Biomedicine & Pharmacotherapy最新文献

{"title":"Role of tumor suppressor genes P53 and PTEN in CD44-mediated gastric adenocarcinoma multidrug resistance","authors":"Laura Perez-Silva ,&nbsp;Elisa Herraez ,&nbsp;Rebeca P. Marijuan ,&nbsp;Maria Reviejo ,&nbsp;Elisa Lozano ,&nbsp;Luis Bujanda ,&nbsp;Mar Abad ,&nbsp;Rocio I.R. Macias ,&nbsp;Oscar Briz ,&nbsp;Jose J.G. Marin","doi":"10.1016/j.biopha.2025.118057","DOIUrl":"10.1016/j.biopha.2025.118057","url":null,"abstract":"<div><div>Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages, when curative options are limited and marked chemoresistance is already present. Although tumor suppressor genes (TSGs) are frequently altered in GAC, their impact on chemoresistance is not well understood. Gene expression data from The Cancer Genome Atlas cohort TCGA-STAD were validated by RT-qPCR in a Spanish cohort of GAC. In the human GAC cell line AGS, gene knocking-out was performed using CRISPR/Cas9. Cell viability (MTT-formazan test) and proliferation rate (digital holographic microscopy) were determined. Among the most frequently inactivated TSGs, <em>TP53</em>, <em>PTEN</em>, and <em>ARID1A</em> were selected for further studies. In GAC samples, <em>TP53</em> was upregulated, whereas <em>PTEN</em> and <em>ARID1A</em> were downregulated. Mutations in these TSGs led to a consistent alteration in the expression of their target genes. AGS cells exhibited TSG expression profiles like those observed in GAC, which supports their suitability as an <em>in vitro</em> model. Knocking-out <em>ARID1A</em> (ARID1A^KO) enhanced cell chemosensitivity. In contrast, silencing <em>TP53</em> (p53^KO) or <em>PTEN</em> (PTEN^KO) led to increased resistance to platinum-based drugs, doxorubicin, epirubicin, and docetaxel. Characterization of the resistome was performed using TaqMan Low-Density Arrays. In p53^KO and PTEN^KO cells, the expression of <em>UGT1A</em> and <em>CD44</em> was altered. Additional silencing of <em>CD44</em> in these cells partially reversed their chemoresistance. Moreover, pharmacological inhibition of CD44 with verbascoside sensitized p53^KO and PTEN^KO cells to anticancer drugs. In conclusion, dysfunctional <em>TP53</em> and <em>PTEN</em> contribute to altered drug responses of GAC. Moreover, we identified pharmacological vulnerabilities that could be useful to chemosensitize these tumors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118057"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869510","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":"Piperine and its nanoformulations: A mechanistic review of their anti-cancer activities","authors":"Mahshad Ghasemi ,&nbsp;M. Hossein Nowroozzadeh ,&nbsp;Fereshteh Ghorat ,&nbsp;Aida Iraji ,&nbsp;Mohammad Hashem Hashempur","doi":"10.1016/j.biopha.2025.118075","DOIUrl":"10.1016/j.biopha.2025.118075","url":null,"abstract":"<div><div>Piperine, an active compound found in black pepper, exhibits promising anti-cancer properties by targeting critical signaling pathways involved in cancer cell proliferation, migration, and invasion. This review explores the diverse mechanisms through which piperine exerts its effects, including inhibition of the PI3K/Akt/mTOR and ERK1/2 pathways, activation of p38 and JNK pathways, and suppression of NF-kB/AP-1 signaling. Piperine disrupts Wnt/β-catenin signaling by inhibiting β-catenin nuclear translocation and TCF binding, thereby impairing cancer cell growth and metastasis. Additionally, piperine demonstrates anti-inflammatory actions by reducing CXCL8 expression and modulating the p38 MAPK and JNK pathways. To overcome the issues of low solubility and bioavailability, several nanoformulations of piperine<!--> <!-->were developed, such as polymer nanoparticles, nanoemulsion, liposomes, micelles, metal-organic frameworks and inorganic carriers, establishing promising cytotoxicity, prolonged-release, enhanced cellular influx, and directed drug delivery. The mechanisms involve G₀ and G₂/M arrest of the cell cycle, mitochondria-mediated apoptosis (involving Bax/Bcl-2 modulation and caspase activation), and cancer cell<!--> <!-->death. <em>In vivo</em> studies underscore the efficacy of piperine, while synergistic effects with other natural products and chemotherapy highlight its potential as a versatile therapeutic agent as an anticancer agent. These findings underscore piperine's potential as a multifaceted therapeutic agent for cancer treatment, emphasizing its diverse mechanisms of action and promising role in oncology.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118075"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858799","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":"Comparative effects of extracellular vesicles and liposomal nanocarriers on bleomycin-induced stress in A549 human adenocarcinoma cells","authors":"Thomas Conlon ,&nbsp;Maximilian Schaaf ,&nbsp;Ana Mateos-Maroto ,&nbsp;Sabrina Picciotto ,&nbsp;Svenja Morsbach ,&nbsp;Giorgia Adamo ,&nbsp;Shutian Si ,&nbsp;Ingo Lieberwirth ,&nbsp;Christine Rosenauer ,&nbsp;Katharina Landfester ,&nbsp;Antonella Bongiovanni ,&nbsp;Nicolas Touzet","doi":"10.1016/j.biopha.2025.118081","DOIUrl":"10.1016/j.biopha.2025.118081","url":null,"abstract":"<div><div>Lung cancer and chronic respiratory diseases are among the leading causes of death worldwide. Key factors in their pathogenesis include reactive oxygen species (ROS), transforming growth factor-β1 (TGF-β1) and epithelial-mesenchymal transition (EMT). Exogenous antioxidants can mitigate the oxidative stress that drives TGF-β1-mediated respiratory pathologies. Given their role in cellular communication and natural biocompatibility, extracellular vesicles (EVs) are emerging as promising candidates for the delivery of therapeutic cargo to pathological cells. Notably, microalgal-derived EVs (i.e., nanoalgosomes) have been shown to exhibit antioxidant and anti-inflammatory activity. In this study, the bioactivity of EVs derived from <em>Tetraselmis chuii</em> (CCAP 66/21B) was investigated in a bleomycin-stressed (8 µg mL⁻¹) human adenocarcinoma alveolar epithelial cell model (A549). Moreover, the effects of these EVs were compared to liposomes loaded with established therapeutics (pirfenidone and quercetin), synthesised using the lipid film hydration method. <em>In vitro</em> assessments included cell viability (MTS), intracellular ROS, morphological changes, cell migration, EMT-related mRNA expression (qPCR), and TGF-β1 release (ELISA). Both the EVs (nanoalgosomes) and pirfenidone- and quercetin-loaded liposomal nanocarriers (1–4 µg mL⁻¹) effectively attenuated bleomycin-induced EMT, inhibited cell migration, suppressed profibrotic TGF-β1, lowered intracellular ROS and upregulated glutathione peroxidase 4 (<em>GPX4</em>). Importantly, the innate bioactive cargo of the naturally derived nanoalgosomes exhibited comparable effects to the liposome therapeutic formulations in mitigating bleomycin-induced stress in A549 cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118081"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864534","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":"3'-epi-12β-hydroxyfroside induces autophagic degradation of ABCG2 to overcome drug resistance in lung cancer cells","authors":"Ri-Hong Wu,&nbsp;Wei-Jing Xie,&nbsp;Shu-Zhen Dai,&nbsp;Ming-Hui Chen,&nbsp;Guang-Hong Tan,&nbsp;Feng-Ying Huang","doi":"10.1016/j.biopha.2025.118085","DOIUrl":"10.1016/j.biopha.2025.118085","url":null,"abstract":"<div><h3>Aims</h3><div>ABCG2 contributes to multidrug resistance by transporting chemicals across cell membranes. 3′-epi-12β-hydroxyfroside (HyFS) is known for its anticancer properties as an autophagy inducer. This study investigates whether HyFS can overcome drug resistance by promoting autophagy-mediated ABCG2 degradation.</div></div><div><h3>Methods</h3><div>Two non-drug-resistant lung cancer cell lines, H460 and A549, along with their drug-resistant sublines, H460/MX20 and A549/MX10, were used as experimental models. Immunoblotting, immunofluorescence, and flow cytometry were used to assess the expression of ABCG2 and autophagy-related molecules. Flow cytometry was also used for quantitative analysis of ABCG2 efflux and cell death. Cell viability was assessed using the MTT assay. Additionally, murine models of H460/MX20 and A549/MX10 were established to evaluate the efficacy of various combination therapies and ABCG2 expression.