Curr. Med. Chem. [JOURNAL]
Sun
200 papers
Antimicrobial Coating for Healthcare Settings Based on an Acrylic Binder Modified with Nanosized Hexa[(pyridin-4-yl)amino]cyclotriphosphazene.
Maksimova E, Tamboura B, Butorova I … +1 more , Chistyakov E
Curr Med Chem · 2026 Jun · PMID 42300301 · Publisher ↗
INTRODUCTION/OBJECTIVE: Healthcare-associated infections (HAIs) represent a major challenge in medical facilities, necessitating the development of self-disinfecting surfaces. This study investigates the performance of a...
INTRODUCTION/OBJECTIVE: Healthcare-associated infections (HAIs) represent a major challenge in medical facilities, necessitating the development of self-disinfecting surfaces. This study investigates the performance of a newly synthesized compound, hexa[( pyridin-4-yl)amino]cyclotriphosphazene (HPP), as a promising modifier for acrylic coatings aimed at reducing microbial surface contamination. METHODS: HPP was synthesized by grafting six pyridinamine groups onto a hexachlorocyclotriphosphazene core. Its structure was confirmed by NMR spectroscopy and MALDI-TOF mass spectrometry. The potential of HPP as an antimicrobial modifier was evaluated using computational modeling (the SwissADME platform for QSPR/QSAR predictions). Coating compositions were prepared by incorporating HPP (0-5 wt%) into a fast-drying, water-based acrylic paint (Elcon brand). Physicochemical properties (adhesion, water absorption, chemical resistance, abrasion resistance, and UV-aging resistance) and antimicrobial activity against Escherichia coli and Candida albicans were assessed according to ISO standards. RESULTS: HPP is a nanoscale molecule (diameter ~1.25 nm) with a high molecular weight (693.58 g/mol), low water solubility (Log S = -7.31), and moderate lipophilicity (Consensus Log P = 2.94). Compared to unmodified samples, coatings containing HPP demonstrated improved adhesion (score 0 on concrete starting from 1 wt% and on wood starting from 3 wt%), reduced water absorption, increased abrasion resistance, and good chemical resistance to NaOH and H2O2. Antimicrobial activity reached 18.9% inhibition for E. coli and 41.9% for C. albicans at 5 wt% HPP. DISCUSSION: The predicted low systemic absorption and low skin permeability (Log Kp = -6.69 cm/s) confirm the safety profile of HPP for use in coating formulations. The absence of PAINS alerts indicates stability, while the nanoscale size favors immobilization within the polymer matrix, explaining the improved physicochemical properties and sustained antimicrobial activity. CONCLUSION: HPP is an effective multifunctional additive for acrylic paints intended for healthcare settings. The resulting modified paint is suitable for application in facilities where a reduction in microbial surface contamination is required.
Novel Monoazo Dispersion Dyes Incorporating a 4-thiazolidinone Moiety: Synthesis, Structural Characterization, Molecular Docking, and Anticancer Investigations.
El-Samoly MM, Lotfy DR, Al Kamaly O … +5 more , Shahat AA, El-Fakharany EM, Taher FA, Dawoud NTA, El-Maradny YA
Curr Med Chem · 2026 Jun · PMID 42300300 · Publisher ↗
INTRODUCTION: In our method for synthesizing potent anticancer derivatives against both liver and breast tumors, a series of novel azo dispersion dyes was produced by coupling salicylaldehyde with diazonium ions derived...
INTRODUCTION: In our method for synthesizing potent anticancer derivatives against both liver and breast tumors, a series of novel azo dispersion dyes was produced by coupling salicylaldehyde with diazonium ions derived from aryl amines to evaluate their anticancer efficacy while ensuring high safety for human normal cells. METHODS: The diazenyl thiosemicarbazones (3a-f), resulting from the reaction of 5-arylazo-2-hydroxybenzaldehyde (1a-f) with thiosemicarbazide, subsequently reacted with ethyl chloroacetate to yield a series of diazenyl-4-thiazolidinones (4a-f). The chemical structures of these derivatives were well-characterized utilizing numerous analytical approaches, including FT-IR, 13C-NMR, 1H-NMR, and UV-Visible spectroscopy. Furthermore, the synthesized derivatives were assessed for their anticancer activity against HepG2 (liver cancer) and MDA-MB-231 (breast cancer) cell lines, compared to normal HSF cells. RESULTS: The synthesized compounds exhibited anticancer activity while maintaining high safety for normal cells. Compounds 3f, 4d, and 4f demonstrated significant cytotoxic efficacy against HepG2 cells, with selectivity index (SI) values of 109.47, 116.63, and 116.48, respectively. Additionally, the SI of the same compounds 3f (78.18), 4d (48.91), and 4f (71.82) displayed the highest cytotoxic property against MDA-MB-231 cells. Remarkably, neither of the tested azo compounds (3f and 4f) caused any detectable damage to normal skin cells. The findings of the molecular docking investigation were consistent with the biological assessments. DISCUSSION: The new synthesized diazenyl thiosemicarbazones have demonstrated potent anticancer activity. This is due to the presence of electron-donating groups at the para position of the diazo ring. The positive charge generated in this cationic form facilitates their adhesion to the negatively charged surfaces of the cell membrane of the treated cancer cells and enhances their permeability. However, some limitations of this study warrant further examination, such as the lack of a comprehensive pharmacokinetic analysis and long-term safety assessments. Furthermore, the pharmacokinetics and immunogenicity of the newly synthesized derivatives have not been studied. Furthermore, further research is needed to explore the effects of the synthetic derivatives in various animal models. These features should be investigated in future studies to clearly clarify the therapeutic potential and systemic performance of the synthesized derivatives. CONCLUSION: This study suggests that compounds 3f and 4f are very selective anticancer agents. in silico ADMET investigation exposed the superior pharmacokinetic properties of the newly synthesized derivatives and can serve to offer valuable insight for developing an effective cancer therapy.
