Biomedicine & Pharmacotherapy最新文献

{"title":"Comparative analysis of micellar and native formulations of Boswellia serrata oleogum extracts in T-cell receptor-activated lymphocytes","authors":"Amira Duweb ,&nbsp;Michael Schmiech ,&nbsp;Judith Ulrich ,&nbsp;Emaad Abdel-Kahaar ,&nbsp;Maximilian Pfeiffer ,&nbsp;Menna El Gaafary ,&nbsp;Holger Barth ,&nbsp;Thomas Simmet ,&nbsp;Tatiana Syrovets","doi":"10.1016/j.biopha.2025.118009","DOIUrl":"10.1016/j.biopha.2025.118009","url":null,"abstract":"<div><div>Chronic inflammatory disorders represent one of the predominant healthcare burdens. There is evidence that the oleogum resin from <em>Boswellia serrata</em> trees can downmodulate pro-inflammatory processes. Lipid micellar preparations of <em>Boswellia serrata</em> have been introduced to the market to overcome the low bioavailability of nonformulated <em>Boswellia</em> oleogum resin preparations. In this study, we aimed to compare the anti-inflammatory effects of two different <em>Boswellia serrata</em> nutraceuticals: the native, nonformulated Biotikon® BS-85 and the micellar Boswellia-Loges®. We have previously shown that single oral administration of 800 mg of either formulation reduces the release of proinflammatory cytokines TNF-α, IL-1β, and IL-6 by LPS-activated blood of donors. Here we show that under the same conditions, the production of IL-17A was increased by the nonformulated, native extract of <em>Boswellia serrata</em> oleogum resin. <em>In vitro</em>, the nonformulated but not the micellar formulation of <em>Boswellia serrata</em> oleogum resin decreased the release of IFN-γ, TNF-α, and IL-2 by TCR-activated lymphocytes<em>.</em> Both formulations as well as the bioactive principles boswellic acids lowered NF-κB activity in TCR-activated T lymphocytes<em>.</em> Similarly, both <em>Boswellia serrata</em> formulations and boswellic acids reduced NFAT activity in TCR-activated T lymphocytes. The nonformulated <em>Boswellia serrata</em> extract exhibited higher inhibitory activity on the release of T-cell cytokines. The results suggest that nutraceuticals containing the nonformulated oleogum extract of <em>Boswellia serrata</em> might be more effective in hampering chronic inflammatory disorders characterized by increased activity of T cells than the micellar formulations.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118009"},"PeriodicalIF":6.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and anticancer activity of Streptomyces ambofaciens (Myt 8) and S. globisporus ONU 1019 (Myt 11) secondary metabolites isolated from the Odesa Bay, the Black Sea: An in vitro study","authors":"Kateryna Potapenko ,&nbsp;Gennadii Lisiutin ,&nbsp;Nataliia Vasylieva ,&nbsp;Iryna Strashnova ,&nbsp;Raimo Franke ,&nbsp;Nataliia Petriv ,&nbsp;Oladimeji Paul Duduyemi ,&nbsp;Kyrylo Baklan ,&nbsp;Nadiia Korotaieva ,&nbsp;Tetyana Gudzenko ,&nbsp;Michael P. Manns ,&nbsp;Mark Broenstrup ,&nbsp;Henrike Lenzen ,&nbsp;Marius Vital ,&nbsp;Volodymyr Ivanytsia ,&nbsp;Tetyana Yevsa","doi":"10.1016/j.biopha.2025.117981","DOIUrl":"10.1016/j.biopha.2025.117981","url":null,"abstract":"<div><div>We investigated the antimicrobial and anticancer capacity of secondary metabolites from six strains of marine actinobacteria belonging to the genus <em>Streptomyces</em>. Bacteria strains were isolated from the Black Sea and identified using 16S rRNA gene sequencing. Exometabolites were extracted using ethyl acetate. Antagonistic activity was investigated by agar block-diffusion method against ten strains of indicator microorganisms. The anticancer activities of the extracts were assessed on murine cholangiocarcinoma (CCA) cells while normal mouse fibroblasts CBA-310 served as a control. The extracts were tested as monotherapy or in combination with a standard chemotherapeutic drug for CCA, gemcitabine. Cell proliferation and viability were assessed using crystal violet and cell counting kit-8 assays. The induction of cellular senescence was investigated by senescence-associated β-galactosidase assay. Fluorescence-activated cell sorting analysis was used to determine cellular apoptosis and necroptosis. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was used to define the main players in the extracts. <em>Streptomyces</em> strains showed antagonistic activity against at least one indicator microorganism. Two extracts, <em>S. ambofaciens</em> (Myt 8) and <em>S. globisporus</em> ONU 1019 (Myt 11), displayed anticancer activity. Extracts Myt 8 and Myt 11 alone or in combination with low doses of gemcitabine inhibited CCA cells in a time and dose-dependent manner and induced early apoptosis and cellular senescence. LC-MS/MS analysis identified daidzein, germicidin, staurosporine alpha-curcumene, and alpha-calacorene - with potential antibacterial and anticancer effects. <em>Streptomyces</em> extracts showed antimicrobial and anticancer properties, potentially reducing chemotherapy doses for CCA. These findings suggest a dual therapeutic role against infections and CCA, warranting further <em>in vivo</em> studies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 117981"},"PeriodicalIF":6.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AhR/P38 MAPK pathway mediates kynurenine-induced cardiomyocyte damage: The dual role of resveratrol in apoptosis and autophagy","authors":"Sara Mohiti ,&nbsp;Effat Alizadeh ,&nbsp;Line S. Bisgaard ,&nbsp;Mehrangiz Ebrahimi-Mameghani ,&nbsp;Christina Christoffersen","doi":"10.1016/j.biopha.2025.118015","DOIUrl":"10.1016/j.biopha.2025.118015","url":null,"abstract":"<div><div>Chronic kidney disease increases the risk of cardiovascular disease, partly due to uremic toxins, such as Kynurenine (KYN). While KYN contributes to tissue damage, its role in cardiomyocyte apoptosis and autophagy remains unclear. Resveratrol (RSV) can protect against oxidative stress and inflammation, whereas its specific effects on KYN-induced cardiomyopathy are less understood. This study aimed to investigate the role of KYN in cardiomyocyte apoptosis and autophagy and examine the protective effects of RSV against KYN-induced damage. H9C2 cardiomyocytes were cultured and treated with KYN in presence or absence of RSV or inhibitors of the AhR/Src/MAPKs pathway. Cell viability, apoptosis, mitochondrial membrane potential, and autophagy were assessed using MTT, TUNEL, JC-1, and autophagy detection assays. KYN induced apoptosis, and autophagy in H9C2 cells. RSV pretreatment reduced apoptosis but enhanced autophagy in KYN-treated cells. Inhibiting autophagy or blocking apoptosis, increased KYN-induced apoptosis and autophagy, respectively. Additionally, KYN treatment enhanced AhR activation and the phosphorylation of Src and MAPKs proteins, whereas RSV pretreatment decreased AhR activation and ERK phosphorylation. Inhibitors of p38 MAPK and JNK reduced expression of apoptotic proteins. AhR inhibition also reduced the phosphorylation of p38 MAPK and expression of apoptotic proteins while it enhanced autophagy-related protein expression in KYN treated H9C2 cells. In conclusion, our findings suggest that KYN induces cardiomyocyte apoptosis via the AhR/p38 MAPK pathway whereas RSV can protect against the KYN-induced apoptosis while promoting autophagy. Given the high cardiovascular risk in CKD patients, these findings provide in-sight into potential therapeutic strategies targeting KYN-induced cardiomyopathy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118015"},"PeriodicalIF":6.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current knowledge on the mechanisms underpinning vasculogenic mimicry in triple negative breast cancer and the emerging role of nitric oxide","authors":"Belete Kassa Alemu ,&nbsp;Sara Tommasi ,&nbsp;Julie-Ann Hulin ,&nbsp;Jai Meyers ,&nbsp;Arduino A. Mangoni","doi":"10.1016/j.biopha.2025.118013","DOIUrl":"10.1016/j.biopha.2025.118013","url":null,"abstract":"<div><div>Vasculogenic mimicry (VM) is the process by which cancer cells form vascular-like channels to support their growth and dissemination. These channels lack endothelial cells and are instead lined by the tumour cells themselves. VM was first reported in uveal melanomas but has since been associated with other aggressive solid tumours, such as triple-negative breast cancer (TNBC). In TNBC patients, VM is associated with tumour aggressiveness, drug resistance, metastatic burden, and poor prognosis. The lack of effective targeted therapies for TNBC has stimulated research on the mechanisms underpinning VM in order to identify novel druggable targets. In recent years, studies have highlighted the role of nitric oxide (NO), the NO synthesis inhibitor, asymmetric dimethylarginine (ADMA), and dimethylarginine dimethylaminohydrolase 1 (DDAH1), the key enzyme responsible for ADMA metabolism, in regulating VM. Specifically, NO inhibition through downregulation of DDAH1 and consequent accumulation of ADMA appears to be a promising strategy to suppress VM in TNBC. This review discusses the current knowledge regarding the molecular pathways underpinning VM in TNBC, anti-VM therapies under investigation, and the emerging role of NO regulation in VM.