</div></div><div><h3>Results</h3><div>The efficacy of HyFS treatment depends on dosage and duration, which influence autophagy flux in treated cells. Inhibition of autophagy restores ABCG2 expression, causing intracellular accumulation of ABCG2 substrates and promoting their efflux. HyFS treatment sensitizes mitoxantrone-resistant H460/MX20 and A549/MX10 cells to mitoxantrone, enhancing mitoxantrone-induced reduction in cell viability and triggering cell apoptosis. Inhibiting autophagy mitigates these effects. In addition, HyFS treatment reduces mitoxantrone resistance mediated by ABCG2 and hinders tumor progression. Moreover, the combination of mitoxantrone with HyFS shows promising synergistic antitumor effects in both MX-sensitive and MX-resistant murine tumor models without inducing any obvious side effects.</div></div><div><h3>Significance</h3><div>These findings highlight the potential of HyFS in overcoming drug resistance through autophagy-dependent degradation of ABCG2, suggesting its promise as a therapeutic approach against ABCG2-mediated drug resistance in lung cancer cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118085"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858800","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":"RvD1 and LXA4 inhibitory effects on cardiac voltage-gated potassium channels","authors":"Alicia De la Cruz ,&nbsp;Carlotta Ronchi ,&nbsp;Chiara Bartolucci ,&nbsp;Paula G. Socuéllamos ,&nbsp;Angela de Benito-Bueno ,&nbsp;Stefano Severi ,&nbsp;Antonio Zaza ,&nbsp;Carmen Valenzuela","doi":"10.1016/j.biopha.2025.118083","DOIUrl":"10.1016/j.biopha.2025.118083","url":null,"abstract":"<div><div>The resolution of inflammation is modulated by specialized pro-resolving lipid mediators (SPMs), which can be modified in some cardiovascular diseases. Among these SPMs, RvD1 and LXA₄ prevent atrial fibrillation (AF) remodeling and cardiac hypertrophy, respectively in animal models. However, little is known about their electrophysiological effects on cardiac voltage-gated (VG) ion channels. We used the patch-clamp technique in heterologous systems and cardiomyocytes to assess the acute effects of RvD1, and LXA₄, on VG potassium currents. <em>In silico</em> simulations were used to predict the effect of current modulation on the atrial and ventricular action potentials (AP). RvD1 (5 nM) reduced <em>I</em>_Ks (channel K_V7.1/KCNE1) in COS-7 cells and guinea-pig cardiomyocytes by 50.3 ± 7.3 % and 29.9 ± 5.4 % at + 40 mV, respectively, without modifying its voltage dependence. RvD1 was more potent than LXA₄. In heterologous systems, RvD1 was also tested on <em>I</em>_Kur (channel K_V1.5), <em>I</em>_to (channel K_V4.3/KChIP2), <em>I</em>_Kr (channel K_V11.1), and <em>I</em>_K1 (channel K_ir2.1) with the largest inhibitory effect on <em>I</em>_Ks and <em>I</em>_Kr. In <em>in silico</em> simulations RvD1 prolonged repolarization significantly in both atrial and ventricular myocytes. All these results provide a comprehensive evaluation of RvD1 and LXA₄ on cardiac human potassium channels, at pathophysiologically relevant concentrations, being RvD1 more potent than LXA₄. The predicted effects on the AP suggest that, along with their antiinflammatory action, RvD1 may reverse AF-induced electrical remodeling in the atria by their modulation of K⁺ currents. The same action might instead contribute to ventricular functional remodeling; however, direct evidence for this is missing.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118083"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858801","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":"The mechanism of patchouli alcohol in treating IBS-D based on BMP-Smad pathway","authors":"Yu-lin Lu ,&nbsp;Chen Huang ,&nbsp;Shu-yan Huang ,&nbsp;Ting Li ,&nbsp;Wan-yu Chen ,&nbsp;Shu-lin Yi ,&nbsp;Ying Pei ,&nbsp;Jin-tong Lu ,&nbsp;Zhuo-ying Chen ,&nbsp;Hong-ying Cao ,&nbsp;Bo Tan","doi":"10.1016/j.biopha.2025.118050","DOIUrl":"10.1016/j.biopha.2025.118050","url":null,"abstract":"<div><div>Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal condition, and diarrhea predominant (IBS-D) is the most common subtype.The enteric nervous system (ENS) regulates major gastrointestinal motility and function, and the intestinal neuronal BMP-SMAD signaling pathway is closely related to intestinal motility. Patchouli alcohol (PA) has been reported to modulate IBS-D, but whether its mechanism of action ameliorates IBS-D through the BMP-SMAD signaling pathway is unclear.This study preliminarily confirmed the abnormal colonic contraction of IBS-D functional bowel disease, and PA can not only improve gastrointestinal motor function, effectively inhibit the characteristic diarrhea and increased visceral sensitivity in IBS-D rats, but also regulate the neurohomeostasis of the gastrointestinal tract. In this study, in vivo and ex vivo studies confirmed that the neurohomeostatic regulation of patchouli alcohol was related to the increase of BMPRII⁺ neuronal subsets in the intestinal myenteric plexus and the regulation of BMP-SMAD signal pathway; PA increased the phosphorylation level of BMP-SMAD pathway-related proteins in IBS-D rat intestinal neurons.The findings can provide evidence for subsequent clinical research and drug development.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118050"},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855914","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":"Quinine-chalcone hybrids as potent inhibitors of P-glycoprotein with apoptotic effects on EBC-1 cells","authors":"Angéla Takács ,&nbsp;Malin Jessen ,&nbsp;Eszter Lajkó ,&nbsp;Zsófia Szász ,&nbsp;Márton Kalabay ,&nbsp;Antal Csámpai ,&nbsp;László Kőhidai","doi":"10.1016/j.biopha.2025.118076","DOIUrl":"10.1016/j.biopha.2025.118076","url":null,"abstract":"<div><div>Chincona alkaloids extracted from the bark stem of <em>Cinchona officinalis</em> have been historically used to treat fever and malaria. More recently, cinchona alkaloid derivatives have been attributed to apoptotic effects in the context of cancer. Similarly, chalcones are plant-derived polyphenolic compounds with known anti-fungal, -microbial, -malarial, and -carcinogenic properties. Here, we reveal cytotoxic and antiproliferative characteristics of synthetic quinine-chalcone hybrids in human cancer cell lines. Two derivatives (AD-12 and AD-13) presented IC₅₀ values below 2 µM in the lung squamous cell carcinoma cell line (EBC-1). Our study shows that AD-12 and AD-13 increased intracellular ROS levels and promoted caspase-3/7, and −8 activity in EBC-1 cells. These apoptotic effects were accompanied by short-term inhibition of P-gp efflux activity, while expression levels of P-gp transporters remained stable. Together, our study illustrates the potential of quinine-chalcone hybrids as novel anticancer drug candidates.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118076"},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Exploring the molecular mechanisms of MSC-derived exosomes in Alzheimer's disease: Autophagy, insulin and the PI3K/Akt/mTOR signaling pathway” [Biomed. Pharmacother. 176 (2024) 116836]","authors":"Nesrine Ebrahim ,&nbsp;Hajir A. Al Saihati ,&nbsp;Faris Q.B. Alenzi ,&nbsp;Mohamed El-Sherbiny ,&nbsp;Nimer F. Alsabeelah","doi":"10.1016/j.biopha.2025.118042","DOIUrl":"10.1016/j.biopha.2025.118042","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118042"},"PeriodicalIF":6.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058472","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":"Novel genipin-crosslinked acellular biogenic conduits for tissue engineering applications","authors":"Óscar Darío García-García ,&nbsp;Sandra Escalante-Quirós ,&nbsp;Claudia Llinares-Monllor ,&nbsp;Paula Ávila-Fernández ,&nbsp;David Sánchez-Porras ,&nbsp;Miguel Etayo-Escanilla ,&nbsp;Fernando Campos ,&nbsp;Jesús Chato-Astrain ,&nbsp;Víctor Carriel","doi":"10.1016/j.biopha.2025.118064","DOIUrl":"10.1016/j.biopha.2025.118064","url":null,"abstract":"<div><h3>Background</h3><div>Collagen-based conduits have been generated <em>in-vivo</em> stimulating a fibrotic response through the implantation of a non-resorbable material in animal models, creating biogenic substitutes. However, they often exhibit clinical limitations due to prolonged generation times, exclusive autologous use and insufficient mechanical strength. Consequently, decellularization and cross-linking could solve the aforementioned drawbacks, providing a non-immunogenic and ready-to-use natural substitute with enhanced biomechanical properties. Nevertheless, these processes may alter microarchitecture and biocompatibility. Hence, this is the first study to characterize <em>ex-vivo</em> the biogenic conduits of 1-and 2-months maturation time which were subjected to decellularization and genipin (GP) cross-linking procedures performing histological, structural, biomechanical, biocompatibility, and immunological analyses to identify the most suitable option for peripheral nerve regeneration.</div></div><div><h3>Results</h3><div>Histological examination indicated consistent uniformity of the biogenic conduits at both timepoints post-implantation, maintaining their overall structural integrity and collagen pattern following decellularization and GP crosslinking treatments. Furthermore, no evidence of nuclear debris was observed in the decellularized groups at either stage of maturation, confirming the decellularization protocol's efficiency. The substitutes with longer maturation time presented a generally higher preservation of ECM key components. In addition, the GP crosslinking significantly increased the resistance values of decellularized biogenic conduits, without drastically affecting the ex-vivo cell biocompatibility nor macrophage polarization rate phenotype.</div></div><div><h3>Conclusions</h3><div>These findings indicate the suitability of our decellularization protocol for biogenic conduits, and subsequent crosslinking with GP improves their biomechanical properties without altering their biocompatibility or immunological profile, suggesting their potential as a ready-to-use tubular substitute for nerve and other tissue engineering applications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118064"},"PeriodicalIF":6.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855916","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":"Mechanisms of bone regeneration repair and potential and efficacy of small molecule drugs","authors":"Ke Zhang ,&nbsp;Hao Li ,&nbsp;Tao Wang ,&nbsp;Fanchao Li ,&nbsp;Zhihong Xie ,&nbsp;Hong Luo ,&nbsp;Xuesong Zhu ,&nbsp;Pengde Kang ,&nbsp;Qinglin Kang ,&nbsp;Zhang fei ,&nbsp;Wuxun Peng","doi":"10.1016/j.biopha.2025.118070","DOIUrl":"10.1016/j.biopha.2025.118070","url":null,"abstract":"<div><div>Bone regeneration and repair is a complex physiological process of bone formation. To date, existing research has greatly enhanced our understanding of bone regeneration and repair, achieving significant success in treating bone injuries. However, extensive bone defects, bone nonunion, and metabolic bone diseases remain incompletely solved challenges in modern medicine. With the emergence of High-Throughput Screening (HTS) technology, previous studies have identified numerous small molecule compounds with potential for inducing bone formation and enhancing bone metabolism. However, the effects of these small molecules on bone regeneration and repair through related signaling pathways have not been systematically elaborated. Therefore, in this literature review, we focus on summarizing the classical signaling pathways affecting bone regeneration and repair, as well as the research progress and applications of related small molecule drugs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118070"},"PeriodicalIF":6.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851356","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}