Curr. Med. Chem. [JOURNAL]
Sun
200 papers
Global Trends and Research Hotspots in Vascular Ageing: A Comprehensive Bibliometric Analysis.
Zhang X, Lyu X, Li T … +13 more , Jin J, Li J, Cui S, Yang X, Zhang X, Li W, Sun Y, Guo S, Xing Z, Xu R, Zhou B, Jiao L, Wang T
Curr Med Chem · 2026 Mar · PMID 41863165 · Publisher ↗
BACKGROUND: Vascular ageing has garnered increasing attention due to the global rise in ageing populations. Despite this, no comprehensive bibliometric analysis on vascular ageing has been conducted to date. OBJECTIVE: T...
BACKGROUND: Vascular ageing has garnered increasing attention due to the global rise in ageing populations. Despite this, no comprehensive bibliometric analysis on vascular ageing has been conducted to date. OBJECTIVE: This study aims to fill that gap by analyzing the landscape of vascular ageing research through a bibliometric approach. METHODS: We retrieved 1,160 articles published between 1900 and 2023 from the Web of Science Core Collection. Using VOSviewer and CiteSpace, we examined publication trends, journal impact, author contributions, citation analysis, and key research themes. RESULTS: The United States emerged as the leading contributor in publications and international collaborations. The U.S. Department of Veterans Affairs was the most prolific institution. American Journal of Physiology - Heart and Circulatory Physiology accounted for 3.28% of the publications, while Circulation Research had the highest impact factor. The top three authors by publication volume were Seals DR, Donato AJ, and Ungvari Z. The most cited paper, published in The Lancet in 2002, underscored the significant impact of vascular ageing research. Current research keywords include "ageing," "hypertension," "oxidative stress," "arterial stiffness," "atherosclerosis," and "inflammation." DISCUSSION: This study delivers a thorough bibliometric analysis of vascular ageing, yielding insights that contribute to scientific progress. It not only helps researchers identify current hotspots within the field but also uncovers promising directions for future investigation. Furthermore, subsequent research can build upon these findings to explore underlying mechanisms, validate emerging trends through experimental approaches, and translate bibliometric insights into clinical applications aimed at age-related vascular dysfunction. CONCLUSION: This article offers a comprehensive overview of vascular ageing research. We hope these findings will foster novel insights into the mechanisms and therapeutic strategies for vascular ageing.
Molecular Dynamics Simulations Reveal Heavy Water-Induced Structural Changes in Subunit c of ATP Synthase and Formation of Aligned Clusters.
Lanjanian H, Olgun A, Nematzadeh S … +2 more , Torkamanian-Afshar M, Kiyani F
Curr Med Chem · 2026 Mar · PMID 41863164 · Publisher ↗
Deuterium is a stable isotope of hydrogen with an abundance of ~1/6600. Since water contains 2 hydrogens, the abundance of deuterated water (heavy water [D2O] + semiheavy water [HDO]) is ~1/3300. This corresponds to ~15...
Deuterium is a stable isotope of hydrogen with an abundance of ~1/6600. Since water contains 2 hydrogens, the abundance of deuterated water (heavy water [D2O] + semiheavy water [HDO]) is ~1/3300. This corresponds to ~15 mM concentration in human plasma that is several times higher than several common electrolytes. Despite this very high concentration, its effects on human health and aging are generally neglected. Deuterated water can generate deuteron through spontaneous ionization. The exchange of deuteron with ionizable hydrogen in other molecules is called deuteronation and is a common stochastic process that changes the structure and function of proteins and other macromolecules. In this study, we analyzed the effect of different concentrations of D2O on the structure of ATP synthase's c subunit by using molecular dynamics (MD) simulations. D2O changed the structure of the c subunit starting from a concentration that is lower than half of its natural abundance. At high concentrations, D2O started to behave strangely by forming aligned and clustered structures. Our results can be useful in the elucidation of the mechanisms of deuterium-depleted water's (DDW, light water) published health benefits. Our study shows the importance of analysis of structural changes that occur in all macromolecules over a range of D2O concentrations that have biological relevance. At least this structural change observed in the ATP synthase's c subunit could have broader implications for biological processes or health.
Classifying molecular subtypes and establishing a prognosis model using oxidative stress-related genes for lung adenocarcinoma.
Zhang W, Zhao X, Wang Y … +1 more , Li X
Curr Med Chem · 2026 Mar · PMID 41863163 · Publisher ↗
INTRODUCTION: Oxidative stress correlates with the development and prognosis of lung adenocarcinoma (LUAD). This study, on the basis of oxidative stress-related genes (OSRGs), commences to identify molecular subtypes and...
INTRODUCTION: Oxidative stress correlates with the development and prognosis of lung adenocarcinoma (LUAD). This study, on the basis of oxidative stress-related genes (OSRGs), commences to identify molecular subtypes and develop prognostic model for LUAD. METHODS: LUAD samples were derived from the public database. OSRGs were acquired from GeneCards database. Molecular subtypes were classified by "ConsensusClusterPlus" package. Overall survival (OS) rate, clinical and immune infiltration features in different subtypes were compared. Differentially expressed genes (DEGs) were screened employing "limma" package. Thereafter, prognostic OSRGs signatures were identified via LASSO regression analysis. Further, we developed a RiskScore model and validated its predictive performance. Pathway enrichment analysis was carried out in different risk groups. RESULTS: Two molecular subtypes (Cluster1, Cluster2) of LUAD were classified with different survival outcomes, clinical features, and immune cell infiltration. Subsequently, 7-OSRGs prognostic signatures in LUAD were identified to establish RiskScore model, comprising TPSB2, CENPH, HIST1H1E, SULT2B1, CCL20, SERPINE1, and DKK1. High-risk group exhibited lower OS rate than low-risk group. The model exhibited robustness and was an independent indicator in predicting LUAD prognosis. Additionally, high-risk group was chiefly involved in cell function-relevant pathways, while low-risk group was chiefly implicated in immune-relevant pathways. DISCUSSION: This study distinguished two molecular subtypes and developed a prognostic RiskScore model linked to OSRGs in LUAD. However, these findings still require further verification through multiple prospective experiments. CONCLUSION: Taken together, our current research could offer some guidance for the precise stratification and treatment of LUAD.
