Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 490
Filtrar
1.
PLoS One ; 15(7): e0235546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609743

RESUMO

Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies.


Assuntos
Anticorpos Monoclonais/imunologia , Regulação da Expressão Gênica , Resistina/imunologia , Resistina/metabolismo , Espaço Extracelular/metabolismo , Células HEK293 , Humanos , Imuno-Histoquímica , Espaço Intracelular/metabolismo , Especificidade de Órgãos , Transporte Proteico
3.
Chem Biol Interact ; 324: 109093, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298659

RESUMO

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperandrogenismo/tratamento farmacológico , Hormônio Luteinizante/metabolismo , Metformina/uso terapêutico , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Ratos Wistar , Resistina/genética , Resistina/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/metabolismo
4.
Clín. investig. arterioscler. (Ed. impr.) ; 32(1): 8-14, ene.-feb. 2020. graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-187002

RESUMO

Introducción: El incremento de grasa miocárdica ha sido propuesto como uno de los principales precursores de la disfunción miocárdica de etiología diabética independiente de la enfermedad arterial coronaria. Sin embargo, actualmente se carece de biomarcadores que reflejen el contenido de grasa miocárdica para la detección clínica de esta patología. Métodos: Las correlaciones entre el contenido de triglicéridos cardíacos y los niveles plasmáticos de las principales moléculas alteradas durante la diabetes y los niveles cardíacos de ARNm de genes implicados en el metabolismo cardíaco (Cd36 y Pdk4) han sido exploradas en un modelo murino de resistencia a la insulina inducida por una dieta con alto contenido en grasas. Resultados: En ratones resistentes a la insulina, la dieta grasa aumentó los niveles de triglicéridos del miocardio, en comparación con animales controles alimentados con una dieta estándar. El contenido de triglicéridos cardíacos se encontró directamente asociado con los niveles plasmáticos de glucosa, triglicéridos, VLDL, resistina y leptina. Además, se observó una correlación inversa entre el contenido de triglicéridos y los niveles cardíacos de ARNm de Cd36 y Pdk4. Conclusiones: Nuestros datos revelan que el contenido cardíaco de triglicéridos se encuentra asociado con un perfil bioquímico plasmático alterado y con una reprogramación de la expresión de genes dirigida a atenuar el impacto de la acumulación ectópica de lípidos en miocardio


Introduction: The increase in myocardial fat has been proposed as one of the main precursors of myocardial dysfunction due to diabetic aetiology, independently of coronary artery disease. However, biomarkers reflecting the myocardial fat content for the clinical detection of this pathology are currently lacking. Methods: Correlations between 4cardiac triglyceride content and plasma levels of major altered molecules during diabetes and cardiac mRNA levels of genes involved in cardiac metabolism (Cd36 and Pdk4) have been explored in a murine model of insulin resistance induced by a high-fat diet. Results: In insulin-resistant mice, the fatty diet increased myocardial triglyceride levels, compared to control animals fed with a standard diet. The content of cardiac triglycerides was directly associated with plasma levels of glucose, triglycerides, VLDL, resistin and leptin. In addition, an inverse correlation was observed between the content of cardiac triglycerides and the cardiac mRNA levels of Cd36 and Pdk4. Conclusions: Our data reveal that the cardiac triglyceride content is associated with altered plasma biochemical profile and reprogramming of gene expression aimed to mitigate the impact of ectopic lipid accumulation in the myocardium


Assuntos
Animais , Camundongos , Masculino , Cardiomiopatias/veterinária , Resistência à Insulina , Gorduras na Dieta , Triglicerídeos/análise , Biomarcadores/sangue , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Cardiomiopatias/etiologia , Triglicerídeos/metabolismo , Glicemia/metabolismo , Lipoproteínas VLDL/metabolismo , Leptina/metabolismo , Resistina/metabolismo , Miocárdio/patologia , RNA/metabolismo , Ácidos Graxos/sangue
5.
Clin Sports Med ; 39(1): 29-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31767108

RESUMO

The meniscus plays an important, complex role in maintaining the homeostasis and health of the knee. Meniscal tears are a risk factor for early chondral injury and eventually knee osteoarthritis. There is a growing body of evidence about the early biological changes associated with meniscal injury that likely start the process of joint degeneration. This review highlights the basic science, translational and clinical studies of the detrimental effects of meniscal injury and deficiency on the biology of the knee.


Assuntos
Osteoartrite do Joelho/fisiopatologia , Lesões do Menisco Tibial/fisiopatologia , Artroplastia do Joelho , Cartilagem Articular/fisiopatologia , Citocinas/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Meniscectomia , Osteoartrite do Joelho/cirurgia , Resistina/metabolismo , Líquido Sinovial/metabolismo , Lesões do Menisco Tibial/cirurgia
6.
BMC Cardiovasc Disord ; 19(1): 294, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842758

RESUMO

BACKGROUND: Postoperative atrial fibrillation occurs in up to 30% of patients after coronary artery bypass graft (CABG) and its cause is unknown. The aim of the study was to evaluate whether concentration of resistin in surrounding coronary artery perivascular adipose tissue (PVAT) is related to postoperative atrial fibrillation occurrence. METHODS: A total number of 46 patients (35 male, 11 female; median age 66.5) were qualified for elective CABG. Medical history, laboratory test results and echocardiographic parameters were noted. Patients were monitored up to 3 days after CABG and then were divided into groups with and without postoperative atrial fibrillation occurrence. Fragments of PVAT were collected intra-operatively: near the left anterior descending artery and main left coronary artery. The concentration of resistin was determined by Human Resistin Quantikine ELISA Kit and expressed as ng/g. A multivariate stepwise logistic regression analysis was performed to find variables related to postoperative atrial fibrillation occurrence. RESULTS: Postoperative atrial fibrillation occurred in 14 (30.4%) patients. The patients with and without postoperative atrial fibrillation were similar in age, gender, epicardial adipose tissue thickness and laboratory parameters. The concentration of resistin in PVAT near the left main coronary artery was significantly higher in patients with postoperative atrial fibrillation than in those without the complication (P = 0.03). In the multivariate stepwise logistic regression analysis the concentration of resistin above cut-off point 54 ng/g in PVAT near left main coronary artery was independently related to postoperative atrial fibrillation occurrence (OR: 7.7; 95% CI:1.4-42.2 p = 0.02). CONCLUSIONS: The higher concentrations of resistin in PVAT near the left main coronary artery which is located close to the left atrium are associated with postoperative atrial fibrillation.


Assuntos
Tecido Adiposo/metabolismo , Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/efeitos adversos , Resistina/metabolismo , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Regulação para Cima
7.
Oxid Med Cell Longev ; 2019: 2192093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772701

RESUMO

Resistin is an adipokine involved in inflammation and able to induce the expression of other proinflammatory cytokines. It is known that, in human semen, resistin is correlated with inflammatory cytokines and sperm quality. The aim of this prospective study was to explore the potential relationship between resistin, lipid peroxidation (LPO), catalase (CAT) activity, and reduced and oxidized glutathione (GSH/GSSG) ratio in semen samples of infertile patients with leukocytospermia (no. 19), infertile patients with varicocele (no. 17), and fertile men (no. 17). Semen analysis was performed following the WHO guidelines, and sperm apoptosis and necrosis were evaluated with annexin V/propidium iodide assay. Seminal plasma samples were used to determine resistin levels by an immunological method, MDA concentration by a HPLC analysis with UV detection, GSH/GSSG ratio by an enzymatic method, CAT activity by a spectrophotometric method. The results showed that, in both groups of infertile patients, semen parameters were significantly reduced (P < 0.001) and sperm apoptosis and necrosis percentages were increased. Resistin levels were significantly higher in leukocytospermia and varicocele groups (P < 0.001 and P < 0.01, respectively) as well as MDA concentration (P < 0.001) compared to controls. The MDA level was also significantly increased in the leukocytospermia group versus the varicocele group (P < 0.05). The GSH/GSSG ratio was higher in fertile controls than the leukocytospermia group (P < 0.05) and the varicocele group (P < 0.001) and in the leukocytospermia group versus the varicocele group (P < 0.05). Both the leukocytospermia and varicocele groups showed increased values of CAT activities (P < 0.001) than controls. Briefly, the correlation between variables, calculated in the whole patient population, showed that resistin levels positively correlated with MDA levels, CAT activity, sperm apoptosis, and necrosis and negatively with sperm parameters and GSH/GSSG ratio. These results support an active role of resistin in an inflammatory process causing LPO, increase of CAT activity, and decrease of GSH/GSSG ratio in seminal plasma of infertile men vs. fertile controls.


