Search Results (1,849)

Aflatoxin B₁ (AFB₁), a major metabolite of aflatoxin, is a highly toxic carcinogen. It frequently contaminates feed due to improper storage of feed ingredients such as corn and peanut meal, with the contamination risk further escalating alongside the increasing incorporation of plant-based proteins in feed formulations. Upon entering an organism, AFB₁ is metabolized into highly reactive derivatives, which trigger an oxidative stress-inflammation vicious cycle by binding to biological macromolecules, damaging cellular structures, activating apoptotic and inflammatory pathways, and inhibiting antioxidant systems. This cascade leads to stunted growth, impaired immunity, and multisystem dysfunction in animals. Long-term accumulation can also compromise reproductive function, induce carcinogenesis, and pose risks to human health through residues in the food chain. Tannins are natural polyphenolic compounds widely distributed in plants which exhibit significant antioxidant and anti-inflammatory activities and can effectively mitigate the toxicity of AFB₁. They can repair intestinal damage by increasing the activity of antioxidant enzymes and up-regulating the gene expression of intestinal tight junction proteins, regulate the balance of intestinal flora, and improve intestinal structure. Meanwhile, tannins can activate antioxidant signaling pathways, up-regulate the gene expression of antioxidant enzymes to enhance antioxidant capacity, exert anti-inflammatory effects by regulating inflammation-related signaling pathways, further reduce DNA damage, and decrease cell apoptosis and pyroptosis through such means as down-regulating the expression of pro-apoptotic genes. This review summarizes the main harm of AFB₁ to animals and the mitigating mechanisms of tannins, aiming to provide references for the resource development of tannins and healthy animal farming. Full article

Background: Dendritic cells (DCs) are heterogeneous antigen-presenting cells that bridge innate and adaptive immunity. Recent classifications of hematolymphoid neoplasms highlight the complex origins of DC-related neoplasms. DCs have also been associated with the progression of multiple myeloma (MM). This report presents the case of a patient with MM in whom bone marrow analysis revealed an unusual additional clonal population of immature cells, in addition to plasmacytoid DCs, that later evolved into plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia (pDC-AML). Methods: The bone marrow of a 69-year-old man with neutropenia and thrombocytopenia was examined by morphology, immunohistochemistry, flow cytometry, cytogenetics, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Serial assessments were performed before and during treatment with bortezomib and dexamethasone for MM, and later with daunorubicin/cytarabine for AML. Results: Initial bone marrow analysis revealed coexisting clonal plasma cells with t(11;14) and a population of CD34+/CD123+/CD45RA+ cells lacking lineage markers, in addition to pDCs, suggestive of precursor DCs rather than acute undifferentiated leukemia. Cytogenetic analysis identified a small clone with isolated del(20q), which corresponded in size to the clone of undifferentiated cells and to the clone with pathogenic variants detected by NGS in the BCOR, RUNX1, and SRSF2 genes. Myeloma therapy decreased both MM and undifferentiated cells; however, within four months, pDC-AML evolved with del(20q) and higher variant allele frequencies of the previously detected gene variants. Remission was achieved with standard AML chemotherapy. Conclusions: This case supports evidence that MM-associated immune dysfunction and bone marrow niche alterations may promote secondary myeloid malignancies independently of cytotoxic therapy. It demonstrates the earliest events in pDC-AML evolution. Furthermore, the immature immunophenotype raises the question of appropriate treatment, since a diagnosis of acute undifferentiated leukemia can be established. Full article