Linking Polycyclic Aromatic Hydrocarbon Exposure to Cardiometabolic Dysfunction: Evidence from Population Studies and Biological Mechanisms.
Du Z, Pan Y, Zhan H … +2 more , Wang Z, Zhao M
Curr Med Chem · 2026 Jun · PMID 42283193 · Publisher ↗
INTRODUCTION: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse cardiometabolic outcomes. But the molecular mechanism is still unexplored. The purpose of our study is to investigate the...
INTRODUCTION: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse cardiometabolic outcomes. But the molecular mechanism is still unexplored. The purpose of our study is to investigate the relationship between exposure to PAHs and cardiometabolic dysfunction, and to explore the mechanism and molecular pathways. METHODS: We combined National Health and Nutrition Examination Survey (NHANES) data with multiple toxicological databases. Mendelian randomization (MR) was used to evaluate the causal contribution of immune factors to cardiovascular diseases (CVD) and metabolic disorders. Network toxicology and molecular docking were conducted to identify candidate molecular targets and signaling pathways involved in PAHs-related cardiometabolic dysfunction. RESULTS: Higher PAHs exposure was associated with increased cardiometabolic index (CMI) in adults, and this association was partially mediated by monocyte percentage and white blood cell count. MR analyses supported a causal role of these immune-related factors in CVD and metabolic disorders. Network toxicology and molecular docking involved pathways including chemical carcinogenesis-receptor activation, chemical carcinogenesis- DNA adduct formation, cytochrome P450 metabolism, and steroid hormone biosynthesis. CYP1A1, ESR1, and MAO were identified as potential key targets. DISCUSSION: Changes in monocyte percent and white blood count may help explain how PAH exposure is linked to cardiometabolic dysfunction. The implicated pathways and targets provide potential mechanisms. CONCLUSION: Our findings provide epidemiological and mechanistic evidence suggesting that PAH exposure may be linked to adverse cardiometabolic outcomes, potentially through immune-related pathways.
A Novel Acidic Polysaccharide from Inonotus obliquus (IOP-1) Suppresses Growth and Induces Apoptosis in Non-Small Cell Lung Cancer both In Vitro and In Vivo.
Zhao J, Xie W, Liu X … +6 more , Zeng Y, Jin X, Li G, Yang H, Chen C, Wan X
Curr Med Chem · 2026 Jun · PMID 42283192 · Publisher ↗
INTRODUCTION: The aim of this study was to investigate the antitumor effect of IOP-1 on non-small cell lung cancer (NSCLC) and its mechanism Materials: We isolated and purified an acidic polysaccharide component from Ino...
INTRODUCTION: The aim of this study was to investigate the antitumor effect of IOP-1 on non-small cell lung cancer (NSCLC) and its mechanism Materials: We isolated and purified an acidic polysaccharide component from Inonotus obliquus, identified its specific functional groups and monosaccharide composition, and named it IOP-1. We studied the mechanism of IOP-1 on non-small cell lung cancer through a series of in vitro experiments and measured relevant indicators in in vivo experiments. Through the results of both in vivo and in vitro experiments, we explored the mechanism of action and antitumor effects of IOP-1 in non-small cell lung cancer. RESULTS: We isolated and purified an acidic polysaccharide component from Inonotus obliquus, identified its specific functional groups and monosaccharide composition, and named it IOP-1. Studies found that IOP-1 can inhibit the proliferation and migration of NCI-H460 cells and induce their apoptosis. When IOP-1 was applied to NCI-H460 cells, the expression of Bax, Bcl-2, MMP-9, and Parp-1 decreased, while the expression of P53 and Cyto-c increased. Experiments in mice showed that IOP-1 can effectively inhibit tumor growth, increase spleen weight, and reduce blood perfusion in mice. Compared with the model group, dietary conditions improved. DISCUSSION: IOP-1 has significant antitumor activity against NCI-H460 cells, inhibiting the growth and migration of non-small cell lung cancer by regulating apoptosis and migration-related pathways. CONCLUSIONS: As a new drug, IOP-1 provides a new method for the clinical treatment of non-small cell lung cancer.
Challenges and Prospects for Clinical Application of Specialized Pro-resolving Lipid Mediators and Their Synthetic Analogues in Atherosclerosis.
Kotlyarov S
Curr Med Chem · 2026 Jun · PMID 42261168 · Publisher ↗
Atherosclerosis, a major cause of cardiovascular diseases, has a complex pathogenesis involving lipid metabolism disorders and chronic inflammation in the vascular wall. Specialized Pro-resolving Mediators (SPMs) are end...
Atherosclerosis, a major cause of cardiovascular diseases, has a complex pathogenesis involving lipid metabolism disorders and chronic inflammation in the vascular wall. Specialized Pro-resolving Mediators (SPMs) are endogenous lipid molecules that are synthesized from polyunsaturated fatty acids and can switch inflammation from the active phase to resolution. As a result, SPMs are of great clinical interest, as they have the potential to improve the course of atherosclerosis by reducing inflammation and promoting the stabilization of atherosclerotic plaques. However, the direct clinical application of SPMs is limited by a number of objective problems, including their chemical instability, the complexity of targeted delivery to atherosclerotic lesions, and a lack of clinical data on the long-term safety of chronic exposure to immune-modulating pathways. This review critically analyzes the key barriers to the translation of SPMs into clinical practice. The main focus is on strategies to overcome these limitations, in particular, the development of stable synthetic analogues of SPMs and innovative delivery systems. Issues of the therapeutic window, the selection of optimal points of application for therapy, and the prospects for integrating SPMs into existing treatment standards are discussed. Thus, despite the lack of clinical data on the use of SPMs for the treatment of atherosclerosis, the development of stable synthetic analogues and targeted delivery systems is a promising direction for the creation of a fundamentally new class of cardiovascular drugs.
