Search Results (3,969)

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex and debilitating disorder with limited treatment options. Camel milk (CM), known for its rich nutrients and anti-fatigue properties, may offer multi-target benefits for managing this condition. This study utilized an integrated approach combining metabolomics, network pharmacology, and animal experiments. CM metabolites were profiled and screened via ADME. Potential targets were predicted and intersected with CFS/ME-associated genes. Male BALB/c mice were subjected to chronic restraint and forced swimming to evaluate the effects of CM (1000 mg/kg) on behavioral, inflammatory, neuroendocrine, and metabolic parameters. CM administration significantly improved exhaustive swimming time and reduced immobility. It attenuated systemic inflammation (restored IL-10), normalized brain CREB and DRD2/OPRM1 mRNA, and enhanced skeletal muscle AKT/GLUT4 expression and glycogen levels. Camel milk alleviates CFS/ME symptoms through the multi-component, multi-target regulation of neuroendocrine, inflammatory, and energy metabolism pathways. These preclinical findings suggest that CM may have potential as a supportive nutritional intervention for alleviating chronic fatigue, pending validation in human studies. Full article

The colonic epithelial barrier is a multilayered defense system comprising the mucus layer, intestinal epithelial cells (IECs), and the underlying lamina propria. These components collectively maintain mucosal homeostasis and restrict microbial translocation. Disruption of this barrier is a hallmark of chronic intestinal inflammation particularly in IBDs, and is primarily driven by pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, and IL-6. TNF-α and IFN-γ synergistically induce epithelial cell apoptosis and tight junction disassembly through mechanisms involving TNFR2 upregulation, myosin light chain kinase (MLCK) activation, and adherens junction destabilization. IL-1β amplifies paracellular permeability via NF-κB-dependent MLCK induction and OCLN downregulation, while IL-6 promotes barrier leakiness by upregulating CLDN-2 and sustaining self-reinforcing inflammatory loops that maintain chronic inflammation and impede epithelial repair. This leads to persistent immune-cell infiltration, chronic tight junction remodeling, and failure of barrier replenishment. Consequently, leaky colon facilitates microbial and antigen translocation into the lamina propria, further activating immune cells and perpetuating pro-inflammatory signaling. This review synthesizes current evidence and studies on the cooperative and self-reinforcing roles of pro-inflammatory cytokines, providing insight into the mechanisms underlying chronic intestinal barrier dysfunction and highlighting the need for therapeutic strategies that simultaneously target multiple inflammatory axes to restore barrier integrity in inflammatory bowel disorders. Full article

Objectives: We aimed to develop a practical dietary quality score reflecting the Cantonese dietary pattern and evaluate its validity against established indices. Methods: The Cantonese Dietary Index (CDI) was constructed based on Cantonese dietary principles. Reliability was assessed using intraclass correlation coefficients (ICC) over 5–6 years in the GNHS. Validity was evaluated using Spearman correlations with dietary indices (aMed, DASH, and DBI) and by comparing associations with metabolic syndrome (MetS) across dietary indices using regression models. The CDI was developed from the Guangzhou Nutrition and Health Study cohort (GNHS) and validated in the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort and the National Health and Nutrition Examination Survey (NHANES). Results: A total of 4025 (GNHS), 29,165 (TCLSIH), and 28,890 (NHANES) participants were included. Median CDI scores were 58.5, 51.0, and 49.0, respectively. The 5–6-year ICC was 0.33 (p < 0.001). The CDI was moderately correlated with dietary indices across the three studies (GNHS: from −0.55 [DBI-LBS] to 0.61 [DASH], TCLSIH: from −0.61 [DBI-DQD] to 0.71 [DASH], NHANES: from −0.33 [DBI-DQD] to 0.68 [DASH]). The odds ratios (95% CIs) of MetS for CDI, aMed, and DASH scores were 0.80 (0.74, 0.86), 0.91 (0.84,0.99), and 0.83 (0.77, 0.90) in GNHS, 0.95 (0.92, 0.98), 0.99 (0.96, 1.02), and 0.92 (0.89, 0.95) in TCLSIH, and 0.80 (0.77, 0.84), 0.80 (0.76, 0.84), and 0.72 (0.69, 0.76) in NHANES. Conclusions: The CDI demonstrated moderate validity and reliability in Chinese populations and was inversely associated with MetS. Full article

Ocular surface inflammation is a major disruptor of corneal epithelial homeostasis and a key driver of limbal stem cell deficiency (LSCD). Limbal stem cells (LSCs), residing within the specialized limbal niche, maintain corneal transparency through continuous epithelial renewal and by preventing conjunctival encroachment onto the corneal surface. Chronic or severe inflammatory insults—stemming from systemic autoimmune disorders, ocular surface diseases, infections, trauma, or environmental stressors—can damage both LSCs and their microenvironment, ultimately leading to limbal insufficiency. This review synthesizes current insights into the mechanisms by which inflammation impairs LSC survival, including cytokine-mediated cytotoxicity, oxidative stress, immune cell infiltration, and disruption of essential signaling pathways such as Wnt, Notch, and BMP. The distinction between LSC depletion and LSC dysfunction is highlighted, as residual stem cells may persist even in clinically advanced disease and can regenerate the corneal surface once the inflammatory milieu is corrected. Clinical manifestations, staging systems, and diagnostic markers—including p63α, ABCG2, and additional emerging molecular indicators—are summarized to support accurate assessment of LSCD severity. Current therapeutic strategies, ranging from anti-inflammatory medical management to surgical approaches such as SLET, CLET, and allogeneic transplantation, are reviewed alongside evolving regenerative and cell-based therapies. By integrating mechanistic understanding with clinical implications, this review underscores the critical interplay between inflammation and limbal niche failure and emphasizes the importance of early recognition and targeted intervention to preserve or restore LSC function. Full article

Background: The contribution of oral inflammatory conditions to systemic disease burden remains underexplored within multimorbidity frameworks. Emerging evidence suggests that periodontal inflammation may play a role in the clustering of chronic diseases, yet few studies have evaluated this at a population level using robust datasets. The aims of this study were to investigate whether periodontal diseases are associated with Multiple long-term conditions (MLTCs) burden and severity in two population-based cohorts and to examine whether systemic inflammatory biomarkers mediate these associations. Materials and Methods: We analyzed two population-based cohorts: the UK Biobank (UKB; n = 500,612) and the US National Health and Nutrition Examination Survey (NHANES; n = 10,714). MLTCs were defined as the coexistence of ≥2 chronic diseases. Associations between periodontal diseases and MLTCs were assessed using multivariable logistic and multinomial logistic regression. Causal mediation analyses examined the contribution of systemic inflammatory markers. Results: Approximately half of all participants had MLTCs. The prevalence of periodontal diseases was 17.8% in UKB (self-reported symptoms), and 42.3% in NHANES (clinically assessed). Periodontal diseases were independently associated with greater odds of MLTCs in both UKB (OR 1.12; 95% CI 1.10–1.14) and NHANES (OR 1.22; 95% CI 1.09–1.37). Associations were stronger among adults aged ≤ 60 years. A consistent dose-response relationship was observed between periodontal status and the number and severity of chronic conditions, as well as inflammatory-related MLTCs. Mediation analyses suggested partial effects through white blood cell count, neutrophils, and C-reactive protein. Conclusions: Periodontal inflammation is independently associated with greater multimorbidity burden, particularly in younger adults. Systemic inflammation may offer a plausible biological link, and these findings position oral health as an underrecognized and modifiable target in multimorbidity prevention and management frameworks, warranting prospective investigation. Full article

Apitherapy is a complementary therapeutic approach based on the use of bee-derived products, particularly bee venom (BV), also known as apitoxin. Bee venom is a complex mixture of biologically active compounds, including peptides, enzymes, and biogenic amines, that exhibit diverse pharmacological activities. Major bioactive constituents such as melittin, apamin, adolapin, and phospholipase A2 have attracted increasing scientific interest due to their anti-inflammatory, antioxidant, antimicrobial, analgesic, and immunomodulatory properties. This review provides a comprehensive overview of the biological effects and therapeutic potential of bee venom in the management of chronic diseases, particularly diabetes, cancer, and neurological disorders. Evidence from experimental and clinical studies suggests that BV and its components can modulate multiple molecular pathways associated with oxidative stress, inflammation, apoptosis, and immune responses. These mechanisms contribute to potential benefits in glycemic control, tumor suppression, neuroprotection, and pain management. Additionally, bee venom has been investigated for its capacity to influence signaling pathways involved in cellular proliferation and survival, highlighting its potential as a complementary strategy in the treatment of complex diseases such as neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Despite these promising therapeutic effects, the clinical use of BV remains limited due to safety concerns, particularly the risk of allergic reactions, systemic toxicity, and anaphylaxis. Recent advances in drug delivery systems and nanotechnology may help improve the safety and efficacy of BV-based therapies by enabling targeted delivery and controlled dosing. Overall, bee venom represents a promising source of bioactive compounds with potential applications in translational and integrative medicine; however, further well-designed clinical trials and mechanistic studies are necessary to establish its safety, efficacy, and long-term therapeutic value. Full article

Cancer is attributed to being caused by multiple genetic, epigenetic, and various direct and indirect environmental factors. Microplastics are defined as pieces of plastic that are smaller than five millimeters. Microplastics have been emphasized as ubiquitous environmental contaminants found in terrestrial and aquatic systems, food webs, and the human body. Moreover, microplastics can bind to environmentally harmful pollutants, heavy metals, and refractory organic pollutants that can aggravate the biological effects of these pollutants. Microplastics are suggested to induce chronic inflammation, oxidative stress, and genotoxicity by adsorbing and modifying the biomolecules in the biological systems. Oxidative stress, inflammation, and chemical-induced genetic and epigenetic changes in cancer cells and cancer-associated cells are considered as crucial processes in the development, progression, and therapeutic outcome of cancer. Among numerous tumor-promoting environmental factors, preclinical and clinical evaluations of how microplastics contribute to cellular and non-cellular pro-tumorigenic mechanisms like inflammation, genomic instability, and epigenetic modulation are emerging. This review will contribute to a better understanding of microplastics as additional environmental components apart from established carcinogens and genotoxic substances that directly or indirectly influence the pro-tumor microenvironment. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative disorder ranking first as cause of dementia in the elderly. It is characterized by the progressive deterioration of the central nervous system, leading to impaired cognitive function and reduced ability to perform daily activities. Pathological hallmarks of AD include the accumulation of β-amyloid plaques and neurofibrillary tangles which ultimately cause neuronal death and synaptic loss. The vast majority of AD cases are sporadic, with aging representing the primary non-modifiable risk factor contributing to disease susceptibility and progression. However, several factors encompassing genetic predisposition, systemic inflammation, chronic diseases, infections, traumatic brain injury, lifestyle factors, and environmental exposures may affect AD onset. This work aims to describe and discuss the main molecular pathways involved in AD pathophysiology and to examine how these mechanisms cross-interact in promoting neurodegeneration and disease progression. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article

Background: Endometriosis is traditionally conceptualized as a localized gynecological disorder characterized by the presence of ectopic endometrial tissue. However, high recurrence rates following apparently complete surgical excision challenge this lesion-based paradigm and suggest the existence of underlying biological mechanisms that extend beyond residual disease. Increasing evidence indicates that endometriotic cells exhibit persistent molecular alterations, including dysregulated gene expression, epigenetic modifications, and immune dysfunction, which may contribute to disease maintenance and recurrence. Objective: This study aims to critically examine whether endometriosis can be considered a molecularly reprogrammed disease, characterized by persistent cellular and microenvironmental alterations that are not reversed by surgical removal of visible lesions. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases including studies published from January 2016 to March 2026. Studies investigating molecular, genetic, epigenetic, and immunological mechanisms of endometriosis persistence and recurrence were included. Particular attention was given to pathways involved in cellular survival, inflammation, hormone resistance, and epigenetic regulation. Results: Endometriotic cells demonstrate stable alterations in gene expression profiles, including pathways related to estrogen signaling, progesterone resistance, inflammation, and cellular proliferation. Epigenetic mechanisms, such as aberrant DNA methylation and histone modifications, appear to sustain these changes over time, contributing to a form of “molecular memory.” In parallel, the peritoneal microenvironment is characterized by chronic inflammation, immune tolerance, and impaired clearance of ectopic cells. These factors collectively support lesion persistence and may explain recurrence even after complete surgical excision. Emerging evidence also highlights the role of systemic factors, including endocrine–immune interactions and microbiome-related pathways, reinforcing the concept of endometriosis as a systemic rather than purely localized condition. Conclusions: Endometriosis may be more accurately defined as a persistent, molecularly reprogrammed disease driven by stable alterations in cellular behavior and the surrounding microenvironment. This paradigm shift has important clinical implications, suggesting that surgical treatment alone may be insufficient and that future therapeutic strategies should target the underlying molecular and immunological mechanisms responsible for disease persistence. Full article

Plant-derived bioactive metabolites have emerged as promising modulators of oxidative stress and inflammation, two interconnected processes involved in the pathogenesis of numerous chronic diseases. Arid ecosystems, particularly the Sonoran Desert, constitute an underexplored source of structurally diverse phytochemicals with significant pharmacological potential. This review provides a comprehensive overview of major classes of plant-derived bioactives, including polyphenols, flavonoids, terpenoids, and alkaloids, with emphasis on their molecular mechanisms of antioxidant and anti-inflammatory action. These compounds exert cytoprotective effects through direct reactive oxygen species (ROS) scavenging and indirect regulation of endogenous defense systems, primarily via activation of the Nrf2/Keap1 pathway and suppression of NF-κB signaling. Additional pathways, including MAPK, PI3K/Akt, AMPK, and mitochondrial regulatory networks, are discussed as critical mediators of redox balance and inflammatory control. Particular attention is given to Sonoran Desert plant species such as Bucida buceras, Phoradendron californicum, Larrea tridentata, Opuntia spp., and Agave deserti, all of which demonstrate promising biological activities associated with enhanced adaptation to environmental stress. Experimental approaches used to evaluate phytochemical bioactivity, including chemical assays, cellular models, omics technologies, and translational strategies, are also examined. Furthermore, this review discusses current limitations related to bioavailability, phytochemical variability, and clinical validation, highlighting emerging nanodelivery systems and precision medicine approaches as potential solutions. Collectively, the evidence supports the therapeutic relevance of Sonoran Desert plant bioactives as multi-target agents for modulating oxidative stress, inflammation, and chronic disease progression Full article

Objective: This study aimed to evaluate the prognostic value of inflammatory biomarkers and their interaction with nutritional status for risk stratification in patients with chronic limb-threatening ischemia (CTLI). Material and Methods: This was a prospective, single-center observational cohort study including adult patients admitted with CTLI. Clinical outcomes included major amputation, major vascular events (MACE), and all-cause mortality. Multivariate logistic regression analyses were performed using two separate models, one including IL-6 and another including hsCRP, to avoid potential collinearity between biomarkers. Model discrimination was assessed using ROC curves, and Kaplan–Meier survival analyses were performed. Results: A total of 170 patients were included (mean age 72 ± 12 years; 74% male), with high cardiovascular risk and frequent malnutrition and sarcopenia. At 6 months, major amputations occurred in 35.3% of patients, MACE in 35%, and all-cause mortality in 32%. In multivariable analyses, malnutrition was the strongest independent predictor of the composite endpoint. IL-6 (OR 2.90, 95% CI 1.45–5.81; p = 0.003) and hsCRP values above the median (OR 4.22, 95% CI 2.04–8.72; p < 0.001) remained independently associated with adverse outcomes, together with age > 72 years. The hsCRP-based model showed slightly higher discriminative performance than the IL-6 model (AUC = 0.77 VS AUC = 0.75). Kaplan–Meier analyses demonstrated significantly reduced event-free survival in patients with elevated inflammatory biomarkers. Conclusions: In CTLI, systemic inflammation and nutritional status jointly identify patients at extremely high risk of adverse outcomes. hsCRP, given its availability, may be a practical tool for clinical risk stratification. Full article

Multiple Sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system characterized by leukocyte infiltration, inflammation, demyelination, and progressive neurodegeneration. Susceptibility to MS is influenced by genetic factors, including variants within the human leukocyte antigen (HLA) region, (notably HLA-DR15), and multiple single nucleotide polymorphisms that modulate T cell function and immune regulation. Clinically, early manifestations such as visual disturbances, sensory deficits, fatigue, and impaired coordination often precede more advanced features, including cognitive decline and bladder or bowel dysfunction. Although experimental and genetic models of neuroinflammation have facilitated the development of therapies that reduce relapse rates and slow disease progression, the underlying pathological mechanisms remain incompletely understood. Emerging evidence points to the importance of cytoskeletal organization and membrane-associated signaling platforms in maintaining neuronal and immune cell function. Disruption of these systems may contribute to demyelination and neuroinflammatory cascades. Within this context, a systems biology perspective is particularly valuable, as it emphasizes the integration of multiple, interdependent pathways rather than isolated mechanisms. Caveolin-1 (Cav-1), an integral membrane protein of caveolae, has gained attention as a potential central regulator due to its role in coordinating signaling processes across diverse cellular compartments. In this review, we examine the potential genetic and functional contributions of Cav-1 to MS pathophysiology, with a focus on its involvement in oxidative stress, inflammation, blood–brain barrier integrity, and autophagy. By framing these processes as components of an interconnected network, we highlight Cav-1 as a context-dependent modulator that may influence both disease progression and severity. However, despite its mechanistic relevance, the translational potential of Cav-1 remains uncertain, and further studies are required to clarify its precise role and evaluate its suitability as a therapeutic target in MS. Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article