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1.
Int J Chron Obstruct Pulmon Dis ; 19: 1971-1987, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247667

RESUMO

Background: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline. Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships. Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(ß, -23.4061; 95% CI, -42.2805- -4.5317), FEV1(ß, -46.7730; 95% CI, -63.3371- -30.2089), FEV1%(ß, -0.7923; 95% CI, -1.1635- -0.4211), FEV1/FVC(ß, -0.6366; 95% CI, -0.8328- -0.4404) and PEF(ß, -121.4468; 95% CI,-164.1939- -78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly. Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.


Assuntos
Mediadores da Inflamação , Inflamação , Pulmão , Inquéritos Nutricionais , Valor Preditivo dos Testes , Humanos , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Pulmão/fisiopatologia , Pulmão/imunologia , Volume Expiratório Forçado , Estados Unidos/epidemiologia , Adulto , Capacidade Vital , Inflamação/fisiopatologia , Inflamação/imunologia , Inflamação/diagnóstico , Inflamação/sangue , Mediadores da Inflamação/sangue , Idoso , Biomarcadores/sangue , Fatores de Risco , Modelos Lineares
2.
Exp Clin Transplant ; 22(8): 613-621, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39254073

RESUMO

OBJECTIVES: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time. MATERIALS AND METHODS: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels. RESULTS: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels. CONCLUSIONS: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.


Assuntos
Biomarcadores , Índice Vascular Coração-Tornozelo , Mediadores da Inflamação , Transplante de Rim , Valor Preditivo dos Testes , Calcificação Vascular , Rigidez Vascular , Humanos , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Adulto , Estudos de Casos e Controles , Calcificação Vascular/sangue , Calcificação Vascular/fisiopatologia , Calcificação Vascular/etiologia , Calcificação Vascular/diagnóstico , Fatores de Tempo , Mediadores da Inflamação/sangue , Fatores de Risco , Fatores de Crescimento de Fibroblastos/sangue , Fator de Crescimento de Fibroblastos 23 , Quimiocina CCL2/sangue , Uremia/sangue , Uremia/diagnóstico , Uremia/fisiopatologia , Indicã/sangue , Resultado do Tratamento , Doadores Vivos
3.
Curr Aging Sci ; 17(3): 180-188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39248031

RESUMO

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.


Assuntos
Anti-Inflamatórios , Antioxidantes , Estresse Oxidativo , Polifenóis , Envelhecimento da Pele , Pele , Envelhecimento da Pele/efeitos dos fármacos , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Humanos , Pele/efeitos dos fármacos , Pele/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Raios Ultravioleta/efeitos adversos , Mediadores da Inflamação/metabolismo
5.
Immun Inflamm Dis ; 12(9): e70013, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39240033

RESUMO

BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: Malaria-infected children had higher tumor necrosis factor alpha (TNF-α) (p < .001), interferon-gamma (IFN-É£) (p < .001), interleukin (IL)-1ß (p < .001), IL-6 (p < .001), granulocyte macrophage-colony stimulating factor (GM-CSF) (p < .001), and IL-10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but reduced IL-3 (p < .001) and TGF-ß (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but lower IL-3 (p < .001) and TGF-ß (p < .001) than those with uncomplicated malaria. CONCLUSION: Parasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL-10, GM-CSF, IL-6, IL-1ß, IFN-É£, and TNF-α, but negatively associated with IL-3 and TGF-ß. Malaria is associated with enhanced secretion of pro- and anti-inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL-3 and TGF-ß may offer protection against severe malarial anemia.


Assuntos
Anemia , Citocinas , Progressão da Doença , Malária Falciparum , Humanos , Citocinas/sangue , Anemia/sangue , Anemia/imunologia , Anemia/parasitologia , Masculino , Pré-Escolar , Feminino , Estudos Prospectivos , Estudos de Casos e Controles , Lactente , Malária Falciparum/sangue , Malária Falciparum/imunologia , Malária Falciparum/complicações , Malária Falciparum/parasitologia , Malária Falciparum/epidemiologia , Gana/epidemiologia , Criança , Parasitemia/sangue , Parasitemia/imunologia , Plasmodium falciparum/imunologia , Mediadores da Inflamação/sangue
6.
Support Care Cancer ; 32(9): 625, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222245

RESUMO

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.


