Search Results (326)

Chagas disease, caused by Trypanosoma cruzi, affects a significant proportion of patients who develop digestive and cardiac complications, including megaviscera. This pathogenesis has been associated with autoimmune mechanisms mediated by molecular mimicry. In this study, an in silico evaluation of the potential structural basis of cross-reactivity of β-tubulin 1.9 of T. cruzi and the human β-4A tubulin isoform 3 was conducted. Using bioinformatics tools, homologous regions were identified and potentially immunogenic epitopes were predicted, considering their structural modeling and molecular docking. The proteins shared 87% sequence identity and 95% similarity, with an almost identical structural overlap, RMSD 0.291 Å. Three epitopes, VPFPRLHFF, NDLVSEYQQYQDATI, and GQSGAGNNWAKGHYTEGAELIDS, exhibited high predicted antigenicity, with the 9-mer and 16-mer peptides displaying structurally compatible docking poses within the binding grooves of MHC class I and class II molecules, respectively, while B-cell epitope potential was inferred from sequence-based property predictions. Normal mode analysis, used as an exploratory approach, suggested comparable flexibility profiles for the parasitic- and human-derived peptide–MHC complexes. These findings provide an exploratory structural framework supporting a potential role of β-tubulin epitopes in molecular mimicry processes implicated in the development of chagasic megaviscera. Full article

Technological innovation in commercial Remotely Piloted Aircraft Systems (RPASs) is advancing rapidly. However, their operational efficiency remains limited by the need for on-site skilled human operators. Semi-autonomous drone-in-a-box (DIAB) systems are emerging as a practical solution, enabling automated, repeatable missions for applications such as construction site monitoring, security, and critical infrastructure inspection. Beyond industry, these systems hold significant promise for scientific research, particularly in long-term environmental monitoring where cost, accessibility, and safety are critical factors. In this technology demonstration, we detail the system implementation, discuss flight-planning challenges, and assess the overall feasibility of deploying a DJI Dock 2 DIAB system for remote monitoring of the Miles Ridge landslide in the Yukon Territory, Canada. The system was installed approximately 2.5 km from the landslide and operated remotely from across the country in Montreal, QC, about 4000 km away. A total of five datasets were acquired from July to September 2025, enabling three-dimensional reconstruction of the landslide surface from each acquisition. A comparison of extracted cross-sections demonstrated high reproducibility and accurate co-registration across acquisitions. This study highlights the potential of DIAB systems to support reliable, low-maintenance monitoring of remote landslides. Full article

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in medicine, cosmetics, and environmental technologies, yet their interactions with blood cells remain poorly understood, raising cross-species safety concerns. Using frog (nucleated) and human (anucleate) erythrocytes as comparative models, we show that cellular architecture fundamentally shapes responses to ZnO NPs exposure. Human erythrocytes exhibited a dose-dependent progression from membrane deformation to eryptosis and hemolysis, reflecting the pronounced vulnerability of anucleate cells. In contrast, frog erythrocytes sustained nuclear DNA damage while largely preserving membrane integrity, highlighting the protective or reparative role of the nucleus. Molecular docking revealed energetically favorable interactions of ZnO NPs with ERα-LBD and DNA (ΔG = −4.28 and −5.68 kcal/mol, respectively), while quantum chemical analyses indicated electron-accepting properties and a narrow HOMO–LUMO gap, suggesting efficient macromolecular interactions and intracellular ROS generation. Together, these findings demonstrate that the presence of a nucleus shifts the primary target of nanoparticle toxicity from membrane to genome, providing novel mechanistic insights. This comparative study offers a robust framework for understanding nanomaterial reactivity across taxa and informs One Health-oriented risk assessments. Full article

Background: Berberine, a benzylisoquinoline alkaloid, has been traditionally used in Ayurvedic and Chinese medicine. We examined the resistance mechanisms to berberine in a panel of different cancer cells and focused on understanding its molecular mechanisms. Methods: Resazurin assay determined berberine’s cytotoxicity. Molecular docking unraveled the interaction of berberine with the BCRP transporter. Fluorescence microscopy evaluated its effect on microtubules. Further, proteomic profiling identified novel determinants of cellular response to berberine and its derivatives. Results: Cell lines overexpressing ABC transporters displayed cross-resistance to berberine compared to their counterparts. While cells over-expressing EGFR were 3.57-fold resistant, wild-type and p53 knockout cells showed similar sensitivity to berberine. P-glycoprotein/ABCB1, EGFR, and WT1 expression correlated with the log₁₀IC₅₀ values for berberine in the NCI cell line panel. Berberine was bound to the same pharmacophore of BCRP as BWQ, and live cell microscopy showed that BCRP-transfected cells did not uptake considerable amounts of berberine in contrast to wild-type cells. Berberine altered the microtubule cytoskeleton similarly to vincristine. The sensitivity of berberine and its derivatives could be predicted by 40 out of 3171 proteins. Of them, 29 proteins have been previously involved in drug resistance. Their relationship to berberine and its derivatives is novel. Conclusions: Berberine-type compounds may be new candidates against cancer; however, they may develop drug resistance. Full article

