Search Results (11,058)

This study evaluates the chemical composition and bioactivities of essential oils extracted from the leaves and twigs of Glycosmis lanceolata growing in a natural forest in Vietnam. gas chromatography–mass spectrometry identified 42 and 43 constituents in the leaf and twig oils, respectively. The main compounds in the leaf oil were (E)-β-caryophyllene (10.2%), β-bisabolene (23.7%), and brevifolin (21.3%), while the twig oil was dominated by β-bisabolene (11.6%) and brevifolin (12.7%). Neither oil exhibited inhibitory effects against two beneficial bacterial strains, Bacillus subtilis and Lactobacillus fermentum. In contrast, both oils showed weak antimicrobial activity against four pathogenic bacteria—Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa—and one yeast, Candida albicans, with IC₅₀ values ranging from 2012 ± 118 to 10,593 ± 557 µg/mL. Notably, the twig oil demonstrated pronounced anti-inflammatory activity via inhibition of nitric oxide production (IC₅₀ = 29.7 ± 2.58 µg/mL), whereas the leaf oil showed no detectable activity within the tested concentrations. Similarly, DPPH radical scavenging assays indicated stronger antioxidant activity for the twig oil compared to the leaf oil. These findings provide new insights into the phytochemistry and bioactivities of G. lanceolata essential oils and may support further investigations into their potential applications. Full article

Lactic acid bacteria (LAB), particularly members of the genus Lactobacillus, have emerged as promising biological agents with antimicrobial and anti-biofilm properties. While numerous individual studies have reported their inhibitory effects against pathogenic microorganisms, a systematic understanding that integrates their functional components, molecular mechanisms, and material-based applications remains lacking. In this review, we provide a comprehensive and component-oriented overview of LAB-mediated antimicrobial strategies. We first summarize secreted factors, including organic acids, bacteriocins, hydrogen peroxide, and extracellular vesicles, which collectively contribute to direct pathogen inhibition and environmental modulation. We then discuss cell-associated components such as surface-layer proteins and exopolysaccharides, highlighting their roles in adhesion interference and competitive exclusion. In addition, we examine whole-cell effects, including niche competition, quorum sensing disruption, and host immune modulation. Importantly, we place particular emphasis on the anti-biofilm activity of lactobacilli, detailing mechanisms involved in the prevention of the pathogen initial adhesion, disruption of extracellular polymeric substance matrices, and destabilization of mature biofilms. Finally, we explore emerging strategies that integrate lactobacilli with biomaterials, particularly hydrogel-based systems, to achieve controlled delivery, enhanced stability, and sustained antimicrobial activity. These biohybrid approaches represent a promising direction for the development of next-generation antimicrobial materials. These findings support the concept of LAB-based living antimicrobial materials as a next-generation strategy to combat biofilm-associated infections. Overall, this review aims to bridge the gap between molecular functions and translational applications of lactobacilli, providing new insights into its potential as a versatile platform for antimicrobial and anti-biofilm interventions. Full article

The high prevalence and incidence of neurodegenerative diseases pose a public health challenge and drive the search for alternative treatments. This study determined the chemical composition of hydroalcoholic extracts from the Antarctic species Polycauliona candelaria and Placopsis antarctica and evaluated their antioxidant and cholinesterase-inhibitory potential through in vitro assays and molecular docking. Using UHPLC/ESI/QToF/MS, 16 compounds were tentatively identified in P. candelaria and 11 in P. antarctica. P. antarctica exhibited greater antioxidant capacity (2.69 ± 0.15 mg GAE/g in TPC, and an IC₅₀ for DPPH and ABTS of 330.64 ± 0.02 and 63.33 ± 0.02 µg/mL, respectively) and inhibitory activity (IC₅₀ for AChE and BuChE of 654.42 ± 0.03 and 845.58 ± 0.01 µg/mL, respectively) similar to P. candelaria. Molecular docking analyses revealed that gyrophoric acid and stictic acid possess outstanding binding affinities, comparable to the drug galantamine, by effectively interacting with the catalytic sites of the enzymes. This is the first report on the chemical compounds present in extracts of P. antarctica and P. candelaria and contributes to the understanding of their therapeutic potential. Full article

