Search Results (209)

Aeromonas hydrophila is an important zoonotic bacterium that is related to multiple diseases in humans, terrestrial animals, and aquatic animals. Bacterial septicemia caused by A. hydrophila often results in high mortality and severe economic losses. Antibiotics, the major approach to dealing with bacterial infections, are limited due to the occurrence of antibiotic resistance. Anti-virulence strategies provide a promising approach to combat resistant bacterial infections. Here, growth curves, hemolysis, biofilm formation, and animal studies were performed to investigate the effect of fisetin against A. hydrophila. Moreover, RNA-seq technology was employed to determine the potent mechanism of fisetin. The results showed that fisetin could dose-dependently reduce the hemolytic activities mediated by aerolysin and hinder biofilm formation. Animal studies showed that treatment with 50 mg/kg fisetin could remarkably reduce the mortality to 40% in the infected group compared with fish in the fisetin-free group. Further, transcriptome analysis demonstrated that there were 565 differentially expressed genes (DEGs) after treatment with 16 μg/mL fisetin. Fisetin significantly impacted the pathways related to oxidative phosphorylation, the citrate cycle, and virulence factor regulation. Furthermore, 159 virulence-related genes were influenced after fisetin treatment. Collectively, these findings revealed that fisetin could mitigate the pathogenicity of A. hydrophila by affecting oxidative phosphorylation and the citrate cycle pathway as well as inhibiting the production of virulence factors. The study not only identified a powerful substance for managing A. hydrophila-associated diseases in aquaculture but also clarified the mechanism of plant medicines in controlling diseases caused by bacterial pathogens. Full article

Anemia remains a widespread public health concern, and the search for interventions demonstrating potent anti-anemic activity is critical for reducing its impact among high-risk populations. Conventional iron therapies are associated with several complications and potential adverse effects. This study explored a polyherbal approach to develop a safer and more effective alternative treatment for anemia. A molecular docking study was initially performed to screen and evaluate alizarin, catechin, kaempferol, recesmol, rubiadin, and rutin, which are known for their antioxidant and hematinic potential. Using AutoDock Vina, these compounds were docked against the target protein (PDB ID: 6MOE) with EPE and ferrous ions as controls. Rutin demonstrated the highest binding affinity of −6.4 kcal/moL, whereas alizarin and rubiadin both followed closely with −6.3 kcal/moL, while kaempferol and ellagic acid exhibited a binding affinity of −6.2 kcal/moL. In comparison, the reference compounds tested ferrous ions, and native ligand EPE (−5.0 kcal/moL) and iron (−4.8 kcal/moL), showed mild affinities. Moreover, the tested compounds demonstrated stable binding, suggesting their potential relevance in modulating anemia-related pathways. Based on the docking results and traditional therapeutic values, a polyherbal formulation (PHF) was developed using methanolic extracts of Trigonella foenum-graecum, Emblica officinalis, Pterocarpus marsupium, Withania somnifera, Asparagus racemosus, Zingiber officinale, Rubia cordifolia, Boerhavia diffusa, and Adhatoda vasica. Phytochemical screening via HPTLC analysis was used to quantify the presence of gallic and ellagic acids. In addition, PHF showed significant antioxidant potential (DPPH IC₅₀: 14.29 µg/mL; FRAP IC₅₀: 58.57 µg/mL) and iron content (98.47 ppm) values. Furthermore, in vivo evaluation using a phenylhydrazine-induced hemolytic anemia model in Sprague Dawley rats revealed that the PHF achieved complete restoration of RBCs (6.15 ± 0.04), hemoglobin (14.82 ± 0.03 g/dL), and hematocrit (43.08 ± 0.28%) in anemic rats and improved histopathological features in the liver, spleen, and bone marrow. These results demonstrate that combined molecular and pharmacological evidence support the efficacy of PHF as a promising candidate for the management of anemia by enhancing erythropoiesis, improving iron metabolism, and reducing oxidative stress. Full article

