RESUMEN
The natural process of skin aging is influenced by a variety of factors, including oxidative stress, inflammation, collagen degradation, and UV radiation exposure. The potential of polyphenols in controlling skin aging has been the subject of much investigation throughout the years. Due to their complex molecular pathways, polyphenols, a broad class of bioactive substances present in large quantities in plants, have emerged as attractive candidates for skin anti-aging therapies. This review aims to provide a comprehensive overview of the molecular mechanisms through which polyphenols exert their anti-aging effects on the skin. Various chemical mechanisms contribute to reducing skin aging signs and maintaining a vibrant appearance. These mechanisms include UV protection, moisturization, hydration, stimulation of collagen synthesis, antioxidant activity, and anti-inflammatory actions. These mechanisms work together to reduce signs of aging and keep the skin looking youthful. Polyphenols, with their antioxidant properties, are particularly noteworthy. They can neutralize free radicals, lessening oxidative stress that might otherwise cause collagen breakdown and DNA damage. The anti-inflammatory effects of polyphenols are explored, focusing on their ability to suppress pro-inflammatory cytokines and enzymes, thereby alleviating inflammation and its detrimental effects on the skin. Understanding these mechanisms can guide future research and development, leading to the development of innovative polyphenol-based strategies for maintaining healthy skin.
Asunto(s)
Antiinflamatorios , Antioxidantes , Estrés Oxidativo , Polifenoles , Envejecimiento de la Piel , Piel , Envejecimiento de la Piel/efectos de los fármacos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Humanos , Piel/efectos de los fármacos , Piel/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Rayos Ultravioleta/efectos adversos , Mediadores de Inflamación/metabolismoRESUMEN
PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.
Asunto(s)
Antineoplásicos , Mediadores de Inflamación , Neoplasias , Saliva , Estomatitis , Factor de Necrosis Tumoral alfa , Humanos , Estomatitis/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , Antineoplásicos/efectos adversos , Anciano , Adulto , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-6/análisis , Estudios de Cohortes , Índice de Severidad de la EnfermedadRESUMEN
Objectives: The aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression. Methods: We recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-ß. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers. Results: Most ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI. Conclusions: ICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD.
Asunto(s)
Biomarcadores , Citocinas , Terapia de Reemplazo Enzimático , Enfermedad de Fabry , Fenotipo , Humanos , Enfermedad de Fabry/tratamiento farmacológico , Enfermedad de Fabry/genética , Enfermedad de Fabry/inmunología , Masculino , Femenino , Citocinas/metabolismo , Adulto , Persona de Mediana Edad , alfa-Galactosidasa/genética , alfa-Galactosidasa/uso terapéutico , Adulto Joven , Mediadores de Inflamación/metabolismo , Estudios de Casos y Controles , Inflamación/inmunologíaRESUMEN
This study investigated the efficacy and safety of a propolis-mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks, including substantial reductions in IL-1ß, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.
Asunto(s)
Biomarcadores , Líquido del Surco Gingival , Gingivitis , Extractos Vegetales , Própolis , Humanos , Gingivitis/tratamiento farmacológico , Método Doble Ciego , Própolis/farmacología , Masculino , Femenino , Adulto , Extractos Vegetales/farmacología , Líquido del Surco Gingival/metabolismo , Persona de Mediana Edad , Metaloproteinasa 9 de la Matriz/metabolismo , Garcinia mangostana/química , Metaloproteinasa 8 de la Matriz/metabolismo , Interleucina-1beta/metabolismo , Periodontitis/tratamiento farmacológico , Resultado del Tratamiento , Dinoprostona/metabolismo , Adulto Joven , Encía/efectos de los fármacos , Encía/metabolismo , Mediadores de Inflamación/metabolismoRESUMEN
Obesity-related metabolic disorders, including diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease, increasingly threaten global health. Uncontrolled inflammation is a key pathophysiological factor in many of these conditions. In the human body, inflammatory responses generate specialized pro-resolving mediators (SPMs), which are crucial for resolving inflammation and restoring tissue balance. SPMs derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as resolvins, protectins, and maresins hold promise in attenuating the chronic inflammatory diseases associated with lipid metabolism disorders. Recent research has highlighted the therapeutic potential of n-3 PUFA-derived metabolites in addressing these metabolic disorders. However, the understanding of the pharmacological aspects of SPMs, particularly in obesity-related metabolic disorders, remains limited. This review comprehensively summarizes recent advances in understanding the role of SPMs in resolving metabolic disorders, based on studies in animal models and humans. These studies indicate that SPMs have potential as therapeutic targets for combating obesity, as well as offering insights into their mechanisms of action.