Cigarette smoking is the leading preventable cause of chronic diseases (e.g., COPD, cardiovascular disease, cancer), largely driven by persistent immune-inflammatory mechanisms. This review synthesizes the molecular and cellular cascades linking cigarette smoke (CS) exposure to chronic pathology. CS constituents, particularly ROS/RNS, induce rapid oxidative stress that overwhelms antioxidant defenses and generates damage-associated molecular patterns (DAMPs). These DAMPs activate pattern recognition receptors (PRRs) and the NLRP3 inflammasome, initiating NF-κB signaling and the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). CS exposure causes profound innate immune dysregulation, including airway epithelial barrier disruption, hyperactivated neutrophils, and dysfunctional alveolar macrophages (AMs) that release destructive proteases (e.g., MMP-12) and acquire foam-cell–like characteristics. Furthermore, CS drives adaptive immunity toward a Th1/Th17-dominant phenotype while suppressing regulatory T-cell (Treg) function, thereby promoting autoimmunity and chronic tissue injury. Critically, CS induces epigenetic reprogramming (e.g., DNA methylation, miRNA dysregulation), locking immune cells into a persistent pro-inflammatory state. This convergence of oxidative stress, innate and adaptive immune dysregulation, and epigenetic alterations underlies the systemic low-grade inflammation that fuels smoking-related chronic diseases, highlighting key targets for novel therapeutic interventions. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with heart failure (HF) representing a major contributor to hospitalizations, healthcare costs, and death. Effective management of HF is hindered by the limitations of current biomarkers and diagnostic tools. Conventional biomarkers, such as natriuretic peptides, primarily reflect downstream hemodynamic stress and often lack specificity, particularly in HF with preserved ejection fraction or multiple comorbidities. While imaging provides valuable structural and functional information, it is resource-intensive, costly, and unsuitable for frequent longitudinal monitoring. As a result, these conventional approaches are inadequate to capture the dynamic and heterogeneous nature of HF pathophysiology. Circulating cell-free nucleic acids (cfNAs), including cell-free DNA (cfDNA) and RNA (cfRNA), have emerged as promising noninvasive liquid biopsy biomarkers capable of providing real-time insight into upstream pathological events, such as cardiomyocyte injury, immune activation, inflammation, and maladaptive remodeling. Importantly, cfNAs also act as active mediators of CVD pathology. When released under stress or injury, cfNAs interact with pattern recognition receptors (PRRs) that trigger sterile inflammation, cardiovascular cell dysfunction, and adverse cardiac remodeling. This review summarizes the origins, mechanistic roles, and clinical significance of cfNAs in HF and related CVD, highlighting their dual roles as diagnostic biomarkers and mechanistic effectors of disease. Finally, we discuss emerging cfNA-targeted therapeutic strategies, challenges, and future opportunities for precision medicine in HF and HF-associated CVD. Full article

Oxidative stress (OS) is increasingly recognized as a dynamic disturbance of cellular redox networks rather than a simple imbalance between oxidants and antioxidants. In this context, ferroptosis and cuproptosis—two regulated and metal-dependent forms of cell death—emerge as key mechanisms linking OS to metabolic dysfunction, inflammation, and tissue injury. This review integrates findings from biochemical, lipidomic and metallomic studies to describe how lipid peroxidation (LPO), glutathione (GSH)–Glutathione Peroxidase 4 (GPX4) activity, ferritinophagy, copper-induced mitochondrial protein lipoylation, and altered communication between organelles generate distinct redox signatures across diseases. By examining cutaneous, metabolic, cardiovascular, infectious, neurodegenerative, and oncologic conditions, we outline the shared redox pathways that connect iron- and copper-dependent cell death to systemic inflammation, immune dysregulation, and chronic tissue damage. Common oxidative markers—such as oxidized phospholipids, lipid aldehydes including 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), and systemic metal imbalance—are highlighted as potential indicators of disease severity and as emerging therapeutic targets. We also discuss innovative analytical tools, including redox lipidomics, metallomic profiling and artificial-intelligence (AI)-based classification approaches, which improve the characterization of redox vulnerability and may guide the development of precision redox therapies. Overall, ferroptosis and cuproptosis represent unifying mechanisms that connect OS to multisystem disease and provide new opportunities for diagnostic refinement and targeted antioxidant-based interventions. Full article

The blood–brain barrier (BBB) is essential for maintaining cerebral homeostasis, and its dysfunction is increasingly recognized as an active driver of epilepsy. This review explores the mechanisms by which BBB disruption contributes to seizures and the development of chronic epilepsy. Potentially epileptogenic insults, including traumatic brain injury, stroke, and status epilepticus, induce acute and often persistent BBB leakage. This breach permits the extravasation of serum albumin, which activates transforming growth factor-beta (TGF-β) signaling in astrocytes. This cascade leads to astrocytic dysfunction, impaired potassium buffering, neuroinflammation, and synaptic remodeling, collectively fostering neuronal hyperexcitability. Furthermore, BBB disruption facilitates the infiltration of peripheral immune cells, amplifying neuroinflammation and propagating a pathologic cycle of BBB damage and seizure activity. BBB damage is mediated by multiple processes, including the activation of the plasminogen activation (PA) system. Furthermore, these processes of BBB disruption and neuroinflammation provide a shared pathological basis for neuropsychiatric disorders like depression and anxiety, which are common comorbidities of epilepsy, through shared mechanisms of neuroinflammation and neurovascular unit (NVU) dysregulation. BBB dysfunction can also contribute to the resistance to antiepileptic drugs. Finally, we discuss the therapeutic potential of stabilizing the BBB as a viable strategy for developing disease-modifying therapies for epilepsy. Full article

