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1.
Mech Ageing Dev ; 201: 111597, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34780856

RESUMO

Accumulating evidence suggests that the influence on developmental traits might have long-term effects on aging and health later in life. Metformin is a widely used drug for treating type 2 diabetes and is also used for delaying sexual maturation in girls with precocious puberty. The current report focuses on investigating the effects of metformin on development and metabolic traits. Heterogeneous mice (UM-HET3) were treated with i.p. metformin between the ages of 15 and 56 days. Our results show that body weight and food consumption were increased in both sexes, and sexual maturation was delayed in females. Tail length and circulating insulin-like growth factor 1 (IGF1) levels were significantly increased in both sexes. No significant difference was found in insulin tolerance test, but glucose tolerance was significantly reduced in the males. Circulating adiponectin and insulin levels were altered by metformin treatment in a sex-specific manner. Analysis of quantitative insulin sensitivity check index (QUICKI) suggests that metformin treatment increased insulin sensitivity in female pups, but had opposite effect in male pups. This study revealed that early life metformin treatment alters development and metabolism of mice in both sex-specific and non-specific manners. These effects of metformin may have long-term impacts on aging-related traits.


Assuntos
Envelhecimento , Peso Corporal , Comportamento Alimentar , Crescimento e Desenvolvimento/efeitos dos fármacos , Metabolismo/efeitos dos fármacos , Metformina/farmacologia , Adiponectina/sangue , Fatores Etários , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Teste de Tolerância a Glucose , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Resistência à Insulina , Camundongos , Fatores Sexuais
2.
Front Endocrinol (Lausanne) ; 12: 778737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858347

RESUMO

The exponential global increase in the incidence of obesity may be partly attributable to environmental chemical (EC) exposure. Humans are constantly exposed to ECs, primarily through environmental components. This review compiled human epidemiological study findings of associations between blood and/or urinary exposure levels of ECs and anthropometric overweight and obesity indices. The findings reveal research gaps that should be addressed. We searched MEDLINE (PubMed) for full text English articles published in 2006-2020 using the keywords "environmental exposure" and "obesity". A total of 821 articles were retrieved; 102 reported relationships between environmental exposure and obesity indices. ECs were the predominantly studied environmental exposure compounds. The ECs were grouped into phenols, phthalates, and persistent organic pollutants (POPs) to evaluate obesogenic roles. In total, 106 articles meeting the inclusion criteria were summarized after an additional search by each group of EC combined with obesity in the PubMed and Scopus databases. Dose-dependent positive associations between bisphenol A (BPA) and various obesity indices were revealed. Both individual and summed di(2-ethylhexyl) phthalate (DEHP) and non-DEHP metabolites showed inconsistent associations with overweight and obesity indices, although mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), and mono-benzyl phthalate (MBzP) seem to have obesogenic roles in adolescents, adults, and the elderly. Maternal exposure levels of individual POP metabolites or congeners showed inconsistent associations, whereas dichlorodiphenyldichloroethylene (DDE) and perfluorooctanoic acid (PFOA) were positively associated with obesity indices. There was insufficient evidence of associations between early childhood EC exposure and the subsequent development of overweight and obesity in late childhood. Overall, human evidence explicitly reveals the consistent obesogenic roles of BPA, DDE, and PFOA, but inconsistent roles of phthalate metabolites and other POPs. Further prospective studies may yield deeper insights into the overall scenario.


Assuntos
Poluentes Ambientais/toxicidade , Crescimento e Desenvolvimento/efeitos dos fármacos , Obesidade/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Obesidade/etiologia , Gravidez
3.
Toxins (Basel) ; 13(12)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34941712

RESUMO

Fumonisin B1 (FB1) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB1 ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1 group was supplemented with FB1 at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1 group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1 can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1 were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1 by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.


