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PubMed2026

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

Targeting EGFR in cancer using Terminalia arjuna: An integrated In Silico, molecular dynamics, experimental validation, and network pharmacology study.

The Epidermal Growth Factor Receptor (EGFR) plays a pivotal role in 20-60% of cancer cases, including glioblastoma, lung adenocarcinoma, and head and neck squamous cell carcinoma, as reported in The Cancer Genome Atlas (TCGA) dataset. The present study employed an integrated in silico and experimental workflow to evaluate EGFR-targeted compounds from Terminalia arjuna. Drug-likeness and ADMET screening were performed, followed by molecular docking and 1000 ns molecular dynamics simulations. In vitro validation was conducted using cancer cell-based assays and network pharmacology to explore the molecular mechanisms associated with the identified compound. Screening shortlisted eight compounds from T. arjuna. Molecular docking identified Arjunaside C (-8.2 kcal/mol), Arjunapthanoloside (-7.7 kcal/mol), and Beta-sitosterol (-7.4 kcal/mol) as potential EGFR inhibitors compared to Erlotinib (-6.6 kcal/mol). Arjunapthanoloside formed more H-bonds and exhibited most stable interactions with EGFR. MD simulations at 1000 ns revealed lower RMSD, RMSF, SASA, and Rg values for the Arjunapthanoloside-EGFR complex, indicating enhanced stability. Direct binding validation was limited by the unavailability of purified Arjunapthanoloside; therefore, Arjuna extract was evaluated, which demonstrated potent cytotoxicity with an IC₅₀ of 9 µg/mL in H357 oral cancer cells. Flow cytometry confirmed apoptosis-mediated cell death by increased early- and late-apoptotic cell populations. Network pharmacology analysis further identified additional targets (MMP3, MMP7, MMP9, and HRAS) that are directly involved in various cancers. Overall, the findings provide new insights into the therapeutic potential of Arjunapthanoloside as a stable compound that interacts with EGFR from T. arjuna, highlighting its significance in EGFR-targeted anticancer research.

ErbB Receptors↗

PubMed2026

Sanguinarine as a multi-target therapeutic candidate for laryngeal cancer: insights from network pharmacology, molecular dynamics and in vitro validation.

OBJECTIVE: To identify the core targets and elucidate the potential molecular mechanisms of sanguinarine (SA) against laryngeal squamous cell carcinoma (LSCC), and to validate its antitumor effects in vitro. METHODS: Potential targets of SA were predicted using SwissTargetPrediction, TargetNet, and SuperPred and intersected with LSCC-related targets obtained from the GeneCards, OMIM, and DISEASES databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed using the STRING database (combined score > 0.900), and topological parameters including degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EC), and local average connectivity (LAC) were calculated in Cytoscape to identify core genes based on median thresholds. Molecular docking and 100-ns molecular dynamics (MD) simulations were conducted for epidermal growth factor receptor (EGFR), Phosphatidylinositide-3-kinase catalytic subunit alpha (PIK3CA), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), and Non-Receptor Tyrosine Kinase (SRC). The effects of SA on LSCC were evaluated using CCK-8, colony formation, Transwell migration, and wound-healing assays in TU177 cells and TU212. RESULTS: A total of 213 common targets were identified, which were significantly enriched in PI3K-Akt signaling, EGFR tyrosine kinase inhibitor resistance, and adhesion- and migration-related pathways. The PPI network comprised 259 nodes and 259 edges, from which five core genes-PIK3CA, PIK3CB, PIK3CD, EGFR, and SRC-were identified. Molecular docking revealed strong binding affinities between SA and the PI3K family proteins (- 9.79 to - 10.96 kcal/mol), as well as EGFR (- 8.58 kcal/mol) and SRC (- 6.77 kcal/mol). MD simulations indicated greater stability of SA complexes with EGFR and PI3K family members compared with SRC. In vitro assays demonstrated that SA significantly inhibited TU177 cell and TU212 cell proliferation, colony formation, and migration. CONCLUSION: SA may exert anti-laryngeal cancer effects through synergistic multi-target inhibition centered on the EGFR/SRC/PI3K signaling axis, highlighting its potential as a promising therapeutic candidate for LSCC.