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Enfermedades Metabólicas , Obesidad , Humanos , Obesidad/metabolismo , Animales , Enfermedades Metabólicas/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/uso terapéutico , Mediadores de Inflamación/metabolismo , Inflamación/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológicoRESUMEN
BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.
Asunto(s)
Proteína HMGB1 , Hipoglucemiantes , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inhibidores , Animales , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Antiinflamatorios/uso terapéutico , Terapia Molecular Dirigida , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Resistencia a la Insulina , Receptores Toll-Like/metabolismo , Retinopatía Diabética/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Retinopatía Diabética/prevención & control , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológicoRESUMEN
ABSTRACT: The role of intravenous immunoglobulin in protecting the diabetic heart from ischemia/reperfusion (I/R) injury is unclear. Hearts isolated from adult diabetic and nondiabetic Wistar rats (n = 8 per group) were treated with intravenous immunoglobulin (IVIG) either 2 hours before euthanasia, before ischemia, or at reperfusion. Hemodynamic data were acquired using the Isoheart software version 1.524-S. Ischemia/reperfusion (I/R) injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining and troponin T levels. The levels of apoptosis markers, caspases-3/8, antioxidant enzymes, superoxide dismutase and catalase, glucose transporters, GLUT-1 and GLUT-4, phosphorylated ERK1/2, and phosphorylated eNOS were estimated by Western blotting. Proinflammatory and anti-inflammatory cytokine levels were evaluated using enzyme-linked immunosorbent assays. Intravenous immunoglobulin administration abolished the effects of I/R injury in hearts subjected to hyperglycemia when infused at reperfusion, before ischemia, or at reperfusion in 4-week diabetic rat hearts and only at reperfusion in 6-week diabetic rat hearts. IVIG infusion resulted in a significant (P < 0.05) recovery of cardiac hemodynamics and decreased infarct size. IVIG also reduced the levels of troponin T, apoptotic enzymes, and proinflammatory cytokines. IVIG significantly (P < 0.05) increased the levels of anti-inflammatory cytokines, antioxidant enzymes, GLUT-4, and phosphorylated eNOS. Intravenous immunoglobulin protected the hearts from I/R injury if infused at reperfusion in the presence of hyperglycemia, in 4- and 6-week diabetic rat hearts, and when infused before ischemia in 4-week diabetic rat hearts. IVIG exerts its cardioprotective effects associated with the upregulated phosphorylated eNOS/GLUT-4 pathway.
Asunto(s)
Diabetes Mellitus Experimental , Transportador de Glucosa de Tipo 4 , Daño por Reperfusión Miocárdica , Óxido Nítrico Sintasa de Tipo III , Ratas Wistar , Transducción de Señal , Animales , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Inmunoglobulinas Intravenosas/farmacología , Apoptosis/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Miocardio/enzimología , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/prevención & control , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Ratas , Estrés Oxidativo/efectos de los fármacos , Citocinas/metabolismo , Preparación de Corazón Aislado , Mediadores de Inflamación/metabolismoRESUMEN
BACKGROUND: Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. METHODS AND RESULTS: We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate's beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824-0.998). CONCLUSIONS: The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.
