Curr. Med. Chem. [JOURNAL]
Sun
200 papers
Exploring the Lactylation Landscape: A Bibliometric Analysis of Metabolic-Epigenetic Interplay in Disease Mechanisms and Therapeutic Potential.
Chen Y, Zheng S, Mi Y … +5 more , Guo R, Chen X, Li W, Yang C, Lin S
Curr Med Chem · 2026 Jun · PMID 42337886 · Publisher ↗
BACKGROUND: Lactylation, a recently discovered post-translational modification linking lactate metabolism to epigenetic regulation, has become a key player in metabolic reprogramming and disease development. Although thi...
BACKGROUND: Lactylation, a recently discovered post-translational modification linking lactate metabolism to epigenetic regulation, has become a key player in metabolic reprogramming and disease development. Although this field is expanding rapidly, a comprehensive analysis of its growth and trends is still lacking. METHODS: A bibliometric review of 798 publications (2019-2025) from the Web of Science Core Collection was performed using CiteSpace and VOSviewer to analyze research trends, collaboration networks, and knowledge structures. RESULTS: Annual publications grew rapidly, projected to exceed 450 by 2025. China led in research output, while the United States and South Korea achieved higher citation impact. Leading journals (e.g., Nature, Cell Metabolism) have driven key discoveries, with major focus areas including tumor-immune microenvironment interactions (such as therapy resistance), metabolic-epigenetic connections, and neurodegenerative disorders. Studies on histone lactylation dominate, but emerging frontiers involve non-histone targets and advances in detection methods. DISCUSSION: Bibliometric data reveal a disparity between publication volume and citation impact, particularly between China and other leading nations. Research hotspots are evolving from foundational histone mechanisms to systems-level exploration of therapy resistance and neurodegeneration. However, the field faces bottlenecks in non-histone detection technologies and a need for broader international collaboration. CONCLUSION: Despite progress, challenges persist, such as standardizing detection techniques, improving sensitivity for non-histone lactylation analysis, and clarifying microenvironment- specific regulatory pathways. International and interdisciplinary efforts, along with technological advancements, are essential to translate lactylation-mediated metabolic-epigenetic crosstalk into clinical applications, particularly in precision medicine and biomarker discovery.
Metabolic Syndrome-Associated Osteoarthritis: Global Burden and Associations of the C-Reactive Protein-Triglyceride Glucose Index and Platelet-to-HDL-C Ratio in CHARLS and NHANES.
Zhang Y, Zheng JH, Yuan R … +4 more , Wang ZY, Li Y, Liu X, Zhang L
Curr Med Chem · 2026 Jun · PMID 42337885 · Publisher ↗
BACKGROUND: Osteoarthritis (OA) represents a significant global health concern, and metabolic factors may contribute to its development. We assessed the global burden of OA and metabolic-attributable disability and exami...
BACKGROUND: Osteoarthritis (OA) represents a significant global health concern, and metabolic factors may contribute to its development. We assessed the global burden of OA and metabolic-attributable disability and examined associations of two biomarkers-the C-reactive protein-Triglyceride Glucose Index (CTI) and Platelet-- to-High-Density Lipoprotein Cholesterol Ratio (PHR)-with Metabolic Syndrome-associated Osteoarthritis (MetS-OA). METHODS: Three datasets were used in this study: the Global Burden of Disease (GBD) 2021, the China Health and Retirement Longitudinal Study (CHARLS; baseline data from 2011), and the National Health and Nutrition Examination Survey (NHANES; data from 2003 to 2010). GBD data were used to quantify OA burden, metabolic attribution, and projected trends. CHARLS and NHANES were analysed using multivariable logistic regression, subgroup analyses, Restricted Cubic Spline (RCS) modelling, and threshold- effect analysis. Discrimination was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: From 1990 to 2021, annual incident OA cases increased from 20.9 to 46.63 million, with an estimated global prevalence exceeding 600 million. The proportion of OA DALYs attributable to metabolic factors rose from 16% to 21%, and the age-standardised DALY rate is projected to reach 258.24 per 100,000 by 2035. We included 9,183 CHARLS and 3,842 NHANES participants. In fully adjusted models, CTI and PHR were associated with higher odds of MetS-OA (per 1-unit increase: CTI OR = 2.03 and 1.67 in CHARLS and NHANES, respectively; PHR OR = 1.11 and 1.12, respectively). CTI showed non-linearity in CHARLS (threshold 9.20) but not in NHANES (P for non-linearity = 0.136), whereas PHR showed non-linearity in both datasets (thresholds 8.02 and 8.43). Discrimination was moderate for CTI (AUC 0.74/0.66) and modest for PHR (AUC 0.63/0.59). DISCUSSION: These findings place metabolic factors in a broader context as an increasingly important contributor to the global OA burden. CTI and PHR were positively associated with MetS-OA in two independent cross-sectional datasets. These markers showed limited-to-moderate discriminatory ability, but their clinical utility and predictive value require longitudinal and external validation. CONCLUSION: This study highlights the potential role of metabolic factors in osteoarthritis and links CTI and PHR with MetS-OA in adults 45 years or older. However, longitudinal studies are needed to confirm these associations and assess predictive value.
A Global View on the use of Synthetic Peptides in ELISA-Based Serodiagnosis of Human Infectious Diseases.