Humans↗

PubMed2026

A Computational Workflow for Prioritizing Microbial Metabolite-Associated Host Genes in Constipation-Predominant Irritable Bowel Syndrome.

No standardized computational pipeline exists for systematically prioritizing microbial metabolite-associated host genes and protein-ligand complexes from publicly available chemical, genomic, and structural databases. This article describes an eight-stage workflow that accepts a user-defined set of gut microbiota-derived metabolites and produces a ranked shortlist of candidate metabolite-associated host genes, enriched biological pathways, and structurally prioritized protein-ligand complexes for experimental follow-up. The pipeline integrates (i) chemoinformatic metabolite profiling; (ii) multi-database candidate target prediction using protein-chemical interaction and ligand-based target-prediction tool and a molecular docking program; (iii) differential gene expression analysis of publicly available transcriptomic data; (iv) target-differentially expressed gene overlap; (v) protein-protein interaction network construction and pathway enrichment; (vi) molecular docking with a molecular docking program; (vii) 200 ns molecular dynamics simulation using a molecular dynamics engine with a protein force field used for molecular dynamics simulations; and (viii) MM-PBSA binding free-energy estimation. As a worked example, nine gut microbiota-derived or microbiota-modified metabolites representing short-chain fatty acids, bile acids, tryptophan-derived metabolites, and urolithin A were processed using the public IBS-C rectal mucosal transcriptomic dataset GSE36701. The workflow ranked 17 unique predicted metabolite-associated genes that were differentially expressed in this dataset. Docking, molecular dynamics simulation, and MM-PBSA analyses structurally prioritized five metabolite-protein complexes: lithocholic acid-VDR, lithocholic acid-NR1H4/FXR, ursodeoxycholic acid-NR1H4/FXR, tryptamine-HTR2A (simulated in an explicit 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer), and urolithin A-CASP3. The protocol is designed to be adaptable to other metabolite sets, disease transcriptomic datasets, and target classes; all outputs are hypothesis-generating computational predictions that require independent transcriptomic replication, protein-level validation, and functional ligand-response assays before causal or therapeutic conclusions can be drawn.

Irritable Bowel Syndrome↗

PubMed2026

Cross-tissue Mendelian randomization prioritizes RAB27B as a brain-derived candidate protein for postpartum depression.

OBJECTIVE: Postpartum depression (PPD) is one of the most common and debilitating complications of childbirth, yet the candidate proteins linking genetic risk to disease remain poorly defined. Building on recent genome-wide association studies (GWAS), we sought to integrate cross-tissue proteogenomic data to identify candidate proteins for PPD and explore therapeutic opportunities. METHODS: We conducted two-sample Mendelian randomization (MR) using genome-wide significant cis-protein QTLs from brain (n = 608 proteins), cerebrospinal fluid (CSF; n = 214), and plasma (n = 612). PPD summary statistics were obtained from FinnGen R8 (13,657 cases, 236,178 controls) and replicated in an independent GWAS. Phenome-wide association (PheWAS) was used to assess pleiotropy. Potential therapeutic targets were evaluated through DSigDB drug repurposing, molecular docking, and molecular dynamics simulations. RESULTS: Among all proteins tested, RAB27B was the only brain-derived protein surpassing Bonferroni correction (OR = 1.60; 95% CI: 1.30-1.96; P = 6.6 × 10⁻⁶), whereas no significant proteins were identified in CSF or plasma. This association was replicated in an independent GWAS (OR = 1.27; 95% CI: 1.02-1.58; P = 0.037). PheWAS identified no pleiotropic associations at genome-wide significance. In silico drug repurposing identified pregnenolone as a candidate ligand with computationally predicted stable binding to RAB27B, providing a starting point for future experimental validation. CONCLUSION: This study provides the first cross-tissue proteogenomic evidence that RAB27B is a brain-derived, reproducible candidate protein genetically associated with PPD. By extending GWAS signals to functional protein-level mechanisms and therapeutic inference, our findings nominate RAB27B and pregnenolone as promising directions for postpartum psychiatric research.

Humans↗

PubMed2026

CCT2 defines a highly cisplatin-resistant and poor-prognosis subtype of lung adenocarcinoma.

