Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.789
Filtrar
1.
Asia Pac J Ophthalmol (Phila) ; 8(4): 319-323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369407

RESUMO

PURPOSE: The aims of this study were to correlate diabetic retinopathy (DR) changes with insulin-like growth factor 1 (IGF-1) levels in patients with type 1 diabetes of pubertal age group and to correlate the level of retinopathy with IGF-1 levels. METHODS: This cross-sectional study was done over 2 years and involved patients with type 1 diabetes of age 8 to 25 years. Patients presenting to Ophthalmology OPD and inpatient department along with active recruitment from old pediatrics and endocrinology records were taken for the study. Fasting serum IGF-1 was calculated using enzyme-linked immunosorbent assay technique. Fasting blood sugar levels were taken. Detailed ophthalmic examination was done and DR was noted in all the patients and correlated with IGF-1 levels. RESULTS: A total of 46 patients with type 1 diabetes were recruited into the study. The mean age of the patients was 14.33 ±â€Š4.36 years, with a female-to-male ratio of 3:2. No relationship of IGF-1 with age of onset of diabetes (P = 0.7) or fasting capillary blood glucose (CBG) (P = 0.6) was found, but a significant relationship was found with duration of diabetes (P = 0.001) and low IGF-1 levels (P < 0.0001). CONCLUSIONS: Severity of DR in patients with type 1 diabetes is inversely related to serum IGF-1 levels. Low IGF levels are an indicator for closer follow-up and strict management of diabetes and retinopathy.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Puberdade , Adolescente , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Retinopatia Diabética/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Adulto Jovem
2.
Animal ; 13(S1): s26-s34, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31280746

RESUMO

Colostrum plays an essential role in ensuring the survival, growth and health of piglets by providing energy, nutrients, immunoglobulins, growth factors and many other bioactive components and cells. Both colostrum yield and composition are highly variable among sows, yet mechanisms and factors that regulate colostrogenesis are not fully known. Unlike sow milk yield, sow colostrum yield is not highly determined by litter size and suckling intensity but is largely driven by sow-related factors. Colostrum synthesis is under hormonal control, with prolactin and progesterone concentrations prepartum having, respectively, positive and negative influences on colostrum yield. Less is known about the endocrine control of the end of colostrogenesis in swine, which is characterized by the closure of tight junctions in the mammary epithelium and the cessation of transfer of immunoglobulin G (IgG) into lacteal secretions. Recent studies indicate that exogenous hormones may influence colostrogenesis. Inducing parturition by injecting prostaglandin F2α on day 114 of gestation in combination with an oxytocin-like molecule reduced colostrum yield, and injection of prostaglandin F2α alone either reduced colostrum yield or had no effect. Injecting a supraphysiological dose of oxytocin to sows in the early postpartum period delayed the tightening of mammary tight junctions, thereby prolonging the colostral phase and increasing concentrations of IGF-I and IgG and IgA in early milk. The development of strategies to improve colostrum composition in swine through maternal feeding has been largely explored but very few attempts were made to increase colostrum yield. This is most likely because of the difficulty in measuring colostrum yield in swine. The fatty acid content of colostrum greatly depends on the amount of lipids provided in the sow diet during late gestation, whereas the fatty acid profile is largely influenced by the type of lipid being fed to the pregnant sow. Moreover, various ingredients that presumably have immuno-modulating effects (such as fish oil, prebiotics and probiotics) increased concentrations of IgG, IgA and/or IgM in sow colostrum when they were provided during the last weeks of gestation. Finally, there is some evidence that sow nutrition during late gestation may influence colostrum yield but this clearly warrants more research. This review emphasizes that although progress has been made in understanding the control of colostrogenesis in swine, and that strategies exist to manipulate fat and immunoglobulin contents of colostrum, ways to increase colostrum yield are still lacking.