Lopes LDS, Ribeiro AJ, Silva BLN … +20 more , Cassiano CSS, Resende CAA, Barcelos ICS, Gandra IB, Silva KA, Silva LMS, Souza LS, Ferreira LC, Pereira SP, Xavier SR, Campos da Paz M, Giunchetti RC, Machado-de-Ávila RA, Fagundes MÍ, Chavez-Fumagalli MA, Coelho EAF, Martínez JER, Araújo MSS, Gonçalves AAM, Galdino AS
Curr Med Chem · 2026 Jun · PMID 42337884 · Publisher ↗
The development of accurate and efficient diagnostic methods is essential to optimize the quality of life of patients. Serological methods using pathogenic antigens have demonstrated high performance in various applicati...
The development of accurate and efficient diagnostic methods is essential to optimize the quality of life of patients. Serological methods using pathogenic antigens have demonstrated high performance in various applications. The use of synthetic peptides as antigens in serological tests has recently shown promising results, especially in the Enzyme-Linked Immunosorbent Assay (ELISA), as they offer greater specificity, reproducibility, and the ability to overcome limitations associated with crude antigens, which are low in sensitivity and prone to cross-reactions. Combining the advantages of serological testing with synthetic antigens, this review analyzes studies made over the past decade on the use of synthetic peptides in ELISA for the diagnosis of infectious diseases of bacterial, helminthic, protozoan, viral, and fungal origin. A search was conducted on the PubMed database platform using the keywords "serodiagnosis," "peptide," "immunodiagnosis," and "diagnosis." Publications were selected after reading the titles and abstracts using pre-established selection and exclusion criteria, resulting in 31 eligible publications, which were included in this study. The results showed variation in sensitivity and specificity, with some studies reporting values above 90%. However, there were also low sensitivity and specificity due to several factors, including peptide selection methods, antigen concentration, sample quality, storage issues, and disease stage. This study further shows that synthetic peptide prediction and synthesis tools are an emerging area that could improve serological diagnosis.
Metabolic Syndrome and Gastric Cancer: A Concise Narrative Review of Recent Clinical Insights.
Liang T, Ren J
Curr Med Chem · 2026 Jun · PMID 42333550 · Publisher ↗
In contemporary epidemiology, the complex relationship between metabolic syndrome (MetS) and cancer risk has attracted considerable research attention. Gastric cancer (GC) is of particular concern due to its high mortali...
In contemporary epidemiology, the complex relationship between metabolic syndrome (MetS) and cancer risk has attracted considerable research attention. Gastric cancer (GC) is of particular concern due to its high mortality rate and significant global health impact. This concise narrative review, focusing on human observational and genetic studies, synthesizes recent clinical research findings to explore the connection between MetS and GC, emphasizing the underlying biological mechanisms and population-specific variations. It also addresses methodological considerations, research gaps, and implications for clinical practice and future research.
MicroRNA-Based Therapeutic Strategies for Pulmonary Arterial Hypertension under Different Delivery Systems: Progress and Challenges.
Chen J, Zhang X, Zhang J … +3 more , Ren H, Xie J, Ma R
Curr Med Chem · 2026 Jun · PMID 42316499 · Publisher ↗
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious disease with high morbidity and mortality, and current treatments fail to significantly improve prognosis, necessitating the exploration of new therapeutic...
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious disease with high morbidity and mortality, and current treatments fail to significantly improve prognosis, necessitating the exploration of new therapeutic targets. MicroRNAs (miRNAs), as key post-transcriptional regulators, are emerging as potential therapeutic targets for PAH. Due to microRNA's susceptibility to degradation, the choice of delivery method is critical for microRNA therapy in pulmonary hypertension. METHODS: We provide a detailed introduction and comparison of pharmacological methods for regulating miRNAs, including enhancing the stability of nucleoside analogues, viral vectors, non-viral vectors, and combinations of viral and non-viral vectors. RESULTS: Our analysis identifies that while each delivery modality can effectively modulate specific miRNA pathways and influence PAH progression in preclinical models, hybrid delivery systems demonstrate superior potential by balancing delivery efficiency with safety profiles. DISCUSSION: Despite promising preclinical findings, substantial challenges remain regarding biosafety, long-term efficacy, and translational feasibility. Optimization of miRNA stability and delivery specificity is essential for future clinical applications. CONCLUSION: Currently in the early stages of research, there are significant challenges to the safety and efficacy of applications targeting microRNAs, but advances in these strategies may lead PAH therapy into a new era of personalized, precision medicine.
The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden.
Tripathy M, Swain J, Das S
Curr Med Chem · 2026 Jun · PMID 42316498 · Publisher ↗
Diabetes Mellitus (DM) and atherosclerosis are two major chronic, non-communicable diseases that together constitute a critical axis of cardiovascular morbidity and mortality worldwide. Mounting evidence highlights their...
