Search Results (6,400)

Background/Objectives: To evaluate the incidence, characteristics, and clinical outcomes of intraocular inflammation (IOI) associated with intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Web of Science, Scopus, Embase, and CENTRAL databases was performed from their inception to February 2025. Using the random-effects model, weighted proportions, standardized mean differences, and weighted log odds ratios (OR) were pooled and calculated. A two-tailed p-value of <0.05 was considered statistically significant. The χ² (z) test and the Higgins I² test were used to assess studies heterogeneity. Results: We conducted a systematic review and meta-analysis of 24 studies (4761 patients; 5652 eyes). The most common diagnoses were nAMD (n = 4782, 94.6%) and DME (n = 845, 37.1%). The pooled proportion for IOI incidence in eyes receiving IVF was 3.0% (95% CI: 1.0–6.0). The odds of developing IOI did not differ significantly between the DME and nAMD groups (OR: 1.13, p = 0.78). Unspecified IOI was the most common sign (n = 210, 2.9% [95% CI: 1.2–7.3]), followed by anterior uveitis (n = 80, 1.9% [95% CI: 0.1–34.8]), vitritis (n = 63, 2.9% [95% CI: 0.2–32.1]), retinal hemorrhage (n = 27, 0.7% [95% CI: 0.0–15.3]), and endophthalmitis (n = 8, 0.5% [95% CI: 0.3–1.1]). Conclusions: While IVF demonstrates therapeutic efficacy, our findings highlight a clinically relevant risk of IOI. We, therefore, recommend vigilant clinical monitoring in patients receiving this therapy. Full article

Background and Objectives: Intermittent fasting (IF) has emerged as a nutritional strategy capable of modulating circadian alignment, metabolic efficiency, and neuroendocrine regulation in individuals with obesity. Among the neurobiological mediators potentially involved, Orexin-A—a hypothalamic neuropeptide regulating arousal, appetite, and energy balance—may represent a key link between fasting patterns and metabolic homeostasis. This study aimed to evaluate the long-term metabolic and neuroendocrine effects of two intermittent fasting protocols, time-restricted feeding (16:8) and alternate-day fasting (5:2), compared with a hypocaloric Mediterranean diet used as a reference condition. Materials and Methods: Thirty adults with obesity (aged 20–40 years) were allocated to one of three dietary interventions—low-calorie Mediterranean diet, IF 16:8, or IF 5:2—based on habitual dietary patterns and followed prospectively for 12 months. Anthropometric parameters, metabolic indices, inflammatory markers (CRP, TNF-α, IL-6, IL-10), and circulating Orexin-A concentrations were assessed at baseline and at three-month intervals (T0–T3). Results: Both intermittent fasting protocols induced more rapid improvements in body mass index, adiposity, lipid profile, fasting glucose, and inflammatory markers compared with the Mediterranean diet. Among the IF strategies, the 16:8 regimen showed the most consistent and physiologically coherent pattern of adaptation, characterized by a progressive and sustained increase in Orexin-A levels. This response was strongly associated with enhanced metabolic flexibility, reduced systemic inflammation, and improved energy regulation over time. In contrast, the 5:2 protocol produced more variable metabolic and neuroendocrine responses, likely due to alternating cycles of marked caloric restriction and compensatory intake. Conclusions: Intermittent fasting, particularly the 16:8 time-restricted feeding protocol, appears to be an effective and sustainable chrononutritional strategy for obesity management. By reinforcing circadian organization, improving inflammatory balance, and activating orexinergic pathways, the 16:8 model emerges as a promising intervention to address key metabolic and neuroendocrine dysfunctions associated with obesity. Full article

Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key feature identified on ultrasound examination. The lack of data on the effect of L-thyroxine (LT-4) doses on the level of anti-TPO and anti-TG antibodies in Hashimoto’s thyroiditis and the relationship with anthropometric measurements resulted in the desire to fill this niche. Methods: A total of 70 Caucasian patients diagnosed with Hashimoto’s thyroiditis within the past two years were examined. The participants were divided into three groups based on their L-thyroxine dosage (≤50, 50–100, >100 μg). Results: The results revealed no correlation between the dosage of L-thyroxine and anthropometric measurements (age, height, body weight, and body fat content). No correlation was identified between the levels of anti-TPO and anti-TG and the dose of L-thyroxine in patients with Hashimoto’s thyroiditis. Conclusions: The mechanism regulating the levels of anti-TPO and anti-TG appears to be associated with a more advanced thyroid inflammation and disease process. Long-term observation of patients would be advisable. We present evidence of no effect of hormone dose on antibody levels in Hashimoto’s thyroiditis. Regardless of disease severity, immune regulation remains outside the scope of hormonal regulation. Full article