Assuntos
Colostro/metabolismo , Sistema Endócrino/fisiologia , Ácidos Graxos/metabolismo , Leite/metabolismo , Suínos/fisiologia , Animais , Colostro/química , Dieta/veterinária , Feminino , Óleos de Peixe/metabolismo , Hormônios/metabolismo , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Fator de Crescimento Insulin-Like I/metabolismo , Tamanho da Ninhada de Vivíparos , Leite/química , Estado Nutricional , Parto , Gravidez , Proteínas Recombinantes/metabolismo
3.
Animal ; 13(S1): s42-s51, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31280751

RESUMO

Shortening or omitting the dry period improves the energy balance and metabolic status of dairy cows in early lactation. Metabolic, behaviour and welfare effects throughout lactation, however, are unclear. The current paper reviews long-term metabolic and welfare consequences of short and no dry period, as well as feeding strategies and individual cow characteristics that could support in optimising management of cows with a short or no dry period. The paper will conclude with impacts of short and no dry periods at herd level and in practice. Energy balance after no or a short dry period is more positive during the complete subsequent lactation. After the initial improvement in early lactation, cows after no dry period tend to fatten and may have a too low lactation persistency to be continuously milked until the onset of the subsequent lactation. Reducing dietary energy level for cows with no dry period reduced fattening during the complete lactation but did not improve lactation persistency. Feeding a more lipogenic diet for cows with a short or no dry period did not affect the energy balance or lactation persistency during the complete lactation, although a lipogenic diet resulted in lower plasma insulin and IGF-1 concentration and greater plasma growth hormone concentration, compared with a glucogenic diet. Effects of dry period length on udder health are ambiguous, whereas short and no dry periods improved fertility in most studies. Omission of the dry period changed behaviour of cows both before and after calving, with a longer lying time and greater feed intake after calving, suggesting a better adaptation to a new lactation. Individual cow characteristics like parity, genotype, prepartum body condition score, and milk yield level determined the metabolic response of cows to a short or no dry period. In conclusion, short or no dry periods increase the energy balance in the complete lactation. Feeding strategies can be used to limit fattening of cows with no or short dry period, but the studied feeding strategies did not increase lactation persistency. Improved fertility and behavioural changes around calving suggest a better adaptation to a new lactation in case of no dry period. Customised dry period lengths for individual cows could improve metabolic status of cows at risk of a severe negative energy balance while minimising milk losses.


Assuntos
Bem-Estar do Animal , Bovinos/fisiologia , Metabolismo Energético , Lactação/fisiologia , Leite/metabolismo , Animais , Dieta/veterinária , Feminino , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Glândulas Mamárias Animais/fisiologia , Paridade , Gravidez
4.
Genet Sel Evol ; 51(1): 41, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337334

RESUMO

BACKGROUND: This study aimed at estimating genetic parameters of sex-influenced production traits, evaluating the impact of genotype-by-sex interaction, and identifying the selection criteria that could be included in multiple-trait genetic evaluation to increase the rate of genetic improvement in both sexes. To achieve this goal, we used 10 male and 10 female phenotypes, which were measured in a population of 2111 Australian Brahman cattle genotyped at high-density. RESULTS: Heritability estimates ranged from very low (0.03 ± 0.03 for cows' days to calving at first calving opportunity, DC1), to moderate (0.33 ± 0.08 for cows' adult body weight, AWTc), and to high (0.95 ± 0.07 for cows' hip height, HHc). Genetic correlation (rg) estimates between male and female homologous traits were favorable and ranged from moderate to high values, which indicate that selection for any of the traits in one sex would lead to a correlated response with the equivalent phenotype in the other sex. However, the estimated direct response was greater than the indirect response. Moreover, Pearson correlations between estimated breeding values obtained from each sex separately and from female and male homologous traits combined into a single trait in univariate analysis ranged from 0.74 to 0.99, which indicate that small ranking variation might appear if male and female traits are included as single or separate phenotypes. Genetic correlations between male growth and female reproductive traits were not significant, ranging from - 0.07 ± 0.13 to 0.45 ± 0.65. However, selection to improve HHc and AWTc in cows may reduce the percentage of normal sperm at 24 months of age (PNS24), possibly due to correlated effects in the same traits in males, which are related to late maturing animals. CONCLUSIONS: Hip height in cows and PNS24, as well as blood insulin-like growth factor 1 (IGF1) concentration in bulls at 6 months of age are efficient selection criteria to improve male growth and female reproductive traits, simultaneously. In the presence of genotype-by-sex interactions, selection for traits in each sex results in high rates of genetic improvement, however, for the identification of animals with the highest breeding value, data for males and females may be considered a single trait.


Assuntos
Cruzamento , Bovinos/genética , Seleção Genética , Animais , Peso Corporal/genética , Bovinos/crescimento & desenvolvimento , Feminino , Variação Genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Reprodução/genética
5.
Ecotoxicol Environ Saf ; 181: 362-369, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212184

RESUMO

DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5 mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5 mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.


