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1.
Zhonghua Gan Zang Bing Za Zhi ; 29(3): 271-274, 2021 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-33902196

RESUMO

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H(2)O(2)). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-ß-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-ß-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.


Assuntos
Fator de Crescimento Insulin-Like I , Proteína Supressora de Tumor p53 , Senescência Celular , Hepatócitos , Peróxido de Hidrogênio , Proteína Supressora de Tumor p53/genética
2.
Sheng Li Xue Bao ; 73(2): 342-352, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33903895

RESUMO

Insulin-like growth factor-1 (IGF-1) is a peptide with a similar molecular structure to insulin. IGF-1 plays a key role in tissue growth and development, as well as cell metabolism, proliferation, differentiation and apoptosis. Liver is the main source of IGF-1, with the production of IGF-1 up to 75% of the total in the whole body, while the remaining 25% are secreted by skeletal muscles, heart, kidney, spleen and other organs. Target organs of IGF-1 include heart, blood vessels, liver, bone and skeletal muscles. It has been well documented that IGF-1 plays an important role in the prevention and treatment of metabolic diseases. Different types of exercise have different effects on IGF-1 expression with organ differences. In this article, we reviewed the preventive and therapeutic effects of IGF-1 on metabolic diseases and IGF-1-mediated exercise-induced benefits.


Assuntos
Fator de Crescimento Insulin-Like I , Doenças Metabólicas , Terapia por Exercício , Humanos , Fígado , Doenças Metabólicas/terapia , Músculo Esquelético
3.
Medicine (Baltimore) ; 100(15): e25432, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847643

RESUMO

ABSTRACT: To analyze the correlation between IGF-1, ZAG, nesfatin-1, HbA1c levels, and type 2 diabetes mellitus (T2DM) complicated with hypothyroidism.Fifty-five patients with type-2 diabetes who were admitted to our hospital from August 2018 to February 2020 were selected as the control group, and 55 patients with type 2 diabetes combined with hypothyroidism who were admitted to the hospital at the same period were selected as the combined group, and 56 patients who came to our hospital for physical examination at the same period were selected as the healthy group. The general clinical data and relevant laboratory indexes of all patients in the three groups were collected and statistically analyzed. Besides, the correlation between IGF-1, ZAG, nesfatin-1, HbA1c levels, and T2DM complicated with hypothyroidism was analyzed.Levels of FPG, FINS, TC, TG, LDL, 2hPBG, TPOAb, TgAb, and HOMA-IR in the diabetes group and combined group were all significantly higher than those in the healthy group, while HDL and T4 levels in the diabetes group and combined group were lower than those in the healthy group (P < .05). The levels of FPG, FINS, TC, TG, LDL, 2hPBG, TPOAb, and TgAb in the combined group were significantly higher than those in the diabetes group (P < .05), and the levels of HDL and T4 were lower than those in the diabetes group. In addition, the IGF-1 level was positively correlated with ZAG, nesfatin-1, and HbA1c levels in the combined group (P < .05), and IGF-1 (OR: 0.964, 95% CI: 0.943-0.983, P = .001), ZAG (OR: 1.298, 95% CI: 1.121-1.401, P = .005), nesfatin-1 (OR: 0.876, 95% CI: 0.751-0.901, P = .002), and HbA1c (OR: 1.321, 95% CI: 1.121-1.401, P = .012) were independent risk factors for T2DM complicated with hypothyroidism.Regular detection of IGF-1, ZAG, nesfatin-1, and HbA1c levels are of great value for the diagnosis and treatment of patients with T2DM complicated with hypothyroidism.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Hipotireoidismo/epidemiologia , Fator de Crescimento Insulin-Like I/análise , Nucleobindinas/sangue , Proteínas de Plasma Seminal/sangue , Adulto , Fatores Etários , Glicemia , Índice de Massa Corporal , Comorbidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
4.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807089

RESUMO

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9-2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.


