Search Results (2,369)

Extraintestinal pathogenic Escherichia coli (ExPEC) is among the bacterial pathogens associated with infections of the female and male reproductive tracts, where it may contribute to inflammatory processes and impaired reproductive function. In this context, neutrophils constitute a critical component of host defense through the release of neutrophil extracellular traps (NETs), web-like structures composed of decondensed chromatin, histones, and antimicrobial proteins that capture and eliminate invading microorganisms. However, the interaction between E. coli and NETs is highly dynamic, as the bacterium has evolved immune-evasion mechanisms that facilitate persistence within the host. This raises a critical paradox: NETs may shift from an antimicrobial defense mechanism to a microenvironmental factor that inadvertently favors bacterial persistence and chronic inflammation. This review synthesizes current evidence on the colonization, virulence, and immune-evasion mechanisms of E. coli in the reproductive tract, with particular emphasis on the modulation of NETosis, biofilm formation, and their contribution to antimicrobial resistance. We further discuss the dual role of NETs as an innate immune defense mechanism and, conversely, as a potential contributor to tissue injury, oxidative stress, and chronic inflammation when dysregulated. Understanding the interplay among E. coli, extracellular traps, and antimicrobial resistance provides a valuable conceptual framework for the development of novel therapeutic approaches aimed at limiting bacterial persistence, preserving reproductive function, and addressing the growing global threat of antimicrobial resistance. Full article

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) develop over decades, yet their earliest pathogenic drivers remain poorly understood. Epidemiological and experimental animal studies suggest that disturbances in oral sensorimotor regulation, particularly within trigeminal proprioceptive pathways, may contribute to neural dysfunction long before clinical symptoms emerge. The mesencephalic trigeminal nucleus (MesV), the only primary sensory neuron population located entirely within the central nervous system (CNS), links oral proprioception with brainstem and forebrain networks. Chronic occlusal mismatch, impaired mastication, sleep bruxism, and sleep-disordered breathing may generate persistent sensorimotor prediction errors that destabilize MesV-centered circuits and subsequently recruit the locus coeruleus (LC), the brain’s principal noradrenergic stress nucleus. This review proposes an oral–brain axis model in which chronic MesV-related prediction error signaling engages LC-dependent stress systems, leading to neuroimmune activation, locus coeruleus–asparagine endopeptidase (LC-AEP) pathway engagement, and downstream proteinopathic processes. Sustained LC activity may facilitate microglial priming, reactive astrocytosis, and neuroinflammatory signaling, creating conditions that favor LC-AEP pathway activation and downstream tau pathology. Epidemiological studies associate tooth loss, reduced occlusal support, and impaired mastication with increased dementia risk, while experimental models of prodromal PD demonstrate early trigeminal sensory-processing abnormalities preceding motor symptoms. Together, these findings support the hypothesis that chronic disturbances in oral sensorimotor homeostasis may increase neurodegenerative vulnerability. This framework identifies potential biomarkers and preventive targets, suggesting that modulation of oral function and neuroimmune pathways may help reduce neurodegenerative risk before irreversible neuronal loss occurs. Full article

Vitiligo is a chronic acquired depigmenting disorder characterized by progressive melanocyte loss. Its pathogenesis involves a multifactorial interplay among oxidative stress, impaired melanocyte regeneration, immune-mediated cytotoxicity, and neuroendocrine dysregulation. In recent years, traditional Chinese medicine (TCM)-derived active ingredients have attracted increasing research interest as potential interventions for vitiligo, although most isolated compounds remain at the preclinical stage. This review summarizes pharmacological and natural compounds applied in vitiligo treatment and highlights their regulatory mechanisms on core pathogenic modules. A comprehensive analysis of natural and semisynthetic active ingredients is provided, covering their preclinical and clinical evidence, mechanisms of action, and therapeutic relevance. Multiple ingredients, including baicalein, quercetin, curcumin, paeoniflorin, kaempferol, glycyrrhizin, and epigallocatechin-3-gallate (EGCG), have demonstrated antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective effects that are involved in the pathogenesis of vitiligo. Some TCM-derived interventions, such as Ginkgo biloba L. extract and compound glycyrrhizin, have been evaluated clinically, whereas most isolated active compounds, including baicalein and quercetin, remain at the preclinical stage. Overall, TCM-derived active ingredients represent a promising therapeutic strategy for vitiligo. However, continued translational and clinical research is still required to optimize formulations, dosing regimens, and safety profiles, thereby facilitating their integration into routine clinical practice. Full article