Assuntos
Dietilexilftalato/toxicidade , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Puberdade Precoce/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Puberdade Precoce/enzimologia , Puberdade Precoce/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
6.
Anticancer Res ; 39(6): 2811-2819, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177118

RESUMO

BACKGROUND/AIM: Recent knowledge implicates a differential expression of the insulin-like growth factor-I (IGF-I) mRNA splice variants (i.e., IGF-IEa, IGF-IEb and IGF-IEc) in cancerous tissues, implying possible specific roles of the encoded IGF-I protein isoforms in cancer biology. In particular, there is growing evidence that the IGF-IEc isoform may play a distinct biological role in various types of cancers. The present study investigated whether IGF-IEc expression is associated with a particular type of thyroid cancer. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue specimens of different types of thyroid cancers from 92 patients were assessed for IGF-IEc expression by immunohistochemistry. In addition, thyroid cancer biopsies of different TNM staging histological types were evaluated for mRNA expression of the IGF-IEc transcript by real-time polymerase chain reaction (PCR). RESULTS: From the total number of 92 samples, 2 were anaplastic, 10 medullary, 4 hyperplasias of C-cells, 11 follicular, 5 hurtle cell carcinomas, 2 poorly differentiated, 5 nodular hyperplasias, 1 lymphoma and 52 were papillary thyroid cancers. The age of cancer diagnosis or tumor size did not significantly affect the IGF-IEc expression. Among all types of cancers, IGF-IEc was expressed in papillary differentiated thyroid cancer. Its expression/localization was mainly cytoplasmic and significantly associated with TNM staging and the presence of muscular and capsule cancerous invasion (p<0.05). Similarly, a differential profile was revealed regarding the mRNA expression of the IGF-IEc transcript, that exhibited a higher expression in aggressive compared to the non-aggressive papillary cancers. CONCLUSION: IGF-IEc isoform expression in thyroid cancer is positively associated with more advanced stages of papillary thyroid cancer.


Assuntos
Processamento Alternativo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Regulação para Cima , Adolescente , Adulto , Idoso , Citoplasma/genética , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Carga Tumoral , Adulto Jovem
7.
J Dairy Sci ; 102(8): 7522-7535, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155243

RESUMO

The liver becomes resistant to growth hormone before parturition in dairy cows (uncoupling of the somatotropic axis). However, the mechanism of growth hormone insensitivity has not been fully described. The aim of the present study was to improve a previous model of adult bovine hepatocytes in a sandwich culture system to ensure growth hormone receptor (GHR) expression. First, we modified the protocol for hepatocyte retrieval and tested the effect of short (18 min) and long (up to 30 min) warm ischemia on hepatocyte viability. Second, we used medium additives that affect GHR expression in vivo-insulin (INS), dexamethasone (DEX), both (INS+DEX), or no hormone additives (CTRL)-to ensure the functionality of hepatocytes, as measured by lactate dehydrogenase activity and urea concentration in the medium. We also used reverse transcriptase PCR of hepatocytes to evaluate expression of albumin (ALB), hepatocyte nuclear factor 4α (HNF4A), nuclear factor-κ-B-inhibitor α (NFKBIA), cytosolic phosphoenolpyruvate carboxykinase (PCK1), and vimentin (VIM) mRNA. Moreover, we analyzed the expression of GHRtot (GHR), GHR1A, insulin-like growth factor-1 (IGF1), and IGF binding protein-2 (IGFBP2) in response to exposure to media with the different compositions. Modification of the protocol (changes in rinsing and perfusion times, buffer composition, and the volume and standardization of collagenase) led to increased cell counts and cell viability. Short warm ischemia with the modified protocol significantly increased cell count (4.7 × 107 ± 1.9 × 107 vs. 3.5 × 106 ± 1.5 × 106 vital cells/g of liver) and viability (79.1 ± 8.4 vs. 37.1 ± 8.9%). Therefore, we gathered hepatocytes from the liver after short warm ischemia with the modified protocol. For these hepatocytes, lactate dehydrogenase activity was lower in media with INS and with DEX than in media with INS+DEX or CTRL; urea concentrations were highest at d 4 for INS+DEX. As well, HNF4A and ALB were more highly expressed in hepatocytes cultured with INS and INS+DEX than in those cultured with DEX or CTRL, and the substitution of DEX suppressed VIM and NFKBIA expression but increased PCK1 expression. The expression of GHR, GHR1A, and IGF1 was suppressed by dexamethasone (DEX and INS+DEX), whereas INS distinctly increased GHR, GHR1A, and IGF1 mRNA expression. Hepatocytes in a sandwich culture showed influenceable GHR expression; this study provides a model that can be used in studies examining factors that influence the expression and signal transduction of GHR in dairy cows.