Assuntos
Carboxilesterase/metabolismo , Fumonisinas/metabolismo , Fumonisinas/toxicidade , Crescimento e Desenvolvimento/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Suínos/crescimento & desenvolvimento , Animais , Hipotálamo/metabolismo , Jejuno/metabolismo , Venenos/metabolismo , Venenos/toxicidade
4.
BMC Plant Biol ; 21(1): 459, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625028

RESUMO

BACKGROUND: Cadmium (Cd) is a heavy metal with high toxicity that severely inhibits wheat growth and development. Cd easily accumulates in wheat kernels and enters the human food chain. Genetic variation in the resistance to Cd toxicity found in wheat genotypes emphasizes the complex response architecture. Understanding the Cd resistance mechanisms is crucial for combating Cd phytotoxicity and meeting the increasing daily food demand. RESULTS: Using two wheat genotypes (Cd resistant and sensitive genotypes T207 and S276, respectively) with differing root growth responses to Cd, we conducted comparative physiological and transcriptomic analyses and exogenous application tests to evaluate Cd detoxification mechanisms. S276 accumulated more H2O2, O2-, and MDA than T207 under Cd toxicity. Catalase activity and levels of ascorbic acid (AsA) and glutathione (GSH) were greater, whereas superoxide dismutase (SOD) and peroxidase (POD) activities were lower in T207 than in S276. Transcriptomic analysis showed that the expression of RBOHA, RBOHC, and RBOHE was significantly increased under Cd toxicity, and two-thirds (22 genes) of the differentially expressed RBOH genes had higher expression levels in S276 than inT207. Cd toxicity reshaped the transcriptional profiling of the genes involving the AsA-GSH cycle, and a larger proportion (74.25%) of the corresponding differentially expressed genes showed higher expression in T207 than S276. The combined exogenous application of AsA and GSH alleviated Cd toxicity by scavenging excess ROS and coordinately promoting root length and branching, especially in S276. CONCLUSIONS: The results indicated that the ROS homeostasis plays a key role in differential Cd resistance in wheat genotypes, and the AsA-GSH cycle fundamentally and vigorously influences wheat defense against Cd toxicity, providing insight into the physiological and transcriptional mechanisms underlying Cd detoxification.


Assuntos
Adaptação Fisiológica/genética , Ácido Ascórbico/metabolismo , Cádmio/toxicidade , Glutationa/metabolismo , Transcriptoma/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Triticum/genética , Triticum/metabolismo , Ácido Ascórbico/genética , Regulação da Expressão Gênica de Plantas , Variação Genética , Genótipo , Glutationa/genética , Crescimento e Desenvolvimento/efeitos dos fármacos
5.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576089

RESUMO

SLC25A36 is a pyrimidine nucleotide carrier playing an important role in maintaining mitochondrial biogenesis. Deficiencies in SLC25A36 in mouse embryonic stem cells have been associated with mtDNA depletion as well as mitochondrial dysfunction. In human beings, diseases triggered by SLC25A36 mutations have not been described yet. We report the first known case of SLC25A36 deficiency in a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. Whole exome analysis identified the homozygous mutation c.803dupT, p.Ser269llefs*35 in the SLC25A36 gene. Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with oral uridine led to an improvement of thyroid function and obstipation, increase of growth and developmental progress. Our findings suggest an important role of SLC25A36 in hormonal regulations and oral uridine as a safe and effective treatment.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/deficiência , Uridina/uso terapêutico , Criança , Pré-Escolar , Feminino , Crescimento e Desenvolvimento/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas Mutantes/metabolismo , Transporte Proteico/efeitos dos fármacos , Tireotropina/metabolismo , Uridina/farmacologia
6.
Pediatr Infect Dis J ; 40(11): 1004-1010, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34292268

RESUMO

BACKGROUND: Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV <12 years initiating World Health Organization recommended first-line antiretroviral therapy (ART) from 2012 to 2015. METHODS: Z scores for length-for-age (LAZ), weight-for-age (WAZ) and body mass index-for-age were calculated. Lipids (total cholesterol, low-density lipoprotein and high-density lipoprotein) were measured. Hemoglobin A1C ≥5.8 was defined as at risk for type 2 diabetes. Mixed effects models were used to assess the association of VL at ART initiation with Z scores and lipids over time. RESULTS: Of 241 CLHIV, 151 (63%) were <3 years initiating LPV/r-based ART and 90 (37%) were ≥3 years initiating EFV-based ART. Among CLHIV <3 years, higher VL at ART initiation was associated with lower mean LAZ (ß: -0.30, P=0.03), WAZ (ß: -0.32, P=0.01) and low-density lipoprotein (ß: -6.45, P=0.03) over time. Among CLHIV ≥3, a log 10 increase in pretreatment VL was associated with lower mean LAZ (ß: -0.29, P=0.07) trending towards significance and lower WAZ (ß: -0.32, P=0.05) as well as with more rapid increases in LAZ (ß: 0.14 per year, P=0.01) and WAZ (ß: 0.19 per year, P=0.04). Thirty percent of CLHIV were at risk for type 2 diabetes at ART initiation. CONCLUSIONS: CLHIV initiating ART <3 years exhibited positive gains in growth and lipids, though high viremia at ART initiation was associated with persistently low growth and lipids, underscoring the need for early diagnosis and rapid treatment initiation. Future studies assessing the long-term cardiometabolic impact of these findings are warranted.


Assuntos
Antirretrovirais/uso terapêutico , Crescimento e Desenvolvimento/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Metabolismo/efeitos dos fármacos , Índice de Massa Corporal , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lipídeos/sangue , África do Sul , Carga Viral/efeitos dos fármacos
7.
J Hepatol ; 75(4): 879-887, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34052255

RESUMO

BACKGROUND & AIMS: Sorafenib has been the standard of care for patients with advanced hepatocellular carcinoma and although immunotherapeutic approaches are now challenging this position, it retains an advantage in HCV-seropositive patients. We aimed to quantify the rate of tumour progression in patients receiving sorafenib and relate this figure to survival, both overall, and according to viral status. METHODS: Using serial data from an international clinical trial we applied a joint model to combine survival and progression over time in order to estimate the rate of tumour growth as assessed by tumour burden and serum alpha-fetoprotein, and the impact of treatment on liver function. RESULTS: High tumour burden at baseline was associated with an increased risk of death. In patients still alive at the end of the study, the progression in relation to tumour burden was very low compared to those who died within the study. Overall, the change in mean tumour burden was 0.12 mm per day or an absolute growth rate of 3.6 mm/month. Median doubling time was 665 days. For those who progressed above 0.12 mm per day or the 12% rate, median survival was 234 days compared to 384 days if the rate was below 12%. Tumour growth rate and serum alpha-fetoprotein rise were significantly lower in those who were HCV seropositive as was the rate of decline in liver function. These results were replicated in 2 independent patient groups. CONCLUSION: Our analysis suggests that sorafenib treatment is associated with improved survival in patients with advanced hepatocellular carcinoma mainly by decreasing the rate of tumour growth and liver function deterioration among patients with HCV infection. LAY SUMMARY: Among patients receiving sorafenib for advanced hepatocellular carcinoma the rate of tumour growth (as assessed by changes in tumour size and the biomarker alpha-fetoprotein) and the deterioration of liver function is less in those who have the hepatitis C virus, than in those who do not.


Assuntos
Crescimento e Desenvolvimento/efeitos dos fármacos , Hepatite C/complicações , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Adulto , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/fisiopatologia , Feminino , Hepatite C/tratamento farmacológico , Humanos , Fígado/patologia , Testes de Função Hepática/métodos , Testes de Função Hepática/estatística & dados numéricos , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sorafenibe/uso terapêutico
8.
Cells Dev ; 166: 203678, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33994353

RESUMO

Metabolic impairments in childhood are known to promote the development of type 2 diabetes and/or obesity in adulthood. These impairments may result from perinatal exposure to harmful environmental factors, such as pesticide residues or the consumption of a "western" diet. In the present study, we sought to determine whether an obesogenic profile, metabolic disorders and liver damage in offspring (observed during young adulthood) were related to maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) starting 4 months before conception and ending at weaning. After the end of exposure, 51 male rat pups were left to develop under normal conditions and were studied in young adulthood. Despite the absence of direct exposure to harmful factors (other than through the dam's milk), maternal exposure to CPF or an HFD was associated with changes in the offspring's metabolic activity in the liver in the offspring. This indirect exposure to CPF was associated with a relative reduction in the expression of genes coding for enzymes involved in lipid or glucose metabolism but did induce histopathological changes in the offspring at adulthood. Maternal exposure to an HFD alone or to CPF alone gave similar results in offspring, changes in the same direction. Exposure of the mother to HFD did not exacerbate CPF effects. Co-exposure to both CPF and HFD did not increase the observed effects compared to each factor taken separately.


Assuntos
Clorpirifos/toxicidade , Dieta Hiperlipídica , Fígado/patologia , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glucose/metabolismo , Crescimento e Desenvolvimento/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Modelos Biológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
9.
Endocrinology ; 162(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33693673

RESUMO

In healthy conditions, prepubertal growth follows an individual specific growth channel. Growth hormone (GH) is undoubtedly the major regulator of growth. However, the homeostatic regulation to maintain the individual specific growth channel during growth is unclear. We recently hypothesized a body weight sensing homeostatic regulation of body weight during adulthood, the gravitostat. We now investigated if sensing of body weight also contributes to the strict homeostatic regulation to maintain the individual specific growth channel during prepubertal growth. To evaluate the effect of increased artificial loading on prepubertal growth, we implanted heavy (20% of body weight) or light (2% of the body weight) capsules into the abdomen of 26-day-old male rats. The body growth, as determined by change in biological body weight and growth of the long bones and the axial skeleton, was reduced in rats bearing a heavy load compared with light load. Removal of the increased load resulted in a catch-up growth and a normalization of body weight. Loading decreased hypothalamic growth hormone releasing hormone mRNA, liver insulin-like growth factor (IGF)-1 mRNA, and serum IGF-1, suggesting that the reduced body growth was caused by a negative feedback regulation on the somatotropic axis and this notion was supported by the fact that increased loading did not reduce body growth in GH-treated rats. Based on these data, we propose the gravitostat hypothesis for the regulation of prepubertal growth. This states that there is a homeostatic regulation to maintain the individual specific growth channel via body weight sensing, regulating the somatotropic axis and explaining catch-up growth.


Assuntos
Peso Corporal/fisiologia , Hormônio do Crescimento/farmacologia , Crescimento e Desenvolvimento/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Homeostase/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores da Somatotropina/efeitos dos fármacos , Receptores da Somatotropina/metabolismo , Receptores da Somatotropina/fisiologia , Maturidade Sexual/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
10.
Poult Sci ; 100(3): 100947, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33518311

RESUMO

This study investigated whether dietary resistant potato starch (RPS) inclusion could ameliorate the negative impact of a low nonphytate phosphorus (nPP) diet on growth performance, feather growth, feather follicles (FF) development, and carcass traits by improving nutrient utilization and cecal microbiome fermentation capacity in Pekin ducks. The experiment was performed with a 2 × 2 randomized block design with 2 levels of RPS (0 or 12%) and 2 levels of nPP (low or normal, low: 0.22% at 1-14 d and 0.18% at 15-35 d of age; normal: 0.40% at 1-14 d and 0.35% at 15-35 d of age) for a total of 4 treatments, each with 8 replicate pens per treatment of 12 birds per pen. As regards growth performance and carcass traits, RPS inclusion markedly increased (P < 0.05) BW of 14 and 35 d, BWG and FI of 1-14 d, 15-35 d, and 1-35 d as well as abdominal fat and breast meat percentage of 35 d in ducks fed low nPP diets; moreover, RSP inclusion significantly reduced (P < 0.05) mortality in ducks fed low nPP diets. As regards feather growth and follicles development of 35 d, RPS inclusion significantly increased (P < 0.05) the fourth primary feather length, absolute feather weight, and the density of primary FF in the back skin in ducks fed low nPP diets. In regard to nutrition utilization, RPS supplementation significantly increased (P < 0.05) the availability of DM, CP, and energy, as well as dietary AME at 35 d of age in ducks fed low nPP diets. However, RPS supplementation had no effect (P > 0.05) on the concentration of cecal short-chain fatty acids and the activities of cecal phytase and cellulase in ducks fed low nPP diets. These results indicate that RPS can improve nutrient availability to ameliorate the negative effects on performance and feather development caused by a low nPP diet in Pekin ducks.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Suplementos Nutricionais , Patos , Plumas , Crescimento e Desenvolvimento , Amido Resistente , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Plumas/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Fósforo/metabolismo , Distribuição Aleatória , Amido Resistente/farmacologia , Solanum tuberosum/química
11.
Neuropharmacology ; 187: 108494, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587920

RESUMO

Although attention-deficit/hyperactivity disorder (ADHD) is widely studied, problems regarding the adverse effect risks and non-responder problems still need to be addressed. Combination pharmacotherapy using standard dose regimens of existing medication is currently being practiced mainly to augment the therapeutic efficacy of each drug. The idea of combining different pharmacotherapies with different molecular targets to alleviate the symptoms of ADHD and its comorbidities requires scientific evidence, necessitating the investigation of their therapeutic efficacy and the mechanisms underlying the professed synergistic effects. Here, we injected male ICR mice with MK-801 to induce ADHD behavioral condition. We then modeled a "combined drug" using sub-optimal doses of methylphenidate, atomoxetine, and fluoxetine and investigated the combined treatment effects in MK-801-treated mice. No sub-optimal dose monotherapy alleviated ADHD behavioral condition in MK-801-treated mice. However, treatment with the combined drug attenuated the impaired behavior of MK-801-treated animals. Growth impediment, sleep disturbances, or risk of substance abuse were not observed in mice treated subchronically with the combined drugs. Finally, we observed that the combined ADHD drug rescued alterations in p-AKT and p-ERK1/2 levels in the prefrontal cortex and hippocampus, respectively, of MK-801-treated mice. Our results provide experimental evidence of a possible new pharmacotherapy option in ameliorating the ADHD behavioral condition without the expected adverse effects. The detailed mechanism of action underlying the synergistic therapeutic efficacy and reduced adverse reaction by combinatorial drug treatment should be investigated further in future studies.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Cloridrato de Atomoxetina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Fluoxetina/farmacologia , Metilfenidato/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Modelos Animais de Doenças , Maleato de Dizocilpina/toxicidade , Sinergismo Farmacológico , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitatórios/toxicidade , Crescimento e Desenvolvimento/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Teste de Campo Aberto , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sono/efeitos dos fármacos
12.
J Cell Mol Med ; 25(3): 1350-1358, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33393222

RESUMO

The hair follicle (HF) is an important mini-organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the proliferation, upward migration and differentiation of HF stem cell progenitor cells to form other types of HF cells. Thymosin ß4 (Tß4), a major actin-sequestering protein, is involved in various cellular responses and has recently been shown to play key roles in HF growth and development. Endogenous Tß4 can activate the mouse HF cycle transition and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tß4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs (hair follicles) in cashmere goats. However, the molecular mechanisms through which Tß4 promotes HF growth and development have rarely been reported. Herein, we review the functions and mechanisms of Tß4 in HF growth and development and describe the endogenous and exogenous actions of Tß4 in HFs to provide insights into the roles of Tß4 in HF growth and development.


Assuntos
Folículo Piloso/citologia , Folículo Piloso/fisiologia , Organogênese , Timosina/genética , Timosina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Crescimento e Desenvolvimento/genética , Folículo Piloso/efeitos dos fármacos , Humanos , Organogênese/efeitos dos fármacos , Transdução de Sinais , Relação Estrutura-Atividade , Timosina/química , Timosina/farmacologia
13.
Cell Mol Neurobiol ; 41(1): 129-150, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32303879

RESUMO

BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY: Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 µg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS: THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION: Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.


Assuntos
Acetatos/uso terapêutico , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Ciclopropanos/uso terapêutico , Quinolinas/uso terapêutico , Comportamento Social , Sulfetos/uso terapêutico , Timerosal/administração & dosagem , Timerosal/efeitos adversos , Acetatos/administração & dosagem , Acetatos/farmacologia , Animais , Animais Recém-Nascidos , Transtorno Autístico/patologia , Ciclopropanos/administração & dosagem , Ciclopropanos/farmacologia , Crescimento e Desenvolvimento/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/ultraestrutura , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Quinolinas/administração & dosagem , Quinolinas/farmacologia , Sulfetos/administração & dosagem , Sulfetos/farmacologia , Fator de Transcrição RelA/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
14.
J Plant Physiol ; 255: 153275, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33161338

RESUMO

SUMOylation is a post-translational modification process that comprises a tandem enzymatic cascade, i.e., maturation, activation, conjugation, and ligation of a small ubiquitin-like modifier, which triggers the modulated activities and transport of the cellular proteins to other areas of the cell. In Oryza sativa (rice), OsSIZ1/2 encoding E3 SUMO ligase exerts regulatory influences on Pi homeostasis and developmental responses. However, the role of OsSAE1a, SUMO E1 activating enzyme, in regulating phosphate (Pi) utilization and/or growth and development is not known in rice and was thus investigated in this study. The qRT-PCR assay revealed a constitutive and variable spatiotemporal expression pattern of OsSAE1a in the vegetative and reproductive tissues and was comparable in the root and shoot grown under different Pi regimes. RNAi-mediated suppression of OsSAE1a exerted variable effects on the concentrations of Pi and total P in different tissues, uptake and distribution of 32Pi, and relative expression levels of several genes that play pivotal roles in the maintenance of Pi homeostasis. The effects of the mutation in OsSAE1a were also evident in the vegetative and reproductive traits of rice during growth in a hydroponic system and pot soil, respectively. Overall, these results suggest a broad-spectrum role of OsSAE1a in the maintenance of Pi homeostasis and regulating growth and development.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Crescimento e Desenvolvimento/genética , Homeostase/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Oryza/genética , Fosfatos/metabolismo , Técnicas de Silenciamento de Genes , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
15.
Poult Sci ; 99(11): 5844-5857, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33142502

RESUMO

This study evaluated the effects of varying levels of L-arginine (Arg) on performance and intestinal health of broilers challenged with Eimeria. Cobb 500 male chicks (n = 720) were randomly distributed in a 5 × 2 factorial arrangement (6 replicates/12 birds). The main factors were Arg levels (1.04, 1.14, 1.24, 1.34, 1.44%) and challenge or non-challenge with Eimeria. At day 12, in the challenge group, each bird received orally 12,500 Eimeria maxima, 12,500 Eimeria tenella, and 62,500 Eimeria acervulina sporulated oocysts. At 5 d postinfection (dpi), intestinal permeability was measured. At 6 and 14 dpi, performance, intestinal histomorphology, nutrient digestibility, tight junction protein (TJP) gene expression, and antioxidant markers were evaluated. Few interactions were found, and when significant, the supplementation of Arg did not counteract the negative effects of Eimeria challenge. Challenge, regardless of Arg level, increased intestinal permeability, although the expression of Claudin-1, a TJP, was upregulated. At 6 dpi, the antioxidant system was impaired by the challenge. Moreover, growth performance, intestinal histomorphology, and nutrient digestibility were negatively affected by challenge at 6 and 14 dpi. Regardless of challenge, from 0 to 14 dpi, birds fed 1.44% showed higher weight gain than 1.04% of Arg, and birds fed 1.34% showed lower feed conversion than 1.04% of Arg. At 5 dpi, intestinal permeability was improved in birds fed 1.34% than 1.04% of Arg. Moreover, 1.34% of Arg upregulated the expression of the TJP Zonula occludens-1 (ZO-1) as compared with 1.24 and 1.44% of Arg at 6 dpi. At 14 dpi, 1.44% of Arg upregulated the expression of ZO-1 and ZO-2 compared with 1.24 and 1.34% of Arg. The nutrient digestibility was quadratically influenced by Arg, whereas the antioxidant markers were unaffected. Thus, the challenge with Eimeria had a negative impact on growth and intestinal health. The dietary supplementation of levels ranging from 1.24 to 1.44% of Arg showed promising results, improving overall growth, intestinal integrity, and morphology in broilers subjected or not to Eimeria challenge.


Assuntos
Arginina , Galinhas , Coccidiose , Suplementos Nutricionais , Eimeria , Crescimento e Desenvolvimento , Doenças das Aves Domésticas , Ração Animal/análise , Animais , Arginina/farmacologia , Galinhas/crescimento & desenvolvimento , Coccidiose/fisiopatologia , Coccidiose/veterinária , Dieta/veterinária , Crescimento e Desenvolvimento/efeitos dos fármacos , Masculino , Doenças das Aves Domésticas/parasitologia
16.
Poult Sci ; 99(10): 4730-4740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988507

RESUMO

We postulated that the use of appropriate levels and proportions of arginine (Arg) and methionine (Met) in compound feed with high lysine content (Lys) would make it possible to fully exploit the growth potential of modern fattening turkey crossbreds, without compromising their immune system. The aim of this study was to determine the effect of different ratios of Arg and Met in diets with high Lys content on the performance and immune status of turkeys. The turkeys were assigned to 6 groups with 8 replicates per group and 18 birds per replicate. Six feeding programs, with 3 dietary Arg levels (90, 100, and 110%) and 2 dietary Met levels (30 and 45%) relative to dietary Lys content, were compared. During each of 4 feeding phases (weeks 0-4, 5-8, 9-12, and 13-16), birds were fed ad libitum isocaloric diets containing high level of Lys, approximately 1.83, 1.67, 1.49, and 1.20%, respectively. The dietary treatments had no effect on daily feed intake or body weight at any stage of the study. The protein content of the breast meat was higher in the treatments with the highest Arg level (110%) compared with the lowest Arg level (90%). Similarly, protein content was higher in the treatments with the higher Met level compared with the lower Met level. Higher plasma levels of tumor necrosis factor, interleukin 6 (IL-6), and immunoglobulin Y were found in turkeys fed diets with the lowest Arg content. An increase in Met content resulted in a decrease in plasma content of IL-6. In growing turkeys fed diets high in Lys, an Arg level of 90% relative to Lys can be used without negatively affecting production results and immune system. Regardless of dietary Arg levels, an increase in Met content does not stimulate the immune defense system and shows no effect on growth performance of turkeys in current trial.


Assuntos
Arginina , Dieta , Crescimento e Desenvolvimento , Sistema Imunitário , Lisina , Metionina , Perus , Ração Animal/análise , Animais , Arginina/farmacologia , Composição Corporal/efeitos dos fármacos , Dieta/veterinária , Suplementos Nutricionais/estatística & dados numéricos , Crescimento e Desenvolvimento/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Lisina/metabolismo , Metionina/farmacologia , Perus/crescimento & desenvolvimento , Perus/imunologia
17.
Poult Sci ; 99(10): 4769-4775, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988511

RESUMO

Coccidiosis is a high-prevalence disease that annually entails huge costs for the poultry industry. Control of coccidiosis in poultry production is based on the use of coccidiostats and vaccines. However, along with the problem of drug resistance, there is a concern about food safety and drug residues in poultry products. The objective of this study was to evaluate the effect of sodium bisulfate (SBS) in comparison with monensin (M) and their combination (SBSM) effects on controlling coccidiosis in broilers. In a randomized design, 300 chickens (Ross 308) were divided into 5 treatments and 4 replications (15 birds per replicate). All birds, except the negative control (NC), were orally inoculated with 4 Eimeria species on 14 D of age. Treatments included were as follows: NC, an unsupplemented basal diet, nonchallenged; positive control, a basal diet unsupplemented, challenged with Eimeria spp; a basal diet supplemented with 5 g/kg of SBS; a basal diet supplemented with 1 g/kg of M; and a basal diet supplemented with 5 g/kg SBS and 1 g/kg M (SBSM). Oocyst shedding per gram (OPG) of the faecal sample from each experimental unit was counted on 5 to 14 D after inoculation. Two chicks from each experimental unit were euthanized to investigate intestinal lesions on day 5 after inoculation. The NC birds showed the highest BW gain and the lowest feed conversion ratio. The birds in the SBSM group had improved feed consumption compared with the M group in the prechallenge period (P < 0.05). All supplemented treatments resulted in a significant decrease in OPG. The M and SBSM treatments showed more efficacy than the SBS group (P < 0.05) in reducing OPG. There was a significant reduction in cecal lesions owing to supplementation with SBS, but the effect of SBS in the upper part of the intestine was lower than the M and SBSM groups (P < 0.05). Based on the results of this study, SBS has protective effects against coccidiosis in ceca, and the combination of M and SBS (SBSM) did not show any further improvement effect compared with M alone on the control of coccidiosis.


Assuntos
Coccidiose , Coccidiostáticos , Eimeria , Crescimento e Desenvolvimento , Intestinos , Doenças das Aves Domésticas , Sulfatos , Ração Animal/análise , Animais , Galinhas , Coccidiose/tratamento farmacológico , Coccidiose/prevenção & controle , Coccidiose/veterinária , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Dieta/veterinária , Crescimento e Desenvolvimento/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Sulfatos/farmacologia
18.
Poult Sci ; 99(10): 4824-4831, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988519

RESUMO

This study investigated the effects of dietary chitosan oligosaccharides (COS) supplementation on growth performance; corticosterone, growth hormone, and insulin-like growth factor-1 concentration; relative organ weight; liver function; meat quality; muscle glycolytic metabolism; and oxidative status in yellow-feather broilers under heat stress. A total of 108 35-day-old Chinese yellow-feather broilers (BW, 470.31 ± 13.15 g) was randomly allocated to 3 dietary treatments as follow: control group, basal diet and raised under normal temperature (24°C); HS group, basal diet and raised under cycle heat stress (34°C from 10:00 to 18:00 and 24°C for the rest time); and HSC group, basal diet with 200 mg/kg COS supplementation and raised under cycle heat stress. Each treatment had 6 replication pens and 6 broilers per pen. Results indicated that heat stress decreased ADG, ADFI, gain:feed ratio, the relative weight of thymus, bursa of Fabricius, pancreas, proventriculus, gizzard, and liver, growth hormone concentration, pH24h, muscle glycogen content, muscle superoxide dismutase and glutathione peroxidase activity, as well as increased corticosterone, alanine aminotransferase and aspartate aminotransferase level, cooking loss, muscle lactate and malondialdehyde content. Compared with the HS group, broilers in the HSC group had higher ADG, the relative weight of thymus, bursa of Fabricius, and liver, growth hormone concentration, pH24h, muscle glycogen content, muscle superoxide dismutase and glutathione peroxidase activity, and lower serum corticosterone, alanine aminotransferase and aspartate aminotransferase level, cooking loss, and muscle lactate and malondialdehyde content. In conclusion, the results suggested that COS could be used as an effective feed additive to maintain growth performance, liver function, meat quality, muscle glycolytic metabolism, and oxidative status of yellow-feather broilers under heat stress. The improved meat quality is possibly through reducing muscle glycolysis metabolism and improving muscle oxidative status by dietary COS supplementation in broilers under heat stress.


Assuntos
Galinhas , Quitosana , Suplementos Nutricionais , Crescimento e Desenvolvimento , Resposta ao Choque Térmico , Carne , Oligossacarídeos , Ração Animal/normas , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Quitosana/farmacologia , Dieta/veterinária , Glicólise/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Carne/normas , Músculo Esquelético/metabolismo , Oligossacarídeos/farmacologia , Distribuição Aleatória
19.
Sci Rep ; 10(1): 14563, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32884067

RESUMO

Maternal effects via hormonal transfer from the mother to the offspring provide a tool to translate environmental cues to the offspring. Experimental manipulations of maternally transferred hormones have yielded increasingly contradictory results, which may be explained by differential effects of hormones under different environmental contexts. Yet context-dependent effects have rarely been experimentally tested. We therefore studied whether maternally transferred thyroid hormones (THs) exert context-dependent effects on offspring survival and physiology by manipulating both egg TH levels and post-hatching nest temperature in wild pied flycatchers (Ficedula hypoleuca) using a full factorial design. We found no clear evidence for context-dependent effects of prenatal THs related to postnatal temperature on growth, survival and potential underlying physiological responses (plasma TH levels, oxidative stress and mitochondrial density). We conclude that future studies should test for other key environmental conditions, such as food availability, to understand potential context-dependent effects of maternally transmitted hormones on offspring, and their role in adapting to changing environments.


Assuntos
Crescimento e Desenvolvimento/fisiologia , Óvulo/fisiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Hormônios Tireóideos/farmacologia , Animais , Animais Recém-Nascidos , Feminino , Crescimento e Desenvolvimento/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Aves Canoras
20.
Mol Cell Endocrinol ; 518: 111029, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941926

RESUMO

This review covers the current knowledge on the regulation of the somatic growth axis and its interaction with metabolism and feeding regulation. The main endocrine and neuroendocrine factors regulating both the growth axis and feeding behavior will be briefly summarized. Recently discovered neuropeptides and peptide hormones will be mentioned in relation to feeding control as well as growth hormone regulation. In addition, the influence of nutrient and nutrient sensing mechanisms on growth axis will be highlighted. We expect that in this process gaps of knowledge will be exposed, stimulating future research in those areas.


Assuntos
Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Peixes , Nutrientes/fisiologia , Animais , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Peixes/crescimento & desenvolvimento , Peixes/metabolismo , Crescimento e Desenvolvimento/efeitos dos fármacos , Nutrientes/farmacologia
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