This study aimed to combine network pharmacology with in vitro experiments to identify the key targets and potential mechanisms of salidroside (Sal) in the treatment of acute lung injury (ALI). Potential targets related to Sal and ALI were retrieved from the ChEMBL, SuperPRED, SwissTargetPrediction, GeneCards, OMIM, and CTD databases. Overlapping targets were imported into the STRING database and Cytoscape software to construct a protein-protein interaction (PPI) network and identify core targets. Functional enrichment analysis of these core genes, including GO and KEGG pathways, was performed using the DAVID database. Two genes, MAPK14 and GPX4, directly relevant to subsequent validation, were selected for molecular docking analysis. Furthermore, an in vitro model of ALI was established using LPS-induced alveolar type II epithelial cells to verify the protective mechanism of Sal. A total of 355 potential targets associated with Sal in ALI treatment were identified. In vitro experiments showed that, compared to the LPS group, the Sal group exhibited significantly reduced secretion of IL-6, ROS, p-MAPK, MDA, and Fe²⁺, along with increased GPX4 expression and attenuated lung injury. Integrated network pharmacology and experimental validation suggest that Sal pretreatment alleviates inflammatory response and oxidative stress, likely through regulation of the MAPK/GPX4 signaling pathway, thereby providing protection against lung tissue injury.

Introduction Osteoarthritis (OA) is characterized by articular degeneration and chronic joint pain, partly resulting from synovial inflammation. Accumulating evidence suggests that alterations in the synovial ketone body metabolism (KBM) are closely associated with OA pathogenesis. This study aimed to investigate the metabolic changes in synovial tissues to optimize the treatment of clinical OA. Methods Analysis of OA and normal control synovial transcriptomic datasets extracted from the Gene Expression Omnibus (GEO) identified 808 differentially expressed genes (DEGs). These DEGs were integrated with KBM-related genes from the metabolic databases, yielding 50 candidates related to OA progression. Following enrichment analysis, protein-protein interaction network construction via STRING, and machine learning with expression analysis, two genes were identified as OA biomarkers: ACADL, encoding long-chain acyl-CoA dehydrogenase and ADH1B , alcohol dehydrogenase 1 B. Results The nomogram based on these data revealed high accuracy in the training and validation sets. Functional analysis revealed that these genes function in lipid oxidation, a process critical for synovial cell energy metabolism, as well as in the redox balance that prevents oxidative stress from worsening OA inflammation. Immune infiltration analysis revealed that their expression significantly correlated with 21 immune subtypes, including pro-inflammatory M1 macrophages and Th17 cells, which drive synovial inflammation. Molecular docking analysis identified progesterone and fomepizole as potential agents with satisfactory affinities for ACADL and ADH1B , respectively. Assessment of mouse models of OA confirmed a significant reduction in the synovium at the protein level. Discussion ACADL and ADH1B link KBM abnormalities to immune dysregulation in the OA synovium. The nomogram enables the precise early diagnosis of OA, and progesterone and fomepizole are promising targeted therapies. These findings deepen the current understanding of OA pathogenesis and support the advancement of personalized treatments for clinical translation.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and comorbid symptoms including anxiety and cognitive problems. The main pathological mechanisms underlying ASD are synaptic abnormalities and neuroinflammation. Ginger, commonly used as a spice, has been reported to enhance neurogenesis and attenuate inflammation in neurological disease; however, its effects on ASD remain unknown. This study aimed to investigate the therapeutic effects and molecular mechanisms of ginger extract (GE) in ASD. Prenatally valproic acid (VPA)-exposed mice were orally administered GE for 4 weeks from 6 weeks of age. Behavioral tests were performed to assess social interaction, anxiety, and cognitive functions. Network pharmacology and molecular docking analyses were used to predict targets and mechanisms of GE in ASD, which were verified using western blotting. Histological changes, including neurogenesis, neuroinflammation, and synaptic formation, were analyzed using immunostaining, western blotting, and qRT-PCR. GE ameliorated VPA-induced social deficits, anxiety-like behavior, and memory impairments. Network pharmacology identified AKT as a core molecular target of GE, and its active compounds exhibited high binding affinity for AKT. Consistent with these predictions, GE increased AKT and GSK3β phosphorylation in the hippocampus of mice, thereby restoring neuronal development, as evidenced by the increased Ki67- and DCX-positive cells. GE also mitigated gliosis and reduced STAT3 phosphorylation and TNF-α upregulation, thereby suppressing neuroinflammation and synaptic loss. GE alleviates ASD-like behaviors by promoting neuronal and synaptic development while suppressing neuroinflammation through AKT/GSK3β signaling, highlighting its potential as a natural supplement for ASD prevention.

