Search Results (4,879)

Chronic neuroinflammation driven by microglial activation is a pathological hallmark of neurodegenerative diseases, and the NF-$\kappa$B/iNOS signaling axis plays a central role in propagating this damage. NF-$\kappa$B-mediated iNOS transcription generates excessive nitric oxide, causing oxidative neuronal injury. The medicinal mushroom Hericium erinaceus produces cyathane diterpenoid erinacines and isoindolinone erinacerins, both reported to attenuate neuroinflammation; however, the molecular basis of their interactions with iNOS and NF-$\kappa$B remains poorly characterized. We screened 21 erinacerins and 18 erinacines against both targets using validated molecular docking, then subjected top-ranked candidates and negative controls to 100 ns molecular dynamics simulations, MM-PBSA binding free energy calculations (±SEM), per-residue energy decomposition, backbone RMSD, and ligand–protein minimum distance analyses, with quercetin as reference. The analysis revealed scaffold-dependent target selectivity: erinacerins exhibited preferential stability with iNOS (erinacerin L: RMSD 0.185 nm), whereas erinacines formed more stable complexes with NF-$\kappa$B (erinacines G and J: RMSD < 0.36 nm). Minimum-distance monitoring confirmed that the elevated ligand RMSD in iNOS predominantly reflected surface relocation rather than dissociation. Erinacine S emerged as the most promising dual-target candidate ($\Delta G_{bind}$: −24.31 ± 0.16 and −14.24 ± 0.11 kcal/mol for iNOS and NF-$\kappa$B, respectively), over twofold stronger than quercetin for iNOS. Negative controls revealed that docking-based ranking was target-dependent in its discriminative capacity, underscoring the need for MD-based refinement. These results identify erinacine S as a priority candidate for experimental validation. Full article

Healing skin wounds is still difficult in many clinical situations, especially when the wounds are chronic or infected. These wounds often stay inflamed for long periods, and the risk of bacterial invasion is high. Oxidative stress tends to increase as well, while the formation of new blood vessels is often inadequate. Because of these factors, wound repair depends on the proper coordination of several biological events. These include basic antimicrobial activities, the control and resolution of inflammation, protection against oxidative damage, the rebuilding of collagen structures, and the development of new vascular networks. Traditional Chinese Medicine (TCM) provides many active compounds. These compounds work on many targets and through different pathways. They show good potential in wound treatment. But many TCM compounds have poor solubility in water. They are also unstable, have low bioavailability, and do not pass through the skin easily. These problems limit their use in clinical settings. Nanotechnology offers new ways to solve these problems. Nanodelivery systems can improve the solubility and stability of active compounds. They can also help the compounds enter the skin and stay in the wound area. Many types of nanocarriers have been developed, such as liposomes, polymer nanoparticles, nanogels, and inorganic nanomaterials. These systems can also provide controlled release or release that responds to the wound environment. This can make the treatment more accurate. In this review, we summarize how major TCM-derived compounds support wound repair and describe the biological mechanisms behind their effects. We also discuss recent nanodelivery approaches that aim to strengthen these therapeutic actions. These combinations can improve antibacterial performance, shape the immune response, reduce reactive oxygen species, and help the skin close more quickly. We also point out several challenges, such as concerns about material safety, the need for more consistent herbal extraction methods, gaps in mechanistic understanding, and the difficulty of producing these formulations on a large scale. Taken together, these points suggest that nanodelivery approaches using TCM-derived compounds still need more careful study and steady improvement before they can be used more widely in wound care. Full article

Ulcerative colitis (UC) is a highly prevalent chronic non-specific intestinal inflammatory disorder for which effective therapeutic options are urgently needed. The active component cimigenoside (CIM) possesses promising anti-inflammatory bioactivity; however, its therapeutic efficacy and underlying molecular mechanism against UC remain to be fully elucidated. The present study aimed to investigate the effects and possible mechanisms of CIM on dextran sodium sulfate (DSS)-induced UC. Mice received drinking water containing 2.5% DSS to induce a UC model, and were then treated with different dosages of CIM for 10 consecutive days. The results found that CIM restored the colonic length, alleviated pathological damage to the colon, preserved intestinal mucosal barrier integrity, and inhibited colonic oxidative stress and inflammatory responses in DSS-induced mice. Additionally, DSS induction reduced the expression of sirtuin 3 (SIRT3) protein in the colonic tissues of mice; however, this was improved by treatment with CIM. Notably, the above protective roles of CIM on DSS-induced UC were unavailable in SIRT3-knockout (SIRT3-KO) mice. Notably, the docking score of CIM binding to SIRT3 is −11.3 kcal/mol, suggesting that CIM could directly bind to SIRT3. Collectively, CIM directly binds to SIRT3 and upregulates its protein expression, which in turn inhibits colonic inflammation and oxidative stress, thereby exerting anti-UC effects. Full article

