Search Results (10,462)

Background: Among gynecological malignancies, ovarian cancer (OC) remains a leading cause of mortality worldwide, often characterized by the highest fatality-to-case ratio due to its asymptomatic progression and late-stage detection. Despite substantial investigation, the root cause of disease development and pathology remains unknown. Early detection is critical for improving OC prognosis. Unfortunately, because of the lack of identifiable symptoms in the early stages, the disease is frequently detected late. As a result, regular check-ups, being aware of risk factors, and paying attention to unusual symptoms can all help discover OC early. Apolipoproteins (APOs) and Annexins (ANXs) have recently been linked to OC. Aim: We conducted a cutting-edge bioinformatics investigation to find novel therapeutic targets and precise biomarkers linked to OC against APO and ANX. Methods: We started by compiling the ANX and APO families via HUGO Gene Nomenclature Committee (HGNC) homepage. Next, we accessed GEPIA2 to compare the relative messenger RNA (mRNA) expression levels of all ANX and APO family members across the cancer genome atlas (TCGA)-OC cohort and matched normal and GTEx data. Prognostic analysis of all significantly expressed ANXs and APOs was performed via Kaplan–Meier (KM) plotter. cBioPortal was used for mutational analysis of prognostic ANXs and APOs. Finally, we ran functional enrichment, molecular docking, and molecular dynamics (MD) simulation analyses. Results: Overall, the results suggest that ANXA2 and its related genetic changes represent potential focal points for precision oncology, offering a computational rationale for the development of target-driven therapeutic interventions in OC. Conclusions: Molecular docking and MD simulation analyses identified curcumin as a potential inhibitor of ANXA2, demonstrating stable binding affinity and structural conservation throughout the simulation period. These computational findings characterize curcumin as a promising candidate for targeting ANXA2 in OC, warranting further experimental validation to confirm its therapeutic efficacy. Full article

Monkeypox virus, a zoonotic DNA virus belonging to the Orthopoxvirus genus, has emerged as a global health issue because of its fast spread to 104 nations over six continents. In the current study, an immunoinformatics pipeline was used to design a multiepitope-based prophylactic vaccine targeting the A35R glycoprotein and E8L membrane proteins of the monkeypox virus. Selected target proteins were surface-exposed, non-homologous to the human proteome, and essential for viral pathogenesis. B-cell and T-cell (MHC-I and MHC-II) epitopes with high antigenicity (>0.5), non-allergenicity, non-toxicity, and highly soluble in water with strong affinity towards innate and adaptive receptors, were prioritized. Shortlisted epitopes were combined to design the final vaccine utilizing an adjuvant (50S ribosomal L7/L12) and appropriate linkers for improved immunogenicity. Population coverage analysis showed wide HLA representation with 83.57% (MHC-I) and 88.8% (MHC-II) global coverage, including 89.6% for West Africa and 87.3% for Central Africa. Docking analysis of the vaccine construct with the TLR-4 receptor revealed stable interactions (−695.6 kcal/mol). Molecular dynamics simulations and binding free energies further confirmed structural stability. Immune simulations predicted strong activation of both humoral and cellular immune responses. These results indicate that the designed multiepitope vaccine construct is a viable option for additional experimental validation against the monkeypox virus. Full article

Raspberry (Rubus idaeus L.) fruits have been widely used due to their abundance of diverse polyphenolic compounds, whereas research on the chemical composition and bioactivity of their stems and leaves remains limited. In this study, the ethyl acetate extract of raspberry stems and leaves was evaluated for inhibitory activity against α-glucosidase and α-amylase. Guided by affinity ultrafiltration–mass spectrometry, 16 potential active components were further isolated and characterized. Among these, 13 compounds exhibited binding affinity for α-amylase, while 5 compounds showed binding affinity for α-glucosidase. Quercetin-3-O-β-D-glucoside-7-O-β-D-gentiobioside was isolated from raspberry stems and leaves for the first time. Procyanidin C₃ and quercetin exhibited significant inhibitory effects on the two enzymes. Molecular docking studies hinted at the interactions between these compounds and the key active sites of the two enzymes. These findings suggest that phenolic compounds in raspberry stems and leaves may possess potential as α-glucosidase and α-amylase inhibitors, providing a scientific basis for further research on their application as functional components for blood glucose control. Full article