Asunto(s)
Cardiomiopatías Diabéticas , Fenofibrato , Insuficiencia Cardíaca , Hipolipemiantes , Obesidad , Fenofibrato/uso terapéutico , Fenofibrato/farmacología , Animales , Obesidad/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , República de Corea/epidemiología , Humanos , Cardiomiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , PPAR alfa/agonistas , PPAR alfa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factores de Tiempo , Bases de Datos Factuales , Transducción de Señal/efectos de los fármacos , Miocardio/metabolismo , Miocardio/patología , Femenino , Hospitalización , Persona de Mediana Edad , Anciano , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/sangre , Factores de Riesgo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Obesity is a pandemic of the 21st century, and the prevalence of this metabolic condition has enormously increased over the past few decades. Obesity is associated with a number of comorbidities and complications, such as diabetes and cardiovascular disorders, which can be associated with severe and fatal outcomes. Adipose tissue is an endocrine organ that secretes numerous molecules and proteins that are capable of modifying immune responses. The progression of obesity is associated with adipose tissue dysfunction, which is characterised by enhanced inflammation and apoptosis. Increased fat-tissue mass is associated with the dysregulated secretion of substances by adipocytes, which leads to metabolic alterations. Importantly, the adipose tissue contains immune cells, the profile of which changes with the progression of obesity. For instance, increasing fat mass enhances the presence of the pro-inflammatory variants of macrophages, major sources of tumour necrosis factor α and other inflammatory mediators that promote insulin resistance. The pathogenesis of obesity is complex, and understanding the pathophysiological mechanisms that are involved may provide novel treatment methods that could prevent the development of serious complications. The aim of this review is to discuss current evidence describing the involvement of various inflammatory mediators in the pathogenesis of obesity.
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Tejido Adiposo , Mediadores de Inflamación , Inflamación , Obesidad , Humanos , Obesidad/metabolismo , Inflamación/metabolismo , Tejido Adiposo/metabolismo , Mediadores de Inflamación/metabolismo , Resistencia a la Insulina , Animales , Adipocitos/metabolismo , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Inflammation is a normal immune response in organisms, but it often triggers chronic diseases such as colitis and arthritis. Currently, the most widely used anti-inflammatory drugs are non-steroidal anti-inflammatory drugs, albeit they are accompanied by various adverse effects such as hypertension and renal dysfunction. Bioactive peptides (BAPs) provide therapeutic benefits for inflammation and mitigate side effects. Herein, this review focuses on the therapeutic effects of various BAPs on inflammation in different body parts. Emphasis is placed on the immunomodulatory mechanisms of BAPs in treating inflammation, such as regulating the release of inflammatory mediators, modulating MAPK and NF-κB signaling pathways, and reducing oxidative stress reactions for immunomodulation. This review aims to provide a reference for the function, application, and anti-inflammation mechanisms of BAPs.
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Inflamación , Péptidos , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Péptidos/uso terapéutico , Péptidos/farmacología , Animales , Transducción de Señal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , FN-kappa B/metabolismo , Mediadores de Inflamación/metabolismo , Inmunomodulación/efectos de los fármacosRESUMEN
Uterine fibroids (UFs), the most common tumors in women of reproductive age, are characterized by sex steroid-dependent growth and excessive deposition of extracellular matrix (ECM) surrounding UF smooth muscle cells. Women with symptomatic UFs experience heavy menstrual bleeding and consequent iron-deficiency anemia. They also have a risk of recurrent pregnancy loss, preterm birth, and cesarean delivery, indicating that UFs can negatively affect reproductive outcomes. Various types of immune cells, including innate and adaptive cells, are observed in UFs; however, the impact of these cells on the pathophysiology of UFs remains unclear. Inflammation may play important roles in the growth of UFs, and expression levels of proinflammatory and inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-ß, are upregulated in UFs. These cytokines play important roles in the interaction between growth factors and ECM that is regulated by the sex steroids estrogen and progesterone. Furthermore, proinflammatory mediators are upregulated in females with UFs, with higher expression levels in the endometrium with submucosal and intramural UFs than in the endometrium without UFs, indicating that these proinflammatory cytokines may impair endometrial receptivity, leading to implantation failure in in vitro fertilization programs. Hormonal treatments using gonadotropin releasing hormone analogs and the selective progesterone receptor modulator ulipristal acetate significantly shrink UFs and improve UF-related symptoms. These compounds can regulate local inflammation in UFs and adjacent myometrium. Controlling and improving local inflammation caused by UFs may represent a novel therapeutic strategy for UFs and potentially improve reproductive outcomes in women with symptomatic UFs.