Diabetes Mellitus (DM) and atherosclerosis are two major chronic, non-communicable diseases that together constitute a critical axis of cardiovascular morbidity and mortality worldwide. Mounting evidence highlights their bidirectional relationship, emphasizing the need to elucidate the molecular and clinical intersections underpinning this link. Both conditions pose significant global health and economic challenges, with DM not only serving as a major risk factor but also accelerating the onset and progression of atherosclerosis. Understanding these shared pathways is essential to identify novel therapeutic strategies. Literature for this review was sourced from PubMed, Scopus, and Google Scholar databases. Hyperglycemia-induced endothelial dysfunction, reactive oxygen species-driven oxidative stress, Advanced Glycation End product (AGE)-Receptor for AGE (RAGE) interactions, and the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) along with adipokines are well-established mechanisms connecting diabetes mellitus with atherosclerosis. In addition to these classical pathways, emerging evidence highlights the contribution of NLRP3 inflammasome activation, Damage-Associated Molecular Patterns (DAMPs), pathogen-Associated Molecular Patterns (PAMPs), and Toll-Like Receptor (TLR) signaling in promoting vascular inflammation and accelerating disease progression. Furthermore, epigenetic modifications and microRNAs have been identified as novel modulators of this pathogenic interplay. This review synthesizes both the traditional and recently recognized mechanisms, providing a comprehensive understanding of the molecular links between these two conditions. Therapeutic strategies to disrupt this diabetes-atherosclerosis axis must move beyond a glucocentric paradigm. Agents should simultaneously address hyperglycemia and the vascular inflammatory processes that underlie atherosclerosis to reduce cardiovascular events and mortality. Notably, recent antidiabetic classes such as Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) show promising dual benefits in glycemic control and cardiovascular protection. These advances open avenues for integrated approaches to mitigate the global burden of diabetes-related atherosclerotic disease.
Technetium-99m Radiolabeled Carboplatin Polymeric Nanoparticles for Imaging and Treatment of Epithelial Ovarian Cancer.
Felismino CJ, Gomes-da-Silva NC, Soares MAG … +7 more , Yoshiara NMA, Ricci-Junior E, Fechine PBA, de Souza PFN, Özdemir DI, Alencar LMR, Santos-Oliveira R
Curr Med Chem · 2026 Jun · PMID 42316497 · Publisher ↗
INTRODUCTION: Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy due to its typically late diagnosis and high recurrence rates. Conventional carboplatin-based therapies are limited by system...
INTRODUCTION: Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy due to its typically late diagnosis and high recurrence rates. Conventional carboplatin-based therapies are limited by systemic toxicity and chemoresistance. To overcome these barriers, we developed a theranostic system based on Pluronic F-127 nanomicelles encapsulating carboplatin and radiolabeled with technetium-99m (99ᵐTc), aiming for targeted delivery, sustained drug release, and concurrent imaging capability. MATERIALS AND METHODS: Carboplatin-loaded Pluronic nanomicelles were prepared by direct dissolution and characterized via dynamic light scattering (DLS), scanning and cryo-electron microscopy (SEM, Cryo-SEM), and energy-dispersive X-ray spectroscopy (EDS). Drug release was assessed by UV-Vis spectrophotometry. In vitro cytotoxicity was evaluated on SK-OV-3 cells using MTT assays. Nanomicelles were radiolabeled with 99ᵐTc, and radiochemical purity/stability were confirmed by TLC. in vivo pharmacokinetics, biodistribution, and biochemical safety profiles were studied in Wistar and Balb/c mice using gamma counting and serum assays. RESULTS: Nanomicelles exhibited a mean diameter of 274.4 nm with low PDI (0.051), spherical morphology, and high encapsulation efficiency. EDS confirmed homogeneous platinum distribution. The release profile showed a biphasic kinetic with ≈96% cumulative release in 25 h. Cytotoxicity assays revealed time- and dose-dependent effects, with the nanoformulation showing superior or comparable efficacy to free carboplatin. Radiolabeling efficiency exceeded 90% and remained stable for 24 h. Pharmacokinetic modeling indicated a prolonged half-life (12.73 h), extensive volume of distribution, and slow systemic clearance. Biodistribution favored renal elimination with minimal off-target accumulation. Biochemical analyses indicated no significant hepatotoxicity or nephrotoxicity, though elevated lipase suggested potential pancreatic involvement. DISCUSSION: The PLU-carboplatin nanomicelles demonstrated physicochemical robustness, sustained-release kinetics, and effective in vitro cytotoxicity. Radiolabeling with 99ᵐTc enabled simultaneous biodistribution tracking, affirming their theranostic potential. Pharmacokinetic and safety profiles support the feasibility of this nanoformulation as a targeted therapeutic and diagnostic platform for EOC, warranting further translational development. CONCLUSION: Technetium-99m radiolabeled Pluronic F-127 nanomicelles encapsulating carboplatin exhibit desirable theranostic characteristics, including structural integrity, controlled drug release, dual cytotoxic and imaging capacity, and minimal systemic toxicity. These findings position the system as a promising candidate for targeted therapy and real-time monitoring in epithelial ovarian cancer and justify its advancement to more complex preclinical models.
Identification of Neutrophil Extracellular Traps-Related Biomarkers in Multiple Myeloma Using Machine Learning and Experimental Validation.
Wu H, Zhu Y, Wang B … +1 more , Yang W
Curr Med Chem · 2026 Jun · PMID 42316496 · Publisher ↗
BACKGROUND: Multiple Myeloma (MM) is a complex hematological malignancy characterized by the uncontrolled proliferation of malignant plasma cells. Neutrophil Extracellular Traps (NETs) have recently been implicated in ca...