Assuntos
Antineoplásicos , Mediadores da Inflamação , Neoplasias , Saliva , Estomatite , Fator de Necrose Tumoral alfa , Humanos , Estomatite/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Antineoplásicos/efeitos adversos , Idoso , Adulto , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-6/análise , Estudos de Coortes , Índice de Gravidade de Doença
7.
Int J Rheum Dis ; 27(9): e15319, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39223010

RESUMO

OBJECTIVE: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). METHODS: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. RESULTS: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). CONCLUSION: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.


Assuntos
Antirreumáticos , Artrite Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Metotrexato , Qualidade de Vida , Humanos , Metotrexato/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/sangue , Feminino , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Masculino , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto , Fatores de Tempo , Medição da Dor , Biomarcadores/sangue , Idoso , Mediadores da Inflamação/sangue
8.
Front Immunol ; 15: 1367252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234251

RESUMO

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.


Assuntos
Biomarcadores , Citocinas , Terapia de Reposição de Enzimas , Doença de Fabry , Fenótipo , Humanos , Doença de Fabry/tratamento farmacológico , Doença de Fabry/genética , Doença de Fabry/imunologia , Masculino , Feminino , Citocinas/metabolismo , Adulto , Pessoa de Meia-Idade , alfa-Galactosidase/genética , alfa-Galactosidase/uso terapêutico , Adulto Jovem , Mediadores da Inflamação/metabolismo , Estudos de Casos e Controles , Inflamação/imunologia
9.
Nutrients ; 16(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39275315

RESUMO

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.


Assuntos
Biomarcadores , Líquido do Sulco Gengival , Gengivite , Extratos Vegetais , Própole , Humanos , Gengivite/tratamento farmacológico , Método Duplo-Cego , Própole/farmacologia , Masculino , Feminino , Adulto , Extratos Vegetais/farmacologia , Líquido do Sulco Gengival/metabolismo , Pessoa de Meia-Idade , Metaloproteinase 9 da Matriz/metabolismo , Garcinia mangostana/química , Metaloproteinase 8 da Matriz/metabolismo , Interleucina-1beta/metabolismo , Periodontite/tratamento farmacológico , Resultado do Tratamento , Dinoprostona/metabolismo , Adulto Jovem , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Mediadores da Inflamação/metabolismo
10.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273541

RESUMO

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.


Assuntos
Doenças Metabólicas , Obesidade , Humanos , Obesidade/metabolismo , Animais , Doenças Metabólicas/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/uso terapêutico , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
11.
Int J Mol Sci ; 25(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39273602

RESUMO

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.


Assuntos
Biomarcadores , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Citocinas , Inflamação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso , Doenças das Artérias Carótidas/sangue , Citocinas/sangue , Inflamação/sangue , Fatores de Risco , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Artérias Carótidas/patologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Quimiocina CCL2/sangue , Mediadores da Inflamação/sangue , Doenças Assintomáticas
12.
Diab Vasc Dis Res ; 21(5): 14791641241271949, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39271468

RESUMO

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.


Assuntos
Proteína HMGB1 , Hipoglicemiantes , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inibidores , Animais , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Mediadores da Inflamação/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Anti-Inflamatórios/uso terapêutico , Terapia de Alvo Molecular , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Resistência à Insulina , Receptores Toll-Like/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/prevenção & controle , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/tratamento farmacológico
13.
J Cardiovasc Pharmacol ; 84(3): 319-330, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39240727