Shenling Baizhu Decoction Improves Chemotherapy-Induced Sarcopenia by Regulating the NLRP3 Inflammasome and Muscle Metabolism.
Huang J, Jin H, Zhang C … +1 more , Zhang X
Curr Med Chem · 2026 Jun · PMID 42261167 · Publisher ↗
OBJECTIVE: This study investigated the effects of Shenling Baizhu decoction (SLBZD) on chemotherapy-induced sarcopenia and its potential mechanisms. METHODS: A mouse model of chemotherapy-induced sarcopenia was establish...
OBJECTIVE: This study investigated the effects of Shenling Baizhu decoction (SLBZD) on chemotherapy-induced sarcopenia and its potential mechanisms. METHODS: A mouse model of chemotherapy-induced sarcopenia was established and treated with SLBZD. The effects of SLBZD on body weight, food intake, muscle mass, muscle functional markers, muscle tissue architecture, and serum biochemical parameters in mice receiving chemotherapy were determined, and the potential mechanism was investigated. RESULTS: The study indicated that SLBZD effectively alleviated chemotherapy-induced weight loss and decreased food intake, muscle atrophy, and functional loss in mice. It increased the CSA level, decreased the serum IFN-γ, IL-1β, and TNF-α levels, increased ATP content and IGF-1 protein expression in muscle tissue, and down-regulated MSTN expression. SLBZD down-regulated the mRNA expressions of NLRP3, p65, Caspase-1, and MuRF1 and up-regulated the expression of MyoD. The mechanism is that SLBZD activated PPARγ, inhibited NF-κB phosphorylation, and suppressed NLRP3 inflammasome activation. Transcriptome analysis revealed the regulation of immune-inflammatory pathways and metabolic pathways. Additionally, SLBZD promoted myotube formation and diameter, regulated MuRF1/MyoD, and inhibited NLRP3/NF-κB signaling, effects that could be reversed by a PPARγ inhibitor. DISCUSSION: The findings suggest that SLBZD can prevent sarcopenia by activating PPARγ to inhibit NF-κB/NLRP3 and restore metabolic homeostasis, thereby making it a promising adjunctive therapeutic regimen. CONCLUSION: This study identifies SLBZD as a promising therapeutic agent for chemotherapy- induced sarcopenia, whose functions may be attributed to PPARγ-mediated regulation of inflammatory and metabolic pathways.
Salidroside's Multi-Faceted Attack on Cancer: Insights from A Systematic Review of Preclinical Studies.
Chu X, Sun Y, Wang X … +7 more , Zhu X, Zhu G, Xu M, Zhang G, He X, Ma X, Li J
Curr Med Chem · 2026 Jun · PMID 42261166 · Publisher ↗
OBJECTIVE: In recent years, salidroside (SAL) derived from Rhodiola rosea has attracted considerable research interest. SAL is regarded as a potential therapeutic agent for cancer treatment. This study aimed to investiga...
OBJECTIVE: In recent years, salidroside (SAL) derived from Rhodiola rosea has attracted considerable research interest. SAL is regarded as a potential therapeutic agent for cancer treatment. This study aimed to investigate the antitumor effects and underlying mechanisms of SAL using in vitro and in vivo models. METHODS: A systematic review was executed in compliance with the PRISMA guidelines. A systematic literature search was conducted across the Web of Science, PubMed, Embase, and Cochrane Library, covering all original literature published before April 2025. RESULTS: Of the 1415 initially gathered studies, 47 articles met the predefined inclusion criteria for full-text review. A comprehensive assessment across 19 cancer types demonstrated that SAL exhibited multifaceted antitumor effects. These effects encompassed improvement of host physiological status, inhibition of tumor progression, alteration of tumor tissue architecture, suppression of cancer cell proliferation and cell cycle progression, and attenuation of metastatic behaviors, including migration and invasion. The antitumor mechanisms of SAL involved the induction of cellular apoptosis and ferroptosis, modulation of oxidative stress and autophagy, remodeling of the tumor immune microenvironment, inhibition of glycolysis and angiogenesis, and regulation of key signaling pathways such as MAPK, JAK2/STAT3, and PI3K/Akt. DISCUSSION: This systematic review demonstrates that SAL exerts antitumor effects in both in vivo and in vitro experimental models. Nonetheless, well-designed randomized controlled clinical trials are essential to assess SAL's clinical efficacy. CONCLUSION: SAL represents a candidate for clinical translation as an antitumor agent.
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
Bjørklund G, Kriajevskaia M, Semenova Y
Curr Med Chem · 2026 May · PMID 42227537 · Publisher ↗
Abstract loading — click title to view on PubMed.
Inflammatory Cytokines and Sarcopenia: Evidence from Mendelian Randomization and Meta-analysis.
Su S, Bai J, Wang R … +2 more , Zhou F, Zhang Y
Curr Med Chem · 2026 May · PMID 42227536 · Publisher ↗
OBJECTIVE: Several observational studies have found an association between inflammation and sarcopenia. However, it is unclear whether the association with specific inflammatory cytokines is causal or due to bias. To inv...