Assuntos
Bovinos/genética , Hepatócitos/metabolismo , Fígado/citologia , Receptores da Somatotropina/genética , Animais , Bovinos/metabolismo , Células Cultivadas , Dexametasona/farmacologia , Feminino , Hormônio do Crescimento/farmacologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/análogos & derivados , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Cultura Primária de Células , Receptores da Somatotropina/metabolismo , Vimentina/genética , Vimentina/metabolismo
8.
Environ Pollut ; 251: 871-878, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234252

RESUMO

Di(2-ethylhexyl)phthalate (DEHP) is an ubiquitous and emerging contaminant that is widely present in food, agricultural crop, and the environment, posing a potential risk to human health. This study utilized the nematode Caenorhabditis elegans to decipher the toxic effects of early life exposure to DEHP on aging and its underlying mechanisms. The results showed that exposure to DEHP at 0.1 and 1.5 mg/L inhibited locomotive behaviors. In addition, DEHP exposure significantly shortened the mean lifespan of the worms and further adversely affected pharyngeal pumping rate and defecation cycle in aged worms. Moreover, DEHP exposure also further enhanced accumulation of age-related biomarkers including lipofuscin, lipid peroxidation, and intracellular reactive oxygen species in aged worms. In addition, exposure to DEHP significantly suppressed gene expression of hsp-16.1, hsp-16.49, and hsp-70 in aged worms. Further evidences showed that mutation of genes involved in insulin/IGF-1-like signaling (IIS) pathway (daf-2, age-1, pdk-1, akt-1, akt-2, and daf-16) restored lipid peroxidation accumulation upon DEHP exposure in aged worms, whereas skn-1 mutation resulted in enhanced lipid peroxidation accumulation. Therefore, IIS and SKN-1 may serve as an important molecular basis for DEHP-induced age-related declines in C. elegans. Since IIS and SKN-1 are highly conserved among species, the age-related declines caused by DEHP exposure may not be exclusive in C. elegans, leading to adverse human health consequences due to widespread and persistent DEHP contamination in the environment.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Fator de Crescimento Insulin-Like I/metabolismo , Longevidade/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Biomarcadores/metabolismo , Proteínas de Caenorhabditis elegans/biossíntese , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Choque Térmico/biossíntese , Insulina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipofuscina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
9.
Diabetes Res Clin Pract ; 152: 156-165, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31102684

RESUMO

AIM: To investigate the effect of a single and 15 units of high-intensity circuit training (HICT) programme on glucose metabolism, myokines' response and selected genes' expression in women. METHODS: Thirty-three, non-active women (mean age: 38 ±â€¯12) were split into a HICT (n = 20) or a control group (CON, n = 13). The training protocol included three circuits of nine exercises with own body weight as a workload performed 3 times a week for five weeks. The CON group performed HICT twice. Blood samples were taken before, 1 h and 24 h after the first and last unit to determine IGF-1, myostatin, irisin, decorin, HSP27, interleukin-15 concentrations using the ELISA immunoenzymatic method. To evaluate HSPB1, TNF-α and DCN mRNA, real-time PCR was used. Pre- and post-intervention, the oral glucose test and body composition assessment were completed. RESULTS: The following parameters tended to decrease after the 5-week HICT program: insulin and HOMA-IR Training diminished insulin/IGF-1 ratio (51% CI: -63% to -34%) and induced the drop of myostatin concentration but significantly only among middle-aged women and at baseline insulin resistance. CONCLUSION: Obtained data revealed that HICT improved an insulin sensitivity and diminished myostatin concentration among older, insulin-resistant women with lower baseline physical capacity.