The objective of this study was to evaluate the physiological mechanisms and health resilience of Duroc pigs reared in an outdoor system compared to a conventional indoor system. A total of 24 Duroc pigs (approximately 3 months of age) were randomly assigned to either an indoor (IN, n = 12) or an outdoor (OUT, n = 12) rearing system for a 45-day trial. Growth performance (body weight and ADG) and spleen organ index were not significantly different between the two rearing systems (p > 0.05). Hematological profiles, including leukocyte and erythrocyte indices, showed no significant differences (p > 0.05), although plateletcrit tended to decrease in the OUT group (p = 0.08). For serum biochemical parameters, pigs in the OUT group exhibited significantly higher concentrations of total protein, triglycerides, calcium, and sodium compared to those in the IN group (p < 0.05). Additionally, serum albumin and glucose levels tended to be higher in the OUT group (p < 0.01). No significant differences were observed in liver and muscle enzyme activities (AST, ALP, GGT, CK) between the treatments (p > 0.05). In conclusion, outdoor rearing did not compromise growth performance or induce chronic physiological stress or tissue damage in Duroc pigs. Instead, it promoted active energy and lipid mobilization, enhanced protein metabolism, and improved mineral homeostasis, demonstrating the robust physiological adaptability of the Duroc breed to outdoor environments. Full article

Ulcerative colitis (UC) is a multifactorial disease characterized by chronic intestinal inflammation and disrupted oxidative balance, significantly impairing patients’ quality of life. Tannins, a class of polyphenolic compounds widely distributed in plants, have demonstrated notable therapeutic potential against UC due to their inherent antioxidant and anti-inflammatory properties. This study employs a systematic literature review of databases, including PubMed and Web of Science, to investigate the molecular mechanisms by which tannins restore intestinal inflammatory and oxidative homeostasis. The findings indicate that tannins directly scavenge reactive oxygen species (ROS) via their polyphenolic structure, mitigate oxidative damage, upregulate antioxidant enzyme expression, suppress pro-inflammatory cytokine secretion, and preserve intestinal barrier integrity. Despite their significant therapeutic promise, challenges such as low bioavailability and structural complexity remain. Future research should prioritize bioavailability enhancement, clarification of structure-activity relationships, and translational studies to facilitate the clinical application of tannin-based therapies for UC. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central pathogenic mechanism linking metabolic dysregulation to retinal injury. The retina is particularly vulnerable to oxidative damage due to its high metabolic demand, elevated oxygen consumption, and abundance of polyunsaturated fatty acids. Hyperglycemia activates multiple interconnected biochemical pathways, including the polyol and hexosamine pathways, protein kinase C signaling, advanced glycation end-product formation, and lipid peroxidation, all of which converge on excessive ROS production and mitochondrial dysfunction. Growing attention has focused on oxidative stress biomarkers as tools to characterize DR severity and progression. Elevated systemic markers of lipid, protein, and DNA oxidation, together with impaired antioxidant capacity, correlate with disease stage, while oxidative biomarkers detected in aqueous and vitreous humor reflect localized retinal injury. Importantly, oxidative stress biomarkers are also associated with functional outcomes, including best-corrected visual acuity and diabetic macular edema. Integration of systemic and ocular oxidative biomarkers with clinical staging may improve risk stratification and support personalized therapeutic strategies in DR. Full article

Background: Body-focused repetitive behaviors (BFRB), including compulsive skin picking, are observed in patients with anorexia nervosa (AN). However, their functional significance remains unclear. AN is characterized by chronic energy restriction and altered interoceptive processing, which may contribute to persistent internal tension beyond overt eating symptoms. This study aimed to explore the functional meaning of compulsive skin picking as a potential behavioral marker of emotional and interoceptive dysregulation relevant to clinical assessment and treatment planning. Methods: A qualitative descriptive study was conducted among 33 hospitalized patients with AN who reported recurrent skin picking leading to tissue damage. Patients were undergoing structured nutritional rehabilitation. Individual semi-structured interviews were performed. Results: Patients with AN described a consistent emotional and physiological sequence preceding skin picking: increased internal tension followed by short-term relief and subsequent self-directed negative emotions. Episodes occurred in contexts of emotional overload, understimulation, reduced emotional awareness, and, in some cases, hunger- or meal-related stress. Participants described the behavior as partly intentional, serving to reduce tension, but at times occurring almost automatically. It was closely connected with eating-related anxiety and dissatisfaction with the body. Conclusions: The findings indicate that compulsive skin picking in AN may reflect underlying emotional and interoceptive instability, instead of being an unrelated co-occurring symptom. In the broader context of chronic energy restriction, such behaviors may reflect attempts to modulate internally generated physiological arousal. Incorporating routine assessment of BFRB into clinical practice could improve the identification of ongoing emotional instability and support more coordinated multidisciplinary care. Future studies combining qualitative insights with physiological measures would help clarify the mechanisms underlying this association. Full article

Neurodegenerative diseases of the central nervous system, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, represent a growing health challenge in ageing populations. Among the mechanisms underlying these disorders, increasing attention has been directed toward the role of cellular senescence. This process, triggered by chronic cellular and oxidative stress as well as DNA damage, leads to irreversible cell-cycle arrest and the development of the senescence-associated secretory phenotype (SASP). Within the central nervous system, the accumulation of senescent cells induces chronic inflammation, blood–brain barrier disruption, and progression of neurodegenerative processes. In this review, we present current evidence regarding the mechanisms of cellular senescence in the central nervous system, with particular emphasis on the role of SASP in neuroinflammation, vascular dysfunction, and neural tissue damage. Experimental and clinical data supporting the involvement of cellular senescence in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are discussed. The review also covers methods for identifying senescent cells in the brain, including molecular marker-based approaches and machine learning-based tools. Importantly, we discuss the methodological limitations of commonly used senescence markers, such as their limited specificity and the risk of false-positive detection, particularly in the heterogeneous cellular environment of the central nervous system. Strategies to improve detection reliability discussed in this review include the use of multimarker signatures, analysis of SASP components using qRT-PCR and ELISA, as well as transcriptomic approaches such as RNA sequencing and single-cell RNA sequencing. Furthermore, we analyze therapeutic strategies targeting senescent cells—senolytics, senomorphics, and SASP modulation—together with their limitations and associated clinical challenges. The collected evidence indicates that precise characterization of senescent cell populations in the brain is essential for the development of disease-modifying therapies for neurodegenerative disorders. Full article

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies. Full article

Neutrophils are among the early responders of the innate immune system and play a key role in host defense against viral infections. Beyond their classical antimicrobial functions, neutrophils can engage in a specialized defense mechanism by releasing web-like extracellular DNA known as neutrophil extracellular traps (NETs). These extracellular traps are a mesh-like network of chromatin DNA decorated with cellular components, including histones, proteases, and antimicrobial enzymes, that function to contain and limit the spread of pathogens. While NET formation contributes to antiviral immunity, accumulating evidence indicates that excessive or dysregulated NET formation can significantly contribute to immunopathology during viral infections. Thus, depending on the context and outcome, NET formation may be viewed as a double-edged sword. Therefore, understanding the regulatory mechanisms governing NET formation and its harmful effects is critical for developing therapeutic strategies that enhance antiviral defense while minimizing tissue damage. In this review, we provide a comprehensive overview of the molecular mechanisms that drive NET formation and clearance, with a particular focus on how viruses modulate these processes to influence disease outcome. We also discuss the pathways underlying NET formation and subsequent neutrophil cell death (NETosis), including canonical and non-canonical pathways, and highlight key signaling axes involving SYK, MAPKs, and NF-κB. Using SARS-CoV-2 and hepatitis B virus as representative models, we examine how different viral components trigger, exploit, or evade NET targeting and how persistent accumulation of NETs can contribute to hyperinflammation, progressive tissue injury, and post-viral syndromes. We further explore emerging evidence linking impaired NET clearance and neutrophil heterogeneity, particularly low-density neutrophils (LDNs), to chronic inflammation and post-viral sequelae such as long COVID and autoimmune hepatitis. Finally, we summarize current and emerging therapeutic strategies aimed at modulating NET formation or enhancing NET clearance. Altogether, this review underscores the dual nature of NETs in viral infections, highlighting their potential roles in antiviral defense and tissue injury, and provides a framework for the development of targeted interventions to limit virus-induced immunopathology. Full article