Residual cardiovascular risk remains a major challenge in coronary artery disease, even after optimal lipid-lowering and anti-inflammatory therapy. Beyond classical risk factors, persistent low-grade inflammation and fibrotic remodeling contribute to adverse outcomes that current treatments fail to fully prevent. Growing evidence highlights the glyco-inflammatory axis—the interplay between protein glycosylation-dependent signaling and inflammation—as an underappreciated contributor to residual atherosclerotic risk, largely because current therapeutic strategies do not directly target glycan-mediated mechanisms. Within this framework, Galectin-3 (Gal-3), a β-galactoside-binding lectin, has emerged as a key molecular hub linking metabolic stress, lysosomal dysfunction, and vascular remodeling. By recognizing specific glycan motifs on immune and stromal cells, Gal-3 orchestrates macrophage activation, endothelial dysfunction, and extracellular matrix deposition, thereby amplifying chronic inflammation and fibrosis. Elevated circulating Gal-3 levels are associated with plaque vulnerability and major adverse cardiovascular events, independent of lipid or C-reactive protein levels. Experimental Gal-3 inhibition reduces inflammation and fibrosis in preclinical models, supporting its therapeutic potential. This review integrates mechanistic, translational, and clinical evidence to propose Gal-3 as a missing link between intracellular stress responses and extracellular fibro-inflammatory remodeling. Targeting the Gal-3-mediated glyco-inflammatory axis may represent a novel strategy to overcome residual cardiovascular risk and achieve comprehensive vascular protection in the post-statin era. Full article

Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with chronic inflammation both in the placenta and systemically. PE is characterized by placental ischemia, which then results in the production and release of anti-angiogenic factors and inflammatory mediators. Inflammation in PE leads to placental, renal, and vascular damage, which contribute to the phenotype of hypertension and organ dysfunction during pregnancy. T cells, B cells, Natural Killer cells, and macrophages have all been shown to play a role in the inflammation present in the disease. T helper cells contribute to the chronic inflammation in PE. They also activate B cells, which produce agonistic autoantibodies against the angiotensin II type 1 receptor. Natural Killer cells are activated in PE and shift away from decidual Natural killer cells, which produce angiogenic factors, and toward cytotoxic Natural Killer cells, which contribute to tissue damage. Macrophages are polarized towards proinflammatory subtypes and contribute to tissue damage and inflammatory signaling in PE patients. As the immune system plays a role in the pathophysiology of the disease, it may be a potential target for therapeutic intervention to improve maternal and fetal outcomes during and following a PE pregnancy. Full article

Microplastics and nanoplastics (MPs/NPs), emerging as pervasive environmental contaminants, have raised growing concern due to their potential implications for human health. Among their diverse biological effects, recent evidence highlights their capacity to cross biological barriers, accumulate in tissues, and interact with cellular components in ways that may promote carcinogenesis. MPs/NPs can cause oxidative stress, inflammation, and epithelial barrier dysfunction, leading to cellular homeostasis disruption. Their interaction with endothelial cells and immune components further exacerbates pro-tumorigenic processes, including angiogenesis, immune evasion, and epithelial–mesenchymal transition (EMT), thereby potentially facilitating tumor initiation and progression. At the cellular level, these particles are internalized through various endocytic pathways, where they are associated with oxidative stress, inflammation, DNA damage, and barrier dysfunction—processes that have been linked to carcinogenesis. This review synthesizes current evidence on the cellular and molecular mechanisms through which MPs/NPs may contribute to cancer development, with particular emphasis on their interactions with endothelial cells and the tumor microenvironment. It highlights the need for further mechanistic and epidemiological studies to clarify the potential role of these particles in carcinogenesis. Given the increasing global production and environmental ubiquity of plastic particles, understanding their direct contribution to cancer development is critical for advancing both public health strategies and environmental regulations. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance, inflammation and immune signaling remain uncertain. Objectives: This study aimed to evaluate whether the presence of MASLD alone, and the presence of T2D within MASLD, are independently associated with high-risk profiles of oxidative/antioxidant markers, peripheral blood mononuclear cell (PBMC) gene expression and adipocytokines. Methods: A total of 190 participants were categorized via abdominal ultrasound as controls (n = 46), MASLD (n = 83) or MASLD with T2D (n = 61). Measurements included advanced oxidation protein products (AOPP) and paraoxonase-1 (PON1) activity in serum; messenger ribonucleic acids expression of cluster of differentiation 36 (CD36), Toll-like receptor 9 (TLR9), and glutathione peroxidase-1 in PBMC; and adiponectin, leptin, and resistin in plasma. Biomarker values were adjusted and statistical comparisons among groups were performed using the Quade test. Subsequently, biomarkers were stratified into tertiles to examine associations between high-risk biomarker levels and the presence of MASLD or T2D in patients with MASLD using multivariate binary logistic regression. Results: Multivariate analysis showed that MASLD presence was independently associated with both increased AOPP and decreased resistin levels in the circulation. Furthermore, T2D presence in patients with MASLD was independently associated with increased CD36 and decreased TLR9 gene expression in PBMCs, as well as elevated circulating leptin levels. Conclusions: Collectively, these findings underscore the complex interplay between oxidative stress, insulin resistance, inflammation, and immune signaling in the pathogenesis of MASLD, which are fundamental factors contributing to this condition. Full article

Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed in sensory neurons, immune cells, pancreatic islets, and vascular tissues. Initially recognized for its role in thermosensation and nociception, TRPV1 has emerged as a key regulator of immune modulation, β-cell physiology, vascular integrity, and neuroimmune signaling—processes central to the pathogenesis and progression of Type 1 Diabetes (T1D). Experimental evidence demonstrates that TRPV1 exerts opposing effects on β-cell physiology—enhancing insulin release during short-term activation, yet accelerating stress and cell loss under chronic stimulation. In the vascular and renal systems, TRPV1 contributes to hallmark T1D complications, including endothelial dysfunction, nephropathy, and impaired cardiovascular protection, while in the central nervous system it drives neuroinflammation, cognitive decline, and emotional dysregulation. TRPV1 sensitization also accelerates the onset and severity of diabetic neuropathy by amplifying pain and inflammatory signaling pathways. Genetic and epigenetic regulation further links TRPV1 to individual susceptibility and disease progression. Collectively, these findings position TRPV1 as both a disease-modifying factor and a determinant of T1D outcomes, underscoring its potential as a biomarker and therapeutic target in autoimmune diabetes. Full article

Vascular Smooth Muscle Cells (VSMC) dysfunction is a major contributor to Type 1 diabetes (T1D)-associated vascular complications. Ca²⁺ is a key messenger responsible for maintaining VSMC tone and function, and alterations in its cytosolic levels are central to diabetes-related vasculopathy. Heat Shock Protein 70 (HSP70), a multifaceted chaperone present intracellularly (iHSP70), regulates vascular reactivity by supporting Ca²⁺ handling, and extracellularly (eHSP70) activates immune signaling. Disruption of eHSP70/iHSP70 balance has been implicated in T1D-associated VSMC dysfunction. Curcumin, a phytochemical found in turmeric, is an emerging therapeutic adjuvant for treating a wide range of pathologies, including diabetes. However, whether curcumin modulates Ca²⁺ dynamics and HSP70 expression, thereby improving VSMC function, in diabetic aorta remains unclear. To investigate this, Streptozotocin-induced diabetic rats (i.p. 65 mg/kg) were treated with curcumin (300 mg/kg) for 28 days. Vascular function was evaluated using wire myography to assess changes in biphasic contraction curve and Ca²⁺ dynamics, while HSP70 was quantified using Western blotting and ELISA. Structural alterations were analyzed by assessing collagen and elastin using Picrosirius staining and fluorescence microscopy. Chronic curcumin treatment improved vascular function by normalizing Ca²⁺ mishandling, restoring the eHSP70/iHSP70 ratio, reducing hypercontractility, and mitigating arterial structural alterations. These findings indicate that curcumin could potentially ameliorate diabetes-related VSMC dysfunction by restoring Ca²⁺ homeostasis and modulating HSP70. Full article

