Biomedicine & Pharmacotherapy最新文献

{"title":"Macrophage immunometabolism dysregulation and inflammatory disorders","authors":"Karen Pomeyie ,&nbsp;Francis Abrokwah ,&nbsp;Daniel Boison ,&nbsp;Benjamin Amoani ,&nbsp;Foster Kyei ,&nbsp;Cynthia A. Adinortey ,&nbsp;Prince Amoah Barnie","doi":"10.1016/j.biopha.2025.118142","DOIUrl":"10.1016/j.biopha.2025.118142","url":null,"abstract":"<div><div>Macrophages are innate immune cells which are involved in triggering inflammation. Growing evidence shows that, macrophages respond to intracellular and extracellular cues which makes them adopt either anti-inflammatory or pro-inflammatory functions and phenotypes. Immunometabolism has been identified as one of the prominent factors which contributes massively towards the cessation and the development of inflammation as an immune response to infections and autoimmune diseases. However, when inflammation is poorly regulated, it leads to dire consequences. This illustrates that, understanding the role of immunometabolism in the regulation of inflammation, is paramount. In view of this, the review investigated the role of metabolic pathways such as: glycolysis, tricarboxylic acid cycle, pentose phosphate pathway, fatty acid oxidation, amino acid metabolism in macrophage reprogramming. The role of the intermediates and enzymes associated with these metabolic pathways in the regulation of, macrophage reprogramming and polarisation or activation was also reviewed. It was unveiled that, manipulating metabolic intermediates and enzymes could impact cellular immunometabolism. This eventually influences macrophage reprogramming and thus influences the generation of either a pro-inflammatory or anti-inflammatory response.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118142"},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948537","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":"Deciphering the immunomodulatory mechanisms of Bojungikki-tang via systematic transcriptomic and immune cell interaction network analysis","authors":"Sang-Yun Kim ,&nbsp;Jin-Mu Yi ,&nbsp;Jaemoo Chun ,&nbsp;Musun Park ,&nbsp;Heerim Yeo ,&nbsp;Sang-Min Park ,&nbsp;Mi-Kyung Jeong","doi":"10.1016/j.biopha.2025.118129","DOIUrl":"10.1016/j.biopha.2025.118129","url":null,"abstract":"<div><div>Bojungikki-tang (BJIKT), a traditional herbal formula with immunomodulatory properties, has synergistic effects with immune checkpoint inhibitors. However, the detailed molecular mechanisms underlying its effects on various immune cell types remain largely unexplored. Therefore, in this study, we aimed to propose a framework for understanding how herbal medicine modulates immunity through a systematic analysis of the drug-induced transcriptome and immune cell interaction networks. We obtained large-scale RNA-seq data for distinct five immune cell types (T cells, natural killer cells, B cells, macrophages, and dendritic cells) treated with BJIKT and its four major constituent herbs, totaling 180 sequenced samples. Transcriptomic analysis indicated that BJIKT significantly upregulated interferon-γ, TNF-α, and inflammatory pathways in B cells, macrophages, and dendritic cells. Although BJIKT did not directly activate T cells, it indirectly modulated their function through immune cell–cell interactions. The reconstructed network and cytokine assays identified IL-1β, IL-6, IL-8, MIP-1β, CXCL9, CXCL10, and TNF-α as critical cytokines influenced by BJIKT, playing pivotal roles in activating and recruiting various immune cells. Our findings provide insights into the immunomodulatory mechanisms of BJIKT and the unique actions of its constituent herbs. We highlight the potential for combining traditional herbal medicine with omics technologies to explore the therapeutic mechanisms of natural products as complementary therapies for advancing cancer immunotherapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118129"},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948540","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 HASPIN in gemcitabine-resistant pancreatic cancer cells by lead optimization of thioadenosine analogue","authors":"Yoon-Ze Shin ,&nbsp;Yun A Yum ,&nbsp;Eun Seo Bae ,&nbsp;Dnyandev B. Jarhad ,&nbsp;Vikas R. Aswar ,&nbsp;Sushil Kumar Tripathi ,&nbsp;Eun-Ji Kwon ,&nbsp;Yun-Jeong Kim ,&nbsp;Minjae Kim ,&nbsp;Sang Kook Lee ,&nbsp;Lak-Shin Jeong ,&nbsp;Hyuk-Jin Cha","doi":"10.1016/j.biopha.2025.118135","DOIUrl":"10.1016/j.biopha.2025.118135","url":null,"abstract":"<div><div>Despite multiple kinase inhibitors having been developed for cancer therapy, mitotic kinases remain difficult to target with small molecules due to severe adverse effects on proliferating normal cells. Recently, HASPIN, a mitotic kinase responsible for histone H3 phosphorylation, has emerged as a promising cancer-specific target. In this study, we synthesized a novel thioadenosine analogue, LJ5157, based on the structure of the previously developed HASPIN inhibitor LJ4827. <em>In silico</em> transcriptome analysis of pancreatic cancer patient data from The Cancer Genome Atlas identified HASPIN as not only a cancer-specific target but also a potential key player in overcoming gemcitabine resistance. To evaluate the therapeutic potential of LJ5157, we tested its efficacy in pancreatic cancer cells, particularly gemcitabine-resistant Panc-1 (GR) cells. The inhibitor exhibited potent anti-cancer activity, effectively suppressing the growth of GR cells, which showed more dysregulated cell cycle progression and greater proportion of polyploid cells compared to wild-type Panc-1 cells. Furthermore, it demonstrated superior efficacy in reducing the mitotic population of polyploid GR cells, which correlated with significant tumor growth inhibition in a GR-cell-derived xenograft model. Further optimization of LJ4827 led to development of LJ5242, an analogue with enhanced selectivity for HASPIN and improved cell cycle inhibitory potency. These findings highlight HASPIN inhibition as a promising strategy for targeting chemoresistant pancreatic cancer and further identify thioadenosine as a valuable pharmacophore for developing clinically viable HASPIN inhibitors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118135"},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070235","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":"Downregulation of transforming growth factor-β2 enhances the chemosensitivity to gemcitabine with diminished metastasis in pancreatic cancers","authors":"Dohee Ahn ,&nbsp;Hong Kyu Lee ,&nbsp;Sang Hyeok Bae ,&nbsp;Hwayoung Na ,&nbsp;Kyung-Chul Choi","doi":"10.1016/j.biopha.2025.118151","DOIUrl":"10.1016/j.biopha.2025.118151","url":null,"abstract":"<div><div>Pancreatic cancer is characterized by high rates of metastasis, recurrence, and chemoresistance, contributing to its poor prognosis. Transforming growth factor-β2 (TGF-β2), a member of the TGF-β family, plays a pivotal role in promoting cancer cell metastasis and mediating chemoresistance, particularly in advanced stages of tumor progression. However, the precise role of TGF-β in chemoresistance and metastasis in pancreatic cancer has not been studied yet. In the current study, we investigated the potential of human TGF-β2 antisense oligonucleotides (TGF-β2i) to enhance the chemosensitivity to gemcitabine in pancreatic cancer, using human pancreatic cancer cell lines (hPCCs; PANC-1, MIA PaCa-2, and AsPC-1), a co-culture model with human pancreatic stellate cells (hPSCs), a cancer-associated fibroblast-integrated pancreatic cancer organoid model (CIPCO), and an orthotopic xenograft mouse model. TGF-β2i decreased cell proliferation, migration, and viability in hPCCs, and its combination with gemcitabine exhibited a synergistic effect in PANC-1 and MIA PaCa-2 cells. Flow cytometry demonstrated a decrease in CD44 +CD24 +EpCAM^High cancer stem-like cell populations following TGF-β2i treatment. In co-culture models, hPSCs-induced enhancement of hPCCs migration was attenuated by TGF-β2i. In the CIPCOs, TGF-β2i suppressed the gemcitabine-induced expression of extracellular matrix components such as <em>COL1A1</em> and <em>VIM</em> <!-->. Furthermore, in an orthotopic mouse model generated by co-inoculating hPCCs and hPSCs into the pancreatic wall, co-treatment of TGF-β2i with gemcitabine significantly delayed tumor growth and metastasis to the liver compared to vehicle control. These findings suggest that TGF-β2i enhances chemosensitivity and suppresses metastatic properties by regulating both tumor-intrinsic and -extrinsic factors, indicating that targeting TGF-β2 could be a promising strategy for managing pancreatic cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118151"},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070236","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":"Esculetin inhibits liver cancer by targeting glucose-6-phosphate isomerase mediated glycolysis","authors":"Zongchao Hong ,&nbsp;Jingbo Wang ,&nbsp;Baodan Hu ,&nbsp;Xin Tu ,&nbsp;Jin Yang ,&nbsp;Wanjin Sun ,&nbsp;Xueyun Duan","doi":"10.1016/j.biopha.2025.118118","DOIUrl":"10.1016/j.biopha.2025.118118","url":null,"abstract":"<div><h3>Background</h3><div>Liver cancer is challenging to detect in its early stages, and the global incidence rate and mortality associated with this disease have reached alarming levels. Currently, treatment options for liver cancer are limited, and there is a significant lack of safe and effective therapeutic agents. Esculetin is a natural product, exhibits almost non-toxic and inhibitory properties against various malignancies, making it a subject worthy of further investigation in liver cancer.</div></div><div><h3>Methods</h3><div>In this study, potential targets of esculetin in liver cancer were identified through transcriptomics, network pharmacology, and molecular docking technologies, and gene interference. Direct binding targets of esculetin were identified using surface plasmon resonance (SPR). The molecular mechanisms by which esculetin affects glucose metabolism in liver cancer were also explored. Finally, the activity against liver cancer and mechanisms of action of esculetin were validated <em>in vivo</em> using a mouse tumor model.</div></div><div><h3>Results</h3><div>Glucose-6-phosphate isomerase (GPI) was shown to have a direct binding affinity for this compound. Esculetin inhibits glycolysis in liver cancer through its interaction with GPI and it was shown to exert a significant inhibitory effect on the genes and proteins associated with glycolysis such as ALDOA, ENO1, GAPDH, LDHA, PFKL, PGAM1, PGK1, and PKM2. Furthermore, esculetin not only suppresses the growth of liver cancer cells <em>in vitro</em> but also exhibits notable anti-tumor effects <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>This study demonstrated the inhibitory effects of esculetin against liver cancer both <em>in vitro</em> and <em>in vivo</em>, demonstrating inhibition of glycolysis in liver cancer cells. In addition, the key glycolysis enzyme GPI was identified as a direct target of esculetin.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118118"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941320","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":"Stem cell-mediated bone regeneration of marine-derived fibrinolytic compound (FGFC-1) loaded carboxymethyl chitosan hydrogels","authors":"Lakshmi Jeevithan ,&nbsp;Wang Shuyue ,&nbsp;Sabu Thomas ,&nbsp;Jose Eduardo Mate Sanchez de Val ,&nbsp;Wenhui Wu ,&nbsp;Jeevithan Elango","doi":"10.1016/j.biopha.2025.118162","DOIUrl":"10.1016/j.biopha.2025.118162","url":null,"abstract":"<div><div>Carboxymethyl chitosan (CMC)-based hydrogels (HG) have gained significant attention for therapeutic applications due to their biomimetic properties and biocompatibility. This study explores, for the first time, the regenerative and osteogenic potential of CMC-HG incorporated with a marine fungi-derived fibrinolytic compound, FGFC-1. The inclusion of FGFC-1 did not significantly alter the crucial characteristics of the HGs, including secondary structure, thermal stability, protein adhesion, and in vitro degradation. However, incorporation of FGFC1 increased the swelling capacity (from 132.88 % to 157.11 %) and decreased the mineral adhesion (0.416 at 0.1 mg/ml) and porosity (from 72.95 % to 54.29 %). In general, the bacterial adhesion was decreased by 44.3 % in HG than control., Optimal culture conditions for mesenchymal stem cells (MSCs) were achieved with 2 % CMC and FGFC-1 concentrations of 0.01–1 mg/ml (<span><span>Supplementary Fig. S2</span></span><strong>)</strong>, supporting significant MSC growth. SEM image proved more interconnected dense fibrillar clustered morphology of MSCs on HGs than 2D. FGFC-1 accelerated osteogenic differentiation of MSCs by increasing mRNA expression levels of Runx2 (4.98), collagen-1 alpha-1 (3.4), osteocalcin (3.62), and ALP (4.20), which was further validated through enhanced staining for alizarin red, von Kossa, and alkaline phosphatase, as well as immunostaining for osteocollagen and osteocalcin in differentiated MSCs within the hydrogels. Notably, FGFC-1 significantly induced osteogenic differentiation along with supplements. These findings highlight FGFC-1-loaded CMC hydrogels as a promising strategy for stem cell-mediated bone regeneration in biomedical applications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118162"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948538","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":"Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study","authors":"Yoshika Sakamoto ,&nbsp;Takahiro Niimura ,&nbsp;Mitsuhiro Goda ,&nbsp;Nanami Tomochika ,&nbsp;Wakana Murakawa ,&nbsp;Fuka Aizawa ,&nbsp;Kenta Yagi ,&nbsp;Hirofumi Hamano ,&nbsp;Yuki Izawa-Ishizawa ,&nbsp;Yoshito Zamami ,&nbsp;Keisuke Ishizawa","doi":"10.1016/j.biopha.2025.118137","DOIUrl":"10.1016/j.biopha.2025.118137","url":null,"abstract":"<div><div>Sunitinib (SUN), a drug used to treat advanced renal cell carcinoma and other cancers, causes cardiotoxicity. This study aimed to identify a potential drug candidate to counteract SUN-induced cardiotoxicity. We analysed real-world data from adverse event report databases of existing clinically approved drugs to identify potential candidates. Through <em>in silico</em> analyses and <em>in vitro</em> experiments, the mechanisms of action were determined. The study identified calcitriol (CTL), an active form of vitamin D, as a promising candidate against SUN-induced cardiotoxicity. In H9c2 cells, SUN decreased cell viability significantly, whereas CTL mitigated this effect significantly. The SUN-treated group exhibited increased autophagy in H9c2 cells, which was reduced significantly in the CTL group. Bioinformatics analysis using Ingenuity Pathway Analysis revealed the mechanistic target of rapamycin (mTOR) as a common factor between autophagy and CTL. Notably, rapamycin, an mTOR inhibitor, nullified the effects of CTL on cell viability and autophagy. Furthermore, SUN treatment led to significant reductions in cardiomyocyte diameters and increases in their widths, changes that were inhibited by CTL. SUN also induced morphological changes in surviving H9c2 cells, causing them to adopt a rounded shape, whereas CTL improved their morphology to resemble the elongated shape of the control group. In conclusion, the findings of the present study suggest that CTL has the potential to prevent SUN-induced cardiomyocyte damage through autophagy, particularly via mTOR-mediated pathways. The findings indicate that CTL could serve as an effective prophylactic agent against SUN-induced cardiotoxicity, offering a promising avenue for further research and potential clinical applications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118137"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948539","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":"Cancer-associated fibroblasts (CAFs) and plaque-associated fibroblasts (PAFs): Unraveling the cellular crossroads of atherosclerosis and cancer","authors":"Gavino Faa ,&nbsp;Pina Ziranu ,&nbsp;Andrea Pretta ,&nbsp;Flaviana Cau ,&nbsp;Massimo Castagnola ,&nbsp;Dario Spanu ,&nbsp;Giorgio Saba ,&nbsp;Alessandra Pia D’Agata ,&nbsp;Ekta Tiwari ,&nbsp;Jasjit S. Suri ,&nbsp;Mario Scartozzi ,&nbsp;Luca Saba","doi":"10.1016/j.biopha.2025.118145","DOIUrl":"10.1016/j.biopha.2025.118145","url":null,"abstract":"<div><div>Atherosclerosis is a complex process involving various cells and molecules within the atherosclerotic plaque. Recent evidence suggests that plaque-associated fibroblasts (PAFs), also known as atherosclerosis-associated fibroblasts (AAFs), might play a significant role in the development and progression of the disease. The microenvironment of the atherosclerotic plaque, resembling the tumor microenvironment (TME), includes various cellular populations like plaque-associated macrophages (PAMs), plaque-associated neutrophils (PANs), vascular smooth muscle cells (VSMCs), myeloid-derived suppressor cells (MDSCs), and PAFs. Similar to cancer-associated fibroblasts (CAFs) in tumors, PAFs exhibits a wide range of characteristics and functions. Their interactions with endothelial cells, smooth muscle cells, and other stromal cells, including adventitial fibroblast precursors, significantly influence atherosclerosis progression. Moreover, the ability of PAFs to express various markers such as alpha-SMA, Desmin, VEGF, and GFAP, highlights their diverse origins from different precursor cells, including vascular smooth muscle cells, endothelial cells, glial cells of the enteric nervous system, adventitial fibroblast precursors, as well as resident and circulating fibrocytes. This article explores the molecular interactions between PAFs, cells associated with atherosclerosis, and other stromal cells. It further examines the role of PAFs in the development and progression of atherosclerosis, and compares their features with those of CAFs. The research suggests that studying tumor-associated fibroblasts can help understand fibroblast subpopulations in atherosclerotic plaque. Identifying specific subpopulations could provide new insight into atherosclerosis complexity and lead to the development of innovative drugs for medical intervention.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118145"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948473","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":"Rosa multiflora fructus and its active compound ellagic acid improve depressive-like behaviors in mice via monoamine oxidase inhibition","authors":"Minji Kim ,&nbsp;Dong Wook Lim ,&nbsp;Min-Sun Kim ,&nbsp;Heejin Nam ,&nbsp;Sooim Shin ,&nbsp;Changho Lee ,&nbsp;Min Young Um","doi":"10.1016/j.biopha.2025.118169","DOIUrl":"10.1016/j.biopha.2025.118169","url":null,"abstract":"<div><div>Depression is a significant global health challenge, imposing severe social and economic burdens. <em>Rosa multiflora</em> fructus possesses a range of biological properties; however, its role in reducing stress hormone-induced depression remains unclear. This study examined the antidepressant effects of <em>Rosa multiflora</em> fructus extract (RMFE) on corticosterone (CORT)-induced depressive-like behaviors in mice and explored the underlying molecular mechanisms. ICR mice were administered CORT (40 mg/kg/day, i.p.) for 8 weeks to induce depressive-like behaviors. They were then treated with RMFE (100 or 300 mg/kg/day, p.o.) or selegiline (10 mg/kg/day, p.o.) as a positive control. RMFE treatment significantly alleviated depressive-like behaviors, as evaluated by the tail suspension and forced swimming tests. Furthermore, RMFE reduced hippocampal astrocyte hypertrophy and lowered the protein and mRNA expression of monoamine oxidase A and B (MAOA and MAOB). Phytochemical analysis using UPLC-MS/MS identified five flavonoids in RMFE, including ellagic acid (EA), hyperoside, isoquercetin, quercetin, and quercetin-3-glucuronide. In silico molecular docking revealed that these phenolic compounds interact with MAOA and MAOB, with EA exhibiting the strongest binding affinity. Consistently, EA administration effectively alleviated depressive-like behaviors and increased monoamine neurotransmitter levels in CORT-treated mice. These results suggest that RMFE exerts antidepressant effects by inhibiting MAO, restoring monoamine levels, and modulating hippocampal astrocytic hypertrophy, with EA identified as the primary bioactive compound driving its efficacy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118169"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941321","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":"MicroRNA-325 ameliorates angiotensin II-induced abdominal aortic aneurysm by inhibiting the endothelial-to-mesenchymal transition through regulation of the MAPK/SNAI1/MMP-2 pathway","authors":"Jen-Chun Wang ,&nbsp;Min-Chien Tsai ,&nbsp;Shih-Hung Tsai ,&nbsp;Po-Hsun Huang","doi":"10.1016/j.biopha.2025.118140","DOIUrl":"10.1016/j.biopha.2025.118140","url":null,"abstract":"<div><h3>Objective</h3><div>Angiotensin II (Ang II)-induced chronic inflammation can lead to the formation of abdominal aortic aneurysms (AAAs). Previous studies have revealed associations between endothelial-to-mesenchymal transition (EndMT) and microvascular diseases, but the association between EndMT and AAA formation remains unclear. In this study, the protective effects of miRNA-325 against Ang II-induced EndMT and AAA and the related mechanism were investigated.</div></div><div><h3>Methods</h3><div>A murine model of Ang II-induced AAA was used, and human aortic endothelial cells (HAECs) were used to study the underlying mechanism. Markers of EndMT and inflammation were studied both in vitro and in vivo. SNAI1 siRNA and miRNA-325 mimics were used to elucidate the role of EndMT in AAA formation and the possible protective effects of miRNA-325.</div></div><div><h3>Results</h3><div><em>In vitro</em>, silencing of SNAI1 expression suppressed Ang II-induced EndMT. <em>In vivo</em>, Ang II-infused mice presented higher levels of SNAI1, α-SMA, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, and matrix metalloproteinase (MMP)-2 expression and lower levels of CD31 and VE-cadherin in the abdominal aorta than did control mice. Silencing SNAI1 expression decreased the incidence and severity of AAA and suppressed EndMT in Ang II-infused mice. Furthermore, the administration of miRNA-325 decreased the expression of SNAI1 and MMP-2 in Ang II-treated mice and ameliorated AAA.</div></div><div><h3>Conclusions</h3><div>Ang II contributes to EndMT and AAA in mice, and this effect can be prevented via the suppression of SNAI1 expression. MicroRNA-325 decreased the expression of SNAI1 and MMP-2 and ameliorated subsequent AAA by inhibiting EndMT.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118140"},"PeriodicalIF":6.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937146","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}