Search Results (8,889)

Cryptococcus neoformans (C. neoformans) has emerged as a global pathogen of concern. While much is known about its pathobiology, its management is complicated by strains displaying non-fluconazole susceptibility. This contribution assessed the repurposing of artemisinin (ART) as an anti-Cryptococcus antifungal. An in vitro susceptibility assay was performed to assess the drug response of cells. To establish the ART mode of action, assays examining mitochondrial health were set up. The phagocytosis efficiency of a murine macrophage cell line towards ART-treated and non-treated cells was determined. To complement this, the immunomodulatory effects of ART were further characterised in Galleria mellonella (G. mellonella) by assessing haemocytes’ phagocytosis and expression of immune genes, i.e., insect metalloproteinase inhibitor (IMPI) and hemolin, essential for the insect antimicrobial response. In the end, the survival rate of infected larvae was calculated. We established that ART was antifungal, with cell death triggered by the uncoupling of the cytochrome c (cyt c) from the mitochondria, leading to activation of caspase-3-dependent-like apoptosis. Moreover, treatment induced ultrastructural changes with treated cells appearing more deformed than non-treated cells (p < 0.05). Treatment also increased the susceptibility of cells towards both macrophage and haemocyte phagocytosis compared to non-treated cells (p < 0.05). Importantly, treatment seemed to weaken the cells, decreasing their virulence potential based on analysis of the expression of the immune gene markers, which translated into treatment rescuing 75% of the larvae infected with 0.1 ART-treated cells. These preliminary findings support the repurposing of ART as an anti-Cryptococcus antifungal. Full article

Ashitaba (Angelica keiskei) is a perennial herb native to Japan, traditionally consumed as a health-promoting food and herbal medicine. This study evaluated the antimicrobial, anti-halitosis, and anti-inflammatory effects of Ashitaba extract on canine periodontal disease (PD) caused by Porphyromonas gulae (P. gulae). In vitro, Ashitaba extract (0.006–0.1%) significantly inhibited P. gulae viability by up to 80% and reduced biofilm formation by approximately 10% at 0.1%. The extract also suppressed the production of volatile sulfur compounds—hydrogen sulfide and methyl mercaptan—by over 80% and 40%, respectively, within 10 min. Furthermore, Ashitaba extract markedly decreased P. gulae-induced pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α) by up to 90% in murine, canine, and human macrophage and gingival cell lines. In vivo, daily oral application of 0.05% Ashitaba-extract gel for four weeks, with or without tooth brushing, significantly improved gingivitis scores (by 40–60%), reduced halitosis levels, and decreased P. gulae DNA detection and enzymatic activity in dogs with PD. These findings demonstrate that Ashitaba extract possesses potent bactericidal, anti-halitosis, and anti-inflammatory properties, supporting its potential as a natural adjunctive therapy for the prevention and management of canine periodontal disease. Full article

Acute kidney injury (AKI) is a frequent clinical and pathological condition, often resulting from factors like ischemia, toxins, or infections, which cause a sudden and severe decline in renal function. This, in turn, significantly affects patients’ overall health and quality of life. The Sirtuin family (SIRTs), a group of Nicotinamide Adenine Dinucleotide (NAD+)-dependent deacetylases, is critically involved in key biological processes such as cellular metabolism, stress responses, aging, and DNA repair. Recent research has highlighted the vital role of SIRTs, such as SIRT1, SIRT3, and SIRT6, in the development and progression of AKI. These proteins help mitigate renal injury and facilitate kidney repair through mechanisms like antioxidant activity, anti-inflammatory responses, cellular repair, and energy metabolism. Additionally, the deacetylase activity of the SIRTs confers protection against AKI by modulating mitochondrial function, decreasing oxidative stress, and regulating autophagy. Although the precise mechanisms underlying the role of Sirtuins in AKI are still being explored, their potential as therapeutic targets is increasingly being recognized. This paper will discuss the mechanisms by which the SIRTs influence AKI and examine their potential in a future therapeutic strategy. Full article

Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are limited. This study examined the association between TAS2R SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. Methods: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of TAS2R SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). Results: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in TAS2R20 showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in TAS2R1 was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in TAS2R5 was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in TAS2R62P was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in TAS2R1 was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. Conclusions: TAS2R variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies. Full article

Silver nanoparticles (AgNPs) have attracted significant attention in recent years in diverse fields owing to their broad mechanisms of action. In particular, the wound healing process has become one of the main fields where the therapeutic potential of AgNPs is highlighted. AgNPs can be used as monotherapy or incorporated into composite structures in various formulations such as nanogels, hydrogels, powders, ointments, and sprays, for the treatment of a wide range of wound types including burns, excisional and incisional wounds, bone defects, surgical wounds, and diabetic ulcers. This widespread use is attributed to the strong antibacterial, anti-inflammatory, antioxidant, and cell proliferation-promoting biological properties of AgNPs. Moreover, AgNPs exhibit synergistic effects when combined with conventional antibiotics, enhancing their efficiency against resistant bacterial strains or even restoring the lost antibacterial activity. These biological properties enable AgNPs to reduce infection risk while simultaneously promoting high-quality healing by accelerating tissue regeneration. The therapeutic effectiveness of AgNPs is influenced by their physicochemical properties, including particle size, shape, and surface chemistry. In particular, synthesis methods play a significant role in determining both the biological activity and the safety profile of AgNPs. Among various methods, green synthesis approaches stand out for enabling the production of environmentally friendly, non-toxic, and highly biocompatible AgNPs. In this review, the mechanisms of action of AgNPs in wound healing are examined in detail, and recent scientific developments in this field are evaluated based on current in vitro, in vivo, and clinical studies. Full article

We aimed to assess the seroprevalence of anti-Neospora caninum and anti-Toxoplasma gondii antibodies in cattle intended for human consumption in Paraíba, Brazil, and the associated risk factors. A total of 110 serum samples from slaughtered cattle were analyzed using the Indirect Fluorescence Antibody Test (IFAT), with cut-off points of 1:200 for N. caninum and 1:64 for T. gondii. Seroprevalence was 8.2% (9/110) for N. caninum (titers 1:200–1:6400) and 18.2% (20/110) for T. gondii (titers 1:64–1:512). Risk factor analysis revealed that the variable female sex (cows) and the extensive farming system were statistically significantly associated with seroprevalence for N. caninum. Whereas for T. gondii, extensive farming, frequent animal purchase, and the lack of separation between calves and adult cattle were statistically significant. These findings demonstrate the circulation of these parasites in herds, with implications for animal and public health, indicating a potential risk of transmission to definitive hosts and humans through the consumption of raw or undercooked infected meat. Full article

Background: Cefazolin is being increasingly used to treat central nervous system infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) to mitigate the side effects of existing anti-Staphylococcal drugs. This study aims to develop a cerebrospinal pharmacokinetic (PK) model to predict the cefazolin concentration in cerebrospinal fluid (CSF) and to individualize the dosing regimen for MSSA meningitis. Methods: A cerebrospinal PK model was developed based on the existing literature and used to estimate the probability of attaining PK/ pharmacodynamic (PD) targets. These targets were set as 100% time above the minimum inhibitory concentration (T > MIC) in CSF. The cerebrospinal PK/PD breakpoint was defined as the highest MIC at which target attainment probability in CSF was ≥90%. The mean CSF/serum ratio estimated from the literature was 0.0525 after a dose of 1–3 g (sampling time: 1–9 h after dose) in adult patients with suspected meningitis. This ratio was incorporated into this PK model based on a hybrid approach. Results: For patients with creatinine clearance (CL_cr) = 90 mL/min, the cerebrospinal PK/PD breakpoint MICs of continuous infusion regimens (6–12 g/day) reached 0.5 µg/mL, which can inhibit the growth of 90% of the MSSA population (MIC₉₀). Furthermore, for patients with renal dysfunction (CL_cr = 30 mL/min), a dose reduction (4 g/day) may be required to avoid excessive drug exposure. Conclusions: High-dose continuous infusion of cefazolin may be appropriate for MSSA meningitis in patients with normal renal function, while dose adjustments are needed for those with renal impairment. Full article