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118013"},"PeriodicalIF":6.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EAAT3 modulation: A potential novel avenue towards remyelination in multiple sclerosis","authors":"Lieve van Veggel ,&nbsp;Melissa Schepers ,&nbsp;Assia Tiane ,&nbsp;Vijay Kumar ,&nbsp;Emily Willems ,&nbsp;Ben Rombaut ,&nbsp;Jurrie Noordijk ,&nbsp;Tim Vangansewinkel ,&nbsp;Anna Li ,&nbsp;Esther Wolfs ,&nbsp;Berra Ozcan ,&nbsp;Evelien Nouboers ,&nbsp;Pablo R. Moya ,&nbsp;David B. Sauer ,&nbsp;Hanne Diliën ,&nbsp;Niels Hellings ,&nbsp;Rudy Schreiber ,&nbsp;Tim Vanmierlo","doi":"10.1016/j.biopha.2025.117960","DOIUrl":"10.1016/j.biopha.2025.117960","url":null,"abstract":"<div><div>Modulating the excitatory amino acid transporter 3 (EAAT3) can be considered a novel approach for the treatment of multiple sclerosis (MS). EAAT3 plays a crucial role in regulating oxidative stress and oligodendrocyte function through its ability to transport cysteine, the rate-limiting building block in the synthesis of the antioxidant glutathione. Therefore, EAAT3 activation is hypothesised to improve oligodendrocyte health and relieve its differentiation block in MS, improving remyelination capacity. Using a cuprizone-induced demyelination model, the effects of EAAT3 overexpression by viral transduction of oligodendrocytes and pharmacological inhibition of EAAT3 were examined. Surprisingly, EAAT3 overexpression significantly hampered remyelination, while EAAT3 inhibition prevented demyelination and improved functional remyelination as assessed by visual evoked potentials and post mortem myelin basic protein fluorescent staining.</div><div>Next, cellular mechanisms underlying these results were investigated. Consistent with the <em>in vivo</em> findings, post mortem gene expression analysis of the corpus callosum of cuprizone treated animals revealed a trend towards upregulation of oligodendrocyte lineage genes in response to EAAT3 inhibition, supporting its role in oligodendrocyte health and myelination processes. <em>In vitro</em> studies using the human oligodendroglioma (HOG) cell line demonstrated the beneficial effects of EAAT3 inhibition on cellular morphology, indicating potential roles in promoting oligodendrocyte maturation and myelination. In contrast, EAAT3 overexpression appears to hamper these processes.</div><div>These findings suggest that, contrary to our initial hypothesis, EAAT3 inhibition could improve oligodendrocyte function and myelination processes, highlighting its potential as a therapeutic target for demyelinating disorders. Future studies should address the exact molecular mechanism through which this effect is obtained.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 117960"},"PeriodicalIF":6.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical constituents from the Korean endemic plant Pseudolysimachion pusanensis inhibit diffuse-type gastric cancer cells","authors":"Su-Yeon Cho ,&nbsp;Hoseong Hwang ,&nbsp;Hyeon-Seong Lee ,&nbsp;Yujin Kwon ,&nbsp;Ngoc Khanh Vu ,&nbsp;Jong Gwon Baek ,&nbsp;Mukyeong Jeon ,&nbsp;Joonbeom Bae ,&nbsp;Hak Cheol Kwon ,&nbsp;Won Kyu Kim ,&nbsp;Jaeyoung Kwon","doi":"10.1016/j.biopha.2025.118005","DOIUrl":"10.1016/j.biopha.2025.118005","url":null,"abstract":"<div><div>Diffuse-type gastric cancer (GC) is closely associated with genetic abnormalities; however, its exact pathological mechanisms are still not understood. It manifests without symptoms before advanced stages and is often difficult to diagnose using routine imaging tests. Therefore, specific targeted therapies for diffuse GC are currently unavailable. In this study, the extract of <em>Pseudolysimachion pusanensis</em>, which is endemic to Korea, inhibited the proliferation of GC cells, MKN1 and SNU668, while the other extracts of the two endemic <em>Pseudolysimachion</em> species did not show any activity. This led to the molecular networking analysis of <em>Pseudolysimachion</em> species to identify the molecules mostly observed only in <em>P. pusanensis</em>. Thirteen new (<strong>1</strong>–<strong>13</strong>) and eight known (<strong>14</strong>–<strong>21</strong>) compounds were obtained and structurally characterized. Of these, cucurbitacin derivative compounds <strong>1</strong> and <strong>14</strong>–<strong>16</strong> showed activity, and particularly, the IC₅₀ value of compound <strong>1</strong> was 0.65 and 0.21 μM. Ki-67 expression analysis, single-cell originated cell proliferation assay, and western blot analysis of apoptotic cell death-related molecules revealed that compound <strong>1</strong> mediated both cytostasis and cellular death via apoptosis. Particularly, this compound exhibited an anti-tumorigenic effect on the invasion of diffuse-type GC cells by perturbing the epithelial-to-mesenchymal transition (EMT) pathway, as demonstrated by invasion assays using both 2D models and in vivo-like 3D spheroid co-culture models, as well as western blot analysis of EMT markers. In addition, some functional groups that may or may not be necessary for the activity of cucurbitacin derivatives were identified, and some clues that the presence of metal ions may affect the activity were provided.