Biomedicine & Pharmacotherapy最新文献

{"title":"Amlodipine mitigates Cisplatin- and acetaminophen-induced nephrotoxicity associated with alterations in renal gamma-glutamyl transpeptidase and oxidative stress","authors":"Majdi Ali Al-Somat ,&nbsp;Hassan Mohammed Al-Mahbashi ,&nbsp;Afif Saeed Al-Nabehi","doi":"10.1016/j.biopha.2026.119187","DOIUrl":"10.1016/j.biopha.2026.119187","url":null,"abstract":"<div><div>Gamma-glutamyl transpeptidase (GGT) plays a pivotal role in renal glutathione metabolism and redox regulation, and its excessive activation contributes to oxidative stress and tubular injury. Cisplatin (CP) and acetaminophen (Aceta) are well-known nephrotoxic agents primarily inducing renal damage through oxidative mechanisms, whereas amlodipine (Amlo) has been suggested to exert nephroprotective effects. This study aimed to evaluate the protective effect of Amlo against CP- and Aceta-induced nephrotoxicity in rats, with particular emphasis on renal GGT activity and oxidative stress. Fifty-six male albino rats were randomly allocated into seven groups receiving normal saline, CP, Aceta, Amlo, or their respective combinations. Treatments were administered for 14 days, with a single intraperitoneal dose of CP (8 mg/kg) on day 10. Renal GGT activity, oxidative stress markers Reduced Glutathione (GSH), Glutathione Peroxidase (GPx), Catalase (CAT), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Nitric Oxide (NO), kidney function indices blood urea nitrogen (BUN), serum creatinine (SC), and urea, and histopathological alterations were assessed. Cisplatin markedly elevated renal GGT activity, oxidative stress parameters, and renal dysfunction markers, whereas Aceta induced a milder but significant renal injury. Amlodipine treatment attenuated GGT overactivation, reduced oxidative stress, and improved renal functional and histological integrity, while Aceta co-administration exacerbated CP-induced renal damage. Collectively, these findings indicate that CP induces more pronounced renal GGT activation and oxidative injury than Aceta, and that Amlo confers significant nephroprotection, underscoring the critical role of GGT in drug-induced nephrotoxicity.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119187"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358030","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":"Targeting DDR1 with novel synthesized antagonists delays cellular aging and enhances wound healing in mesenchymal stem cells","authors":"Hossam Nada ,&nbsp;Ahmed Abdal Dayem ,&nbsp;Sungdo Kim ,&nbsp;Younggeun Park ,&nbsp;Cho Jaemin ,&nbsp;Yujin Park ,&nbsp;Soo Bin Lee ,&nbsp;Moustafa Gabr ,&nbsp;Ssang-Goo Cho ,&nbsp;Kyeong Lee","doi":"10.1016/j.biopha.2026.119182","DOIUrl":"10.1016/j.biopha.2026.119182","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are central to regenerative medicine; however, their clinical utility is constrained by reduced proliferative capacity and replicative senescence during ex vivo expansion. Here, we report on the rational design and biological characterization of novel phthalimide-based inhibitors targeting discoidin domain receptor 1 (DDR1). Structure–activity relationship optimization efforts led to the identification of <strong>AC-4067</strong> and <strong>AC-4061</strong> as potent DDR1 inhibitors, with IC₅₀ values of 30.9 nM and 53.6 nM, respectively. <strong>AC-4067</strong> demonstrated 18-fold selectivity for DDR1 over DDR2 and exhibited no detectable cytotoxicity in normal or cancer cell lines. In Wharton’s jelly–derived MSCs (WJ-MSCs), pharmacological DDR1 inhibition with <strong>AC-4067</strong> enhanced proliferative capacity and accelerated scratch-wound closure without compromising expression of key pluripotency markers (OCT3/4, SOX2, NANOG). Importantly, sustained DDR1 inhibition significantly attenuated replicative senescence, as evidenced by reduced senescence-associated β-galactosidase activity and coordinated downregulation of the senescence regulators p16, p21, and p53. Mechanistically, DDR1 inhibition markedly reduced γH2AX protein levels, indicating suppression of persistent DNA damage signaling and alleviation of chronic DNA damage response activation in late-passage MSCs. This reduction in genomic stress markers was associated with preservation of cellular function and delayed onset of senescence. Collectively, these findings identify DDR1 as a critical regulator of MSC aging and genomic stability and establish <strong>AC-4067</strong> as a promising pharmacological agent for preserving MSC functional integrity and enhancing their therapeutic potential in regenerative medicine.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119182"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372771","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":"Therapeutic antagonism of a key toxin driving Alzheimer’s disease: Comparison of a peptide variant and small molecule","authors":"Catalina Vigil Cardenal,&nbsp;Kashif Mahfooz,&nbsp;Sara Garcia-Rates,&nbsp;Sibah Hasan,&nbsp;Susan Greenfield","doi":"10.1016/j.biopha.2026.119125","DOIUrl":"10.1016/j.biopha.2026.119125","url":null,"abstract":"<div><div>Among emerging therapeutic targets for Alzheimer’s disease (AD), the α7 nicotinic acetylcholine receptor (α7-nAChR) has received much attention and now merits still more focus due to its role as the exclusive binding site for the toxic 14mer peptide T14. T14 is elevated in presymptomatic AD and initiates a pathological cascade involving calcium influx, mTORC1 activation, impaired autophagy, and β-amyloid accumulation. To interrupt this sequence, the cyclated variant of T14, NBP14, was developed, with consequent cognitive benefits in a preclinical mouse model. However, the high molecular weight of NBP14 posed potential limitations for therapeutic translation, prompting the design of NBP6B, a shorter, linear 6-mer variant with improved efficacy and bioavailability. This study aimed to evaluate the efficacy of NBP6B in antagonising T14-induced toxicity in comparison with two novel small molecules, which due to their lower molecular weight could have greater therapeutic potential. Using PC12 cells, T14 activity was assessed through calcium influx and cell viability assays, alongside therapeutic rescue by the drug candidates. To evaluate receptor specificity, α7-nAChR overexpression was employed to determine whether the small molecules acted via α7-dependent or independent pathways. While the small molecules offered favourable drug-like properties and potential for improved blood–brain barrier (BBB) permeability, NBP6B exhibited greater potency and selectivity, with effective antagonism in the nanomolar range, compared to the micromolar concentrations required for the small molecules. These findings thus support NBP6B as a promising and selective α7-targeted therapeutic for early-stage intervention in AD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119125"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358025","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 “Proinsulin C-peptide inhibits high glucose-induced migration and invasion of ovarian cancer cells” [Biomed. Pharmacother., 172 (2024) 116232]","authors":"Eun-Bin Kim ,&nbsp;Hye-Yoon Jeon ,&nbsp;Yung-Taek Ouh ,&nbsp;Ah-Jun Lee ,&nbsp;Chan-Hee Moon ,&nbsp;Sung Hun Na ,&nbsp;Kwon-Soo Ha","doi":"10.1016/j.biopha.2026.119159","DOIUrl":"10.1016/j.biopha.2026.119159","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119159"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349853","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":"Retraction notice to “Local infiltration of the surgical wounds with levobupivacaine, dexibuprofen, and norepinephrine to reduce postoperative pain: A randomized, vehicle–controlled, and preclinical study” [Biomed. Pharmacother. 92 (2017) 459–467]","authors":"Zongwen Gao ,&nbsp;Feng Cui ,&nbsp;Xuemei Cao ,&nbsp;Dejun Wang ,&nbsp;Xiao Li ,&nbsp;Tianzuo Li","doi":"10.1016/j.biopha.2026.119225","DOIUrl":"10.1016/j.biopha.2026.119225","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119225"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147476563","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":"Cannabinoid receptors orchestrate distinct anti-tumour pathways in gastric cancer via and beyond specialized pro-resolving mediators","authors":"Mattia Costanzo ,&nbsp;Poulami Kumar ,&nbsp;Chiara De Simone ,&nbsp;Maria Marotta ,&nbsp;Sara Zirpoli ,&nbsp;Daniela Esposito ,&nbsp;Maria Pina Mollica ,&nbsp;Federica