The apple (Malus domestica Borkh.) is one of the most widely consumed fruits worldwide due to its pleasant sensory properties and rich phytochemical composition. Therefore, the present study aimed to comprehensively investigate the chemical composition, antioxidant activity, anticancer effects, and molecular interactions of peel and pulp extracts of the Hünkar apple cultivar collected from different locations, using a combined experimental and computational strategy. These factors had a big effect on the extracts’ phenolic composition and biological activity. Moreover, the anticancer results were corroborated by molecular docking analyses, which offered further understanding of the interactions between bioactive compounds and cancer-associated target proteins. This integrative approach underscores the impact of both biological and methodological variables on the antioxidant and anticancer properties of apple-derived extracts, reinforcing their potential as natural sources of bioactive compounds. Cytotoxic activity against HT-22 and C6 cell lines was evaluated using the MTT assay, showing dose- and time-dependent antiproliferative effects. Apple extracts exhibited anticancer effects that were dependent on dosage and duration. The activities of chemicals found in extracts of Hünkar apple samples collected from four different locations against brain cancer proteins (PDB ID: 2DME, 6YPE, 1RV1) were examined. ADME/T analysis was then performed on the three molecules with the highest activity. The quantum chemical properties of these three molecules were also examined using the Gaussian package program with B3LYP, HF, M062X level in 6–31g, 6–31++g, and 6–31++g(d,p) basis sets. Full article

Ebola virus disease remains one of the most serious viral infections with no approved small-molecule treatments. The Ebola virus glycoprotein (EBOV-GP), which enables the virus’s entry to host cells, is a promising target for drug discovery. In this study, a multistage computer-aided drug discovery approach was used to identify new specific EBOV-GP inhibitors. A reliable QSAR model was built using 55 terpenoid derivatives. This model was able to predict the activity of newly designed compounds with good accuracy and validated statistical metrics ($R_{tr}^2$= 0.70; $R_{ext}^2$ = 0.73). It was subsequently applied to screen over 15,500 newly generated compounds from three lead molecules by fragment-based design tools. Predicted activity, binding affinity toward EBOV-GP, and good ADMET drug-like properties prioritized the eleven most promising hits. Through 150 ns molecular dynamics simulations, these compounds remained stable in the EBOV-GP binding site. Further binding free energy analysis (MM/PBSA) showed strong binding affinities, especially for the compounds L-60, L-832, M-1618, and L-1366. This study showed how combining QSAR, fragment-based design, docking, ADMET, and molecular dynamics could help in identifying potent and safe small molecules against the EBOV-GP. The top compounds are ready for further experimental and in vitro biological testing. Full article

Antimicrobial resistance (AMR) represents a critical global health challenge, with methicillin-resistant Staphylococcus aureus (MRSA) posing a significant threat in both hospital-acquired and community-associated infections. Research has demonstrated that biofilm formation is a key factor contributing to drug resistance in MRSA. In this study, we investigated an fungus, Fusarium oxysporum BPF55, isolated from Blaps rynchopetera, which inhibits MRSA biofilm formation. The aim of this research was to identify the fungal strain and comprehensively characterize its genomic features, as well as to evaluate its anti-MRSA biofilm potential. Whole-genome sequencing revealed a genome size of 50,097,681 base pairs, a GC content of 47.36%, and 16,507 predicted coding genes. AntiSMASH analysis identified 56 secondary metabolite biosynthetic gene clusters, including those involved in the synthesis of various natural products such as terpenes, non-ribosomal peptides, and polyketides. Using UPLC-MS/MS, 15 compounds were annotated from the ethyl acetate extract. Molecular docking studies demonstrated that four compounds exhibit varying affinities for SarA and AgrA, two key proteins involved in MRSA biofilm formation. Overall, these findings suggest that the fungus F. oxysporum BPA55 produces a variety of secondary metabolites and contains bioactive compounds with potential anti-MRSA biofilm activity. Full article

In order to find green fungicides derived from natural products, 22 unreported anethole-based thiazolinone-hydrazone compounds were designed and synthesized, and their structures were characterized by FT-IR, ¹H NMR, ¹³C NMR, and HRMS. At a concentration of 50 mg/L, the preliminary antifungal activity of the target compounds against eight plant pathogens was evaluated. The results showed that 5q (R = m-OH C₆H₄) exhibited the best inhibitory activity against most of the tested plant pathogenic fungi, demonstrating that this compound had certain broad-spectrum antifungal activity. In addition, a reasonable and effective 3D-QSAR model (r² = 0.994, q² = 0.529) was established using the comparative molecular field analysis (CoMFA) method to study the relationship between the structures of the target compounds and their antifungal activity against Physalospora piricola. Meanwhile, the results of electrostatic potential calculation of the compounds indicated that the electronic effect caused by different substituents on the benzene ring might be one of the factors affecting antifungal activity. In addition, frontier molecular orbital calculations implied that the anethole moiety and the thiazolinone-hydrazone-benzene structure in the target compounds might play an important role in antifungal activity. The potential binding mode between the target compound 5q (R = m-OH C₆H₄) and the homology-modeled succinic dehydrogenase was explored by molecular docking. Full article

Streptococcus pneumoniae resists host defenses through multiple surface factors, yet their specific contribution to protection against antimicrobial peptides remains incompletely understood. We examined the role of pneumococcal surface protein A (PspA) and the polysaccharide capsule in protection against the human defensin HNP-1. PspA conferred increased resistance to HNP-1-induced killing, shown by a decreased killing in the presence of purified recombinant PspA and an increased sensitivity when PspA was deficient from the surface of strains of two different genetic backgrounds or when anti-PspA antibody was present. The capsule also conferred protection against HNP-1, which was serotype-dependent, with type 2 protecting better than type 4, and free polysaccharides acted as decoys by sequestering HNP-1. Removal of surface PspA from capsule-deficient mutants revealed additive contributions of both factors to survival. Molecular docking analysis suggests a potential electrostatic interaction between PspA and HNP-1. These findings highlight the independent and complementary roles of PspA and the capsule in pneumococcal resistance to HNP-1 and provide novel insights that may inform future vaccine design and antimicrobial strategies. Full article

Synthetic dyes discharged from the textile and dyeing industry present a significant environmental and health hazard due to their inherent toxicity, environmental persistence, and potential carcinogenicity. Microbial degradation has garnered significant interest as a cost-effective and eco-friendly strategy for dye wastewater treatment in recent years. The study systematically evaluated the decolorization performance, degradation pathways, and detoxification effects of three bacterial strains, including Rhodopseudomonas palustris gh32, Bacillus cereus HL7, and Bacillus safensis X64, on the dye indigo carmine (IC) and three azo dyes: reactive black 5 (RB5), direct black G (DBG), and direct blue 15 (DB15). The degradation mechanisms were elucidated through UV-Vis spectroscopy, UPLC-Orbitrap-HRMS analysis, and enzyme activity assays. Molecular docking simulations were employed to investigate the interactions between key redox enzymes (such as laccase, tyrosinase, and azoreductase) and the dye molecules. The results demonstrated that the strain-specific enzymatic systems effectively disrupted the dye structures. Significant detoxification effects were further confirmed through a series of bio toxicity assays involving Escherichia coli, Bacillus subtilis, plant seeds, and erythrocytes. The addition of Fe³⁺, sodium citrate, or yeast extract significantly enhanced both the decolorization efficiency and enzyme activity. This study provides an in-depth understanding of the bacterial dye degradation process at the mechanistic level, highlighting the potential of customized bacterial systems for eco-friendly dye wastewater treatment. It offers theoretical support for elucidating the mechanisms of bacterial dye degradation and advancing bioremediation technologies. Full article

