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1.
Sci Rep ; 14(1): 6136, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480757

RESUMO

Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid-CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Animais , Camundongos , Sobrevivência Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos C57BL
2.
Eur J Pharmacol ; 963: 176248, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056616

RESUMO

Since their discovery in 2000, there has been a continuous expansion of studies investigating the physiology, biochemistry, and pharmacology of endocrine fibroblast growth factors (FGFs). FGF19, FGF21, and FGF23 comprise a subfamily with attributes that distinguish them from typical FGFs, as they can act as hormones and are, therefore, referred to as endocrine FGFs. As they participate in a broad cross-organ endocrine signaling axis, endocrine FGFs are crucial lipidic, glycemic, and energetic metabolism regulators during energy availability fluctuations. They function as powerful metabolic signals in physiological responses induced by metabolic diseases, like type 2 diabetes and obesity. Pharmacologically, FGF19 and FGF21 cause body weight loss and ameliorate glucose homeostasis and energy expenditure in rodents and humans. In contrast, FGF23 expression in mice and humans has been linked with insulin resistance and obesity. Here, we discuss emerging concepts in endocrine FGF signaling in the brain and critically assess their putative role as therapeutic targets for treating metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Humanos , Animais , Camundongos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Homeostase , Encéfalo/metabolismo , Obesidade/tratamento farmacológico
3.
J Nutr Biochem ; 120: 109409, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37364792

RESUMO

Tissue/cellular actions of butyrate on energy metabolism and intestinal barrier in normal metabolic conditions or prediabetes are still unclear. In this work, we investigated the beneficial effect of dietary supplementation with sodium butyrate on energy metabolism, body mass composition, and intestinal epithelial barrier mediated by tight junction (TJ) in chow diet-fed normal and high-fat diet (HF)-fed prediabetic mice, considering the well-known butyrate action as an epigenetic and inflammatory regulator. Butyrate significantly reduced the fat/lean mass ratio, slightly ameliorated dyslipidemia, restored oral glucose tolerance, and increased basal energy expenditure in prediabetic HF-fed mice but had no effect on control animals. Such effects were observed in the absence of significant alterations in the hypothalamic expression of orexigenic and anorexigenic genes and motor activity. Also, butyrate suppressed the whitening effect of HF on brown adipose tissue but did not affect cell bioenergetics in immortalized UCP1-positive adipocytes in vitro. Butyrate reinforced the intestinal epithelial barrier in HF-fed mice and in Caco-2 monolayers, which involved higher trafficking of TJ proteins to the cell-cell contact region of the intestinal epithelia, without affecting TJ gene expression or the acetylation level of histones H3 and H4 in vivo. All metabolic and intestinal effects of butyrate in prediabetic mice occurred in the absence of detectable changes in systemic or local inflammation, or alterations in endotoxemia markers. Butyrate has no effect on chow diet-fed mice but, in the context of HF-induced prediabetes, it prevents metabolic and intestinal dysfunctions independently of its anti-inflammatory and epigenetic actions.


Assuntos
Estado Pré-Diabético , Humanos , Camundongos , Animais , Estado Pré-Diabético/metabolismo , Células CACO-2 , Junções Íntimas/metabolismo , Ácido Butírico/farmacologia , Metabolismo Energético , Anti-Inflamatórios/metabolismo , Epigênese Genética , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos
4.
Environ Toxicol Pharmacol ; 101: 104197, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37356678

RESUMO

Lithium (Li) is now widely used in green energies/clean technologies; however, due to its inefficient recycling and treatment, it is an emerging contaminant in aquatic systems. Bivalves, such as clams, are considered good bioindicators of pollution, hence we evaluated the biochemical effects of Li in the clam Venerupis corrugata. Clams were exposed (14 days) to an increasing Li gradient (0, 200, 400, 800 µg/L). Bioconcentration capacity tended to decrease with increasing Li exposure possibly due to efforts to eliminate Li from the cells, to avert damage. No influences on the clams' metabolic capacity and protein content were observed. Antioxidant and detoxification defences were activated, especially at 400 and 800 µg/L of Li, avoiding lipid damage, while protein injuries were observed at higher concentrations. Furthermore, a loss of redox balance was observed. This study highlights the importance of preventing and regulating Li discharges into the environment, avoiding adverse consequences to aquatic ecosystems.


