Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen with substantial genetic diversity shaped by human co-evolution. Although extensive research has been conducted on H. pylori, the mechanisms underlying its adaptation and virulence remain incompletely understood. Here, we performed a phylogenomic analysis of 1467 isolates from 26 countries by constructing a core-genome single-nucleotide polymorphism (SNP) phylogeny and analyzing population structure, revealing five major lineages with distinct regional adaptations. A genome-wide Fixation Index (Fst) analysis identified 20 highly differentiated genes, with cagE (Fst = 0.8041)—a key component of the Type IV Secretion System (T4SS)—showing the strongest signal of positive selection. We discovered a novel N792D mutation in cagE, fixed in cluster c1, particularly in North America, which may enhance immune evasion and promote persistent colonization. Bayesian Evolutionary Analysis Sampling Trees 2 (BEAST2) analysis estimated that the most recent common ancestor (tMRCA) of highly virulent H. pylori emerged around 1934 (95% HPD: 1933–1934), coinciding with global conflicts and migrations that likely facilitated its spread. This study provides new insights into H. pylori evolution, highlighting the cagE mutation as a potential therapeutic target.
Psoriasis, a prevalent immune-mediated inflammatory skin disease, has a complex pathogenesis involving genetic predisposition, immune system dysregulation, and environmental triggers. Despite its prevalence, treatment options remain limited. Tripteaser wilfordii Hook (TWH), a traditional Chinese medicine, has shown potential in treating psoriasis, and recent studies suggest that its therapeutic effects may be related to its ability to modulate the immune system and microecological balance, similar to how medical ozone therapy has been found to influence immune regulation and inflammation in psoriasis. This study aimed to explore the targets and pathways of psoriasis treatment, focusing on symptom relief, prevention of disease progression, improvement of quality of life, and the integration of psychological health. TWH compound preparation against psoriasis using network pharmacology and molecular dynamics.
The methodology involved screening active compounds of TWH from the TCMSP database and retrieving psoriasis-associated genes from multiple sources. Key hub genes were identified through topological analysis of the constructed protein–protein interaction (PPI) network with Cytoscape 3.8.2. Potential mechanisms were explored via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The interaction between compounds and proteins was predicted using molecular docking and molecular dynamics simulations with Auto Dock Vina and Chimera 1.15.
We identified 15 active compounds from TWH, along with 88 psoriasis-related targets. Network analysis identified key hubs, including AKT1, ESR1, TP53, STAT3, TNF, BCL2, JUN, HSP90AA1, CASP3, and RELA. Pathway enrichment analysis revealed mechanisms primarily involving inflammation and immune responses. SwissADME profiling nominated Zhebeiresinol, Kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5- methylcoumarin-3-yl) coumarin as promising lead candidates. Molecular docking and dynamics simulations confirmed that 5,8-Dihydroxy-7-(4-hydroxy-5-methylcoumarin-3-yl) coumarin and kaempferol bind stably to the STAT3 protein. This binding is primarily driven by van der Waals forces, suggesting their potential as natural product-derived therapeutics for psoriasis.
We have identified fixed-dose combinations of 5,8-Dihydroxy-7-(4-hydroxy-5- methylcoumarin-3-yl) coumarin and kaempferol as part of novel target strategies for psoriasis, which inhibit specific JAK-STAT signaling pathway simultaneously, leading to superior efficacy and the ability to counter drug resistance.