BACKGROUND: Multiple Myeloma (MM) is a complex hematological malignancy characterized by the uncontrolled proliferation of malignant plasma cells. Neutrophil Extracellular Traps (NETs) have recently been implicated in cancer, but the role in MM remains unclear. This study aimed to identify NETs-related biomarkers in MM and explore the underlying mechanisms using machine learning and experimental validation. Methods and Methods: Three MM-related microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression and weighted gene co-- expression network analyses were applied to identify NETs-related hub genes for MM. Machine learning algorithms were used to refine the biomarkers. The core genes were validated using receiver operating characteristic analysis, nomogram construction, and an external dataset. Functional analyses were performed to explore the underlying mechanisms. Drug-gene interaction analysis was performed to predict potential therapeutic drugs. Finally, gene expression was validated by quantitative real-time PCR in peripheral blood mononuclear cells from three MM patients and three healthy controls. RESULTS: A total of 24 NETs-related hub genes were identified. Machine learning algorithms identified three NETs-related core biomarkers for MM: KIT proto-oncogene (KIT), Hepatocyte Growth Factor (HGF), and F2R-like trypsin receptor 1 (F2RL1). The predictive model showed good predictive performance in both the training and external cohorts. Functional analyses showed significant associations between the biomarker genes and immune-related biological processes. Additionally, potential therapeutic drugs targeting these biomarkers were identified, including diphenylpyraline, Crizotinib, 1,4-chrysenequinone, and histamine. The expression patterns of the biomarker genes were confirmed in clinical MM samples. DISCUSSION: This study combined multiple machine learning models to identify key NETs-related biomarkers for MM. Clinical validation confirmed the relevance of the biomarkers in clinical practice. These findings provide a foundation for further research into the immune microenvironment and therapeutic strategies for MM. CONCLUSION: This study successfully identified and validated NETs-related biomarkers for MM through machine learning and experimental validation. Understanding the role of NETs-related biomarkers in MM could not only deepen our understanding of the disease but also offer information for clinical applications.
Protective Role and Mechanism of Action of Garlic in Organ Ischemia-reperfusion Injury: Where do we Stand?
Besharatloo M, Rezaei P, Barjasteh AH … +5 more , Esfahani MS, Imanizadeh M, Karimian A, Shokri K, Pourhanifeh MH
Curr Med Chem · 2026 Jun · PMID 42316495 · Publisher ↗
INTRODUCTION: Ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality in surgeries and conditions like stroke and organ transplantation. Despite restoring blood flow, IRI-induced damage remains a cr...
INTRODUCTION: Ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality in surgeries and conditions like stroke and organ transplantation. Despite restoring blood flow, IRI-induced damage remains a critical unmet therapeutic challenge. This review aims to summarize the protective effects of garlic against organ IRI, focusing on its underlying cellular and molecular mechanisms. METHODS: We conducted a comprehensive narrative review of the current literature to gather and synthesize data from preclinical and clinical studies investigating the effects of garlic and its bioactive compounds (e.g., allicin) on various models of organ IRI. RESULTS: The compiled evidence demonstrates that garlic and its constituents exert significant protective effects against IRI in multiple organs, including the heart, brain, liver, and kidney. Key mechanisms include potent reductions in oxidative stress markers (e.g., MDA), inflammation (e.g., TNF-α, IL-6), and apoptosis, alongside enhancements in antioxidant defenses (e.g., SOD, GSH). DISCUSSION: The findings position garlic as a promising multi-target therapeutic agent against IRI, primarily by modulating pivotal pathways involved in inflammation and oxidative damage. Its efficacy across diverse organ systems underscores its translational potential. Limitations of the current evidence include variability in study designs, garlic formulations, and doses used. CONCLUSION: Garlic demonstrates substantial potential for mitigating IRI-related complications. Further standardized clinical research is warranted to validate these protective effects and establish optimal treatment protocols for human application.
Trends in Ubiquitination Research in Brain Diseases from 1999 to 2024: A Bibliometric Analysis.
Wu B, Duan R, Tu R … +4 more , Luo M, Ge L, Chen C, Lu M
Curr Med Chem · 2026 Jun · PMID 42316494 · Publisher ↗
BACKGROUND: Ubiquitination is a fundamental biological process that plays several critical roles in cellular regulation. In recent years, extensive research worldwide has investigated the involvement of ubiquitination in...
BACKGROUND: Ubiquitination is a fundamental biological process that plays several critical roles in cellular regulation. In recent years, extensive research worldwide has investigated the involvement of ubiquitination in the pathogenesis of various brain diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and glioblastoma (GBM). However, to date, no comprehensive bibliometric analysis has systematically examined the research landscape concerning the role of ubiquitination in brain diseases. METHODS: A detailed exploration of the Web of Science Core Collection (WoSCC) database was carried out, encompassing studies from 1999 to 2024, to evaluate the interplay between ubiquitination mechanisms and various brain disorders. The database was retrieved on January 20, 2025. Bibliometric and visualization analyses were performed using various tools such as Microsoft Excel, VOSviewer, CiteSpace, the R package 'bibliometrix', and an online bibliometric platform. RESULTS: A marked growth in scholarly articles investigating ubiquitination's role in brain diseases has been observed over the 25-year period from 1999 through 2024. A total of 1,658 articles were published in 539 journals. The United States leads in national research output, with the Chinese Academy of Sciences ranking first among all institutions in terms of publication output. Among authors, Ted M. Dawson has contributed the most articles, and the Journal of Biological Chemistry has the highest number of publications. Research on ubiquitination in brain diseases primarily focuses on AD, PD, ischemic stroke, and GBM. DISCUSSION: The rapid expansion of this field highlights ubiquitination as a key regulatory mechanism in brain diseases. Future studies should focus on mechanistic depth and translational potential, particularly targeting ubiquitin related pathways for therapeutic intervention. CONCLUSION: Increasing attention is being paid to the research field exploring the relationship between brain diseases and ubiquitination. The insights from our findings may serve as a valuable reference for scholars interested in investigating ubiquitination in brain disorders in the future.