Assuntos
Bivalves , Poluentes Químicos da Água , Animais , Lítio/toxicidade , Lítio/metabolismo , Estresse Oxidativo , Ecossistema , Biomarcadores/metabolismo , Bivalves/metabolismo , Poluentes Químicos da Água/análise
5.
Environ Pollut ; 326: 121416, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906057

RESUMO

Coastal areas, such as estuaries and coastal lagoons, are among the most endangered aquatic ecosystems due to the intense anthropogenic activities occurring in their vicinity. These areas are highly threatened by climate change-related factors as well as pollution, especially due to their limited water exchange. Ocean warming and extreme weather events, such as marine heatwaves and rainy periods, are some of the consequences of climate change, inducing alterations in the abiotic parameters of seawater, namely temperature and salinity, which may affect the organisms as well as the behaviour of some pollutants present in water. Lithium (Li) is an element widely used in several industries, especially in the production of batteries for electronic gadgets and electric vehicles. The demand for its exploitation has been growing drastically and is predicted a large increase in the coming years. Inefficient recycling, treatment and disposal results in the release of Li into the aquatic systems, the consequences of which are poorly understood, especially in the context of climate change. Considering that a limited number of studies exist about the impacts of Li on marine species, the present study aimed to assess the effects of temperature rise and salinity changes on the impacts of Li in clams (Venerupis corrugata) collected from the Ria de Aveiro (coastal lagoon, Portugal). Clams were exposed for 14 days to 0 µg/L of Li and 200 µg/L of Li, both conditions under different climate scenarios: 3 different salinities (20, 30 and 40) at 17 °C (control temperature); and 2 different temperatures (17 and 21 °C) at salinity 30 (control salinity). Bioconcentration capacity and biochemical alterations regarding metabolism and oxidative stress were investigated. Salinity variations had a higher impact on biochemical responses than temperature increase, even when combined with Li. The combination of Li with low salinity (20) was the most stressful treatment, provoking increased metabolism and activation of detoxification defences, suggesting possible imbalances in coastal ecosystems in response to Li pollution under extreme weather events. These findings may ultimately contribute to implement environmentally protective actions to mitigate Li contamination and preserve marine life.


Assuntos
Bivalves , Poluentes Químicos da Água , Animais , Ecossistema , Lítio/farmacologia , Mudança Climática , Água , Salinidade , Poluentes Químicos da Água/análise
6.
Cureus ; 15(1): e33698, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36788820

RESUMO

Introduction In outpatient surgery, post-discharge follow-up calls are essential for identifying complications and are considered a cost-effective intervention. Currently, there is a lack of scientific evidence to support the development and validation of standardized protocols adjusted to patients' specificities. Our aim is to develop a personalized model for our outpatient surgery unit (OSU) to create an individualized follow-up strategy in the future. Material and methods We performed a retrospective, cohort, single-center study, including patients undergoing surgery at an OSU of a tertiary hospital in Portugal, for three months. Follow-up calls were performed on the seventh and fourteenth days after discharge. The variables analyzed included: sex, age, surgical specialty, anesthetic technique, American Society of Anesthesiologists (ASA) physical status classification, surgery duration, and complications. A binary logistic regression was adjusted for the complications detected in each call. Results Nine-hundred eighty-four (984) patients were included, of which 79.8% (n=785) and 75.3% (n=741) answered the follow-up calls on the seventh and fourteenth days after discharge, respectively. Complications were reported in 47.1% (n=370) and 29.8% (n=221) of these calls, respectively, with pain having the highest incidence rate (44.7% in the first call; 26.6% in the second). The type of anesthesia and surgical specialty were independent risk factors for complications (p<0.001). Each minute increase in surgery duration increased by 1.1% the odds of complications (95% confidence interval 1.003-1.018) in the first call. Compared with no anesthesiology involvement, general anesthesia, regional anesthesia, and monitored anesthetic care are 2.52, 2.04, and 1.75 times more likely to have complications detected in the first call and 3.21, 2.36, and 3.11 times more likely to have complications on the second (p<0.05 for all). A model that predicts the detection of complications in each call was created. Discussion Outpatient surgery may allow procedures to be carried out safely, efficiently, and cost-effectively. To optimize the outcomes, it is important to quantify results as a tool for honing our strategies. The present study recognized the influence of several variables in the incidence of post-discharge complications. Also, considering the complications reported, pain was the most frequent among the reports and should not be neglected. In our reality, no follow-up calls are routinely performed after the seventh day, and complications were reported in that period, meaning some patients probably should be accompanied for a longer period. Conclusions To ensure the quality of care and patient safety and satisfaction, it is essential to identify and manage postoperative complications. Despite not being a routine contact, the incidence rate of complications on the seventh and fourteenth postoperative days is noted. According to our investigation, the type of anesthesia, surgical specialty, and duration of surgery should be carefully considered when establishing individualized follow-up plans. These plans, using tools adjusted to the population of each OSU, such as the calculator presented, may allow the available resources to be used with the greatest potential benefit for both patients and healthcare systems.