Fermented apple juice (FAJ), a nutrient-dense beverage rich in vitamins, offers multiple health benefits, including improved digestion, enhanced fat metabolism, and sustained energy provision with reduced caloric intake. To advance the development of probiotic-enriched flavored and functional juices, this study establishes Lactiplantibacillus plantarum (L. plantarum) as a safe and effective starter culture for apple juice fermentation. The selected strain exhibited minimal biogenic amine synthesis, producing only 30.55 ± 1.2 mg/L of putrescine and 0.59 ± 0.55 mg/L of cadaverine, while histamine and tyramine were undetectable. Furthermore, the strain demonstrated no hemolytic activity and exhibited robust biofilm-forming capacity, reinforcing its suitability for fermentation applications. An electronic nose analysis revealed that L. plantarum significantly enriched the volatile compound profile of FAJ, leading to an improved flavor profile. The strain also displayed excellent growth adaptability in the apple juice matrix, further optimizing fermentation efficiency and sensory quality. Crucially, 16S rRNA sequencing demonstrated that FAJ specifically restructures the gut microbiota in obese individuals, significantly elevating the relative abundance of beneficial genera, including Enterococcus, Parabacteroides, and Bifidobacterium (p < 0.05). Concurrently, FAJ enhanced glycolytic activity, suggesting a potential role in metabolic regulation. Collectively, these findings confirm that L. plantarum-fermented FAJ combines favorable sensory properties and safety with promising anti-obesity effects mediated through gut microbiome modulation and metabolic pathway activation. This study provides a critical scientific foundation for designing next-generation functional fermented beverages with targeted health benefits. Full article

Nowadays, healthcare systems face two global challenges: the rise of multidrug-resistant pathogens and the growing incidence of cancer. Due to their broad spectrum of activities, antimicrobial peptides emerged as potential alternatives against both threats. Our group previously described the antifungal activity of the α-helical peptide Cm-p5, a derivative of the natural peptide Cm-p1, isolated from the coastal mollusk Cenchritis muricatus; however, its anti-cancer properties remained unexplored. Analyses through calorimetry and molecular dynamics simulations suggest the relevance of phosphatidylserine for the attachment of Cm-p5 to cancer cell membranes. Cm-p5 exhibited cytotoxic activity in a dose-dependent manner against A375 melanoma cells, without toxicity against non-malignant cells or hemolytic activity. DAPI/PI and DiSC3(5) staining confirmed permeabilization, disruption, and depolarization of A375 cytoplasmic membranes by Cm-p5. Furthermore, Annexin V-FITC/PI assay revealed the induction of cellular death in melanoma cells, which can result from the cumulative membrane damage and oxidative stress due to the overproduction of reactive oxygen species (ROS). Moreover, after the treatment, the proliferation of A375 cells was dampened for several days, suggesting that Cm-p5 might inhibit the recurrence of melanomas. These findings highlight the multifunctional nature of Cm-p5 and its potential for treating malignant melanoma. Full article

Herpes simplex virus type 1 (HSV-1) is a globally prevalent pathogen that can infect a variety of animal species as well as humans. However, existing antiviral therapies are constrained in their capacity to effectively target viral latency and prevent recurrent infections. Antimicrobial peptides (AMPs), particularly cathelicidins, as part of innate immune system have demonstrated broad-spectrum efficacy against viral pathogens. In this study, four peptides derived from Elephas maximus cathelicidin EM were designed and optimized (EM-1 to EM-4). We identified low toxicity peptide derivatives through hemolytic and cytotoxicity assays, quantified their anti-HSV-1 activity by determining IC₅₀. Antiviral mechanisms were investigated using RT-qPCR and antiviral efficacy was ultimately validated in C57BL/6J mice through viral load quantification in brain, lung, and heart tissues. Our findings revealed that EM-1 significantly inhibited HSV-1 replication in U251 cells. In a murine footpad inoculation model, EM-1 administration substantially reduced viral loads and alleviated inflammatory responses. Histological assessment demonstrated that EM-1 treatment mitigated HSV-1 induced tissue damage in infected mice. We also found that EM-1 exerted its antiviral effects by upregulating the expression of interferon-gamma and its downstream genes, such as ISG15 and MX1. These findings indicated that EM-1 is a dual function peptide that inhibits replication of HSV-1 as well as enhances host antiviral immunity. Collectively, this study highlights the therapeutic potential of elephant cathelicidin derived peptides in antiviral development. Full article

Chagas disease (ChD) caused by Trypanosoma cruzi remains a major public health concern, affecting approximately 8 million people worldwide. However, the number of undiagnosed cases is likely much higher. Existing treatments rely on benznidazole and nifurtimox which, despite their efficacy during the acute phase of infection, are often associated with severe side effects that can be life-threatening. As a promising alternative, actinomycetes—which are renowned for producing pharmacologically and industrially relevant metabolites—have demonstrated potent antimicrobial properties; however, their antiparasitic potential remains largely unexplored. This study evaluated the anti-trypanocidal activities of extracellular metabolites produced by Streptomyces thermocarboxydus strain Chi-43 (ST-C43) and Streptomyces sp. strain Chi-104 (S-C104) against epimastigote, trypomastigote, and amastigote forms of T. cruzi. The strains were cultured in ISP2 broth, and their extracellular metabolites were assessed via antiparasitic diffusion assays in microplates. The 50% lethal concentration (LC₅₀) values ranged from 102 to 116 μg/mL against epimastigotes and trypomastigotes. The antiparasitic activity was confirmed through 3-(4,5-dimetiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based spectrophotometric assays and optical microscopy. Toxicity assays revealed that the extracellular metabolites were non-toxic to Artemia salina, non-cytotoxic to Huvecs, and non-hemolytic to human erythrocytes. Dose–response regression analysis showed statistically significant differences (p ≤ 0.05). LC-MS/MS analysis identified amphomycin and K-252c aglycone staurosporine as the active antiparasitic compounds. These findings highlight the potential of Streptomyces-derived extracellular metabolites as novel, selective, and safe anti-T. cruzi agents. Nevertheless, further studies in murine or preclinical models are needed to validate their efficacy and support future clinical applications for the treatment of ChD. Full article

Background/Objectives: Medicinal plants such as Santolina chamaecyparissus L., an evergreen shrub from the Asteraceae family, have long been valued for their bioactive compounds and traditional therapeutic uses. Materials: In this study, the essential oil of S. chamaecyparissus (EOSC) was isolated via hydrodistillation and then comprehensively evaluated for its phytochemical composition and antioxidant, anti-inflammatory, hemolytic, and cytotoxic properties, as well as its in silico bioactivity. Results: In total, 89.5% of the essential oil composition was successfully identified using GC-MS analysis. Hydrocarbon sesquiterpenes constituted the largest fraction (36.0%), followed by oxygenated sesquiterpenes (19.7%). Phytochemical screening revealed high phenolic content (839.50 ± 5.0 mg GAE/g E.O), while the Total Antioxidant Capacity (TAC) assay confirmed its strong antioxidant potential. The oil showed moderate hemolytic activity and significant lipoxygenase inhibition, indicating anti-inflammatory capability. The cytotoxic effects of the EOSC were evaluated using the MTT assay and HepG2 liver cancer cells. A dose-dependent reduction in cell viability was observed, confirming the oil’s strong anticancer activity. Molecular docking and ADMET analyses supported the bioactivity of the identified compounds, which showed good drug-likeness and pharmacokinetic properties. Conclusions: These findings demonstrate that EOSC has promising antioxidant and anti-inflammatory properties, suggesting that it could have potential as a safe natural substance for use in drug development and food preservation. Full article

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against Candida species. We evaluated the responses of nine reference species of Candida spp. and one hundred clinical isolates of C. albicans to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive Candida species, C. albicans and C. parapsilosis. The frequency of spontaneous mutations occurring in these two Candida species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in C. albicans and C. parapsilosis cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10⁻⁵ to 1.2 × 10⁻⁴ per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti-Candida agent. Full article

