Search Results (6,414)

The indiscriminate use of antibiotics in food-producing animals serves as a major catalyst for the emergence of antibiotic-resistant infections. This study aimed to assess the genetic diversity and antibiotic resistance of Enterobacterales in animal-derived foods. A total of 905 animal-derived food samples, including meat, dairy, poultry, fish, and environmental sources, were collected from various locations in Pakistan. Isolates were confirmed through selective subculturing, morphological, biochemical, and MALDI-TOF analysis, followed by antibiotic susceptibility testing. Subsequently, PCR-based detection of antibiotic resistance genes and virulence-associated genes. Overall, a total of 263 (29.06%) Enterobacterales were identified, as follows: 58.55% (154/263) E. coli, 6.84% (18/263) K. pneumoniae, 21.29% (56/263) P. mirabilis, and 13.30% (35/263) Salmonella spp. Isolates showed a varying resistance pattern against different studied antibiotics, e.g., beta-lactams and inhibitors, ciprofloxacin, and tetracycline, while colistin and tigecycline remained most effective. All the isolates displayed an array of antibiotic resistance and virulence-associated genes. Particularly significant (<0.05) co-existence of bla_NDM and mcr-1 was observed among the Enterobacterales isolated from various animal-derived foods. This study underscores the need to monitor Enterobacterales in animal-derived foods, especially in developing countries, to curb the spread of resistant pathogens and ensure effective food safety measures. Full article

Porcine deltacoronavirus (PDCoV) is an emerging pathogen that causes severe, often fatal, diarrhea in suckling piglets and has zoonotic potential. Its nonstructural protein 12 (Nsp12), functioning as the RNA-dependent RNA polymerase (RdRp), is a central component of the viral replication–transcription complex and a critical target for host antiviral mechanisms. Here, we identified eukaryotic elongation factor 1 gamma (eEF1G) as a host interactor of PDCoV Nsp12 by immunoprecipitation-coupled mass spectrometry in IPEC-J2 cells. This interaction was confirmed by co-immunoprecipitation, pull-down assays, and confocal microscopy. Functional analyses involving siRNA knockdown and overexpression of eEF1G, combined with viral titration, strand-specific real-time quantitative PCR, and RNA immunoprecipitation assays, demonstrated that eEF1G directly binds to Nsp12. Knockdown of eEF1G significantly enhanced viral replication and increased negative-stranded RNA synthesis, whereas overexpression did not affect viral proliferation. Furthermore, eEF1G was found to bind PDCoV genomic RNA and competitively disrupt the interaction between Nsp12 and viral RNA, thereby impairing RdRp activity. Our results indicate that eEF1G acts as a novel host restriction factor that inhibits PDCoV replication by competing with Nsp12 for genomic RNA binding, ultimately blocking negative-stranded RNA synthesis. This study unveils a new antiviral mechanism and highlights a potential target for developing interventions against PDCoV. Full article

Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies. Full article

Cancer remains one of the leading causes of mortality worldwide and continues to pose significant therapeutic challenges despite decades of research. Conventional treatments such as chemotherapy and radiotherapy often lack selectivity, damaging both malignant and healthy tissues and resulting in severe side effects. Photodynamic therapy (PDT) has emerged as a promising non-invasive alternative that selectively eradicates cancer cells or pathogens using a photosensitizer (PS), light, and oxygen. PDT induces necrosis or apoptosis in cancer cells by locally generating cytotoxic reactive oxygen species through targeted laser irradiation. However, its clinical efficacy is limited by factors such as tumor hypoxia, poor PS delivery efficiency, and light attenuation within biological tissues. Recent advances in liposomal nanoplatforms have shown considerable potential in overcoming these barriers. Liposomes can co-deliver PS, therapeutic agents, and oxygen, thereby enhancing PDT outcomes. This review outlines the fundamental principles of PDT and the physicochemical properties of liposomes. It then explores two major strategies for improving PDT efficacy using liposomes: PS-drug co-delivery and oxygen delivery to mitigate tumor hypoxia for synergistic therapeutic effects. Finally, current limitations and future perspectives of liposome-based nanomedicine in photodynamic cancer therapy are discussed. Overall, this review provides a foundation for advancing liposome-based strategies toward clinical implementation in photodynamic cancer treatment. Full article

Constructed wetlands (CWs) are sustainable and cost-effective systems that utilise plant–microbe interactions and natural processes for wastewater treatment. Microbial communities play a pivotal role in pollutant removal by crucial processes like nitrogen transformations, phosphorus cycling, organic matter degradation and the breakdown of emerging contaminants. Dominant phyla, such as Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes, collectively orchestrate these biogeochemical functions. Advances in molecular tools, including high-throughput sequencing and metagenomics, have revealed the diversity and functional potential of wetland microbiomes, while environmental factors, i.e., temperature, pH and hydraulic retention time, strongly influence their performance. Phosphorus removal efficiency is often lower than nitrogen, and large land requirements and long start-up times restrict broader application. Microplastic accumulation, the spread of antibiotic resistance genes and greenhouse gas emissions (methane, nitrous oxide) present additional challenges. The possible persistence of pathogenic microbes further complicates system safety. Future research should integrate engineered substrates, biochar amendments, optimised plant–microbe interactions and hybrid CW designs to enhance treatment performance and resilience in the era of climate change. By acknowledging the potential and constraints, CWs can be further developed as next-generation, nature-based solutions for sustainable water management in the years to come. Full article

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

Bacterial lysates have emerged as promising immunomodulatory agents that can enhance innate immune responses. Given the crucial role of macrophages in recognizing and controlling intracellular pathogens such as Mycobacterium tuberculosis, this study aimed to evaluate the immunological effects of selected bacterial lysates on human monocyte-derived macrophages (MDMs). We examined the ability of commercial bacterial lysates, Pulmonarom, Ismigen, Uro-Vaxom, and a lysate of M. tuberculosis H37 Ra (LMtb) to stimulate the production of key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-8. In addition, we investigated whether these lysates could modulate the expression of bactericidal/permeability-increasing protein (BPI), a critical antimicrobial effector, and assessed their ability to reduce the intracellular burden of mycobacteria and induce autophagy. The results demonstrate diverse immunostimulatory profiles among the lysates, highlighting differences in both inflammatory and antimicrobial responses that may be relevant for host-directed therapeutic strategies against tuberculosis. Notably, beyond the in vitro antimycobacterial activity observed for BPI, this protein was also found to be elevated in both serum and bronchoalveolar lavage fluid from patients with active TB, reflecting local and systemic immune activation. Furthermore, the reduction in BPI levels after treatment suggests its potential utility for following the dynamics of infection. Full article

Neopestalotiopsis zimbabwana is an emerging phytopathogen with multiple hosts. Considering the environmental, toxicological, and resistance issues linked to synthetic fungicides, Origanum vulgare L. essential oil (OEO) was evaluated through in vitro, in vivo, and in silico approaches. The pathogen, isolated from Watsonia borbonica L., was molecularly identified. Gas chromatography–mass spectrometry (GC–MS) analysis showed hexadecanoic acid (15.98%), dodecanoic acid (15.74%), terpinen-4-ol (11.61%), and thymol (7.65%) as the main components. In vitro assays determined a minimum inhibitory concentration (MIC) of 30% OEO and a minimal fungicidal concentration (MFC) of 60% OEO. Growth chamber trials demonstrated that preventive sprays maintained 0% foliar damage—similar to Captan^®—while controls reached ≈98%; suspending applications after week 4 resulted in ≈45% damage by week 8. These results confirm that OEO lacks systemic residual activity, acting only as a protectant within preventive integrated pest management (IPM) schemes. Docking to cytochrome b (protein data bank, PDB: 5TL8) indicated strong binding of α-farnesene (−7.638 kcal·mol⁻¹), isoterpinolene (−6.944), and α-terpineol (−6.918), suggesting disruption of mitochondrial respiration via Complex III. OEO represents a promising eco-friendly alternative for managing N. zimbabwana under controlled conditions and reducing reliance on synthetic fungicides. Full article