7.
Sci Total Environ ; 857(Pt 2): 159374, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36240931

RESUMO

The Lithium (Li) industry has been expanding worldwide, over the last decades, and projections expect an increasing demand for its production in the coming years. It has been identified as an emerging pollutant and it occurs widely in aquatic environments, raising concern about its effects on ecosystems. Besides the increasing research on this topic, there is still limited understanding and discussion on the marine and coastal implications of Li occurrence. The present review aims to fill these knowledge gaps by analysing the literature concerning Li occurrence and its effects on marine and coastal ecosystems, including transition areas. Since 1960, the number of publications has increased, especially over the last decade, and available information has reported Li in water and sediments of these areas, while few studies investigated Li in tissues of biota. Among all the studied ecosystems, Chile reported one of the highest Li concentrations. Regarding the adverse effects of Li in aquatic organisms, Bacillariophyceae, Scyphozoa, Bivalvia, Gastropoda, Cephalopoda, Polychaeta, Malacostraca, Echinoidea and Actinopteri were the studied taxonomic classes, and development inhibition, malformations, cellular and metabolic alterations, and behaviour changes were some of the observed impacts. This review might be particularly important in the mitigation of Li pollution as well as in the implementation of new directives and thresholds, as it highlights the impacts of Li and the urgent need to address new solutions and alternatives, meeting the Agenda 2030 for sustainable development.


Assuntos
Ecossistema , Poluentes Químicos da Água , Animais , Lítio , Poluentes Químicos da Água/análise , Organismos Aquáticos , Peixes
8.
Curr Med Chem ; 30(22): 2542-2561, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35996245

RESUMO

The development of clinically viable metformin analogs is a challenge largely to be overcome. Despite being an extremely efficient drug for the treatment of type 2 diabetes mellitus, multiple studies were conducted seeking to improve its hypoglycemic activity or to ameliorate aspects such as low oral absorption and the incidence of gastrointestinal side effects. Furthermore, efforts have been made to attribute new activities, or even to expand the pre-existing ones, that could enhance its effects on diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this paper, we describe the analogs of metformin developed in the last three decades, highlighting the lack of computationally based rational approaches to guide their development. We also discuss this is probably a consequence of how unclear the mechanism of action of the parent drug is and highlight the recent advances towards the establishment of the main molecular target(s) for metformin. We also explored the binding of metformin, buformin and phenformin to the mitochondrial respiratory chain complex I through molecular docking analyses and reviewed the prospects of applying computational tools to improve the success in the development of such analogs. Therefore, it becomes evident that the wide range of molecular targets and the multiple activities displayed by metformin make this drug a promising prototype for developing novel entities, particularly for treating type 2 diabetes mellitus.