Background: Major Depressive Disorder (MDD) is more common in patients with Inflammatory Bowel Disease (IBD) than in the general population, suggesting a shared but unclear pathogenesis. Autophagy, a conserved intracellular cleaning process, maintains cellular health by removing debris and recycling nutrients. Given the limited research on autophagy in this comorbidity, this study investigated the role of autophagy-related genes in both disorders. Aim: This study aimed to identify shared autophagy-related mechanisms between IBD and MDD and to explore potential therapeutic strategies. Methods: We identified differentially expressed autophagy-related genes (DE-ARGs) in diseased versus normal tissues. Shared DE-ARGs between IBD and MDD were designated Co-DEGs. We analyzed correlations among Co-DEGs and their association with immune cell infiltration. Four machine-learning algorithms were used to pinpoint key biomarkers. Potential therapeutic agents were predicted and validated via molecular docking. Results: We identified 47 shared Co-DEGs. Among these, CASP1 emerged as a cross-disease shared susceptibility-associated gene (SSAG), consistently selected by all machine-learning models. Drug-gene interaction analysis and molecular docking identified compounds that could regulate CASP1. Single-cell analysis suggested CASP1 helps reshape the immune microenvironment in Crohn’s disease. Furthermore, Mendelian randomization identified WDR6 as a shared genetic risk factor for both conditions. Conclusions: Our findings illuminate autophagy-mediated mechanisms linking gut and brain disorders. The identification of CASP1 as a SSAG, along with candidate therapeutics, provides a foundation for future research and targeted treatments for IBD and MDD comorbidity. Full article

Background/Objectives: Mecasin (KCHO-1) is a standardized multi-herb formulation containing diverse bioactive compounds predicted to engage multiple molecular targets. This study applied an integrative network pharmacology approach to explore how Mecasin may interact with Alzheimer’s disease (AD)-related molecular networks. Methods: Bioactive constituents from 9 herbs were screened through OASIS and PubChem, and their predicted targets were cross-referenced with 8886 AD-associated genes from GeneCards. Overlapping genes were analyzed using protein–protein interaction mapping, Gene Ontology, and KEGG to identify potential Mecasin–AD core nodes and pathways. Co-expression, co-regulation, and molecular docking analyses were performed to further characterize mechanistic relevance. Results: Network integration identified 6 core genes—AKT1, STAT3, IL6, TNF, EGFR, and IL1B—positioned within signaling pathways related to neuronal survival, inflammatory regulation, and cellular stress responses, including FoxO, JAK–STAT, MAPK, and TNF pathways. Molecular docking suggested that several Mecasin compounds may interact with targets such as AKT1 and TNF. Conclusions: These in silico findings indicate that Mecasin, a multi-component formulation containing numerous phytochemicals that generate broad compound–target associations, may interface with interconnected neuroimmune pathways relevant to AD. While exploratory, the results highlight potential multi-target mechanisms that merit further investigation and provide a systems-level framework to inform future experimental validation. Full article

Protein glycation and oxidation contribute to the pathogenesis of neurodegenerative diseases. This study evaluated the antiglycative and antioxidative effects of donepezil, rivastigmine, galantamine, memantine, lamotrigine, sodium valproate, and carbamazepine using bovine serum albumin (BSA) as a model protein. Glycation was induced with fructose, ribose, or methylglyoxal (MGO), and oxidation with chloramine T (ChT). Concentrations of glycation products—Amadori products (APs), amyloid cross-β structure (βA), argpyrimidine (ARG), crossline (CRO), vesperlysine (VES), pentosidine (PEN), total AGEs and glycoxidation products—dityrosine (DT), kynurenine (KN), N-formylkynurenine (NFK) as well as oxidation biomarkers, total thiols (TTs), protein carbonyls (PCs), and advanced oxidation protein products (AOPPs), were determined via spectrophotometric and spectrofluorimetric methods. Molecular docking and a systematic literature review (PRISMA) complemented the experimental data. Lamotrigine showed the strongest antiglycative and antioxidative effects, surpassing aminoguanidine in reducing ARG, PEN, DT, and NFK levels. In contrast, donepezil markedly increased APs, βA, ARG, VES, DT, and PEN, suggesting proglycative and pro-oxidative activity. Docking revealed a high affinity of donepezil for RAGE (–7.2 kcal/mol), possibly explaining its impact on carbonyl stress. Overall, anti-dementia drugs showed weak to moderate antiglycative potential, with lamotrigine being the most effective. Full article

Antibodies against low-molecular-weight compounds exhibit cross-reactivities (CRs) with their structural analogs, varying by orders of magnitude for different substances. This variability limits the informativeness of antibody applications as analytical reagents and for other aims when samples contain several members of the same family, their derivatives, or partial degradation products. Therefore, there is a demand to find some criteria for understanding the relationships between the structural characteristics of antigens of a given chemical class and their immunochemical activity. This study presents an experimental and theoretical investigation of the properties of a monoclonal antibody (MAb) against the S-stereoisomer of gatifloxacin, a member of the widely used (fluoro)quinolone (FQ) family of antibiotics, characterized by high structural diversity. The aim was to determine FQs that form complexes with MAb and suggest a methodology to predict their CRs in silico. For this, the interaction of MAb with 26 FQs was studied using the enzyme-linked immunosorbent assay and presented as CR values to the target antigen. The most pronounced CRs were observed for lomefloxacin, sarafloxacin, and ciprofloxacin. Molecular dynamics (MD) simulations were performed to identify differences in analyte interactions at the MAb antigen-binding site, which determines binding affinity. It has been shown that molecular docking fails to discriminate cross-reactive from non-cross-reactive compounds because FQs have similar cores. Therefore, advanced analysis of MD trajectories was carried out. It allowed for clarification of the dynamic features of analyte–antibody interactions responsible for binding. It was shown by the dynamical network analysis that the sum of betweenness centrality between a node corresponding to the quinolone ring and nodes representing MAb amino acids is higher for cross-reactive haptens. The found regularities can be transferred to other analyte–antibody systems as a binary classifier that discriminates cross-reactive and non-cross-reactive compounds. Full article

Background/Objectives: GuaB, which is known as inosine 5′-phosphate dehydrogenase (IMPDH), is an enzymatic target involved in the de novo guanine biosynthetic pathway of the multidrug-resistant (MDR) Acinetobacter baumannii. GuaB has emerged as a potential therapeutic target to cope with increasing antibiotic resistance. Here, we used machine learning-based virtual screening as a verification technique to find potential inhibitors possessing different chemical scaffolds, using structure-based drug design as a discovery platform. Methods: Four machine learning models, built based on chemical fingerprint data, were trained, and the best models were used for virtual screening of the ChEMBL library, which covers 153 active molecules. Molecular dynamics (MD) simulations of 200 ns were carried out for all three compounds in order to explain conformational changes, evaluate stability, and provide validation of the docking results. Post-simulation analyses include principal component analysis (PCA), bond analysis, free-energy landscape (FEL), dynamic cross-correlation matrix (DCCM), radial distribution function (RDF), salt-bridge identification, and secondary-structure profiling, etc. Results: For molecular docking, the screened compounds were used against the GuaB protein to achieve proper docked conformation. Upon visual examination of the best-docked compounds, three leads (lead-1, lead-2, and lead-3) were found to have better interaction with the GuaB protein in comparison to the control. The mean RMSD scores between the three leads and the control were between 2.54 and 2.89 Å. In addition, the three leads as well as the control were characterized for pharmacokinetic features. All three leads met Lipinski’s Rule 5 and were thus drug-like. PCA and FEL analyses showed that lead-2 exhibited improved conformational stability, identified as deeper energy minima, whereas RDF and DCCM analyses revealed that lead-2 and lead-3 exhibited strong local structuring and concerted dynamics. In addition, lead-2 displayed a very rich hydrogen-bonding network with a total of 460 frames possessing such interactions, which is the highest among the complexes investigated here. Based on entropy calculations and the maximum entropy method of gamma–gram, lead-1 proved to be the most stable one with the lowest binding free-energy. Conclusions: This study provides an integrated machine learning-based virtual screening pipeline for the identification of new scaffolds to moderate infections associated with AMR; however, in vitro validation is still required to assess the efficacy of such compounds. Full article

Chrysanthemum (Chrysanthemum morifolium Ramat.) has been recognized as both a food and medicinal substance in China since 2002 and possesses antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities. Previous studies suggest that Chrysanthemum may alleviate skin lesions resembling atopic dermatitis (AD); however, its underlying mechanisms remain unclear. In this study, we integrated network pharmacology and machine learning to systematically explore the potential mechanisms of Chrysanthemum in AD treatment. Four algorithms—Random Forest (RF), Lasso regression with cross-validation (LassoCV), Elastic Net (EN), and Extreme Gradient Boosting (XGB)—were compared, among which the XGB model achieved the best performance (accuracy = 0.9393). Further analysis identified 15 optimal features, two core targets (PTGS2 and MMP9), and one critical pathway (NF-κB signaling). To experimentally validate these findings, HaCaT keratinocytes were co-stimulated with TNF-α and IFN-γ to establish an in vitro inflammatory model, and co-treatment with three major flavonoids from Chrysanthemum—Acacetin, Diosmetin, and Chryseriol—significantly suppressed cytokine-induced COX-2 overexpression and reduced NF-κB p65 phosphorylation, confirming their inhibitory effects on NF-κB activation. These results were consistent with molecular docking and dynamics simulations, which demonstrated that these flavonoids, along with celecoxib, could stably bind to COX-2, thereby enhancing system stability and reducing residue fluctuations at the binding interface, revealing the molecular basis by which Chrysanthemum alleviates AD and supporting its modernization and therapeutic potential. Full article

Background: Disability-linked neurodegeneration involves cholinergic dysfunction, amyloidogenesis, glutamatergic excitotoxicity, and dopaminergic imbalance, highlighting the need for multi-target modulation. Catharanthus roseus contains a diverse array of metabolites with potential polypharmacological properties. Methods: We curated 318 Catharanthus roseus metabolites and performed structure-based virtual screening against five CNS targets, namely BACE1, AChE, MAO-B, NMDAR, and D1, using target-specific positive controls. Cross-target intersection ranking nominated three hits. We assessed dynamic stability by 200 ns all-atom molecular dynamics simulations (MDS) and MM/PBSA; ADMET-AI profiled CNS-relevant properties. Results: The three metabolites (PubChem CIDs 485711, 56964592, and 162963996) repeatedly ranked among top binders across targets. All five protein–ligand complexes reached stable MD plateaus (RMSD < ~0.30 nm) with sustained key interactions; BACE1 and AChE showed the highest contact persistence and most favorable ΔG_total/ligand-efficiency. Conclusions: Convergent docking, MDS, and MM/PBSA support these metabolites as tractable multi-target leads, with BACE1/AChE prioritized for enzyme-level validation and the remaining targets for follow-up studies. Full article

Duck viral hepatitis (DVH), a highly contagious disease, is caused primarily by duck hepatitis A virus (DHAV). The viral genotypes exhibit significant diversity, creating a challenge as monovalent vaccines fail to provide cross-genotype protection in ducklings. This study aimed to design a multi-epitope peptide vaccine targeting different genotypes of DHAV. Using immunoinformatics approaches, we systematically identified key antigenic determinants, including linear B-cell epitopes, cytotoxic T-cell epitopes (CTL), and helper T-cell epitopes (HTL). Based on these, a novel vaccine candidate was developed. The vaccine construct was subjected to rigorous computational validation: (1) Molecular docking with Toll-like receptors (TLRs) predicted immune interaction potential. (2) Molecular dynamics simulations assessed complex stability. (3) In silico cloning ensured prokaryotic expression feasibility. Then, we conducted preliminary experimental validation for the actual effect of the vaccine candidate, including recombinant protein expression in E. coli, enzyme-linked immunosorbent assay (ELISA) quantification of humoral responses, and Western blot analysis of cross-reactivity. ELISA results demonstrated that the vaccine candidate could induce high-titer antibodies in immunized animals, with potency reaching up to 1:128,000, and the immune serum showed strong reactivity with recombinant VP proteins. Western blot analysis using duck sera confirmed epitope conservancy across genotypes. Collectively, the multi-epitope vaccine candidate developed in this study represents a highly promising broad-spectrum strategy against DHAV. The robust humoral immunity it elicits, coupled with its demonstrated cross-reactivity, constitutes compelling proof-of-concept, laying a solid foundation for advancing to subsequent challenge trials and translational applications. Full article