OBJECTIVE: Several observational studies have found an association between inflammation and sarcopenia. However, it is unclear whether the association with specific inflammatory cytokines is causal or due to bias. To investigate the relationship between genetically predicted levels of inflammatory cytokines and sarcopenia, we performed bidirectional two-sample Mendelian randomization (MR) and systematic review and meta-analysis. METHODS: The genome-wide association study data of 44 inflammatory cytokines and 4 sarcopenia-associated traits were selected. A bidirectional MR analysis was performed. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and clinicaltrials.gov from inception to October 12, 2023, for eligible studies. The primary outcomes were serum insulin-like growth factor-1 (IGF-1) levels. A systematic review and meta-analysis were performed. RESULTS: We found IGF-1 was associated with the decrease in hand grip strength (left) (β=-0.032, SE=0.0084, P=1.25×10-4). No pleiotropy was detected. Conversely, we didn't find any sarcopenia-associated traits significantly affected inflammatory cytokines. A total of 20 studies with 404061 participants were included in our systematic review and meta-analysis. The pooled data indicated IGF-1 level in the sarcopenia group was lower than that in the non-sarcopenia group (SMD = -0.53, 95% CI [-0.61 to -0.45], P < 0.00001). DISCUSSION: Our study will provide evidence for diagnostic or therapeutic targets for sarcopenia. Serological diagnostic tools and molecular targeted therapeutic drugs can be developed based on IGF-1 in the future. CONCLUSION: In our study, MR and clinical data support a causal effect of inflammatory cytokines on sarcopenia, especially IGF-1. This finding requires further validation in the large-scale MR using multi-ethnic cohorts and IGF-1 isoform-specific assays.
Pharmacovigilance of SSRIs in Children and Adolescents with Depression: Disproportionality Analysis of Serotonin Adverse Events Using the FAERS Database.
Du H, Liu J, Zhou R … +2 more , Kuang C, Ma K
Curr Med Chem · 2026 May · PMID 42227535 · Publisher ↗
INTRODUCTION: Depression in minors is a growing global health concern with limited pharmacological options. This study evaluated the safety profiles of four selective serotonin reuptake inhibitors (SSRIs)-fluoxetine, ser...
INTRODUCTION: Depression in minors is a growing global health concern with limited pharmacological options. This study evaluated the safety profiles of four selective serotonin reuptake inhibitors (SSRIs)-fluoxetine, sertraline, escitalopram, and fluvoxamine- in children and adolescents, focusing on serious adverse events (SAEs). METHODS: Pediatric adverse event reports from the FAERS database (Q1 2004-Q1 2025) were analyzed. Only reports listing the study drugs as Primary Suspect were included; duplicates were removed. Events were coded using MedDRA 26.1 and analyzed at system organ class (SOC) and preferred term (PT) levels. Disproportionality analyses used reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker (MGPS), with Bayesian shrinkage (EBGM05) applied to low-frequency signals. RESULTS: Psychiatric events, including suicidal ideation, suicide attempts, and self-injury, showed the most consistent signals. Fluoxetine and sertraline had broad profiles; escitalopram showed higher disproportionality for psychiatric, cardiac, and perinatal events; fluvoxamine showed elevated signals for impulsive behaviors and rare systemic events. Neurological events, such as serotonin syndrome and tremor, were consistently reported; congenital and perinatal signals had limited statistical stability. DISCUSSION: SSRIs share common psychiatric AE signals in minors, but differences in strength and distribution likely reflect real-world exposure, metabolic pathways, and structural properties rather than causal differences. CONCLUSION: FAERS-based pharmacovigilance provides a comparative overview of SSRI safety, with multi-algorithm assessment and Bayesian shrinkage enhancing low-frequency signal reliability, informing safer SSRI use and guiding future studies integrating pharmacokinetics and pharmacogenomics.
Therapeutic Effects of Phosphodiesterase Inhibitors on Hypertensive Disorders in Pregnancy and Fetal Growth Restriction: A Drug Targeted Mendelian Randomization Study.
Xia D, Li S, Liu W … +4 more , Zhang Y, Zhang C, She G, Wang H
Curr Med Chem · 2026 May · PMID 42227534 · Publisher ↗
OBJECTIVE: Phosphodiesterases (PDEs) are considered promising drug targets due to their close association with various pathological and physiological processes. We aimed to investigate the causal relationship between PDE...
OBJECTIVE: Phosphodiesterases (PDEs) are considered promising drug targets due to their close association with various pathological and physiological processes. We aimed to investigate the causal relationship between PDE inhibitors and hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR). METHODS: We used expression quantitative trait loci (eQTLs) related to PDEs as surrogate indicators of PDE gene expression levels and conducted single-sample Mendelian randomization (SMR) analysis and two-sample MR validation through the pharmacological target. RESULTS: SMR analysis showed that PDE4B, PDE5A, PDE8A, and PDE9A were associated with pregnancy outcomes. Two-sample MR validation revealed that PDE5A in blood was negatively correlated with the occurrence of FGR (OR = 0.91, CI = 0.81-1.00, p = 0.045), while PDE4B was a risk factor for gestational hypertension (GH) (OR = 1.24, 95% CI = 1.09-1.39, p = 0.006). We performed SMR analysis again using protein quantitative trait loci (pQTLs) related to PDE5A as a surrogate for PDE5A protein levels, and the results showed no significant association between PDE5A and HDP or FGR. Further validation of the causal relationship between PDE4B and GH using a two-step MR approach revealed that PDE4B promotes the occurrence of GH through multiple metabolic factors. DISCUSSION: Our MR results prioritize PDE4B, but not PDE5A, as a causal driver of GH, offering genetically anchored justification for repositioning selective PDE4B inhibitors in pregnancy. Protective signals for PDE5A on fetal growth require tissue-level confirmation and cautious dose-finding before any clinical re-evaluation. CONCLUSION: PDE5A is not a potential therapeutic target for HDP and FGR, while PDE4B is closely related to the occurrence of GH. This suggests that PDE4B inhibitors may have therapeutic potential for GH and provides an important reference for the treatment of HDP and FGR.