Assuntos
Antimaláricos , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Açúcares , Simulação de Acoplamento Molecular , Antimaláricos/uso terapêutico
10.
Sci Rep ; 12(1): 22273, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564463

RESUMO

Aging is associated with glucose metabolism disturbances, such as insulin resistance and hyperinsulinemia, which contribute to the increased prevalence of type 2 diabetes (T2D) and its complications in the elderly population. In this sense, some bile acids have emerged as new therapeutic targets to treat TD2, as well as associated metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic acid (TUDCA) improves glucose homeostasis in T2D, obesity, and Alzheimer's disease mice model. However, its effects in aged mice have not been explored yet. Here, we evaluated the actions of TUDCA upon glucose-insulin homeostasis in aged C57BL/6 male mice (18-month-old) treated with 300 mg/kg of TUDCA or its vehicle. TUDCA attenuated hyperinsulinemia and improved glucose homeostasis in aged mice, by enhancing liver insulin-degrading enzyme (IDE) expression and insulin clearance. Furthermore, the improvement in glucose-insulin homeostasis in these mice was accompanied by a reduction in adiposity, associated with adipocyte hypertrophy, and lipids accumulation in the liver. TUDCA-treated aged mice also displayed increased energy expenditure and metabolic flexibility, as well as a better cognitive ability. Taken together, our data highlight TUDCA as an interesting target for the attenuation of age-related hyperinsulinemia and its deleterious effects on metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Idoso , Camundongos , Masculino , Humanos , Animais , Ácidos e Sais Biliares , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos Endogâmicos C57BL , Hiperinsulinismo/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Tauroquenodesoxicólico/uso terapêutico , Insulina/metabolismo , Obesidade/tratamento farmacológico , Glucose/metabolismo
11.
Cureus ; 14(12): e32895, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36699750

RESUMO

Cerebrospinal fluid (CSF) cutaneous fistula is an unusual but potentially serious complication of neuraxial procedures. While combined spinal-epidural (CSE) technique or spinal/epidural techniques alone are standard in obstetric anesthesia, subsequent persistent CSF leak is rarely reported in the obstetric population. Clinical presentation ranges from asymptomatic states and only abnormal leakage through the puncture site to severe cases with meningitis or subdural hematoma. Both conservative and invasive approaches are suitable for management, but no formal guidelines on how to diagnose and manage this condition are available, and hence clinicians have to rely on their experience. We present a case of a 35-year-old parturient scheduled for an elective cesarean delivery with a persistent CSF leak three days after epidural catheter removal. The leakage was managed with both suturing of the skin site and conservative methods such as hydration, bed rest, and oral analgesics, with no adverse effects for the patient.

12.
Prog Biophys Mol Biol ; 167: 26-31, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34547326

RESUMO

Bile acids have received increasing attention over the past years as their multiple alternative roles became clearer. Tauroursodeoxycholic Acid (TUDCA) in specific has generated special interest due to its ability to promote pancreatic survival and function, as well as reduce endoplasmic reticulum stress. However, there are few studies explaining the molecular mechanisms behind TUDCA's beneficial actions on pancreatic beta cells. In this review, we decided to review the literature in order to craft a primer for researchers on what is known about TUDCA's receptors and the molecular pathways involved in this bile acid's function in the endocrine pancreas. We review the studies that focused on G protein-coupled bile acid receptor (TGR5), Sphingosine-1-phosphate receptor 2 (S1PR2) and α5ß1 Integrin function in pancreatic cells. Our hope is to provide a basis for future studies to expand upon, especially considering the current lack of studies focusing on the importance of these receptors, either through TUDCA signaling or other signaling molecules.


Assuntos
Células Secretoras de Insulina , Receptores Acoplados a Proteínas G , Transdução de Sinais , Ácido Tauroquenodesoxicólico
13.
Sci Rep ; 11(1): 18114, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518585

