Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Long-term use of Glucocorticoids produces skeletal muscle atrophy and microvascular rarefaction. Hydrogen sulfide (H2S) has a potential role in skeletal muscle regeneration. However, the mechanisms still need to be elucidated. This is the first study to explore the effect of Sodium hydrosulfide (NaHS) H2S donor, against Dexamethasone (Dex)-induced soleus muscle atrophy and microvascular rarefaction and on muscle endothelial progenitors and M2 macrophages. Rats received either; saline, Dex (0.6 mg/Kg/day), Dex + NaHS (5 mg/Kg/day), or Dex + Aminooxyacetic acid (AOAA), a blocker of H2S (10 mg/Kg/day) for two weeks. The soleus muscle was examined for contractile properties. mRNA expression for Myostatin, Mechano-growth factor (MGF) and NADPH oxidase (NOX4), HE staining, and immunohistochemical staining for caspase-3, CD34 (Endothelial progenitor marker), vascular endothelial growth factor (VEGF), CD31 (endothelial marker), and CD163 (M2 macrophage marker) was performed. NaHS could improve the contractile properties and decrease oxidative stress, muscle atrophy, and the expression of NOX4, caspase-3, Myostatin, VEGF, and CD31 and could increase the capillary density and expression of MGF with a significant increase in expression of CD34 and CD163 as compared to Dex group. However, AOAA worsened the studied parameters. Therefore, H2S can be a promising target to attenuate muscle atrophy and microvascular rarefaction.

Microbial exopolysaccharides (EPSs) are gaining interest as alternatives to chemical antioxidants and pharmaceuticals. This study mines the promising biomedical and antimicrobial potential of a marine bacterium, a prolific EPS producer, isolated from the Red Sea. Pseudomonas sp. strain AHG22 generated an EPS weighing 6.98 g·L⁻¹, coded EPSF8, subjected to FT-IR and HPLC chemical analysis. EPSF8 was then investigated for antioxidant assessment by 2,2-diphenyl-1-picrylhydrazyl (DPPH), H₂O₂, ABTS˙ ⁺ , nitric oxide, total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP). EPSF8 had an IC₅₀ of 46.99 μg·mL⁻¹ in the DPPH antioxidant assay and antioxidant capacities of 219.45 μg·mg⁻¹ ascorbic acid equivalent (AAE) in the TAC assay and 54.15 μg·mg⁻¹ AAE in the FRAP assay. The in vitro anti-inflammatory effect of EPSF8 was tested against 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymes and compared with the drugs ibuprofen and celecoxib used as controls. The IC₅₀ values of 5-LOX, COX-2, ibuprofen, and celecoxib were found to be 14.82, 15.49, 1.5, and 0.28 μg·mL⁻¹, respectively. Additionally, EPSF8 revealed antidiabetic activity toward α-amylase and α-glucosidase, and the IC₅₀ values were 93.1 and 127.28 μg·mL⁻¹, compared to those of acarbose (50.93 and 4.13 μg·mL⁻¹, respectively). Anti-obesity activity of EPSF8 by lipase inhibition revealed IC₅₀ = 56.12 μg·mL⁻¹ compared to orlistat (IC₅₀ = 20.08 μg·mL⁻¹) as a control. EPSF8 displayed antibiofilm and bactericidal activity against Gram-positive (G +ve) and Gram-negative (G −ve) ATCC pathogenic bacterial strains. It had a minimum bactericidal concentration/minimum inhibitory concentration ratio ≤2, indicating a broad bactericidal spectrum. Furthermore, EPSF8 is evidenced to have a promising anti-butyrylcholinesterase activity for the control of Alzheimer’s disease. The findings of the present analysis suggest that the isolated Pseudomonas sp. strain AHG22 EPS can potentially be explored as a promising green therapeutic compound.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

Introduction: Exopolysaccharides (EPSs) derived from marine microorganisms are a newly recognized reservoir of bioactive therapeutic compoundsMaterial and methods: We isolated a high EPS-yielding bacterial strain from the Red Sea, identified as Bacillus rugosus SYG20. Its purified EPS (EPSR9) contains 45.33% uronic acid, 9.98% sulfate groups, and 5.40% N-acetyl glucosamine. The HPLC chromatogram revealed four monosaccharides - glucose, xylose, galacturonic acid, and arabinose, in a distinct molar ratio of 2:3:1:1. EPSR9 showed a wide array of bioactivities.Results: It displayed antioxidant activity with an IC50 of 25.6 μg/ml in the DPPH assay and a total antioxidant capacity (TAC) of 417.77μg/ml equivalent AAE and 62.67 μg/ml equivalent AAE in Ferric reducing antioxidant power (FRAP) assays. It exhibited substantial anti-inflammatory properties. The anticoagulant effect of the EPS was demonstrated by a dose-dependent increase in prothrombin time. The scratch assay resulted in a 72.66% increase in wound closure, promoting in vitro wound healing after 48 h. Anti-obesity activity was evidenced by 83.8% lipase inhibition at 1000 μg/ml with IC50 of 107.73μg/ml. EPSR9 demonstrated inhibitory effects on α-amylase with an IC50 value of 14.37μg/ml and α-glucosidase with an IC50 value of 26.73 μg/ml, highlighting its potential as an anti-diabetic agent. Then, EPS showed bactericidal properties with MBC/MIC≤2 against both G+ve and G-ve bacteria, Staphylococcus aureus , Enterococcus faecalis (MIC=3.9μg/ml), Salmonella typhi, and Helicobacter pylori.Conclusions: The marine EPSR9 exhibited considerable potential for pharmaceutical applications as a multi-bioactive microbial metabolite. Its in vivo potency and mechanisms of action warrant further investigation.