Underweight and the Risk of Atrial Fibrillation in the Asian Population.
Zhang M, Deng Y, Tang X … +7 more , Zhao H, Bai J, Deng Z, Yu P, Zhang J, Zhang J, Liu X
Curr Med Chem · 2026 Mar · PMID 41863162 · Publisher ↗
INTRODUCTION: While previous studies suggest a higher incidence of atrial fibrillation (AF) among underweight individuals, this association remains underexplored in Asian populations. We aimed to systematically assess th...
INTRODUCTION: While previous studies suggest a higher incidence of atrial fibrillation (AF) among underweight individuals, this association remains underexplored in Asian populations. We aimed to systematically assess this relationship in Asians. METHODS: The association between genetically predicted underweight (using summary GWAS data from the Korean Genome and Epidemiology Study Consortium) and AF (using data from BioBank Japan) was assessed using a two-sample Mendelian randomization analysis. A pooled analysis of cohort studies from PubMed, EMBASE, and Web of Knowledge was conducted to examine the relationship between underweight [body mass index (BMI) <18.5 kg/m2] and AF risk in Asians. RESULTS: The genetically predicted underweight showed a significant causal relationship with AF (odds ratio: 1.91, 95% CI: 1.51, 2.42, p value = 7.51E-08). The meta-analysis included six cohort studies involving 427,844 participants, 27,273 of whom were classified as underweight. Compared with normal weight, underweight was associated with a 31 percent greater risk of AF (RR: 1.31; 95% CI: 1.13, 1.51). The dose-response analysis revealed that each 1-unit decrease in BMI was associated with a 6 percent higher risk of AF (95% CI: 1.04, 1.09) in individuals who were underweight. DISCUSSION: Our findings, supported by both genetic and observational results, suggest that underweight is a risk factor for AF. Further research is needed to determine whether these results apply to populations outside of Asia. Additional clinical trials are required to explore whether addressing underweight can help prevent new-onset AF or recurrence after ablation. CONCLUSION: Our findings suggest that in Asian populations, underweight individuals have a higher risk of AF.
From Biomarker to Drug Target: Integrating ceRNA Networks and Pharmacogenomics to Reposition C5orf34 in Uterine Corpus Endometrial Cancer Therapy.
Yan J, Zhu X, Yang X … +2 more , Yang Y, Li D
Curr Med Chem · 2026 Mar · PMID 41863161 · Publisher ↗
INTRODUCTION: This study aimed to systematically investigate the expression, prognostic value, biological roles, and therapeutic relevance of C5orf34 in uterine corpus endometrial carcinoma (UCEC). METHODS: Using TCGA-UC...
INTRODUCTION: This study aimed to systematically investigate the expression, prognostic value, biological roles, and therapeutic relevance of C5orf34 in uterine corpus endometrial carcinoma (UCEC). METHODS: Using TCGA-UCEC data (554 tumor vs. 35 normal samples), we performed differential expression analysis, survival modeling, gene-set enrichment (GSEA), immune-infiltration profiling (TIMER/CIBERSORT), drug-sensitivity prediction (RNAactDrug), and ceRNA network construction. C5orf34 expression was validated by qRT-PCR in UCEC cell lines (Ishikawa, KLE) and by immunohistochemistry via the Human Protein Atlas. RESULTS: The expression of C5orf34 was significantly higher in UCEC tissues than in normal endometrial tissues (p &lt; 0.001). Increased C5orf34 expression was linked to advanced clinical stage (p &lt; 0.001), older age (p &lt; 0.001), higher weight (p = 0.011), and specific histological types (p &lt; 0.001). Elevated C5orf34 expression was identified as an independent risk factor for poorer overall survival (OS, HR: 2.184; p = 0.015), progression-free survival (PFS, HR: 1.68; p = 0.004), and disease-specific survival (DSS, HR: 3.28; p &lt; 0.001). GSEA analysis indicated that C5orf34 was associated with pathways like cell cycle regulation, cytokine-cytokine receptor interaction, DNA replication, and immune-related processes. The expression of C5orf34 was negatively correlated with immune cell infiltration, such as NK CD56bright cells, and immune scores, implying an immunosuppressive tumor microenvironment. Furthermore, C5orf34 expression was associated with resistance to several drugs, including AT-7519, Navitoclax, Tivozanib, Ruxolitinib, and Erlotinib. A ceRNA network involving LNC01224/miR-455-5p/C5orf34 was constructed, providing insights into the regulatory mechanisms of C5orf34 in UCEC. DISCUSSION: C5orf34 emerges as a novel oncogenic driver and immunomodulator in UCEC, linking tumor proliferation, immune evasion, and chemoresistance. Limitations include reliance on public databases and the need for functional mechanistic studies. CONCLUSION: This research identifies C5orf34 as a potential prognostic indicator and therapeutic target for UCEC. The results underscore the significance of C5orf34 in tumor progression, immune regulation, and drug resistance. Future studies should concentrate on clarifying the molecular mechanisms of C5orf34 and verifying its clinical application in larger cohorts.
Potential of HSP90AA1 as Diagnostic, Prognostic, and Immunological Biomarkers in Human Cancer Demonstrated through Pan-Cancer Investigation: A Bioinformatics Analysis.