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive deficits remain the major manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in food intake, body weight and energy balance are also present, both in AD patients and animal models. In this sense, the tauroursodeoxycholic acid (TUDCA) has shown beneficial effects both in reducing the central and cognitive markers of AD, as well as in attenuating the metabolic disorders associated with it. We previously demonstrated that TUDCA improves glucose homeostasis and decreases the main AD neuromarkers in the streptozotocin-induced AD mouse model (Stz). Besides that, TUDCA-treated Stz mice showed lower body weight and adiposity. Here, we investigated the actions of TUDCA involved in the regulation of body weight and adiposity in Stz mice, since the effects of TUDCA in hypothalamic appetite control and energy homeostasis have not yet been explored in an AD mice model. The TUDCA-treated mice (Stz + TUDCA) displayed lower food intake, higher energy expenditure (EE) and respiratory quotient. In addition, we observed in the hypothalamus of the Stz + TUDCA mice reduced fluorescence and gene expression of inflammatory markers, as well as normalization of the orexigenic neuropeptides AgRP and NPY expression. Moreover, leptin-induced p-JAK2 and p-STAT3 signaling in the hypothalamus of Stz + TUDCA mice was improved, accompanied by reduced acute food intake after leptin stimulation. Taken together, we demonstrate that TUDCA treatment restores energy metabolism in Stz mice, a phenomenon that is associated with reduced food intake, increased EE and improved hypothalamic leptin signaling. These findings suggest treatment with TUDCA as a promising therapeutic intervention for the control of energy homeostasis in AD individuals.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Metabolismo Energético/efeitos dos fármacos , Homeostase , Estreptozocina/efeitos adversos , Ácido Tauroquenodesoxicólico/farmacologia , Adiposidade , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Biomarcadores , Peso Corporal , Gerenciamento Clínico , Modelos Animais de Doenças , Expressão Gênica , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Especificidade de Órgãos , Transdução de Sinais , Termogênese
14.
Mol Cell Endocrinol ; 535: 111379, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34252492

RESUMO

The endoplasmic reticulum (ER) stress is one of the mechanisms related to decreased insulin secretion and beta cell death, contributing to the progress of type 2 diabetes mellitus (T2D). Thus, investigating agents that can influence this process would help prevent the development of T2D. Recently, the growth-hormone-releasing hormone (GHRH) action has been demonstrated in INS-1E cells, in which it increases cell proliferation and insulin secretion. As the effects of GHRH and its agonists have not been fully elucidated in the beta cell, we proposed to investigate them by evaluating the role of the GHRH agonist, MR-409, in cells under ER stress. Our results show that the agonist was unable to ameliorate or prevent ER stress. However, cells exposed to the agonist showed less oxidative stress and greater survival even under ER stress. The mechanisms by which GHRH agonist, MR-409, leads to these outcomes require further investigation.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Indóis/efeitos adversos , Células Secretoras de Insulina/citologia , Sermorelina/análogos & derivados , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/agonistas , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Sermorelina/farmacologia
15.
Life Sci ; 272: 119252, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636170

RESUMO

Bear bile has been used in Traditional Chinese Medicine for thousands of years due to its therapeutic potential and clinical applications. The tauroursodeoxycholic acid (TUDCA), one of the acids found in bear bile, is a hydrophilic bile acid and naturally produced in the liver by conjugation of taurine to ursodeoxycholic acid (UDCA). Several studies have shown that TUDCA has neuroprotective action in several models of neurodegenerative disorders (ND), including Alzheimer's disease, Parkinson's disease, and Huntington's disease, based on its potent ability to inhibit apoptosis, attenuate oxidative stress, and reduce endoplasmic reticulum stress in different experimental models of these illnesses. Our research extends the knowledge of the bile acid TUDCA actions in ND and the mechanisms and pathways involved in its cytoprotective effects on the brain, providing a novel perspective and opportunities for treatment of these diseases.


Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/métodos , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/farmacologia
16.
Mol Cell Endocrinol ; 521: 111116, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33321116