Assuntos
Biomarcadores , Fator de Crescimento Insulin-Like I/metabolismo , Miocárdio/metabolismo , Lesões por Radiação/metabolismo , Transdução de Sinais/efeitos da radiação , Animais , Células Sanguíneas/metabolismo , Células Sanguíneas/efeitos da radiação , Peso Corporal/efeitos da radiação , Colágeno/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Fibrose/etiologia , Regulação da Expressão Gênica/efeitos da radiação , Frequência Cardíaca/efeitos da radiação , Hematopoese/efeitos da radiação , Metabolismo dos Lipídeos/efeitos da radiação , Especificidade de Órgãos/efeitos da radiação , Lesões por Radiação/genética , Suínos
5.
Eur J Endocrinol ; 184(6): 813-821, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33830940

RESUMO

Background: Glucocorticoid excess leads to muscle atrophy and weakness in patients with endogenous Cushing's syndrome. Insulin-like growth factor I (IGF-I) is known to have protective effects on muscle loss. We hypothesized that individual serum IGF-I concentrations might be predictive for long-term myopathy outcome in Cushing's syndrome. Patients and methods: In a prospective longitudinal study of 31 patients with florid Cushing's syndrome, we analyzed IGF-I and IGF binding protein 3 (IGFBP 3) concentrations at the time of diagnosis and following surgical remission over a period of up to 3 years. We assessed muscle strength by grip strength measurements using a hand grip dynamometer and muscle mass by bio-impedance measurements. Findings: Individual serum IGF-I concentrations in the postoperative phase were strongly predictive of long-term grip strength outcome (rs = 0.696, P ≤ 0.001). Also, lower IGF-I concentrations were associated with a lower muscle mass after 3 years (rs = 0.404, P = 0.033). While patients with high IGF-I s.d. scores (SDS; >1.4) showed an improvement in grip strength within the follow-up period (P = 0.009), patients with lower IGF-I SDS (≤-0.4) had a worse outcome with persisting muscle dysfunction. In contrast, preoperative IGF-I concentrations during the florid phase of Cushing's syndrome did not predict long-term muscle function outcome (rs = 0.285, P = 0.127). Conclusion: Lower individual IGF-I concentrations 6 months after curative surgery for Cushing's syndrome are associated with adverse long-term myopathy outcome and IGF-I might be essential for muscle regeneration in the early phase after correction of hypercortisolism.


Assuntos
Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Fator de Crescimento Insulin-Like I/análise , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Adulto , Feminino , Força da Mão , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Força Muscular , Doenças Musculares/sangue , Estudos Prospectivos , Resultado do Tratamento
6.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799501

RESUMO

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Leptina/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Metabolismo Energético/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hormônio do Crescimento/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraventriculares , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Somatostatina/genética , Somatostatina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
7.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799503

RESUMO

Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory pathway. In addition, GH deficiency conditions hearing loss or central auditory processing disorders. There are promising animal studies that reflect a possible regenerative role when exogenous GH is used in hearing impairments, demonstrated in in vivo and in vitro studies, and also, even a few studies show beneficial effects in humans presented and substantiated in the main text, although they should not exaggerate the main conclusions.


Assuntos
Vias Auditivas/metabolismo , Hormônio do Crescimento/genética , Perda Auditiva Funcional/genética , Perda Auditiva Neurossensorial/genética , Hipocampo/metabolismo , Fator de Crescimento Insulin-Like I/genética , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Vias Auditivas/patologia , Cóclea/metabolismo , Cóclea/patologia , Nervo Coclear/metabolismo , Nervo Coclear/patologia , Regulação da Expressão Gênica , Hormônio do Crescimento/metabolismo , Perda Auditiva Funcional/metabolismo , Perda Auditiva Funcional/fisiopatologia , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/fisiopatologia , Hipocampo/patologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Regeneração Nervosa/fisiologia , Ruído/prevenção & controle
8.
Neurosci Lett ; 751: 135809, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33713748