With the global increase in population aging, allergic diseases in older adults are becoming an increasingly relevant clinical and public health challenge. Age-related molecular and cellular alterations significantly affect the pathophysiology, clinical manifestations, diagnosis, and management of major allergic diseases in the elderly. This review focuses on immunosenescence in major allergic conditions, including asthma, chronic urticaria and angioedema, dermatitis, food and drug allergies, and hymenoptera venom hypersensitivity. Particular emphasis is placed on molecular mechanisms underlying immune aging, such as inflammaging, dysregulation of innate and adaptive immune responses, epithelial barrier dysfunction, microbiota alterations, neuro-immune interactions, and age-related comorbidities. Sex-related differences in immune responses are also addressed, together with current diagnostic and therapeutic strategies, including the opportunities and limitations of biologic therapies in aging populations. Despite growing interest in this field, a major limitation remains the paucity of studies specifically targeting geriatric populations, underscoring the need for age- and sex-specific research and dedicated clinical trials. A personalized approach integrating frailty assessment and immune profiling is essential to optimize the management of allergic diseases in older adults. Full article

Kidney aging is receiving growing attention in middle- to high-income societies due to increasing longevity in general population. Chronic Kidney Disease (CKD) has been widely accepted as a major non-communicable human disease affecting over 10% of the adult population in industrialized countries. CKD is mainly caused by metabolic and cardiovascular disorders such as diabetes mellitus and hypertension, disproportionally affecting older people, whereas natural kidney aging is driven by age-dependent systemic and renal low-grade inflammation. Interleukin-6 (IL-6) is the key cytokine mediating age-related inflammation. At the same time, IL-6 has been implicated in the pathophysiology of cardiovascular and renal disorders as a major pro-inflammatory cytokine. Thereby, IL-6 is placed at the intersection between natural and pathophysiological kidney aging, and the latter accelerates systemic aging and substantially limits life quality and expectancy. Growing clinical availability of IL-6 inhibitors for treatment of autoimmune and autoinflammatory disorders demands clarification of potential renal consequences as well. Available data suggests that IL-6 inhibition may be renoprotective in some kidney disorders, but the setting of kidney aging has received only minor attention. The present review focuses on the known effects of IL-6 associated with natural or pathophysiological renal aging. Full article

Porcine circovirus 3 (PCV3), first reported in 2016, is associated with diverse clinical conditions, including porcine dermatitis and nephropathy syndrome, reproductive disorders, and systemic inflammation, and affects pigs of all ages. To investigate the prevalence and genetic evolution of PCV3 in Hunan Province, China, 700 lymph node tissue specimens were collected from slaughterhouses and hazard-free disposal centers across 14 prefecture-level cities between 2021 and 2024 and screened using real-time quantitative PCR (qPCR). Epidemiological investigation revealed an overall PCV3 positivity rate of 29.4% (206/700) in the province. The highest prevalence was observed in Yiyang City (56%, 28/50), whereas no positive samples were detected in Zhuzhou City (0/30). Among the positive samples, 34 specimens from different cities with Ct values < 25 were selected for Cap gene amplification and sequencing. Phylogenetic analysis showed that PCV3c was the predominant genotype (67.6%, 23/34), followed by PCV3a (32.4%, 11/34), while PCV3b was not detected. We identified twelve amino acid substitution sites within Cap proteins. Furthermore, B-cell linear epitope prediction and homology modeling of the Cap protein identified seven linear epitopes, with ten amino acid variation sites located within these epitopic regions. This study enriches the molecular epidemiological data of PCV3 in southern China and provides a reference for future PCV3 control strategies. Full article

Age-related osteoporosis is driven in part by senescence-associated rewiring of bone marrow mesenchymal stem cells (MSCs) from osteogenic toward adipogenic fates. Accumulating evidence indicates that epigenetic drift and reduced autophagy are not isolated lesions but are mechanistically coupled through a bidirectional DNA methylation and autophagy axis. Here, we summarize how promoter hypermethylation of genes involved in autophagy and osteogenesis suppresses autophagic flux and osteoblast lineage transcriptional programs. Conversely, autophagy insufficiency reshapes the methylome by limiting methyl donor availability, most notably S-adenosylmethionine (SAM), and by reducing the turnover of key epigenetic regulators, including DNA methyltransferases (DNMTs), ten-eleven translocation (TET) dioxygenases, and histone deacetylases (HDACs). This self-reinforcing circuitry exacerbates mitochondrial dysfunction, oxidative stress, and inflammation driven by the senescence-associated secretory phenotype (SASP), thereby stabilizing adipogenic bias and progressively impairing marrow niche homeostasis and bone remodeling. We further discuss therapeutic strategies to restore balance within this axis, including selective modulation of epigenetic enzymes; activation of AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) signaling with downstream engagement of Unc-51-like autophagy-activating kinase 1 (ULK1) and transcription factor EB (TFEB); targeting sirtuin pathways; mitochondria- and autophagy-supportive natural compounds; and bone-targeted delivery approaches or rational combination regimens. Full article

Oxidative stress is a major factor in skin aging and various skin pathologies. Environmental pollutants exacerbate this stress by generating reactive oxygen species (ROS), disrupting the skin’s redox balance. Pycnogenol^®, a French maritime pine bark, extract is standardized to contain 70 ± 5% procyanidins and known to mitigate oxidative damage and inflammation. This study aims to evaluate the potential antipollution and antioxidant effects of Pycnogenol^® on skin. Ex vivo human skin explants were treated with varying concentrations of Pycnogenol^® (0.5%, 1%, and 2%) and then exposed to a mixture of pollutants. The expression of stress markers Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) and AHR (Aryl Hydrocarbon Receptor) were evaluated using immunostaining. Lipid peroxidation levels were measured by quantifying malondialdehyde (MDA) concentrations. The extract significantly decreased Nrf2 expression by 40% (p = 0.003) and 23% (p = 0.048) with a dose of 2% and 1%, respectively. After pollutant exposure, Pycnogenol^® (0.5%, 1%, and 2%) reduced Nrf2 over-expression in a dose–response manner by 29% (p = 0.03), 58% (p = 0.004) and 64% (p = 0.002) respectively. Pycnogenol^® at 0.5%, 1%, and 2% significantly reduced AHR over-expression by 61% (p < 0.0001), 76% (p < 0.0001) and 85% (p < 0.0001), respectively. Pycnogenol^® (1%, and 2%) decreased MDA levels following pollutant exposure by 17% (p = 0.06) and 25% (p = 0.01) respectively. In a dose-dependent manner, Pycnogenol^® exhibited a strong protective effect against pollution, significantly reducing pollutant-induced basal oxidative stress (MDA) and over-expression of Nrf2 and AHR, key factors in oxidative stress and detoxification. Pycnogenol^® also increased AHR expression in the absence of pollutants, which may reflect an adaptive cellular response. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Biological aging disrupts liver–gut intercommunication, resulting in the development of insulin resistance and type 2 diabetes, coupled with the imbalance of gut microbiome composition known as gut dysbiosis. Fermented red ginseng (FRG) is a renowned functional food substance showing its notable anti-inflammatory and anti-diabetic effects owing to its unique bioactive compounds known as ginsenosides. However, whether FRG could impact biological aging and age-related metabolic dysfunction is still unclear. The current study aimed to determine the health benefits of FRG in improving age-associated impaired insulin homeostasis and gut dysbiosis in 19-month-old male mice. Mice were fed with a normal chow diet (NCD) or NCD with FRG (300 mg/kg) for 14 weeks. FRG supplementation significantly improved insulin homeostasis by activating the hepatic protein kinase B (AKT) and proline-rich AKT substrate of 40 kDa (PRAS40). We also observed suppressed mRNA expression of proinflammatory cytokines and diminished inflammatory infiltrates in the liver of FRG-fed mice compared with NCD-only controls. Furthermore, alongside a decreased ratio of Firmicutes to Bacteroidetes, FRG administration enriched beneficial genera, including Muribaculaceae, Borkfalkiaceae, Parasutterella, and Clostridia vadin BB60 group, whereas FRG reduced the abundance of Erysipelotrichaceae and Dubosiella at the genus level. In summary, we suggest that FRG can be a potential anti-aging dietary supplement to manage age-driven dysregulation of insulin homeostasis and gut microbiota composition. Full article

Bone homeostasis and regeneration depend on tightly regulated interactions between skeletal cells and the immune system within the bone microenvironment. Disruption of this crosstalk by ageing, chronic inflammation, or systemic disease contributes to osteoporosis, inflammatory bone loss, and impaired fracture healing. Osteoimmunology has reframed bone biology as an immune-regulated process, highlighting mesenchymal stem cells (MSCs) as central coordinators of bone-immune communication. Beyond their differentiation capacity, MSCs act primarily through paracrine mechanisms, releasing a secretome composed of soluble factors and extracellular vesicles (EVs) that modulate immune responses, regulate osteoblast and osteoclast activity, promote angiogenesis, and support extracellular matrix remodelling. MSC-derived EVs have emerged as key nanoscale mediators that transfer bioactive cargo to target cells in a context-dependent manner, enabling precise regulation of osteoimmune processes. This review summarises current knowledge on the role of MSCs in osteoimmunology, with a focus on how their secretome and EVs integrate immune modulation with bone regeneration. We discuss the mechanisms underlying MSC-mediated regulation of innate and adaptive immune cells, examine emerging cell-free therapeutic strategies based on secretome and EV delivery, and outline the main challenges that must be addressed to advance these approaches towards clinical application. Full article

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with pSS. Method: This cross-sectional study involved 61 patients diagnosed with pSS based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA. Statistical analyses, including univariate linear regression, were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 pSS patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤ 0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the tricuspid annular plane systolic excursion (TAPSE)/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (<30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusions: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in primary Sjögren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population. Full article

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood–retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity. Full article

The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T [T-reg] cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3^fl/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart. Full article