Uncovering Shared Diagnostic Genes and Mechanisms in Chronic Kidney Disease and Atherosclerosis: A Bioinformatics Approach.
Li H, Guo J, Luo H … +2 more , Huang R, Su H
Curr Med Chem · 2026 May · PMID 42227533 · Publisher ↗
OBJECTIVE: The purpose of this study was to screen for common diagnostic genes and identify possible molecular mechanisms underlying CKD combined with AS using bioinformatic methods. METHODS: We retrieved the gene expres...
OBJECTIVE: The purpose of this study was to screen for common diagnostic genes and identify possible molecular mechanisms underlying CKD combined with AS using bioinformatic methods. METHODS: We retrieved the gene expression profiles of CKD and AS from the Gene Expression Omnibus (GEO). Using differential expression combined with WGCNA, we identified hub genes shared by CKD and AS. GO and KEGG enrichment analyses were conducted. To screen the diagnostic biomarker, we constructed PPI networks and applied three ML methods: least absolute shrinkage and selection operator (ASSO), random forest (RF), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). The diagnostic performance for the candidate gene was assessed by a receiver operating characteristic curve (ROC) on the training set and the external validation dataset. CIBERSORT is used to evaluate immune cell infiltration the DGIdb database predicts possible drugs for treatment. RESULTS: We found a total of 119 common genes highly correlated between CKD and AS. The enrichment results showed that these genes are mainly related to the cytoskeleton in the muscle cell, vascular smooth muscle contraction, cGMP-PKG signaling pathway and NF-kappa B signaling pathway. By the integrative PPI and ML analysis, TAGLN was selected as the hub common gene. TAGLN had good diagnostic efficiency (AUC > 0.70) across the training and validation cohorts. Immune infiltration analysis showed significant dysregulation of several immune cells for both diseases. Moreover, two candidate drugs acting on TAGLN were found. DISCUSSION: In this research, we have revealed that TAGLN was an effective diagnostic indicator in CKD-AS comorbidity. The multi-algorithms confirmed TAGLN's outstanding diagnostic ability among six independent samples. Mechanistically, cytoskeletal dysregulation seems to be the key connection of the two diseases, and there is a strong correlation between TAGLN expression and immune cell infiltration. Recombinant transforming growth factor-β1 and azacitidine could possibly function by modulating TAGLN. Our study not only reveals the molecular basis of CKD-AS comorbidity but also provides some useful targets for developing novel diagnostic or therapeutic strategies. CONCLUSION: We believe our results provide clues to the possibility of using TAGLN as an ideal common diagnostic marker for CKD and AS, and point out some common molecular mechanisms and possible treatment targets between the two diseases that will provide new clues to future research on their pathogenesis, diagnosis, and therapy.
Mitophagy in Pulmonary Fibrosis: Molecular Interactions, Hypoxia Interactions, and Therapeutic Strategies.
Zhang X, Wang L, Yan H … +2 more , Chen Y, He C
Curr Med Chem · 2026 May · PMID 42227532 · Publisher ↗
Mitophagy plays a central role in the pathogenesis of Pulmonary Fibrosis (PF). Defective mitophagy leads to the accumulation of damaged mitochondria, resulting in bursts of mitochondrial Reactive Oxygen Species (mtROS),...
Mitophagy plays a central role in the pathogenesis of Pulmonary Fibrosis (PF). Defective mitophagy leads to the accumulation of damaged mitochondria, resulting in bursts of mitochondrial Reactive Oxygen Species (mtROS), ferroptosis, and cellular senescence. These processes collectively promote aberrant fibroblast activation and excessive extracellular matrix deposition. This review systematically explored the molecular regulatory network of mitophagy in PF and its interactions with hypoxia-responsive pathways. These abnormalities create a vicious cycle of autophagy inhibition and fibrosis activation, which accelerates disease progression. Regarding therapeutic strategies, various small-molecule drugs and natural compounds have shown anti-fibrotic potential by activating mitophagy, alleviating oxidative stress, and delaying cellular senescence. Emerging technologies, such as gene therapy, nanocarriers, and combination therapies, are providing additional avenues for clinical translation. However, targeting mitophagy still faces challenges, including cell type specificity, dynamic conversion thresholds, and delivery efficiency. Future efforts will require integrating single-cell multi-omics and artificial intelligence approaches to develop spatiotemporally precise intervention systems for personalized, precision treatment of PF.
Advancing Regenerative Medicine with 3D Bioprinting: Techniques, Biomaterials, and Clinical Applications.
Yadav PK, Alsaidan OA, Altemani FH … +7 more , Alsenani F, Aodah A, Almalki WH, Almujri SS, Alrobaian M, Sahoo A, Rahman M
Curr Med Chem · 2026 May · PMID 42227531 · Publisher ↗
Three-dimensional (3D) bioprinting represents a transformative technology in regenerative medicine, enabling the precise fabrication of patient-specific, multicellular tissue constructs and organoids with complex archite...