The Potential Role of Taurine in Cancer Therapy: Mechanisms of Action and Future Directions.
Bjørklund G, Izmailovich M, Nurpeissov T … +2 more , Glushkova N, Semenova Y
Curr Med Chem · 2026 Jun · PMID 42312502 · Publisher ↗
Taurine, a sulfur-containing amino acid, has been shown to exhibit various biological activities, including antioxidant, anti-inflammatory, and anti-cancer properties. This review provides a comprehensive summary of curr...
Taurine, a sulfur-containing amino acid, has been shown to exhibit various biological activities, including antioxidant, anti-inflammatory, and anti-cancer properties. This review provides a comprehensive summary of current preclinical and clinical evidence regarding taurine's role in cancer prevention and treatment. in vitro studies have demonstrated that taurine induces apoptosis, suppresses cell proliferation, and inhibits angiogenesis and metastasis. Animal studies support these findings, indicating that taurine supplementation has anti-cancer effects in vivo. Epidemiological studies have reported mixed results on the association between taurine intake and cancer risk, while clinical studies on taurine supplementation have reported promising outcomes in cancer patients. Limitations of current studies include small sample sizes, lack of standardization in study design, and inconsistent dosages of taurine supplementation. Future research directions involve elucidating the underlying mechanisms of action and conducting rigorously designed clinical trials with larger cohorts. In conclusion, the available evidence suggests that taurine may have potential as a complementary or alternative therapy for cancer; however, further research is needed to establish its safety and efficacy.
Multi-Omics Analysis of the Dual Role of PIP5K1B in Gastric Adenocarcinoma: Regulation of Myofibroblasts, Remodeling of the Immune Microenvironment, and Novel Strategies for Precision Treatment.
Liang T, Cui Y
Curr Med Chem · 2026 Jun · PMID 42311015 · Publisher ↗
OBJECTIVE: Phosphatidylinositol-4-phosphate 5-kinase type 1 beta (PIP5K1B), an enzyme linked to actin cytoskeleton dynamics, has a paradoxical role in cancer. While pan-cancer analyses show its dual nature, its impact on...
OBJECTIVE: Phosphatidylinositol-4-phosphate 5-kinase type 1 beta (PIP5K1B), an enzyme linked to actin cytoskeleton dynamics, has a paradoxical role in cancer. While pan-cancer analyses show its dual nature, its impact on overall survival (OS) in stomach adenocarcinoma (STAD) is unclear. METHODS: We combined bulk RNA sequencing data (TCGA/GTEx, 33 cancers) and single- cell transcriptomics data (STAD cohort) to track PIP5K1B expression in STAD. Cox regression and Kaplan-Meier models assessed their prognostic effect on OS, with immune infiltration and methylation-epigenetic correlation analyses. GDSC pharmacogenomic data evaluated drug sensitivity links. RESULTS: Pan-cancer analysis found PIP5K1B had a unique prognostic impact in STAD, with high expression raising death risk (OS: hazard ratios (HR) = 1.55, 95% confidence interval [CI] = 1.31 - 1.84, P = 3.5e-07). Single-cell mapping showed PIP5K1B in tumor-associated myofibroblasts, regulating tumor cell antigen processing via toll-like receptor signaling. Clinically, STAD patients had higher PIP5K1B expression (P = 0.0013), and death risk rose with cancer stage (HR = 2.375, 95% CI = 1.499 - 3.762, P = 0.00058). Despite immune evasion in high-PIP5K1B tumors, they were sensitive to bleomycin (P < 0.001, R2 = 0.06) and docetaxel (P < 0.001, R2 = 0.21). DISCUSSION: The study's findings underscore the potential of PIP5K1B as a prognostic biomarker and therapeutic target in gastric cancer, opening up new possibilities for personalized treatment approaches. CONCLUSION: Integrating pan-cancer multi-omics data, we found PIP5K1B serves as a significant prognostic biomarker in STAD, with its high expression linked to poor survival outcomes. Its expression in tumor - associated myofibroblasts and involvement in antigen processing suggest a complex role in the tumor immune landscape. Furthermore, the sensitivity of high - PIP5K1B tumors to specific chemotherapies offers new avenues for targeted treatment strategies in STAD.
Active Components and Potential Molecular Mechanisms of Panax Notoginseng in Alleviating Intestinal Ischemia/Reperfusion-induced Acute Lung Injury: A Study Integrating UHPLC-MS/MS, Network Pharmacology, and Molecular Docking.
Zhao Y, Ren K, Ding C … +2 more , Zhang G, Yang M
Curr Med Chem · 2026 Jun · PMID 42311014 · Publisher ↗
INTRODUCTION: Intestinal ischemia/reperfusion (I/R)-induced acute lung injury (ALI) is a key contributing factor to mortality and disability following surgery for acute abdominal emergencies. Panax notoginseng (PN) exert...
