Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to late diagnosis, rapid progression, and frequent chemoresistance. Despite advances in targeted therapy, durable responses are uncommon, underscoring the need for novel multitarget agents capable of modulating key oncogenic networks. Medicarpin, a natural pterocarpan phytoalexin, exhibits diverse pharmacological activities; however, its molecular mechanisms in OC are poorly defined. This study employed an integrative in silico framework combining network pharmacology, pathway enrichment, molecular docking, and survival analysis to elucidate medicarpin’s therapeutic landscape in OC. A total of 107 overlapping targets were identified, resulting in a dense protein–protein interaction network enriched in kinase-mediated and apoptotic signaling pathways. Ten hub genes were emphasized: CASP3, ESR1, mTOR, PIK3CA, CCND1, GSK3B, CDK4, PARP1, CHEK1, and ABL1. Gene Ontology and KEGG analyses demonstrated substantial enrichment in the PI3K–Akt/mTOR and prolactin signaling pathways. Docking revealed the stable binding of medicarpin to CASP3 (−6.13 kcal/mol) and ESR1 (−7.68 kcal/mol), supporting its dual regulation of hormonal and apoptotic processes. Although CASP3 and ESR1 expression alone lacked prognostic significance, their network interplay suggests synergistic relevance. Medicarpin exhibits multitarget anticancer potential in OC by modulating kinase-driven and hormone-dependent pathways, warranting further experimental validation.

The increasing prevalence of multidrug-resistant (MDR) pathogens, particularly ESKAPE bacteria, necessitates alternative antimicrobial strategies. Probiotics, particularly lactic acid bacteria, protect against pathogenic infections. This study aimed to characterize Schleiferilactobacillus harbinensis WU01, isolated from fermented palm sap, and evaluate its probiotic potential and antimicrobial activity. Its probiotic characteristics were assessed based on low-pH and bile tolerance, auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells. Antimicrobial activity against ESKAPE pathogens was evaluated using the agar well diffusion assay. Whole-genome sequencing (WGS) and in silico analysis were performed to identify bacteriocin-related genes, virulence factors, and antibiotic-resistance genes. WU01 exhibited a strong tolerance to gastrointestinal conditions, with high survival rates under acidic and bile-salt environments. S. harbinensis WU01 demonstrated significant auto-aggregation, high hydrophobicity, and strong adhesion to Caco-2 cells. Antimicrobial assays revealed inhibitory activity against MDR ESKAPE pathogens, which correlated with the presence of bacteriocin-related genes, including those homologous to Carnocin_CP52. Molecular dynamics (MDs) simulations confirmed the interaction of Carnocin_CP52 with bacterial membranes, suggesting a mechanism for pathogen disruption. WGS confirmed the absence of virulence and antimicrobial-resistance genes, confirming its safety for probiotic applications. These findings suggest that S. harbinensis WU01 possesses probiotic properties and antimicrobial activity against ESKAPE pathogens. The combined results highlight its potential application in functional foods and therapeutic interventions.

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer whose prevalence is rising, particularly in Thailand, is marked by elevated oxidative stress driven by chronic inflammation, parasitic infections, and dysregulated redox signaling. This study investigates the anticancer potential of tiliacorinine using a silico approach, including drug-likeness, ADMET, network pharmacology, molecular docking, and dynamics simulations. Tiliacorinine and 216 predicted targets were identified, with 79 overlapping CCA-related genes from GeneCards. GO and KEGG analyses revealed involvement in cell migration, membrane structure, kinase activity, and cancer-associated pathways. Network and PPI analyses identified ten key targets, including SRC, HIF1A, HSP90AA1, NFKB1, MTOR, MMP9, MMP2, PIK3CA, ICAM1, and MAPK1. Tiliacorinine showed the strongest affinity for MTOR (−10.78 kcal/mol, K_i = 12.62 nM), binding at the same site as known inhibitors with superior energy and specificity, supported by hydrogen bonding at ASP950 and hydrophobic interactions. Tiliacorinine also demonstrated strong binding to SRC, MMP9, and MAPK1. Molecular dynamics simulations revealed stable binding of tiliacorinine to MTOR, particularly at residues ASP950, TRP1086, and PHE1087. Comparative analysis with the MTOR–GDC-0980 complex confirmed consistent interaction patterns, reinforcing the structural stability and specificity of tiliacorinine. These results highlight its strong pharmacological potential and support its candidacy as a promising lead compound for cholangiocarcinoma therapy.

Background/Objectives: Severe and recurrent infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa necessitate alternative antimicrobial strategies. Fermented cacao beans represent a niche microbial ecosystem with the potential to harbor beneficial lactic acid bacteria (LAB). This study aimed to isolate and characterize LAB strains from fermented cacao beans in southern Thailand and to evaluate their probiotic potential and antimicrobial activity against MDR P. aeruginosa. Methods and Results: Five Lactiplantibacillus plantarum isolates were identified via MALDI-TOF MS and whole-genome sequencing (WGS). All strains demonstrated antimicrobial activity against 17 clinical MDR P. aeruginosa isolates and CR14 exhibited the largest inhibition zone. The isolates displayed robust probiotic traits, including survival under simulated gastrointestinal conditions. Acid tolerance (pH 2.0) reached 61.15 ± 7.75%, while resistance to pepsin, pancreatin, and bile salts exceeded 88%, 91%, and 92%, respectively. Strong adhesion was confirmed via auto-aggregation (55.02 ± 1.75%), hydrophobicity (45.58 ± 0.96%) and Caco-2 cell attachment (up to 98.11 ± 3.28%). WGS revealed multiple plantaricin-encoding clusters. Coarse-grained molecular dynamic simulations showed that two-peptide plantaricins (plnJ/K and plnNC8-αβ) self-assembled and formed stable pores in bacterial membrane models, confirming a pore-forming antimicrobial mechanism. The strains lacked acquired resistance genes and virulence factors, confirmed by in silico safety assessments. Conclusions: Thus, these L. plantarum strains are promising probiotics for managing MDR P. aeruginosa via functional foods or adjunct therapies.

Acne vulgaris is a common chronic inflammatory skin condition. Conventional acne treatments are often limited by adverse effects, driving interest in alternative therapies. This study explored the multifunctional bioactivities of a lyophilized cell-free supernatant (LCFS) derived from Lacticaseibacillus paracasei T0901, isolated from fermented palm sap, with a focus on its antimicrobial, antibiofilm, and antimelanogenic potential for dermatological applications. Antimicrobial activity was evaluated using agar well diffusion and broth microdilution assays against acne-associated pathogens, while antibiofilm effects were quantified via crystal violet staining. Antimelanogenic activity was assessed in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells by measuring melanin content and tyrosinase activity. Whole-genome sequencing was performed to identify genes linked to observed bioactivities, and molecular docking was used to predict metabolite–protein interactions. The LCFS exhibited strong inhibitory activity against acne-associated bacteria, with inhibition zones of C. acnes (10.67 ± 0.58 mm), S. epidermidis (21.00 ± 0.00 mm), and S. aureus (20.00 ± 0.00 mm), and a minimum inhibitory concentration of 25 mg/mL. Biofilm formation was significantly reduced by 62.98 ± 3.54%. In α-MSH-stimulated B16F10 cells, LCFS treatment (10 mg/mL) significantly decreased melanin content (73.23 ± 2.36%) and intracellular tyrosinase activity (68.19 ± 6.29%) relative to control. Genomic analysis revealed antioxidant-related genes (sodA, trxB, nox), pigmentation regulators (mco, fcbD), and buk (butyrate kinase), supporting the observed bioactivities. Molecular docking further demonstrated strong binding affinities of LCFS-derived metabolites to tyrosinase and MITF, suggesting modulation of melanogenic pathways. Collectively, these results indicate that L. paracasei T0901 produces safe postbiotic compounds with potent antimicrobial, antibiofilm, and antimelanogenic activities, highlighting its promise as a multifunctional ingredient in probiotic-based skincare formulations.

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 $\mathsf{\mu }$s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins.