Current drug metabolism最新文献

{"title":"BushenQiangxin Formula Inhibits Inflammation and Apoptosis in Doxorubicin- Induced Heart Failure via the NF-κB/Bcl-2 Axis.","authors":"Wenchu Zhao, Jiejun Hou, Xiaofei Zhang, Jinyi Chen, Meiyan Wu, Ruiting Zhang, Mengke Wei, Yitong Liu, Qiying Zhang","doi":"10.2174/0113892002498146260907071827","DOIUrl":"https://doi.org/10.2174/0113892002498146260907071827","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of chronic heart failure continues to rise annually, making improved prognosis central to reducing its high mortality rate. BushenQiangxin Formula (BSQX) demonstrates significant clinical efficacy, yet its molecular mechanisms for cardiac protection through inhibition of myocardial inflammation and apoptosis remain to be elucidated.</p><p><strong>Methods: </strong>A doxorubicin-induced rat CHF model was established. The efficacy of the formula was evaluated via echocardiography, Hematoxylin and Eosin (HE) staining, and TUNEL staining. Non-tar-geted serum metabolomics explored altered metabolic profiles, while Western blot and immunohisto-chemical analyses assessed key proteins in the NF-κB/Bcl-2 signaling axis.</p><p><strong>Results: </strong>BSQX intervention significantly improved Left Ventricular Ejection Fraction (LVEF) in CHF rats while mitigating myocardial tissue injury and apoptosis. Metabolomic analysis revealed that the formula significantly re-regulated dysregulated bile acid metabolic pathways. Molecular mechanism studies confirmed that the formula markedly downregulated proinflammatory factor IL-17 and NF-κB protein expression while upregulating the anti-apoptotic protein Bcl-2 and inhibiting Caspase-9 activation.</p><p><strong>Discussion: </strong>The ability of BSQX to concurrently restore bile acid metabolic homeostasis and suppress the NF-κB/Bcl-2-mediated inflammatory and apoptotic cascades underscores its multi-target, holistic therapeutic advantage. This regulation of the \"metabolism-inflammation-apoptosis\" cross-talk provides a novel molecular rationale for its cardioprotective effects against chronic heart failure.</p><p><strong>Conclusion: </strong>BSQX exerts cardioprotective effects by repairing metabolic dysregulation and inhibiting the NF-κB/Bcl-2 signaling axis, thereby effectively alleviating myocardial inflammation and apoptosis.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Yueju Pill on the Pharmacokinetics and Antidepressant Effect of Fluoxetine in Rats.","authors":"Benlu Zhong, Jinzhen Wang, Ming Gong, Boling Liu, Xiaolu Fan, Kanghao Zhu, Maierdan Maimaiti, Mingyu Cui","doi":"10.2174/0113892002502047260904105709","DOIUrl":"https://doi.org/10.2174/0113892002502047260904105709","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to investigate the effect of Yueju Pill (YJW) on the pharmacokinetics and antidepressant effect of Fluoxetine (FLX) in rats.</p><p><strong>Methods: </strong>The depression rat model was established using lipopolysaccharide. Pharmacokinetics parameters of Fluoxetine were analyzed via HPLC. Behavioral changes were assessed using the open field test, sucrose preference test, and forced swim test. Gastrointestinal motility function was evaluated. The levels of IL-1β, IL-6, TNF-α, SOD, and MDA in Serum, and 5-HT, DA, NE, and BDNF in the hippocampus were measured by ELISA. Hippocampal histopathology and 16S rRNA gut microbiota sequencing were performed.</p><p><strong>Results: </strong>AUC0-t (24.52 ± 1.09 mg/Lh), AUC0-∞ (25.09 ± 1.11 mg/Lh), Cmax (1.10 ± 0.04 mg/L), and t1/2 (12.63 ± 0.30 h) of FLX in the YJW group significantly increased, while CL/F (0.07 L/(hkg)) decreased. Pharmacodynamic studies demonstrated that the combination therapies, compared with monotherapies, significantly ameliorated depressive-like behaviors, restored neurotransmitter and BDNF levels, reduced pro-inflammatory cytokines, alleviated oxidative stress damage, and mitigated gastrointestinal motility disorders induced by FLX. Notably, the combination of YJW with low-dose FLX was particularly effective in alleviating gastrointestinal hypomotility. Histopathology revealed superior neuroprotective effects on hippocampal neurons in the combination groups. Gut microbiota analysis indicated that combination treatments, especially in the low-dose FLX group, more effectively reversed dysbiosis.</p><p><strong>Discussion: </strong>YJW may alter the pharmacokinetics of FLX by modulating the activity of CYP enzymes and transporters. Further in vitro and in vivo research should be done to assess the effect of YJW on the activity of CYP enzymes and transporters. The combination therapy exerts synergistic antidepressant effects via multi-target and multi-pathway mechanisms, effectively regulating neurotransmitters, suppressing neuroinflammation, alleviating oxidative stress, and restoring gut microbiota homeostasis. The key molecular targets and core regulatory pathways need further investigation.