Echinocandin B (ECB) biosynthesis in Aspergillus nidulans is primarily governed by multiple genes located within the biosynthetic echinocandin (ecd) gene cluster. The contributory functions of many genes, including transcription factors and tailoring enzymes of the ecd gene cluster, have been previously studied. The present study focused on determining the role of transporter proteins, EcdLp, EcdCp, and EcdDp, in ECB efflux using in silico and biochemical approaches. The molecular docking analysis revealed that ECB relatively showed higher binding affinity for EcdLp than the other co-clustered MFS transporters EcdCp and EcdDp, suggesting a preferred substrate of EcdLp. These results were further confirmed by heterologous integration of the ecdL gene in the ABC transporters-deficient Saccharomyces cerevisiae AD1-8u⁻, confirming active efflux. However, the binding of ECB in EcdLp is distinct from the R6G binding, overlapping the promiscuous site of farnesol, resulting in inhibition of R6G efflux in a dose-dependent manner. In conclusion, these results decipher the ECB binding and efflux mechanism and unveil the evolutionarily specialized architecture of EcdLp that permits targeted metabolite export in addition to environmental responsiveness, and lay the groundwork for optimizing ECB production via transporter engineering.

MG-101, a cysteine protease inhibitor identified through high-throughput screening, exhibits in vivo efficacy and synergy with remdesivir against SARS-CoV-2.

There is a need for dual action anti-virulence and anti-biofilm agents that target the opportunistic pathogen Staphylococcus aureus . Previous research determined that 0.8 mg/mL 4-ethoxybenzoic acid (4EB) reduced S. aureus ATCC 6538 biofilm formation by 88% relative to untreated controls with moderate inhibition of planktonic cell growth. Here we report that 4EB impacted S. aureus virulence phenotypes across all growth phases, including alpha-hemolysin (Hla) and serine protease (SplB/C) exoprotein production (60% reduction), staphyloxanthin pigment accumulation (73% reduction) and alpha-hemolysis (>87% reduction) compared to untreated control cells. RT-qPCR analysis demonstrated that 4EB downregulated virulence gene expression, including >100-fold reduction of alpha-hemolysin ( hla ) and leukocidins ( lukDvEv ), and a 35-fold decrease of the response regulator SaeR. Phenol-soluble modulin (PSM) transcription by biofilm-grown cells was upregulated by 4EB more than 4-fold for α1-4 psm and β1-2 psm genes, while δ -toxin ( hld ) was unaffected. In silico molecular docking analysis revealed that 4EB has a strong binding affinity (ΔG < −6.0 kcal/mol) for 9 virulence-associated transcriptional regulators, including SaeS, IcaR and CodY. Analysis of gene transcription during late exponential phase growth determined that genes controlled by 7 of the 9 identified regulators were significantly impacted by 4EB. The docking analysis identified putative 4EB binding sites that share common features including valine and tyrosine amino acid residues. The combined in vitro and in silico analyses identified interactions with well-known virulence genes but also implicated an effect of 4EB on proteins less commonly associated with S. aureus pathogenesis. These findings suggested potential alternative targets for anti-virulence and anti-biofilm therapeutics.