Cisplatin-based chemotherapy is a standard treatment for lung adenocarcinoma (LUAD), yet acquired cisplatin resistance remains a marked cause of treatment failure. The molecular mechanisms driving cisplatin resistance in LUAD have not been fully elucidated. The present study integrated bulk transcriptomic data, genomic mutation profiles and single-cell RNA sequencing data to systematically investigate cisplatin resistance in LUAD. Resistance-associated genes were identified through differential expression, survival analysis and database integration. Unsupervised clustering was used to define cisplatin resistance-associated subtypes. Functional characteristics were explored using pathway enrichment, immune infiltration, tumor mutation burden and weighted gene co-expression network analysis. A machine learning framework incorporating 101 algorithms was applied to identify key genes and construct a prognostic model. Single-cell analyses and in vitro experiments were performed to validate the biological role of the core gene. Molecular docking and molecular dynamics simulations were conducted to identify potential therapeutic compounds. A total of two molecular subtypes with distinct cisplatin resistance levels and prognostic outcomes were identified. The high-resistance subtype exhibited enhanced cell cycle activity, DNA repair signaling and immune heterogeneity. Machine learning analysis revealed a five-gene signature, with chaperonin-containing TCP1 subunit 2 (CCT2) emerging as a key regulator of cisplatin resistance. Single-cell analyses showed that CCT2 was predominantly enriched in resistant epithelial cell subpopulations. Functional experiments demonstrated that CCT2 knockdown significantly inhibited cell proliferation and enhanced cisplatin sensitivity in LUAD cell lines. A number of candidate compounds targeting CCT2 exhibited stable binding in silico. The present findings identified CCT2 as a key mediator of cisplatin resistance in LUAD and provided potential therapeutic strategies to overcome chemotherapy resistance.

chaperonin-containing TCP-1 subunit 2↗

PubMed2026

Polyphenol-Rich Opuntia ficus-indica Cladodes: An Integrated Metabolomic, In Vivo and In Silico Study Supporting Their Hypolipidemic and Hepatoprotective Effects.

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPARα, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.

Animals↗

PubMed2026

Novel environmental contaminant 6PPD-quinone promotes malignant phenotypes in colorectal cancer cells and identifies candidate response-associated genes.

6PPD-quinone (6PPDQ), an oxidative transformation product of the widely used tire antioxidant 6PPD, is a ubiquitous environmental contaminant with bioaccumulation potential and widespread human exposure. Recent epidemiological evidence indicates a positive association between urinary 6PPDQ levels and colorectal cancer (CRC) risk; however, its biological effects on CRC-related phenotypes and associated molecular responses remain unclear. We integrated bioinformatics analysis, prognostic modeling, molecular docking and dynamics simulations, and in vitro experiments to investigate cellular and molecular responses to 6PPDQ in CRC models. Predicted 6PPDQ targets were intersected with CRC prognosis-related genes from The Cancer Genome Atlas, followed by functional enrichment and LASSO regression to construct a prognostic risk model, with 1-, 3-, and 5-year AUC values of 0.727, 0.754, and 0.778, respectively. Molecular docking and 100-ns molecular dynamics simulations suggested interactions between 6PPDQ and candidate proteins, including CPT2, SHC2, SRMS, and STK35. Functional assays showed that 6PPDQ exposure altered proliferation, wound-closure capacity, and invasion in Caco-2 and HCT116 cells across the nanomolar concentration range, with non-monotonic and cell-line-dependent responses. In contrast, NCM460 cells showed no increase in EdU incorporation at 10 or 100 nM, whereas reduced proliferation at higher concentrations was accompanied by increased LDH release. 6PPDQ also altered the expression of several prognosis-associated candidate genes. These findings identify cellular phenotypes and candidate molecular responses associated with 6PPDQ exposure under the tested in vitro conditions, but do not establish their causal roles or in vivo relevance. Further mechanistic and in vivo studies are required.

Humans↗

PubMed2025

Mechanism of action of curculigoside ameliorating osteoporosis: an analysis based on network pharmacology and experimental validation.

OBJECTIVE: This study aimed to predict and verify the mechanism of curculigoside in treating osteoporosis using network pharmacology, molecular docking technology, and micro-CT technology. METHODS: Herb databases were searched to identify and screen potential targets of curculigoside. The GeneCards platform was utilized to mine osteoporosis-related targets. Cytoscape 3.6.0 software was employed to construct a compound-target-disease network. A protein-protein interaction (PPI) network for curculigoside in osteoporosis treatment was established, and core targets were screened. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and GO biological process analyses were performed using the Metascape database. Finally, molecular docking and micro-CT were used to validate core targets relevant to osteoporosis. RESULTS: A total of 166 potential curculigoside targets and 4,313 osteoporosis-related targets were identified, with 91 common targets. Ten key targets, including matrix metalloproteinase (MMP)3, MMP9, interleukin (IL)-6, and caspase-3, were screened. KEGG pathway enrichment analysis indicated involvement in 10 pathways, such as the Rap1 signaling pathway and tumor necrosis factor (TNF) signaling pathway. Molecular docking results demonstrated strong binding affinity between curculigoside and the core targets. Micro-CT analysis revealed that curculigoside not only improved BMD, BV/TV, BS/BV, and Tb.Th but also reduced Tb.Sp in osteoporotic bone. CONCLUSIONS: Curculigoside is likely to treat osteoporosis through targets such as MMP3, MMP9, IL-6, and caspase-3, acting on signaling pathways including Rap1 and TNF. These results indicate that curculigoside exhibits multitarget and multipathway characteristics in osteoporosis treatment, providing a theoretical basis for further clinical investigation.

Osteoporosis↗

PubMed2026

Leveraging bioinformatics approaches for drug repositioning in space radiation protection.

The health effects of space radiation, primarily Galactic Cosmic Rays (GCRs), on humans remain largely unknown, with potential cardiovascular consequences posing a significant threat to astronauts on long-duration spaceflight missions. Currently, there are no established pharmacological countermeasures for GCR exposure. Drug repositioning offers a promising strategy to accelerate pharmaceutical research in space medicine. This study leverages existing bioinformatics techniques to identify and prioritize potential drug candidates associated with proteomic perturbations following simulated GCR exposure using previously published murine cardiac proteomic data. A protein-protein interaction (PPI) network was constructed using the top differentially expressed proteins (DEPs) from murine heart tissue following exposure to 5-ion GCRs as seed nodes, focusing on experimentally supported interactions. Network topology, Markov clustering, and functional enrichment analyses were used to characterize biologically relevant proteins and pathways. Drug-protein interactions were predicted using Drugst.One and mapped to PPI clusters of interest to identify candidate drugs. Selected drug-macromolecule interactions were further explored using CB-Dock2 molecular docking and short-duration molecular dynamics simulations as hypothesis-generating structural assessments. Analysis of a key PPI network cluster consisting of several ATP synthase proteins identified 23 unique drug candidates. These analyses demonstrate a systematic approach for leveraging bioinformatics techniques to identify candidate molecular targets and generate pharmacological hypotheses in the context of space radiation countermeasures. Ultimately, this strategy introduces a hypothesis-generating framework for the prioritization of potential drug candidates for future computational characterization and experimental investigation against spaceflight stressors.

Animals↗

PubMed2026

Integrated immunoinformatics for the design of novel multi-epitope vaccine and identification of new drug targets against Stenotrophomonas maltophilia, a multidrug-resistant superbug.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets. METHODS: A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of S. maltophilia proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of S. maltophilia. MEV-TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened via a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets. RESULTS: From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for S. maltophilia, providing new therapeutic insights. CONCLUSION: The designed MEV and identified immunogenic targets represent promising vaccine candidates against S. maltophilia. Further in vitro and in vivo studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.

Drug targets↗

PubMed2025

Genetic targets related to aging for the treatment of coronary artery disease.

BACKGROUND: Coronary Artery Disease (CAD) is the most common cardiovascular disease worldwide, threatening human health, quality of life and longevity. Aging is a dominant risk factor for CAD. This study aims to investigate the potential mechanisms of aging-related genes and CAD, and to make molecular drug predictions that will contribute to the diagnosis and treatment. METHODS: We downloaded the gene expression profile of circulating leukocytes in CAD patients (GSE12288) from Gene Expression Omnibus database, obtained differentially expressed aging genes through "limma" package and GenaCards database, and tested their biological functions. Further screening of aging related characteristic genes (ARCGs) using least absolute shrinkage and selection operator and random forest, generating nomogram charts and ROC curves for evaluating diagnostic efficacy. Immune cells were estimated by ssGSEA, and then combine ARCGs with immune cells and clinical indicators based on Pearson correlation analysis. Unsupervised cluster analysis was used to construct molecular clusters based on ARCGs and to assess functional characteristics between clusters. The DSigDB database was employed to explore the potential targeted drugs of ARCGs, and the molecular docking was carried out through Autodock Vina. Finally, single-cell data (GSE159677) of arterial intima was used to further explore the expression of aging signature genes in different cell subpopulations. RESULTS: We identified 8 ARCGs associated with CAD, in which HIF1A and FGFR3 were up while NOX4, TCF7L2, HK3, CDK18, TFAP4, and ITPK1 were down in CAD patients. Based on this, CAD patients can be divided into two molecular clusters, among which cluster A mainly involves functional pathways such as ECM receptor interaction and focal adhesion; cluster B mainly involves functional pathways such as amimo sugar and nucleotide sugar metabolism and pyrimidine metabolism. In addition, the molecular docking results showed that retinoic acid and resveratrol had good binding affinity with targets genes. Further single-cell analysis results showed that NOX4, TCF7L2, ITPK1, and HIF1A were specifically expressed in different types of cells in atherosclerotic tissues. CONCLUSION: Our study identified several ARCGs that may be involved in the pathogenesis and progression of CAD. Further, retinoic acid and resveratrol were potential candidate molecule drugs for inhibiting these targets.

Humans↗

PubMed2026

Genome-wide identification and expression profiling of CSP and OBP genes in Stictocephala bisonia reveals candidate genes potentially associated with insecticide response.

Stictocephala bisonia is an important invasive agricultural pest. Due to the frequent application of insecticides in its habitat, this species is under intense selection pressure. Chemosensory proteins (CSPs) and odorant-binding proteins (OBPs) are known to play key roles in insecticide resistance, but their specific functions in S. bisonia remain unclear. In this study, we identified a total of 22 SbisCSPs and 16 SbisOBPs based on the S. bisonia genome. To screen for candidate genes potentially linked to insecticide resistance, we adopted a multi-criteria screening strategy that integrated phylogenetic analysis, molecular docking with three insecticides, and tissue-specific expression profiling. Phylogenetic analysis identified several SbisCSPs and SbisOBPs clustering with genes known to be involved in insecticide resistance, serving as an initial evolutionary filter. Molecular docking results indicated that λ-Cyhalothrin exhibited the strong predicted binding affinity with most of SbisCSPs and SbisOBPs. Subsequent qPCR validation of seven prioritized candidates revealed distinct expression patterns: SbisCSP22 was highly expressed in adults and demonstrated strong binding affinity to all three insecticides tested, suggesting a potential role in mediating multi-insecticide response. Conversely, SbisCSP17 was significantly upregulated in larvae, clustered with genes known to mediate imidacloprid resistance, and exhibited strong binding affinity to imidacloprid. Given its larval-specific expression and the soil-dwelling behavior of larvae, we hypothesize that SbisCSP17 is a key candidate gene for larvae coping with soil-treated insecticides.

Animals↗

PubMed2025

Computational identification of potential antifungal targets against Claviceps purpurea via MD simulation and MM/GBSA.

Ergot alkaloids produced by the fungus Claviceps purpurea pose significant risks to agriculture and human health. This study systematically investigates the pathogenicity of C. purpurea, analyzing five strains for their proteomic profiles, which revealed genetic variability in size and GC content. We identified proteins localized in various cellular compartments, contributing to our understanding of essential cellular processes. A focus on potential drug targets led to the identification of Alpha-N-acetylglucosaminidase, a hydrolase with significant mass and functional relevance, despite not matching a UniProt entry. The 3D structure prediction confirmed its integrity, making it a suitable target for further analysis. Molecular docking identified ligands CID:51,535,944 and CID:145,242,255 with strong binding affinities to Alpha-N-acetylglucosaminidase, highlighting interactions with key residues like TRP138, ARG651. Molecular docking interactions were validated and showed consistency through MD simulation analyses with greater RMSD, RMSF and PL contacts. This research enhances our understanding of C. purpurea, offering insights into its genetic diversity and cellular mechanisms while identifying promising therapeutic targets. The findings contribute to strategies for mitigating the economic and health impacts of C. purpurea infections, paving the way for innovative interventions in sustainable agriculture.

Molecular Docking Simulation↗

PubMed2026

Proteomic regulation of anti-proliferative and anti-migratory activity by potent phytochemicals from Pistacia integerrima J.L. Steward Ex Brandis via PI3K, AKT1, and KRAS for Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of mortality worldwide and remains a major therapeutic challenge due to high metastasis, drug resistance and limited treatments. Pistacia integerrima J.L. Steward Ex Brandis (PI) consists of flavonoids, steroids, terpenoids and phenolic compounds reported for pharmacological activities. The efficacy of potent bioactives from P. integerrima may be ascertained employing cytotoxic, antiproliferative, anti-migratory, and anti-metastatic evaluations in A549 NSCLC cells with proteomic profiling, molecular docking, and dynamics simulation study. METHODS AND RESULTS: PI EtAc produced significant dose-dependent cytotoxicity in A549 cells (100 µg/mL, p < 0.0001 in the MTT assay. There was a pronounced decrease in colony formation after treatment with EtAc, with 18.41% (p < 0.002), and markedly. Furthermore. PI EtAC markedly inhibited cell migration emphasized by wound healing and Transwell migration (p < 0.01) assays, indicating reduced metastatic migratory potential. Proteomic analysis demonstrated significant downregulation of Endoglin (CD105), KLK5 and MMP-2, indicating suppression of angiogenic and metastatic signalling pathways in the Human XL Oncology protein array. The interaction of major PI phytochemicals with key NSCLC-associated targets was recorded in Molecular docking, revealing favourable binding affinities of kaempferol, β- sitosterol, luteolin, and quercetin towards several oncogenic targets, including AKT1(- 7.6 kcal/mol), PI3K(- 9.4 kcal/mol), KRAS (- 8.5 kcal/mol) and MMP9 (- 8.1 kcal/mol). Molecular dynamics simulation confirmed the structural stability of the kaempferol -AKT1 complex throughout the 100 ns simulation. CONCLUSION: Pistacia integerrima bioactives exhibited significant anti-proliferative, anti-migratory, and anti-metastatic activities in vitro, which may provide scientific rationale identifying newer promising candidates for NSCLC.

Humans↗

PubMed2025

Mechanisms of Baishao () and Gancao () on major depressive disorder: network pharmacology and o validation.

OBJECTIVE: To elucidate the potential molecular mechanisms of Baishao (Radix Paeoniae Alba) (APR) and Gancao (Radix Glycyrrhizae) (GR) in the treatment of major depressive disorder (MDD). METHODS: Based on the network pharmacology strategy, the therapeutic targets of APR-GR for MDD are predicted, differentially expressed genes from the Integrated Gene Expression database for MDD patients. Topological networks are constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched, their pharmacological potential molecular mechanisms are discussed, and molecular docking analysis is performed to further motivate compositional and target interactions. Finally, the CUMS mouse model is used for validation. RESULTS: Based on the pharmacological network analysis, 17 candidate genes were identified, including muscarinic acetylcholine receptor M1(CHRM1), muscarinic acetylcholine receptor M2 (CHRM2), β2-adrenergic receptor (ADRB2), adrenergic α1A receptor (ADRA1A) and 5-hydroxytryptamine transfer protein (SLC6A4), etc. which are primarily involved in reactive oxygen species metabolism, neural response, oxidative stress response and other biological processes. Further analysis revealed that these targets are closely related to Ca2+, cyclic adenosine monophosphate, etc., and exhibit optimal binding sites after molecular docking. Finally, in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models, increasing brain levels of 5-hydroxytryptamine, dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone, corticosterone and adreno cortico tropic hormone, while upregulating the expression of CHRM1, CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2. CNCLUSION: This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.

Major Depressive Disorder↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