RESUMO

Migraineurs experience increased oxidative stress which drives the initiation and maintenance of migraine-related pain in animal models and, by extension, migraine in humans. Oxidative stress augments calcitonin gene-related peptide (CGRP) levels, a mediator of migraine pain. Insulin-like growth factor-1 (IGF-1), a neuroprotective growth factor, reduces susceptibility to spreading depression, a preclinical model of migraine, in cultured brain slices by blocking oxidative stress and neuroinflammation from microglia. Similarly, nasal delivery of IGF-1 inhibits spreading depression in vivo. After recurrent cortical spreading depression, nasal administration of IGF-1 also significantly reduces trigeminal ganglion oxidative stress and CGRP levels as well as trigeminocervical c-Fos activation. Here, we probed for the impact of nasal IGF-1 pretreatment on trigeminal system activation using a second well-established preclinical model of migraine, systemic nitroglycerin injection. Adult male rats were treated with one of three doses of IGF-1 (37.5, 75 or 150 µg) and the optimal dose found in males was subsequently used for treatment of female rats. One day later, animals received an intraperitoneal injection of nitroglycerin. Measurements taken two hours later after nitroglycerin alone showed increased surrogate markers of trigeminal activation - oxidative stress and CGRP in the trigeminal ganglion and c-Fos in the trigeminocervical complex compared to vehicle control. These effects were significantly reduced at all doses of IGF-1 for trigeminal ganglion metrics of oxidative stress and CGRP and only at the lowest dose in both males and females for c-Fos. The latter inverted U-shaped or hormetic response is seen in enzyme-targeting drugs. While the specific mechanisms remain to be explored, our data here supports the ability of IGF-1 to preserve mitochondrial and antioxidant pathway homeostasis as means to prevent nociceptive activation in the trigeminal system produced by an experimental migraine model.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Nitroglicerina/farmacologia , Estresse Oxidativo , Gânglio Trigeminal/metabolismo , Administração Intranasal , Animais , Feminino , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/uso terapêutico , Masculino , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/fisiologia
9.
Environ Toxicol ; 36(6): 1195-1205, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33720504

RESUMO

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose-depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF-1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p < .05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p < .05), suggesting that ammonia exposure could perturb both GH/IGF-axis and HPT-axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase-polypeptide 1(s6k1) in the dorsal muscle were significantly down-regulated in the fish exposed to ammonia (p < .05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress.


Assuntos
Amônia , Somatomedinas , Amônia/toxicidade , Animais , Regulação para Baixo , Hormônio do Crescimento , Fator de Crescimento Insulin-Like I/genética , Fosfatidilinositol 3-Quinases
10.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672678

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein-protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.


Assuntos
Fibrose Pulmonar Idiopática/genética , Anexina A3/genética , Colágeno Tipo I/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Cadeias beta de Integrinas/genética , Metaloproteinases da Matriz/genética , Osteopontina/genética , Mapas de Interação de Proteínas , Proteínas Qa-SNARE/genética , Trombospondinas/genética
11.
Zhongguo Gu Shang ; 34(3): 275-81, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787175

RESUMO

OBJECTIVE: To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein. METHODS: Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot. RESULTS: In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (P<0.05). (2) Compared with YC group, the increase of the expression of IGF-I mRNA in YEA group was more obvious(P=0.051). (3)The expression of p-Akt and p-mTOR in YA group was significantly higher than that in YC group (P<0.05), and the expressionof p-mTOR, p-p70S6K also showed an increasing trend in YEA group (P>0.05). CONCLUSION: Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.


Assuntos
Eletroacupuntura , Envelhecimento , Animais , Exercício Físico , Fator de Crescimento Insulin-Like I/genética , Masculino , Músculo Esquelético , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley
12.
BMC Psychiatry ; 21(1): 157, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731067

RESUMO

BACKGROUND: Hormones of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), and hypothalamic-pituitary-somatotropic (HPS) axes are potentially involved in major depressive disorder (MDD), but these hormones have not been simultaneously investigated in male patients with MDD. We investigated the association between male MDD symptoms and estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF1). METHODS: Serum estradiol, testosterone, cortisol, DHEAS, and IGF1 levels were measured in 54 male patients with MDD and 37 male controls and were compared with clinical factors. We investigated the associations between hormone levels and Hamilton Depression Rating Scale (HAM-D) scores. The correlations among hormones were also investigated. RESULTS: Patients had significantly lower estradiol levels than controls (22.4 ± 8.4 pg/mL vs. 26.1 ± 8.5 pg/mL, P = 0.040). Serum estradiol levels were negatively correlated with HAM-D scores (P = 0.000094) and positively correlated with Global Assessment of Functioning scores (P = 0.000299). IGF1 levels and the cortisol:DHEAS ratio were higher in patients than in controls (IGF1: 171.5 ± 61.8 ng/mL vs. 144.1 ± 39.2 ng/mL, P = 0.011; cortisol:DHEAS ratio: 0.07 ± 0.05 vs. 0.04 ± 0.02, P = 0.001). DHEAS levels were lower in patients than in controls (227.9 ± 108.4 µg/dL vs. 307.4 ± 131.2 µg/dL, P = 0.002). IGF1, cortisol:DHEAS ratio, and DHEAS were not significantly correlated with HAM-D scores. Cortisol and testosterone levels were not significantly different between patients and controls. Serum estradiol levels were positively correlated with DHEAS levels (P = 0.00062) in patients, but were not significantly correlated with DHEAS levels in controls. CONCLUSION: Estradiol may affect the pathogenesis and severity of patients with MDD in men, and other hormones, such as those in the HPA and HPS axes, may also be involved in male MDD. Additionally, a correlation between estradiol and DHEAS may affect the pathology of MDD in men.


Assuntos
Transtorno Depressivo Maior , Sulfato de Desidroepiandrosterona , Humanos , Hidrocortisona , Fator de Crescimento Insulin-Like I , Masculino , Testosterona
13.
Nat Commun ; 12(1): 1789, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741976

RESUMO

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.


Assuntos
Envelhecimento , Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Flagelos/metabolismo , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Animais Geneticamente Modificados , Transporte Biológico , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Longevidade/genética , Percepção/fisiologia , Interferência de RNA , Fator Regulador X1/genética , Fator Regulador X1/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(3): 199-204, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33766226

RESUMO

Objective To investigate the effect of insulin-like growth factor 1 (IGF-1) on the phagocytic activity of mouse BV-2 microglial cells. Methods Western blotting was performed to detect the protein levels of IGF-1 and IGF-1 receptor (IGF-1R) in the murine brain after the establishment of acute central nervous system inflammation models by intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg). The protein level of IGF-1R on BV-2 microglial cells that had been stimulated by 500 ng/mL LPS for 4, 12 and 24 hours was measured by Western blotting. To assess the phagocytic activity of microglial cells in response to IGF-1, BV-2 microglial cells were stimulated by IGF-1 at different concentrations for 24 hours after pretreated with or without wortmannin (PI3K/AKT signaling pathway blocker), and then incubated with fluorescent microbeads for 2 hours followed by measurement of phagocytosis of the fluorescent microbeads by flow cytometry. After treatment of IGF-1 (50 ng/mL), p-AKT and AKT signaling pathways in the BV-2 microglial cells were detected by Western blotting. Results Intraperitoneal LPS injection caused increased levels of IGF-1 and IGF-1R in the mouse brain. LPS upregulated the protein expression of IGF-1R on BV-2 microglial cells. The activity of BV-2 microglial cells to phagocytose fluorescent microbeads gradually increased with IGF-1 concentration rising and peaked in the IGF-1 treatment at 50 ng/mL, and gradually decreased thereafter. And IGF-1 induced the phosphorylation of AKT in BV-2 microglial cells. However, after the PI3K/AKT signaling pathway was blocked via wortmannin, the effect of IGF-1 on the activity of BV-2 microglial cells to phagocytose fluorescent microbeads was significantly alleviated. Conclusion IGF-1 can promote phagocytic activity of BV-2 cells via activating PI3K/AKT signaling pathway, which suggests a potential role of IGF-1 in regulating the cerebral inflammation.


Assuntos
Fator de Crescimento Insulin-Like I , Fosfatidilinositol 3-Quinases , Animais , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Microglia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1 , Transdução de Sinais
16.
Nutrients ; 13(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530512

RESUMO

Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1ß, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p < 0.001). Conclusions: KD may be used during body building preparation for health and leaning purposes but with the caution that hypertrophic muscle response could be blunted.


Assuntos
Composição Corporal , Dieta com Restrição de Carboidratos , Dieta Cetogênica , Força Muscular/fisiologia , Tecido Adiposo , Adolescente , Adulto , Atletas , Metabolismo Basal , Glicemia , Fator Neurotrófico Derivado do Encéfalo/sangue , Carboidratos , Citocinas/sangue , Dieta Ocidental , Glucose , Humanos , Insulina , Fator de Crescimento Insulin-Like I , Masculino , Músculos , Treinamento de Resistência , Testosterona/sangue , Triglicerídeos/sangue , Perda de Peso , Adulto Jovem
17.
Poult Sci ; 100(2): 467-473, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518098

RESUMO

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.


Assuntos
Embrião de Galinha/efeitos da radiação , Somatotrofos/metabolismo , Animais , Embrião de Galinha/química , Hormônio do Crescimento/sangue , Hormônio Liberador de Hormônio do Crescimento/análise , Hormônios/análise , Hormônios/sangue , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Luz , Fígado/química , Óvulo/efeitos da radiação , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Somatotrofos/efeitos da radiação , Fatores de Tempo
18.
J Anim Sci ; 99(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587143

RESUMO

The aim of this study was to evaluate the effect of bovine somatotropin (bST) on fetal and placental development during the first third of gestation in beef heifers. Angus heifers (n = 97) were randomly assigned to either receive a 500-mg injection of bST (BST) biweekly on days 0, 15, 29, 43, and 57 of gestation or not receive bST (CTL) throughout the experiment. Body weight (BW) was assessed on days -9, -3, 0, 15, 22, 29, 43, 50, 57, 64, and 77, while blood samples were collected on days 0, 22, 50, and 64. Pregnancy status was determined via transrectal ultrasonography on days 29 and 64. A subset of pregnant heifers (BST, n = 7; CTL, n = 5) were harvested on day 84, and complete gravid reproductive tracts and liver tissue were collected for analysis. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A), and uridine 5'-diphospho-glucuronosyltransferase (UGT) activities were determined. Mean change in BW and average daily gain of heifers between fixed-time artificial insemination (day 0) and day 77 did not differ between treatments (P ≥ 0.05). Mean concentrations of insulin-like growth factor 1 (IGF-1) were greater (P < 0.001) in BST (347 ± 27.7 ng/mL) compared with CTL (135 ± 32.8 ng/mL) heifers. Mean placental weight, fetal membrane weight, uterine weight, and ovarian and corpus luteum (CL) weights, as well as fetal morphometric data, did not differ (P ≥ 0.05) between treatments. However, BST heifers had greater (P = 0.03) quantities of combined fetal fluid compared with CTL (521.6 ± 22.9 vs. 429.6 ± 27.14 g, respectively). Tendencies were observed for BST heifers to have reproductive tracts with fewer placentomes (P = 0.08) and fetuses with greater umbilical diameters (P = 0.09) compared with CTL. The activity of CYP1A did not differ (P ≥ 0.05) within the maternal and fetal liver, caruncle, cotyledon, or CL tissue samples between treatments. Furthermore, CYP3A activity was only observed in maternal liver samples and was not different between treatments (P ≥ 0.05). Interestingly, CYP2C activity was greater (P = 0.01) in the liver of BST vs. CTL heifers, and UGT activity was greater (P = 0.02) in the CL from BST heifers compared with CTL. In conclusion, the administration of bST during the first third of gestation increased plasma concentrations of IGF-1, which resulted in an increase in fetal fluid, decrease in placentome number, and greater umbilical diameter, but failed to alter fetal development.


Assuntos
Hormônio do Crescimento , Inseminação Artificial , Animais , Bovinos , Eicosanoides , Feminino , Hormônio do Crescimento/farmacologia , Inseminação Artificial/veterinária , Fator de Crescimento Insulin-Like I , Gravidez , Esteroides
19.
Am J Physiol Regul Integr Comp Physiol ; 320(5): R653-R662, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33621475

RESUMO

Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 growth factor (hIGF1) gene delivery (NP-Plac1-hIGF1) increased hIGF1 expression and maintained fetal growth. However, whether it can restore fetal growth remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS-/-) mouse model, a genetic model of FGR, we found that despite inducing expression of hIGF1 in the placentas treated with NP-Plac1-hIGF1 (P = 0.0425), FGR did not resolve. This was associated with no change to the number of fetal capillaries in the placental labyrinth; an outcome which was increased with NP-Plac1-hIGF1 treatment in the ligated mouse model, despite increased expression of angiopoietin 1 (P = 0.05), and suggested IGF1 signaling in the placenta requires eNOS to modulate placenta angiogenesis. To further assess this hypothesis, BeWo choriocarcinoma cell line and human placental explant cultures were treated with NP-Plac1-hIGF1, oxidative stress was induced with hydrogen peroxide (H2O2), and NOS activity was inhibited using the inhibitor NG-monomethyl-l-arginine (l-NMMA). In both BeWo cells and explants, the protective effect of NP-Plac1-hIGF1 treatment against H2O2-induced cell death/lactate dehydrogenase release was prevented by eNOS inhibition (P = 0.003 and P < 0.0001, respectively). This was associated with an increase in mRNA expression of oxidative stress markers hypoxia inducing factor 1α (HIF1α; P < 0.0001) and ADAM10 (P = 0.0002) in the NP-Plac1-hIGF1 + H2O2 + l-NMMA-treated BeWo cells. These findings show for the first time the requirement of eNOS/NOS in IGF1 signaling in placenta cells that may have implications for placental angiogenesis and fetal growth.


Assuntos
Retardo do Crescimento Fetal/terapia , Feto/irrigação sanguínea , Terapia Genética , Fator de Crescimento Insulin-Like I/metabolismo , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Placenta/irrigação sanguínea , Trofoblastos/enzimologia , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/enzimologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/fisiopatologia , Técnicas de Transferência de Genes , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator de Crescimento Insulin-Like I/genética , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas , Óxido Nítrico Sintase Tipo III/genética , Estresse Oxidativo , Gravidez , Transdução de Sinais , Técnicas de Cultura de Tecidos , Trofoblastos/patologia
20.
Medicine (Baltimore) ; 100(1): e23705, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429739

RESUMO

RATIONALE: Osteonecrosis of the femoral head is a common orthopedic disease. Some studies have shown that osteonecrosis of the femoral head is related to susceptibility genes, but there are few reports of familial osteonecrosis of the femoral head. Here, we reported two first-degree relatives with osteonecrosis of the femoral head. PATIENT CONCERNS: A 27-year-old man with bilateral hip pain was diagnosed with osteonecrosis of the femoral head. The patient's mother also had a history of this disease. DIAGNOSES: Whole exome sequencing revealed the same mutation (c.15+3G>A) in the insulin-like growth factor 1 (IGF1) gene of the proband and his mother but not in his elder sister. INTERVENTIONS: The patient underwent bilateral total hip arthroplast. OUTCOMES: The patient recovered well, and was discharged. LESSONS: We found a heterozygous mutation (c.15+3G>A) in IGF1 in this family, which could be related to osteonecrosis of the femoral head. Early genetic counseling and gene locus detection could, thus, prove helpful for early diagnosis of osteonecrosis of the femoral head.


Assuntos
Cabeça do Fêmur/anormalidades , Fator de Crescimento Insulin-Like I/análise , Osteonecrose/genética , Adulto , Artroplastia de Quadril/métodos , Cabeça do Fêmur/patologia , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Osteonecrose/patologia
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