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118005"},"PeriodicalIF":6.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess heme orchestrates progesterone resistance in uterine endometrial cancer through macrophage polarization and the IL-33/PAX8/PGR axis","authors":"Jia-Jing Lu ,&nbsp;Yan Ning ,&nbsp;Wen-Ting Hu ,&nbsp;Yan-Ran Sheng ,&nbsp;Yu-Kai Liu ,&nbsp;Feng Xie ,&nbsp;Ming-Qing Li ,&nbsp;Xiao-Yong Zhu","doi":"10.1016/j.biopha.2025.118008","DOIUrl":"10.1016/j.biopha.2025.118008","url":null,"abstract":"<div><div>Progesterone is an important drug for hormone therapy in uterine endometrial cancer (UEC). However, the therapeutic efficacy of progestogen is often limited by resistance, and the underlying mechanism remains unknown. In this study, we observed heme metabolism is more active in progesterone-insensitive patients. Heme induced macrophages (Mφs) bias towards M2-like phenotype and downregulated the expression of IL-33, resulting in increased levels of Paired box gene 8 (PAX8). Further study showed PAX8 inhibited the transcriptional activity of PGR by binding to the PGR promoter region. In addition, PGR can also act as a transcriptional factor to regulate the transcription of autophagy-related gene 7 (ATG). Low expression of PGR decreases the transcriptional activity of ATG7 promoter, which decreases cell autophagy and promotes the progression of UEC. Overall, this study reveals the important interaction between heme metabolism, IL-33 and PGR in progesterone-insensitive UEC, and is promising to provide new therapeutic targets for overcoming progesterone resistance.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118008"},"PeriodicalIF":6.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological solutions activated by cold plasma at atmospheric pressure: A new therapeutic approach for skin wound healing","authors":"Solène Roux ,&nbsp;Aurélie Marchès ,&nbsp;Stéphane Galiacy ,&nbsp;Nofel Merbahi ,&nbsp;Michel Simon","doi":"10.1016/j.biopha.2025.118001","DOIUrl":"10.1016/j.biopha.2025.118001","url":null,"abstract":"<div><div>Chronic wounds are a major public health problem, and nearly 35 % of them do not heal with conventional treatments. The direct application of cold plasmas at atmospheric pressure, partially ionized gases, is an emerging technology with a range of potential biomedical applications, including the improvement of wound healing. A new method that is easier to implement has been developed: the use of biological solutions exposed to cold plasmas at atmospheric pressure, known as plasma-activated media (PAM). Numerous preclinical studies and in vitro models indicate that PAM treatments facilitate wound healing by promoting the migration of cell types such as keratinocytes, fibroblasts and mesenchymal stem/stromal cells, stimulating angiogenesis, and inhibiting bacterial proliferation, all of which are critical to this vital process. PAM treatments modulate the inflammatory response, induce the expression of growth factors and matrix metalloproteinases, reduce cellular adhesion, promote cytoskeletal modifications and activate several biochemical pathways involved in the wound healing process, possibly through the action of plasma-generated reactive oxygen and nitrogen species. Some studies have shown that PAM may have applications in the treatment of other skin conditions either by reducing the production of pro-inflammatory cytokines or by inducing apoptosis of tumor cells. PAM treatments therefore represent a promising new therapy for the management of dermatological conditions, particularly for chronic skin and mucosal wounds.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118001"},"PeriodicalIF":6.