Strophanthus sarmentosus is recognised for various ethnomedicinal applications, including treatment after snakebites. However, only limited scientific evidence exists on its antivenomous capabilities. This study investigates the efficacy of methanol and ethylacetate extracts from S. sarmentosus leaves and roots against Echis ocellatus venom. A non-toxic range for the extracts was determined in rats, and assays were performed to test their anti-hemorrhagic and anti-hemolytic activity as well as their influence on venom-induced blood clotting. In all of these experiments, the extracts demonstrated significant positive effects equal to or better than antivenom. Moreover, the extracts strongly inhibited and even abolished the digestion of the vasoactive neuropeptide bradykinin by snake venom metalloproteinases. Strophantus plants are known for their high content of cardiac glycosides, one of which is the commercially available ouabain, that by itself also considerably inhibited venom-induced bradykinin cleavage. Although ouabain is only present in low amounts in S. sarmentosus when compared to other cardenolides of similar structure, it can be hypothesized that members of this substance class may also have inhibitory properties against venom proteases. S. sarmentosus additionally contains bioactive substances such as flavonoids, terpenoids, tannins, saponins, and alkaloids, which contribute to its protective effects. The study provides scientific data to explain the success of the traditional use of S. sarmentosus plant extracts as a first aid against envenomation in rural Africa. Full article

Listeriosis is a disease associated with the consumption of food contaminated with Listeria monocytogenes. Probiotic lactic acid bacteria (LAB) or their postbiotics have been of interest for their anti-listerial effect. This study focused on isolating LAB from artisanal cheeses and characterizing their potential as probiotics. Twelve LAB isolates exhibiting typical LAB traits were evaluated for their ability to survive in simulated gastric juice, hydrolyze bile salts, auto-aggregate, hydrophobicity, and antagonistic activity against L. monocytogenes. The four most promising LAB strains demonstrated anti-listerial probiotic potential and were identified as Latilactobacillus (Lat.) curvatus SC076 and Lactiplantibacillus (Lact.) paraplantarum SC291, SC093, and SC425. The antimicrobial activity of these strains was mainly attributed to bacteriocin-like substances and organic acids. While three Lact. paraplantarum strains were resistant to ampicillin, Lat. curvatus was sensitive to all tested antibiotics. All selected strains exhibited no hemolytic, gelatinase, and lecithinase activity. Exposure to LAB supernatants resulted in a significant reduction in the adhesion and intracellular count of L. monocytogenes in Caco-2 cells, with Lat. curvatus SC076 showing the most significant effect. Based on its probiotic characteristics, Lat. curvatus SC076 is a promising candidate for functional foods, pending further in vivo studies to assess its potential in the food industry. Full article

Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization. Methods: WT and Nrf2-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli. Results: Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation. Conclusions: These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization. Full article

Dairy cows are highly susceptible to mastitis caused by Klebsiella pneumoniae, and treating these infections poses a challenge due to the resistance of the bacterium to common antibiotics. This study aimed to evaluate the safety of W. cibaria SDS2.1 and investigate its protective effects against K. pneumoniae-induced mastitis. The safety of W. cibaria SDS2.1 was assessed through comprehensive analyses, including antibiotic resistance profiling, hemolysis assays, cell cytotoxicity tests, and whole-genome sequencing. Furthermore, its ability to protect against cellular and tissue damage caused by K. pneumoniae-induced mastitis was evaluated using both in vitro and in vivo models. Our results revealed that W. cibaria SDS2.1 was non-hemolytic, non-cytotoxic, and significantly inhibited the growth of K. pneumoniae (p < 0.05). Additionally, W. cibaria SDS2.1 effectively reduced the adhesion and invasion of K. pneumoniae. In the K. pneumoniae-induced mouse mastitis model, W. cibaria SDS2.1 significantly reduced myeloperoxidase (MPO) activity, mammary tissue damage, and the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) (p < 0.05). In K. pneumoniae-infected bovine mammary epithelial cells (bMECs), W. cibaria SDS2.1 significantly decreased lactate dehydrogenase (LDH) release, indicating reduced cellular damage. These findings demonstrate that W. cibaria SDS2.1 exhibits anti-inflammatory properties in experimental models, suggesting its potential role in mitigating K. pneumoniae-induced mastitis. Full article

Lactiplantibacillus plantarum GUANKE (L. plantarum GUANKE) is a Gram-positive bacterium isolated from the feces of healthy volunteers. Whole-genome sequencing analysis (WGS) revealed that the genome of L. plantarum GUANKE consists of one chromosome and two plasmids, with the chromosome harbors 2955 CDS, 66 tRNAs, and 5 rRNAs. The genome is devoid of virulence factors and Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems. It contains three intact prophage regions and bacteriocin biosynthesis genes (plantaricins K, F, and E), as well as seventeen genomic islands lacking antibiotic resistance or pathogenicity determinants. Functional prediction outcomes identified that the genome of L. plantarum GUANKE is closely related to transcription, carbohydrate transport and metabolism, and amino acid transport and metabolism. Carbohydrate-active enzymes (CAZymes) analysis and GutSMASH analysis revealed that the genome of L. plantarum GUANKE contained 100 carbohydrate-active enzyme genes and two specialized metabolic gene clusters. Safety assessments confirmed that L. plantarum GUANKE neither exhibited β-hemolytic activity nor harbored detectable transferable drug resistance genes. The strain exhibited remarkable acid tolerance and bile salt resistance. Cellular adhesion assays demonstrated moderate binding capacity to Caco-2 intestinal epithelium (4.3 ± 0.007)%. In vitro analyses using lipopolysaccharide (LPS)-stimulated macrophage models demonstrated that L. plantarum GUANKE significantly suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), exhibiting dose-dependent anti-inflammatory activity. In vivo experiments showed that L. plantarum GUANKE was involved in the regulation of the apical junction pathway and interferon pathway in colon tissue of normal mice. Full article

Nosocomial fungal infections caused by Candida auris pose a threat to public health due to their increased resistance to common antifungal drugs. Four thiourea derivatives of 2-thiophenecarboxylic acid were evaluated for their antifungal and antioxidant activity. The antifungal activity of the compounds was tested against strains of C. auris isolated from a hospital in Romania. With a notable inhibitory effect on C. auris biofilm growth and microbial adherence, the ortho-methylated derivative (SB2) showed the highest antifungal activity. Furthermore, emphasizing the impact of structural factors on the electron-donating capacity of these compounds, antioxidant activity assays (DPPH, FRAP, TEAC and CUPRAC) identified the SB2 compound as having the highest antihemolytic and antioxidant effects. The low cytotoxicity validated by hemocompatibility assays makes these compounds options for antifungal treatment. The results show that antifungal and antioxidant action is greatly influenced by structural modifications, especially the position of the methyl group on the aromatic ring. The possible clinical uses of these molecules as drugs for the treatment of multidrug-resistant C. auris infections needs further investigation. Full article

K. pneumoniae is a major cause of bovine mastitis worldwide, making it difficult to control due to its resistance to multiple drugs. L. paraplantarum has been explored as a promising new approach to fighting bovine mastitis. In this study, the probiotic potential and safety of L. paraplantarum SDN1.2, as well as its ex vivo and in vivo anti-inflammatory effects against K. pneumoniae-induced mastitis, were comprehensively investigated using bioinformatics analyses and experimental validation methods. The results revealed that L. paraplantarum SDN1.2 exhibits non-hemolytic activity, is not cytotoxic, lacks virulence genes (e.g., adhesion factors, toxins, and invasion factors) and antibiotic resistance genes (e.g., beta-lactamases and tetracycline resistance genes), as supported by whole-genome sequencing, and significantly inhibits the growth of K. pneumoniae, as evaluated by antimicrobial tests. Following further validation in vitro, L. paraplantarum SDN1.2 demonstrated the capability to inhibit the adhesion and invasion of K. pneumoniae to bMECs. In a mouse model of K. pneumoniae-induced mastitis, L. paraplantarum SDN1.2 reduced the extent of neutrophil infiltration and inflammatory lesions. Furthermore, L. paraplantarum SDN1.2 pretreatment significantly reduced myeloperoxidase (MPO) activity and the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-a) in mouse mammary gland tissue. In K. pneumoniae-infected bMECs, L. paraplantarum SDN1.2 significantly lowered lactate dehydrogenase (LDH) levels and expression of inflammatory cytokines such as IL-6, IL-1β, and TNF-α. The results demonstrated that the newly isolated L. paraplantarum SDN1.2 from bovine sources exhibits promising characteristics as a safe probiotic for the alleviation of bovine mastitis due to its safety profile and anti-inflammatory and antibacterial properties. Full article