INTRODUCTION: Intestinal ischemia/reperfusion (I/R)-induced acute lung injury (ALI) is a key contributing factor to mortality and disability following surgery for acute abdominal emergencies. Panax notoginseng (PN) exerts a significant alleviating effect on intestinal I/R-induced ALI. The objective of this study is to use Ultra-high performance liquid chromatography-Mass spectrometry (UHPLC-MS/MS), network pharmacology, and molecular docking methods to investigate the main active components of PN in alleviating intestinal I/R-induced ALI and their molecular mechanisms. METHODS: The chemical compositions of PN were identified using UHPLC-MS/MS, and potential targets for these compounds were predicted using the Swiss Target Prediction database. Subsequently, Cytoscape 3.7.2 was utilized to design a network that demonstrates the interactions of drugs, components, and targets. Targets associated with intestinal I/R-induced ALI were detected using the GeneCards and OMIM databases. Cross-- targets between the drug and the disease were analyzed, and a PPI network was established via the STRING database. The targets that overlap were subjected to GO and KEGG enrichment analyses. The interactions between core bioactive substances and key proteins were validated through molecular docking. RESULTS: UHPLC-MS/MS analysis identified 71 major chemical constituents in PN. Protein- protein interactions (PPI) network analysis revealed that TNF, IL-6, AKT1, and IL-1β were the most highly interconnected hub targets. The GO analysis revealed a notable enrichment in biological processes such as response to xenobiotic stimulus, positive regulation of gene expression, and inflammatory response. According to the KEGG pathway analysis, significant signaling pathways include PI3K-Akt, TNF, and HIF-1. The stable binding conformations of L-Tryptophan, Quercetin, Adenosine, Linolenic acid ethyl ester, and Bryodulcosigenin with core targets TNF, IL-6, AKT1, IL-1β, and GAPDH were confirmed through molecular docking. DISCUSSION: This computational study provides a systematic framework for deciphering the complex mechanisms of traditional medicines. Our analysis proposes that PN alleviates intestinal I/R-induced ALI through a "multi-component, multi-target, multi-pathway" mechanism. The findings serve as a robust hypothesis-generating resource, offering precise candidates and pathways for future experimental validation. CONCLUSION: This research predicts the effective components of PN and their potential molecular mechanisms in treating intestinal I/R-induced ALI, laying a theoretical groundwork for future experimental confirmation and clinical application.
Unravelling the Critical Interplay of Oral and Gut Microbiota in Disease Development.
Pouliou C, Poulios P, Piperi C
Curr Med Chem · 2026 Jun · PMID 42311013 · Publisher ↗
The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, th...
The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, the gut microbiota, consisting of trillions of microorganisms, functions as a barrier protection, modulating the immune system and facilitating the absorption of nutrients. Although they have distinct anatomical locations, these ecosystems are highly interconnected and play a pivotal role in human health and disease. The most common routes of interaction between the oral and gut microbiota are the enteral, the hematogenous, and the immune cell migration routes. Many oral pathogens interact with intestinal microbes, activating the host's mechanisms that establish dysbiosis and pave the way for the development of various diseases, ranging from inflammatory bowel disease and colorectal cancer to metabolic and neurodegenerative disorders. In this review, we delineate the mechanisms underlying these ecosystems to offer novel insights into disease pathogenesis while also unveiling new avenues for preventive and therapeutic interventions. Although current therapeutic approaches include the administration of antibiotics, prebiotics, and probiotics, novel personalized therapeutic approaches have also emerged. Fecal microbiota transplantation (FMT), gut bacteria engineering, nanomedicine-based techniques, and the use of miRNA to foster microbiota balance in both compartments hold great promise and may prove critical for the prevention and management of systemic diseases.
Cellular Heterogeneity in Erectile Dysfunction: An In-silico Analysis Revealing PER1, BHLHE40, NFIL3, and KLF10 as Circadian Rhythm Genes.
Mao J, Cheng P, Tian Q … +7 more , Qiu T, Wu X, Xing F, Tao Y, Cheng L, Tao L, Huang H
Curr Med Chem · 2026 Jun · PMID 42304925 · Publisher ↗
INTRODUCTION: Despite advances in understanding the vascular basis of erectile dysfunction (ED), the cellular heterogeneity and gene regulatory dynamics underlying organic ED remain unclear. In this study, we characteriz...
INTRODUCTION: Despite advances in understanding the vascular basis of erectile dysfunction (ED), the cellular heterogeneity and gene regulatory dynamics underlying organic ED remain unclear. In this study, we characterize the cell type-specific expression and roles of circadian rhythm genes (CRGs) in the human corpus cavernosum affected by organic ED. METHODS: We performed an integrative single-cell analysis of human corpus cavernosum tissues (GSE206528) from healthy controls and patients with organic ED. Cell identities were annotated using Seurat, followed by pseudotemporal trajectory inference with Monocle 2, intercellular communication profiling via CellChat, and quantification of circadian rhythm gene activity using AUCell. Candidate therapeutics targeting dysregulated circadian genes were prioritized through Enrichr-based drug enrichment analysis and evaluated by AutoDock 4-mediated molecular docking. RESULTS: Single-cell RNA-seq analysis of the corpus cavernosum in organic ED revealed reduced fibroblasts and expanded pericytes. The identified core circadian genes (PER1, BHLHE40, NFIL3, KLF10) displayed stage-specific pseudotime dynamics: monotonic decline in endothelial cells versus early-peak decay in fibroblasts, and correlated with pathological crosstalk, including TGF-β/ECM-mediated fibroblast-vascular interactions and enhanced endothelial-immune adhesion. NFIL3 harbored a conserved druggable pocket, and in silico docking confirmed stable binding of repurposable clinical compounds, highlighting circadian targets for therapy. DISCUSSION: This study utilized single-cell RNA sequencing to elucidate the cellular and molecular landscape of the corpus cavernosum in patients with organic ED. The findings revealed significant alterations in cellular composition, circadian gene regulation, and intercellular communication networks. CONCLUSION: Our research characterized circadian rhythm dysregulation as an active, cell type-specific contributor to organic ED and identified NFIL3 as a promising druggable target for chronotherapeutic intervention.