Three-dimensional (3D) bioprinting represents a transformative technology in regenerative medicine, enabling the precise fabrication of patient-specific, multicellular tissue constructs and organoids with complex architectures. This additive manufacturing approach leverages biomaterials, living cells, and biologics to replicate functional tissues and organ systems. The bioprinting process encompasses three pivotal stages-preprinting, bioprinting, and post-printing-each governed by advanced imaging, computer-aided design modeling, bioink formulation, and bioreactor-based maturation. Key bioprinting modalities, including extrusion-based, laser-assisted, inkjet-based, and stereolithographic techniques, differ in resolution, cell viability, and scalability but collectively show promise in generating cartilage, skin, bone, esophageal, and tracheal tissues. Natural and synthetic polymers, such as collagen, alginate, gelatin, polycaprolactone, and polylactic acid (PLA), serve as important bioink components, affecting cell adhesion, proliferation, and biocompatibility. Despite considerable progress, clinical translation remains limited by issues such as limited vascularization and innervation, bioink standardization, and ethical, regulatory, and sterility concerns. Successful in vivo transplantation requires the integration of biomimicry, vascular-like networks, and optimized degradation kinetics. Emerging efforts focus on improving resolution, cell density, and regulatory guidance-highlighted by agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to ensure safety and efficacy in clinical applications. This review consolidates advances in bioprinting strategies, materials, and applications, emphasizing the importance of interdisciplinary approaches for functional tissue reconstruction. With continued innovation and standardization, 3D bioprinting has the potential to revolutionize personalized medicine, tissue engineering, transplantation, reduce organ donor dependency, and advance therapeutics through bioprinted constructs tailored for individual patients.
Exploring the Therapeutic Effects of Linarin on Ischemic Stroke: An Experimental Assessment, Network Pharmacology, and Molecular Docking.
Chen L, Xie Q, Lin W … +3 more , Ke X, Fan Z, Zhang Y
Curr Med Chem · 2026 May · PMID 42227530 · Publisher ↗
INTRODUCTION: Linarin (LIN) is a flavone glycoside that has been reported to have analgesic, anti-inflammatory, and neuroprotective activities. This study aims to investigate the protective role of LIN against IS and exp...
INTRODUCTION: Linarin (LIN) is a flavone glycoside that has been reported to have analgesic, anti-inflammatory, and neuroprotective activities. This study aims to investigate the protective role of LIN against IS and explore its underlying mechanisms. METHODS: The neuroprotective effect of LIN on CIRI was evaluated in the MCAO model mice through behavioral and pathological studies. Mechanistically, public databases were used to identify overlapping targets between LIN and IS. Then, the core genes were filtered by Cytoscape. The binding affinity between LIN and core targets was assessed by molecular docking simulations using AutoDock Vina. Additionally, GO and KEGG pathway enrichment analyses were conducted, and a "LIN-target-pathway" network was constructed. Finally, hub genes involved in LIN-mediated protection against IS were identified. RESULTS: LIN has been confirmed to have a neuroprotective effect on MACO mice. Network pharmacology analysis suggests the effects are primarily associated with the PI3K/AKT and MAPK signaling pathways and core genes such as MAPK8. Six targets were considered central to how LIN exerts its protective role against CIRI as they are frequently involved in critical signaling pathways and exhibit strong binding affinity with LIN. DISCUSSION: The therapeutic time window for mainstream IS treatment modalities remains narrow. This study, with a view to the preventive effect of Ischemic Stroke (IS), may provide novel insights into the management of IS. CONCLUSION: LIN has been shown to alleviate brain tissue damage in MCAO mice, potentially through modulation of multiple targets within the PI3K/AKT and MAPK signaling pathways, thereby exerting anti-inflammatory, anti-apoptotic, and neuroprotective effects.
Exploring the Possible Role of Gut Microbiota with Ischemic Stroke Subtypes: A Mendelian Randomization Study with Insights into Immune Cell Mediators.
Yu N, Zhao L, Zhao Z … +8 more , Xu W, Deng H, Guo Y, Zhang Y, Cheng X, Qin X, Bao H, Xu S
Curr Med Chem · 2026 May · PMID 42227529 · Publisher ↗
INTRODUCTION: Ischemic Stroke (IS) is a complex cerebrovascular disorder in which the gut microbiota has been identified as a key modulator. This study aims to explore the potential causal relationships between gut micro...
INTRODUCTION: Ischemic Stroke (IS) is a complex cerebrovascular disorder in which the gut microbiota has been identified as a key modulator. This study aims to explore the potential causal relationships between gut microbiota and three IS subtypes- Large-Artery Atherosclerosis (LAA), Small-Artery Stroke (SAS), and Cardiogenic Stroke (CES)-and to elucidate the mediating role of immune cells. METHODS: We performed a two-sample bidirectional Mendelian Randomization (MR) analysis using multi-cohort data to examine the associations of 207 gut microbial taxa and 205 metabolic pathways with IS subtypes, further incorporating immune phenotypes as mediating factors. RESULTS: Specific gut microbial taxa and metabolic pathways showed significant associations with the three IS subtypes. Thirty immune cell phenotypes were identified as mediators in the gut microbiota-IS relationship. Among these, 14 mediating pathways explained more than 10% of the observed effects; for example, Parabacteroides johnsonii influenced LAA via HLA-DR on CD33-HLA-DR+ cells, with a mediation proportion of 11.34%. DISCUSSION: These findings reveal distinct immune-mediated mechanisms linking the gut microbiota to different IS subtypes, highlighting the complex tripartite interactions among the microbiota, immunity, and cerebrovascular pathology. CONCLUSION: This study provides evidence supporting immune-mediated associations between gut microbiota and IS subtypes. The results clarify potential mechanisms through which the microbiota contribute to different IS subtypes and offer new insights for developing therapeutic targets.