Background/Objectives: Endocrine autoimmune diseases, including autoimmune thyroid, pituitary, parathyroid, adrenal, and gonadal diseases, result from complex interactions between genetic susceptibility and environmental triggers. Advances in genomics and epigenomics have provided novel insights into the molecular pathways leading to immune dysregulation and endocrine tissue destruction. This review summarizes recent progress in understanding the genetic and epigenetic bases, emphasizing shared and disease-specific mechanisms that contribute to autoimmunity and endocrine dysfunction. Methods: A comprehensive literature search was performed in PubMed, Scopus, and Web of Science up to August 2025, focusing on genome-wide association studies (GWAS), next-generation sequencing, and epigenetic profiling (DNA methylation, histone modification, and non-coding RNA regulation). Results: More than 60 susceptibility loci have been identified across endocrine autoimmune diseases (EADs), including key genes in immune tolerance (HLA, CTLA4, PTPN22) and endocrine-specific pathways. Epigenetic studies reveal that altered DNA methylation and histone acetylation patterns in immune and endocrine cells modulate gene expression without changing the DNA sequence, linking environmental exposures to disease onset. Dysregulated microRNAs further influence immune signaling and cytokine networks. Conclusions: Genetic and epigenetic discoveries highlight the multifactorial nature of EADs and reveal potential biomarkers for early detection and targets for precision immunotherapy. Future research integrating multi-omics and longitudinal analyses will be crucial to unravel causal mechanisms and develop personalized preventive strategies. Full article

Dysregulated T-cell-mediated immune responses are a hallmark of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). MicroRNAs (miRNAs) regulate various biological processes and play a significant role in the pathophysiology of numerous diseases. In this study, we aim to clarify the relationship between dysregulated immune response and altered miRNA signatures in patients with IBD. Our goal is to identify differentially expressed miRNAs that could potentially serve as diagnostic markers to differentiate between CD and UC. To quantify circulating miRNAs, we employed small RNA sequencing. To describe immune dysregulation, we determined the levels of circulating T-cell-related cytokines and the distribution of T-cell subpopulations in both circulation and in tissue samples. Our analysis revealed that 14 miRNAs exhibited significant expression differences between IBD patients and control subjects. These miRNAs may also implicate pathways associated with colitis-related colorectal carcinogenesis, suggesting their value in early risk assessment. Furthermore, we found that five miRNAs demonstrated a strong ability to discriminate between CD and UC patients. Additionally, levels of IL-22 and IFN-γ were significantly elevated in individuals with IBD. Notably, miRNA levels showed strong correlations with cytokine levels and T-cell subset distribution in both blood and tissue samples, exhibiting disease-specific patterns. In conclusion, we identified differentially expressed miRNAs in IBD patient groups, and a subset of these miRNAs might exhibit diagnostic potential to distinguish between CD and UC. Analyzing miRNAs in the blood of IBD patients may provide valuable insights into the underlying immune dysfunction. Full article

Chronic inflammatory diseases are driven by persistent immune activation and metabolic imbalance that disrupt tissue homeostasis. Mitochondrial dysfunction disrupts cellular bioenergetics and immune regulation, driving persistent inflammatory signaling. Mitochondrial dysfunction, characterized by excessive production of ROS, release of mitochondrial DNA, and defective mitophagy, amplifies inflammatory signaling and contributes to disease progression. Meanwhile, metabolic reprogramming in immune and stromal cells establishes distinct bioenergetic profiles. These profiles maintain either pro-inflammatory or anti-inflammatory phenotypes through key signaling regulators such as HIF-1α, AMPK, mTOR, and SIRT3. Crosstalk between mitochondrial and metabolic pathways determines whether inflammation persists or resolves. Recent advances have identified critical molecular regulators, including the NRF2–KEAP1 antioxidant system, the cGAS–STING innate immune pathway, and the PINK1–Parkin mitophagy pathway, as potential therapeutic targets. Pharmacologic modulation of metabolic checkpoints and restoration of mitochondrial homeostasis represent key strategies for re-establishing cellular homeostasis. Developing approaches, including NAD⁺ supplementation, mitochondrial transplantation, and gene-based interventions, also show significant therapeutic potential. This review provides a mechanistic synthesis of how mitochondrial dysfunction and metabolic reprogramming cooperate to maintain chronic inflammation and highlights molecular pathways that represent promising targets for precision therapeutics in inflammatory diseases. Full article