Asunto(s)
Inflamación , Leiomioma , Humanos , Femenino , Leiomioma/inmunología , Leiomioma/patología , Embarazo , Inflamación/inmunología , Citocinas/metabolismo , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/patología , Endometrio/inmunología , Endometrio/patología , Mediadores de Inflamación/metabolismoRESUMEN
Macrophages are a dynamic cell type of the immune system implicated in the pathophysiology of vascular diseases and are a major contributor to pathological inflammation. Excessive macrophage accumulation, activation, and polarization is observed in aortic aneurysm (AA), atherosclerosis, and pulmonary arterial hypertension. In general, macrophages become activated and polarized to a pro-inflammatory phenotype, which dramatically changes cell behavior to become pro-inflammatory and infiltrative. These cell types become cumbersome and fail to be cleared by normal mechanisms such as autophagy. The result is a hyper-inflammatory environment causing the recruitment of adjacent cells and circulating immune cells to further augment the inflammatory response. In AA, this leads to excessive ECM degradation and chemokine secretion, ultimately causing macrophages to dominate the immune cell landscape in the aortic wall. In atherosclerosis, monocytes are recruited to the vascular wall, where they polarize to the pro-inflammatory phenotype and induce inflammatory pathway activation. This leads to the development of foam cells, which significantly contribute to neointima and necrotic core formation in atherosclerotic plaques. Pro-inflammatory macrophages, which affect other vascular diseases, present with fragmented mitochondria and corresponding metabolic dysfunction. Targeting macrophage mitochondrial dynamics has proved to be an exciting potential therapeutic approach to combat vascular disease. This review will summarize mitochondrial and metabolic mechanisms of macrophage activation, polarization, and accumulation in vascular diseases.
Asunto(s)
Metabolismo Energético , Macrófagos , Mitocondrias , Fenotipo , Enfermedades Vasculares , Humanos , Animales , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/patología , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Vasculares/metabolismo , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/inmunología , Transducción de Señal , Activación de Macrófagos , Mediadores de Inflamación/metabolismo , Dinámicas MitocondrialesRESUMEN
As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.
Asunto(s)
Antiinflamatorios , Antioxidantes , Hidrógeno , Enfermedades Pulmonares , Estrés Oxidativo , Animales , Humanos , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Citocinas/metabolismo , Hidrógeno/análisis , Mediadores de Inflamación/metabolismo , Enfermedades Pulmonares/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine's protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.
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Alcaloides , Proteína Axina , Factores de Crecimiento de Fibroblastos , Análisis de la Aleatorización Mendeliana , Alcamidas Poliinsaturadas , Sepsis , Humanos , Sepsis/metabolismo , Sepsis/genética , Alcamidas Poliinsaturadas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Proteína Axina/metabolismo , Proteína Axina/genética , Piperidinas/uso terapéutico , Benzodioxoles , Inflamación/metabolismo , Interleucina-2/metabolismo , Interleucina-2/genética , Mediadores de Inflamación/metabolismo , Factor-23 de Crecimiento de FibroblastosRESUMEN
Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1ß, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.