Assuntos
Dissulfeto de Glutationa/metabolismo , Resistina/metabolismo , Sêmen/metabolismo , Adulto , Humanos , Peroxidação de Lipídeos , Masculino
8.
Arch Med Res ; 50(6): 333-341, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31677538

RESUMO

BACKGROUND: Inflammatory is one of the main cause of aortic valve stenosis (AS), so discovering novel biomarkers for the targeted therapy of inflammation could be an attractive strategy in AS prevention. The objectives of our study were to clarify the modulatory role of resistin and silent information regulator 1 (SIRT1) before and after surgery and also to evaluate the therapeutic effects of resveratrol. METHODS: Nineteen AS patients and 15 healthy subjects were studied as the case and control groups, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured to determine the levels of resistin and SIRT1 and the effects of resveratrol on them. RESULTS: Significant increase in resistin expression was observed in the patients compare to the control (p ≤0.01), and this upregulation was augmented 72 h following surgery (p ≤0.01). The SIRT1 expression decreased in the AS group compare to the control but this reduction was not significant. Aortic valve replacement caused a higher decrease in the protein (p ≤0.01) and mRNA level (p ≤0.05) of SIRT1. Resveratrol in the AS group significantly diminished the resistin level (p ≤0.05) but increased the SIRT1 level (p ≤0.001). CONCLUSIONS: In our patients with AS, the resistin level was increased, whereas the expression of SIRT1 was reduced and surgery augmented these alterations. Resveratrol improved inflammation in the PBMCs of the patients through the SIRT1/resistin pathway. These findings suggest that pharmacological therapy with resveratrol might be a novel approach to alleviating inflammation in patients with AS.


Assuntos
Estenose da Valva Aórtica/terapia , Inibidores Enzimáticos/uso terapêutico , Resistina/metabolismo , Resveratrol/uso terapêutico , Sirtuína 1/metabolismo , Adulto , Idoso , Animais , Biomarcadores/análise , Feminino , Humanos , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Estilbenos , Regulação para Cima/efeitos dos fármacos
9.
Int J Mol Sci ; 20(20)2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31635187

RESUMO

Synovial membrane inflammation actively participate to structural damage during osteoarthritis (OA). Adipokines, miRNA, and oxidative stress contribute to synovitis and cartilage destruction in OA. We investigated the relationship between visfatin, resistin and miRNA in oxidative stress regulation, in human OA synovial fibroblasts. Cultured cells were treated with visfatin and resistin. After 24 h, we evaluated various pro-inflammatory cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma (BCL)2 by qRT-PCR, apoptosis and mitochondrial superoxide production by cytometry, p50 nuclear factor (NF)-κB by immunofluorescence. Synoviocytes were transfected with miRNA inhibitors and oxidative stress evaluation after adipokines stimulus was performed. The implication of NF-κB pathway was assessed by the use of a NF-κB inhibitor (BAY-11-7082). Visfatin and resistin significantly up-regulated gene expression of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor (TNF)-α, MMP-1, MMP-13 and reduced Col2a1. Furthermore, adipokines induced apoptosis and superoxide production, the transcriptional levels of BCL2, superoxide dismutase (SOD)-2, catalase (CAT), nuclear factor erythroid 2 like 2 (NRF2), miR-34a, miR-146a, and miR-181a. MiRNA inhibitors counteracted adipokines modulation of oxidative stress. Visfatin and resistin effects were suppressed by BAY-11-7082. Our data suggest that miRNA may represent possible mediators of oxidative stress induced by visfatin and resistin via NF-κB pathway in human OA synoviocytes.