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosuvastatin restores liver tissue-resident NK cell activation in aged mice by improving mitochondrial function","authors":"Johnny Amer ,&nbsp;Ahmad Salhab ,&nbsp;Rifaat Safadi","doi":"10.1016/j.biopha.2025.118000","DOIUrl":"10.1016/j.biopha.2025.118000","url":null,"abstract":"<div><h3>Background and aim</h3><div>Aging has an impact on Natural Killer (NK) cells surveillance against tumors and infections. Our study aims to assess the aging effects on metabolic and mitochondrial markers influencing NK cell activity.</div></div><div><h3>Methods</h3><div>C57BL/6 J mice aged 12, 24, 48, and 72 weeks were used. Liver injury serum and histological markers, pro-inflammatory cytokines [IL-1β, IL-2, IL-6] and chemoattractant markers [CCL2, CXCL8] were assessed. Moreover, cholesterol metabolic markers [HMG-CoA synthetase, HMG-CoA reductase, mevalonate kinase], mitochondrial biogenesis [PGC1α] and functional gene markers [TFAM, HSPA9, Seahorse, apoptosis] in liver trNK cells, were assessed by RT-PCR. Senescence [p16, p21], exhaustion [PD-1, TIGIT, LAG3], activation [CD107a, NKp46], and chemokine receptor [CCR2, CXCR1] markers were assessed in trNK cells using flow cytometry. Liver trNK cells of aged mice were treated with Rosuvastatin [10μM] for 12 h.</div></div><div><h3>Results</h3><div>Data showed a linear increase in liver injury markers, pro-inflammatory and chemotaxis along aging. These results were associated with reductions in liver trNK cell counts and activations with a noticeable decrease in their chemoattractant receptor expressions. TrNK cells of aged mice exhibited elevated markers of senescence and exhaustion with a gradual increase in cholesterol accumulation. Mitochondrial biogenesis and functional gene markers showed a decrease in their expressions in aged mice while ameliorated following rosuvastatin treatment. Results were correlated with a decrease in cholesterol metabolism and restoring their NK cell activity.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates age-related cholesterol accumulation in trNK cells correlated with senescence and functional impairment. Rosuvastatin is suggested to boost, rejuvenate and recover NK cell functionality.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118000"},"PeriodicalIF":6.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effects of proteins secreted from trigonelline-treated renal cells on calcium oxalate crystals in vitro: Implications for kidney stone prevention","authors":"Sunisa Yoodee,&nbsp;Paleerath Peerapen,&nbsp;Wanida Boonmark,&nbsp;Visith Thongboonkerd","doi":"10.1016/j.biopha.2025.118003","DOIUrl":"10.1016/j.biopha.2025.118003","url":null,"abstract":"<div><div>Trigonelline is a bioactive alkaloid with therapeutic effects on various kidney diseases. Although previous studies have implicated its potential to prevent kidney stone disease (KSD), its anti-lithiatic mechanisms were poorly understood and thus addressed herein. Secretome (a set of secreted proteins) was collected and purified from MDCK renal cells treated with 100 µM trigonelline (termed “trigonelline-treated secretome”) to examine its effects on calcium oxalate (CaOx) crystals compared with that derived from untreated cells (termed “control secretome”). Trigonelline-treated secretome significantly reduced CaOx crystal size, number and abundance during initial crystallization, and also inhibited crystal growth, aggregation and adhesion to renal cells. Quantitative proteomics using nanoLC-ESI-Qq-TOF tandem mass spectrometry revealed 46 differentially secreted (11 decreased and 35 increased) proteins, mainly from extracellular compartments, in the trigonelline-treated secretome. While most of the identified proteins were acidic, significantly increased secreted proteins had an increased proportion of basic proteins, resulting in a slightly greater isoelectric point. In concordance, significantly increased secreted proteins had a greater proportion of positively charged amino acids as compared with significantly decreased secreted proteins. However, proportions of aromatic, polar, non-polar, and negatively charged amino acids were comparable. In summary, we report herein direct evidence of the inhibitory effects of trigonelline against CaOx crystallization, growth, aggregation and adhesion to renal cells via the altered secreted proteins that show some unique physicochemical properties when the increased secreted proteins were compared with the decreased compartments. These data may lead to a better understanding of mechanisms underlying the anti-lithiatic effects of trigonelline to prevent KSD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"186 ","pages":"Article 118003"},"PeriodicalIF":6.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}