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Permeabilidad Capilar , Células Endoteliales , Hipoglucemia , Mediadores de Inflamación , Microglía , Vasos Retinianos , Humanos , Células Endoteliales/patología , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Microglía/patología , Microglía/metabolismo , Animales , Vasos Retinianos/patología , Vasos Retinianos/metabolismo , Mediadores de Inflamación/metabolismo , Línea Celular , Hipoglucemia/metabolismo , Hipoglucemia/patología , Modelos Animales de Enfermedad , Ocludina/metabolismo , Microvasos/patología , Microvasos/metabolismo , Uniones Estrechas/metabolismo , Uniones Estrechas/patología , Uniones Estrechas/ultraestructura , Citocinas/metabolismo , Claudina-1/metabolismo , Claudina-1/genética , Masculino , Glucemia/metabolismo , Ratones Endogámicos C57BL , Barrera Hematorretinal/patología , Barrera Hematorretinal/metabolismo , Transducción de SeñalRESUMEN
Acute vascular injury provokes an inflammatory response, resulting in neointimal hyperplasia (NIH) and downstream pathologies. The resolution of inflammation is an active process in which specialized proresolving lipid mediators (SPM) and their receptors play a central role. We sought to examine the acute phase response of SPM and their receptors in both circulating blood and the arterial wall in a rat angioplasty model. We found that the ratio of proresolving to pro-inflammatory lipid mediators (LM) in plasma decreased sharply 1 day after vascular injury, then increased slightly by day 7, while that in arteries remained depressed. Granulocyte expression of SPM receptors ALX/FPR2 and DRV2/GPR18, and a leukotriene B4 receptor BLT1 increased postinjury, while ERV1/ChemR23 expression was reduced early and then recovered by day 7. Importantly, we show unique arterial expression patterns of SPM receptors in the acute setting, with generally low levels through day 7 that contrasted sharply with that of the pro-inflammatory CCR2 receptor. Overall, these data document acute, time-dependent changes of LM biosynthesis and SPM receptor expression in plasma, leukocytes, and artery walls following acute vascular injury. A biochemical imbalance between inflammation and resolution LM pathways appears persistent 7 days after angioplasty in this model. These findings may help guide therapeutic approaches to accelerate vascular healing and improve the outcomes of vascular interventions for patients with advanced atherosclerosis.
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Ratas Sprague-Dawley , Animales , Masculino , Ratas , Lesiones del Sistema Vascular/metabolismo , Lesiones del Sistema Vascular/patología , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Leucotrieno B4/metabolismo , Mediadores de Inflamación/metabolismoRESUMEN
Introduction: Gut microbiota (GM) influences the occurrence and development of pancreatic cancer (PC), potentially through the involvement of inflammatory cytokines (IC) and immune cells (IM). We aimed to investigate the causal impact of the gut microbiota (GM) on pancreatic cancer (PC) and identify potential IC and IM mediators. Methods: The summary statistics data from whole-genome association studies of gut microbiota, immune cells, inflammatory cytokines, and four types of pancreatic tumors (MNP: Malignant neoplasm of pancreas; BNP: Benign neoplasm of pancreas; ADCP: Adenocarcinoma and ductal carcinoma of pancreas; NTCP: Neuroendocrine tumor and carcinoma of pancreas). Two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis were employed to assess the causal relationship between gut microbiota (GM) and pancreatic cancer (PC), as well as potential IC and IM mediators. Results: The two-sample UVMR analysis showed causal relationships between 20 gut microbiota species and pancreatic cancer, with pancreatic cancer affecting the abundance of 37 gut microbiota species. Mediation analysis revealed that Interleukin-6 (IL-6), "CD4 on naive CD4+ T cell" and "SSC-A on HLA DR+ Natural Killer" mediated the causal effects of gut microbiota on pancreatic cancer. Conclusion: This Mendelian randomization study demonstrates causal relationships between several specific gut microbiota and pancreatic cancer, as well as potential mediators (IC, IM).
Asunto(s)
Citocinas , Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/microbiología , Microbioma Gastrointestinal/inmunología , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Mediadores de Inflamación/metabolismoRESUMEN
ABSTRACT: Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder.
Asunto(s)
Trastornos de Ansiedad , Fibrilación Atrial , Modelos Animales de Enfermedad , Atrios Cardíacos , Ratas Sprague-Dawley , Receptores AMPA , Animales , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/metabolismo , Masculino , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/fisiopatología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Receptores AMPA/metabolismo , Remodelación Atrial/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Potenciales de Acción/efectos de los fármacos , Fosforilación , Transducción de Señal , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismo , Factor de Transcripción ReIA/metabolismo , Ratas , Antiinflamatorios/farmacología , Periodo Refractario Electrofisiológico/efectos de los fármacos , Inhibidor NF-kappaB alfa/metabolismoRESUMEN
Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.