Objectives: Neuroinflammation is recognized as a significant characteristic of Alzheimer’s disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation. Methods: In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism. Results: Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner. Conclusions: Maltol exhibits significant protective effects against Alzheimer’s disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer’s disease neuroinflammation using traditional Chinese medicine. Full article

This study focuses on the synthesis of glucovanillin mediated by UGT109A1 and its mechanism against Type 2 Diabetes Mellitus (T2DM). Recombinant UGT109A1 successfully synthesized glucovanillin from vanillin using UDP-Glc as the sugar donor. Through network pharmacology, 140 potential targets were identified. Seven key targets were further screened using LASSO and SVM-RFE algorithms. Among these, SLC5A1 and ADK showed strong diagnostic potential, with AUC values ranging from 0.85 to 0.89. Immune infiltration analysis linked these core targets to M2 macrophages. Single-cell transcriptomics revealed that ADK is widely expressed but enriched in B cells, while TLR9 is confined to plasmacytoid dendritic cells (pDCs). Cell-to-cell communication analysis identified a pDC-to-B cell signaling axis. In vitro assays demonstrated that glucovanillin exhibits concentration-dependent inhibitory activity against α-glucosidase with moderate potency, with an IC₅₀ of 413.84 ± 12.80 μM. Molecular docking, 200 ns molecular dynamics simulations (MD), and MM/PBSA calculations showed that glucovanillin binds more strongly to α-glucosidase (−7.4 kcal/mol) than vanillin (−5.4 kcal/mol). Therefore, the glycosylation mediated by UGT109A1 enhanced the bioactivity and targeting specificity of vanillin. In summary, glucovanillin exerts anti-T2DM effects through a dual mechanism involving α-glucosidase inhibition and regulation of key targets, making it a promising lead compound for T2DM treatment. Full article

Diabetes mellitus remains a major metabolic disorder requiring the development of new and effective α-glucosidase inhibitors. The present study aimed to identify, design, and optimize novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-α]pyrimidine derivatives with promising inhibitory activity against the α-glucosidase enzyme using a comprehensive in silico strategy. Approximately 300 molecular descriptors were calculated to characterize a dataset of 32 compounds (Peytam et al.) and to investigate the structural factors governing their biological activity. Based on these descriptors, a multiple linear regression model was developed to predict the inhibitory activities of the compounds against alpha-glucosidase. The developed model demonstrated satisfactory predictive performance and was internally and externally validated to ensure its accuracy, robustness, and reproducibility. In addition, the applicability domain analysis confirmed the reliability of the predictions. Using the validated QSAR model, seven new derivatives were designed with predicted pIC₅₀ values exceeding the maximum activity of the parent compounds. The leverage analysis demonstrated that all newly designed compounds were located within the applicability domain of the model, supporting the reliability of the predictions. To further evaluate their inhibitory potential, molecular docking studies were performed to investigate the interactions between the designed compounds and the α-glucosidase active site. The docking results revealed favorable binding interactions comparable to those reported for known α-glucosidase inhibitors. Furthermore, ADMET analysis indicated generally favorable pharmacokinetic properties, although potential CYP3A4 inhibition-related pharmacokinetic risks were identified and discussed. Molecular dynamics simulations, including replicated runs and MM/GBSA binding free energy calculations, confirmed the stability of the most promising protein–ligand complexes throughout the simulation period. In conclusion, this study proposes a robust and integrated computational workflow combining descriptor generation, QSAR modeling, applicability domain analysis, molecular docking, ADMET prediction, and molecular dynamics simulations for the rational design of potential α-glucosidase inhibitors. The findings highlight the therapeutic potential of the designed derivatives and provide a valuable in silico framework for the future development of antidiabetic agents. Full article

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of jellyfish venom in clinical practice. In our previous study, polyphenol epigallocatechin-3-gallate (EGCG) was found to neutralize the toxicity of jellyfish Nemopilema nomurai venom (NnV) in vivo and in vitro. Herein we further demonstrated that EGCG exerted its antagonistic effect against NnV through inhibiting the oxidative stress, pro-apoptotic proteins, and systemic inflammatory responses. Subsequently, we constructed a polyethylene glycol (PEG)-EGCG/tetracycline hydrochloride (HTC) co-loaded micellar nanocomplex in order to enhance the stability and bioavailability of EGCG in vivo, which successfully integrated the membrane-repair function of PEG, the enzyme inhibitory effect of HTC and the antioxidant properties of EGCG. Notably, this micellar nanocomplex demonstrated significant protective effects against both functional damage and pathological alterations in a non-lethal NnV-envenomed mouse model. When administered 1 h after NnV envenomation, EGCG (40 mg/kg), HTC and PEG-EGCG (containing 40 mg/kg EGCG) only partially improved abnormal blood biochemical indicators and moderately alleviated histopathologic damage, and PEG-EGCG/HTC containing merely 8 mg/kg EGCG completely mitigated the toxic reactions in envenomed mice. In the preventive regimen, the administration of EGCG, HTC or PEG-EGCG 30 min before exposure showed no significant improvement in abnormal blood biochemical indicators and histopathologic damage, while PEG-EGCG/HTC could still significantly improve the functional impairments and histopathologic damage of the heart and liver in NnV-envenomed mice. These findings suggest the clinical translational potential of PEG-EGCG/HTC against jellyfish envenomation. Full article

Secreted frizzled-related protein 4 (sFRP4) has traditionally been regarded as a Wnt antagonist with tumor-suppressive properties. However, growing evidence indicates that its role in cancer is far more complex and highly context-dependent. Depending on tumor type, molecular subtype, epigenetic state, and microenvironmental conditions, sFRP4 may exert either inhibitory or tumor-promoting effects. This functional heterogeneity has important implications for understanding cancer biology and for evaluating the clinical relevance of sFRP4. In this review, we summarize current knowledge of the structural features, regulatory mechanisms, and signaling functions of sFRP4, and discuss how these factors shape its diverse roles across malignancies. We further examine its potential significance in diagnosis, prognosis, therapeutic stratification, and systemic metabolic regulation. A clearer understanding of the context-specific behavior of sFRP4 may help refine its value as a biomarker and support the development of more precise and mechanism-informed therapeutic strategies. Full article

The COVID-19 pandemic highlighted the urgent need to develop effective and broad-spectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log₁₀), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle. Full article

The antimicrobial effect of Eucalyptus radiata essential oil nanoemulsion (EON) on Staphylococcus aureus and spoilage microorganisms was evaluated on fresh beef chunks during cold storage at days 0, 2, 4, 6, and 8. For this purpose, nanoemulsion was prepared using 2% eucalyptus oil combined with high methoxyl pectin, glycerol, and Tween 80, employing high shear force. Then the following were evaluated: (1) the essential oil’s chemical profile and in vitro antioxidant and antimicrobial capacities; (2) the nanoemulsion characteristics; and (3) the microbial counts of the beef treatments. The results showed that the essential oil’s primary components were o-cymene (45.4%), 2-bornene (26.29%), 1,8-cineole (11.31%), and α-pinene (9.25%). The EON had a particle size of 52.04 nm and a zeta potential of −9.16 mV. The in vitro studies revealed that both the essential oil and its nanoemulsion demonstrated significant antibacterial activity. Similarly, in in situ examinations, when the meat samples were spiked with S. aureus (0.1 × 10⁸ CFU/mL), the EON-treated meat samples had significantly (p ≤ 0.05) lower microbial counts than the untreated meat samples throughout the storage period; the difference between the treatments ranged between 1.62 and 2.44 log CFU/g. Additionally, the EON exhibited excellent antimicrobial efficacy against spoilage microorganisms on beef pieces during shelf life. On day 4, the maximum inhibitory activity was observed against total coliform, Pseudomonas spp., and yeast in reductions of 1.96, 2.09, and 2.18 log CFU/g in microbial counts, respectively. Moreover, application of meat samples with the EON delayed spoilage by 4 days. Therefore, the results of this study showed that coating beef chunks with the EON enhanced both product safety and shelf life. Full article

Photobiomodulation (PBM) is a non-invasive therapeutic strategy that uses red and near-infrared (NIR) light in the 590–950 nm range to modulate the cellular and molecular pathways involved in retinal homeostasis. At the molecular level, PBM acts primarily through photon absorption by cytochrome c oxidase (CcO, complex IV of the mitochondrial electron transport chain), whose four metal centres—two copper (CuA and CuB) and two heme groups (heme a and heme a₃)—absorb light across approximately 600–1000 nm. Photon capture promotes photodissociation of inhibitory nitric oxide (NO) from the binuclear CuB–heme a₃ centre, accelerates electron transfer, restores the proton-motive force and increases ATP synthesis. These primary events trigger a coordinated molecular programme that includes (i) transient mitochondrial reactive oxygen species (ROS) bursts that activate the Nrf2/Keap1/ARE axis and upregulate phase II antioxidant enzymes (HO-1, NQO1, GCLC, SOD2, catalase, GPx); (ii) calcium- and cAMP-dependent secondary signalling that converges on PI3K/Akt, MAPK/ERK, AMPK and mTOR pathways; (iii) suppression of NF-κB-driven cytokine production (TNF-α, IL-1β, IL-6) and of NLRP3 inflammasome activation; (iv) downregulation of the HIF-1α/VEGF axis, particularly at 590 nm; (v) anti-apoptotic remodelling of the Bcl-2/Bax ratio with reduced cytochrome c release and caspase-3/9 activation; and (vi) PGC-1α/TFAM/NRF1-driven mitochondrial biogenesis, alongside restoration of fission/fusion homeostasis (Drp1, Mfn1/2, Opa1) and PINK1/Parkin-mediated mitophagy. Wavelength specificity has a defined molecular basis: 590 nm modulates VEGF signalling and RPE pump activity, 660 nm interacts with the CuB centre and enhances O₂ binding at CcO, and 850 nm is absorbed by CuA and supports electron entry into complex IV. A second molecular axis is the bidirectional crosstalk between PBM and the circadian system: mitochondrial respiration, ATP turnover and CcO activity oscillate over the 24 h cycle under the control of the BMAL1/CLOCK and PER/CRY core machinery, the NAD⁺/SIRT1–SIRT3 axis and REV-ERBα. Preliminary preclinical and human observations suggest that NIR-induced bioenergetic and functional gains may be coupled to this rhythm, with greater benefit reported when light is delivered in the morning window (≈08:00–11:00); this time dependence should be regarded as an emerging hypothesis rather than an established clinical principle. The clinical evidence is unevenly developed across indications. It is most robust for non-exudative age-related macular degeneration, where multiwavelength PBM (590/660/850 nm; Valeda Light Delivery System) has shown disease-modifying potential in randomized controlled trials (LIGHTSITE I–III and the LIGHTSITE IIIB extension), with sustained BCVA gains and reduced incidence of geographic atrophy over 24 months and beyond. Evidence for retinitis pigmentosa, central serous chorioretinopathy and, with red-light monotherapy, childhood myopia is at present limited to small or short-term studies and remains preliminary. This narrative review synthesizes the molecular machinery engaged by PBM, integrates clinical findings across retinal diseases and discusses how chronotherapeutic delivery of light, aligned with the molecular clock, may further optimize therapeutic efficacy. Full article

Aronia melanocarpa is a rich source of anthocyanins with well-documented antioxidant and antidiabetic potential; however, their application is limited by low stability. In this study, extraction conditions were optimized using response surface methodology, with the highest total polyphenol content obtained at an ethanol concentration of 36.9% (v/v), an extraction temperature of 34.1 °C, and a solvent-to-solid ratio of 54.5 mL/g. The extract exhibited antioxidant activity and inhibited α-amylase in vitro, with an IC₅₀ value of 3.18 ± 0.27 mg/mL, compared with 6.76 ± 0.21 mg/mL for acarbose under the same assay conditions. Molecular modeling suggested that cyanidin derivatives may play a major role in the observed α-amylase inhibitory activity. The optimized extract was subsequently incorporated into yeast-derived β-glucan systems at different ratios to improve anthocyanin stability and formulation performance. Incorporation of β-glucan significantly modified dissolution behavior and reduced anthocyanin degradation in a ratio-dependent manner. The highest stabilization effect was observed for the aronia: β-glucan 1:2 system, in which the degradation rate decreased approximately 4.7-fold. Full article

The accumulation of histamine in fish products represents a significant food safety issue, particularly in skipjack tuna (Katsuwonus pelamis), due to its elevated histidine content. This study sought to isolate histamine-producing bacteria from skipjack tuna and assess the inhibitory effects of six plant-derived essential oils on bacterial proliferation and histamine synthesis. Seven bacterial isolates were obtained and screened, with histamine concentrations quantified via high-performance liquid chromatography (HPLC) following dansyl chloride derivatization. The isolate exhibiting the highest histamine production (1.2 ± 0.2 mM) was identified as Aeromonas hydrophila through 16S rDNA sequencing. Essential oils were administered to bacterial cultures prior to histamine quantification, and their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined in vitro. Among the tested oils, oregano and cinnamon demonstrated the strongest antibacterial activity, with MIC and MBC values below 1 mg/mL. Scanning electron microscopy analysis revealed pronounced structural damage to bacterial cells treated with these oils. At the MBC, histamine production was entirely suppressed; at half the MBC, histamine synthesis was reduced by more than 90%, whereas lower concentrations yielded moderate inhibition ranging from 15% to 22%. These findings suggest that selected essential oils, notably oregano and cinnamon, possess considerable potential as natural preservatives to reduce histamine formation in skipjack tuna. However, further investigation is necessary to confirm their effectiveness under practical storage conditions. Full article

Background: The global emergence of antibiotic resistance highlights the urgent need for novel therapeutic strategies, including adjuvants and potentiating compounds, against multidrug-resistant bacteria. Pseudomonas aeruginosa is classified by the World Health Organization (WHO) as a critical priority pathogen due to its high resistance potential and its ability to cause severe nosocomial infections. Beauvericin (BEA), a frequently detected mycotoxin, has been reported to exhibit various bioactive properties, including potential antibacterial and potentiating effects. Methods: The interaction between BEA and a last-resort antibiotic, colistin (COL), was evaluated in seven multidrug-resistant P. aeruginosa isolates using a microplate-based growth assay after preliminary MIC tests. Results: BEA at non-inhibitory concentrations (2.5–10 µg/mL) significantly enhanced the antibacterial activity of COL (1 and 2 µg/mL) in six out of seven isolates, resulting in a marked reduction in residual bacterial growth. Conclusions: BEA exhibited no measurable antibacterial activity at the concentrations used in the combination experiments but acted as a strain-dependent potentiator of colistin activity against multidrug-resistant P. aeruginosa. The observed enhancement of colistin-mediated growth inhibition supports the potential of BEA as an antibiotic adjuvant at clinically relevant colistin concentrations and provides a basis for further mechanistic investigation. Full article

Sand fly midgut microbiota plays a critical role in shaping Leishmania development and vector competence, yet functional evidence from natural vector populations remains limited. In this study, sand flies were collected between 2020 and 2022 in Cukurova region, Türkiye to characterize the gut bacterial composition of Phlebotomus tobbi and evaluate the anti-leishmanial potential of cultivable isolates. A total of 1739 sand flies were captured (878 females, 861 males), of which Ph. tobbi was the predominant species (n = 1312). 16S rRNA amplicon sequencing (V4–V6) showed that the gut microbiota was dominated by Proteobacteria, with Erwinia aphidicola/persicina representing the most abundant species across all analyzed groups. Fourteen cultivable bacterial species were identified by MALDI-TOF MS, including Serratia liquefaciens, Pantoea agglomerans, and Micrococcus luteus. Functional XTT assays against Leishmania infantum promastigotes demonstrated variable inhibitory activity among isolates. The strongest leishmanicidal effects were observed with S. liquefaciens (32.3%) and M. luteus (28.8%). Morphological examination confirmed promastigote rounding and cell death in isolates showing >25% activity. These findings define the gut bacterial landscape of Ph. tobbi in an endemic region and identify bacterial taxa with in vitro anti-leishmanial activity, highlighting their potential for future microbiota-based or paratransgenic control strategies. Full article