Search Results (498)

Chronic low-grade inflammation is a hallmark of both metabolic and neurodegenerative diseases. In recent years, several studies have highlighted the pivotal role of systemic metabolic dysfunction, particularly insulin resistance, in shaping neuroinflammatory processes and contributing to impaired cognitive performance. Among metabolic disorders, type 2 diabetes mellitus has emerged as a major risk factor for the development of age-related neurodegenerative conditions, suggesting a complex and bidirectional crosstalk between peripheral metabolic imbalance and central nervous system function. This review aims to explore the cellular and molecular mechanisms underlying the interaction between metabolic dysregulation and brain inflammation. By integrating current findings from endocrinology, immunology, and neuroscience, this work provides a comprehensive overview of how chronic metabolic inflammation may contribute to the onset and progression of neurodegenerative conditions. This interdisciplinary approach could offer novel insights into potential therapeutic strategies targeting both metabolic and neuroinflammatory pathways. Full article

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article

Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and a shift toward potentially harmful species. The aim of this review is, therefore, to provide an overview of oral–gut communications in mediating frailty and sarcopenia. PubMed, EMBASE and Scopus databases were searched for relevant articles. We limited our search to manuscripts published in the English language. Interactions between oral and gut microbiota occur mainly through three pathways namely the enteral, the bloodstream and the fecal-oral routes. Alterations in the oral–gut microbiota axis contribute to chronic low-grade inflammation (i.e., “inflamm-ageing”) and mitochondrial dysfunction, key mechanisms underlying frailty and sarcopenia. Microbial metabolites, such as short-chain fatty acids and modified bile acids, appear to play an emerging role in influencing microbial homeostasis and muscle metabolism. Furthermore, poor oral health associated with microbial dysbiosis may contribute to altered eating patterns that negatively impact gut microbiota eubiosis, further exacerbating muscle decline and the degree of frailty. Strategies aimed at modulating the microbiota, such as healthy dietary patterns with reduced consumption of ultra-processed foods, refined carbohydrates and alcohol, ensuring an adequate protein intake combined with physical exercise, as well as supplementation with prebiotics, probiotics, and omega-3 polyunsaturated fatty acids, are increasingly recognized as promising interventions to improve both oral and gut microbiota health, with beneficial effects on frailty and sarcopenia. A better understanding of the oral–gut microbiota axis offers promising insights into nutritional interventions and therapeutic strategies for the age-related muscle decline, frailty and systemic health maintenance. Full article

Background/Objectives: We evaluated the efficacy of a good lifestyle intervention on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children with Down syndrome (DS). Methods: This retrospective longitudinal study included 31 children with Down syndrome (DS) who were affected by MASLD and attended nutritional counseling based on a nutritional approach (e.g., Mediterranean diet and antioxidant supplements), as well as physical exercise. Clinical parameters, markers of low-grade systemic inflammation, and hepatic steatosis, as assessed by ultrasound, were evaluated at baseline (T0) and after 6 months (T1). Results: Several anthropometric and biochemical parameters, including body mass index, waist circumference, diastolic and systolic blood pressure, aspartate aminotransferase, basal insulin, insulin resistance, pro-inflammatory interleukin-1β, and anti-inflammatory interleukin-10, showed significant improvement after 6 months of a nutritional approach. This study also found a regression of at least one grade of hepatic steatosis in a significant portion of patients, especially in those who received antioxidant supplements. Conclusions: Our study further supports the hypothesis that a healthy lifestyle intervention, based on adherence to the Mediterranean diet, natural supplements with antioxidant properties, and regular physical activity, can be considered a safe therapeutic approach for reducing the risk and severity of MASLD in children with DS. Full article

