Biomedicine & Pharmacotherapy最新文献

{"title":"Mechanistic insights into the protective potential of ambrisentan against L-arginine induced acute pancreatitis and multiorgan damage (role of NRF2/HO-1 and TXNIP/NLRP3 pathways)","authors":"Khaled H. Almutary ,&nbsp;Marwa S. Zaghloul ,&nbsp;Manar A. Nader ,&nbsp;Ahmed R. Elsheakh","doi":"10.1016/j.biopha.2025.118119","DOIUrl":"10.1016/j.biopha.2025.118119","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is an abrupt inflammation of the pancreatic tissue. The severity of AP varies from mild and self-limiting to severe, potentially fatal, and can affect several organ systems. The most severe type of AP causes multiple organ damage (MOD) due to systemic inflammation. In this study, ambrisentan (AMB), an endothelin A receptor antagonist (ETA), was investigated for its potential to ameliorate L-arginine (L-Arg) induced AP and MOD in rats. AP was induced using L-Arg (100 mg/100 g). Two doses of AMB were tested and compared to N-acetylcystiene (NAC) effect. AMB restored the normal structure of the pancreatic, hepatic, pulmonary, and renal tissues. In addition, it normalized the levels of pancreatic enzymes, lactate dehydrogenase (LDH), serum liver enzymes, and kidney biomarkers. Furthermore, AMB corrected the imbalance in the levels of oxidants/antioxidants caused by L-Arg. In contrast, AMB (5 mg/kg) significantly upregulated the protein levels of adenosine monophosphate protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxidase-1(HO-1) and thioredoxin reductase 1 (TXNRD1) by approximately 69.59 %, 85.14 %, 688 % and 96 % respectively, compared with those in rats treated with L-Arg. Furthermore, AMB (5 mg/kg) significantly lowered the thioredoxin-interacting protein (TXNIP), nod-like Receptor Protein 3 (NLRP3), glycogen synthase kinase-3β (GSK-3β), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), CD68, autophagic markers (P62 and LC3) and apoptotic marker caspase 3 by around 62.43 %, 73.56 %, 62.5 %,70 %, 80.3 %, 93 %, 96.7 %, 95 %, 39.6 % respectively, compared to the group treated with L-Arg. AMB effectively improved the AP and MOD produced by L-Arg through its anti-inflammatory and antioxidant properties. NRF2/HO-1 and TXNIP/NLRP3 pathways play major roles in these protective effects.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118119"},"PeriodicalIF":6.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899330","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":"A novel butyrylcholinesterase inhibitor induces antidepressant, pro-cognitive, and anti-anhedonic effects in Flinders Sensitive Line rats: The role of the ghrelin-dopamine cascade","authors":"Nadia Olivier ,&nbsp;Brian H. Harvey ,&nbsp;Stanislav Gobec ,&nbsp;Mohammed Shahid ,&nbsp;Urban Košak ,&nbsp;Simon Žakelj ,&nbsp;Christiaan B. Brink","doi":"10.1016/j.biopha.2025.118093","DOIUrl":"10.1016/j.biopha.2025.118093","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Major depressive disorder (MDD) is often treatment resistant, particularly in addressing anhedonia and cognitive deficits. Novel pharmacological strategies are needed. While butyrylcholinesterase, ghrelin, and dopamine (DA) have been well studied in the context of stress and MDD, their interaction remains unclear.</div></div><div><h3>Experimental approach</h3><div>The dose-dependent antidepressant effects of a novel butyrylcholinesterase inhibitor (BChEI) were evaluated in the Flinders Sensitive Line (FSL) rat model of MDD. Behavioural assessments included the forced swim test (despair), sucrose preference test (reward-related), and novel object recognition test (cognition). Brain-derived neurotrophic factor (BDNF), acetylcholine (ACh), and brain monoamines were analysed, as well as serum growth hormone and acyl- and desacyl-ghrelin. To confirm the role of ghrelin, pharmacological exploration was undertaken using the ghrelin receptor antagonist, D-Lys-3-GHRP-6.</div></div><div><h3>Key results</h3><div>FSL rats had significantly lower ghrelin ratios, BDNF, ACh, DA and growth hormone levels. In FSL rats, both BChEI and escitalopram significantly reduced despair. BChEI significantly outperformed escitalopram in enhancing reward-related and cognitive behaviours. Biochemically, BChEI treatment significantly increased ghrelin ratios and brain DA levels without altering brain 5-HT, ACh or BDNF. D-Lys-3-GHRP-6 significantly reversed the antidepressant-like, rewarding, and pro-cognitive effects of BChEI, accompanied by significant reductions in BDNF and DA.