Background/Objectives: Staphylococcus haemolyticus is a common commensal bacterium that has emerged as an important nosocomial pathogen. Its multi-antibiotics resistance presents substantial therapeutic challenges in healthcare settings worldwide. Despite its growing clinical relevance, most investigations into antimicrobial resistance determinants have been focused on Staphylococcus aureus or Staphylococcus epidermidis, leaving S. haemolyticus comparatively understudied. This study aimed to elucidate the genetic basis of multi-drug resistance by characterizing mobile genetic elements associated with predominant S. haemolyticus clones circulating in Taiwan. Methods: From 2010 to 2017, 140 clinical targeted isolates of S. haemolyticus were obtained from individual patients. Two representative strains, SH53 (ST3) and SH51 (ST42), were sequenced using the PacBio^TM platform. The structural organization of SCCmec cassettes and phage-associated resistance islands in the remaining 138 isolates was analyzed by polymerase chain reaction (PCR) using specifically designed primers. Results: Of the 140 isolates, 92 (65.7%) were ST42 and 48 (34.3%) were ST3. PCR analysis showed that over two-thirds harbored heavy metal resistance genes. cadD, cadX, arsC, arsB, and arsR occurred in 90.2% of ST42 isolates, with copA in 71.7%. In ST3, these five genes were present in 89.6%, and copA in 64.6%. Fusidic acid (FA) resistance was more frequent in ST42 (46.7%) than ST3 (22.9%) (p = 0.015). Only one ST42 isolate carried fusC. The remaining 52 FA-resistant isolates contained a type I aj1–leader peptide (LP)–fusB structure downstream of smpB, except for a single ST42 isolate with the type IV structure. Conclusions: MDR ST42 S. haemolyticus carrying SCCmec cassettes with heavy metal resistance genes and phage-related islands carrying type I aj1–leader peptide (LP)–fusB structures may represent emerging opportunistic pathogens in Taiwan. Continued longitudinal surveillance is warranted to track the evolution of resistance-associated mobile elements under selective antimicrobial pressure. Full article

Melasma is a chronic, acquired hyperpigmentation disease that occurs on light-exposed skin, especially in women of childbearing age. This common dyschromic disorder significantly impairs quality of life, yet treatments are unsatisfactory due to an incomplete understanding of its etiology. Its pathogenesis is multifactorial: ultraviolet (UV) radiation exposure, sex hormone fluctuations, and familial genetics are known triggers. Meanwhile, the persistence of focal hyperpigmentation suggests additional mechanisms beyond enhanced melanocyte activity. Emerging evidence highlights that melasma skin exhibits features of chronic photoaging: solar elastosis, basement membrane (BM) disruption and increased vascularity can be seen in the skin lesions. Senescent dermal fibroblasts under UV stress secrete melanogenic cytokines (e.g., SCF, HGF) that further stimulate melanocytes. In addition, melasma lesions harbor subclinical inflammation: infiltrates of CD4⁺ T cells, macrophages, and mast cells are visible, accompanied by elevated IL-17 and COX-2, implying an immune-driven component sustains pigment production. Collectively, these observations suggest that melasma behaves as a chronic inflammatory disorder of the skin microenvironment, rather than an isolated pigmentary defect. Concurrently, epidermal alterations such as barrier dysfunction and abnormal melanosome transport exacerbate melanin retention. In this review, by integrating these emerging insights into a unified pathogenic framework, we recognize melasma as a disorder of epidermal–dermal crosstalk and immune modulation, offering novel therapeutic perspectives for this recalcitrant condition. Full article