</p><p><strong>Conclusion: </strong>YJW enhances the blood exposure of FLX by influencing pharmacokinetics and synergizes with FLX through multi-target mechanisms. The strategy of combining YJW with low-dose FLX not only enhances efficacy but also mitigates FLX-associated gastrointestinal adverse effects. It provides a basis for the combination of YJW and FLX, which highlights the gut-brain axis as a critical target for developing novel therapeutic strategies.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Applications of the Tetrahedral Framework Nucleic Acid in Orthopaedics.","authors":"Bingling Chen","doi":"10.2174/0113892002468732260816165149","DOIUrl":"https://doi.org/10.2174/0113892002468732260816165149","url":null,"abstract":"<p><p>Tetrahedral framework nucleic acids (tFNA) are specialised three-dimensional DNA nanostructures with precise self-assembly, structural rigidity, programmability, and excellent biocompatibility. Their resistance to enzymatic degradation is enabled by their unique tetrahedral geometry, which also facilitates efficient cellular internalisation without the need for transfection agents. Thus, establishing tFNA as both a versatile regulator and a nanocarrier. Healing in orthopaedics is often stalled by limited tissue regeneration, unpredictable inflammation and infection, and suboptimal drug localisation within complex microenvironments. This review summarises recent advances in the application of tFNA across key orthopaedic domains, including bone and cartilage regeneration, angiogenesis, immunomodulation, anti-microbial therapy, and bone cancer treatment. tFNA have been shown to enhance osteogenic and chondrogenic differentiation of multiple mesenchymal stem cell populations by indirectly activating the Wnt/β-catenin and PI3K/AKT pathways. When functionalised with peptides, small molecules, nucleic acids, or natural compounds, tFNA promote angiogenesis, suppress oxidative stress, inhibit inflammatory and pyroptotic signalling, and restore extracellular matrix homeostasis in degenerative joint diseases. Furthermore, integration of tFNA with antibiotics, antimicrobial peptides, hydrogels, and implant surfaces demonstrates promising efficacy in combating orthopaedic infections and biofilm formation while supporting tissue regeneration. Emerging tFNA-based delivery systems for osteosarcoma therapy further illustrate their translational versatility. Despite these encouraging findings, several challenges hinder clinical translation: large-scale synthesis, long-term biosafety, immune responses, pharmacokinetics, and controlled degradation within mechanically and biologically complex orthopaedic environments. Interdisciplinary research and optimisation are ongoing to advance tFNA-based platforms toward safe, effective, and personalised nanotherapeutic strategies in orthopaedics. These developments may ultimately redefine precision therapies for the global management of musculoskeletal diseases.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interconnected Metabolic and Cellular Pathways in Drug-Induced Hepatotoxicity: Translational Safety Implications.","authors":"Sushant Jain, Avijit Mazumder, Bhavani Pentela","doi":"10.2174/0113892002497372260809213500","DOIUrl":"https://doi.org/10.2174/0113892002497372260809213500","url":null,"abstract":"<p><p>Drug-induced liver injury remains a principal trigger of acute hepatic failure, late-stage drug attrition, and post-marketing withdrawal, reflecting persistent limitations in mechanistic prediction and translational safety assessment. Owing to its central role in xenobiotic biotransformation, the liver is highly vulnerable to metabolic bioactivation and reactive intermediate formation. This review presents a metabolism-centered; systems level framework that integrates Phase-I and Phase-II enzymatic processes with downstream cellular stress responses governing hepatocellular fate. Cytochrome 450-mediated oxidation and subsequent conjugative pathways determine the balance between detoxification and electrophilic burden; disruption of this equilibrium initiates oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, bile-acid transport impairment, immune-inflammatory activation, and regulated cell death. Emphasis is placed on the dynamic crosstalk among these pathways, which explains interindividual variability, idiosyncratic