Versatile 1,2,3-Triazole Hybrids in Breast Cancer Treatment: From Molecular Mechanisms to Therapeutic Promise.
Zehra N, Maheshwari R, Shah P … +4 more , Patel N, Patel M, Patel A, Shah U
Curr Med Chem · 2026 Jun · PMID 42304924 · Publisher ↗
The 1,2,3-triazole ring system has emerged as a versatile scaffold in medicinal chemistry, owing to its remarkable physicochemical stability, hydrogen-bonding potential, and ability to act as a bioisostere. In recent yea...
The 1,2,3-triazole ring system has emerged as a versatile scaffold in medicinal chemistry, owing to its remarkable physicochemical stability, hydrogen-bonding potential, and ability to act as a bioisostere. In recent years, its incorporation into anticancer drug design has shown significant promise, particularly in the development of targeted therapies against breast cancer. This review provides a comprehensive overview of the diverse anticancer mechanisms exhibited by 1,2,3-triazole-based compounds, including apoptosis induction, cell cycle arrest, inhibition of kinases and signaling pathways, antiangiogenic and antimetastatic effects, as well as DNA intercalation and topoisomerase inhibition. Special emphasis is placed on their therapeutic relevance in breast cancer, highlighting the structural hybridization of triazoles with pharmacologically active moieties such as coumarins, chalcones, azoles, and other heterocycles. The review further consolidates structure-activity relationship (SAR) trends, identifying key substitutions and linker designs that enhance cytotoxicity and selectivity. By integrating mechanistic insights and SAR data, this article aims to provide a valuable framework for the rational design of next-generation 1,2,3-triazole-based therapeutics in breast cancer treatment. This comprehensive overview aims to support ongoing drug discovery efforts by consolidating key insights into the design and therapeutic potential of 1,2,3-triazole-based hybrids in breast cancer treatment.
Exploring the Toxicological Impact and Mechanisms of DEHP Exposure on Prostate Cancer Through Network Toxicology and Machine Learning Algorithms.
Chen J, Chen J, Huang J … +2 more , Chen S, Feng G
Curr Med Chem · 2026 Jun · PMID 42304923 · Publisher ↗
INTRODUCTION: Prostate Cancer (PCa) is the most common male malignancy, and its initiation and progression may be influenced by environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP). METHODS: Potential targe...
INTRODUCTION: Prostate Cancer (PCa) is the most common male malignancy, and its initiation and progression may be influenced by environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP). METHODS: Potential targets of DEHP were retrieved from ChEMBL, SwissTargetPrediction, and PharmMapper databases. DEHP-related genes correlated with PCa were identified by intersecting the DEHP target gene set with PCa-associated genes. Machine learning approaches were employed to identify and characterize the core genes linked to PCa. SHapley Additive exPlanations (SHAP) analysis was used to evaluate model interpretability. Molecular docking was performed to assess the binding interactions between DEHP and the key target proteins. Cellular validation was performed using CCK-8 assay, quantitative reverse transcription PCR (RT-qPCR), and western blot analysis. RESULTS: A total of 53 genes were identified as potential actionable targets of DEHP in PCa pathobiology. Through machine learning, these genes were reduced to 12 genes (ACACB, CD200, FERMT2, GCNT1, GNAI2, GSTM2, IMPDH2, ITGA2, MMP26, PMM2, PRKCA, and SRD5A2), which exhibited distinct dysregulation patterns in PCa tissues. Furthermore, molecular simulation docking simulations demonstrated its robust binding interactions with key targets, including PMM2, ITGA2, GSTM2, IMPDH2, and PRKCA, warranting further experimental validation. DISCUSSION: DEHP, an industrial chemical, may contribute to PCa via multiple pathways. A 12-gene model for DEHP-associated PCa was identified, among which PMM2 may play a key role in mediating oncogenic effects via metabolic, redox, and signaling reprogramming. CONCLUSIONS: The findings indicated that DEHP can influence the development of PCarelated pathways through targeting specific genes and signaling, exhibiting the potential to serve as a biomarker to assess the risk of PCa related to DEHP exposure.
Metabolic Reprogramming and Molecular Mechanisms in Renal Cell Carcinoma: Therapeutic Implications and Future Perspectives.
Faghihkhorasani F, Zhu G
Curr Med Chem · 2026 Jun · PMID 42300304 · Publisher ↗
Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy with distinct metabolic dependencies that differentiate it from many other solid tumors. Despite recent advances in targeted therapies and immunothera...
Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy with distinct metabolic dependencies that differentiate it from many other solid tumors. Despite recent advances in targeted therapies and immunotherapies, therapeutic resistance and variable clinical responses remain major challenges, underscoring the need for a deeper understanding of RCC-specific metabolic vulnerabilities. Current evidence indicates that metabolic reprogramming is a central driver of RCC progression, involving enhanced glycolysis, glutaminolysis, one-carbon metabolism, altered lipid metabolism, and mitochondrial adaptations. These metabolic shifts are largely regulated by dysregulated oncogenic signaling, constitutive activation of hypoxia-inducible factors (HIFs), and dynamic interactions within the tumor microenvironment. Key metabolic regulators and enzymes, including HIF-2α, glutaminase (GLS), fatty acid synthase (FASN), and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), have emerged as clinically relevant targets with therapeutic potential. In this review, we synthesized current knowledge on RCC metabolism while highlighting features that distinguish RCC from other malignancies, particularly its HIF-driven metabolic landscape and pronounced microenvironmental influences. Importantly, we extended descriptive metabolism by focusing on clinically actionable pathways, biomarker-driven patient stratification, and rational combination strategies integrating metabolic inhibitors with immunotherapy or targeted agents. We also discussed some emerging methodologies, including metabolic imaging and spatial profiling approaches, to address intratumoral metabolic heterogeneity. Overall, this review emphasizes how leveraging RCC-specific metabolic vulnerabilities can inform precision medicine approaches and improve therapeutic outcomes for patients with RCC.