The rising demand for sustainable agriculture and circular resource management has intensified interest in converting wastewater sludge into value-added products. This review explores the transformation of sewage sludge into slow- and controlled-release fertilizers (CRFs), with a focus on biochar production and encapsulation technologies. Sewage sludge is rich in essential macronutrients (N, P, K), micronutrients, and organic matter, making it a promising feedstock for agricultural applications. However, its use is constrained by challenges including compositional variability, presence of heavy metals, pathogens, and emerging contaminants such as microplastics and PFAS (Per- and Polyfluoroalkyl Substances). The manuscript discusses a range of stabilization and conversion techniques, such as composting, anaerobic digestion, pyrolysis, hydrothermal carbonization, and nutrient recovery from incinerated sludge ash. Special emphasis is placed on coating and encapsulation technologies that regulate nutrient release, improve fertilizer efficiency, and reduce environmental losses. The role of natural, synthetic, and biodegradable polymers in enhancing release mechanisms is analyzed in the context of agricultural performance and soil health. While these technologies offer environmental and agronomic benefits, large-scale adoption is hindered by technical, economic, and regulatory barriers. The review highlights key challenges and outlines future perspectives, including the need for advanced coating materials, improved contaminant mitigation strategies, harmonized regulations, and field-scale validation of CRFs. Overall, the valorisation of sewage sludge into CRFs presents a viable strategy for nutrient recovery, waste minimization, and sustainable food production. With continued innovation and policy support, sludge-based fertilizers can become a critical component of the green transition in agriculture. Full article

Background and Objectives: Periodontitis is a common chronic inflammatory disease and a leading cause of tooth loss worldwide. Traditional diagnostic methods, such as probing and radiographic assessment, are retrospective and fail to detect ongoing disease activity. In recent years, salivary biomarkers and oral microbiome profiling have emerged as promising tools for earlier detection and precision-based management. The aim of this review is to synthesize current evidence on salivary and microbiome-derived biomarkers in periodontitis and to evaluate their translational potential in diagnostics and therapy. Materials and Methods: A narrative review was performed using PubMed, Scopus, and Web of Science to identify studies published between 2020 and 2025. Search terms included periodontitis, salivary biomarkers, oral microbiome, dysbiosis, and precision therapy. Priority was given to systematic reviews, meta-analyses, and translational studies that addressed diagnostic or therapeutic applications. Eligible publications included English-language original studies and reviews reporting on the diagnostic or therapeutic relevance of salivary or microbiome biomarkers in periodontitis. Results: Salivary biomarkers such as cytokines, matrix metalloproteinases (MMPs), oxidative stress markers, microRNAs, and extracellular vesicles (EVs) show consistent associations with disease activity and treatment outcomes. Oral microbiome studies reveal that both classical pathogens and community-level dysbiosis contribute to disease risk. Translational advances include chairside immunoassays, biosensors, lab-on-a-chip devices, and artificial intelligence (AI)-driven analyses. Biomarker-guided therapies—such as microbiome modulation, natural bioactive compounds, host-response modulation, and smart biomaterials—are being evaluated with increasing frequency in translational studies. Conclusions: By integrating salivary and microbiome biomarkers with novel diagnostic technologies and emerging therapies, this review complements existing systematic evidence and offers a translational roadmap toward precision periodontology. Full article

Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article

Background: Antimicrobial drugs are used to treat bacterial diseases in livestock production systems, including bovine respiratory disease (BRD) in feedlot cattle. It is recommended that therapeutic antimicrobial use (AMU) in food animals be informed by diagnostic tests to limit the emergence of antimicrobial resistance (AMR) and preserve the effectiveness of available drugs. Recent evidence demonstrates preliminary support for the pen as a prospective target for AMR testing-based interventions in higher-risk cattle. Methods: A previously reported agent-based model (ABM) was modified and then used in this study to investigate the potential for different pen-level sampling and laboratory testing-informed BRD treatment strategies to favorably impact selected antimicrobial stewardship and management outcomes in the western Canadian context. The incorporation of sample testing to guide treatment choice was hypothesized to reduce BRD relapses, subsequent AMU treatments and resultant AMR in sentinel pathogen Mannheimia haemolytica. The ABM was extended to include a discrete event simulation (DES) workflow that models the testing process, including the time at sample collection (0 or 13 days on feed) and the type of AMR diagnostic test (antimicrobial susceptibility testing or long-read metagenomic sequencing). Candidate testing scenarios were simulated for both a test-only control and testing-informed treatment (TI) setting (n = 52 total experiments). Key model outputs were generated for both the pen and feedlot levels and extracted to data repositories. Results: There was no effect of the TI strategy on the stewardship or economic outcomes of interest under baseline ecological and treatment conditions. Changes in the type and number of uses by antimicrobial class were observed when baseline AMR in M. haemolytica was assumed to be higher at feedlot arrival, but there was no corresponding impact on subsequent resistance or morbidity measures. The impacts of sample timing and diagnostic test accuracy on AMR test positivity and other outputs were subsequently explored with a theoretical “extreme” BRD treatment protocol that maximized selection pressure for AMR. Conclusions: The successful implementation of a pen-level sampling and diagnostic strategy would be critically dependent on many interrelated factors, including the BRD treatment protocol, the prevalences of resistance to the treatment classes, the accuracy of available AMR diagnostic tests, and the selected “treatment change” thresholds. This study demonstrates how the hybrid ABM-DES model can be used for future experimentation with interventions proposed to limit AMR risk in the context of BRD management. Full article

The parallel global increase in obesity and Alzheimer’s disease (AD) underscores an urgent public health challenge, with converging evidence indicating that metabolic dysfunction strongly contributes to neurodegeneration. Obesity is now recognized not only as a systemic metabolic condition but also as a modifiable risk factor for AD, acting through mechanisms such as chronic low-grade inflammation, insulin resistance, and adipose tissue dysfunction. Among the molecular mediators at this interface, adipokines have emerged as pivotal regulators linking metabolic imbalance to cognitive decline. Adipokines are hormone-like proteins secreted by adipose tissue, including adiponectin, leptin, and resistin, that regulate metabolism, inflammation and can influence brain function. Resistin, frequently elevated in obesity, promotes neuroinflammation, disrupts insulin signaling, and accelerates β-amyloid (Aβ) deposition and tau pathology. Conversely, adiponectin enhances insulin sensitivity, suppresses oxidative stress, and supports mitochondrial and endothelial function, thereby exerting neuroprotective actions. The imbalance between resistin and adiponectin may shift the central nervous system toward a pro-inflammatory and metabolically compromised state that predisposes to neurodegeneration. Beyond their mechanistic relevance, adipokines hold translational promise as biomarkers for early risk stratification and therapeutic monitoring. Importantly, natural compounds, including polyphenols, alkaloids, and terpenoids, have shown the capacity to modulate adipokine signaling, restore metabolic homeostasis, and attenuate AD-related pathology in preclinical models. This positions adipokines not only as pathogenic mediators but also as therapeutic targets at the intersection of diabetes, obesity, and dementia. By integrating mechanistic, clinical, and pharmacological evidence, this review emphasizes adipokine signaling as a novel axis for intervention and highlights natural compound-based strategies as emerging therapeutic approaches in obesity-associated AD. Beyond nutraceuticals, antidiabetic agents also modulate adipokines and AD-relevant pathways. GLP-1 receptor agonists, metformin, and thiazolidinediones tend to increase adiponectin and reduce inflammatory tone, while SGLT2 and DPP-4 inhibitors exert systemic anti-inflammatory and hemodynamic benefits with emerging but still limited cognitive evidence. Together, these drug classes offer mechanistically grounded strategies to target the adipokine–inflammation–metabolism axis in obesity-associated AD. Full article