Chronic exposure to even low levels of pesticides is a serious public health issue, mainly due to the role of oxidative stress in damaging the liver and promoting cancer. This has driven interest in finding natural, plant-based antioxidants that can counteract this kind of chemical injury. In this study, we tested whether a methanol extract from the leaves of Pteropyrum scoparium (PSE) could protect the liver against oxidative harm caused by four common pesticides: acetochlor, deltamethrin, thiamethoxam, and rotenone. Chemical analysis showed that the extract contains high levels of phenolics (345.1 ± 7.6 mg GAE/g) and flavonoids (17.3 ± 1.3 mg CAE/g). GC–MS profiling revealed a diverse set of compounds, including fat-soluble antioxidants like squalene, α-tocopherol, and γ-sitosterol, and water-soluble phenolics like pyrogallol and catechol, suggesting PSE is equipped with a multi-layered antioxidant defence. In the animal experiment, rats were given each pesticide for 30 days, with or without PSE. All four pesticides caused clear oxidative stress in the liver: glutathione (GSH), total antioxidant capacity (TAC), antioxidant enzymes activities dropped, while markers of lipid damage (MDA) and free radical activity (DPPH) rose. Co-administration of PSE significantly restored GSH, TAC and antioxidant enzymes levels and reduced MDA and residual DPPH values compared to pesticide-only groups; these parameters were statistically comparable to the controls (p > 0.05), indicating a substantial recovery of hepatic redox balance. Histopathological examination of liver tissues confirmed these findings, as pesticide treatment caused visible liver injury; deltamethrin and thiamethoxam led to congestion in central veins, while rotenone and acetochlor triggered clusters of inflammatory Kupffer cells. In animals that also received PSE, liver structure remained largely normal, with much less congestion and inflammation. These results show that the combination of antioxidant constituents in PSE might contribute to hepatoprotection through redox modulation and preservation of endogenous antioxidant balance, as suggested by the observed biochemical and histological improvements. Full article

Background: Recurrent vulvovaginal candidiasis (RVVC) is a chronic inflammatory disease primarily caused by Candida albicans (C. albicans). Its pathogenesis remains incompletely understood, and clinical management is challenged by recurrence and drug resistance. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various infectious and inflammatory diseases. However, its role in RVVC remains unclear, with a particular lack of evidence from clinical samples and animal experiments. Objective: This study aimed to investigate the association between RVVC and ferroptosis. First, we analyzed high-throughput sequencing data from human RVVC samples in the Gene Expression Omnibus (GEO) database to identify the expression profile of ferroptosis-related genes. Second, using an established murine model of chronic vulvovaginal candidiasis (CVVC), we validated changes in ferroptosis-related markers in vaginal tissues in vivo. Furthermore, an in vitro model of C. albicans-infected bone marrow-derived macrophages (BMDMs) was employed to explore the underlying mechanisms. This study provides experimental evidence for elucidating the pathogenesis of RVVC and exploring novel therapeutic strategies. Methods: The RVVC-related gene expression dataset GSE278036 was obtained from the GEO database. Differentially expressed genes (DEGs) were screened using the DESeq2 algorithm and intersected with ferroptosis-related genes from the FerrDb database to identify key targets. A protein–protein interaction (PPI) network was constructed using the STRING database and Cytoscape software, and hub genes were identified via the Betweenness centrality algorithm. Functional and pathway analyses, including gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways, were performed. Immune infiltration analysis characterized the immune microenvironment in RVVC patients. A CVVC mouse model was established in vivo, and a C. albicans-BMDMs infection model was established in vitro. The ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to investigate the pathological function and regulatory mechanisms of ferroptosis in RVVC at the molecular, cellular, and tissue levels. Results: Differential analysis identified 3132 DEGs in RVVC, which intersected with ferroptosis-related genes to yield 194 key targets. Among them, 20 hub genes were identified, including ferroptosis regulators and inflammatory factors. Functional enrichment analysis confirmed that these shared targets regulate RVVC pathology through a “ferroptosis-inflammation-immunity” multi-pathway network. Immune infiltration analysis revealed a specific immune disorder in RVVC patients characterized by “activation of the pro-inflammatory innate immune axis and suppression of the adaptive immune axis,” which was closely associated with ferroptosis-related genes. In vivo and in vitro experiments confirmed that C. albicans infection induced ferroptosis in vaginal tissues and macrophages, as manifested by lipid ROS accumulation, Fe²⁺ overload, GSH depletion, downregulation of GPX4 and SLC7A11, upregulation of ACSL4, 4-HNE, and MDA, and mitochondrial structural damage. Macrophages were identified as key target cells for ferroptosis, and their ferroptosis led to impaired antifungal function. Fer-1 treatment significantly inhibited ferroptosis, reduced vaginal histopathological damage and inflammatory cell infiltration, decreased fungal burden, downregulated abnormally elevated inflammatory factors, and restored Th1/Th2 immune balance. Furthermore, Fer-1 preserved macrophage viability and enhanced their antifungal killing capacity. Conclusions: This study provides the first evidence linking RVVC to ferroptosis through a combination of clinical data analysis and experiments, suggesting that ferroptosis is involved in its pathological process. These findings offer a new perspective for elucidating RVVC pathogenesis and developing targeted therapeutic strategies. Full article

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) occurs mainly by inhalation. Studies indicate that respiratory allergic reactions are induced by this pesticide. This study analyzed the effects of chronic inhalation exposure to 2,4-D in the trachea of rats. We exposed the animals during six months to three different concentrations of 2,4-D used for crop spraying. Animals exposed to low concentrations had an increase in the mast cells count, showing that this herbicide can cause allergic reactions in the airways. The tracheal epithelium thickness, the nuclear area and number of nucleolar organizing regions increased proportionally to the exposure concentration and in correlation with each other. These histological tissue changes correspond to epithelial hypertrophy and increased cell activity and multiplication, and show an adaptation to tissue damage caused by 2,4-D. There was a tendency for inversion in the mucus pattern to acid and a decrease in goblet cells in the groups exposed to 2,4-D, which alters the protective mechanisms of the respiratory tract. The 2,4-D induced adaptations in the tracheal epithelium associated with an increase in herbicide concentrations, which may compromise mucociliary function and predispose the epithelium to additional lesions over time. Therefore, it should be used with appropriate respiratory protection equipment to avoid injury. Full article

Chronic crop diseases caused by uncultured, obligate, or host-dependent pathogens challenge traditional pathogen-centric paradigms that often interpret symptoms as direct outcomes of pathogen toxins, effectors, or tissue colonization. Here, we advance a host-centric immune framework that reframes disease as an emergent consequence of dysregulated host immune network activity, including prolonged activation, signaling miscoordination, and systemic physiological disruption. Using citrus huanglongbing (HLB) as a primary exemplar and canola clubroot as a parallel system, we synthesize evidence that persistent immune stimulation can drive self-damaging outputs, including sustained reactive oxygen species accumulation, chronic vascular and transport dysfunction, hormone imbalance, and growth–defense trade-offs. While many observations derive from transcriptomic, physiological, and genetic studies conducted under controlled experimental conditions, the available evidence collectively suggests that persistent immune activation may contribute substantially to disease-associated decline in these systems. We argue that pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) operate as an integrated immune network whose feedback structure can become destabilized under chronic infection, generating immune states that are simultaneously harmful and often ineffective at pathogen clearance. We further discuss how panomic profiling, spatially resolved analyses, and network inference can diagnose host immune states at tissue and cell-type resolution, and how genome editing enables causal tests and rational immune tuning strategies that optimize defense amplitude, timing, and localization rather than indiscriminately amplifying resistance. By centering the host immune system as both a source of protection and pathology, this framework provides a conceptual and practical roadmap for understanding and engineering resilience in HLB, clubroot, and other chronic crop diseases in which pathogen biology remains experimentally opaque. Full article

PRAME (Preferentially Expressed Antigen in Melanoma) is increasingly used as an immunohistochemical marker in the evaluation of melanocytic lesions; however, its expression in benign melanocytic proliferations remains incompletely characterized. This study investigated PRAME expression in melanoacanthomas, with particular emphasis on its relationship with ultraviolet exposure and chronic solar damage. A consecutive series of melanoacanthomas was retrospectively analyzed. Melanocytes were identified and quantified using SOX10 immunohistochemistry, while PRAME-positive melanocytes were counted and graded semiquantitatively according to nuclear staining intensity. PRAME expression was correlated with lesion site (photoexposed versus non-photoexposed skin) and with the degree of solar elastosis. Eighty-four cases were evaluated, of which 25 (29.8%) showed at least focal PRAME positivity in melanocytes. Overall melanocytic density assessed by SOX10 did not differ significantly between photoexposed and non-photoexposed lesions. Similarly, stratification based on total PRAME-positive melanocyte counts, irrespective of staining intensity, revealed no significant association with photoexposure. In contrast, analysis restricted to melanocytes with strong nuclear PRAME expression demonstrated a significant enrichment in photoexposed lesions compared with non-photoexposed sites (p < 0.01). Moreover, high-intensity PRAME expression showed a positive association with increasing grades of solar elastosis. These findings indicate that strong PRAME expression in melanoacanthoma could be associated with chronic sun damage and may reflect non-specific, ultraviolet-related modulation rather than malignant transformation, underscoring the importance of contextual interpretation of PRAME immunohistochemistry in diagnostic practice. Full article