohammed Alorabi , Simona Cavalu , Hayder M. Al-kuraishy , Ali I. Al-Gareeb , Gomaa Mostafa-Hedeab , Walaa A. Negm , Amal Youssef , Aya H. El-Kadem , Hebatallah M. Saad , Gaber El-Saber Batiha","doi":"10.1016/j.biopha.2026.119133","DOIUrl":"10.1016/j.biopha.2026.119133","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119133"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222416","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}
Agata Knabe , Michał Bartmański , Monika Sakowicz-Burkiewicz , Lucjan Samson , Grzegorz Ronowski , Anna Ronowska
{"title":"Protection of osteoblasts from Zn²⁺ toxicity in titanium implant surface modification: Lipoic acid against induced metabolic collapse","authors":"Agata Knabe , Michał Bartmański , Monika Sakowicz-Burkiewicz , Lucjan Samson , Grzegorz Ronowski , Anna Ronowska","doi":"10.1016/j.biopha.2026.119157","DOIUrl":"10.1016/j.biopha.2026.119157","url":null,"abstract":"<div><div>Zinc-modified titanium coatings hold great promise for improving implant osseointegration through their osteoinductive properties. Excessive Zn²⁺ may induce cytotoxicity by metabolic dysfunction in osteoblasts. This study evaluates the metabolic and osteogenic responses of human fetal osteoblasts and primary osteoblasts derived from osteoarthritic patients following exposure to Zn²⁺, lipoic acid (LA), lipoamide (LAM) and their combinations. Cells were treated with Zn²⁺ (0.15 mM), LA (0.10 mM), LAM (0.10 mM), or their combinations. The citrate metabolism and mitochondrial activity were quantified as well as the parameters engaged in osteoblastic mineralization. Zn²⁺ reduced mitochondrial activity resulting in decreased viability. Zn²⁺ induced substantial lactate accumulation in POB and markedly suppressed ACLY activity, leading to intracellular citrate retention and altered epigenetic metabolic signatures. Zn²⁺ significantly upregulated RUNX2 expression in POB aligning with improved mineralization capacity. LA consistently rescued Zn-evoked metabolic dysfunction in POB, restoring aconitase and LDH activity. Lipoates markedly enhanced mineralization in osteoblastic cells. Primary osteoblasts exhibited substantially higher basal inflammatory activity than hFOB 1.19, reflecting their pathological origin, yet Zn²⁺ and lipoates did not exacerbate cytokine release. This study demonstrates that primary osteoblasts derived from osteoarthritic bone provide a more physiologically relevant model for evaluating implant-associated cytotoxicity and osteogenic potential. While Zn²⁺ at 0.15 mM impairs mitochondrial metabolism, LA effectively prevents Zn-induced oxidative dysfunction, restores key metabolic pathways, and markedly enhances mineralization. These findings identify lipoic acid as a promising cytoprotective additive for zinc-based titanium implant coatings, offering a strategy to preserve antibacterial efficacy while minimizing cytotoxicity and promoting osseointegration.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119157"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313435","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":"Non-coding RNA Trojan nanocarriers in CRC: Mechanistic crossroads and therapeutic challenges","authors":"Mingrong Cheng , Yucheng Ni , Wei Zhang , Qinghua Wu","doi":"10.1016/j.biopha.2026.119098","DOIUrl":"10.1016/j.biopha.2026.119098","url":null,"abstract":"<div><div>Chemoresistance in colorectal cancer (CRC) represents a core bottleneck in clinical treatment, primarily driven by the cross-regulatory network formed by cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Non-coding RNAs (ncRNAs) play a central role in this regulatory network, providing crucial molecular targets for chemoresistance intervention. However, the clinical translation of ncRNAs is limited by delivery challenges. The nanoscale \"Trojan Horse\" drug delivery system achieves precise delivery through triple-targeting design: at the tissue level, tumor accumulation is realized via the enhanced permeability and retention effect and targeted modification; at the cellular level, it targets CSCs and other chemoresistant cells; at the molecular level, it interferes with core pathways of stemness, EMT, and chemoresistance. Additionally, this system enables synergistic combination of chemotherapy with gene therapy, immunotherapy, phototherapy, and other modalities through multi-drug co-delivery, while integrating theranostic functions to synchronize chemoresistance monitoring and treatment. This review systematically elaborates on the mechanisms of ncRNA-mediated regulation of CRC chemoresistance, the design strategies and application efficacy of the nanoscale \"Trojan Horse\" system, providing critical insights for overcoming CRC cross-resistance and advancing the clinical translation of ncRNA nanotherapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119098"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145009","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}
Won Seok Kim , Jeongyoon Choi , Seong-Seop Kim , June Hee Kim , Young-Eun Han , Myoung Jin Kwak , Soo-Jin Oh , Bonggi Lee , Ik-Hyun Cho , Chun Whan Choi , Gyu-Sang Hong , Min Soo Kim
{"title":"Vitisin B, extracted from Vitis vinifera, enhances memory function and neuroprotective effects in scopolamine-induced memory-impaired mice","authors":"Won Seok Kim , Jeongyoon Choi , Seong-Seop Kim , June Hee Kim , Young-Eun Han , Myoung Jin Kwak , Soo-Jin Oh , Bonggi Lee , Ik-Hyun Cho , Chun Whan Choi , Gyu-Sang Hong , Min Soo Kim","doi":"10.1016/j.biopha.2026.119019","DOIUrl":"10.1016/j.biopha.2026.119019","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is characterized by progressive cognitive decline and memory dysfunction, with prominent roles in cholinergic deficits and synaptic plasticity impairments. Vitisin B, a resveratrol tetramer derived from <em>Vitis vinifera</em>, exhibits potent antioxidant and neuroprotective properties. However, its potential to influence cognitive function in AD models remains inadequately explored. In this study, we first tested vitisin B in an in vitro model using SH-SY5Y cells exposed to scopolamine-induced cytotoxicity, where vitisin B significantly enhanced cell viability and promoted cell survival. We evaluated its therapeutic potential in vivo using both systemic administration and direct delivery into the third ventricle of the brain in a scopolamine-induced AD mouse model. Across both administration routes, vitisin B exerted a broad pro-cognitive effect, restoring multiple domains of learning and memory disrupted by scopolamine. Vitisin B recovered spatial working memory in the Y-maze, normalized exploratory activity in the open field, improved recognition memory in the novel object recognition (NOR) test, and enhanced long-term memory retention in the passive avoidance assay. This treatment restored cognitive function, alleviated cholinergic deficits, increased hippocampal brain-derived neurotrophic factor (BDNF) levels, and enhanced synaptic plasticity. These results suggest that vitisin B exerts reliable cognitive and neuroprotective effects through both systemic and cerebral administration, highlighting its potential as a promising therapeutic compound for restoring cholinergic function and enhancing hippocampal synaptic plasticity in AD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119019"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127953","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}
Mohammed Bouzelha , Karine Pavageau , Sarah Renault , Enora Ferron , Nicolas Jaulin , Maia Marchand , Dimitri Alvarez-Dorta , Roxanne Peumery , Mathieu Scalabrini , Héloïse Delépée , Allwyn Pereira , Elise Enouf , Mathieu Cinier , Oumeya Adjali , Sébastien G. Gouin , Christelle Retière , Mickaël Guilbaud , David Deniaud , Mathieu Mével
{"title":"Ultrafast tyrosine-based cell membrane modification via diazonium salts: A new frontier for biomedical applications","authors":"Mohammed Bouzelha , Karine Pavageau , Sarah Renault , Enora Ferron , Nicolas Jaulin , Maia Marchand , Dimitri Alvarez-Dorta , Roxanne Peumery , Mathieu Scalabrini , Héloïse Delépée , Allwyn Pereira , Elise Enouf , Mathieu Cinier , Oumeya Adjali , Sébastien G. Gouin , Christelle Retière , Mickaël Guilbaud , David Deniaud , Mathieu Mével","doi":"10.1016/j.biopha.2026.119095","DOIUrl":"10.1016/j.biopha.2026.119095","url":null,"abstract":"<div><div>In this study, we present an ultrafast, efficient, and broadly applicable strategy for cell membrane modification <em>via</em> tyrosine-selective bioconjugation using diazonium salt derivatives. This chemical approach enables both one-step and two-step