Search Results (1,963)

Inflammatory diseases are caused by overactivation of the immune system and lead to tissue damage; their high incidence and complications seriously threaten human health. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are the mainstay of clinical practice, but their long-term use can cause gastrointestinal damage, drug resistance, and other problems. In recent years, traditional Chinese medicine has become a research hotspot for the treatment of inflammatory diseases, among which Icariin (ICA), the main active ingredient of Epimedium, has demonstrated significant anti-inflammatory potential. In this review, a comprehensive literature search of PubMed and Web of Science was conducted, and original studies on the anti-inflammatory effects and mechanisms of ICA were included. The roles and mechanisms of ICA in inflammatory diseases in different systems are summarized. Specifically, ICA suppresses NF-κB and MAPK signaling, inhibits NLRP3 inflammasome activation, and activates the Nrf2/HO-1 antioxidant axis, thereby reducing the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Overall, the current evidence indicates broad anti-inflammatory effects of ICA across multiple organ systems, particularly in atherosclerosis and myocardial infarction; however, clinical translation is limited by poor bioavailability and the lack of standardized dosage data. Future efforts should focus on pharmacokinetic optimization and well-designed clinical trials to facilitate its application in inflammatory diseases. Full article

Ageing and obesity represent major public health challenges and are associated with metabolic dysfunction, chronic inflammation, and loss of skeletal muscle mass. Resistance training (RT) is an effective strategy to increase muscle mass; however, its effects on metabolic and immune parameters in older women with obesity remain unclear. The study aimed to compare the effects of 12-week progressive overload RT programme on metabolic and immune responses in women aged 60–79 years with obesity and normal-weight women. Thirty older women were allocated into two groups according to body composition: women with obesity (OB: 68 ± 4.21 years; body mass index [BMI] = 33.01 ± 2.62 kg/m²; body fat percentage = 42.23% ± 2.98%; n = 16) and normal-weight women (NW: 66 ± 4.31 years; BMI = 22.60 ± 1.36 kg/m²; body fat percentage = 33.11% ± 3.61%; n = 14). At baseline, the OB group showed higher serum concentrations of leptin, insulin, triglycerides, and HOMA-IR and lower HDL cholesterol concentrations compared with the NW group, while no differences were observed in circulating cytokines or NETosis. After 12 weeks of RT, fasting glucose decreased only in the OB group (p = 0.030). Both groups exhibited reductions in total cholesterol and adiponectin, along with an increase in NETosis. Leptin, insulin, and pro-inflammatory cytokines were associated with lower muscle quality, whereas higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group (p < 0.05). In conclusion, baseline metabolic differences were observed between normal-weight older women and those with obesity; however, both groups showed changes after 12 weeks of RT in metabolic and immune parameters. Furthermore, higher baseline adiponectin concentrations were associated with greater muscle mass gains in the NW group. Full article

Pharmaceutical waste is a challenge for the environment and public health in the European Union (EU). Although EU legislation requires Member States to establish collection systems for unwanted household pharmaceutical products, there is no common legal framework governing the application of extended producer responsibility (EPR) in this area, which has led to differences in the financing, organization, and effectiveness of national waste collection systems. Against this background, the aim of this work was to critically examine the role of EPR in the management of household pharmaceutical waste in the EU by analyzing its legal foundations, comparing selected national take-back systems, identifying the barriers to its implementation and indicating the key elements of a future EU regulatory framework. The analysis indicates that key elements of the future EPR framework for pharmaceutical products should include financing for producers through producer responsibility organizations (PROs), free and accessible collection of medicinal products from patients through community pharmacies, full cost compensation for collection point operators, common reporting requirements, environmentally differentiated producer contributions, consumer education, and independent public oversight. The future EU framework could build on good practices developed in Member States with established EPR systems and on the regulatory solutions adopted in EU environmental legislation. Full article

Background/Objectives: Structural inequalities in access to healthcare persist even within systems that have achieved near-universal coverage, reflecting the enduring influence of social determinants of health on service utilization. This study examines horizontal inequity in rehabilitation and specialist care in Türkiye and investigates whether access inequality mediates the well-documented income–depression gradient. Methods: Analyzing the nationally representative 2022 Türkiye Health Survey (adults aged ≥15; N = 22,742), we employed Latent Profile Analysis (LPA) to construct people-centered, multidimensional bodily burden profiles, and assessed need-adjusted access using survey-weighted logistic regression, Erreygers-corrected concentration-index decomposition, Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA), and restricted cubic splines, with measurement-invariance and classification-uncertainty sensitivity analyses. Statistical mediation was examined with natural-effect models and E-value sensitivity analysis. Results: Although the system demonstrated responsiveness to need—78.8% of the highest-burden profile accessed specialist services—only 13.7% of this same group reached dedicated physiotherapy or rehabilitation, revealing a profound structural bottleneck in care coordination for marginalized populations with the greatest functional impairment. A persistent pro-rich gradient was confirmed by an Erreygers-corrected concentration index of 0.058 (95% CI 0.043–0.072), driven additively by income and education. Access did not mediate the income–depression pathway (natural indirect effect OR 1.001, 95% CI 1.0003–1.002). Conclusions: The mental health burden of low income operates through pathways that equitable healthcare access alone cannot address. These findings call for macroeconomic and people-centered health system reforms—including direct physiotherapy access, transportation subsidies, and social protection interventions—to advance health equity in rehabilitation utilization. Full article

This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly divided into a control group, a heat-stress group, and three intervention groups treated with 400, 800, and 1600 mg/kg silybin under heat-stress from 21 d to 35 d for two weeks. The function indices, oxidative stress, inflammatory factor levels, histopathological changes and non-targeted lipidomic profiling in liver as well as growth performance were evaluated. Results showed that silybin supplementation partially alleviated the heat-stress-induced decreases in average daily feed intake and body weight gain (p > 0.05). Silybin supplementation at 400 and 800 mg/kg significantly reduced the heat-stress-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), whereas the effect of 1600 mg/kg silybin was not significant. Albumin (ALB) and globulin (GLB) levels were mainly improved in the 800 mg/kg group, and GLB was also increased in the 400 mg/kg group (p < 0.05). Silybin supplementation significantly improved hepatic antioxidant capacity, especially in the 400 and 800 mg/kg groups, as indicated by increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels (p < 0.05). In addition, the 400 and 800 mg/kg groups showed more significant reductions in the pro-inflammatory factors IL-6 and TNF-α, while IL-10 was increased in silybin-supplemented groups (p < 0.05). Lipid metabolism disorders were improved through regulation of the sphingolipid and glycerophospholipid metabolism pathways, while it alleviated heat stress damage by reducing the expression of heat shock proteins. In conclusion, silybin holds promise as an effective feed additive to alleviate heat stress in poultry. This study provides a theoretical basis and practical approach for improving the health and productive performance of Peking ducks under heat-stress conditions. Full article

Skeletal muscle mitochondria possess the ability to autoregulate their health and functioning by the orchestration of mitochondrial quality control (MQC) pathways. This plasticity allows them to adapt to various stimuli, such as exercise. However, under pathological conditions, mitochondria can become dysfunctional, generating damage-associated molecular patterns (DAMPs), such as reactive oxygen species (ROS) and oxidized mitochondrial DNA (mtDNA). These DAMPs can launch an innate immune response, with consequences of widespread inflammation and atrophy. Integral to this is the NLRP3 inflammasome complex. Activation of the NLRP3 inflammasome results in maturation of caspase-1, which processes pro-inflammatory cytokines IL-1β and IL-18, as well as GSDMD. Consequently, the pore-forming GSDMD-N fragment induces pyroptosis, releasing mature IL-1β and IL-18. Exercise training is widely accepted as a potent mechanism to promote skeletal muscle health, particularly by remodeling the mitochondrial network and reducing the production of DAMPs. It has also been shown promote an anti-inflammatory milieu with the release of various myokines. Indeed, the potential of exercise to mitigate NLRP3 inflammasome-mediated inflammation and atrophy is promising. This review will examine the mechanisms underpinning inflammasome priming and activation, as well the effects of exercise, with an emphasis on the skeletal muscle. Full article

Global population growth, climatic extremes and rising resource pressures necessitate innovative agricultural methods to boost food, feed, fibre and fuel production sustainably. Seed enhancement technologies (SETs), such as seed coating and priming, have emerged as effective strategies to improve seed viability and vigour, seedling establishment and overall crop yield. Conventional seed treatments include seed coating (film coating, encrusting, pelleting) and seed priming (hydro-, osmo-, halo- bio-, nutri-, hormonal-, chemical- and solid matrix priming). They offer advantages such as improved seed handling, uniform germination and promotion of early growth. However, they also have significant drawbacks, including on soil health and off-target pollution from synthetic polymers and pesticides, seed longevity issues from re-drying and outcomes that can vary among different crops, soils and environments. To tackle these issues, new non-traditional SETs are being investigated, including nanotechnology, novel biodegradable coatings and agrichemical-free biostimulants, such as plant growth promoting microorganisms. These innovative methods demonstrate great promise in enhancing active and crop performance while minimising environmental impacts by providing alternatives to materials derived from fossil fuels and that contribute to waste and pollution. This review critically examines both conventional and novel SETs, discusses their pros and cons and outlines strategic research and industry directions to enhance agricultural sustainability and productivity in light of global food and resource security challenges. Full article

Plastic contamination (plastamination) has become a pervasive environmental threat with growing implications for human health. Among plastic-derived contaminants, micro- and nano-plastics (MNPs) are of particular concern due to their persistence, widespread distribution, and capacity to interact with biological systems. Humans are exposed to MNPs through ingestion, inhalation, dermal contact, and maternal transfer, and these particles can cross biological barriers, including the blood–brain barrier, reaching the central nervous system. MNPs disrupt cellular homeostasis by inducing oxidative stress, mitochondrial dysfunction, and inflammation. In the brain, these processes drive glial activation and chronic neuroinflammation, which are closely associated with neuronal damage and neurological disorders, including Parkinson’s disease (PD). MNPs can also affect systemic pathways such as the gut–brain axis (GBA) and neuroendocrine regulation, suggesting broader physiological consequences. This narrative review synthesizes current evidence on the neurotoxic and pro-inflammatory potential of MNPs. Since MNPs may promote the aggregation of proteins implicated in neurodegeneration, such as alpha-synuclein, their possible role in PD is discussed. Despite several knowledge gaps, MNPs may be emerging environmental risk factors for brain health and neurodegenerative diseases such as PD. Nevertheless, there is a need for further studies in the field, standardized methodologies and longitudinal studies to implement effective mitigation strategies. Full article

Obesity-related complications have long been significant risk factors threatening human health. Sanhua tea is an instant tea composed of Rosa rugosa Thunb., Jasminum sambac (L.) Ait., Citrus aurantium L. var. amara Engl., Nelumbo nucifera Gaertn., and Ligusticum chuanxiong Hort. This study aimed to investigate the protective effects and underlying mechanisms of Sanhua tea in obese mice. An obesity model was established by feeding C57BL/6J mice a high-fat diet. Mice received intragastric Sanhua tea at doses (500, 1500, and 2500 mg/kg/day) for three weeks. Biochemical analyses indicated that Sanhua tea significantly reduced total cholesterol, triglyceride, low-density lipoprotein cholesterol, and pro-inflammatory cytokine levels in serum. Sanhua tea also alleviated liver oxidative stress by reducing malondialdehyde levels and regulating the activities of related enzymes. Additionally, Sanhua tea maintained gut microbiota diversity and reshaped microbial composition, reducing the Firmicutes/Bacteroidota ratio, increasing beneficial bacterial communities, and significantly decreasing harmful bacterial communities. Metabolomics analysis revealed that Sanhua tea altered liver metabolites, which were significantly associated with specific gut microbes. These metabolites influenced pathways such as ABC transporters, general metabolic pathways, and central carbon metabolism in cancer, contributing to obesity alleviation. In conclusion, Sanhua tea alleviated obesity symptoms in mice by modulating blood lipid levels, liver metabolism, and gut microbiota. Full article