Background: Spinal cord injury (SCI) represents a form of traumatic damage to the central nervous system, and oligodendrocytes play a central role in SCI recovery. Ferroptosis is a major factor in the pathophysiological development of SCI symptoms. Pterostilbene (Pte) has antioxidant, anti-inflammatory, and neuroprotective effects. This study aims to investigate the potential role of Pte in SCI. Methods: A SCI model of rats was constructed. The BBB score assessment, the footprint test, EC staining, immunofluorescence (IF), and Western blot (WB) were conducted to observe the neuroprotective effects of Pte. The factors of ferroptosis, such as Glutathione (GSH), Malondialdehyde (MDA), Fe2+, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), were assessed. Then, transcriptomic data, network pharmacology, molecular docking analysis, and the erastin-induced ferroptosis model of OLN-93 cell lines were used to investigate the mechanism of inhibiting ferroptosis by Pte. Results: Pte treatment restored motor function and spinal cord tissue in SCI rats. Furthermore, Pte dramatically decreased oligodendrocyte ferroptosis. Finally, we discovered that Pte can repair SCI by blocking ferroptosis via the Keap1/Nrf2/SLC7A11/GPX4 axis. Conclusions: Pte reduces lipid peroxidation via the Keap1/Nrf2/SLC7A11/GPX4 axis, which reduces the development of ferroptosis in oligodendrocytes and improves locomotor function in rats with SCI.

In vitro and in silico evaluation of nematicidal lectin compounds from Artocarpus heterophyllus seeds targeting gastrointestinal helminths.

Integrated strategy of serum metabolomics, network pharmacology and experimental validation on revealing the bioactive metabolites and mechanism of Lycium ruthenicum Murr. against colorectal carcinoma.

Conformational dynamics and energetic perturbations in human β-spectrin-II mediated by calpain cleavage-related mutations: Insights from enhanced sampling simulations.

Herpetrione alleviates ANIT-induced cholestatic liver injury by targeting FXR to suppress NF-κB signaling.

Novel heterosteroids induce anabolic effects in human skeletal muscle cells: An integrated analysis of anabolic and catabolic signaling pathways.

Methyl 2-(7-hydroxy-3-methyloctyl)-1,3-dimethyl-4-oxocyclohex-2-enecarboxylate as a natural and potent antitubercular lead: An in silico study integrating molecular docking, molecular dynamics, FMO, and DFT analyses.

Phytochemicals as potential AXL inhibitors for cancer therapy: A computational study.

Epigallocatechin gallate (EGCG), the predominant catechin in green tea, has limited application due to its poor water solubility and instability. To address these issues, this study utilized recombinant sucrose phosphorylase to catalyze the glucosylation of EGCG, successfully synthesizing (-)-epigallocatechin gallate 4',4″-O-α-D-diglucopyranoside (EGCG-2G). The process was optimized using response surface methodology, achieving a 97.46% conversion rate of EGCG. EGCG-2G was purified to ≥ 99% purity by semi-preparative liquid chromatography. It exhibited approximately 124-fold higher water solubility than EGCG and demonstrated significantly enhanced stability under thermal and acidic conditions (50°C, pH = 5), with an 84.82% and 35.36% improvement over EGCG and commercial (-)-epigallocatechin-3-gallate-4'-O-α-D-glucoside (EGCG-1G), respectively. Furthermore, EGCG-2G displayed notable antioxidant, anti-inflammatory, and anti-melanogenic activities. It effectively scavenged intracellular and extracellular free radicals, reduced inflammatory cytokine levels, and inhibited melanin synthesis. Molecular docking and gene expression analyses suggested that its anti-melanogenic effect might be associated with the MC1R/cAMP/MITF signaling pathway.

Discovery of novel indoline derivatives as potent small molecule PD-L1 inhibitors.

Investigating the olfactory function of microplusin-like proteins in Rhipicephalus microplus through molecular docking and dynamics simulations.

The fate, acute and subchronic risks of momfluorothrin in the water-sediment system: A systematic study from the biological responses perspective.

Allicin attenuates age-related cognitive and neural decline in a rat model by modulating amyloid burden and regulating BDNF/NrF2 gene expression.

Integrated transcriptomic, metabolomic, and molecular docking analysis reveals the inhibitory mechanism of plumbagin against Penicillium expansum