Liotti ,&nbsp;Rosa Marina Melillo ,&nbsp;Alessia Ligresti ,&nbsp;Nella Prevete","doi":"10.1016/j.biopha.2026.119186","DOIUrl":"10.1016/j.biopha.2026.119186","url":null,"abstract":"<div><div>Endocannabinoids (ECS) and specialized pro-resolving mediators (SPMs) are both lipid-based compounds, but differ significantly in origin, mechanisms, and functions. Their mechanistic interaction in cancer remains undefined, particularly in gastric cancer (GC). Several interconnections have been described between these two “bioactive lipids” involved in inflammation resolution, homeostatic and anti-tumour functions. Cannabinoid signalling can modulate SPM biosynthesis in immune cells, thus we investigated whether this crosstalk operates in GC cells, and whether SPMs mediate part of the anti-tumour activity of cannabinoid receptors. Using synthetic and selective agonists for the cannabinoid G-protein-coupled receptors CB1 and CB2 (ACEA and JWH133, respectively), we found that receptor activation in GC cells (AGS and MKN45) sustains the synthesis of two SPMs, Resolvin D1 and Lipoxin B4, which in turn suppresses the angiogenic potential of GC cells. These CB1/CB2-driven activities required a SRC/MAPK signalling. At physiological concentrations, these SPMs further enhanced the binding affinity of ACEA and JWH133 for CB1 and CB2, indicating a functional crosstalk between the two systems. Beyond angiogenesis, CB1/2 stimulation reduced cell proliferation and viability, induced apoptosis, impaired the migration and the epithelial-to-mesenchymal program in GC cells. Only CB2 activation reduced the stemness properties of GC cells. Interestingly, while the anti-angiogenic properties of CB1 and CB2 required SPM production, their other anti-tumour actions were independent of the pro-resolving pathway. Our results extend the current knowledge of the endocannabinoid system by defining a new dual mechanism, SPM-dependent and SPM-independent, that restrains GC progression and identify the ECS-SPM axis as a potential target for therapeutic intervention.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119186"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349983","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":"Noble metal/dextran-graft-polyacrylamide branched polymer nanocomposites induce ROS-dependent apoptosis in diffuse large B-cell lymphoma cells","authors":"Anton Tkachenko ,&nbsp;Kristyna Kupcova ,&nbsp;Pavlo Virych ,&nbsp;Oksana Nadtoka ,&nbsp;Nataliya Kutsevol ,&nbsp;Ondrej Havranek","doi":"10.1016/j.biopha.2026.119176","DOIUrl":"10.1016/j.biopha.2026.119176","url":null,"abstract":"<div><div>In general, polymer/metal nanocomposites might have better anti-cancer properties in comparison to standalone metal nanoparticles (NPs). This emerging class of functional nanomaterials shows improved and more selective tumor delivery with lower toxicity against non-tumor tissues, providing a better biocompatibility and higher effectiveness. Herein, the cytotoxicity of four two-component nanocomposites comprising a metal NP (Au or Ag) and a star-like polymer (dextran-graft-polyacrylamide, <span>D</span>-PAA, or its anionic form, <span>D</span>-PAAan) was tested against multiple diffuse large B-cell lymphoma (DLBCL) cell lines. Our findings suggest that these nanocomposites reduce the viability of DLBCL cells in a dose-dependent manner. The cytotoxic effect of the investigated two-component nanocomposites was mediated by overproduction of reactive oxygen species (ROS, especially in the case of AuNP-based nanocomposites), elevation of intracellular Fe²⁺ levels, with consequent activation of lipid peroxidation and reduced glutathione (GSH) downregulation. Unexpectedly, the nanocomposites did not trigger ferroptosis, which is a type of regulated cell death heavily dependent on ROS and Fe²⁺. Nanocomposite-induced cell death occurred via apoptosis, as evidenced by the activation of caspase-3/7. Interestingly, the tested nanocomposites induced substantial compensatory activation of the pro-survival PI3K/AKT (phosphatidylinositol 3‑kinase/protein kinase B) pathway. However, this was not sufficient to prevent nanocomposite-induced apoptosis. We have demonstrated the anti-lymphoma potential of four noble metal/polymer