Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues.

Paraprobiotics are inactivated microbial cells or cell fractions that confer health benefits to the consumer, and possess the ability to regulate both the adaptive and innate immune systems. They exhibit anti-inflammatory, antiproliferative, antioxidant properties, and antimicrobial activities. The aim of this study is to evaluate these activities of Lacticaseibacillus paracasei lysates isolated from fermented palm sap. The bacterial cell lysates were prepared via sonication, and their antibacterial activity was assessed against three pathogens using agar well diffusion assay. Antioxidant activity was evaluated using DPPH and ABTS radical scavenging assays. Cytotoxicity and anti-inflammatory activity were determined in LPS-stimulated RAW 264.7 cells by measuring nitric oxide production, secretion, and mRNA level of cytokines (IL-1β, IL-6, and IL-10). Among the lysates, L. paracasei T1901 demonstrated the strongest antibacterial activity against Escherichia coli, Bacillus cereus, and Acinetobacter baumannii. Most lysates exhibited potent antioxidant activity, especially T0601 that showed the highest DPPH and ABTS radical scavenging activities. In LPS-stimulated RAW 264.7 cells, the lysates effectively reduced nitric oxide levels and suppressed the production of pro-inflammatory cytokines (IL-1β and IL-6); simultaneously, the lysates enhanced immunosuppressive cytokine IL-10 secretion. Furthermore, no cytotoxic effect was observed in the lysate-treated RAW 264.7 cells. The study highlights the potential of L. paracasei lysates as multifunctional agents with antibacterial, antioxidant, and anti-inflammatory properties. These findings support their application in developing functional foods or therapeutic agents for managing oxidative stress and inflammatory diseases.

Background and Aim: Acinetobacter baumannii is a multidrug-resistant (MDR) pathogen notorious for its biofilm formation and persistence in clinical and veterinary settings. Its resistance is exacerbated by quorum sensing (QS) pathways that regulate virulence and biofilm maturation. Disrupting QS and biofilm integrity using plant-derived compounds presents a promising alternative to traditional antibiotics. This study aimed to evaluate the antibiofilm and anti-QS potential of Paederia foetida Linn. ethanolic extract against A. baumannii, integrating gas chromatography–mass spectrometry (GC-MS) profiling, molecular docking, and in vitro assays. Materials and Methods: Leaves of P. foetida were extracted with ethanol and analyzed by GC-MS to identify major bioactive constituents. Molecular docking was conducted against five QS and biofilm-associated A. baumannii proteins (AF-A0A7S8WE28-F1-v4, AF-A0A059ZL64-F1-v4, AF-Q2VSW6-F1-v4, AF-A0A2P1B9S4-F1-v4, and AF-A0A5P9VY74-F1-v4). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and drug-likeness of key compounds were assessed in silico. Antimicrobial activity was determined by broth microdilution (minimum inhibitory concentration [MIC]/minimum bactericidal concentration [MBC]), and biofilm inhibition was evaluated through crystal violet microtiter assays. Morphological damage was examined using field emission scanning electron microscopy (FE-SEM). Results: GC-MS identified 30 phytoconstituents, with 5-hydroxymethyl-2-furaldehyde, 4H-pyran-4-one derivative, and eugenol as predominant compounds. Eugenol exhibited the highest binding affinity, particularly with AbaR (−6.3 kcal/mol). The extract showed significant antimicrobial activity (MIC = 7.81 mg/mL; MBC = 31.25 mg/mL) and dose-dependent inhibition of biofilm biomass (p < 0.001). FE-SEM imaging confirmed dose-responsive membrane damage and disruption of the biofilm. ADMET predictions revealed favorable oral bioavailability and low toxicity for selected compounds. Conclusion: P. foetida extract exhibits potent antibacterial, anti-QS, and antibiofilm activity against MDR A. baumannii, supported by its phytochemical diversity, favorable pharmacokinetics, and strong protein-ligand interactions. These findings suggest its promise as a plant-derived therapeutic aligned with the One Health framework to combat antimicrobial resistance in both human and veterinary medicine. Keywords: Acinetobacter baumannii, absorption, distribution, metabolism, excretion, and toxicity, biofilm disruption, eugenol, gas chromatography–mass spectrometry, molecular docking, One Health, Paederia foetida, quorum sensing inhibition.

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.

Staphylococcus aureus remains a major human pathogen and biofilm formation and antibiotic resistance make the treatment more difficult. Helianthus tuberosus L. (Jerusalem artichoke) is a phenolic-rich plant with reported antimicrobial properties, but its antibiofilm activity and putative AgrA-targeting constituents are poorly documented. In this study, an ethanolic H. tuberosus extract (SS-WU-1) was investigated against S. aureus ATCC 25923 and methicillin-resistant S. aureus (MRSA) ATCC 43300 using an integrated in vitro–in silico workflow. Minimum inhibitory concentration (MIC) values were >2.250 mg/mL and 1.125 mg/mL, respectively, and Minimum Bactericidal Concentration (MBC) values were >2.250 mg/mL for both strains. Sub-inhibitory treatment significantly reduced MRSA biofilm formation with 96.6 ± 0.5% inhibition at 1/2× MIC. Scanning electron microscopy showed decreased bacterial coverage, greater dispersal of cells and altered biofilm architecture. UHPLC-ESI-QTOF-MS/MS profiling yielded 677 tentatively annotated molecular features (481 ESI+ and 196 ESI−). A multiple linear regression QSAR model trained on 15 experimentally characterized AgrA inhibitors showed good fit (R² = 0.8749; Q²_LOOCV = 0.7017). Virtual screening and applicability-domain assessment prioritized P273, P385, and P348 for molecular docking against the AgrA LytTR domain. These compounds represent computationally prioritized candidates for experimental validation. Inhibition of biofilm formation without concomitant growth inhibition suggests a potential anti-virulence effect relevant to the prevention of device-associated infection. SS-WU-1 therefore represents a promising source for further investigation of antibiofilm phytochemicals, although the potential involvement of AgrA remains a hypothesis requiring experimental validation.

Muscle atrophy is defined as reductions in muscle size and function and represents a critical concern affecting elderly populations, immobilized patients, and individuals following specific dietary regimens, such as fasting and low-protein diets. This study investigated the protective effects of Stellaria dichotoma root extract and its isolated bioactive compounds during muscle atrophy using both in vitro and in vivo experimental models. First, S. dichotoma root extract prevented dexamethasone (DEX)-induced atrophy in C2C12 myotubes. Through systematic solvent partitioning and resin chromatography, five compounds (1–5) were successfully isolated from the n-butanol fraction. Dichotomine B (2) was identified as the most abundant and bioactive constituent. Treatment with dichotomine B significantly preserved the myotube diameter, enhanced the fusion index, and maintained the myosin heavy chain protein level while suppressing key atrophic biomarkers, including FoxO3a, MuRF-1, and Atrogin-1, in DEX-treated myotubes. Furthermore, dichotomine B (2) reduced proteolysis in serum-free cultured C2C12 myotubes and in mice subjected to 48 h of fasting, preserving muscle mass and strength. These findings suggest that S. dichotoma root extract and its principal compound, dichotomine B (2), have promising therapeutic potential and provide an opportunity to develop novel pharmacological interventions against muscle wasting through suppression of proteolysis pathways.