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Transportador de Glucose Tipo 4 , Traumatismo por Reperfusão Miocárdica , Óxido Nítrico Sintase Tipo III , Ratos Wistar , Transdução de Sinais , Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico Sintase Tipo III/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Transportador de Glucose Tipo 4/metabolismo , Masculino , Imunoglobulinas Intravenosas/farmacologia , Apoptose/efeitos dos fármacos , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/tratamento farmacológico , Ratos , Estresse Oxidativo/efeitos dos fármacos , Citocinas/metabolismo , Preparação de Coração Isolado , Mediadores da Inflamação/metabolismo
14.
Medicine (Baltimore) ; 103(36): e39521, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252217

RESUMO

In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1ß (OR = 0.956, 95% CI: -0.08 to -0.006; P = .02) and IFN-G (OR = 0.915, 95% CI: -0.16 to -0.02; P = .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (OR = 0.967, 95% CI: -0.063 to -0.004; P = .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.


Assuntos
Estudo de Associação Genômica Ampla , Degeneração do Disco Intervertebral , Análise da Randomização Mendeliana , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/sangue , Masculino , Feminino , Finlândia/epidemiologia , Citocinas/sangue , Citocinas/genética , Polimorfismo de Nucleotídeo Único , Pessoa de Meia-Idade , Mediadores da Inflamação/sangue , Inflamação/genética , Inflamação/sangue , Predisposição Genética para Doença
15.
RMD Open ; 10(3)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39242113

RESUMO

OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1ß (IL-1ß), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.


Assuntos
Artrite Juvenil , Biomarcadores , Indução de Remissão , Humanos , Artrite Juvenil/sangue , Artrite Juvenil/diagnóstico , Biomarcadores/sangue , Feminino , Masculino , Criança , Adolescente , Prognóstico , Curva ROC , Pré-Escolar , Estudos Longitudinais , Metaloproteinase 3 da Matriz/sangue , Estudos de Coortes , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Seguimentos , Mediadores da Inflamação/sangue
16.
Cardiovasc Diabetol ; 23(1): 343, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285303

RESUMO

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.


Assuntos
Cardiomiopatias Diabéticas , Fenofibrato , Insuficiência Cardíaca , Hipolipemiantes , Obesidade , Fenofibrato/uso terapêutico , Fenofibrato/farmacologia , Animais , Obesidade/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Masculino , República da Coreia/epidemiologia , Humanos , Cardiomiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Camundongos Endogâmicos C57BL , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , PPAR alfa/agonistas , PPAR alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fatores de Tempo , Bases de Dados Factuais , Transdução de Sinais/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Feminino , Hospitalização , Pessoa de Meia-Idade , Idoso , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/sangue , Fatores de Risco , Função Ventricular Esquerda/efeitos dos fármacos
17.
Nutrients ; 16(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39275140

RESUMO

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.


Assuntos
Tecido Adiposo , Mediadores da Inflamação , Inflamação , Obesidade , Humanos , Obesidade/metabolismo , Inflamação/metabolismo , Tecido Adiposo/metabolismo , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Animais , Adipócitos/metabolismo , Macrófagos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Front Immunol ; 15: 1413179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247182

RESUMO

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.


Assuntos
Inflamação , Peptídeos , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Animais , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Imunomodulação/efeitos dos fármacos
19.
J Reprod Immunol ; 165: 104317, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39154624

RESUMO

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.


Assuntos
Inflamação , Leiomioma , Humanos , Feminino , Leiomioma/imunologia , Leiomioma/patologia , Gravidez , Inflamação/imunologia , Citocinas/metabolismo , Neoplasias Uterinas/imunologia , Neoplasias Uterinas/patologia , Endométrio/imunologia , Endométrio/patologia , Mediadores da Inflamação/metabolismo
20.
Vascul Pharmacol ; 156: 107419, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39181483

RESUMO

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.


Assuntos
Metabolismo Energético , Macrófagos , Mitocôndrias , Fenótipo , Doenças Vasculares , Humanos , Animais , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/imunologia , Transdução de Sinais , Ativação de Macrófagos , Mediadores da Inflamação/metabolismo , Dinâmica Mitocondrial
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