Assuntos
Citocinas/metabolismo , Fibroblastos/patologia , MicroRNAs/genética , NF-kappa B/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Osteoartrite/patologia , Estresse Oxidativo , Resistina/metabolismo , Membrana Sinovial/patologia , Apoptose , Células Cultivadas , Citocinas/genética , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , NF-kappa B/genética , Nicotinamida Fosforribosiltransferase/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Resistina/genética , Transdução de Sinais , Membrana Sinovial/metabolismo
10.
Curr Obes Rep ; 8(4): 434-457, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637623

RESUMO

PURPOSE: Sepsis has become a global health problem with rising incidence and high mortality, creating a substantial social and economic burden. Early diagnosis and treatment can improve outcome, but reliable sepsis biomarkers are lacking. This review summarizes current evidence of the pathophysiological mechanisms linking adipose tissue to sepsis and presents experimental and clinical data on adipokines and sepsis along with important insights into the obesity paradox in sepsis survival. RECENT FINDINGS: Sepsis is characterized by significant alterations in circulating cytokines and adipokines, biologically active molecules produced by the adipose tissue, being implicated in metabolic and inflammatory processes. Although data are inconclusive regarding classic adipokines such as leptin and adiponectin, recent evidence have highlighted the striking elevation of resistin and visfatin in critical illness and sepsis as well as their association with sepsis severity and outcomes. Given that inflammatory and metabolic pathways are involved in sepsis, studying adipokines presents an attractive, innovative, and promising research field that may provide more powerful diagnostic and prognostic biomarkers as well as novel therapeutic targets, empowering the therapeutic armamentarium for sepsis management in order to improve survival.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Sepse/metabolismo , Adiponectina/metabolismo , Animais , Biomarcadores/sangue , Citocinas/metabolismo , Humanos , Hiperglicemia/complicações , Resistência à Insulina , Leptina/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Obesidade/complicações , Resistina/metabolismo , Sepse/complicações , Índice de Gravidade de Doença
11.
Curr Obes Rep ; 8(4): 413-433, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637624

RESUMO

PURPOSE: The current review shows evidence for the role of adipokines in breast cancer (BC) pathogenesis summarizing the mechanisms underlying the association between adipokines and breast malignancy. Special emphasis is given also on intriguing insights into the relationship between obesity and BC as well as on the role of novel adipokines in BC development. RECENT FINDINGS: Recent evidence has underscored the role of the triad of obesity, insulin resistance, and adipokines in postmenopausal BC. Adipokines exert independent and joint effects on activation of major intracellular signal networks implicated in BC cell proliferation, growth, survival, invasion, and metastasis, particularly in the context of obesity, considered a systemic endocrine dysfunction characterized by chronic inflammation. To date, more than 10 adipokines have been linked to BC, and this catalog is continuously increasing. The majority of circulating adipokines, such as leptin, resistin, visfatin, apelin, lipocalin 2, osteopontin, and oncostatin M, is elevated in BC, while some adipokines such as adiponectin and irisin (adipo-myokine) are generally decreased in BC and considered protective against breast carcinogenesis. Further evidence from basic and translational research is necessary to delineate the ontological role of adipokines and their interplay in BC pathogenesis. More large-scale clinical and longitudinal studies are awaited to assess their clinical utility in BC prognosis and follow-up. Finally, novel more effective and safer adipokine-centered therapeutic strategies could pave the way for targeted oncotherapy.


Assuntos
Adipocinas/metabolismo , Neoplasias da Mama/metabolismo , Obesidade/metabolismo , Adipocinas/classificação , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Animais , Apelina/metabolismo , Neoplasias da Mama/complicações , Proliferação de Células , Citocinas/metabolismo , Feminino , Fibronectinas/metabolismo , Humanos , Inflamação , Leptina/metabolismo , Lipocalina-2/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Obesidade/complicações , Oncostatina M/metabolismo , Osteopontina/metabolismo , Resistina/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31500356