nanocomposites. Their cytotoxic and anti-lymphoma effects are primarily attributable to oxidative stress with consequent induction of apoptosis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119176"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373738","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":"Interleukin-30 promotes melanoma spreading and triggers LAG-3 expression and T cell exhaustion","authors":"Simona Marchetti ,&nbsp;Carlo Sorrentino ,&nbsp;Cristiano Fieni ,&nbsp;Stefania Livia Ciummo ,&nbsp;Esther Bertuccio ,&nbsp;Maria Crescenti ,&nbsp;Irene Bonaccorsi ,&nbsp;Guido Ferlazzo ,&nbsp;Emma Di Carlo","doi":"10.1016/j.biopha.2026.119183","DOIUrl":"10.1016/j.biopha.2026.119183","url":null,"abstract":"<div><div>Melanoma is an aggressive and highly metastatic malignancy with significant mortality. Although immune checkpoint inhibitors have improved outcomes in advanced disease, immune resistance remains a critical barrier to durable responses, emphasizing the need to define the molecular mechanisms underlying therapeutic failure. Interleukin (IL)30 has been identified as a cancer progression driver with immunosuppressive function in the tumour-microenvironment. Whether it is involved in melanoma aggressiveness and metastasis is unknown. Immunopathological studies, RNA-Seq and CIBERSORTx analyses of tissue samples from the <em>TCGA-SKCM</em> patient cohort, reveal that IL30 expression is absent in normal skin, while it can be found in melanoma and infiltrating immune cells, mostly macrophages. The putative IL30 receptor complex, IL-6Rα/gp130, is expressed by melanoma cells, which respond to IL30 stimulation with increased proliferation and migration, consistent with IL30-mediated upregulation of metastasis-associated genes, including ANG2, CXCR4, ITGB1, MMP2, NME, SNAI2, VEGFA, VEGFC, and L1CAM. Bioinformatic analysis of IL30 transcript levels in TCGA-SKCM tissue specimens, reveals increased IL30 expression in metastases compared with primary tumors, corroborating the experimental findings at the translational level. IL30 reprograms the melanoma immunophenotype by inducing multiple immune checkpoint molecules, including LSECtin, LGALS3, LGALS9, LAG-3, TIM-3, B7-H4, B7-H3, VISTA, and PD-1. Concurrently, IL30 suppresses T cell function by reducing CD25 and HLA-DR expression on CD4⁺ and CD8⁺ T cells, inhibiting their activation and proliferation, decreasing TNF-α and IFN-γ production, and boosting LAG-3 expression, which strongly correlates with IL30 levels in clinical samples. Collectively, these findings identify IL30 as a critical driver of melanoma dissemination and T cell exhaustion, providing a mechanistic link to immune resistance and failure of combination immunotherapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119183"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373769","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":"Retraction notice to \"AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation\" [Biomedicine & Pharmacotherapy 146 (2022) 112563]","authors":"Maliheh Entezari ,&nbsp;Danial Hashemi ,&nbsp;Afshin Taheriazam ,&nbsp;Amirhossein Zabolian ,&nbsp;Shima Mohammadi ,&nbsp;Farima Fakhri ,&nbsp;Mehrdad Hashemi ,&nbsp;Kiavash Hushmandi ,&nbsp;Milad Ashrafizadeh ,&nbsp;Ali Zarrabi ,&nbsp;Yavuz Nuri Ertas ,&nbsp;Sepideh Mirzaei ,&nbsp;Saeed Samarghandian","doi":"10.1016/j.biopha.2026.119190","DOIUrl":"10.1016/j.biopha.2026.119190","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119190"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373747","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":"Retraction notice to “Niosome-based hydrogel of resveratrol for topical applications: An effective therapy for pain related disorder(s)” [Biomedicine & Pharmacotherapy 88 (2017) 480-487]","authors":"Poonam Negi ,&nbsp;Madhur Aggarwal ,&nbsp;Gajanand Sharma ,&nbsp;Charul Rathore ,&nbsp;Gaurav Sharma ,&nbsp;Bhupinder Singh ,&nbsp;O.P. Katare","doi":"10.1016/j.biopha.2026.119191","DOIUrl":"10.1016/j.biopha.2026.119191","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"197 ","pages":"Article 119191"},"PeriodicalIF":7.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379789","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}