Tear film alterations are commonly associated with ocular pathology. The tear film plays a vital role in maintaining the optical properties of the cornea and contains essential elements required for healing and preserving the integrity of the ocular surface. As a biological fluid, the tear film is easily collected using non-invasive techniques, making it a promising candidate for analysis and often referred to as an ideal biofluid. Several studies have attempted to identify biomarkers in the tear film that could be linked to systemic or ocular disorders, with the goal of developing tools for diagnosis or even early prevention. The quality and quantity of the tear film are influenced by hormonal status, emotional experiences related to social and familial events, and the work environment. Systemic disorders are often reflected at the ocular level through alterations in the tear film. Obesity is a well-recognized public health concern, extensively studied and investigated, much like other common systemic conditions. The presence of low-grade, chronic inflammation associated with excess body weight has been validated in several studies. The strategies for preventing obesity induced dry eye disease are based on regular physical activity, maintaining adequate hydration through sufficient fluid intake, weight loss, and the supplementation of essential fatty acids. This narrative literature review aims to highlight the tear film alterations associated with obesity. The article is intended for ophthalmologists, general practitioners, nutritionists, and researchers. Full article

Due to being correlated with metabolic syndrome, diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer, obesity is a global health issue that predisposes those affected to morbidity and mortality. Obesity can be defined as an excessive amount of fat accretion in the body. According to current research, visceral adipose tissue performs a critical function as an active endocrine organ due to its function in releasing adipokines that facilitate complex physiological events. These adipokines exacerbate both low-grade inflammation and oxidative stress (OS), two key constituents of obesity-related comorbidities. This review summarizes the most recent data on the relationship between inflammation, OS, and diseases linked to obesity, focusing on how OS overexpression causes cellular damage by weakening antioxidant mechanisms. To understand the mechanisms by which OS is related to comorbidities, we assess a wide range of models, including animal models, biochemical analysis, and clinical research. The most important discoveries are that heightened OS exacerbates inflammation and cellular damage by increasing the formation of ROS and weakening antioxidant defenses. Increased lipid peroxidation and oxidative damage in adipose tissue associated with insulin resistance and metabolic dysfunction have been identified through data from research conducted on KKAy mice, a model of diabetes obesity. Adipokines, like adiponectin, have been shown to have protective functions against inflammation and OS. Thereby, some of these candidates may become promising therapeutic targets. Understanding the mechanism of these systems is a must for developing therapies to decrease OS, restore antioxidant balance, and reprogram inflammatory pathways. Such tactics may further augment clinical outcomes and reduce the occurrence of obesity-associated diseases in global populations. Unlike previous reviews, this work bridges basic mechanisms and therapeutic implications, with a unique emphasis on translational barriers and future clinical directions. Full article

Background: Nutraceuticals have emerged as promising alternatives to conventional pharmacological treatments for managing joint pain and low-grade inflammation in physically active individuals. However, few clinical studies have evaluated the combined metabolic, inflammatory, and neuroendocrine effects of multi-ingredient supplements. This study aimed to evaluate the effects of Flector Softgel FS Integratore, a multi-component food supplement, on joint pain, inflammatory markers, metabolic health, and orexin-A levels in physically active adults. Methods: In this randomized, controlled, low-intervention study, 25 adult participants (aged 30–60 years and amateur athletes engaging in at least 3 sessions/week of moderate physical activity) were assigned to either a treatment group (n = 15 received Flector Softgel FS for 14 days) or a placebo group (n = 10). The supplement contained 500 mg of Cannabis sativa seed oil (THC-free), 250 mg of Boswellia serrata extract, 250 mg of fish oil, 160 mg of omega-3 fatty acids, and 0.6 mg of undenatured type II collagen (UC-II). Pain was assessed using the Visual Analog Scale (VAS). Metabolic parameters, inflammatory cytokines (IL-6, IL-8, TNF-α, IFN-γ, and IL-10), and serum orexin-A levels were measured before and after the intervention. Results: Compared with the placebo, the treatment group showed a significant reduction in VAS scores (p < 0.001), as well as improvements in BMI, insulin, and lipid profiles, and a decrease in pro-inflammatory cytokines (IL-6, IL-8, TNF-α, and IFN-γ). A reduction in orexin-A levels was also observed in the treatment group (p < 0.001), with a positive correlation between orexin-A and perceived pain. No adverse effects were reported. Conclusions: Flector Softgel FS Integratore may be effective in reducing joint pain and systemic inflammation while supporting metabolic health in active adults. These effects may involve indirect modulation of orexin-A, though the exact mechanisms remain to be clarified. Despite the promising results, conclusions regarding efficacy in comparison with NSAIDs should be approached with caution in the absence of a pharmacological control group. Further studies with larger samples and a longer duration are needed. Full article