susceptibility and preclinical-clinical discordance. Emerging insights from network toxicology, transcriptomics, metabolomics and computational modelling have enhanced mechanistic resolution beyond conventional biomarkers. Concurrently, advanced experimental systems including three-dimensional hepatic cultures, organoids, micro-physiological liver-on-chip platforms, humanized animal models and integrative in vitro-in silico approaches are improving translational fidelity. Collectively, this synthesis advances a cohesive mechanistic perspective and highlights integrative strategies to strengthen early risk stratification, mechanistically informed evaluation and predictive safety assessment in drug development.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jujuboside A: Distribution, Pharmacological Effects, Pharmacokinetics, and Alternative Production Strategies.","authors":"Xingjie Tao, Chenxi Yu, Xiaoxiao Wang, Jinrui Liu, Junbo Xie","doi":"10.2174/0113892002484035260803070627","DOIUrl":"https://doi.org/10.2174/0113892002484035260803070627","url":null,"abstract":"<p><p>This study summarizes the chemical features, pharmacological effects, pharmacokinetic profiles, and current limitations arising from the limited natural distribution of Jujuboside A (JuA). Since demand for JuA is increasing while natural resources are scarce, our review focuses is its biosynthetic pathway and production challenges. Recent advances and perspectives on alternatives for production are also discussed, such as directed glycosylation based on structurally related homologs, metabolic pathway regulation of sour jujuba (Ziziphus jujububa var. spinosa (Bunge) Hu ex H.F.Chou), microbial cell factory development, and plant callus culture. This review summarizes the pharmacological activities, pharmacokinetics, and biosynthesis of JuA, and discusses current limitations and potential production strategies. Collectively, these insights highlight the pharmacological potential of JuA and provide a theoretical basis for future mechanistic studies and sustainable large-scale production.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of Framework Nucleic Acids in Tumor Diagnosis and Therapy.","authors":"Mengting Liu, Tiantian Wu, Qifeng Zhang, Huiyong Zhu","doi":"10.2174/0113892002461750260727104653","DOIUrl":"https://doi.org/10.2174/0113892002461750260727104653","url":null,"abstract":"<p><strong>Introduction: </strong>Framework Nucleic Acids (FNAs) are precisely self-assembled two- or three-dimensional nucleic acid architectures renowned for their excellent programmability, monodisperse structures, and near-atomic precision. These distinctive properties enable FNAs to function as versatile nanocarriers for targeted biomarker recognition, efficient co-delivery of therapeutics and imaging agents, and stimuli-responsive release within the tumor microenvironment, driving rapid advances in framework nucleic acid-based nanomaterials for tumor theranostics in recent years.</p><p><strong>Methods: </strong>We extensively searched bibliographic databases using keywords such as \"framework nucleic acids\", \"FNA\", \"DNA nanostructures,\" and \"tumor theranostics\". Based on the literature retrieved, we summarized the design and functionalization strategies of FNA-based nanomaterials, reviewed their applications in various tumor therapeutic modalities, and discussed the major challenges for clinical translation.</p><p><strong>Results: </strong>FNAs exhibited excellent application prospects across diverse tumor therapeutic modalities. They markedly enhanced targeted drug delivery and therapeutic efficacy in chemotherapy, enabled efficient gene silencing in gene therapy, strengthened antitumor immune responses in immunotherapy, and significantly improved precision in tumor imaging and phototherapy. Collectively, these advantages position FNAs as a highly promising and versatile platform for precision tumor theranostics.</p><p><strong>Discussion: </strong>We have further provided a comprehensive discussion of the multifaceted challenges that continue to impede the clinical translation of Framework Nucleic Acid (FNA)-based nanomaterials despite their considerable preclinical promise in tumor theranostics, as well as an in-depth outlook on their future potential in this evolving field.</p><p><strong>Conclusion: </strong>This review summarizes the remarkable potential of Framework Nucleic Acids (FNAs) as an intelligent nanoplatform for tumor diagnosis and therapy. Nevertheless, several critical challenges persist for clinical translation, including long-term biosafety, scalable manufacturing, and efficient in vivo delivery. Future efforts to address these barriers are expected to accelerate the clinical implementation of FNAs in precision oncology.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Multi-Omics Reveals BCAA Metabolic Remodeling Associated with the Antifibrotic Effects of Ku-Cai-Gao in Liver Fibrosis.","authors":"Xinjian Guo, Hui Gao, Xiaomei Zhang, Yue Feng, Yu Bai, Yin Li, Jing Yan, Huanhuan Wang, Yanhua Liu, Jingtao Li, Fanrong Liu","doi":"10.2174/0113892002480918260723105428","DOIUrl":"https://doi.org/10.2174/0113892002480918260723105428","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Ku-Cai-Gao (KCG) is a traditional Chinese medicinal preparation with both therapeutic and dietary functions. Preliminary clinical observations suggest that KCG may alleviate liver fibrosis-related manifestations and improve liver function, but whether its antifibrotic effects involve hepatic amino acid metabolic remodeling remains unclear. This study investigated the hepatoprotective pathways of KCG using an integrated multi-omics strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established and treated with KCG. KCG constituents were profiled by ultra-performance liquid chromatography-tandem mass spectrometry. Liver histopathology and collagen deposition were evaluated, and serum transaminases, oxidative stress markers, and inflammatory cytokines were measured. Fibrosis- and apoptosis-related proteins were assessed by immunohistochemistry/immunofluorescence and Western blotting. Transcriptomics and proteomics were integrated to identify key pathways, with selected targets validated by reverse transcription-quantitative polymerase chain reaction and Western blotting. Targeted metabolomics assessed Branched-Chain Amino Acid (BCAA) metabolism, and 16S ribosomal RNA sequencing characterized gut microbiota changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;KCG markedly ameliorated CCl4-induced liver injury, as shown by improved liver morphology, reduced liver injury scores, decreased collagen deposition, and attenuation of inflammatory cell infiltration. KCG treatment reduced serum ALT, AST, ALP, and T-BIL levels, decreased MDA, IL-6, and TNF-α levels, and restored SOD activity. Histological and molecular analyses showed that KCG reduced α-SMA, collagen I, TGF-β1, PCNA, and caspase-3 expression, indicating attenuation of hepatic stellate cell activation, extracellular matrix accumulation, inflammation, and apoptosis. Integrated transcriptomic and proteomic analyses converged on the valine, leucine, and isoleucine degradation pathway, and targeted metabolomics showed decreased hepatic Branched-Chain Amino Acid (BCAA) levels after KCG treatment. These changes were accompanied by upregulation of Peroxisome Proliferator-Activated Receptor Alpha (PPARα)-related signaling. In addition, KCG treatment was associated with changes in gut microbiota composition, including alterations in Firmicutes, Bacteroidetes, and Muribaculaceae.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;These findings suggest that the antifibrotic effects of KCG are associated with PPARα-related signaling, BCAA metabolic remodeling, and improvement of inflammatory and metabolic disturbances. However, the causal roles of PPARα signaling, BCAA metabolism, and gut microbiota changes require further validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;KCG alleviated CCl4-induced liver fibrosis in mice, and its protective effects were associated with BCAA metabolic remodeling, PPARα-related signaling, and changes in gut m","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Branched-Chain Amino Acids (BCAAs): Metabolism and Their Roles In Inflammation Regulation and Disease.","authors":"Xuan Zhao, Yuyu An, Leilei Shi, Shiyu Yuan, Chaojun Han, Jiping Liu","doi":"10.2174/0113892002454247260618095436","DOIUrl":"https://doi.org/10.2174/0113892002454247260618095436","url":null,"abstract":"<p><p>Branched-chain amino acids (BCAAs)-encompassing leucine, isoleucine, and valine-constitute a class of essential amino acids indispensable for protein synthesis and a myriad of metabolic functions. Beyond their canonical roles as substrates, BCAAs are now recognised as potent signalling molecules and key regulators of immunometabolism. They exert pleiotropic effects and demonstrate a profound capacity to modulate inflammatory responses. Inflammation, an intricate biological response to harmful stimuli, is a pathogenic driver underpinning the initiation and exacerbation of numerous chronic and acute diseases. This review critically synthesises the scientific literature, systematically examining the therapeutic potential of BCAAs in mitigating inflammation-related pathologies. We delve into the mechanistic intricacies through which BCAAs exert their anti-inflammatory and immunomodulatory actions. A thorough comprehension of these mechanisms is not merely an academic exercise but a crucial prerequisite for developing effective pharmacotherapies and precision nutrition approaches, ultimately forging new paradigms for the prophylaxis and clinical management of diseases with an inflammatory component.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleic Acid Nanomaterials Targeting Autophagy in Bone Regeneration.","authors":"Xiao Yang, Yuehan Wang, Zhong Hu, Jinyou Geng, Yuanyuan Sun, Xiaoru Shao","doi":"10.2174/0113892002458922260601054117","DOIUrl":"https://doi.org/10.2174/0113892002458922260601054117","url":null,"abstract":"<p><p>Impairment or irreversible loss of bone tissue function remains a prevalent clinical challenge, frequently compounded by donor scarcity, perioperative infection, and immune-mediated rejection, which collectively constrain therapeutic success rates. Novel functional nanomaterials based on nucleic acids-endowed with superior biocompatibility, predictable biodegradability, negligible systemic toxicity, and an abundance of programmable modification sites-have emerged as versatile platforms in bone tissue engineering. Currently, these materials are principally exploited across four interrelated domains: sustained release, bone targeting, scaffold materials for bone regeneration, and bioimaging, all aimed at orchestrating efficient bone regeneration. Recent mechanistic investigations into nano-bio interactions reveal that autophagy, a conserved catabolic pathway in eukaryotes that maintains energetic and metabolic homeostasis, critically governs skeletal repair by directing the timely degradation of intracellular cargo and the turnover of damaged organelles. Through direct modulation of osteoclast and osteoblast differentiation, autophagy fine-tunes the coupled process of bone remodeling. Concurrently, it shapes the regenerative milieu by reprogramming immune cell responses. Consequently, targeted modulation of autophagy represents a rational and promising strategy through which nucleic acid nanomaterials can accelerate bone regeneration. This review synthesizes current knowledge on the contributions of nucleic acid nanomaterials to bone healing, delineates the regulatory functions of autophagy in skeletal regeneration, and explains how these nanomaterials exploit autophagy as a mechanistic lever to enhance bone repair.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide N-Methyltransferase (NNMT): A Central Regulator in Hepatocellular Carcinoma Metabolism and Therapeutic Targeting - A Systematic Review.","authors":"Shatrudhan Prajapati, Shikha Yadav, Ajay Pal Singh","doi":"10.2174/0113892002416170251209103247","DOIUrl":"https://doi.org/10.2174/0113892002416170251209103247","url":null,"abstract":"<p><strong>Introduction: </strong>The purpose of this systematic review was to assess the expression of nicotinamide N-methyltransferase (NNMT), its mechanistic value, and clinical importance in Hepatocellular Carcinoma (HCC).</p><p><strong>Methods: </strong>A search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and the Cochrane Library in accordance with PRISMA guidelines. Studies published between 2010 and 2024 that evaluated NNMT expression and its functional implications in HCC were included. Data extraction, synthesis, and qualitative analysis were performed according to standardized criteria.</p><p><strong>Results: </strong>Sixty studies were included in this review. Most studies reported significantly higher NNMT overexpression in liver tumor tissue compared to non-tumor liver tissue. High NNMT levels were associated with aggressive tumor behavior, poor prognosis, and disruptions in methylation and energy metabolism. However, comparability across studies was limited due to heterogeneity in detection methods and small cohort sizes.</p><p><strong>Discussion: </strong>The findings indicate that NNMT plays a crucial role in hepatocarcinogenesis by regulating methyl-donor balance and epigenetic remodeling. Although NNMT shows strong diagnostic and therapeutic potential, the current evidence is largely preclinical, high-lighting the need for multicenter validation.</p><p><strong>Conclusion: </strong>NNMT is a promising biomarker and therapeutic target for HCC. Future research should include quantitative assessment of NNMT expression, mechanistic validation, and clinical studies exploring NNMT inhibition strategies.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}