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to predictions of the World Health Organization, more than 150 million people worldwide will suffer from dementia by 2050. An increasing number of studies have associated AD with type 2 diabetes mellitus (T2DM), since most of the features found in T2DM are also observed in AD, such as insulin resistance and glucose intolerance. In this sense, some bile acids have emerged as new therapeutic targets to treat AD and metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA), reduces amyloid oligomer accumulation and improves cognition in APP/PS1 mice model of AD, and also improves glucose-insulin homeostasis in obese and type 2 diabetic mice. Herein, we investigated the effect of TUDCA upon glucose metabolism in streptozotocin-induced AD mice model (Stz). The Stz mice that received 300 mg/kg TUDCA during 10 days (Stz + TUDCA), showed improvement in glucose tolerance and insulin sensitivity, reduced fasted and fed glycemia, increased islet mass and ß-cell area, as well as increased glucose-stimulated insulin secretion, compared with Stz mice that received only PBS. Stz + TUDCA mice also displayed lower neuroinflammation, reduced protein content of amyloid oligomer in the hippocampus, improved memory test and increased protein content of insulin receptor ß-subunit in the hippocampus. In conclusion, TUDCA treatment enhanced glucose homeostasis in the streptozotocin-induced Alzheimer's disease mice model, pointing this bile acid as a good strategy to counteract glucose homeostasis disturbance in AD pathology.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Ácidos e Sais Biliares/metabolismo , Glicemia/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Glucose/metabolismo , Glucose/farmacologia , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/tratamento farmacológico , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Testes de Memória e Aprendizagem , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Estreptozocina/toxicidade , Ácido Tauroquenodesoxicólico/administração & dosagem
17.
Front Endocrinol (Lausanne) ; 11: 599165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324349

RESUMO

ARHGAP21 is a RhoGAP protein implicated in the modulation of insulin secretion and energy metabolism. ARHGAP21 transient-inhibition increase glucose-stimulated insulin secretion (GSIS) in neonatal islets; however, ARHGAP21 heterozygote mice have a reduced insulin secretion. These discrepancies are not totally understood, and it might be related to functional maturation of beta cells and peripheral sensitivity. Here, we investigated the real ARHGAP21 role in the insulin secretion process using an adult mouse model of acute ARHGAP21 inhibition, induced by antisense. After ARHGAP21 knockdown induction by antisense injection in 60-day old male mice, we investigated glucose and insulin tolerance test, glucose-induced insulin secretion, glucose-induced intracellular calcium dynamics, and gene expression. Our results showed that ARHGAP21 acts negatively in the GSIS of adult islet. This effect seems to be due to the modulation of important points of insulin secretion process, such as the energy metabolism (PGC1α), Ca2+ signalization (SYTVII), granule-extrusion (SNAP25), and cell-cell interaction (CX36). Therefore, based on these finds, ARHGAP21 may be an important target in Diabetes Mellitus (DM) treatment.


Assuntos
Proteínas Ativadoras de GTPase/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Hiperinsulinismo/prevenção & controle , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Homeostase , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Edulcorantes/farmacologia
18.
Licere (Online) ; 23(3): 485-522, set.2020. ilus, graf
Artigo em Português | LILACS | ID: biblio-1145286

RESUMO

As desordens psicológicas têm se ampliado neste século e acometem pessoas de diferentes idades e perfis socioeconômicos. Diante desse cenário, o presente trabalho busca debater e demonstrar como o lazer e a arteterapia podem ser alternativas para o tratamento de pessoas com depressão, além de auxiliares no controle do avanço dessa doença, por meio da conexão entre lazer, arte e saúde. Utilizou-se como metodologia as pesquisas bibliográfica e de campo com enfoque qualitativo, cujos dados evidenciaram a carência de trabalhos com o mesmo enfoque e apresentaram um panorama de como psicólogos e arteterapeutas de Belém-PA têm (ou não) utilizado o lazer e a arteterapia como auxiliares ao bem-estar do indivíduo e na prevenção de doenças.


Psychological disorders have expanded in this century and affect people of different ages and socioeconomic conditions. Given this scenario, the present study seeks to discuss and demonstrate how leisure and art therapy can be alternatives for the treatment of people with depression, in addition to helping to control the progress of this disease through the connection between leisure, art, and health. The methods used were bibliographic and field research with a qualitative approach, whose data showed the lack of similar works and showed an overview of how psychologists and art therapists in Belém-PA have (or not) used leisure and art therapy as aids to people's well-being and disease prevention.