Background: Since lung cancer remains a health problem worldwide and is the leading cause of cancer death, finding new tools that can help in the early identification of high-risk patients remains a key target. Methods: A retrospective descriptive study of 70 patients diagnosed with lung cancer at the Clinical County Hospital Mureș was conducted. Information regarding the histopathological type of the tumor, the TNM stage at diagnosis, and the CBC-derived inflammatory status was obtained for all the included patients. Skeletal muscle area was measured at the level of the third lumbar vertebra (L3SMA), based on the patients’ native CT scans, to identify sarcopenia. These four primary characteristics (the histopathological type of the tumor, the TNM stage, the systemic inflammatory status, and the sarcopenic changes) were integrated into a new severity score: the histology, sarcopenia, and lung inflammation score (HISLIS). Subsequently, based on the HISLIS score, the patients were divided into three severity grades (high, medium, and low). Results: Our results showed that patients diagnosed in late advanced TNM stages (III or IV) had the highest severity grade. The severity grade strongly correlated with the systemic inflammatory biomarkers, with the highest severity grades being associated with an increased inflammatory status. In addition, sarcopenic patients were diagnosed in more advanced TNM stages, exhibited higher HISLIS levels, and had a higher degree of systemic inflammation than non-sarcopenic patients. Sarcopenic patients also showed an impaired hematological profile, with hemoglobin (Hb) and hematocrit (Ht) levels being significantly decreased in sarcopenic patients. Conclusions: Future prospective studies are needed to validate the HISLIS and integrate it into the routine clinical and paraclinical assessment of lung cancer patients, as it could represent a triage tool for the early identification of patients at higher risk of unfavorable outcomes. Combining critical information regarding the tumors’ characteristics, such as TNM stage and histological characteristics, together with biological and imaging-derived information like the CBC-derived inflammatory status and the associated degree of sarcopenia, could lead to a complex approach and a personalized therapeutic regimen for this highly deadly condition. Full article

Obesity and Type 2 Diabetes Mellitus (T2DM) are interrelated chronic conditions whose global prevalence continues to rise, posing significant clinical and socioeconomic challenges. Their pathophysiological intersection—commonly referred to as “diabesity”—is sustained by a complex interplay of mechanisms, including visceral adipose tissue inflammation, macrophage polarization, disrupted insulin signaling, and adipokine imbalance. These processes contribute to chronic low-grade systemic inflammation, impair pancreatic β-cell function, and exacerbate glucose intolerance. This review critically explores the mechanistic connections between obesity and T2DM, with a focus on recent advances in pharmacological therapies—such as GLP-1 receptor agonists, SGLT2 inhibitors, and dual GIP/GLP-1 receptor agonists—alongside evidence-based lifestyle modifications and bariatric procedures. By integrating current translational and clinical findings, we aim to provide a comprehensive perspective to support the development of more effective and individualized treatment strategies for diabesity. Full article

Obesity and low back pain (LBP) are major contributors to global disability and healthcare burden in both adults and children. Although a growing body of research supports a bidirectional relationship between these conditions, the underlying mechanisms remain poorly integrated in the current literature. While mechanical overload has traditionally been viewed as the principal link, emerging evidence points to additional roles for metabolic dysregulation, chronic low-grade inflammation, and adipokine activity in the development and persistence of LBP. This review addresses the need for a comprehensive synthesis of how obesity affects spinal structures, including the intervertebral discs, paraspinal muscles, facet joints, and epidural fat, through both biomechanical and systemic biological pathways. We specifically highlight key mechanisms such as oxidative stress, adipokine signalling, and neuroinflammation that may accelerate spinal degeneration and promote chronic pain. In doing so, we aim to bridge gaps between anatomical, biochemical, and clinical perspectives. Additionally, we assess current clinical evidence on weight loss as a potential strategy for alleviating LBP symptoms. By consolidating diverse lines of evidence, this review provides a clearer framework for understanding obesity-related spinal pathology and outlines priorities for future research and targeted interventions. Full article

Obesity is characterized by excessive fat accumulation that triggers chronic low-grade inflammation and systemic immune dysregulation, significantly increasing the risk of metabolic disorders including insulin resistance, type 2 diabetes, and cardiovascular disease. This review examines the bidirectional relationship between obesity and immune dysfunction, focusing on how immune cell infiltration in adipose tissue drives inflammatory processes. We highlight the phenotypic shifts in key immune populations—macrophages polarized toward proinflammatory M1 phenotypes, T cell exhaustion occurrs, and alterations appear in B cells, natural killer (NK) cells, and dendritic cells—that collectively contribute to metabolic deterioration. The gut microbiome emerged as a critical mediator in this relationship, influencing both immune responses and metabolic regulation through gut–liver and gut–brain axes. We explore emerging immunomodulatory therapeutic strategies, including anti-inflammatory agents, microbiota interventions, and targeted immune therapies such as innovative nanomedicine approaches. The review also addresses the challenges of immunotherapy in obesity, particularly the paradoxical effects observed in cancer immunotherapy outcomes and the need for personalized treatment approaches. Artificial intelligence is highlighted as a potential tool to enhance patient stratification and treatment optimization in future immunomodulatory interventions. Understanding these immunometabolic interactions provides a foundation for developing more effective therapeutic strategies that could transform obesity management and reduce the burden of obesity-related metabolic diseases. Full article

Background and Objectives: Over the past few decades, a substantial body of evidence has linked periodontitis to systemic diseases—including hypertension—but the mechanisms underlying this association are not fully understood. This study aims to identify the factors that may mediate this relationship, including an analysis of the inflammatory biomarker NLRP3 and IL-1β levels in serum and saliva in patients with both diseases. Materials and Methods: This study included 108 individuals (mean age, 47.8 years, SD 12.8), 38.9% male and 61.1% female. The participants were divided into four groups: Group I—26 healthy participants; Group II—24 participants with periodontitis; Group III—26 participants with hypertension; and Group IV—32 participants with both periodontitis and hypertension. Clinical examinations were performed to diagnose hypertension and periodontitis, including a survey and blood tests in all patients. NLRP3 and IL-1β levels in serum and saliva were measured using ELISA. Results: Patients with periodontitis and hypertension were significantly older than those without these conditions (respectively, p < 0.001 and p < 0.001) and had more missing teeth (respectively, p < 0.001 and p = 0.037). Higher values were found in the periodontitis and hypertension group than in healthy individuals for VLDL (p = 0.001), triglycerides (p = 0.001), CRP (p = 0.003), WBC (p = 0.007), blood sugar (p = 0.002), total cholesterol (p = 0.003), and LDL (p = 0.010). Significantly higher levels of NLRP3 in saliva (p = 0.038) and serum (p = 0.021) were observed in patients with periodontitis than in those without periodontitis. Significant correlations were found between serum NLRP3 levels and the presence of hypertension (p = 0.001) and between saliva IL-1β levels and the presence of hypertension (p = 0.010). Serum NLRP3 levels demonstrated a predictive value for hypertension (AUC 0.693, 95% CI 0.590–0.796, and p = 0.001), with an established cutoff value of 0.68 ng/mL (sensitivity 0.623, specificity 0.630). Conclusions: The higher levels and correlations of pro-inflammatory markers in serum and saliva observed in patients with periodontitis and hypertension support the hypothesis of a relationship between these diseases, likely mediated by low-grade systemic inflammation. Full article