Chen S, Huang W, Jiang W … +1 more , Zhou S
Curr Med Chem · 2026 Mar · PMID 41863160 · Publisher ↗
INTRODUCTION: The HSP90AA1 gene has been linked to a number of malignancies, but its precise function is still unknown, and no research has examined the connection between HSP90AA1 and pan-cancer. Therefore, further inve...
INTRODUCTION: The HSP90AA1 gene has been linked to a number of malignancies, but its precise function is still unknown, and no research has examined the connection between HSP90AA1 and pan-cancer. Therefore, further investigation into the relationship between HSP90AA1 and pan-cancer is required. METHODS: We utilized the human protein atlas (HPA) to analyze HSP90AA1 mRNA and protein expression levels in human organs, tissues, and cell lines. Subsequently, the 33 different cancer types' levels of HSP90AA1 mRNA expression were assessed, and a range of tumor types had their diagnostic and prognostic values assessed. Additionally, the regions with the most prevalent HSP90AA1 mutation types were found. HSP90AA1's PPI and miRNA regulatory networks were established, and its activating or inhibiting effects in established pathways were examined. Finally, we looked at the connection between immune cell and regulator infiltration levels in various cancers and the expression levels of HSP90AA1. RESULTS: The nasopharynx, testis, fallopian tube, bronchus, duodenum, gallbladder, and epididymis are the primary organs that express the HSP90AA1 protein. Thirty-three cancers have elevated HSP90AA1 mRNA expression as compared to normal tissues. The most prevalent HSP90AA1 mutation location is X585. Analysis of HSP90AA1 as a diagnostic marker in pan-cancer showed that the good diagnostic utility of HSP90AA1 in a range of cancer types. High HSP90AA1 expression groups had poorer prognosis and were associated with clinical parameters. GO/KEGG and GSEA analyses showed that HSP90AA1 was mostly associated with pathways that are linked to tumor molecules and the immune system. HSP90AA1 was associated with immune cells and regulatory factors in various cancers. DISCUSSION: HSP90AA1 plays a role in immune microenvironment modulation in a range of tumor types and is correlated with prognosis. We hope to further validate the role of HSP90AA1 in tumors through cellular and functional assays, so as to achieve the validation of the theory, basic experiments, and clinical applications, and thus promote it as a recognized prognostic marker. And the development of corresponding targeted drugs for the HSP90AA1 locus may become a major challenging direction for future development. CONCLUSION: HSP90AA1 was mostly associated with pathways that are linked to tumor molecules and the immune system, and was considered a potential diagnostic, prognostic, and immunological biomarker in human cancer.
Withdrawn: Dual Antitumor Effects of Solanum incanum L. in Lung and Colonic Adenocarcinomas via TRAIL-Mediated Extrinsic Apoptotic Pathway: A Network Pharmacology and Multi-Omics Investigation.
Lin CT, Yeh LR, Wu JT … +2 more , Hung CM, Lee CY
Curr Med Chem · 2026 Mar · PMID 41863159 · Publisher ↗
UNLABELLED: The article has been withdrawn at the request of the Editor-in-Chief of the journal Current Medicinal Chemistry. Bentham Science apologizes to the readers of the journal for any inconvenience this may have ca...
UNLABELLED: The article has been withdrawn at the request of the Editor-in-Chief of the journal Current Medicinal Chemistry. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
Characterization of Pathogens in Respiratory Tract Infection Using Targeted Next-Generation Sequencing: A Population-Based Study in Foshan City from 2022 to 2024.
Chen Y, Deng Y, Xian X … +4 more , Deng J, Guo X, Yang D, Zeng Y
Curr Med Chem · 2026 Mar · PMID 41863158 · Publisher ↗
INTRODUCTION: Respiratory Tract Infection (RTI) is a leading cause of mortality worldwide and represents one of the major complications in patients with respiratory syndrome. MATERIALS AND METHODS: A total of 3,836 RTI p...
INTRODUCTION: Respiratory Tract Infection (RTI) is a leading cause of mortality worldwide and represents one of the major complications in patients with respiratory syndrome. MATERIALS AND METHODS: A total of 3,836 RTI patients in Foshan City between 2022 and 2024 were enrolled. Specimens, including alveolar lavage fluid, sputum, pleural effusion, and throat swab, were collected. Pathogen identification was performed using the t-NGS technology. Raw sequencing data were processed via Fastp software, and human host sequences were removed by alignment to the hg19 reference genome using BWA-mem. Microbial sequences were aligned against the NCBI RefSeq/nt and FDA ARGOS databases for pathogen identification. Pathogens, contaminants, and commensal bacteria were distinguished according to the Pathogen Pathogenicity Classification Table. Chi-square test was applied to compare pathogen distributions across genders, age groups, and sample types, and to assess the trend of mixed and single infection. Additionally, 23S rRNA mutations were analyzed, and the response of the known pathogenic bacteria to the antibiotics was determined. RESULTS: A total of 129 potential pathogens were identified, predominantly including bacteria (57.28%) and RNA viruses (24.65%). The most frequently detected pathogenic bacteria were Haemophilus influenzae (11.56%), Mycoplasma pneumoniae (9.57%), and Streptococcus pneumoniae (6.31%), while the predominant viruses included Rhinovirus (6.6%), human respiratory syncytial virus (4.07%), and Influenza A virus (3.57%). Pathogen profiles varied across age groups, such as Mycoplasma pneumoniae and Haemophilus influenzae were more common in children (1- to 12-year-olds), while Candida albicans and Epstein-Barr virus were more frequently detected in the elderly (≥ 60 years old). Furthermore, Moraxella catarrhalis and Rhinovirus were more frequently detected in throat swabs, whilst Epstein-Barr virus, Candida albicans, and Pseudomonas aeruginosa were more commonly detected in alveolar lavage fluid samples. Mixed infections were relatively frequent, with a higher incidence observed in spring and winter. The macrolide resistance mutation rate in 23S rRNA reached 96.79%, predominantly involving the A2063G mutation, with higher rates observed in children and the elderly. Additionally, known pathogenic bacteria also exhibited varying levels of resistance to different antibiotics. DISCUSSION: While numerous studies have demonstrated the utility of t-NGS in identifying RTI pathogens, our study provided detailed epidemiological data from a retrospective cohort in Foshan city. CONCLUSION: The application of t-NGS effectively revealed the pathogenic characteristics of RTI patients with respiratory syndrome. Overall, these data provided valuable insights into the clinical diagnosis and management of RTI.