functionalization of adherent, suspension, and primary cells with a wide range of ligands, including imaging probes, carbohydrates, biotin, and proteins, without inducing cytotoxicity or immune activation. Cell membrane engineering through bioconjugation has emerged as a powerful tool in biomedical research, given the central role of the membrane in signaling, transport, and cell-cell interactions. In contrast to conventional glyco-engineering methods, which typically require multiday incubations and can induce cellular stress, our approach achieves rapid, precise, and high-density surface functionalization in less than one hour, with improved reproducibility and biological compatibility. We further demonstrate the applicability of this strategy across diverse cell types, including immortalized cell lines and clinically relevant primary cells such as peripheral blood mononuclear cells (PBMCs) and human natural killer (NK) cells. Notably, surface grafting of an EGFR-targeting Nanofitin enhances the cytotoxic activity of NK cells against EGFR-positive cancer cells. In addition, we show that the bioconjugated signal progressively diminishes over successive cell divisions, providing a self-limiting and transient alternative to permanent genetic modifications such as CAR-based engineering, thereby potentially reducing the risk of prolonged immune activation. Finally, the ability to store pre-functionalized cells at −80 °C increases the practicality of this platform for future ready-to-use applications. Overall, this versatile and non-genetic bioconjugation strategy offers a compelling alternative to existing technologies for applications in targeted therapy, diagnostics, and cell-based immunotherapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119095"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133759","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}
Yen-Dun Tony Tzeng , Chen-Yueh Wen , Su-Boon Yong, Chia-Jung Li
{"title":"Mitoxyperilysis links organelle positioning to inflammatory lysis: A new lens for pharmacotherapy design","authors":"Yen-Dun Tony Tzeng , Chen-Yueh Wen , Su-Boon Yong, Chia-Jung Li","doi":"10.1016/j.biopha.2026.119103","DOIUrl":"10.1016/j.biopha.2026.119103","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119103"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138248","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}
Jin Yoo , Hanhee Cho , Heewon Yang , Jinseong Kim , Seung Hwan Lee , Kwangmeyung Kim , Tai Hyun Park
{"title":"Nanodiscs embedded with μ-opioid receptors as decoy receptors to reverse opioid overdose","authors":"Jin Yoo , Hanhee Cho , Heewon Yang , Jinseong Kim , Seung Hwan Lee , Kwangmeyung Kim , Tai Hyun Park","doi":"10.1016/j.biopha.2026.119043","DOIUrl":"10.1016/j.biopha.2026.119043","url":null,"abstract":"<div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (267KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span><span><span><p>The clinical reversal of opioid overdose, such as that caused by fentanyl, is achieved using opioid receptor antagonists such as naloxone. While naloxone is lifesaving, its abrupt blockade of μ-opioid receptors (μORs) can precipitate severe acute withdrawal symptoms, partly driven by underlying molecular mechanisms such as receptor desensitization and internalization. In addition, naloxone has a short half-life (30–90 min), requiring repeated administration in cases involving opioids with prolonged pharmacokinetic profiles, such as fentanyl. To address these limitations, we propose a decoy-receptor strategy using μOR-embedded nanodiscs (μOR-NDs) that sequester opioid molecules, thereby attenuating opioid effects without abrupt receptor blockade. μOR-NDs exhibit high in vivo stability and demonstrate brain-associated biodistribution. These results suggest that μOR-NDs can cross the blood–brain barrier (BBB) and have the potential to treat opioid overdose. Overall, this decoy-receptor approach offers an innovative paradigm for safer opioid neutralization with more controlled mitigation of withdrawal.</p><div>Graphical abstract</div></span></span></figure></span></div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"196 ","pages":"Article 119043"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183768","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}