Assuntos
Atividades de Lazer
19.
Movimento (Porto Alegre) ; 26: e26070, 2020. tab, graf
Artigo em Português | LILACS | ID: biblio-1154917

RESUMO

O objetivo desta revisão sistemática é identificar a influência das redes sociais e tecnologias na retenção de clientes em ginásios. A pesquisa foi efetuada em quatro bases de dados online, de 2011 a 2019. Através do método PRISMA (MOHER et al., 2009), foram selecionados dez artigos. Os resultados evidenciaram que as redes sociais e o uso de tecnologias são fundamentais no processo de retenção. Após a análise dos dez artigos, foram também identificadas e analisadas as variáveis características pessoais dos sócios, frequência e tempo de utilização e qualidade do serviço e satisfação, como influenciadoras da retenção de clientes. Resumindo, este estudo fez uma revisão dos artigos que estudam o impacto das tecnologias e redes sociais na retenção de clientes em ginásios e ajudou a identificar outros fatores que incidem na retenção clientes, agrupando-os em duas dimensões, associadas à empresa e ao cliente.


The purpose of this systematic review is to identify the influence of social media and technologies on customer retention in gyms. The survey was conducted on four online databases from 2011 to 2019. Ten articles were selected through the PRISMA method (MOHER et al., 2009). The results showed that social media and the use of technologies are crucial in the retention process. After analyzing the ten articles, we also identified and analyzed the variables 'personal characteristic of members,' 'attendance and time of use,' 'quality of service and satisfaction' as influencing customer retention. In summary, this study reviewed the articles that study the impact of technologies and social networks on customer retention by gyms and helped to identify other factors that focus on retention, grouping them into two dimensions associated with the company and customers.


El objetivo de esta revisión sistemática es identificar la influencia de las redes sociales y las tecnologías en la retención de clientes en gimnasios. La investigación se llevó a cabo en cuatro bases de datos on-line, de 2011 a 2019. A través del método PRISMA (MOHER et al., 2009), se seleccionaron diez artículos. Los resultados mostraron que las redes sociales y el uso de tecnologías son fundamentales en el proceso de retención. Después de analizar los diez artículos, también se identificaron y analizaron las variables características personales de los socios, frecuencia y tiempo de uso, calidad del servicio y satisfacción, como elementos que influyen en la retención de clientes. En resumen, este estudio revisó los artículos que estudian el impacto de las tecnologías y las redes sociales en la retención de clientes en los gimnasios y ayudó a identificar otros factores que inciden en la retención de clientes, agrupándolos en dos dimensiones, empresa y cliente.


Assuntos
Humanos , Masculino , Feminino , Tecnologia , Academias de Ginástica , Rede Social , Satisfação Pessoal , Inquéritos e Questionários , Revisão , Mídias Sociais
20.
Sci Rep ; 9(1): 12804, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488852

RESUMO

Coffee production is a global industry valued at approximately 173 billion US dollars. One of the main challenges facing coffee production is the management of the coffee berry borer (CBB), Hypothenemus hampei, which is considered the primary arthropod pest of coffee worldwide. Current control strategies are inefficient for CBB management. Although biotechnological alternatives, including RNA interference (RNAi), have been proposed in recent years to control insect pests, characterizing the genetics of the target pest is essential for the successful application of these emerging technologies. In this study, we employed RNA-seq to obtain the transcriptome of three developmental stages of the CBB (larva, female and male) to increase our understanding of the CBB life cycle in relation to molecular features. The CBB transcriptome was sequenced using Illumina Hiseq and assembled de novo. Differential gene expression analysis was performed across the developmental stages. The final assembly produced 29,434 unigenes, of which 4,664 transcripts were differentially expressed. Genes linked to crucial physiological functions, such as digestion and detoxification, were determined to be tightly regulated between the reproductive and nonreproductive stages of CBB. The data obtained in this study help to elucidate the critical roles that several genes play as regulatory elements in CBB development.


Assuntos
Coffea/parasitologia , Genes de Insetos , Gorgulhos/crescimento & desenvolvimento , Gorgulhos/genética , Animais , Feminino , Perfilação da Expressão Gênica , Larva/genética , Larva/crescimento & desenvolvimento , Masculino , RNA-Seq , Transcriptoma
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