Biomarker-Based Analysis of the Association Between Obstructive Sleep Apnea Syndrome and Oxidative Stress: A Univariable, Bidirectional, and Multivariable Mendelian Randomization Study.
Liu Y, Liu S, Deng J … +4 more , Li W, Chen D, Zhou L, Tian L
Curr Med Chem · 2026 Mar · PMID 41837488 · Publisher ↗
OBJECTIVE: This study aimed to investigate the potential genetic association between obstructive sleep apnea syndrome (OSAS) and oxidative stress (OS) using multi- -dimensional Mendelian randomization (MR) analysis. METH...
OBJECTIVE: This study aimed to investigate the potential genetic association between obstructive sleep apnea syndrome (OSAS) and oxidative stress (OS) using multi- -dimensional Mendelian randomization (MR) analysis. METHODS: We conducted bidirectional univariable MR analyses using FinnGen-derived OSAS genetic data and summary statistics for 16 oxidative stress biomarker indicators (OSBIs) from IEU OpenGWAS and GWAS Catalog, employing five methods with sensitivity analyses to evaluate robustness and heterogeneity. Multivariable MR (MVMR) was further applied to adjust for confounders and estimate the direct effect of OSAS on OSBIs. RESULTS: OSAS might be a risk factor for elevated lactate (OR = 1.06, 95% CI = 1.02-1.11, p < 0.01). MVMR supported an independent causal effect (OR = 1.16, 95% CI = 1.02-1.32, p = 0.03), although significant heterogeneity suggests interpretation requires caution. Reverse MR suggested that decreased superoxide dismutase (OR = 0.96, 95% CI = 0.93-0.98, p < 0.01) and matrix metalloproteinase-9 (OR = 0.98, 95% CI = 0.96-0.99, p < 0.01) were associated with OSAS. Furthermore, MVMR suggested a potential effect of OSAS on elevated vitamin E levels (OR = 1.15, 95% CI = 1.01-1.32, p = 0.04). DISCUSSION: Our study provides genetic evidence for a bidirectional causal relationship between OSAS and OSBIs. Potential mechanisms may include hypoxia-disordered glucose metabolism and a compensatory upregulation of the antioxidant system. Future research should utilize larger, multi-ethnic samples and incorporate a broader range of OSBIs to systematically delineate these relationships. CONCLUSION: OS is both a driver and a pathological consequence of OSAS.
Pioneering of New Generation Therapies for Oral Cancer Involves the Integration of Small Molecules, Nanotechnology, and Artificial Intelligence - A Review.
Alkan AH, Bozkurt FZ, Şengün DN … +3 more , Orhan K, Mutlu P, Cansaran-Duman D
Curr Med Chem · 2026 Mar · PMID 41837487 · Publisher ↗
Oral cancer remains a significant global health challenge, characterized by high morbidity, poor survival rates, and a tendency for late-stage diagnosis. Although conventional treatment modalities-namely surgery, radioth...
Oral cancer remains a significant global health challenge, characterized by high morbidity, poor survival rates, and a tendency for late-stage diagnosis. Although conventional treatment modalities-namely surgery, radiotherapy, and chemotherapy- are partially effective, they are frequently accompanied by substantial functional and aesthetic morbidity, therapeutic resistance, and limited long-term efficacy. In light of these limitations, a paradigm shift is underway in the therapeutic landscape of oral squamous cell carcinoma (OSCC). This shift is driven by three converging innovations: small molecule inhibitors, nanotechnology-based targeted drug delivery systems, and artificial intelligence (AI)-enabled diagnostic and prognostic tools. This review provides a comprehensive synthesis of recent preclinical and clinical advancements in these areas, emphasizing their underlying mechanisms, therapeutic benefits, and potential for synergy. Small molecule therapies modulate oncogenic signaling cascades in a pathway-specific manner, while nanocarrier platforms deliver cytotoxic and immunomodulatory agents precisely and locally, thereby reducing systemic toxicity. Concurrently, AI-driven models are transforming early detection, risk stratification, and outcome prediction by leveraging high-throughput omics data and imaging analytics. Together, these transformative technologies represent a significant advancement in precision oncology and underscore the importance of translating laboratory innovations into clinical applications. This review critically evaluates these emerging strategies, highlighting the potential of an interdisciplinary approach to redefine therapeutic standards and overcome long-standing clinical challenges in oral cancer management.
Antibacterial Depsipeptides: One Common Feature, Diversity of Structures and Mechanisms of Action.
Guglya EB, Shcheglov AS, Yampolsky IV
Curr Med Chem · 2026 Mar · PMID 41837486 · Publisher ↗
The emergence and spread of drug-resistant pathogens have made the development of new antibiotics a global priority. Innovative agents with new mechanisms of action and/or membership in new drug classes are urgently need...
The emergence and spread of drug-resistant pathogens have made the development of new antibiotics a global priority. Innovative agents with new mechanisms of action and/or membership in new drug classes are urgently needed. Antimicrobial peptides have been widely studied and show promise as therapeutics. Depsipeptides are a large group of peptides in which one or more amide bonds are replaced by ester bonds. They are nonribosomal peptides that typically contain up to 20 amino acids, often arranged in cyclic scaffolds with diverse side chains, and they display varied biological activities. Many depsipeptide antibiotics have now been identified, and this class merits focused attention. This review surveys roughly two dozen compounds with pronounced antibacterial properties that have been discovered or actively investigated in recent years. These include daptomycin, a clinically important systemic antibiotic; teixobactin, a candidate in clinical development; acyldepsipeptides, which are preclinical leads; and several recent hits with drug-development potential, such as clovibactin, lysocin E, ecumicin, and empedopeptin. We also discuss ramoplanin, which underwent clinical evaluation but is no longer considered a leading candidate, and the enniatins, once used clinically but now recognized as mycotoxins. The review focuses primarily on mechanisms of action and summarizes each compound to the extent these mechanisms have been characterized.
Research Prospects for the Mitochondria in Glaucoma: A Bibliometric Analysis.
Liang L, Wang MJ, Liu ZY … +1 more , Wang SC
Curr Med Chem · 2026 Mar · PMID 41837485 · Publisher ↗
BACKGROUND: Growing evidence implicates mitochondrial dysfunction as a pivotal contributor to glaucoma pathogenesis through oxidative stress, autophagy, and apoptotic pathways. However, systematic analyses of research co...
BACKGROUND: Growing evidence implicates mitochondrial dysfunction as a pivotal contributor to glaucoma pathogenesis through oxidative stress, autophagy, and apoptotic pathways. However, systematic analyses of research collaboration patterns, key themes, and emerging trends in this field remain limited. METHODS: We retrieved relevant publications from the Web of Science (WOS) database (1999-2024) for bibliometric analysis. Visualization was generated using VOSviewer and CiteSpace, with complementary analysis in Charticulator and Excel. Journal impact factors from WOS were used to assess publication influence. RESULTS: This study analyzed 397 publications and found a fluctuating annual increase in both publications and citations in this research area. The United States emerged as the most productive nation in terms of publication volume. Investigative Ophthalmology & Visual Science was identified as the predominant journal in this field. Among individual researchers, Dr. Kim Keun Young was distinguished as a leading contributor. The most frequently occurring terms were: glaucoma, mitochondria, Oxidative Stress (OS), apoptosis, and Ischemia-Reperfusion Injury (IRI). Notably, the mitochondrial inhibitors were identified as promising therapeutic candidates for ophthalmic disorders. Our findings demonstrated the therapeutic potential of mitochondria through metabolic modulation and neuroprotective mechanisms, while identifying oxidative stress, autophagy dysregulation, and apoptotic pathways as critical pathological mediators. The analysis offered valuable insights for developing mitochondria-targeted therapies. DISCUSSION: This comprehensive bibliometric analysis reveals a steady growth in research focusing on mitochondrial dysfunction in glaucoma, with the United States leading in scholarly output. The identified trends underscore a critical shift: emerging cellular and molecular insights are actively guiding the development of targeted and personalized therapeutic strategies for glaucoma. We acknowledge that our study has limitations inherent to bibliometric methodology. The literature search was restricted to articles and reviews within the Web of Science Core Collection. However, the exclusion of other major databases and clinical publication types may create a bias, overrepresenting basic research and underrepresenting clinical findings. Additionally, variations in the analytical algorithms of tools such as VOSviewer and CiteSpace may influence the resultant data patterns. Despite these limitations, the study offers a systematic mapping of the research landscape and provides a clear guide for future research directions in this field. CONCLUSION: This study provided a comprehensive analysis of scientific advancements in this field, highlighting the pivotal role of mitochondrial dysfunction in glaucoma pathogenesis and proposing strategic directions for developing novel therapeutic approaches in ophthalmic disorders.
Plasma Proteins Mediate the Causal Effect of Diet on the Development of Osteoporosis: A Mendelian Randomization Study.
Luan W, Fan S, Li C
Curr Med Chem · 2026 Mar · PMID 41837484 · Publisher ↗
INTRODUCTION: The causal relationship between dietary intake, plasma proteins, and osteoporosis (OP) remains uncertain. We investigated whether 38 dietary factors and 2,940 plasma proteins have a causal effect on OP usin...
INTRODUCTION: The causal relationship between dietary intake, plasma proteins, and osteoporosis (OP) remains uncertain. We investigated whether 38 dietary factors and 2,940 plasma proteins have a causal effect on OP using Mendelian randomization (MR). METHODS: Single-nucleotide polymorphisms (SNPs) robustly associated with 38 dietary factors and 2,940 plasma proteins were used as instrumental variables (IVs). We performed four MR approaches, including inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median. Multivariate MR analysis and mediation effect estimation were employed to evaluate potential mediating effects. RESULTS: Higher consumption of ground coffee and instant coffee was statistically associated with increased OP prevalence, whereas greater water intake showed a protective trend. Among plasma proteins, 152 demonstrated significant associations with OP, with 26 linked to ground coffee consumption, 23 to instant coffee, and 5 to water intake. Notably, RAB GTPase-activating protein 1-like (RABGAP1L) appeared to mediate the association between ground coffee consumption and OP. DISCUSSION: MR analysis indicated that ground coffee and instant coffee intake are risk factors, while water consumption is a protective factor for OP, and suggested a potential mediating role of RABGAP1L in ground coffee-induced OP. These findings should be interpreted as potential mechanistic insights rather than definitive causal proof. CONCLUSION: The observed associations between coffee consumption and OP likely involve complex biological pathways, and the protective effect of water intake warrants further investigation in longitudinal studies.
The Efficacy of Palbociclib-Conjugated ZnO-Ordered Mesoporous Carbon Nanohybrid against MCF-7 Breast Cancer Cell Line.
Lajimi FZF, Sabeti B, Chekin F … +1 more , Esboei BR
Curr Med Chem · 2026 Mar · PMID 41837483 · Publisher ↗
INTRODUCTION: Breast cancer is the most common cancer in females. The inhibitors of cyclin-dependent kinase 4/6 (CDK 4/6) have revolutionized the treatment of breast cancer. Palbociclib (Pal) is a highly potent CDK 4/6 i...
INTRODUCTION: Breast cancer is the most common cancer in females. The inhibitors of cyclin-dependent kinase 4/6 (CDK 4/6) have revolutionized the treatment of breast cancer. Palbociclib (Pal) is a highly potent CDK 4/6 inhibitor. The side effects and poor absorption of Pal may influence efficiency. This prompted us to conjugate Pal drug into the nanomaterial based on ZnO-ordered mesoporous carbon (ZnO-OMC) as a nanocarrier in drug delivery and investigate the anticancer activity of the Pal-conjugated ZnO-OMC (Pal@ZnO-OMC) on breast cancer cells (MCF-7). METHODS: The ZnO-OMC composite was synthesized by the green method using Callicarpa plant extract, and Pal anticancer drug was loaded on the mentioned composite at different pHs, times, and ratios of drug to composite. The loading of Pal on ZnO-OMC composite was investigated by FE-SEM, UV-Vis, Raman, and FT-IR spectroscopy methods. The controlled Pal release from Pal@ZnO-OMC hybrid was investigated at different pH values and times. Moreover, the cytotoxicity of Pal@ZnO-OMC was evaluated on MCF-7 cells by MTT assay. RESULTS: The results showed that ZnO-OMC is a highly efficient carrier with high loading of Pal, 82.5% at pH 7.0 for 3 h. The prepared Pal@ZnO-OMC exhibited favorable physico-chemical characteristics such as the controlled and targeted release pattern (15.2% of Pal is released at pH 7.4 for 10 h, while 58.1% of Pal is released at pH 4.0) and efficient cytotoxicity (cell viability of 50.4% and 38.8% at 24 and 48 h, respectively). Free Pal was significantly less efficient (with half-maximal inhibitory concentration (IC50) of 151.9 μg/mL for 48 h) than Pal@ZnO-OMC (with IC50 of 2.6 μg/mL for 48 h). DISCUSSION: The synergistic effects of Pal@ZnO-OMC nanoformulation due to the presence of ZnO in hybrid seemed to improve antiproliferation efficacies against MCF-7 cells compared with the free Pal. CONCLUSION: All findings demonstrated that the designed Pal@ZnO-OMC hybrid can be a potent nanoformulation for the treatment of MCF-7 breast cancer.
A Lactylation-based Gene Signature in Lung Adenocarcinoma Provides a Novel Perspective to Predict the Prognosis and Therapeutic Response.
Zhao M, Li B, Li H … +5 more , Nan H, Sun Y, Pei Y, Zhang X, Geng N
Curr Med Chem · 2026 Mar · PMID 41837482 · Publisher ↗
INTRODUCTION: Lactylation, a novel post-translational modification in tumor cells, is studied here to explore its relevant gene signature in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: Transcriptome data of LUAD f...
INTRODUCTION: Lactylation, a novel post-translational modification in tumor cells, is studied here to explore its relevant gene signature in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: Transcriptome data of LUAD from The Cancer Genome Atlas (TCGA) were retrieved from UCSC Xena, while the gene expression dataset GSE31210 was acquired from the Gene Expression Omnibus (GEO) database. Lactation-related genes (LRGs) were identified based on previous literature. Lactation levels were quantified using single-sample gene set enrichment analysis (ssGSEA). After screening LRGs associated with prognosis, the ConsensusClusterPlus package was employed for clustering. Subsequently, a RiskScore model was constructed through univariate Cox and LASSO analyses. The prognostic relevance and robustness of the RiskScore were evaluated, and the association of the RiskScore with both immunotherapy response and the tumor microenvironment (TME) was determined. RESULTS: An overall high lactylation score was noticed in the LUAD sample, which could be assigned into 2 molecular subtypes (C1 and C2). Meanwhile, 83 LRGs were preliminarily explored to have prognostic relevance, of which 5 genes (CDKN3, FSCN1, PKP2, FAM83A, and ABCC2) were further revealed as the hub genes for the RiskScore model. Such RiskScore, independent of other clinicopathological features, displayed a satisfying efficacy in predicting the prognosis and the response to immunotherapy. Additionally, the formulated RiskScore, including the expression level of each gene, displayed a varied correlation with the predicted drug candidates. DISCUSSION: From the lactylation perspective, this study reveals LUAD's molecular heterogeneity, proposes and externally validates a 5-gene RiskScore model. The model independently predicts prognosis, correlates with immunotherapeutic response and drug sensitivity, and points to potential links among lactate metabolism, key signaling pathways, and clinical outcomes. CONCLUSION: 5 prognosis-relevant LRGs could provide a novel perspective for the individualized therapeutic regimens for LUAD.
Discovery of New Hydrazonothiazolines as Bovine and Human Carbonic Anhydrase-II Inhibitors: In-vitro, Kinetics, Selectivity and Molecular Dynamics Exploration.
Ahsan Halim S, Khan M, Tariq Shehzad M … +9 more , Mabood F, N Mali S, Rout S, Jan A, Bin Muhsinah A, Shafiq Z, Kashtoh H, Khan A, Al-Harrasi A
Curr Med Chem · 2026 Mar · PMID 41837481 · Publisher ↗
INTRODUCTION: Carbonic Anhydrase II (CA-II) is crucial for several physiopathological processes, including bone calcification, osteoporosis, tumorigenicity, and epilepsy, among others. Usually, the intraocular pressure o...
INTRODUCTION: Carbonic Anhydrase II (CA-II) is crucial for several physiopathological processes, including bone calcification, osteoporosis, tumorigenicity, and epilepsy, among others. Usually, the intraocular pressure observed in glaucoma exacerbates the condition, and CA-II inhibitors have the potential to be used for the reduction of this pressure. METHODS: Moreover, to search for novel CA-II inhibitors with high potency, a series of hydrazonothiazoline derivatives (5a-q) were synthesized. The inhibitory potency of our synthesized compounds was investigated for human and bovine CA-II through in-vitro and computational methods. The in vitro screening revealed that 5a-5f, 5g, 5h, and 5l have significant inhibitory action for bCA-II (IC50 = 13.1 μM to 44.6 μM), whereas 5a, 5d, 5f, 5h, and 5l exhibited excellent inhibition of hCA-II (IC50 = 7.0 μM to 33.1 μM). Therefore, binding pattern of those active hits was elucidated by in silico docking, which reflects that the thiazole group of ligands is responsible for binding of compounds with the target proteins and consequent functional inhibition of the enzyme. Moreover, the type of inhibition of active hits (5a and 5h for hCA-II and bCA-II, respectively) was explored by kinetics experiment in which both 5a (for hCA-II, Ki = 5.25±0.004 μM) and 5h (for bCA-II, Ki = 5.5±0.001 μM) competitively inhibited CA-II. RESULTS: The molecular dynamics simulation, MMPBSA analysis, revealed that 5a has better stability in 1BN1 than 5h in 1V9E. CONCLUSION: Those identified inhibitors could serve as a skeleton to design more potent CA-II inhibitors in the future.
A Multimodal Diagnostic Model for Hepatocellular Carcinoma Integrating Biomarkers Related to Programmed Cell Death and Radiomics Features.
Lei L, Liu N, Tang L … +3 more , Liu Q, Pan K, Huang X
Curr Med Chem · 2026 Mar · PMID 41837480 · Publisher ↗
INTRODUCTION: Hepatocellular carcinoma (HCC) is characterized by its insidious onset and rapid progression. Investigating diagnostic and therapeutic strategies targeting programmed cell death (PCD) represents a promising...
INTRODUCTION: Hepatocellular carcinoma (HCC) is characterized by its insidious onset and rapid progression. Investigating diagnostic and therapeutic strategies targeting programmed cell death (PCD) represents a promising research direction. METHODS: PCD pathway activation in HCC was assessed via single-sample GSEA (ss- GSEA). Differentially expressed genes (DEGs) were screened by WGCNA, FindMarkers, and the limma package from bulk and single-cell data. Intersecting DEGs were refined by LASSO regression in the glmnet package, and diagnostic performance was validated using ROC analysis. Functional enrichment analysis was conducted with the clusterProfiler package, and drug prediction was performed with Enrichr package. Py- MOL, AutoDockTools, and AutoDock Vina software were employed to perform molecular docking simulations. A radiomics-driven LASSO model was applied to construct a diagnostic nomogram. RESULTS: PCD plays a crucial part in the development of HCC. Three genes (CAPG, MS4A6A, and TREM2) were identified as the PCD-related diagnostic genes for HCC. The reliability of the three genes was confirmed by ROC analysis, with AUC values exceeding 0.7. Drug prediction screened 46 candidate compounds, from which Tamibarotene and Vorinostat were selected for molecular docking. Finally, a nomogram was established based on the radiomics features of the CAPG gene, reaching an AUC above 0.8. DISCUSSION: Using interpretable machine learning to integrate transcriptomic, single-- cell, and radiomic data, we revealed systemic dysregulation of PCD-related pathways in HCC and validated the diagnostic value of CAPG, MS4A6A, and TREM2 across datasets. A CAPG-based radiomics nomogram showed favorable discrimination and calibration, suggesting translational potential. CONCLUSION: We developed a reusable multimodal diagnostic framework with candidate biomarkers and a radiomics tool to facilitate the early detection and risk stratification of HCC.
Cyasterone Improves Mitochondrial Function and Protects against Knee Osteoarthritis by Activating PPARγ.
Liang D, Yao Z, Zhang Y … +6 more , Lin W, Li H, Zhu J, Ren L, Zeng X, Xu L
Curr Med Chem · 2026 Mar · PMID 41837479 · Publisher ↗
INTRODUCTION: Studies have demonstrated that mitochondrial dysfunction plays an important role in the development of knee osteoarthritis. Our previous study reported that cyasterone accelerates fracture healing by promot...
INTRODUCTION: Studies have demonstrated that mitochondrial dysfunction plays an important role in the development of knee osteoarthritis. Our previous study reported that cyasterone accelerates fracture healing by promoting the migration and osteogenesis of mesenchymal stem cells (MSCs). However, the effect of cyasterone on osteoarthritis (OA) has not been investigated. Therefore, this study aimed to investigate the effects of cyasterone on mitochondrial function in chondrocytes of mice and its potential therapeutic impact on knee osteoarthritis (OA) in mice. METHODS: Primary chondrocytes were isolated from C57BL/6 mice, and the optimal cyasterone concentration was determined via CCK-8 assay. An osteoarthritis chondrocyte model was established using lipopolysaccharide (LPS) induction. Chondrocytes were assigned to control, LPS, and cyasterone treatment groups. ATP production, NAD+/NADH ratio, oxidative stress levels, and mitochondrial membrane potential were measured in each group. Adult C57BL/6 mice were allocated into three groups (n=8 per group): control, model, and cyasterone treatment. After 4 weeks of cyasterone intervention, histopathological changes in knee joints and expression of extracellular matrix-related proteins in cartilage tissue were assessed. RESULTS: Compared to the LPS group, cyasterone treatment significantly increased ATP production, elevated the NAD+/NADH ratio, and reduced oxidative stress levels in LPS- induced chondrocytes. Mechanically, we found that the expression of Peroxisome proliferator- activated receptor γ (PPARγ) was significantly increased by cyasterone. In the OA group treated with cyasterone, the mice exhibited marked improvement in cartilage histopathological scores compared to the model group, with enhanced expression of aggrecan and PPARγ proteins and decreased expression levels of MMP13 and phosphorylated- p65. DISCUSSION: Consistent with previous findings, our results showed that cyasterone significantly increased PPARγ expression in primary chondrocytes, thereby maintaining chondrocyte function and preventing the progression of OA. CONCLUSION: In summary, the results indicated that cyasterone could restore mitochondrial function in LPS-induced mouse chondrocytes by upregulating PPARγ expression. in vivo, cyasterone was found to reduce extracellular matrix degradation and inhibit the progression of osteoarthritis (OA). These findings suggest that cyasterone could be a potential natural compound for the effective treatment of OA.
Association Between Atherogenic Index of Plasma and Cardiovascular Events or Mortality in the General Population: A Meta-Analysis of Longitudinal Studies.
Cai J, Zhang Y, Fan Y
Curr Med Chem · 2026 Mar · PMID 41832710 · Publisher ↗
INTRODUCTION: The balance between plasma triglycerides and high-density lipoprotein cholesterol is evaluated using the Atherogenic Index of Plasma (AIP). We aimed to synthesize evidence from meta-analyses on the associat...
INTRODUCTION: The balance between plasma triglycerides and high-density lipoprotein cholesterol is evaluated using the Atherogenic Index of Plasma (AIP). We aimed to synthesize evidence from meta-analyses on the association between the AIP and major adverse cardiovascular events (MACEs) or mortality in the general population. METHODS: Embase, Web of Science, and PubMed were searched for publications up to January 28, 2025. Cohort studies reporting the association between AIP and the risks of MACEs and mortality in the general population were included. RESULTS: Fifteen studies (16 articles), encompassing a total of 901,640 individuals, met the inclusion criteria. Comparing individuals with the highest AIP to those with the lowest, the pooled adjusted HR indicated significantly elevated risks MACEs (hazard ratios [HR] 1.33; 95confidence intervals [CI] 1.22-1.46), coronary heart disease (CHD) (HR 1.72; 95% CI 1.51-1.95), stroke (HR 1.49; 95% CI 1.03-2.15), all-cause mortality (HR 1.24; 95% CI 1.10-1.39), and cardiovascular mortality (HR 1.17; 95% CI 1.05-1.31). However, the observed association between elevated AIP and stroke was not confirmed in the sensitivity analysis. DISCUSSION: These findings suggest that measuring blood AIP level may help identify high-risk individuals for death and cardiovascular events in the general population. However, the results of subgroup analyses should be interpreted cautiously due to the limited number of studies available within each subgroup. CONCLUSION: Elevated AIP is an independent predictor of MACEs, CHD, cardiovascular mortality, and all-cause mortality in the general population. Further prospective studies are essential to validate these findings and to optimize the clinical application of AIP.
Mendelian Randomization Analyses Indicate a Causal Association Between Sodium-Glucose Cotransporter-1 Inhibition and Mitochondrial Function.
Fan G, Qu ZH
Curr Med Chem · 2026 Mar · PMID 41832709 · Publisher ↗
INTRODUCTION: The role of sodium-glucose cotransporter-1 (SGLT1) in mitochondrial biology function remains unclear. This study aimed to investigate the causal association between SGLT1 inhibition and mitochondrial biolog...
INTRODUCTION: The role of sodium-glucose cotransporter-1 (SGLT1) in mitochondrial biology function remains unclear. This study aimed to investigate the causal association between SGLT1 inhibition and mitochondrial biology function via Mendelian randomization (MR) analysis. METHODS: A two-sample MR study was conducted to evaluate the association of SGLT1 inhibition with mitochondrial biology. The identification of genetic instruments for SGLT1 inhibition as genetic variants was achieved, and these were found to be associated with the expression of the SLC5A1 gene and glycated hemoglobin level (HbA1c). The principal analysis employed was the random inverse variance weighted (IVW) algorithm. The weighted median and the MR-Egger method are supplementary methods for IVW analysis. Sensitivity analyses were performed to assess the reliability of the results. RESULTS: The results indicated that genetically predicted SGLT1 inhibition was positively related with mitochondrial Serine tRNA ligase (βIVW = 1.40 [95% confidence interval (CI) 0.59, 2.22]), NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 (βIVW = 2.35 [95% CI 1.00, 3.69]), and other up-regulated mitochondrial components. Meanwhile, SGLT1 inhibition was negatively associated with mitochondrial Glutaredoxin-2 (βIVW = -2.52 [95% CI -3.56, -1.48]), Pyruvate carboxylase (βIVW = -1.07 [95% CI -1.89, -0.26]), Mitochondrial glutamate carrier 2 (βIVW = -1.78 [95% CI -2.62, -0.93]), and other down-regulated mitochondrial components in European population. DISCUSSION: This study found that SGLT1 inhibition is causally associated with NDUFB8, MICU3, MLYCD, SOD2, Serine tRNA ligase, MCAD, REXO2, SIRT5, TIM14, ETHE1, HOGA, GRX2, PC, and MTC2. By regulating these proteins, SGLT1 contributes to the modulation of mitochondrial biological function. It is imperative that further basic and clinical studies be conducted to elucidate the mechanisms underlying this causal relationship. CONCLUSION: We determined for the first time that genetically predicated SGLT1 inhibition is causally linked to a variety of mitochondrial biology processes in the European population.
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