RESUMO

Liposuction is becoming an increasingly common procedure of aesthetic surgery, that patients choose to shape the body. Apart from the risks associated with the surgery, one should also consider whether the reduction of adipose tissue can significantly affect the metabolism of lipids and carbohydrates and, indirectly, that of bone tissue. The aim of the presented study was to assess the effects of small-volume liposuction surgery in the gluteal-femoral region on the selected markers of carbohydrate, lipid, and bone metabolism. The study included 27 women (40.75 ± 13.67 years of age, BMI = 25.9 ± 4.13 kg/m2) subjected to the removal of 3.35 ± 0.994 L of adipose tissue to shape the body. Following the procedure, significant changes in the body composition and body adiposity indicators were observed in these women. A slight decrease in adiponectin, leptin, resistin and insulin levels and HOMA-IR value was found three months after the procedure. No changes in the lipid profile of the subjects were found. It can be concluded that the removal of a small volume of adipose tissue from the gluteal-femoral region has a slight but positive effect on carbohydrate and lipid metabolism, providing a decreased risk of developing insulin resistance.


Assuntos
Tecido Adiposo/metabolismo , Lipectomia/métodos , Adiponectina/metabolismo , Adulto , Composição Corporal , Feminino , Humanos , Insulina/metabolismo , Leptina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Pessoa de Meia-Idade , Resistina/metabolismo
13.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505789

RESUMO

It is well known that adipokines are endocrine factors that are mainly secreted by white adipose tissue. Their central role in energy metabolism is currently accepted. More recently, their involvement in fertility regulation and the development of some reproductive disorders has been suggested. Data concerning the role of leptin and adiponectin, the two most studied adipokines, in the control of the reproductive axis are consistent. In recent years, interest has grown about some novel adipokines, chemerin, visfatin, resistin and apelin, which have been found to be strongly associated with obesity and insulin-resistance. Here, we will review their expression and role in male and female reproduction in humans and animal models. According to accumulating evidence, they could regulate the secretion of GnRH (Gonadotropin-Releasing Hormone), gonadotropins and steroids. Furthermore, their expression and that of their receptors (if known), has been demonstrated in the human and animal hypothalamo-pituitary-gonadal axis. Like leptin and adiponectin, these novel adipokines could thus represent metabolic sensors that are able to regulate reproductive functions according to energy balance changes. Therefore, after investigating their role in normal fertility, we will also discuss their possible involvement in some reproductive troubles known to be associated with features of metabolic syndrome, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia and intra-uterine growth retardation in women, and sperm abnormalities and testicular pathologies in men.


Assuntos
Apelina/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Diabetes Gestacional/metabolismo , Retardo do Crescimento Fetal/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Síndrome do Ovário Policístico/metabolismo , Pré-Eclâmpsia/metabolismo , Resistina/metabolismo , Doenças Testiculares/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Resistência à Insulina , Masculino , Obesidade/metabolismo , Gravidez
14.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443349

RESUMO

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.


Assuntos
Adipocinas/metabolismo , Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Adipocinas/genética , Animais , Artrite Reumatoide/patologia , Biomarcadores , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Leptina/genética , Leptina/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Resistina/genética , Resistina/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
15.
Diabetes Res Clin Pract ; 155: 107803, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31362052

RESUMO

AIM: The aim of the study was to investigate the serum and vitreous levels of resistin in patients with the proliferative diabetic retinopathy (PDR) and to compare those with age-matched control subjects. METHODS: The study included 45 eyes with PDR (group 1) and a control group of 22 (group 2). All eyes underwent vitrectomy surgery. The lipid profile, fasting blood glucose (FBG), HbA1c and resistin levels were investigated in blood samples of all subjects. Complete ophthalmological examinations were evaluated. Vitreous samples were collected from both groups during vitrectomy surgery and resistin levels were investigated in those samples. The results were evaluated using SPSS 9.0 software. RESULTS: The demographic characteristics of the diabetic group and the control group were similar (p > 0.05). There was no significant difference between the groups in respect of mean visual acuity (VA), body mass index (BMI) values, or lipid profiles (p ˃ 0.05). There was no measurable value of resistin in the vitreous samples of all the eyes. The mean blood resistin level was 367 ng/ml in the control group and 387 ng/ml in the study group and the difference was not statistically significant (p > 0.05). CONCLUSIONS: In the light of the findings of this study, it can be assumed that resistin did not pass through the vitreous at measurable levels. However, the serum resistin levels of the diabetic patients were higher than those of the control group although not statistically significant. Therefore, it can be considered that resistin does not play a major role in retinal neovascularization.


Assuntos
Retinopatia Diabética/fisiopatologia , Resistina/sangue , Resistina/metabolismo , Corpo Vítreo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acuidade Visual
16.
Am J Physiol Gastrointest Liver Physiol ; 317(4): G441-G446, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31343254

RESUMO

Mesenteric ischemia is a devastating process that can result in intestinal necrosis. Mesenchymal stem cells (MSCs) are becoming a promising treatment modality. We hypothesized that 1) MSCs would promote vasodilation of mesenteric arterioles, 2) hydrogen sulfide (H2S) would be a critical paracrine factor of stem cell-mediated vasodilation, 3) mesenteric vasodilation would be impaired in the absence of endothelial nitric oxide synthase (eNOS) within the host tissue, and 4) MSCs would improve the resistin-to-adiponectin ratio in mesenteric vessels. H2S was measured with a specific fluorophore (7-azido-3-methylcoumarin) in intact MSCs and in cells with the H2S-producing enzyme cystathionine ß synthase (CBS) knocked down with siRNA. Mechanical responses of isolated second- and third-order mesenteric arteries (MAs) from wild-type and eNOS knockout (eNOSKO) mice were monitored with pressure myography, after which the vessels were snap frozen and later analyzed for resistin and adiponectin via multiplex beaded assay. Addition of MSCs to the myograph bath significantly increased vasodilation of norepinephrine-precontracted MAs. Knockdown of CBS in MSCs decreased H2S production by MSCs and also decreased MSC-initiated MA dilation. MSC-initiated vasodilation was further reduced in eNOSKO vessels. The MA resistin-to-adiponectin ratio was higher in eNOSKO vessels compared with wild-type. These results show that MSC treatment promotes dilation of MAs by an H2S-dependent mechanism. Furthermore, functional eNOS within the host mesenteric bed appears to be essential for maximum stem cell therapeutic benefit, which may be attributable, in part, to modifications in the resistin-to-adiponectin ratio.NEW & NOTEWORTHY Stem cells have been shown to improve survival, mesenteric perfusion, and histological injury scores following intestinal ischemia. These benefits may be due to the paracrine release of hydrogen sulfide. In an ex vivo pressure myography model, we observed that mesenteric arterial dilation improved with stem cell treatment. Hydrogen sulfide release from stem cells and endothelial nitric oxide synthase within the vessels were critical components of optimizing stem cell-mediated mesenteric artery dilation.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Células-Tronco Mesenquimais/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Circulação Esplâncnica/fisiologia , Vasodilatação/fisiologia , Adiponectina/metabolismo , Animais , Arteríolas/fisiologia , Cistationina beta-Sintase/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Técnicas In Vitro , Masculino , Isquemia Mesentérica , Camundongos , Camundongos Endogâmicos C57BL , Resistina/metabolismo
17.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195622

RESUMO

Diabetes is a contributor to morbidity across the globe and is often associated with obesity, metabolic syndrome and other inflammatory diseases associated with aging. In addition to genetic and lifestyle factors, environmental factors such as metals and persistent organic pollutants may increase the severity or lower the threshold of these conditions. In cell culture, methylmercury is toxic to adipocytes and may impact adipokine secretions. In this study, we determined the effects of different concentrations of theaflavin digallate on methylmercury exposed 3T3-L1 adipocytes in cell culture. Secretions of resistin, adiponectin and lipid peroxidation product, 4-hydroxynonenal (4-HNE) were monitored using ELISA assays. Cell morphology of methylmercury and theaflavin-3,3'-digallate treated adipocytes was assessed using Lipid (Oil Red O) staining. Exposure to methylmercury increased the levels of resistin and adiponectin as well as 4-HNE when compared to the control cells. Methylmercury treated cells resulted in smaller number of adipocytes and clumped lipid droplets. These results suggest that methylmercury induces reactive oxygen species leading to development of an inflammatory response. Theaflavin-3,3'-digallate reduced the impact of methylmercury by maintaining the adipocytes morphology and secretion patterns of adiponectin, resistin and 4-hydroxynonenal. With this experimental model system other anti-inflammatory and signaling agents could be tested at the biochemical level before eventually leading to studies in animal models.


