Search Results (8,276)

Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disorder marked by impaired insulin action, pancreatic β-cell dysfunction, and the involvement of several interconnected mechanisms, including inflammation, oxidative stress, and epigenetic alterations. Despite progress in conventional therapies, achieving durable glycemic control and minimizing complications remain major challenges. This review discusses the emerging role of bioactive phytochemicals—such as curcumin, berberine, resveratrol, flavonoids, and polysaccharides—in modulating essential molecular pathways including AMPK, PI3K/AKT, and cAMP/PKA, which contribute to enhanced insulin sensitivity, glucose regulation, and β-cell protection. These natural compounds also influence gut microbiota modulation and epigenetic mechanisms, offering additional metabolic and anti-inflammatory benefits. This review synthesizes evidence from peer-reviewed studies published between 2000 and 2024, incorporating bibliometric trends showing an increasing research focus on phytochemicals for T2DM management. However, limitations such as low solubility, instability, and poor absorption restrict their clinical application. Advances in nanotechnology-based delivery systems, including nanoparticles, liposomes, and nanoemulsions, have shown potential to overcome these barriers by improving stability, bioavailability, and targeted delivery of phytochemicals. The integration of gut microbiota modulation with nanocarrier-enabled phytochemical therapy supports a precision medicine approach for managing T2DM. Preliminary clinical evidence highlights significant improvements in glycemic control and inflammatory status, yet further large-scale, well-controlled trials are essential to ensure safety, optimize dosages, and standardize combination regimens. Overall, phytochemical therapies, reinforced by nanotechnology and microbiota modulation, present a promising, safe, and holistic strategy for T2DM management. Continued interdisciplinary research and clinical validation are crucial for translating these advances into effective therapeutic applications and reducing the global diabetes burden. Full article

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system marked by inflammatory demyelination and progressive neurodegeneration. Although current immunomodulatory therapies can reduce relapse rates, they are often associated with limited long-term efficacy and adverse effects, highlighting the need for safer and more comprehensive complementary approaches. Dietary bioactive phytochemicals—notably, the polyphenols epigallocatechin-3-gallate (EGCG), curcumin, and resveratrol—have demonstrated potential to modulate the immune and inflammatory pathways implicated in MS pathogenesis. In addition to their immunomodulatory roles, emerging evidence suggests that these compounds also exert neuroprotective effects independent of immune modulation, including antioxidant activity, mitochondrial stabilization, and enhancement of neurotrophic signaling. Furthermore, recent studies identify the gut microbiota as a central mediator of MS pathophysiology and of how dietary phytochemicals are metabolized and exert their effects. This review examines experimental data evaluating the therapeutic potential of selected bioactive phytochemicals in MS, focusing on their mechanisms of action—including both immune-dependent and immune-independent neuroprotective effects—and interactions with the gut microbiota. Current limitations in translating findings from animal models to clinical settings are also discussed, and future directions for research in this evolving area are highlighted. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca²⁺) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca²⁺ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies. Full article

Oxidative stress and inflammation are key drivers in the pathogenesis of various chronic diseases, including cardiovascular disease, neurodegenerative disorders, chronic kidney disease, and diabetes. This study evaluated the antioxidant and anti-inflammatory activities of SHE, CME, and FCME, all cultivated in northern Thailand. Human embryonic kidney cells (HEK293) were exposed to FeSO₄ to induce oxidative stress and to LPS to stimulate inflammation. Cell viability was assessed using the MTT assay, while intracellular ROS production was measured using the DCFH-DA. Lipid peroxidation was quantified using the thiobarbituric acid reactive substances assay, and the interleukin-6 (IL-6) release was determined by ELISAs. All extracts demonstrated low cytotoxicity; however, cell death increased at 48 h compared to 24 h. At 200 µg/mL, SHE, CME, and FCME significantly reduced the H₂O₂-induced ROS generation, with the combined treatment of SHE and FCME producing a more pronounced reduction than the individual treatments. Furthermore, the combination of SHE and FCME markedly decreased malondialdehyde (MDA) and IL-6 levels compared with other groups. These findings suggest that shallot and cha-miang extracts, particularly in combination, exhibit promising antioxidant and anti-inflammatory properties in kidney cell models. This combination could therefore be explored as a nutraceutical strategy for the prevention and management of chronic kidney disease, in which oxidative stress and inflammation play pivotal roles. Overall, our finding highlight the potential of the combined use of SHE and FCME as a functional ingredients in the food and pharmaceutical industries. Full article

Women exhibit a higher prevalence of depression, anxiety, stress-related disorders, and autoimmune conditions compared to men, yet the biological mechanisms underlying this sex difference remain incompletely understood. Growing evidence identifies neuroinflammation as a central mediator of psychiatric vulnerability in women, shaped by interactions between sex hormones, immune activation, and neural circuit regulation. Throughout the female lifespan, fluctuations in estrogen and progesterone, such as those occurring during puberty, the menstrual cycle, pregnancy, postpartum, and perimenopause, modulate microglial activity, cytokine release, and neuroimmune signaling. These hormonal transitions create windows of heightened sensitivity in key brain regions involved in affect regulation, including the amygdala, hippocampus, and prefrontal cortex. Parallel variations in systemic inflammation, mitochondrial function, and hypothalamic–pituitary–adrenal (HPA) axis responsivity amplify stress reactivity and autonomic imbalance, contributing to increased risk for mood and anxiety disorders in women. Emerging data also highlight sex-specific interactions between the immune system and monoaminergic neurotransmission, gut–brain pathways, endothelial function, and neuroplasticity. This review synthesizes current neuroscientific evidence on the sex-dependent neuroinflammatory mechanisms that bridge hormonal dynamics, brain function, and psychiatric outcomes in women. We identify critical periods of vulnerability, summarize converging molecular pathways, and discuss novel therapeutic targets including anti-inflammatory strategies, estrogen-modulating treatments, lifestyle interventions, and biomarkers for personalized psychiatry. Understanding neuroinflammation as a sex-specific process offers a transformative perspective for improving diagnosis, prevention, and treatment of psychiatric disorders in women. Full article

Background: Allergic rhinitis (AR) is a chronic immunoglobulin E (IgE)-mediated inflammatory disorder triggered by aeroallergens. Oxidative stress (OS) is increasingly recognized as a key factor in AR pathophysiology. This study aimed to investigate dynamic thiol–disulfide homeostasis (TDH) and OS markers in AR patients compared to healthy controls. Methods: Sixty-two participants (31 AR patients, 31 controls) were enrolled. Hematological and biochemical parameters were measured. OS markers including total thiol (TT), native thiol (NT), disulfide, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed. Correlations between OS markers and laboratory parameters were analyzed. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of OS markers. Results: TT and NT levels were significantly lower in AR patients, whereas disulfide, disulfide/NT and disulfide/TT ratios, TOS and OSI were significantly higher. TAS levels were slightly lower in AR patients. TT and NT correlated positively with eosinophil counts and negatively with monocyte, platelet, AST, and creatinine levels. ROC analysis indicated strong diagnostic potential: TT (AUC = 0.749, cutoff 415 µmol/L, sensitivity 90%, specificity 61%), NT (AUC = 0.786, cutoff 373.2 µmol/L, sensitivity 90%, specificity 71%), and disulfide (AUC = 0.690, cutoff 20 µmol/L, sensitivity 74%, specificity 61%). Conclusions: AR patients exhibit disrupted TDH and elevated OS. These markers may serve as sensitive indicators of oxidative imbalance, offering potential diagnostic and therapeutic insights into AR management. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurrent disorder of the pilosebaceous unit with numerous comorbidities. Growing evidence suggests that depression and anxiety occur more frequently in HS patients, yet their relationship with clinical severity and especially subjective symptoms remains insufficiently understood. The aim of this study was to assess the prevalence and severity of probable depressive and anxiety symptoms in Polish patients with HS and to examine their associations with clinical disease severity, pain and itch intensity, and quality of life (QoL). Methods: Eighty-four HS patients were included in this cross-sectional study. Disease severity was assessed using Hurley staging and the IHS4. Pain and itch intensity were evaluated using the Numeric Rating Scale (NRS). Psychological assessment included self-administered screening questionnaires, such as PHQ-9 and HADS-D for depression and GAD-7 and HADS-A for anxiety. QoL was measured using DLQI and HiSQOL instruments. Statistical analyses were performed with p < 0.05 considered significant. Results: Possible depressive disorders were identified in 25.0% of patients. PHQ-9 and HADS-D scores differed significantly across Hurley stages and correlated positively with IHS4. Possible anxiety disorder according to GAD-7 criteria was present in 15.5% of patients. Both GAD-7 and HADS-A correlated with IHS4. They also showed correlations with pain and/or itch intensity. All psychological measures showed strong correlations with both QoL instruments. Conclusions: Depression and anxiety seem to be common in HS and closely associated with clinical severity and reduced QoL. Their relation with pain and itch requires further studies. These findings underscore the need for multidisciplinary management in HS care. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, resulting in cardinal motor symptoms such as tremor, rigidity, and bradykinesia. Neuroinflammation is increasingly recognized as a central driver of PD onset and progression in which oligodendrocytes, astrocytes, and microglia engage in complex bidirectional crosstalk that shapes the inflammatory milieu of the central nervous system. Pathological activation of glial cells triggers the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, thereby exacerbating neuronal injury and contributing to sustained disease progression. Modulating maladaptive glial activation states and their intercellular communication represents a promising therapeutic avenue aimed at mitigating neuroinflammation and slowing PD pathology. This review synthesizes current knowledge on neuroinflammation in PD, focusing on the distinct roles of microglia, astrocytes, and oligodendrocytes, their interaction networks, and emerging therapeutic strategies. Full article

The enteric nervous system (ENS) is a critical component of the gut–brain axis, playing a pivotal role in gastrointestinal homeostasis and systemic health. Emerging evidence suggests that ENS dysfunction precedes central neurodegenerative disorders. Progesterone, known for its neuroprotective and anti-inflammatory properties in the central nervous system (CNS), has received growing attention for its potential role in ENS physiology. This study aimed to map the expression of nuclear and membrane-bound progesterone receptors in the human ENS, considering regional intestinal, sex, and age variations. Immunofluorescence and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) were used to evaluate receptor distribution in anatomically distinct intestinal regions. Consistent expression of classical nuclear progesterone receptors (PR-A/B) and the non-classical Progesterone receptor membrane component 1 (PGRMC1) in myenteric ganglion cells across all intestinal segments was observed. RT-PCR confirmed the expression of PR-A/B, PGRMC1, mPRα, and mPRβ, with regional variations. Sex-specific patterns were evident along with age-related downregulation. Our findings provide a detailed characterization of progesterone receptor expression in human ENS, highlighting sex- and age-dependent regulation. The identification of progesterone signaling within the myenteric plexus suggests a hormonal influence in gut–brain communication. Targeting ENS progesterone receptors may open novel therapeutic avenues to modulate neurodegenerative CNS disorders via peripheral intervention along the gut–brain axis. Full article

Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article

This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus. Full article

Maternal immune tolerance and controlled inflammatory responses are essential for fetal development and successful pregnancy. Regulatory T cells (Tregs) and B cells with regulatory properties (Bregs) maintain this balance by limiting excessive immune activation through the secretion of anti-inflammatory and tolerogenic cytokines, such as IL-10, TGF-β, and IL-35. Moreover, alterations in the costimulatory potential of antigen-presenting cells (APCs), including B cells, modulate the activation and differentiation of T cells. Toll-like receptors (TLRs), particularly TLR9, influence B-cell antigen presentation and cytokine production, thereby affecting the balance between pro-inflammatory and tolerogenic responses at the maternal–fetal interface. TLR9 overexpression has been observed in several pregnancy-related disorders in both humans and murine models. In this study, we examine whether blocking TLR9 shortly after mating could improve pregnancy outcomes and modulate the regulatory and antigen-presenting functions of B cells, as well as their interactions with T cells. Using an abortion-prone murine model (CBA/J × DBA/2J), we show that intraperitoneal administration of a TLR9 antagonist (ODN 2088) shortly after mating increases embryo resorption in CBA/J females compared to controls without affecting implantation. Flow cytometry analysis further reveals that mice receiving the TLR9 antagonist are characterized by downregulation of CD80 and upregulation of CD86 on B cells, accompanied by reduced expression of CD40L and CD28 on T cells, as well as a lower percentage of Tregs and activated T cells. In conclusion, blocking TLR9 signaling shortly after mating does not improve pregnancy outcomes; conversely, it exacerbates pregnancy loss in the CBA/J × DBA/2J abortion-prone model, while altering the costimulatory phenotype of B and T cells and impairing Treg development during pregnancy. Full article

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks—including glucose metabolism, amino acid metabolism, lipid metabolism, and mitochondrial metabolism—and explores their molecular basis, particularly how curcumin facilitates systemic metabolic improvements by alleviating oxidative stress and interacting with inflammation. Preclinical studies indicate that curcumin accumulates in the intestines, where it remodels the microbiota through prebiotic effects, enhances barrier integrity, and reduces endotoxin influx—all of which are critical drivers of systemic oxidative stress and inflammation. Consequently, curcumin improves insulin resistance, hyperglycemia, and dyslipidemia across multiple organs (liver, muscle, adipose) by activating antioxidant defense systems (e.g., Nrf2), enhancing mitochondrial respiratory function (via PGC-1α/AMPK), and suppressing pro-inflammatory pathways (e.g., NF-κB). Clinical trials have corroborated these effects, demonstrating that curcumin supplementation significantly enhances glycemic control, lipid profiles, adipokine levels, and markers of oxidative stress and inflammation in patients with obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Therefore, curcumin emerges as a promising multi-target therapeutic agent against metabolic diseases through its systemic antioxidant and anti-inflammatory networks. Future research should prioritize addressing its bioavailability limitations and validating its efficacy through large-scale trials to translate this natural antioxidant into a precision medicine strategy for metabolic disorders. Full article