Etoxazole Induces Dose-Dependent Oxidative Stress in Rat Heart, Lung, and Spleen Tissues.
Konuk EY, Bati B, Tekce S … +2 more , Demir H, Demir C
Curr Med Chem · 2026 Jun · PMID 42300303 · Publisher ↗
BACKGROUND: Etoxazole (ETX) is a widely used acaricide, yet its systemic toxicity and effects on oxidative balance in non-hepatic tissues remain poorly understood. This study investigated the dose-dependent impact of ETX...
BACKGROUND: Etoxazole (ETX) is a widely used acaricide, yet its systemic toxicity and effects on oxidative balance in non-hepatic tissues remain poorly understood. This study investigated the dose-dependent impact of ETX on oxidative stress markers in rat heart, lung, and spleen tissues. METHODS: Forty-two female Wistar albino rats were divided into six groups: one control and five treatment groups receiving 25-750 mg/kg ETX via oral gavage for 28 days. Total sulfhydryl (t-SH), adenosine deaminase (ADA), ischemia-modified albumin (IMA), and asymmetric dimethylarginine (ADMA) levels were measured spectrophotometrically. RESULTS: ETX exposure was associated with significant, dose-dependent alterations in oxidative stress biomarkers across all examined tissues. t-SH levels decreased, whereas ADA, IMA, and ADMA levels increased with increasing ETX doses. Cardiac IMA rose 2.7-fold increase at higher doses, indicating enhanced oxidative stress-related biochemical alterations. Elevated ADMA levels suggested alterations in nitric oxide-related pathways. DISCUSSION: These findings indicate that subchronic ETX exposure disrupts redox homeostasis in extrahepatic tissues in a dose-dependent manner. CONCLUSION: ETX induces systemic oxidative imbalance in rat tissues, highlighting the need for further mechanistic investigations. This study was conducted in female rats and focused on biochemical biomarkers without histopathological evaluation or inclusion of a positive control, which should be considered when interpreting the findings.
Synthesis and Biological Evaluation of Novel Flavone-Sulfonamide Hybrid Derivatives as Potential Anticancer Agents.
Semenyuta I, Frasinyuk M, Bondarenko S … +1 more , Brovarets V
Curr Med Chem · 2026 Jun · PMID 42300302 · Publisher ↗
INTRODUCTION: Flavone derivatives are naturally occurring compounds with diverse biological activities, including anticancer effects. However, the anticancer potential of sulfonamide-substituted flavones remains largely...
INTRODUCTION: Flavone derivatives are naturally occurring compounds with diverse biological activities, including anticancer effects. However, the anticancer potential of sulfonamide-substituted flavones remains largely unexplored. MATERIALS AND METHODS: Compounds 7a-7l were synthesized via Claisen-Schmidt condensation of N-(3-acetyl-4-hydroxyphenyl)acetamide with various aromatic aldehydes. Structural characterization was performed using 1H, 13C, and 19F NMR spectroscopy, LC-MS, and elemental analysis. Molecular docking was conducted using AutoDock Vina, with input files prepared via AutoDockTools (ADT). The pharmacokinetic properties of compound 7f were predicted in silico using the PreADMET web tool. RESULTS: Among the synthesized compounds, 7f exhibited the highest anticancer activity against the NCI-60 panel, with GI50 values ranging from 0.58 to 14.6 μM and total growth inhibition (TGI) values from 9.17 μM to >100 μM. The strongest activity was observed against leukemia (K-562, GI50 = 0.58 μM), melanoma (MDA-MB-435, GI50 = 1.03 μM), renal (TK-10, GI50 = 1.08 μM; A498, GI50 = 1.88 μM), lung (HOP-92, GI50 = 1.34 μM), and CNS (SNB-75, GI50 = 1.63 μM) cancer cell lines. Low cytotoxicity was observed for most subpanels (LC50 > 100 μM). Molecular docking analysis suggested poly( ADP-ribose) polymerases (PARP1, TNKS1, and TNKS2) as potential molecular targets, with TNKS1 exhibiting the most favorable binding affinity (ΔG = -11.1 kcal/mol). in silico ADME predictions indicated a favorable pharmacokinetic profile. DISCUSSION: A series of sulfonamide-flavone hybrids was designed, synthesized, and evaluated using a combination of in vitro and in silico approaches. The results support the flavone-sulfonamide scaffold as a viable platform for further anticancer drug development. CONCLUSION: In summary, twelve novel flavone-sulfonamide hybrids were successfully synthesized and characterized. Biological evaluation identified compound 7f as the most active derivative against the NCI-60 panel, exhibiting broad-spectrum anticancer activity with low cytotoxicity. Molecular docking and ADME analyses further supported its potential, identifying compound 7f as a promising lead compound for further optimization. Incorporation of a sulfonamide group at the 6-position of the flavone scaffold resulted in an eightfold increase in anticancer activity (GI), from 7% for the flavone to 55% for lead compound 7f.
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