Assuntos
Envelhecimento/fisiologia , Exercícios em Circuitos , Terapia por Exercício/métodos , Tolerância ao Exercício/fisiologia , Resistência à Insulina/fisiologia , Aptidão Física/fisiologia , Adulto , Fatores Etários , Glicemia/metabolismo , Composição Corporal/fisiologia , Exercícios em Circuitos/métodos , Decorina/genética , Decorina/metabolismo , Metabolismo Energético/genética , Exercício/fisiologia , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Pessoa de Meia-Idade , Miostatina/genética , Miostatina/metabolismo , Treinamento de Resistência/métodos , Adulto Jovem
10.
Toxicol Lett ; 311: 17-26, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31039417

RESUMO

Prenatal ethanol exposure (PEE) causes intrauterine growth retardation (IUGR), and the occurrence of glomerulosclerosis is closely related to IUGR. This study aimed to confirm the kidney toxic effect of PEE and explore its intrauterine programming mechanism in female offspring. The Wistar female fetuses on gestational day (GD) 20 and the adult offspring at postnatal week 24 were anesthetized and decapitated. The adult offspring kidneys in the PEE group displayed glomerular hyperplasia and glomerulosclerosis. Blood urea nitrogen (BUN) and the BUN / Serum creatinine (Scr) concentration ratio in the PEE group was increased significantly compared to the control group (P<0.01, P<0.05). Meanwhile, the renal glucocorticoid-activation system was inhibited, whereas the insulin-like growth factor 1 (IGF1) signaling pathway was activated in the female adult offspring of the PEE group. In the fetal kidney of the PEE group, pathological observation showed kidney dysplasia, and the gene expression of the glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway was reduced compared to that of the control group. Moreover, the glucocorticoid-activation system was activated, whereas the IGF1 signaling pathway was inhibited in the fetal kidneys of the PEE group. In conclusion, PEE caused fetal kidney dysplasia and adult glomerulosclerosis in the female offspring rats, and the intrauterine programming alteration of glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis might be involved in fetal-originated glomerulosclerosis.


Assuntos
Etanol/toxicidade , Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Nefropatias/induzido quimicamente , Glomérulos Renais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Idade Gestacional , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator de Crescimento Insulin-Like I/genética , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Gravidez , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Ratos Wistar , Fatores Sexuais , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 20(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096580

RESUMO

Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.


Assuntos
Cognição , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Microglia/metabolismo , Modelos Animais , Óxido Nítrico , Estresse Oxidativo , Pericitos/metabolismo
12.
Anim Sci J ; 90(7): 857-869, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099142

RESUMO

This experiment evaluated the effects of subnutrition during early gestation on hematology in cows (Bos Taurus) and on hematological, metabolic, endocrine, and vitality parameters in their calves. Parda de Montaña and Pirenaica dams were inseminated and assigned to either a control (CONTROL, 100% requirements) or a nutrient-restricted group (SUBNUT, 65%) during the first third of gestation. Dam blood samples were collected on days 20 and 253 of gestation, and calf samples were obtained during the first days of life. Pirenaica dams presented higher red series parameters than Parda de Montaña dams, both in the first and the last months of gestation. During early pregnancy, granulocyte numbers and mean corpuscular hemoglobin were lower in Pirenaica-SUBNUT than in Pirenaica-CONTROL cows. Calves from the SUBNUT cows did not show a physiological reduction in red series values in early life, suggesting later maturation of the hematopoietic system. Poor maternal nutrition affected calf endocrine parameters. Newborns from dystocic parturitions showed lower NEFA concentrations and weaker vitality responses. In conclusion, maternal nutrition had short-term effects on cow hematology, Pirenaica cows showing a higher susceptibility to undernutrition; and a long-term effect on their offspring endocrinology, SUBNUT newborns showing lower levels of IGF-1 and higher levels of cortisol.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Animais Recém-Nascidos/sangue , Bovinos/sangue , Bovinos/metabolismo , Desnutrição/sangue , Desnutrição/veterinária , Complicações na Gravidez/veterinária , Prenhez/sangue , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Animais , Feminino , Granulócitos , Hemoglobinas , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Contagem de Leucócitos , Desnutrição/fisiopatologia , Gravidez
13.
Heart Fail Clin ; 15(3): 399-408, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079698

RESUMO

In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure in untreated and uncontrolled patients. Additional relevant cardiovascular complications are represented by arterial hypertension, valvulopathies, arrhythmias, and vascular endothelial dysfunction, which, together with the respiratory and metabolic complications, contribute to the development of cardiac disease and the increase cardiovascular risk in acromegaly. Disease duration plays a pivotal role in the determination of acromegalic cardiomyopathy. The main functional disturbance in acromegalic cardiomyopathy is the diastolic dysfunction, observed in 11% to 58% of patients, it is usually mild, without clinical consequence, and the progression to systolic dysfunction is generally uncommon, not seen or observed in less than 3% of the patients. Consequently, the presence of overt CHF is rare in acromegaly, ranging between 1 and 4%, in patients with untreated and uncontrolled disease. Control of acromegaly, induced by either pituitary surgery or medical therapy improves cardiac structure and performance, limiting the progression of acromegaly cardiomyopathy to CHF. However, when CHF is associated with dilative cardiomyopathy, it is generally not reversible, despite the treatment of the acromegaly.


Assuntos
Acromegalia/epidemiologia , Insuficiência Cardíaca/epidemiologia , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/sangue , Biomarcadores/sangue , Comorbidade , Saúde Global , Insuficiência Cardíaca/sangue , Humanos , Morbidade/tendências , Taxa de Sobrevida/tendências
14.
Biomed Res Int ; 2019: 2761241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016187

RESUMO

The aim of the present study was to investigate the effects of phosphorylatable nucleus localization signal linked nucleic kinase substrate short peptide (pNNS)-conjugated chitosan (pNNS-CS) mediated miR-140 and IGF-1 in both rabbit chondrocytes and cartilage defects model. pNNS-CS was combined with pBudCE4.1-IGF-1, pBudCE4.1-miR-140, and negative control pBudCE4.1 to form pDNA/pNNS-CS complexes. Then these complexes were transfected into chondrocytes or injected intra-articularly into the knee joints. High levels of IGF-1 and miR-140 expression were detected both in vitro and in vivo. Compared with pBudCE4.1 group, in vitro, the transgenic groups significantly promoted chondrocyte proliferation, increased glycosaminoglycan (GAG) synthesis, and ACAN, COL2A1, and TIMP-1 levels, and reduced the levels of nitric oxide (NO), MMP-13, and ADAMTS-5. In vivo, the exogenous genes enhanced COL2A1, ACAN, and TIMP-1 expression in cartilage and reduced cartilage Mankin score and the contents of NO, IL-1ß, TNF-α, and GAG contents in synovial fluid of rabbits, MMP-13, ADAMTS-5, COL1A2, and COL10A1 levels in cartilage. Double gene combination showed better results than single gene. This study indicate that pNNS-CS is a better gene delivery vehicle in gene therapy for cartilage defects and that miR-140 combination IGF-1 transfection has better biologic effects on cartilage defects.


Assuntos
Doenças das Cartilagens/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Quitosana/farmacologia , Condrócitos/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , MicroRNAs/metabolismo , Peptídeos/farmacologia , Animais , Doenças das Cartilagens/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Técnicas de Transferência de Genes , Humanos , Articulação do Joelho/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Coelhos , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Transfecção/métodos
15.
Cell Biol Int ; 43(5): 553-564, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30958584

RESUMO

Insulin resistance (IR) is a common etiology of type 2 diabetes (T2D) defined by a state of decreased reactivity to insulin in multiple organs, such as the liver. This study aims to investigate how microRNA-122-5p (miR-122) regulates the hepatic IR in vitro. We first found that the miR-122 level was upregulated in the liver of rats fed with a high-fat diet and injected with streptozotocin (T2D rats), while the expression level of insulin-like growth factor 1 receptor (IGF-1R), a potential target of miR-122, was downregulated in the diabetic liver. In vitro, glucosamine-induced IR was introduced in HepG2 hepatic cells, and the levels of miR-122 and IGF-1R were further assessed. An increase of miR-122 level and a decrease of IGF-IR level were observed in IR hepatic cells, which was the same as that in the diabetic liver. Results of the luciferase reporter assay validated IGF-1R as a direct target of miR-122. Moreover, in IR HepG2 cells, antagonizing miR-122 with its specific inhibitor enhanced glucose uptake and suppressed the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, two key enzymes in regulating gluconeogenesis. Such alterations induced by the miR-122 inhibitor in IR hepatic cells were impaired when IGF-1R was simultaneously knocked down. In addition, the PI3K/Akt pathway was deactivated in IR cells, and then reactivated with miR-122 inhibitor transfection. In conclusion, our study demonstrates that miR-122 is able to regulate IR in hepatic cells by targeting IGF-1R.