Given the increasing global concern over antimicrobial resistance in poultry health, this study investigated the potential of Javanese cardamom essential oil (JCEO) and dried turmeric (DT) as alternative therapies for colibacillosis by evaluating their effects on the spleen organ. A total of 72 Cobb-strain day-old chickens were allocated into eight groups, which received different doses of JCEO (0.06 mL/kg BW and 0.1 mL/kg BW), DT (400 mg/kg feed) and ciprofloxacin. Infection was induced intraperitoneally (E. coli O78 strain, 10⁶ CFU/mL/chicken) at 28 days, while the treatments were administered orally from day 7 to week 5. Histopathological evaluation was graded on a 1–5 scale based on the five primary lesion criteria. The herb combination groups had the lowest severity grade, characterized by compact lymphoid follicles and reduced vasculitis. The JCEO single-dose group, both in vitro and in vivo, reduced bacterial growth and had a mild vasculitis score, indicating its antibacterial activity. In contrast, the single treatment of DT and the antibiotic groups showed moderate spleen lesion damage. These findings suggest that JCEO acts bactericidally, while DT provides an anti-inflammatory effect, and both combinations work synergistically. Full article

The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

Background: The treatment of wounds remains a significant clinical challenge, particularly in chronic and infected wounds, where delayed healing often results in complications. Recent advances in biomaterials have highlighted the potential of polymer-based scaffolds as promising platforms for wound management due to their ability to mimic the extracellular matrix, support tissue regeneration, and provide a moist environment conducive to healing. Objectives: This review aims to provide a comprehensive overview of the recent progress in the design and application of polymer-based scaffolds loaded with essential oil (EO) components, emphasizing their role in promoting effective wound healing. Methods: Relevant literature on polymeric scaffolds and EO-based bioactive agents was systematically reviewed, focusing on studies that investigated the biological activities, fabrication techniques, and therapeutic performance of EO-loaded scaffolds in wound management. Results: Findings from recent studies indicate that EO components, particularly monoterpenoids such as thymol, carvacrol, and eugenol, exhibit remarkable antimicrobial, anti-inflammatory, antioxidant, and analgesic properties that accelerate wound healing. When incorporated into polymer matrices, these components enhance scaffold biocompatibility, antimicrobial efficacy, and tissue regeneration capacity through synergistic interactions. Conclusions: The integration of essential oil components into polymeric scaffolds represents a promising strategy for developing multifunctional wound dressings. Such systems combine the structural advantages of polymers with the therapeutic benefits of EOs, offering an effective platform for accelerating healing and preventing wound infections. Full article

To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4⁺ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKCλ/ι in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT–qPCR and ELISA were used to analyze the effects of PKCλ/ι on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKCλ/ι deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10⁺ B cells increased. Additionally, hepatic neutrophils decreased and Treg/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKCλ/ι deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target. Full article

The interaction between microorganisms in the dental microfilm (plaque) at the gingival margin, the immune system, and the brain is vital for gingival health. The brain constantly receives information regarding microbial composition and inflammation status through afferent nerves and the bloodstream. It modulates immune responses via efferent nerves and hormonal systems to maintain homeostasis. This relationship determines whether the gingiva remains healthy or develops into gingivitis (non-destructive inflammation) or periodontitis (a destructive condition), collectively referred to as periodontal disease. Factors associated with severe periodontitis heighten the responsiveness of this homeostatic system, diminishing the adaptive immune system’s defence against symbiotic microorganisms with pathogenic properties, known as pathobionts. This leads to excessive innate immune system activation, effectively preventing infection but damaging the periodontium. Consequently, investigating the microbiota–brain axis is vital for understanding its impact on periodontal health and disease. Herein, we examine recent advancements in how the defence against pathobionts is organised within the brain, and how it regulates and adapts the pro-inflammatory and anti-inflammatory immune balance, controlling microbiota composition. It also discussed how pathobionts and emotional stress can trigger neurodegenerative diseases, and how inadequate coping strategies for managing daily stress and shift work can disrupt brain circuits linked to immune regulation, weakening the adaptive immune response against pathobionts. Full article

Helicobacter pylori infects the human stomach and causes various gastrointestinal diseases. Saucerneol D is a type of lignan, which is a polyphenol compound that exists naturally in plants, and it is abundant in flaxseed, sesame seeds, whole grains, vegetables, and fruits. Saucerneol D is found in Saurus chinensis extract and has been reported to exert a variety of effects, such as antioxidant and anti-inflammatory abilities. However, its antibacterial effect against H. pylori has not been reported; therefore, we analyzed the effect of saucerneol D on H. pylori in the present study. Changes in the expression of pathogenic factors and gene transcription in H. pylori were observed after treatment with saucerneol D using Western blotting and RT-PCR. It was confirmed that saucerneol D suppressed the growth of H. pylori by decreasing the expression of the genes dnaN and polA, which are required for bacterial replication. Saucerneol D also reduced the secretion of the major pathogenic toxin protein, CagA, by downregulating the expression of type IV secretion system-composing proteins. Furthermore, saucerneol D reduced ammonia production by inhibiting the expression of urease proteins, which are essential for the survival of H. pylori in the acidic gastric environment. Additionally, saucerneol D decreased the expression of flaB, potentially reducing motility. Finally, it was confirmed that the expression of the sabA gene, associated with cell adhesion, was reduced. These results suggest that saucerneol D inhibits the growth of H. pylori and the expression of several pathogenic factors, indicating that saucerneol D has an antimicrobial effect against H. pylori. Full article

In Africa, the folkloric practices involving plant-based remedies play a crucial role in livestock farming, often attributed to the limited access to modern veterinary services. The use of Acacia species (including those reclassified as Vachellia species) in ethnoveterinary medicine has garnered increasing interest due to their high protein content and medicinal (including anti-parasitic) properties, offering a sustainable source of fodder particularly in arid and semi-arid regions. However, scientific assessment of their efficacy and safety remains limited. This systematic review examines the ethnoveterinary uses, biological efficacy and safety of Acacia species across Africa. A literature search was conducted using PubMed, Google Scholar and Scopus, yielding 519 relevant studies published between 2001 and 2024. After applying the inclusion and exclusion criteria, 43 eligible studies were analyzed based on their relevance, geographical location and livestock disease applications. Plants of the World online database was used to validate the names of the species and authority. Ethiopia had the highest usage of Acacia species (25%), then Nigeria (20%) followed by both South Africa (15%) and Namibia (15%). Vachellia nilotica (Acacia nilotica) was the most frequently cited species (26.3%), followed by Vachellia karroo (Acacia karroo) (15.8%). Ethnobotanical records indicate that the different Acacia species have been traditionally used to treat conditions such as diarrhea, wound infections and complications such as retained placenta. Pharmacological studies corroborate the therapeutic benefits of Acacia species with evidence of their antimicrobial, anti-inflammatory, antioxidant and anthelmintic effects, though some toxicity concerns exist at high dosages. The systematic review revealed the efficacy and safety (to some extent) of Acacia species in livestock disease management, emphasizing their potential integration into veterinary medicine. However, the dearth of in vivo studies underscores the need for pre-clinical and clinical trials to establish safe and effective dosages for use in livestock. Full article