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Chronic enteropathy (CE) is a common cause of persistent gastrointestinal signs in dogs, and dietary management represents the cornerstone of treatment. Probiotics have been proposed as adjunctive strategies to support intestinal health, although evidence of their efficacy remains limited. This randomised, double-blind crossover trial evaluated the effects of a hydrolysed protein diet supplemented or not with Bacillus velezensis DSM 15544 applied during post-extrusion coating. Thirteen CE dogs were randomly assigned to receive the Diet with Probiotic (DIET+PRO) or the Diet without Probiotic (DIET) during two consecutive 60-day feeding periods, with parameters assessed at baseline (T0) and after 30 (T1) and 60 (T2) days of each dietary treatment. Clinical response was assessed using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) andfecal core (FS). Gut microbiota was evaluated by the qPCR Dysbiosis Index (DI) and 16S rRNA gene sequencing, including taxonomic composition, alpha and beta diversity analyses. Compared with baseline (CIBDAI: 4.2 ± 1.7; FS: 3.9 ± 1.5), both dietary treatments significantly improved clinical scores (CIBDAI: 1.3–1.5; FS: 2.2–2.3; p < 0.02), irrespective of probiotic supplementation. Neither microbiota composition, alpha diversity, beta diversity, nor the DI (−2.7 ± 2.3 to −2.1 ± 2.3) differed between dietary treatments. Clinical responses to B. velezensis DSM 15544 supplementation varied among dogs. Overall, the hydrolysed diet effectively improved gastrointestinal clinical signs in dogs with CE, whereas the effects of B. velezensis DSM 15544 remain unclear and warrant further investigation, as any additional benefit may have been masked by the marked clinical response to the hydrolysed diet. Full article

Background/Objectives: Obesity and its metabolic comorbidities, including dyslipidemia and non-alcoholic fatty liver disease (NAFLD), are a growing global health burden, and current pharmacotherapies have limited efficacy and notable adverse effects. The gut microbiome has emerged as a key regulator of host metabolism, and its dysregulation is implicated in obesity. This study investigated the therapeutic potential of Piper sarmentosum Roxb. aqueous extract (PSRW) on metabolic dysfunction and gut microbiota composition in a high-fat diet (HFD)-induced obese rat model. Methods: HFD-induced obese male Wistar rats received PSRW, simvastatin, or their combination for 12 weeks. Serum lipids (TC, TG, HDL, LDL), liver enzymes (AST, ALT), and renal markers were measured, and gut microbiota were profiled by 16S rRNA (V4) sequencing with PICRUSt2/KEGG functional prediction. The phenolic composition of the same extract was characterized by HPLC in a companion study. Results: PSRW did not cause weight loss but significantly lowered serum TC, AST, and ALT, with efficacy comparable to simvastatin and significantly lower TG than control, though not significantly different from HFD. Co-administration of PSRW and simvastatin produced a greater reduction in TC and liver enzymes than either agent alone. HFD shifted microbial community structure and enriched pro-inflammatory phyla such as Desulfobacterota; PSRW partially reversed these changes, suppressing obesogenic Lachnospiraceae genera while enriching beneficial microbes including Dwaynesavagella, and functionally reprogrammed taxa such as Kineothrix and Muribaculum from detrimental to protective associations. HFD enriched microbial glycosphingolipid biosynthesis, whereas the PSRW simvastatin combination uniquely enhanced glycine, serine, and threonine metabolism. Conclusions:P. sarmentosum extract ameliorates HFD-induced dyslipidemia and hepatotoxicity, and these effects are accompanied by remodeling of the composition and predicted functional capacity of the gut microbiome. Its ability to act in combination with statins highlights its potential as a candidate complementary therapy for hyperlipidemia and NAFLD. Full article

