Frontiers in Pharmacology最新文献

{"title":"Exosomes enriched with miR-124-3p show therapeutic potential in a new microfluidic triculture model that recapitulates neuron-glia crosstalk in Alzheimer's disease.","authors":"Artemizia Évora, Gonçalo Garcia, Ana Rubi, Eleonora De Vitis, Ana Teresa Matos, Ana Rita Vaz, Francesca Gervaso, Giuseppe Gigli, Alessandro Polini, Dora Brites","doi":"10.3389/fphar.2025.1474012","DOIUrl":"10.3389/fphar.2025.1474012","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), a complex neurodegenerative disease associated with ageing, is the leading cause of dementia. Few people with early AD are eligible for the novel Food and Drug Administration (FDA)-approved drug treatments. Accordingly, new tools and early diagnosis markers are required to predict subtypes, individual stages, and the most suitable personalized treatment. We previously demonstrated that the regulation of microRNA (miR)-124 is crucial for proper neuronal function and microglia reshaping in human AD cell models.</p><p><strong>Objective: </strong>The aim of this study was to develop an efficient miR-124-3p-loaded exosome strategy and validate its therapeutic potential in using a multi-compartment microfluidic device of neuron-glia that recapitulates age-AD pathological features.</p><p><strong>Methods and results: </strong>Using cortical microglia from mouse pups, separated from glial mixed cultures and maintained for 2 days <i>in vitro</i> (stressed microglia), we tested the effects of SH-SY5Y-derived exosomes loaded with miR-124-3p mimic either by their direct transfection with Exo-Fect™ (ET124) or by their isolation from the secretome of miR-124 transfected cells (CT124). ET124 revealed better delivery effciency and higher potent effects in improving the stressed microglia status than CT124. Tricultures of human SH-SY5Y neuroblastoma cells (SH-<i>WT</i>) were established in the presence of the human microglia cell line (HMC3) and immortalized human astrocytes (IM-HA) in tricompartmentalized microfluidic devices. Replacement of SH-<i>WT</i> cells with those transfected with APP695 (SH-<i>SWE</i>) in the tricultures and addition of low doses of hydrogen peroxide were used to simulate late-onset AD. The system mimicked AD-associated neurodegeneration and neuroinflammation processes. Notably, ET124 exhibited neuroprotective properties across the three cell types in the AD model by preventing neuronal apoptosis and neurite deficits, redirecting microglial profiles towards a steady state, and attenuating the inflammatory and miRNA fingerprints associated with astrocyte reactivity.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this is the first study supporting the neuro- and immunoprotective properties of miR-124-engineered exosomes in a microfluidic triculture platform, recapitulating age-related susceptibility to AD. Our system offers potential to develop personalized medicines in AD patient subtypes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1474012"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718497","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":"Deciphering the role of IGFBP5 in delaying fibrosis and sarcopenia in aging skeletal muscle: therapeutic implications and molecular mechanisms.","authors":"Luze Shi, Zheci Ding, Jiwu Chen","doi":"10.3389/fphar.2025.1557703","DOIUrl":"10.3389/fphar.2025.1557703","url":null,"abstract":"<p><strong>Introduction: </strong>Sarcopenia is a condition characterized by the loss of muscle fibers and excessive deposition of extracellular matrix proteins. The interplay between muscle atrophy and fibrosis is a central feature of sarcopenia. While the mechanisms underlying skeletal muscle aging and fibrosis remain incompletely understood, cellular senescence has emerged as a key contributor. This study investigates the role of D-galactose (D-gal) in inducing fibroblasts senescence and skeletal muscle fibrosis, and aims to find the key regulator of the process to serve as a therapeutical target.</p><p><strong>Methods: </strong>To discover the role of D-gal in inducing cellular senescence and fibrosis, the senescence markers and the expression of fibrosis-related proteins were assessed after introducing D-gal among fibroblasts, and muscle strength and mass. The severity of muscle atrophy and fibrosis were also verified by using H&E staining and Masson trichrome staining after D-gal treatment via subcutaneous injection among mice. Subsequently, mRNA sequencing (RNA-seq) was performed and the differential expressed genes were identified between under D-gal or control treatment, to discover the key regulator of D-GAL-driven fibroblasts senescence and fibrosis. The role of the key regulator IGFBP5 were then validated in D-GAL treated IGFBP5-knockdown fibroblasts <i>in vitro</i> by analyzing the level of senescence and fibrosis-related markers. And the results were further confirmed <i>in vivo</i> in IGFBP5-knockdown SAMP8 mice with histological examinations.