Background: Pediatric obesity represents a multifactorial condition in which gut microbiota dysbiosis, low-grade systemic inflammation, and metabolic dysfunction are intricately connected. Objectives: This systematic review sought to evaluate and integrate current findings regarding the interactions between gut microbial composition, dietary influences, inflammatory status, and metabolic outcomes in obese pediatric populations. Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted for studies published from January 2010 onward. Eligible studies comprised randomized controlled trials, and cohort, cross-sectional, and longitudinal designs involving individuals aged ≤18 years. Study quality was appraised using the NIH Study Quality Assessment Tool. Results: Sixteen studies fulfilled the inclusion criteria. Dysbiosis was consistently observed among obese children, characterized by alterations in microbial diversity and abundance associated with increased inflammation and adverse metabolic profiles. Dietary interventions, notably symbiotic supplementation and adherence to Mediterranean diet patterns, were associated with favorable modulation of gut microbiota and inflammatory parameters. The majority of studies demonstrated high methodological quality, although minor observational limitations were noted. Conclusions: Gut microbiota dysregulation plays a central role in the development of metabolic and inflammatory complications associated with pediatric obesity. Although dietary and microbiota-modifying strategies show therapeutic promise, their effectiveness must be substantiated through robust, long-term studies. Full article

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a chronic condition associated with systemic low-grade inflammation. Elevated levels of inflammatory markers such as C-reactive protein (CRP), fibrinogen, TNF-α, and IL-6 have been observed in OSA patients, independent of obesity. Tobacco use, a known pro-inflammatory factor, may further exacerbate this burden. This study aimed to evaluate whether smoking influences inflammatory markers and OSA severity in newly diagnosed patients. Methods: We conducted a retrospective, observational study on individuals newly diagnosed with OSA between 1 January 2024 and 31 December 2024 at the Clinical Hospital of Pulmonary Diseases Iași. All participants underwent overnight respiratory polygraphy using the SleepDoc Porti 9 system (Löwenstein Medical), with OSA severity classified according to the American Academy of Sleep Medicine (AASM) criteria. Inflammatory status was assessed using CRP and the erythrocyte sedimentation rate (ESR). Smokers were defined as individuals who had smoked within the past year; non-smokers had a lifetime history of fewer than 50 cigarettes. Statistical analysis was performed using IBM SPSS Statistics. Results: Smokers (n = 55) shoation Index (ODI) values, compared to non-smokers (n = 49): AHI 45.29 ± 20.94 vs. 38.40 ± 19.84 events/hour, ODI 45.69 ± 21.05 vs. 38.44 ± 19.40 events/hour (p < 0.05 for both). Mean CRP levels were approximately 3.5 times higher in smokers (10.32 ± 11.69 mg/dL) than in non-smokers (2.97 ± 2.45 mg/dL), indicating a significantly elevated inflammatory burden. Conclusions: The inflammatory burden and clinical severity of OSA may be influenced by smoking. Routine inflammatory marker screening, particularly CRP, may improve risk stratification and treatment planning in OSA patients, especially those who smoke or are obese. Routine assessment of CRP and other inflammatory markers may improve risk stratification and guide personalized treatment strategies, particularly in smokers and obese patients with OSA. Full article

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by low-grade inflammation, cartilage breakdown, and persistent pain. Despite its prevalence, current therapeutic strategies primarily focus on symptom management rather than modifying disease progression. Monoclonal antibodies and cytokine inhibitors targeting inflammatory pathways, including TNF-α and IL-1, have shown promise but remain limited by inconsistent efficacy and safety concerns. Long-acting biologic therapies—ranging from extended-release formulations, such as monoclonal antibodies and cytokine inhibitors, to gene therapy approaches—have emerged as promising strategies to enhance treatment durability and improve patient outcomes. Extracellular vesicles (EVs) have gained particular attention as a novel delivery platform due to their inherent stability, biocompatibility, and ability to transport therapeutic cargo, including biologics and immunomodulatory agents, directly to joint tissues. This review explores the evolving role of EVs in OA treatment, highlighting their ability to extend drug half-life, improve targeting, and modulate inflammatory responses. Additionally, strategies for EV engineering, including endogenous and exogenous cargo loading, genetic modifications, and biomaterial-based delivery systems, are discussed. Full article