Clinical Advances in Analgesic Drug Development from Ion Channel Modulators.
Kang R, Wang D
Curr Med Chem · 2026 May · PMID 42227528 · Publisher ↗
Traditional analgesics, including Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and strong opioid analgesics, remain foundational in managing diverse pain conditions, especially chronic pain. However, their clinical uti...
Traditional analgesics, including Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and strong opioid analgesics, remain foundational in managing diverse pain conditions, especially chronic pain. However, their clinical utility is frequently hampered by inadequate efficacy and significant adverse effects, such as gastrointestinal complications from NSAIDs and addiction risks from opioids, prompting an urgent need for safer and more effective alternatives. Consequently, substantial efforts have been directed toward discovering more effective pain therapeutics through the development of novel administration routes, analgesic targets, and drugs, aiming to broaden options for pain management. Ion channel modulators have emerged as particularly promising candidates, leveraging the essential functions of ion channels in pain signaling pathways. Key channels involved include voltage-gated calcium (VGCCs), sodium (VGSCs), and potassium channels (VGKCs), alongside Transient Receptor Potentials (TRPs), nicotinic acetylcholine receptors (nAChRs), P2X receptors, and Acid-Sensing Ion Channels (ASICs). These channels regulate neuronal excitability, neurotransmitter release, and nociceptive transduction, making their modulation a strategic approach for pain intervention. This review comprehensively examines the clinical development landscape of ion channel modulators for pain relief. It systematically discusses each aforementioned channel class, including VGCCs, VGSCs, VGKCs, TRPs, nAChRs, P2X, and ASICs, highlighting breakthrough drugs (e.g., ziconotide for VGCCs) and summarizing recent advances in clinical trials for emerging candidates. By elucidating both the successes and challenges in translating ion channel-targeted therapies, this review underscores their potential to overcome the limitations of conventional analgesics. This study aims to inform future research directions and accelerate the development of optimized, mechanism-based pain therapeutics.
Mechanism Study on How PTX3 Drives EMT and Fibrosis of Renal Tubular Epithelial Cells in Diabetic Kidney Disease by Activating the JNK Pathway.
Ma X, Ma C, Zhou X … +5 more , Wang J, Zhang W, Niu Q, Li X, Zhang Y
Curr Med Chem · 2026 May · PMID 42227527 · Publisher ↗
BACKGROUND: Diabetic kidney disease (DKD) is characterized by tubular EMT and fibrosis. So far, the pathogenesis of DKD is still not fully understood. Pentraxin 3 (PTX3), an inflammatory regulator, is overexpressed in DK...
BACKGROUND: Diabetic kidney disease (DKD) is characterized by tubular EMT and fibrosis. So far, the pathogenesis of DKD is still not fully understood. Pentraxin 3 (PTX3), an inflammatory regulator, is overexpressed in DKD due to hyperglycemia. PTX3 amplifies inflammation by promoting inflammatory cytokine release (TNF-α, IL-6) and activating the nuclear factor kappa-B (NF-κB) pathway. Subsequently, it triggers the c-Jun N-terminal kinase (JNK) signaling pathway, enhancing AP-1-mediated transcription of inflammatory genes (MCP-1, ICAM-1). JNK also upregulates EMT markers (α-SMA, N-cadherin) through increased transforming growth factor TGF-β1, accelerating renal fibrosis. Targeting the PTX3-JNK axis with neutralizing antibodies or inhibitors mitigates inflammation and EMT, suggesting PTX3 as a potential anti-fibrotic target in DKD. OBJECTIVE: We believe that PTX3 induces EMT in HK-2 cells to further lead to fibrosis by activating the JNK signaling pathway. Thus, investigate the role of Pentraxin 3 (PTX3) in diabetic kidney disease (DKD) and explore the therapeutic potential of targeting the PTX3-JNK signaling pathway. METHODS: Human renal tubular epithelial cells (HK-2) were stimulated with high glucose (HG); a DKD mouse model was established using streptozotocin (STZ) induction; and renal biopsy tissues were collected from DKD patients. PTX3 expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. Recombinant human PTX3 protein (Rh-PTX3) was added to HK-2 cells to examine the expression of EMT markers (E-cadherin, α-SMA, Vimentin, N-cadherin, Snail) and the key JNK pathway molecule (p- JNK). The JNK inhibitor SP600125 was used to assess changes in EMT and fibrosis. In vitro experiments were conducted using human renal tubular epithelial cells (HK-2) stimulated with high glucose (HG) in (The Key Laboratory of Nephrology) facilities. A DKD mouse model was established through streptozotocin (STZ) induction in (C57). Renal biopsy tissues were obtained from DKD patients at (The Second Hospital of Lanzhou University) between (2024-09-01) and (2025-09-01). PTX3 expression was detected by qRT-PCR. Western blotting and immunofluorescence. Recombinant human PTX3 protein (Rh-PTX3) was added to HK-2 cells to examine the expression of EMT markers (E-cadherin, α-SMA, Vimentin, N-cadherin, Snail) and the key JNK pathway molecule (p-JNK). The JNK inhibitor SP600125 was used to assess changes in EMT and fibrosis. Data collection occurred between (2024-09-01) and (2025-09-01). RESULTS: PTX3 expression was significantly increased in the HG cell model and DKD models, accompanied by EMT and JNK pathway activation. The JNK inhibitor reversed the EMT phenotype induced by PTX3 overexpression. DISCUSSION: This study reveals that PTX3 promotes renal fibrosis in DKD by activating the JNK pathway, leading to EMT of renal tubular epithelial cells. This finding, supported by clinical samples, animal models, and cell experiments, suggests PTX3-JNK signaling as a potential therapeutic target for DKD. CONCLUSION: PTX3 promotes renal tubular EMT and fibrosis by activating the JNK signaling pathway. Targeting the PTX3-JNK axis may provide a novel therapeutic strategy for DKD.
CD44, CDH6, ITGAV, and SERPINE1 are Epithelial‒Mesenchymal Transition Markers in Gastric Cancer.
Han X, Sun L, Wang W … +6 more , Li W, Jia Y, Niu Y, Liu B, Li X, Tian W
Curr Med Chem · 2026 May · PMID 42227526 · Publisher ↗
INTRODUCTION: The Epithelial‒Mesenchymal Transition (EMT) is correlated with poor prognosis in patients with Gastric Cancer (GC). Traditional EMT markers are quantified to identify the activated processes. However, these...
INTRODUCTION: The Epithelial‒Mesenchymal Transition (EMT) is correlated with poor prognosis in patients with Gastric Cancer (GC). Traditional EMT markers are quantified to identify the activated processes. However, these molecules are not universally present. Thus, identifying more representative EMT markers is important for a better understanding of the EMT process, metastasis, and the progression of GC. METHODS: Univariate Cox analysis was performed to identify the EMT-related genes associated with GC prognosis. Lasso Cox analysis was further applied to identify candidate genes and generate a signature to predict the overall survival of GC patients. Then, EMT and non-EMT groups were established in GC cell lines to compare candidate gene expression levels. Finally, the associations between the expression levels of the candidates and TNM stage were explored by using immunohistochemistry (IHC) and the UALCAN database. RESULTS: From a total of 200 EMT-related genes, 47 EMT-related genes associated with GC prognosis were identified. Subsequently, 12 EMT-related genes were selected as candidates to predict the overall survival of patients with GC. The 12-gene signature demonstrated strong predictive performance. Furthermore, in vitro analysis revealed that the expression levels of CD44, CDH6, ITGAV, and SERPINE1 were upregulated in the EMT group. In addition, the expression levels of CD44, CDH6, ITGAV, and SERPINE1 were associated with TNM stage. DISCUSSION: The 12-gene signature was validated to be an independent prognostic factor for GC, highlighting its potential predictive ability, and these genes are more likely to be EMT markers in GC. Future studies are warranted to confirm the predictive performance of the 12-gene signature in larger population samples. CD44, CDH6, ITGAV, and SERPINE1 were identified as EMT markers in an in vitro model, which is conducive to a comprehensive understanding of EMT. However, these findings should be validated in an in vivo model in subsequent studies. CONCLUSION: CD44, CDH6, ITGAV, and SERPINE1 are strongly related to GC prognosis and may be useful EMT markers in GC.
Combination of Triglyceride Glucose Index and Obesity-Related Parameters for Predicting Nonalcoholic Fatty Liver Disease in Overweight/Obese Men.
Zhou F, Tian H, Liu D … +3 more , Ye Y, He X, Tian L
Curr Med Chem · 2026 May · PMID 42227525 · Publisher ↗
INTRODUCTION/OBJECTIVE: A robust correlation has been reported between the triglyceride and glucose (TyG) index and progression of Nonalcoholic Fatty Liver Disease (NAFLD), which includes several long-term liver abnormal...
INTRODUCTION/OBJECTIVE: A robust correlation has been reported between the triglyceride and glucose (TyG) index and progression of Nonalcoholic Fatty Liver Disease (NAFLD), which includes several long-term liver abnormalities influenced by obesity. In this cross-sectional study, the capacity of three modified TyG indices was evaluated, i.e., the TyG-body mass index (BMI), TyG-waist-to-height ratio (WHR), and TyGwaist circumference (WC) to predict NAFLD in overweight/obese men from a western Chinese cohort. METHODS: The study included 714 men classified as overweight/obese and confirmed to have NAFLD through abdominal ultrasonography. The BMI threshold for overweight and obesity was set at≥ 24 kg/m2, according to the criteria of the Working Group on Obesity in China (WGOC). The indices TyG, TyG-BMI, TyG-WC, and TyG-WHR were estimated using set formulas. Subsequently, the predictive values of these indices were compared by receiver operating characteristic (ROC) curves. RESULTS: As shown by regression analysis employing the crude model, the TyG-BMI index remarkably predicted NAFLD in overweight/obese men. In the ROC curve analysis, the TyG-BMI index exhibited the highest area under the ROC curve value for detecting NAFLD (0.891, 95% CI: 0.873-0.909). DISCUSSION: Based on WGOC BMI categories, the present study focuses exclusively on Western Chinese men who were diagnosed to have NAFLD and were classified as overweight or obese (BMI ≥ 24 kg/m2). Therefore, further research is required to determine the predictive value of these indices across different populations or according to the WHO criteria for overweight/obesity. Moreover, this study relies on cross-sectional data, and its design does not allow for the elucidation of causal relationships. CONCLUSION: The findings of this study indicate that the TyG-BMI index is more effective than the other two indices in predicting the risk of NAFLD among overweight or obese males in the western Chinese population. An important issue is the potential for variations in the use of suitable TyG-related indices to determine NAFLD risk across populations of different ethnicities and races. Hence, these results should be validated in cohorts from other global regions.
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