</p><p><strong>Results: </strong>D-gal treatment effectively induced cellular senescence and fibrosis in fibroblasts, as well as skeletal muscle atrophy, fibrosis and loss in muscle mass and function in mice. IGFBP5 was identified as a key regulator of D-GAL induced senescence and fibrosis among fibroblasts using RNA-seq. And further validation tests showed that IGFBP5-knockdown could alleviate D-GAL-induced fibroblast cellular senescence and fibrosis, as well as the severity of muscle atrophy and fibrosis in SAMP8 mice.</p><p><strong>Discussion: </strong>IGFBP5 emerging as a key regulator of D-GAL-induced fibroblast cellular senescence and fibrosis. The findings provide new insights into the molecular mechanisms underlying age-related skeletal muscle fibrosis and highlight IGFBP5 as a potential therapeutic target. Further research is needed to validate these findings and explore related clinical applications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1557703"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718485","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":"Exploring the antibacterial potential of <i>Clidemia hirta</i> leaf extract against the pathogenicity of <i>Pseudomonas aeruginosa: in vitro</i> and <i>in silico</i> approaches.","authors":"Vignesh Murugesan, Pargovan Palanivel, Gokul Ramesh, Dwarakesh Ganesh, Helan Soundra Rani Michael, Shivakumar Bandhumy Lingam, Rathish Kumar Sivaraman","doi":"10.3389/fphar.2025.1555542","DOIUrl":"10.3389/fphar.2025.1555542","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant bacterial pathogen <i>P. aeruginosa</i> has emerged as a significant global health challenge, underscoring the urgent need to identify and develop alternative therapeutic agents including plant natural products. In this study, the extract from <i>Clidemia hirta</i> plant extract was analyzed for antibacterial properties against <i>Pseudomonas aeruginosa</i> and component composition.</p><p><strong>Material and methods: </strong>The plant extract was obtained from leaves of <i>C. hirta</i> and its antibacterial activity against <i>P. aeruginosa</i> was determined in Kirby-Bauer disc diffusion assay. In this assay, the activity of the extract was tested at two different concentrations of 50 and 100 μg/mL. The minimum inhibitory concentration (MIC) of the extract against <i>P. aeruginosa</i> was used with its MIC values against Vero cells to determine the selectivity index. GC-MS determined the phytochemical composition of the plant extract. The property of different extract components to bind the target receptor Penicillin Binding Protein 2a (7KIS) was assessed <i>in silico</i> studies including docking and molecular dynamics (MD) analyses. In these analyses, the stability and interaction dynamics of the Penicillin Binding Protein 2a (7KIS) protein complexed with selected extract components.</p><p><strong>Results: </strong>The plant extracts had antibacterial activity against <i>P. aeruginosa</i>, with inhibition zones measuring 13 mm and 19 mm for 50 and 100 μg/mL concentrations, respectively. The MIC of the plant extract was determined to be 20 μg/mL, while its selectivity index was 4.54, indicating its antibiotic potential. One extract component, 2, 4-di-tert-butylphenol compound holds a binding affinity of -6.2 kcal/mol in molecular docking studies. MD simulations revealed stable binding interactions between the 7KIS protein and the tested ligands, characterized by reduced atomic fluctuations and energetically favorable binding profiles.</p><p><strong>Conclusion: </strong>This study showed that <i>C. hirta</i> extract has a robust antibacterial potential against <i>P. aeruginosa</i>. Furthermore, GC-MS profiling molecular docking, and dynamic simulation data showed that such antibacterial potential might be attributed to its one component, 2, 4-di-tert-butylphenol. Further, <i>in vivo</i> and <i>in vitro</i> studies are needed to show the applicability of bioactive compounds from <i>C. hirta</i> in combating resistant bacterial pathogens.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1555542"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718505","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":"Prediction of neoadjuvant chemotherapy efficacy and prognostic biomarker analysis in patients with triple-negative breast cancer.","authors":"Xiao-Wen Liao, Jia-Bin Gao, Hong Sun, Hong-Dan Chen, Min-Hui Zheng, Lei Han, Xiao-Geng Chen, Yu-Nan Su, Ding-Long Pan, Min Wu, Shuang-Long Cai, Xiuquan Lin, Guo-Zhong Chen","doi":"10.3389/fphar.2025.1553831","DOIUrl":"10.3389/fphar.2025.1553831","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy has become a common and effective treatment modality for triple-negative breast cancer (TNBC). The primary goal is to reduce the size of the primary tumor, enabling breast-conserving surgery, axillary preservation, and a transition to operability, thereby providing patients with more therapeutic options. Although neoadjuvant chemotherapy (NAC) has demonstrated favorable outcomes in clinical practice, predicting its efficacy and prognostic value in TNBC remains a key challenge in current clinical research.</p><p><strong>Methods: </strong>This study included 248 TNBC patients who received NAC at two breast cancer treatment centers. By employing a modeling validation approach, we aim to explore predictors of treatment efficacy and potential prognostic biomarkers associated with NAC.</p><p><strong>Results: </strong>In the multivariable analysis of the training set, the factors predicting the pathological complete response (pCR) to NAC in TNBC patients include high biopsy-sTILs expression, biopsy-Ki67 > 20%, and positive expression of biopsy-androgen receptor (AR). The factors predicting disease-free survival (DFS) are ypN3, high postoperative sTIL expression, receipt of postoperative radiotherapy, and effective NAC. The factors predicting overall survival (OS) include ypN2, ypN3, high postoperative sTIL expression, postoperative Ki67 > 20%, receipt of postoperative radiotherapy, and effective NAC. The C-indices in the training and validation sets for the prediction of pCR using the nomogram were 0.729 and 0.816, respectively. The C-indices for predicting DFS were 0.895 and 0.865, respectively. The C-indices for predicting OS were 0.899 and 0.860, respectively.</p><p><strong>Conclusion: </strong>This study established and validated a nomogram model predicting the pCR, DFS, and OS in TNBC patients undergoing NAC. This model demonstrates good discrimination and accuracy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1553831"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718521","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":"Vortioxetine alleviates motor, cognitive and emotional disorders in post-stroke rats by regulating the TLR-2/NF-<i>κ</i>B pathway.","authors":"Ziqiang Dong, Zhihui Dong, Lili Xu, Jinfeng Zhang, Lin Li, Rongjuan Wang, Xiaoyan Huang, Zhengqiang Zou","doi":"10.3389/fphar.2025.1555079","DOIUrl":"10.3389/fphar.2025.1555079","url":null,"abstract":"<p><p>Cognitive impairments following post-stroke significantly hinder neurological recovery and exacerbate patient morbidity, underscoring urgent need for effective therapeutic strategies. Vortioxetine (VTX), a prominent Selective Serotonin Reuptake Inhibitor (SSRI), boasts notable antidepressant, cognition-enhancing, and anti-inflammatory properties. This investigation delves into VTX's influence on motor skills, spatial learning-memory capabilities, and depressive behaviors in Middle Cerebral Artery Occlusion (MCAO) rats, alongside its underlying mechanisms. Our findings reveal that while VTX fails to entirely reverse ischemic-reperfusion damage, it substantially ameliorates spontaneous locomotor functions, augments post-stroke learning-memory capacities, and exhibits potent antidepressant and anxiety-like efficacy. Preliminary data propose that these beneficial effects may stem from inflammation modulation via the Toll-Like Receptor 2 (TLR-2)/Nuclear Factor-Kappa B (NF-<i>κ</i>B) signaling pathway. Collectively, our work underscores VTX's promising role in enhancing motor, cognitive functions, and mitigating depressive symptoms following cerebrovascular accidents, potentially through inflammation regulation. These insights pave the way for novel interventions addressing post-stroke complications, warranting further exploration.