Assuntos
Adipócitos/citologia , Adipocinas/metabolismo , Biflavonoides/farmacologia , Catequina/farmacologia , Diferenciação Celular , Ácido Gálico/análogos & derivados , Compostos de Metilmercúrio/toxicidade , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/metabolismo , Aldeídos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Ácido Gálico/farmacologia , Camundongos , Resistina/metabolismo
18.
Eur J Histochem ; 63(2)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31060349

RESUMO

Resistin is a polypeptide hormone of the adipokine-family, primarily, but not exclusively, produced by the adipose tissue. Recent studies suggested that resistin may affect the male and female reproductive activity. The study aim was to immunohistochemically evaluate the presence and distribution of resistin in the ovine uterus. Uterine samples were collected from two groups of ewes at the end of an experimental trial during which the animals of the first group (CTRL) were fed only by grazing while those of the second one (EXP) were supplemented with barley and corn. Using a monoclonal antibody against resistin, tested by Western Blot, the immunopositive reaction was identified in the cytoplasm of epithelial lining cells and uterine glands. The endogenous production of resistin seemed to be affected by different diet, as evidenced by staining differences between the CTRL and EXP groups. Our findings support the existence of a peripheral resistin system in the sheep uterus. It is possible that this system is involved in the functionality of the uterus, which is also affected by the animal's nutritional status.


Assuntos
Dieta/veterinária , Resistina/análise , Útero/metabolismo , Animais , Anticorpos Monoclonais , Feminino , Hordeum , Imuno-Histoquímica , Estado Nutricional , Resistina/imunologia , Resistina/metabolismo , Ovinos , Útero/química , Útero/citologia , Zea mays
19.
Cell Host Microbe ; 25(6): 777-788.e8, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31101494

RESUMO

Vitamin A deficiency increases susceptibility to skin infection. However, the mechanisms by which vitamin A regulates skin immunity remain unclear. Here, we show that resistin-like molecule α (RELMα), a small secreted cysteine-rich protein, is expressed by epidermal keratinocytes and sebocytes and serves as an antimicrobial protein that is required for vitamin-A-dependent resistance to skin infection. RELMα was induced by microbiota colonization of the murine skin, was bactericidal in vitro, and was protected against bacterial infection of the skin in vivo. RELMα expression required dietary vitamin A and was induced by the therapeutic vitamin A analog isotretinoin, which protected against skin infection in a RELMα-dependent manner. The RELM family member Resistin was expressed in human skin, was induced by vitamin A analogs, and killed skin bacteria, indicating a conserved function for RELM proteins in skin innate immunity. Our findings provide insight into how vitamin A promotes resistance to skin infection.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Fatores Imunológicos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Dermatopatias Bacterianas/prevenção & controle , Pele/imunologia , Vitamina A/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Camundongos , Resistina/metabolismo , Dermatopatias Bacterianas/imunologia , Ativação Transcricional/efeitos dos fármacos
20.
Med Hypotheses ; 126: 78-81, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31010504

RESUMO

Type-II Endometrial Cancer (EMC) is one of the most common types of gynaecological cancer affecting more than 2.7 million people worldwide. Clinical evidence shows that adipokines levels are abnormally altered in Type-II EMC and reported to be one of the major responsible factor for uncontrolled proliferation and metastasis in Type-II EMC. Reversing the altered adipokine levels, therefore, help to control Type-II EMC proliferation and metastasis. In the present hypothesis we focus on the possible role of Thiazolidinediones in favourably altering the adipokine levels to benefit in the management of Type-II EMC.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Adipocinas/metabolismo , Adiponectina/metabolismo , Animais , Proliferação de Células , Neoplasias do Endométrio/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Leptina/metabolismo , Camundongos , Modelos Biológicos , Metástase Neoplásica , Resistina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA