Potentilla nepalensis belongs to the Rosaceae family and has numerous therapeutic applications as potent plant-based medicine. Forty phytoconstituents (PCs) from the root and stem through n-hexane (NR and NS) and methanolic (MR and MS) extracts were identified in earlier studies. However, the PCs affecting human genes and their roles in the body have not previously been disclosed. In this study, we employed network pharmacology, molecular docking, molecular dynamics simulations (MDSs), and MMGBSA methodologies. The SMILES format of PCs from the PubChem was used as input to DIGEP-Pred, with 764 identified as the inducing genes. Their enrichment studies have shown inducing genes’ gene ontology descriptions, involved pathways, associated diseases, and drugs. PPI networks constructed in String DB and network topological analyzing parameters performed in Cytoscape v3.10 revealed three therapeutic targets: TP53 from MS-, NR-, and NS-induced genes; HSPCB and Nf-kB1 from MR-induced genes. From 40 PCs, two PCs, 1b (MR) and 2a (MS), showed better binding scores (kcal/mol) with p53 protein of −8.6 and −8.0, and three PCs, 3a, (NR) 4a, and 4c (NS), with HSP protein of −9.6, −8.7, and −8.2. MDS and MMGBSA revealed these complexes are stable without higher deviations with better free energy values. Therapeutic targets identified in this study have a prominent role in numerous cancers. Thus, further investigations such as in vivo and in vitro studies should be carried out to find the molecular functions and interlaying mechanism of the identified therapeutic targets on numerous cancer cell lines in considering the PCs of P. nepalensis.

In this work, the leaves of K. tomentosa were macerated with hexane, chloroform, and methanol, respectively. The phytochemical profiles of hexane and chloroform extracts were unveiled using GC/MS, whereas the chemical composition of the methanol extract was analyzed using UPLC/MS/MS. The antibacterial activity of extracts was determined against gram-positive and gram-negative strains through the minimal inhibitory concentration assay, and in silico studies were implemented to analyze the interaction of phytoconstituents with bacterial peptides. The antioxidant property of extracts was assessed by evaluating their capacity to scavenge DPPH, ABTS, and H₂O₂ radicals. The toxicity of the extracts was recorded against Artemia salina nauplii and Caenorhabditis elegans nematodes. Results demonstrate that the hexane and chloroform extracts contain phytosterols, triterpenes, and fatty acids, whereas the methanol extract possesses glycosidic derivatives of quercetin and kaempferol together with sesquiterpene lactones. The antibacterial performance of extracts against the cultured strains was appraised as weak due to their MIC₉₀ values (>500 μg/mL). As antioxidants, treatment with extracts executed high and moderate antioxidant activities within the range of 50–300 μg/mL. Extracts did not decrease the viability of A. salina, but they exerted a high toxic effect against C. elegans during exposure to treatment. Through in silico modeling, it was recorded that the flavonoids contained in the methanol extract can hamper the interaction of the NAM/NAG peptide, which is of great interest since it determines the formation of the peptide wall of gram-positive bacteria. This study reports for the first time the biological activities and phytochemical content of extracts from K. tomentosa and proposes a possible antibacterial mechanism of glycosidic derivatives of flavonoids against gram-positive bacteria.

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood–brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski’s criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor–metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders.

Purpose The current treatment for Chagas disease, caused by Trypanosoma cruzi , presents significant limitations due to its variable efficacy depending on the stage of the disease and its associated adverse effects. This issue has driven research and the development of new therapeutic and preventive strategies, with a particular emphasis on vaccine design. Materials and methods In the present study, a bioinformatics approach was employed to evaluate T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) as a potential vaccine candidate by analysing its physicochemical and immunogenic properties. Results In this analysis, epitopes for B and T lymphocytes were predicted, and a predictive immune response determined that TcGAPDH has the capacity to induce a Th1-type response driven by IFN-γ and IL-2. Finally, molecular docking and dynamics simulation demonstrated favourable interaction between TcGAPDH and TLR2/TLR4 receptors, which remained constant throughout a 300 ns simulation. Conclusions These findings highlight the immunogenic potential of TcGAPDH and support its feasibility as a promising candidate for the development of a vaccine against Chagas disease.

Multiple sclerosis (MS), the most prevalent chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults, exhibits marked sexual dimorphism, with a 3:1 female-to-male ratio, but more severe symptoms and greater neurological damage in males. Increasing attention has focused on identifying circulating molecules that reflect inflammatory activity within the central nervous system and could clarify the mechanisms underlying MS. Pleiotrophin (PTN), a cytokine implicated in autoimmune and neurological diseases, is significantly elevated in patients with relapsing-remitting MS (RRMS). To explore the potential contribution of PTN and its receptors to neuroinflammatory signaling, we quantified the mRNA expression of PTN receptors in peripheral blood mononuclear cells from RRMS patients compared to untreated RRMS patients and healthy control subjects. We further performed an in silico molecular docking and molecular dynamics analysis to assess the possible functional significance of PTN-receptor interactions. Our results show a significant overexpression of integrin subunit beta-3 (ITGB3) mRNA in peripheral blood mononuclear cells from RRMS patients compared to healthy control subjects. Molecular docking shows that PTN could binds to the metal ion-dependent adhesion site domain of ITGB3 via Mg²⁺/Ca²⁺-mediated stabilization and has a higher binding affinity than fibrinogen, the canonical endogenous ligand. These findings suggest that ITGB3 could be a dynamically regulated integrin receptor in RRMS that may participate in PTN-driven neuroinflammatory pathways in peripheral blood immune cells, influenced by disease stage, sex, and immunotherapy. While our results support the biological plausibility of PTN–ITGB3 engagement, they remain hypothesis-generating and require functional validation. The integration of molecular expression data and computational modeling underscores the potential involvement of ITGB3 as a possible participant in MS and warrants further investigation of its clinical and mechanistic role.

The insecticidal property of ring C-seco limonoids has been discovered empirically and the target protein identified, but, to date, the molecular mechanism of action has not been described at the atomic scale. We elucidate on computational grounds whether nine C-seco limonoids present sufficiently high affinity to bind specifically with the putative target enzyme of the insects (ecdysone 20-monooxygenase). To this end, 3D models of ligands and the receptor target were generated and their interaction energies estimated by docking simulations. As a proof of concept, the tetrahydro-isoquinolinyl propenamide derivative QHC is the reference ligand bound to aldosterone synthase in the complex with PDB entry 4ZGX. It served as the 3D template for target modeling via homology. QHC was successfully docked back to its crystal pose in a one-digit nanomolar range. The reported experimental binding affinities span over the nanomolar to lower micromolar range. All nine limonoids were found with strong affinities in the range of −9 < ΔG < −13 kcal/mol. The molt hormone ecdysone showed a comparable ΔG energy of −12 kcal/mol, whereas −11 kcal/mol was the back docking result for the liganded crystal 4ZGX. In conclusion, the nine C-seco limonoids were strong binders on theoretical grounds in an activity range between a ten-fold lower to a ten-fold higher concentration level than insecticide ecdysone with its known target receptor. The comparable or even stronger binding hints at ecdysone 20-monooxygenase as their target biomolecule. Our assumption, however, is in need of future experimental confirmation before conclusions with certainty can be drawn about the true molecular mechanism of action for the C-seco limonoids under scrutiny.