</div></div><div><h3>Conclusions and implications</h3><div>FSL rats display impaired ghrelin, DA, serotonin, growth hormone, and BDNF signalling, akin to MDD. BChEI exerts antidepressant-like effects across despair, reward, and cognitive domains, most likely via the BChE-ghrelin-DA cascade. Reversal of these effects by ghrelin antagonism underscores the critical role of ghrelin, specifically via growth hormone secretagogue receptor-ghrelin interaction. These findings suggest a potentially novel multimodal neurobiological target for the treatment of MDD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118093"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899443","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":"Two cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factors","authors":"Miguel M. Leitão ,&nbsp;Ariana S.C. Gonçalves ,&nbsp;Sérgio F. Sousa ,&nbsp;Fernanda Borges ,&nbsp;Manuel Simões ,&nbsp;Anabela Borges","doi":"10.1016/j.biopha.2025.118090","DOIUrl":"10.1016/j.biopha.2025.118090","url":null,"abstract":"<div><h3>Introduction</h3><div>Quorum sensing (QS) is a bacterial communication mechanism that regulates gene expression, playing a crucial role in various physiological processes. Interfering with this signalling pathway is a promising strategy to control bacterial pathogenicity and virulence.</div></div><div><h3>Objectives</h3><div>This study evaluated the potential of two cinnamic acid derivatives, ferulic and sinapic acids, to inhibit the <em>las</em> and <em>pqs</em> systems in <em>Pseudomonas aeruginosa</em>. Their effects on biofilm architecture, virulence factor production and bacterial motility were also investigated.</div></div><div><h3>Methods</h3><div>Bioreporter strains and bioluminescence-based assays were used to evaluate the modulation of QS-activity by cinnamic acid-type phenolic acids. In addition, <em>in silico</em> docking analysis was performed to validate the binding interactions of the cinnamic acid derivatives with QS-receptors. The biofilm architecture was analysed by optical coherence tomography, and virulence factors production (pyoverdine, pyocyanin, total proteases, lipases, gelatinases and siderophores) and motility were measured by absorbance measurement and plate agar method.</div></div><div><h3>Results</h3><div>Ferulic and sinapic acids at 1000 µg mL⁻¹ inhibited the <em>las</em> and <em>pqs</em> systems by 90 % and 80 %, respectively. The N-3-oxododecanoyl-homoserine lactone production was reduced by 70 % (6.25 µg mL^-¹). <em>In silico</em> analysis demonstrated that cinnamic acid derivatives exhibited comparable interactions and higher docking scores than reference ligands and inhibitors. Biofilm thickness decreased from 96 µm to 11 µm, and virulence factors and swarming motility were significantly impaired. The comparable anti-QS activity of cinnamic acid derivatives suggests that the additional methoxy group in sinapic acid does not directly contribute to its anti-QS effect.</div></div><div><h3>Conclusion</h3><div>Ferulic and sinapic acids compromised the biofilm architecture and virulence of <em>P. aeruginosa</em> through QS inhibition.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118090"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895633","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":"Transforming growth factor-β receptor I kinase plays a crucial role in oligodendrocyte regeneration after demyelination","authors":"Yunkyoung Lee ,&nbsp;Inyoung Jung ,&nbsp;Dong-Won Lee ,&nbsp;Yongbo Seo ,&nbsp;Suhyun Kim ,&nbsp;Hae-Chul Park","doi":"10.1016/j.biopha.2025.118094","DOIUrl":"10.1016/j.biopha.2025.118094","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an autoimmune disease characterized by the loss of oligodendrocytes (OLs) and axon demyelination in the central nervous system. Most therapeutic agents focus on regulating the immune response by suppressing autoimmune reactions. Therefore, developing therapeutic agents that promote remyelination by OLs at disease sites that have already undergone demyelination is necessary. In this study, we generated a new transgenic zebrafish with high efficiency for OL ablation and established a high-throughput screening (HTS)-based platform to identify therapeutic candidates that promote remyelination. Next, we screened a library of kinase inhibitors and identified one candidate, a transforming growth factor-β receptor I (TGF-βRI) kinase inhibitor. Treatment with this kinase inhibitor rapidly recruited microglia to induce clearance of myelin debris, early after OL removal. It also increased the proliferation of OL progenitor cells in demyelinating zebrafish larvae, resulting in restored OL numbers and reduced locomotor activity. Based on these results, we expect our HTS-based platform, along with our newly developed zebrafish model, to be very useful for identifying therapeutic agents that promote remyelination. Furthermore, since the candidate TGF-βRI kinase inhibitor identified in this study restored the phenotype following demyelination, we suggest that TGF-βRI kinase may potentially be a therapeutic target for the treatment of demyelinating diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118094"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890653","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":"Duloxetine improves hyperosmia in mice with pancreatic cancer by increasing dopamine levels in the olfactory bulb","authors":"Tomoya Kuramochi ,&nbsp;Tomoaki Itaya ,&nbsp;Yukino Oshima ,&nbsp;Jinsuk Kim ,&nbsp;Osamu Kitajima ,&nbsp;Takahiro Nakamura ,&nbsp;Taku Homma ,&nbsp;Hideaki Ijichi ,&nbsp;Makoto Sano ,&nbsp;Takahiro Suzuki","doi":"10.1016/j.biopha.2025.118098","DOIUrl":"10.1016/j.biopha.2025.118098","url":null,"abstract":"<div><div>The mechanism and therapeutic insights regarding hyperosmia to food odors in patients with cancer are poorly understood. We therefore evaluated the mechanism and effect of duloxetine in <em>KPPC</em> (<em>LSL-Kras</em>^{<em>G12D/+</em>}<em>; Trp53</em>^{<em>flox/flox</em>}<em>; Pdx-1</em>^{<em>cre/+</em>}) mice with pancreatic cancer. Six-week-old <em>KPPC</em> mice were orally administered 4 mg/kg/day duloxetine (n = 7) or vehicle water (n = 6) daily until the humane endpoint. In healthy mice (n = 6), the buried pellet test (BPT) time was stable during the observation period, whereas BPT time was shortened in vehicle-treated <em>KPPC</em> mice, and this effect was inhibited by administration of duloxetine. The number of degenerated glomerular/mitral cells in the ventral olfactory bulb increased in vehicle-treated <em>KPPC</em> mice compared with healthy mice, and this effect was inhibited by duloxetine. Electron microscopic analysis revealed enlarged mitochondria in the degenerated neural cells. High-performance liquid chromatography analysis revealed a decrease in dopamine levels in the olfactory bulb of <em>KPPC</em> mice compared with healthy mice. The shortened BPT time in vehicle-treated <em>KPPC</em> mice was extended by <span>L</span>-dopa injection and wheel activity (n = 6 each). These findings suggest that duloxetine improves hyperosmia to food odors in mice with pancreatic cancer by increasing dopamine levels in the olfactory bulb.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118098"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895629","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":"Lipid metabolism in cancer: Exploring phospholipids as potential biomarkers","authors":"Dominique Delmas ,&nbsp;Aurélie Mialhe ,&nbsp;Alexia K. Cotte ,&nbsp;Jean-Louis Connat ,&nbsp;Florence Bouyer ,&nbsp;François Hermetet ,&nbsp;Virginie Aires","doi":"10.1016/j.biopha.2025.118095","DOIUrl":"10.1016/j.biopha.2025.118095","url":null,"abstract":"<div><div>Aberrant lipid metabolism is increasingly recognized as a hallmark of cancer, contributing to tumor growth, metastatic dissemination, and resistance to therapy. Cancer cells reprogram key metabolic pathways—including <em>de novo</em> lipogenesis, lipid uptake, and phospholipid remodeling—to sustain malignant progression and adapt to microenvironmental demands. This review summarizes current insights into the role of lipid metabolic reprogramming in oncogenesis and highlights recent advances in lipidomics that have revealed cancer type– and stage–specific lipid signatures with diagnostic and prognostic relevance. We emphasize the dual potential of lipid metabolic pathways—particularly those involving phospholipids—as sources of clinically relevant biomarkers and therapeutic targets. Enzymes and transporters involved in these pathways have emerged as promising candidates for both diagnostic applications and pharmacological intervention. We also examine persistent challenges hindering the clinical translation of lipid-based approaches, including analytical variability, insufficient biological validation, and the lack of standardized integration into clinical workflows. Furthermore, the review explores strategies to overcome these barriers, highlighting the importance of incorporating lipidomics into multi-omics frameworks, supported by advanced computational tools and AI-driven analytics, to decipher the complexity of tumor-associated metabolic networks. We discuss how such integrative approaches can facilitate the identification of actionable metabolic targets, improve the specificity and robustness of lipid-based biomarkers, and enhance patient stratification in the context of precision oncology.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118095"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890715","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":"Methyleugenol alleviates pulmonary vascular remodeling in rats with high-altitude pulmonary hypertension by improving pulmonary smooth muscle cell function","authors":"Yang Yu ,&nbsp;Yurong Wang ,&nbsp;Ziqi Yang ,&nbsp;Zhanqiang Li ,&nbsp;Dianxiang Lu ,&nbsp;Xingmei Nan","doi":"10.1016/j.biopha.2025.118109","DOIUrl":"10.1016/j.biopha.2025.118109","url":null,"abstract":"<div><div>Pulmonary hypertension is divided into five groups, and chronic exposure to hypoxia causes pulmonary hypertension in the third group -- high altitude pulmonary hypertension, which is commonly seen in patients with chronic obstructive pulmonary disease, sleep-disordered breathing, and interstitial lung disease. Its clinicopathological features include right heart overload and right ventricular hypertrophy, with severe patients potentially experiencing right heart failure or even death. The pathogenesis of high altitude pulmonary hypertension is complex; it includes oxidative stress, mitochondrial dysfunction, apoptosis, and pyroptosis. Pharmacological therapy may alleviate the condition if immediate descent to lower altitudes or supplemental oxygen is not possible. Herein, we preliminarily investigated the effect of methyleugenol on high altitude pulmonary hypertension through <em>in vitro</em> and <em>in vivo</em> experiments. Methyleugenol alleviated pulmonary arteriole constriction by acting on potassium ion channels, and inhibited the proliferation of pulmonary artery smooth muscle cells(PASMCs) by decreasing and reactive oxygen species levels, as well as inhibiting the expression of HIF-1α. The cardiac systolic function improved and mitochondrial structure of pulmonary artery smooth muscle cells in rats with high altitude pulmonary hypertension was significantly improved after methyleugenol gavage intervention, and malondialdehyde levels in serum of rats were decreased while those of superoxide dismutase and glutathione increased, suggesting that the reduction of oxidative stress may be one of the mechanisms to improve mitochondrial function. Western blot experiments showed that methyleugenol regulated the oxidative stress level in rats by activating Nrf2/HO-1 signaling pathway, activate p27Kip1, inhibit CDK4/CCND1/ p-ERK1/2 and inhibited HIF-1α/RASSF1/Ras axis to inhibit cell proliferation, thereby improving the occurrence and development of high altitude pulmonary hypertension in rats. The results of this study reveal that methyl eugenol has the potential to alleviate pulmonary vasoconstriction and remodeling in rat models of high-altitude pulmonary hypertension, providing a scientific basis for the application of this compound in improving pulmonary vascular remodeling.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118109"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890651","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":"Mitigation of nicotine-induced podocyte injury through inhibition of thioredoxin interacting protein","authors":"Sayantap Datta ,&nbsp;Mohammad Atiqur Rahman ,&nbsp;Saisudha Koka ,&nbsp;Krishna M. Boini","doi":"10.1016/j.biopha.2025.118110","DOIUrl":"10.1016/j.biopha.2025.118110","url":null,"abstract":"<div><div>Nicotine has been reported to initiate NLRP3 inflammasome formation and activation in different pathological conditions. The current study assessed whether thioredoxin-interacting protein (TXNIP) mediates nicotine-induced NLRP3 inflammasome activation and consequent podocyte injury. Co-immunoprecipitation analysis demonstrated that nicotine-induced TXNIP/NLRP3 interaction in podocytes relative to control groups. However, pre-treatment with TXNIP inhibitors, verapamil (Vera) or SRI-37330 (SRI) attenuates nicotine-induced TXNIP/NLRP3 interaction. Confocal microscopic analysis showed that nicotine treatment significantly increased the colocalization of Nlrp3 with Asc, Nlrp3 with caspase-1 and Nlrp3 with TXNIP in podocytes compared to control cells. Pretreatment with TXNIP inhibitor Vera or SRI abolished nicotine-induced Nlrp3/Asc, Nlrp3/caspase-1 or Nlrp3/TXNIP colocalization. Correspondingly, nicotine treatment significantly increased the caspase-1 activity and IL-1β production compared to control cells. However, prior treatment with TXNIP inhibiting Vera or SRI significantly attenuated the nicotine-induced caspase-1 activity and IL-1β production. Further immunofluorescence analysis showed that nicotine treatment significantly decreased podocin and nephrin expression compared to control cells. However, pretreatment with TXNIP inhibiting Vera or SRI attenuated the nicotine-induced podocin and nephrin reduction. In addition, confocal, flow cytometry and biochemical analysis showed that nicotine treatment significantly increased desmin expression, apoptosis and cell permeability compared to control cells. However, prior treatment with TXNIP inhibiting Vera or SRI significantly attenuated the nicotine-induced desmin expression, apoptosis and cell permeability. Taken together, our results demonstrate that TXNIP/NLRP3 interaction constitutes a potentially key signalling mechanism driving nicotine-induced NLRP3 inflammasome formation, activation and subsequent podocyte damage.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118110"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890652","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":"Mitochondria-targeted rosmarinic acid: Its role against oxidative damage","authors":"Antonella Girgenti ,&nbsp;Pasquale Picone ,&nbsp;Miriam Buttacavoli ,&nbsp;Laura Palumbo ,&nbsp;Flores Naselli ,&nbsp;Elena Lo Presti ,&nbsp;Desirée Pecora ,&nbsp;Chiara Cipollina ,&nbsp;Francesca Annunziata ,&nbsp;Andrea Pinto ,&nbsp;Lucia Tamborini ,&nbsp;Domenico Nuzzo","doi":"10.1016/j.biopha.2025.118114","DOIUrl":"10.1016/j.biopha.2025.118114","url":null,"abstract":"<div><div>Mitochondria plays a key role in the physiological function of neurons, and alteration of this organelle results in severe and irreversible cell damage. Altered mitochondrial activity usually leads to cell degeneration that compromises the function of the neuronal network. Oxidative stress represents the main critical point of this mitochondrial alteration. Research focuses on finding specific treatments for the mitochondrion to target molecules capable of acting in that specific organelle. In this study, we synthesized and evaluated a series of mitochondria-targeted compounds derived from natural phenolic acids, including caffeic, syringic, gallic and rosmarinic acid, intending to enhance their antioxidant and neuroprotective properties. Among these, MITO-rosmarinic was a highly effective compound, demonstrating the ability to mitigate oxidative stress-induced damage in neuronal cells. Our findings underscore the potential of MITO-rosmarinic as a candidate for preventing mitochondrial dysfunction in neurodegenerative diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118114"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890786","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":"From cancer to heart fibrosis ‐ GLIPR1 highlights a subset of myofibroblasts responsive to mesenchymal stem cell therapy after myocardial infarction","authors":"Catalina-Iolanda Marinescu-Colan ,&nbsp;Evelyn-Gabriela Nastase-Rusu ,&nbsp;Carmen-Alexandra Neculachi ,&nbsp;Fabio Martelli ,&nbsp;Laudy Cherry ,&nbsp;Mihai Bogdan Preda ,&nbsp;Alexandrina Burlacu","doi":"10.1016/j.biopha.2025.118087","DOIUrl":"10.1016/j.biopha.2025.118087","url":null,"abstract":"<div><div>Despite recent advances in pre-clinical research on cardiac remodeling following myocardial infarction (MI), the precise molecular pathways remain poorly understood and effective therapies for heart failure are still delayed in development. Aged animal models may more accurately reflect the clinical scenario, as aging alters the cellular identities and impedes cardiac repair. In this manuscript, we investigated the expression profile of mouse cardiac fibroblasts following myocardial infarction, using both young and aged animals to enhance the translational significance. The initial studies aimed to identify fibroblast changes common to both young and old animals. Additionally, a group of young animals that underwent mesenchymal stem cells (MSC) therapy after MI surgery was included to help identify the molecular changes amenable to therapeutic modulation. The analysis uncovered Glioma- Pathogenesis Related Protein 1 (GLIPR1) activation during the post-MI maturation phase in a subset of myofibroblasts, localized to the infarct zone in young subjects and widespread throughout the ventricle in aged animals. Further investigations indicated that the inflammatory environment post-MI induced the upregulation of GLIPR1, which in turn promoted increased TIMP3 expression. These findings provide valuable insights for future research aimed at exploring the therapeutic potential of targeting GLIPR1 to reduce cardiac fibrosis post-MI.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118087"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890791","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}