Wle vanillin is widely used as a flavoring agent in food products, its potential as a non-antibiotic feed additive for broilers remains unexplored. This study primarily investigated the effects of dietary supplementation of vanillin on antioxidant activity, anti-inflammatory response, immune function, and gut microbiota composition in broilers. One-day-old male broilers were randomly assigned to five groups: a basal diet group, a positive control group (basal diet + 100 mg/kg chlortetracycline (CTC)), and three vanillin-supplemented groups (0.1%, 0.2%, or 0.4%) for 42 days. Results showed that vanillin improved antioxidant capacity, with elevated serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels. Broilers receiving vanillin supplementation showed lower levels of pro-inflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) and higher interleukin-10 (IL-10) expression compared with controls. Additionally, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were also greater in the vanillin group. It also enhanced intestinal health by increasing the duodenal villus height-to-crypt depth ratio, improving intestinal morphology, raising the Firmicutes-to-Bacteroidetes ratio, and promoting Lactobacillus proliferation compared with CTC. Notably, growth performance data were exploratory in nature; vanillin was associated with numerical improvements in average daily gain (ADG) and feed conversion (F/G) ratio. These preliminary findings suggest that vanillin requires further investigation as a potential feed additive. Full article

Inflammation can either encourage or suppress tumor growth, thus having a two-sided effect on cancer development. This depends on the balance between pro-tumor and anti-tumor immune responses within the tumor microenvironment (TME). Pro-tumor inflammation, driven by specific immune cells, enhances blood flow and nutrient supply to tumors, promoting the activation of dormant cancer cells (DCCs). Conversely, antitumor inflammation hinders blood flow and can force active cancer cells into a state of dormancy. Tumors actively shift this balance towards pro-tumor inflammation to create a favorable environment for growth. Therefore, anti-inflammatory therapy may be an integral part of comprehensive cancer immunotherapy. This review explores how different anti-inflammatory medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, anti-leukotrienes, statins, drugs that block pro-inflammatory cytokines, agents that inhibit oxidative phosphorylation, antioxidant vitamins, anti-angiogenic drugs, and low-dose chemotherapy, can be used to combat cancer. Granulocyte counts and erythrocyte sedimentation rate (ESR) can be used to assess inflammation levels and the effectiveness of anti-inflammatory treatments. We advocate for a paradigm shift in cancer treatment, moving away from aggressive tumor destruction, which triggers uncontrolled tumor regeneration, toward long-term immunological control of tumor growth while preserving the patient’s overall health. Full article

Chronic stress is increasingly recognized as a major contributor to systemic disease. Prolonged or repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathoadrenal systems may contribute to glucocorticoid receptor resistance and chronic low-grade inflammation, although stress-related responses vary depending on stressor characteristics, population, age, sex, health status, and study design. Elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), oxidative stress, and NF-κB activation contribute to immune dysfunction, neuroinflammation, metabolic disturbances, reproductive and endocrine imbalance, as well as structural and functional alterations in stress-sensitive brain regions. Prolonged exposure to stress may contribute to the development of neuropsychiatric, cardiovascular, metabolic, neurodegenerative, and malignant diseases, highlighting the need for effective strategies to mitigate the detrimental consequences of chronic stress. Given the limitations and adverse effects associated with conventional pharmacological approaches, increasing attention has been directed toward natural bioactive compounds. Terpenes represent a diverse class of phytochemicals with reported anti-inflammatory, antioxidant, and neuromodulatory properties. Terpenes such as limonene and β-caryophyllene, as well as terpenoids such as linalool, may modulate NF-κB, MAPK, and Nrf2 signaling pathways and interact with the endocannabinoid system, thereby attenuating neuroinflammation, oxidative stress, and stress-induced immune dysregulation. This review summarizes current evidence regarding the mechanisms linking chronic stress, HPA axis dysfunction, and systemic disease, with particular emphasis on endocrine, immune, and nervous system alterations. In addition, it critically evaluates the mechanistic and translational potential of terpenes as possible indirect neuroimmune and redox modulators of stress-related pathophysiology. Full article