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1555079"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718527","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 role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation.","authors":"Xizheng Wang, Jianfeng Yuan, Chenchen Zhang, Lingyu Kong, Enzhen Wu, Jianxin Guo, Zhongbing Wu","doi":"10.3389/fphar.2025.1563435","DOIUrl":"10.3389/fphar.2025.1563435","url":null,"abstract":"<p><strong>Background: </strong>Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an E3 ubiquitin ligase and scaffolding protein that contribute to the progression of various malignant tumors. However, the role of TRAF2 expression in epigenetic, cancer prognosis, and immune responses in tumor microenvironment is unclear.</p><p><strong>Methods: </strong>We used The Human Protein Atlas (HPA) database, TIMER 2.0 database, and TCGA database to evaluate TRAF2 expression in human normal and tumor tissues. Correlation of TRAF2 expression with mutations and epigenetic in tumors was evaluated using the cBioPortal platform and the GSCA database. To assess the prognostic value of TRAF2, we performed Kaplan-Meier plots and Cox regression analysis. LinkedOmics database was used for PANTHER Pathways enrichment analysis. The relationship between TRAF2 expression and immune checkpoint genes, as well as immune cell infiltration, was examined using TIMER 2.0 and the R language. Single-cell sequencing data and multiple immunofluorescence staining were used to observe the co-expression of TRAF2 on hepatocellular carcinoma cells and immune cells. Furthermore, using siRNA-mediated knockdown, we explored the potential role of TRAF2 in liver cancer cell biology.</p><p><strong>Results: </strong>Our findings indicate that TRAF2 is frequently mutated and significantly overexpressed in various types of cancers, and this overexpression is linked to a poor prognosis. The epigenetic alterations in TRAF2 was significant across various types of cancers. TRAF2 is associated with the levels of various immune checkpoint genes and multiple tumor-infiltrating immune cells, suggesting its potential involvement in tumor microenvironment. Of note, enrichment analysis revealed a significant correlation between TRAF2 and T cell activation, and single-cell sequencing indicated that TRAF2 was overexpressed in malignant cells and T cells. <i>In vivo</i> results demonstrated that TRAF2 was closely associated with T lymphocytes in hepatocellular carcinoma. The results of our <i>in vitro</i> experimental studies confirmed that the loss of TRAF2 function inhibits the malignant behavior of HepG2 cells in hepatocellular carcinoma.</p><p><strong>Conclusion: </strong>TRAF2 represents a potential prognostic biomarker and therapeutic target for cancer immunotherapy, particularly in patients with hepatocellular carcinoma.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1563435"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718443","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":"Assessing the effects of antidepressant use on stroke recurrence and related outcomes in ischemic stroke patients: a propensity score matched analysis.","authors":"Faisal F Alamri, Daniyah A Almarghalani, Yasser Alatawi, Eman A Alraddadi, Omar Babateen, Ahmed Alayyafi, Ziyad Almalki, Khaled Alsalhi, Khaled Alzahrani, Ahmed Alghamdi, Hussain Aldera, Vardan T Karamyan","doi":"10.3389/fphar.2025.1558703","DOIUrl":"10.3389/fphar.2025.1558703","url":null,"abstract":"<p><p>The effect of antidepressant use, particularly that of selective serotonin reuptake inhibitors, on stroke outcomes remains unclear. This hospital-based, retrospective, observational study utilized propensity score-matching (PSM) to assess the association between antidepressant use, stroke-related outcomes, and complications. The study was conducted at King Abdulaziz Medical City (KAMC) in Jeddah and Riyadh and included 1,125 patients with acute-subacute ischemic stroke, of whom 1,025 were antidepressant non-users and 100 antidepressant users. After PSM, 200 patients (100 antidepressant users and 100 non-users) were included in the final analysis. This study aimed to assess the association between antidepressant use, stroke recurrence, and mortality. Additionally, the study examined the association between antidepressant use and stroke severity, functional independence, and incidence of post-stroke complications. The Kaplan-Meier analysis revealed no statistically significant differences in stroke recurrence (<i>p</i> = 0.5619) or mortality (<i>p</i> = 0.6433) between antidepressant users and non-users over the 1-year follow-up period. Additionally, no significant differences were observed in stroke severity at admission and discharge (<i>p</i> = 0.33210 and <i>p</i> = 0.78410, respectively) or functional independence (<i>p</i> = 0.9176 and <i>p</i> = 0.4383, respectively) between the two groups. These findings suggest that antidepressant use does not significantly affect stroke recurrence, mortality, stroke severity, or functional independence. However, further large-scale studies are warranted to validate these findings and investigate potential confounding factors, such as stroke subtypes, co-use of certain medications, and physical activity.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1558703"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718428","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":"Molecular determinants of neuroprotection in blood-brain interfaces of the cynomolgus monkey.","authors":"Nathalie Strazielle, Sandrine Blondel, Joachim Confais, Rita El Khoury, Hugues Contamin, Jean-François Ghersi-Egea","doi":"10.3389/fphar.2025.1523819","DOIUrl":"10.3389/fphar.2025.1523819","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) formed by the cerebral microvessel endothelium and the blood-CSF barrier (BCSFB) formed by the choroid plexus epithelium impact the cerebral bioavailability of drugs and endogenous molecules that contribute to neuroinflammatory and neurodegenerative diseases. Species specificities in tight junction proteins and efflux transporters governing the barrier functions of these interfaces hamper the direct translation of pharmacokinetic and pathophysiological data from rodents to human. We defined the molecular composition of tight junctions and identified the efflux transporters present at the BBB and BCSFB of cynomolgus monkey to assess whether this species is a relevant alternative to rodents. Choroid plexuses, cerebral microvessels, cortex and cerebellum were isolated from adult cynomolgus monkeys, and analysed by RT-qPCR and immunohistochemistry. Results were compared with data available in the literature for rat and human. In monkeys as in rat and human, claudin-5 in the BBB and claudin-1, -2, -3 in the BCSFB were landmark tight junction proteins. ABCB1 was strictly associated with the BBB, and ABCC1 was predominant at the BCSFB compared to the BBB. The monkey, like human, differed from rat by the localization of ABCG2 protein in choroidal vessels, a low expression of ABCC4 and SLC22A8 in the BBB, and the presence of SLC47A1 at the BCSFB. While the main characteristics of brain barriers are common to all three species, cynomolgus monkey and human share specificities in the expression and localization of selected claudins and efflux transporters that are not met in rat.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1523819"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718515","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":"Effect of injecting adipose stem cells combined with platelet-rich fibrin releasate at Shenshu acupoint (BL23) on acute kidney injury in rabbits.","authors":"Hsin-Ni Chuang, Wen Pei, Tzong-Fu Kuo, Yu-Hao Liu, Chia-Yih Wang, Yen-Wei Chang, Chi-Hsuan Chuang, Chang-Huan Yang, Ming-Hsi Chuang","doi":"10.3389/fphar.2025.1409056","DOIUrl":"10.3389/fphar.2025.1409056","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) is a major and unmet medical need, characterized by a sudden onset of kidney dysfunction that often occurs within 7 days. Adipose-derived stem cells (ADSCs) are known for their regenerative, differentiative, and repair abilities, making them a promising therapeutic option for kidney injury. Platelet-rich fibrin releasate (PRFr), derived from platelet-rich fibrin after static incubation, contains numerous growth factors that may promote the differentiation and proliferation of stem cells. Additionally, acupoints such as Shenshu (BL23) have been used in clinical practice and experimental settings, particularly in renal failure treatments.</p><p><strong>Methods: </strong>This study aimed to evaluate the synergistic effects of ADSCs and PRFr, administered separately or in combination, at the Shenshu acupoint (BL23) in New Zealand white rabbits with acute kidney injury. The treatment groups were injected with ADSCs, PRFr, or a combination of both. Serum creatinine (CRE) and blood urea nitrogen (BUN) levels were measured to assess kidney function. Additionally, histological examination of kidney tissue was performed to observe morphological changes and tissue repair.</p><p><strong>Results: </strong>The PRFr + ADSCs treatment group exhibited a significant reduction in CRE and BUN levels during the second week following transplantation. After 7 weeks of treatment, the PRFr + ADSCs group showed the most favorable kidney repair outcomes, with intact glomeruli, no edema or vacuole-like changes in the renal tubular epithelial cells, and no significant infiltration of inflammatory cells in the surrounding tissues.</p><p><strong>Discussion: </strong>The administration of PRFr, ADSCs, and their combination at the Shenshu acupoint (BL23) demonstrated a potential therapeutic effect in repairing damaged renal cells, improving kidney function, and reducing serum CRE and BUN levels. These findings suggest that injection of PRFr, ADSCs, and their combination at the Shenshu acupoint (BL23) can effectively repair damaged renal cells and improve kidney function in AKI. The observed synergistic effect indicates that this approach holds potential as a novel therapeutic strategy for kidney injury. Further research is needed to optimize treatment protocols and elucidate the underlying mechanisms.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1409056"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718490","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":"Unraveling the molecular mechanisms of Fufangduzhong formula in alleviating high-fat diet-induced non-alcoholic fatty liver disease in mice.","authors":"Yu Mou, Yao Tang, Xiuyan Zheng, Xiang Liu, Xuemei Wu, Hongji Wang, Jie Zeng, Qing Rao, Yaacov Ben-David, Yanmei Li, Lei Huang","doi":"10.3389/fphar.2025.1542143","DOIUrl":"10.3389/fphar.2025.1542143","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by hepatic lipid accumulation. The Fufangduzhong formula (FFDZ) is a traditional Chinese medicine (TCM) formulation composed of <i>Eucommia ulmoides</i> Oliv.<i>, Leonurus artemisia</i> (Lour.) S. Y. Hu, <i>Prunella vulgaris</i> Linn<i>, Uncariarhynchophylla</i> (Miq.) Miq. ex Havil., <i>and Scutellaria baicalensis</i> Georgi. It has demonstrated hepatoprotective effects and the ability to reduce lipid accumulation. However, its mechanisms against NAFLD remain unclear.</p><p><strong>Methods: </strong>UPLC-MS/MS was used to identify FFDZ metabolites. C57BL/6J mice were fed a high-fat diet (HFD) supplemented with or without FFDZ (HFD+L, 0.45 g/kg/d; HFD+H, 0.9 g/kg/d) for 12 weeks. Biochemical indicators and histopathological observations were utilized to assess the extent of metabolic homeostasis disorder and hepatic steatosis. An analysis of differentially expressed genes and regulated signaling pathways was conducted using hepatic transcriptomics. Metabolomics analysis was performed to investigate the significantly changed endogenous metabolites associated with NAFLD in mice serum using UPLC-Q-TOF/MS. Western blot was employed to detect proteins involved in the lipid metabolism-related signaling pathways. Oleic acid-induced hepatic steatosis was used to examine the lipid-lowering effect of FFDZ-containing serum <i>in vitro</i>.</p><p><strong>Results: </strong>A total of eight active metabolites were identified from the FFDZ formula and FFDZ-containing serum through UPLC-MS/MS analysis. FFDZ reduced body weight, liver weight, and levels of inflammatory cytokines, and it ameliorated hepatic steatosis, serum lipid profiles, insulin sensitivity, and glucose tolerance in mice with HFD-induced NAFLD. Transcriptomics revealed that FFDZ modulated the lipid metabolism-related pathways, including the PPAR signaling pathway, Fatty acid metabolism, and AMPK signaling pathway. Meanwhile, Western blot analysis indicated that FFDZ downregulated the expression of lipid synthesis-related proteins (Srebp-1c, Acly, Scd-1, Fasn, Acaca, and Cd36) and upregulated the fatty acid oxidation-related proteins (p-Ampk, Ppar-α, and Cpt-1). Furthermore, metabolomics identified FFDZ-mediated reversal of phospholipid dysregulation (PC, PE, LPC, LPE). Additionally, FFDZ-containing serum remarkedly reduced OA-induced lipid accumulation in HepG2 cells.</p><p><strong>Conclusion: </strong>The present results demonstrate that FFDZ exerts anti-NAFLD effects by enhancing glucose tolerance and insulin sensitivity, as well as regulating the Ampk signaling pathway to ameliorate lipid metabolism disorder, lipotoxicity, hepatic steatosis, and inflammatory responses.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1542143"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718525","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}