The porcine epidemic diarrhea virus (PEDV) causes a gastrointestinal disease generating mortality rates approaching 100% in piglets worldwide. The S glycoprotein of PEDV is the main target for the development of vaccines. Two vaccines approved by the Ministry of Agriculture and Rural Development are used in Mexico: the first vaccine is based on an inactivated virus isolated more than a decade ago, whereas the second vaccine is based on mRNA technology. The most important tool for controlling PEDV outbreaks is vaccination; however, coronaviruses are characterized by the accumulation of multiple mutations, which compromise the immune response elicited by outdated vaccines. In this work, we classified the Mexican strains of PEDV reported so far in GenBank, according to their genotypes. Subsequently, we searched for B and T cell epitopes conserved in Mexican PEDV strains using bioinformatic tools. In addition, we explored whether these epitopes can induce allergies, autoimmunity, and/or toxic effects. Next, we determined the localization of B cell epitopes in the S glycoprotein using the protein crystal and protein modeling of several S glycoproteins. Finally, we carried out molecular docking analysis to assess whether these T cell epitopes could interact with the peptide-binding groove of the Swine Leukocyte Antigens (SLAs). Five conserved B cell epitopes were found to be exposed on the surface of the S glycoprotein, whereas several promiscuous CTL and HTL epitopes were bound, with low free energy, to the peptide-binding grooves of SLA-I and SLA-II, respectively. The best epitopes were used to generate a plasmid carrying the sequence to produce a recombinant protein. This plasmid was used for transfection experiments in PK-15 cell culture. The B cell epitopes reported here were recognized by the sera from pigs infected with PEDV but not by the sera from uninfected animals. These results justify future evaluations of the ability of these epitopes to stimulate cytokine production by T cells, antibody generation, and their neutralizing activity. Full article

Human rhinoviruses (HRVs) are the primary cause of the common cold, a highly contagious upper respiratory tract infection characterized by nasal congestion, sneezing, and sore throat. HRV replication depends on its 3C protease (HRV-3Cpro), a key enzyme that cleaves the viral polyprotein into functional proteins essential for viral maturation. Currently, no FDA-approved inhibitors specifically target HRV-3Cpro. While rupintrivir, a synthetic inhibitor, advanced to clinical trials, it ultimately failed due to limited efficacy. This study investigated the potential of Vitex negundo (or lagundi)—a medicinal plant traditionally used in the Philippines for treating colds and respiratory ailments—as a source of natural HRV-3Cpro inhibitors through in silico molecular docking and pharmacokinetic (ADMET) evaluation. Fifteen phytochemicals were screened, with five compounds exhibiting strong binding affinities exceeding that of the reference inhibitor rupintrivir (−6.1 kcal/mol): agnuside (−6.9 kcal/mol), luteolin 7-O-glucoside (−6.7 kcal/mol), 2′-p-hydroxybenzoyl mussaenosidic acid (−6.5 kcal/mol), 6′-(p-hydroxybenzoyl) mussaenosidic acid (−6.5 kcal/mol), and luteolin (−6.2 kcal/mol). Among these, luteolin emerged as a particularly promising lead compound, forming stable hydrogen bonding and hydrophobic interactions with HRV-3Cpro. Luteolin also demonstrates a favorable ADMET and safety profile, predicted to be non-mutagenic and non-hepatotoxic. These findings position luteolin as a potential plant-based HRV-3Cpro inhibitor, warranting further in vitro and in vivo studies to validate its antiviral efficacy and pharmacokinetic properties. Full article

Ochratoxin A (OTA), a prevalent food contaminant, is closely linked to the development of various cancers, including clear cell renal cell carcinoma (ccRCC). However, the potential mechanisms remain to be explored. In this study, we employed network toxicology, machine learning, and molecular docking techniques to systematically investigate the potential molecular mechanisms underlying OTA-associated ccRCC. We normalized transcriptional data from two Gene Expression Omnibus (GEO) datasets and analyzed it using differential expression analysis and weighted gene co-expression network analysis (WGCNA), identifying 3224 ccRCC-associated target genes. These were intersected with 232 predicted OTA target genes, yielding a total of 56 overlapping targets. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these targets were primarily enriched in critical biological processes, including extracellular matrix remodeling, immune microenvironment regulation, signaling pathway transduction, cellular metabolism, and protein homeostasis. Machine learning analysis identified “glmBoost + RF” (a sequential combination of feature selection and classifier) as the optimal model, from which nine key genes were extracted. SHapley Additive exPlanations (SHAP) analysis revealed five core genes (IGFBP3, ITGA5, PYGL, SLC22A8, LTB4R), with IGFBP3 and ITGA5 serving as the principal driver genes of the model. Validation of the model’s diagnostic efficacy and single-cell transcriptome analysis indicated that the core genes exhibited significant differential expression patterns, cell-type-specific expression characteristics, and high independent diagnostic efficacy. Molecular docking analyses predicted stable interactions between OTA and the core target proteins. These findings suggest potential molecular links between OTA exposure and ccRCC, providing a foundation for hypothesis generation and future experimental validation. Full article