Neurological damage, a debilitating condition closely associated with chronic neuroinflammation, currently lacks disease-modifying treatments, with management limited to symptomatic relief. Vitamins B6 (VB6), B12 (VB12), and proteolipid protein 1 (PLP-1) exhibit multimodal neuroprotective and anti-inflammatory effects; however, their therapeutic potential is limited by low bioavailability and inadequate ability to cross the blood–brain barrier (BBB). To address these limitations, we developed an ursolic acid-based nanoparticle system for the intranasal co-delivery of VB6, VB12, and recombinant PLP-1. The PLP-1 model predicted by AlphaFold3 was used for molecular docking. The docking results confirmed high-affinity binding interactions with VB6 and VB12, elucidating the mechanistic basis of their synergy. In vitro studies using a glucose-deprived PC12 cell injury model identified an optimal synergistic molar ratio of 10:1:2 (VB6: VB12: PLP-1). This combination significantly upregulated neuroprotective markers (PLP-1 and PGC-1α) and downregulated the pro-inflammatory cytokine TNF-α. In a mouse model of neural damage, the nano-encapsulated combination therapy demonstrated improved pharmacokinetics and significantly attenuated neuroinflammation and oxidative stress in brain tissue. This was evidenced by lower TNF-α and IL-1β levels and elevated GSH and SOD concentrations compared to free drug controls. The treatment regimen showed no detectable hepatorenal toxicity. Our findings demonstrate that this nanoformulation represents a safe, effective, and promising disease-modifying strategy to treat vestibular dysfunction by synergistically targeting its underlying neuroimmunological mechanisms. Full article

New β-amino ketone Mannich derivatives were synthesized in good yields. Molecular docking studies were conducted to evaluate their potential as inhibitors of acetylcholinesterase and tubulin, while their antioxidant activity was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. ADMET study (pharmacokinetic properties) predictions further indicated that these compounds can cross the blood–brain barrier and display high gastrointestinal absorption. Collectively, these findings highlight the derivatives as promising candidates for drug development, with favorable oral bioavailability and potential applications in the treatment of neurodegenerative diseases and cancer. Full article

Colonoscopy remains the gold standard for colorectal cancer (CRC) screening, but its invasiveness, cost, and limited availability in resource-constrained settings pose major barriers. Stool-based methylated DNA biomarkers, such as vimentin, offer sensitive, non-invasive alternatives. Given the high burden of HIV and helminth co-infections in sub-Saharan Africa and their potential contribution to cancer susceptibility, this study investigated whether stool-derived vimentin methylation could detect early oncogenic changes in these high-risk groups. In this retrospective cross-sectional study, archived stool samples from 62 South African adults were stratified into five groups: uninfected controls, HIV-infected only, helminth-infected only, HIV-helminth co-infected, and CRC-confirmed patients. DNA was extracted, bisulfite-converted, and analyzed for vimentin methylation using a high-resolution melt assay. Fecal occult blood testing (FOBT) was also performed. Vimentin methylation differed significantly across groups (p < 0.0001). CRC cases showed 90% methylation, confirming its role as a CRC biomarker. Interestingly, vimentin methylation frequencies were also observed in HIV-only (92.9%, p < 0.0001 vs. controls), helminth-only (93.3%, p < 0.0001), and HIV-helminth co-infected (77.9%, p < 0.0001) individuals without diagnosed cancer, compared to 10% in controls. Methylation levels in infected groups were not significantly different from CRC patients (all p > 0.05), suggesting infection-induced epigenetic changes of comparable magnitude to malignancy. To support these results, DNMT1–RG108 molecular docking (PDB 4WXX, Maestro 2025-3) demonstrated stable binding (GlideScore −6.285 kcal/mol; ΔG_bind −49.61 kcal/mol) via hydrogen bonding with Glu1266 and Asn1578 and π–π stacking with Phe1145, providing a mechanistic explanation for infection-driven vimentin methylation. No significant differences were found between infected groups. FOBT was positive in 83.3% of CRC cases, with only sporadic positives in infected groups. These findings provide novel evidence that chronic HIV and helminth infections are associated with vimentin promoter methylation at levels indistinguishable from CRC. This supports the hypothesis that persistent infection-driven inflammation promotes early epigenetic reprogramming toward oncogenesis. In high-burden African settings, stool-based methylation assays could serve as early diagnostic tools to identify at-risk individuals long before clinical disease manifests, enabling targeted surveillance and prevention. Full article