Background/Objectives: Alzheimer’s disease (AD), one of the most prevalent neurodegenerative disorders in the elderly, is characterized by progressive cognitive loss, amyloid-β (Aβ) plaque deposition, and neurofibrillary tangle formation. Cerebral hypoxia has been reported as a complex modulator of AD pathology, with hypoxia-inducible factor-1 (HIF-1) emerging as a central molecular marker associated with neurodegeneration. This review aims to comprehensively report the roles of HIF-1 signaling in AD pathogenesis, emphasizing its neuroprotective and neurotoxic mechanisms along with demonstrating the therapeutic potential and challenges of translating this pathway for AD therapeutics. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, Embase, and Google Scholar databases for articles published between January 2000 and December 2025 on the context. Results: Under mild hypoxic conditions, HIF-1 activation enhances neuronal survival through upregulation of glucose transporters, glycolytic enzymes, angiogenic factors, erythropoietin, and antioxidant defense mechanisms. In contrast, chronic hypoxia modulates HIF-1 into a pathogenic marker through transcriptional activation of β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and γ-secretase, facilitating amyloidogenic APP processing, along with tau hyperphosphorylation. Moreover, HIF-1 exacerbates neuroinflammation through microglial activation and pro-inflammatory cytokine release. The cell-type-specific expression patterns of HIF-1α and the temporal dynamics of its activation regulate whether the pathway exerts neuroprotective or neurodegenerative effects. Conclusions: This review discusses the current understanding of HIF-1-mediated mechanistic insights in AD pathology and impacts of existing HIF-1 modulators on AD pathology, along with the therapeutic implications of targeting this pathway for translational application in AD therapeutics. Full article

Campylobacter jejuni and Campylobacter coli are major foodborne pathogens whose accurate species-level discrimination is important for outbreak investigations as well as rapidly assessing putative antimicrobial resistance profiles and the pathogenic potential of the bacterium. To facilitate species differentiation, a novel assay that integrates the nucleic acid-sensing capability of the oligo-Alpha with the multiplexing capacity of the AlphaPlex bead chemistries was developed. This wash-free system (designated as oligo-Plex) enables the detection and differentiation of C. jejuni and C. coli within a single reaction and can be completed in approximately 75 min. It works by using custom oligonucleotides modified for bead attachment, which hybridize sequentially along Campylobacter’s glyA gene and ultimately bridge the donor and acceptor beads. Improvements in assay stringency were made by increasing incubation temperatures, thus allowing the resolution of target from non-target. Comparisons of FITC–europium and DIG–terbium labeling systems revealed superior performance by the FITC–europium pair and suggested that helical positioning and steric accessibility likely influence donor–acceptor efficiency. Maximized signal separation was seen when using terbium for the detection of C. coli and europium for the detection of C. jejuni. Testing was performed in a Tris-based buffer and milk to confirm matrix tolerance, with potential areas for further optimization identified. The oligo-Plex presented here establishes a streamlined, adaptable platform suitable for high-throughput screening of multiple nucleic acid analytes that is readily extendable to a diverse array of pathogens through appropriate oligo selection. Full article

Chinese hickory (Carya cathayensis Sarg.) is an economically important tree species widely cultivated in southeastern China, where trunk canker disease caused by Botryosphaeria dothidea poses a serious threat to tree health and production. Pectin-degrading enzymes are important virulence-associated factors that facilitate fungal colonization and host tissue maceration, but their evolutionary diversification and functional roles in B. dothidea during woody host infection remain poorly understood. Comparative genomic analysis revealed lineage-specific variation in the GH28 glycoside hydrolase family among the examined Botryosphaeriaceae species, with B. dothidea exhibiting an expanded GH28 repertoire relative to the analyzed species. Expression analysis and functional assays revealed that BdGH28_3 showed the highest transcript abundance during infection stage and contributed to the full virulence of B. dothidea. A predicted protein–protein interaction (PPI) network suggested potential associations between BdGH28_3 and other pectinolytic enzymes, including polygalacturonases, pectin lyases, and pectinesterases. Collectively, these findings identify GH28 diversification as a distinctive feature of the B. dothidea genome and establish BdGH28_3 as a virulence-associated member, providing a foundation for investigating GH28-mediated pathogenicity in woody hosts. Full article

Pathogen surveillance contributes to the prediction of outbreaks and implementation of strategies to minimize disease transmission. White-tailed deer (Odocoileus virginianus) host important disease vectors and often support the proliferation of associated pathogens. Such vectors include ticks: hematophagous acarids that facilitate pathogen transmission between animals through blood feeding. Piroplasmida, an order of blood-borne protozoa including Babesia and Theileria, exploits this feeding to infect definitive hosts. Accordingly, we investigated the prevalence of Theileria cervi infections in Massachusetts white-tailed deer. Conventional polymerase chain reaction (PCR) was used to detect parasite gene fragments encoding the small ribosomal subunit (18S rRNA). Confirmation of species identity was determined by Oxford nanopore sequencing and Sequencher analysis. This revealed a 32.6% prevalence of T. cervi across Massachusetts. Whilst surveillance of deer blood uncovers parasite abundance and distribution, inversely, this allows us to also monitor vector populations. As Amblyomma americanum is the only vector implicated in the transmission of T. cervi, the detection of T. cervi in regions without anticipated Amblyomma presence may indicate expansion of vector populations. These findings provide valuable insights into the prevalence and ecology of this piroplasm and its vector, with possible implications for veterinary and public health. Full article

5′-Adenosine monophosphate-activated protein kinase (AMPK) is the principal cellular energy sensor that coordinates metabolic adaptation by balancing anabolic and catabolic pathways in response to energic stress. Beyond its canonical role in maintaining energy homeostasis, AMPK has emerged as a central regulator of host–pathogen interactions by integrating lipid metabolism, autophagy, mitochondrial dynamics, oxidative stress, and innate immune signaling. Flaviviruses, including dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus, extensively remodel host metabolism to establish productive infection. As a master regulator of cellular metabolism, AMPK can either restrict or facilitate flavivirus replication in a context-dependent manner by regulating lipid droplet biogenesis, fatty acid synthesis and beta-oxidation, autophagy, mitochondrial homeostasis, and interferon-mediated antiviral responses. Conversely, flaviviruses actively manipulate AMPK signaling and its downstream metabolic networks to promote endoplasmic reticulum remodeling, replication organelle biogenesis, energy production, and immune evasion. In this review, we summarize recent advances in understanding the multifaceted roles of AMPK during flavivirus infection, with an emphasis on its regulation of metabolic reprogramming, organelle remodeling, and antiviral immunity. We further discuss the therapeutic potential of pharmacologically targeting AMPK and its downstream pathways as a host-directed strategy for broad-spectrum antiviral intervention against flaviviruses. Full article

Cold atmospheric plasma (CAP), a non-thermal ionized gas, is gaining attention in biomedicine due to its unique properties such as the generation of reactive oxygen and nitrogen species (RONS), immunomodulatory effects, and selective cytotoxicity. This review explores the potential of CAP as a therapeutic tool in otorhinolaryngology (ORL). CAP has shown promising applications in wound healing, pathogen eradication, and antitumor strategies, particularly in head and neck cancers. Mechanistically, CAP promotes tissue regeneration through redox signaling, stimulates immune cell activity, induces immunogenic cell death, and enhances epithelial proliferation while offering broad-spectrum antimicrobial efficacy. The review also discusses the development of miniaturized CAP delivery systems, including endoscope-integrated plasma jets (e.g., PLASMASKOP), to facilitate clinical use in anatomically complex ORL regions. Given the nascent stage of clinical translation in ORL, the authors highlight the need for interdisciplinary research and device innovation to realize the full therapeutic potential of CAP in this field. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health threat. A key virulence mechanism involves the pathogen’s ability to inhibit apoptosis in infected macrophages, thereby facilitating immune evasion and persistent infection. The pro-apoptotic protein Bcl-2-interacting killer (BIK) represents a critical mediator of macrophage apoptosis. In this study, we engineered a recombinant Mycobacterium smegmatis strain (rMs-BIK) designed to secrete BIK via fusion with the Ag85B signal peptide (ASP). Secretion and expression of the BIK protein were confirmed by Western blotting. Quantitative flow cytometric analysis revealed that rMs-BIK induced significant apoptosis in RAW264.7 macrophages, with rates of 14.49%, 14.22%, and 22.24% at 12, 24, and 48 h post-infection, respectively. These values were markedly higher than those observed in cells infected with the wild-type strain (7.68%, 9.24%, and 10.90%) or the empty vector control (8.80%, 11.19%, and 14.43%). Our findings demonstrate the feasibility of functional pro-apoptotic protein delivery using a mycobacterial vector, providing a robust foundation for the future development of recombinant BCG-based vaccine candidates. Full article

Regulatory T cells (Tregs) play a pivotal role in maintaining immune homeostasis by exerting precise control over immune activation, suppressing excessive responses, and facilitating tissue repair. These specialized CD4+ T cells, characterized by FOXP3 expression, function as key regulators that prevent pathogen-directed immune responses from progressing to deleterious autoimmunity or chronic inflammation. Tregs mediate suppression via secretion of cytokines such as IL-10 and TGF-β, metabolic disruption, and direct modulation of effector immune cells, thereby maintaining equilibrium between protective immunity and peripheral tolerance. Both thymically derived natural Tregs (nTregs) and peripherally induced Tregs (pTregs) exhibit phenotypic plasticity, adapting to diverse inflammatory milieus and tissue microenvironments through an array of suppressive mechanisms that orchestrate immune regulation and facilitate tissue repair. This functional heterogeneity manifests across lymphoid and non-lymphoid tissues, wherein Tregs dynamically adapt to distinct microenvironments to mount tailored responses to infection, tissue injury, and inflammatory insults. Conversely, Tregs may promote disease progression in malignancies and persistent infections by attenuating antitumor and antimicrobial immune effector responses. Treg activity is essential for averting autoimmune pathologies, tempering inflammatory cascades, and fostering tissue regeneration, thereby rendering them indispensable for upholding both systemic and tissue-specific immune homeostasis. Elucidation of Treg immunobiology unveils substantial therapeutic prospects across a diverse array of pathologies; targeted modulation of Treg frequency and functionality offers promise for ameliorating autoimmunity, mitigating transplant rejection, and combating malignancy. This narrative review delineates the multifaceted roles of Tregs in immune homeostasis, elucidates emerging insights into their mechanistic underpinnings, and evaluates prospective applications in next-generation immunotherapeutic interventions. Full article

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), remains a major global health challenge. The prolonged duration of treatment and the emergence of multidrug-resistant strains have highlighted the need for alternative therapeutic strategies. This study investigated the therapeutic potential of Ag85A aptamer-conjugated PEGylated niosomes encapsulating ethanolic extract of propolis (Ag85A-PEGNio/EEP) using Mtb-infected macrophage model. Ag85A-PEGNio/EEP exhibited efficient cellular uptake, with more than 99.8% internalization by macrophages, and trafficked host phagolysosome, facilitating targeted delivery of EEP to intracellular Mtb. Ag85A-PEGNio/EEP treatment showed an anti-mycobacterium efficacy by reducing intracellular Mtb viability by approximately 51.2% compared with untreated controls. Moreover, Ag85A-PEGNio/EEP modulated macrophage immune responses by significantly increasing the expression of the pro-inflammatory cytokines IL-12 (8.4-fold) and IL-6 (3.8-fold), while markedly decreasing the expression of the anti-inflammatory cytokine IL-10 (6.4-fold). Protein–protein interaction (PPI) network analysis further revealed the association of proteins with immune regulation and antioxidant responses in treated cells. These findings suggest that Ag85A-PEGNio/EEP functions as a dual-action therapeutic platform by enhancing intracellular anti-mycobacterial activity while balancing host immune responses. This targeted nano-delivery system represents a promising candidate for host-directed TB therapy and further investigations are needed to validate these outcomes and explore their potential applications against TB treatment challenges. Full article

Neurotoxicity is generally thought to result from exogenous agents like environmental chemicals, drugs and biological toxins. However, increasing evidence suggests that many endogenous molecules that play a critical role in normal brain function can become neurotoxic when the regulatory mechanism involved in their production, metabolism, compartmentalization and clearance are disrupted. This shift underlies the basis of endogenous neurotoxicity. This review discusses the major endogenous sources of neurotoxicity: metabolic neurotoxins, dysfunctional neurotransmitters, protein aggregates and inflammatory mediators. These endogenous factors arise from different physiological pathways, but share common pathogenic mechanisms, all of which involve an underlying state of oxidative stress, mitochondrial dysfunction, impaired proteostasis, excitotoxic signalling, neurovascular dysfunction and maladaptive neuroglial responses. This is not a singular process but a network of interconnected processes, which work together to progressively diminish neuronal resilience and promote synaptic dysfunction and neurodegeneration. The review also underscores the critical role of astrocytes, microglia and other glial cells in the maintenance of neuronal homeostasis. By integrating diverse endogenous neurotoxic pathways within a unified homeostasis-centred framework, this review provides a broader perspective on the mechanisms linking metabolic disorders, aging and neurodegenerative diseases. This framework suggests that effective therapeutic strategies may require restoration of physiological regulatory networks rather than targeting individual neurotoxic molecules in isolation. A systems-level understanding of endogenous neurotoxicity may therefore facilitate the development of earlier biomarkers and more effective interventions aimed at preserving neuronal homeostasis and preventing progressive neurological dysfunction. Full article

Shigella is a foodborne bacterial pathogen with a low infectious dose and significant public health impact. Culture-based and molecular techniques provide reliable identification but are time-consuming. Nanoparticle-based biosensors offer sensitive, selective, and compact alternatives. Recent advances in nanoparticle-based biosensors for Shigella spp. (S. flexneri, S. sonnei, S. dysenteriae, and S. boydii) detection have been reviewed in terms of signal amplification, biorecognition, biological targets, sensor types, and performance in real food matrices. Detection strategies rely on gene-level and whole-cell recognition. Targeting virulence genes, invasion plasmid antigen H (ipaH), provides stable genus-level identification, whereas whole-cell recognition facilitates rapid detection without extensive sample preparation. Optical biosensors, including fluorescence-based methods, surface-enhanced Raman spectroscopy (SERS), and localized surface plasmon resonance (LSPR), achieve low detection limits with strong tolerance to complex food matrices. Electrochemical biosensors offer operational simplicity, portability, and suitability for food screening. Lateral flow and hybrid systems provide rapid detection through simplified assay formats and visual readout, with performance influenced by the balance between speed and sensitivity. Validation in real food matrices shows acceptable recoveries, minimal cross-reactivity, and agreement with reference methods. This overview provides a design-oriented framework for nanoparticle-based biosensor selection in food safety by integrating nanomaterial function, biosensor design, and performance characteristics. Full article

The genus Cladosporium represents one of the largest genera of dematiaceous hyphomycetes, which are commonly found on plants. The species comprising this group predominantly function as plant endophytes, producing important bioactive compounds, or act as pathogens damaging crops of significant economic interest. Nevertheless, their association with Camellia spp. remains to be fully elucidated, with only seven recorded cases mentioning three known species. During an investigation into fungi associated with tea plant, several Cladosporium isolates were obtained from symptomatic leaves of Camellia sinensis cv. Fenghuang Dancong. Using a polyphasic approach that combined morphological observations with multi-locus phylogenetic analyses based on the internal transcribed spacer (ITS), actin (act), and translation elongation factor 1-α (tef1-α), these isolates were identified as three new species in the C. cladosporioides complex, namely C. dancongensis sp. nov., C. fenghuangensis sp. nov., and C. leptosporum sp. nov. These new species can be distinguished from their close relatives (e.g., C. benschiae, C. dracaenae, C. kuwanaspidi, and C. tenuissimum) by distinct morphological features such as conidial dimensions, mycelial width, and colony characteristics. This study expands the understanding of fungi associated with Camellia sinensis and is the first case in which new Cladosporium species inhabit tea plants. Moreover, it will facilitate further research into the phylogenetic relationships of these new species and their role relative to tea plant disease. Full article