Background: Avian pathogenic Escherichia coli (APEC) contributes substantially to colibacillosis outbreaks in chickens. Because APEC cells readily attach to surfaces and develop biofilms, they pose a notable hazard to poultry production and food safety. This study investigated the antibiofilm and anti-adhesion activities of deep eutectic solvent-based emulsion containing Piper betle L. extract (DEPE) and hydroxychavicol, a pure compound isolated from P. betle leaves against APEC. Methods: Antibiofilm and anti-adhesion activities of DEPE and hydroxychavicol against APEC were investigated. Molecular docking and dynamics simulation of DEPE and hydroxychavicol was conducted. In addition, anti-adhesion activity of DEPE on chicken meat during storage was evaluated. Results: DEPE and hydroxychavicol significantly inhibited biofilm formation at sub-MIC, with DEPE achieving up to 80% inhibition and hydroxychavicol up to 69%. At 8 × MIC, DEPE and hydroxychavicol diminished the viability of both early and established biofilms. Furthermore, DEPE and hydroxychavicol reduced APEC adhesion on the surface as observed by SEM. In silico analyses demonstrated the stable binding of hydroxychavicol to adhesion-related proteins, particularly EcpA and FimH, suggesting a possible mechanism for its anti-adhesion activity. At day 5, DEPE at 4 × MIC significantly reduced 63% bacterial adhesion to chicken meat surfaces during storage, while maintaining the meat’s color. Conclusions: These findings indicate that DEPE and hydroxychavicol are promising candidates for limiting APEC biofilm formation and surface attachment and may serve as alternative antibacterial agents in poultry-related food safety applications. Full article

Structure-based strategies are widely used in tuberculosis drug discovery; however, their translational impact remains limited. This review examines how structure-based virtual screening (SBVS) is applied in practice to Mycobacterium tuberculosis targets and explores why docking-derived predictions frequently fail to translate into measurable biological activity. Rather than treating docking scores as quantitative predictors of potency, representative case studies are analyzed to demonstrate that SBVS is most effective when employed as a prioritization framework integrated with appropriate target preparation, physicochemical filtering, and early experimental validation. Across diverse targets, molecular dynamics simulations emerge as a critical discriminator, enabling the identification of binding instability and false-positive hits that persist after static docking. Tuberculosis-specific constraints—including cofactor-dependent catalysis, resistance-associated mutations, membrane-rich environments, and permeability barriers—are discussed as key factors decoupling in silico affinity from whole-cell efficacy. Collectively, these observations support a workflow-oriented view of computational drug discovery in tuberculosis, in which iterative integration of structural modeling and experimental validation is required for meaningful lead identification. Full article

Wuweiganlu (WGL) is a traditional formulation widely applied in the treatment of rheumatoid arthritis (RA), yet the identity of its bioactive constituents remains inadequately defined. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and untargeted serum metabolomics were employed to characterize the active components of WGL. Fraxin was identified as a principal compound from WGL. To investigate its therapeutic mechanism in RA, a series of in silico and experimental approaches were conducted. Network pharmacology analysis and RNA sequencing identified heat shock protein family member 8 (HSPA8) as a potential molecular target of Fraxin, which was further validated by molecular docking studies. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that Fraxin exerts its effects primarily by modulating cell apoptosis through the PI3K signaling pathway. In vitro experiments demonstrated that Fraxin significantly reduced inflammatory responses and downregulated HSPA8 expression in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLs) and macrophages. In vivo, Fraxin administration markedly reduced paw swelling, alleviated bone deformities, and improved bone volume fraction (BV/TV) in male IL1RA-deficient mice exhibiting spontaneous arthritis. Histological analysis confirmed that Fraxin attenuated joint inflammation by modulating the inflammatory microenvironment. Additionally, Fraxin inhibited synovial hyperplasia by regulating mitochondrial membrane potential collapse in FLs. Functional assays revealed that this regulation occurred via the inhibition of HSPA8/PI3K/AKT signaling axis, thereby suppressing aberrant FLS proliferation and contributing to the attenuation of RA progression. Full article