Assuntos
Resistência à Insulina/fisiologia , MicroRNAs/metabolismo , Receptor IGF Tipo 1/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Regulação para Baixo , Gluconeogênese , Glucose-6-Fosfatase/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Masculino , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/genética , Transdução de Sinais
16.
J Agric Food Chem ; 67(17): 4774-4781, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30963762

RESUMO

Targeted analysis of Coffea arabica and Coffea canephora green coffees (total sample size n = 57) confirmed 2- O-ß-d-glucopyranosyl-carboxyatractyligenin (6) as the quantitatively dominating carboxyatractyligenin derivative. Its abundance in Arabicas (2425 ± 549 nmol/g, n = 48) exceeded that in Robustas (34 ± 12 nmol/g, n = 9) roughly by a factor of 70. Coffee processing involving heat (e.g., steam treatment and decaffeination) reduced concentrations of 6 and increased those of the decarboxylated derivative. The bioavailability of compound 6 in Caenorhabditis elegans was demonstrated by ultraperformance liquid chromatography-tandem mass spectrometry analysis of extracts prepared from nematode cultures incubated in a liquid medium containing 6. A toxicity assay performed to assess the impact of 6 in vivo showed a 20-fold higher median lethal dose (LD50 = 11.7 ± 1.2 mM) concentration compared to that of the known phytotoxic adenine-nucleotide transporters inhibitor carboxyatractyloside (2, LD50 = 0.61 ± 0.05 mM), whereas 1 mM 6 and 0.1 mM 2 were sufficient to decrease the survival of wild type C. elegans, already 10-20-fold lower doses reduced reproduction. Because the insulin/insulin-like growth factors signaling cascade (IIS) is a key regulator of life span and stress resistance, the impact of compound 6 on the survival of long-living daf-2 C. elegans was tested. As the susceptibility of these nematodes to 6 was as high as that in wild type, an impact on central metabolic processes independent of IIS was suggested. Analysis of the in vivo adenosine triphosphate (ATP) content of adult C. elegans revealed no changes after 1 and 24 h, but a 50% reduction after treatment with 1 mM 6 during the entire postembryonic development. These data speak for a developmental-stage-dependent modulation of the ATP pool by 6.


Assuntos
Atractilosídeo/análogos & derivados , Caenorhabditis elegans/efeitos dos fármacos , Coffea/química , Preparações de Plantas/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Atractilosídeo/farmacocinética , Atractilosídeo/farmacologia , Disponibilidade Biológica , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Coffea/toxicidade , Café/química , Feminino , Insulina/genética , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Dose Letal Mediana , Masculino
17.
Mater Sci Eng C Mater Biol Appl ; 101: 415-422, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029335

RESUMO

High nitrogen nickel-free stainless steel (HNNFSS) has excellent mechanical properties, corrosion resistance and biocompatibility, but its strength advantage is not fully used even though with one time higher than that of the conventional 316 L stainless steel. In this work, the lightweight design of HNNFSS bone plate was studied using finite element analysis, and the effect of lightweight plate fixation on histological and biomechanical behavior of healing bone were also researched on fractured rabbit femur. The finite element analysis results showed that the lightweight plate within 18.2% thickness reduction had higher bending strength and more homogeneous stress distribution compared with 316 L stainless steel plate. There was no obvious difference in radiography, histology analysis of callus and expression pattern of insulin like growth factor-1(IGF-1) of callus between the lightweight HNNFSS plate group and 316 L stainless steel plate group in animal test, and the IGF-1 concentrations of callus and the biomechanical bending test results also showed no statistical significance (p > 0.05), even though the data of the lightweight HNNFSS plate group were relatively better than that of 316 L stainless steel plate group. Therefore, the high nitrogen nickel-free stainless steel has the lightweight potential to keep good fixing function and improve bone healing compared with 316 L stainless steel plate.


Assuntos
Placas Ósseas , Teste de Materiais , Níquel/química , Aço Inoxidável/química , Animais , Fenômenos Biomecânicos , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/patologia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Fraturas do Fêmur/cirurgia , Análise de Elementos Finitos , Consolidação da Fratura , Fator de Crescimento Insulin-Like I/metabolismo , Coelhos
18.
Int J Mol Sci ; 20(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987295

RESUMO

Previous studies have demonstrated that monochromatic light affects plasma melatonin (MEL) levels, which in turn regulates hepatic insulin-like growth factor I (IGF-I) secretion via the Mel1c receptor. However, the intracellular signaling pathway initiated by Mel1c remains unclear. In this study, newly hatched broilers, including intact, sham operation, and pinealectomy groups, were exposed to either white (WL), red (RL), green (GL), or blue (BL) light for 14 days. Experiments in vivo showed that GL significantly promoted plasma MEL formation, which was accompanied by an increase in the MEL receptor, Mel1c, as well as phosphorylated extracellular regulated protein kinases (p-ERK1/2), and IGF-I expression in the liver, compared to the other light-treated groups. In contrast, this GL stimulation was attenuated by pinealectomy. Exogenous MEL elevated the hepatocellular IGF-I level, which is consistent with increases in cyclic adenosine monophosphate (cAMP), Gαq, phosphorylated protein kinase C (p-PKC), and p-ERK1/2 expression. However, the Mel1c selective antagonist prazosin suppressed the MEL-induced expression of IGF-I, Gαq, p-PKC, and p-ERK1/2, while the cAMP concentration was barely affected. In addition, pretreatment with Ym254890 (a Gαq inhibitor), Go9863 (a PKC inhibitor), and PD98059 (an ERK1/2 inhibitor) markedly attenuated MEL-stimulated IGF-I expression and p-ERK1/2 activity. These results indicate that Mel1c mediates monochromatic GL-stimulated IGF-I synthesis through intracellular Gαq/PKC/ERK signaling.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteína Quinase C/metabolismo , Receptores de Melatonina/metabolismo , Animais , Galinhas , Luz , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melatonina/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Nat Commun ; 10(1): 1524, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944305

RESUMO

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.


Assuntos
Cabelo/fisiologia , Macrófagos/fisiologia , Regeneração/fisiologia , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Pele/citologia , Pele/metabolismo , Células-Tronco , Estresse Mecânico , Fator de Crescimento Transformador beta
20.
C R Biol ; 342(3-4): 90-96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028003

RESUMO

The objective of our study was to elucidate the role of the transcription factor CREB-1 in controlling ovarian cell proliferation, apoptosis, and hormone release and the significance of CREB-1 phosphorylation in these processes. Human ovarian granulosa cells were transfected with a gene construct encoding wild-type CREB-1 (CREB-1 WT) or CREB-1 nonphosphorylatable mutant (CREB-1 M1). The expression of total and phosphorylated CREB-1, markers of proliferation (PCNA) and apoptosis (bax), as well as the release of progesterone, oxytocin, prostaglandin F2 alpha (PGF2), prostaglandin E2 (PGE2), and insulin-like growth factor I (IGF-I) were compared by immunocytochemistry, enzyme immunoassay (EIA), and immunoradiometric assay (IRMA). Transfection with CREB-1 WT or CREB-1 M1 increased total CREB-1 expression and proliferation and decreased the release of oxytocin, PGE2, and IGF-I by ovarian cells. CREB-1 M1, not CREB-1 WT, promoted apoptosis and inhibited progesterone output. PGF2 release was inhibited by CREB-1 WT but stimulated by CREB-1 M1 construct. Phosphorylated CREB-1 was undetected in any cell group. These observations confirm the involvement of CREB-1 in the control of ovarian cell proliferation, apoptosis, and steroid hormone release. This is the first demonstration of the involvement of CREB-1 in the regulation of the ovarian non-steroidal hormones such as oxytocin, PGF2, PGE2, and IGF-I. The absence of CREB-1 phosphorylation, similar effects exerted by CREB-1 WT and CREB-1 M1 on cell proliferation and release of oxytocin, PGE2, and IGF-I, and the influence of CREB-1 M1 on apoptosis and progesterone suggest that phosphorylation plays no role in the action of CREB-1 on the majority of analyzed functions of human ovarian cells.


Assuntos
Proliferação de Células/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ovário/fisiologia , Fosforilação/fisiologia , Adulto , Animais , Apoptose/fisiologia , Células Cultivadas , Feminino , Células da Granulosa/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Ocitocina/metabolismo , Progesterona/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA