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1.
Environ Sci Pollut Res Int ; 30(21): 60314-60325, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37022543

RESUMO

The current outbreak of the novel coronavirus SARS-CoV-2 (coronavirus disease 2019; previously 2019-nCoV), epicenter in Hubei Province (Wuhan), People's Republic of China, has spread too many other countries. The transmission of the corona virus occurs when people are in the incubation stage and do not have any symptoms. Therefore, the role of environmental factors such as temperature and wind speed becomes very important. The study of Acute Respiratory Syndrome (SARS) indicates that there is a significant relationship between temperature and virus transmission and three important factors, namely temperature, humidity and wind speed, cause SARS transmission. Daily data on the incidence and mortality of Covid-19 disease were collected from World Health Organization (WHO) website and World Meter website (WMW) for several major cities in Iran and the world. Data were collected from February 2020 to September 2021. Meteorological data including temperature, air pressure, wind speed, dew point and air quality index (AQI) index are extracted from the website of the World Meteorological Organization (WMO), The National Aeronautics and Space Administration (NASA) and the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. Statistical analysis carried out for significance relationships. The correlation coefficient between the number of infected people in one day and the environmental variables in the countries was different from each other. The relationship between AQI and number of infected was significant in all cities. In Canberra, Madrid and Paris, a significant inverse relationship was observed between the number of infected people in one day and wind speed. There is a significant positive relationship between the number of infected people in a day and the dew point in the cities of Canberra, Wellington and Washington. The relationship between the number of infected people in one day and Pressure was significantly reversed in Madrid and Washington, but positive in Canberra, Brasilia, Paris and Wuhan. There was significant relationship between Dew point and prevalence. Wind speed showed a significant relationship in USA, Madrid and Paris. AQI was strongly associated with the prevalence of covid19. The purpose of this study is to investigate some environmental factors in the transmission of the corona virus.


Assuntos
COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Cidades/epidemiologia , China/epidemiologia , Fatores de Risco
2.
Sci Rep ; 12(1): 10064, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710710

RESUMO

A new nano-antibiotic was synthesized from the conjugation of multi-walled carbon nanotubes with levofloxacin (MWCNT-LVX) through covalent grafting of drug with surface-modified carbon nanotubes in order to achieve an effective, safe, fast-acting nano-drug with the minimal side effects. This study is the first report on the evaluation of in vitro cell viability and antibacterial activity of nano-antibiotic along in addition to the in vivo antibacterial activity in a burn wound model. The drug-loading and release profile at different pH levels was determined using an ultraviolet-visible spectrometer. MWCNT-LVX was synthesized by a simple, reproducible and cost-effective method for the first time and characterized using various techniques, such as scanning electron microscope, transmission electron microscopy, and Brunauer-Emmett-Teller analysis, and so forth. The noncytotoxic nano-antibiotic showed more satisfactory in vitro antibacterial activity against Staphylococcus aureus compared to Pseudomona aeruginosa. The novel synthetic nano-drug possessed high loading capacity and pH-sensitive release profile; resultantly, it exhibited very potent bactericidal activity in a mouse S. aureus wound infection model compared to LVX. Based on the results, the antibacterial properties of the drug enhanced after conjugating with surface-modified MWCNTs. The nano-antibiotic has great industrialization potential for the simple route of synthesis, no toxicity, proper drug loading and release, low effective dose, and strong activity against wound infections. In virtue of unique properties, MWCNTs can serve as a controlled release and delivery system for drugs. The easy penetration to biological membranes and barriers can also increase the drug delivery at lower doses compared to the main drug alone, which can lead to the reduction of its side effects. Hence, MWCNTs can be considered a promising nano-carrier of LVX in the treatment of skin infections.


Assuntos
Nanotubos de Carbono , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Levofloxacino/farmacologia , Camundongos , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/química , Staphylococcus aureus
3.
J Clin Invest ; 132(2)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34847077

RESUMO

The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine ß3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). ß3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with ß3-adrenergic receptor agonists.


Assuntos
Adipócitos/metabolismo , Catecolaminas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Obesidade/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Células 3T3-L1 , Animais , Regulação para Baixo/genética , Resistência a Medicamentos/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Lipólise/efeitos dos fármacos , Lipólise/genética , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/genética , Receptores Adrenérgicos beta 3/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
4.
Nat Metab ; 2(7): 620-634, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32694788

RESUMO

Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of ß-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.


Assuntos
Adipócitos Brancos/metabolismo , Catecolaminas/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Fator de Transcrição STAT3/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Dieta Hiperlipídica , Metabolismo Energético , Ésteres/metabolismo , Lipólise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Oxirredução , Fosforilação , Fator de Transcrição STAT3/genética
5.
Int J Fertil Steril ; 12(4): 329-334, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30291695

RESUMO

BACKGROUND: Antenatal anxiety or maternal stress is a prevalent chronic mental disorder in pregnant women. We have assessed the effect of maternal stress from positive aneuploidy screening results on the changes in uterine artery blood flow. MATERIALS AND METHODS: We performed a prospective cohort (one sample) pilot study at a hospital in Tehran, Iran. A total of 60 pregnant women who were candidates for amniocentesis due to abnormal sequential screening test results entered the study. We conducted 2 standard psychological tests, the Spielberger's State-Trait Anxiety Inventory and the Beck Anxiety Inventory, to determine anxiety levels in the participants before amniocentesis and two weeks after amniocentesis. The uterine artery resistance index was also measured before and two weeks after amniocentesis. The level of maternal stress was compared with the uterine artery resistance index. RESULTS: Patients had a mean State Trait Anxiety Inventory score before amniocentesis of greater than 40, which meant that the mothers experienced high anxiety. There were no correlations between both inventories' anxiety scores and uterine artery blood flow before amniocentesis. However, two weeks after amniocentesis, we observed significant negative correlations between the State Anxiety (P=0.0041) and Trait Anxiety (P=0.010) Inventory scores and the uterine artery resistance indexes. Also, there was an association between the decreased right uterine artery resistance index and State Anxiety scores (P=0.036). There were significant correlations between State and Trait Anxiety scores and second trimester analytes of ß-human chorionic gonadotropin (ß-hCG, P<0.001), α-fetoprotein (P<0.001), and unconjugated estriol (P=0.048). CONCLUSION: Maternal anxiety because of positive aneuploidy screening serum analytes and amniocentesis can affect perinatal outcomes via mood-based alterations in blood flow of the uterine arteries and the screening markers ß-hCG,unconjugated estriol, and α-fetoprotein.

6.
Cell Rep ; 22(11): 2849-2859, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29539415

RESUMO

Brown adipose tissue (BAT) adaptively transfers energy from glucose and fat into heat by inducing a gene network that uncouples mitochondrial electron transport. However, the innate transcription factors that enable the rapid adaptive response of BAT are unclear. Here, we identify estrogen-related receptor gamma (ERRγ) as a critical factor for maintaining BAT identity. ERRγ is selectively expressed in BAT versus WAT, in which, in the absence of PGC1α, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i.e., thermoneutral) state. Mice lacking ERRγ in adipose tissue (ERRγKO mice) display marked downregulation of BAT-selective genes that leads to a pronounced whitening of BAT. Consistent with the transcriptional changes, the thermogenic capacity of ERRγKO mice is severely blunted, such that they fail to survive an acute cold challenge. These findings reveal a role for ERRγ as a critical thermoneutral maintenance factor required to prime BAT for thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Metabolismo Energético/genética , Receptores de Estrogênio/metabolismo , Termogênese/genética , Animais , Camundongos
7.
Cell Metab ; 26(1): 157-170.e7, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28683283

RESUMO

Numerous studies indicate an inflammatory link between obesity and type 2 diabetes. The inflammatory kinases IKKɛ and TBK1 are elevated in obesity; their inhibition in obese mice reduces weight, insulin resistance, fatty liver and inflammation. Here we studied amlexanox, an inhibitor of IKKɛ and TBK1, in a proof-of-concept randomized, double-blind, placebo-controlled study of 42 obese patients with type 2 diabetes and nonalcoholic fatty liver disease. Treatment of patients with amlexanox produced a statistically significant reduction in Hemoglobin A1c and fructosamine. Interestingly, a subset of drug responders also exhibited improvements in insulin sensitivity and hepatic steatosis. This subgroup was characterized by a distinct inflammatory gene expression signature from biopsied subcutaneous fat at baseline. They also exhibited a unique pattern of gene expression changes in response to amlexanox, consistent with increased energy expenditure. Together, these data suggest that dual-specificity inhibitors of IKKɛ and TBK1 may be effective therapies for metabolic disease in an identifiable subset of patients.


Assuntos
Aminopiridinas/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quinase I-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
8.
Asian Pac J Cancer Prev ; 17(3): 1277-84, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27039760

RESUMO

BACKGROUND: Early detection is a critical part of reducing the burden of breast cancer and breast selfexamination (BSE) has been found to be an especially important early detection strategy in low and middle income countries such as Malaysia. Although reports indicate that Malaysian women report an increase in BSE activity in recent years, additional research is needed to explore factors that may help to increase this behavior among Southeastern Asian women. OBJECTIVE: This study is the first of its kind to explore how the predicting variables of self-efficacy, perceived barriers, and body image factors correlate with self-reports of past BSE, and intention to conduct future breast self-exams among female students in Malaysia. MATERIALS AND METHODS: Through the analysis of data collected from a prior study of female students from nine Malaysian universities (n=842), this study found that self-efficacy, perceived barriers and specific body image sub-constructs (MBSRQ-Appearance Scales) were correlated with, and at times predicted, both the likelihood of past BSE and the intention to conduct breast self-exams in the future. RESULTS: Self-efficacy (SE) positively predicted the likelihood of past self-exam behavior, and intention to conduct future breast self-exams. Perceived barriers (BR) negatively predicted past behavior and future intention of breast self-exams. The body image sub-constructs of appearance evaluation (AE) and overweight preoccupation (OWP) predicted the likelihood of past behavior but did not predict intention for future behavior. Appearance orientation (AO) had a somewhat opposite effect: AO did not correlate with or predict past behavior but did correlate with intention to conduct breast self-exams in the future. The body image sub-constructs of body area satisfaction (BASS) and self-classified weight (SCW) showed no correlation with the subjects' past breast self-exam behavior nor with their intention to conduct breast self-exams in the future. CONCLUSIONS: Findings from this study indicate that both self-efficacy and perceived barriers to BSE are significant psychosocial factors that influence BSE behavior. These results suggest that health promotion interventions that help enhance self-efficacy and reduce perceived barriers have the potential to increase the intentions of Malaysian women to perform breast self-exams, which can promote early detection of breast cancers. Future research should evaluate targeted communication interventions for addressing self-efficacy and perceived barriers to breast self-exams with at-risk Malaysian women. and further explore the relationship between BSE and body image.


Assuntos
Imagem Corporal , Neoplasias da Mama/diagnóstico , Autoexame de Mama/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Autoeficácia , Estudantes/psicologia , Adolescente , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Autoexame de Mama/psicologia , Detecção Precoce de Câncer/psicologia , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Malásia/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Adulto Jovem
9.
Cell Metab ; 23(4): 622-34, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27076077

RESUMO

Pancreatic ß cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal ß cells. Postnatal induction of ERRγ drives a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. Mice deficient in ß cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived ß-like cells enables glucose-responsive secretion of human insulin in vitro, obviating in vivo maturation to achieve functionality. Moreover, these cells rapidly rescue diabetes when transplanted into ß cell-deficient mice. These results identify a key role for ERRγ in ß cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human ß cell therapeutics.


Assuntos
Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Diabetes Mellitus Experimental/terapia , Células Endoteliais da Veia Umbilical Humana , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/transplante , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Mitocôndrias/metabolismo , Receptores de Estrogênio/genética , Regulação para Cima
10.
Glob J Health Sci ; 8(1): 277-85, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26234996

RESUMO

BACKGROUND: Despite continuous argument about the efficacy of breast self-examination; it still could be a life-saving technique through inspiring and empowering women to take better control over their body/breast and health. This study investigated Malaysian female university students' knowledge about breast cancer risk factors, signs, and symptoms and assessed breast self-examination frequency among students. METHOD: A cross-sectional survey was conducted in 2013 in nine public and private universities in the Klang Valley and Selangor. 842 female students were respondents for the self-administered survey technique. Simple descriptive and inferential statistics were employed for data analysis. RESULTS: The uptake of breast self-examination (BSE) was less than 50% among the students. Most of students had insufficient knowledge on several breast cancer risk factors. CONCLUSION: Actions and efforts should be done to increase knowledge of breast cancer through the development of ethnically and traditionally sensitive educational training on BSE and breast cancer literacy.


Assuntos
Neoplasias da Mama/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Estudantes/psicologia , Adolescente , Adulto , Autoexame de Mama/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Malásia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Universidades
11.
Biochem Biophys Res Commun ; 461(4): 630-5, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-25918019

RESUMO

Preadipocyte factor-1 (Pref-1) is made as a transmembrane protein containing EGF-repeats at the extracellular domain that can be cleaved to generate a biologically active soluble form. Pref-1 is found in islet ß-cells and its level has been reported to increase in neonatal rat islets upon growth hormone treatment. We found here that Pref-1 can promote growth of pancreatic tumor derived AR42J cells. To examine Pref-1 function in pancreatic islets in vivo, we generated transgenic mouse lines overexpressing the Pref-1/hFc in islet ß-cells using rat insulin II promoter (RIP). These transgenic mice exhibit an increase in islet mass with higher proportion of larger islets in pancreas compared to wild-type littermates. This is in contrast to pancreas from Pref-1 null mice that show higher proportion of smaller islets. Insulin expression and insulin secretion from pancreatic islets from RIP-Pref-1/hFc transgenic mice are increased also. Thus, RIP-Pref-1/hFc transgenic mice show normal glucose levels but with higher plasma insulin levels in both fasting and fed conditions. These mice show improved glucose tolerance. Taken together, we conclude Pref-1 as a positive regulator of islet ß-cells and insulin production.


Assuntos
Proliferação de Células , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Insulina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Feminino , Resistência à Insulina , Secreção de Insulina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regulação para Cima
13.
Nat Commun ; 6: 6047, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25581158

RESUMO

The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-ε and TBK1 with amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the phosphorylation of hepatic Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving glucose handling in obese mice. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue-liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for type 2 diabetes.


Assuntos
Gluconeogênese , Fígado/metabolismo , Transdução de Sinais , Gordura Subcutânea/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Idoso , Aminopiridinas/farmacologia , Animais , AMP Cíclico/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Gluconeogênese/efeitos dos fármacos , Glucose-6-Fosfatase/metabolismo , Humanos , Inflamação/patologia , Resistência à Insulina , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptores Adrenérgicos beta/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Gordura Subcutânea/efeitos dos fármacos , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Asian Pac J Cancer Prev ; 15(21): 9499-503, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25422246

RESUMO

This study aimed to examine the relationship between body image satisfaction and breast self-screening behavior and intentions. The sample for this cross-sectional study consisted of 842 female university students who were recruited from a number of public and private universities. Data were obtained between the months of November and December, 2013, using multistage random cluster sampling. Main research variables were breast cancer screening behavior and intentions, demographic factors, and the total scores on each of the Multidimensional Body-Self Relations Questionnaire (MBSRQ-Appearance Scales) subscales. Results of multivariate analysis showed that having higher satisfaction and more positive evaluation of appearance were related to having performed breast self-examination more frequently in the last year and intending to perform breast self-examination more frequently in the next year. Longitudinal research can potentially provide detailed information about overall body image satisfaction and breast cancer screening behavior among various communities.


Assuntos
Imagem Corporal/psicologia , Neoplasias da Mama/diagnóstico , Autoexame de Mama/psicologia , Detecção Precoce de Câncer/psicologia , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Autoexame de Mama/métodos , Estudos Transversais/métodos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Intenção , Malásia , Pessoa de Meia-Idade , Estudantes/psicologia , Inquéritos e Questionários , Universidades , Adulto Jovem
15.
Nature ; 513(7518): 436-9, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25043058

RESUMO

Fibroblast growth factor 1 (FGF1) is an autocrine/paracrine regulator whose binding to heparan sulphate proteoglycans effectively precludes its circulation. Although FGF1 is known as a mitogenic factor, FGF1 knockout mice develop insulin resistance when stressed by a high-fat diet, suggesting a potential role in nutrient homeostasis. Here we show that parenteral delivery of a single dose of recombinant FGF1 (rFGF1) results in potent, insulin-dependent lowering of glucose levels in diabetic mice that is dose-dependent but does not lead to hypoglycaemia. Chronic pharmacological treatment with rFGF1 increases insulin-dependent glucose uptake in skeletal muscle and suppresses the hepatic production of glucose to achieve whole-body insulin sensitization. The sustained glucose lowering and insulin sensitization attributed to rFGF1 are not accompanied by the side effects of weight gain, liver steatosis and bone loss associated with current insulin-sensitizing therapies. We also show that the glucose-lowering activity of FGF1 can be dissociated from its mitogenic activity and is mediated predominantly via FGF receptor 1 signalling. Thus we have uncovered an unexpected, neomorphic insulin-sensitizing action for exogenous non-mitogenic human FGF1 with therapeutic potential for the treatment of insulin resistance and type 2 diabetes.


Assuntos
Fator 1 de Crescimento de Fibroblastos/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Fator 1 de Crescimento de Fibroblastos/efeitos adversos , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Mitógenos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo
16.
Asian Pac J Cancer Prev ; 15(12): 5097-105, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24998591

RESUMO

Knowledge of health and community psychology in health professionals influences psychosocial and community determinants of health and promoting participation in disease prevention at the community level. This paper appraises the potential of knowledge on psychology in health care professionals and its contribution to community empowerment through individual behavior change and health practice. The authors proposed a schematic model for the use of psychological knowledge in health professionals to promote participation in health interventions/disease prevention programs in developing countries. By implication, the paper provides a vision on policies towards supporting breast cancer secondary prevention efforts for community health development in Asian countries.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias da Mama/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Necessidades e Demandas de Serviços de Saúde , Padrões de Prática Médica , Psicologia/educação , Serviços de Saúde Comunitária/legislação & jurisprudência , Atenção à Saúde , Feminino , Humanos , Prognóstico
17.
Glob J Health Sci ; 6(3): 165-74, 2014 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-24762359

RESUMO

PURPOSE: This paper presents the findings of a cross-sectional survey on the risk and protective factors of premarital sexual behavior among rural female adolescents in Peninsular Malaysia. METHODS: We investigated data on 770 female respondents aged 13-17 years in rural areas to identify predictive factors for premarital sexual intercourse. Data were analyzed using bivariate and multivariate regression. Specific socio-demographic factors, psychological and family domains, peer delinquency, and knowledge and attitudes about sexuality were considered in risky sexual behaviors in rural Malay girls. The effects of other covariates for premarital sexual intercourse were controlled by logistic regression model. RESULTS: Of the 770 rural female students, about 3.2% of respondents reported experience of sexual intercourse in the past three months. Out of those sexually active girls, 36% were 17 years old and 20% stated having sexual intercourse with more than one partner, and 72% did not use contraception during the most recent sexual intercourse. Midnight activities, peer-sexual disorder, self-evaluation, and attitude toward sexual health were significant predictors of sexual intercourse in rural girls in Malaysia. CONCLUSION: The finding highlights the impact of psychological factors and peer group influences on the challenges of premarital sexual behavior among rural girls and the notion of school-based sexual health education for adolescents. This study triggers other researchers take into account a comprehensive view of protective factors operating in adolescents' risky sexual behaviors in Asian culture seeing that family domain variables, unexpectedly, exerted no predicting influence on sexually active female teens in rural areas in Malaysia.


Assuntos
Comportamento do Adolescente , Assunção de Riscos , Comportamento Sexual/estatística & dados numéricos , Adolescente , Anticoncepção/psicologia , Anticoncepção/estatística & dados numéricos , Estudos Transversais , Depressão/epidemiologia , Relações Familiares , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estilo de Vida , Malásia/epidemiologia , Fatores de Risco , População Rural , Fatores Socioeconômicos
18.
Diabetologia ; 57(5): 860-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24619218

RESUMO

The ability to adapt to cycles of feast and famine is critical for survival. Communication between multiple metabolic organs must be integrated to properly metabolise nutrients. By controlling networks of genes in major metabolic organs, nuclear hormone receptors (NHRs) play central roles in regulating metabolism in a tissue-specific manner. NHRs also establish daily rhythmicity by controlling the expression of core clock genes both centrally and peripherally. Recent findings show that many of the metabolic effects of NHRs are mediated through certain members of the fibroblast growth factor (FGF) family. This review focuses on the roles of NHRs in critical metabolic organs, including adipose tissue, liver and muscle, during the fed and fasted states, as well as their roles in circadian metabolism and downstream regulation of FGFs.


Assuntos
Receptores Citoplasmáticos e Nucleares/fisiologia , Tecido Adiposo/metabolismo , Animais , Ritmo Circadiano , Jejum , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose/metabolismo , Homeostase , Humanos , Ligantes , Fígado/metabolismo , Modelos Biológicos , Músculos/metabolismo , Tiazolidinedionas/química
19.
Cell Metab ; 18(6): 883-95, 2013 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-24268737

RESUMO

Excessive caloric intake leading to obesity is associated with insulin resistance and dysfunction of islet ß cells. High-fat feeding decreases desnutrin (also called ATGL/PNPLA2) levels in islets. Here we show that desnutrin ablation via RIP-Cre (ßKO) or RIP-CreER results in hyperglycemia with impaired glucose-stimulated insulin secretion (GSIS). Due to decreased lipolysis, islets have higher TAG content but lower free FA levels. ßKO islets exhibit impaired mitochondrial respiration and lower production of ATP required for GSIS, along with decreased expression of PPARδ target genes involved in mitochondrial oxidation. Furthermore, synthetic PPARδ, but not PPARα, agonist restores GSIS and expression of mitochondrial oxidative genes in ßKO mice, revealing that desnutrin-catalyzed lipolysis generates PPARδ ligands. Finally, adenoviral expression of desnutrin in ßKO islets restores all defects of ßKO islet phenotype and function, including GSIS and mitochondrial defects, demonstrating the critical role of the desnutrin-PPARδ-mitochondrial oxidation axis in regulating islet ß cell GSIS.


Assuntos
Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Lipase/metabolismo , Mitocôndrias/metabolismo , PPAR delta/metabolismo , Animais , Glicemia/análise , Células Cultivadas , Dieta Hiperlipídica , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Glucose/farmacologia , Intolerância à Glucose , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Lipase/antagonistas & inibidores , Lipase/genética , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR delta/agonistas , PPAR delta/genética , RNA Mensageiro/metabolismo , Tiazóis/farmacologia
20.
Asian Pac J Cancer Prev ; 14(7): 4005-13, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991945

RESUMO

BACKGROUND: Although breast cancer is a major public health worry among Asian women, adherence to screening for the disease remains an obstacle to its prevention. A variety of psycho-social and cultural factors predispose women to delay or avoidance of screening for breast cancer symptoms at the early stages when cure is most likely to be successful. Yet few interventions implemented to date to address this condition in this region have drawn on health behavior theory. MATERIALS AND METHODS: This paper reviews the existing literature on several cognitive theories and models associated with breast cancer screening, with an emphasis on the work that has been done in relation to Asian women. To conduct this review, a number of electronic databases were searched with context-appropriate inclusion criteria. RESULTS: Little empirical work was found that specifically addressed the applicability of health theories in promoting adherence to the current breast cancer prevention programs Among Asian women. However, a few studies were found that addressed individual cognitive factors that are likely to encourage women's motivation to protect themselves against breast cancer in this region of the world. The findings suggest that multi-level, socio-cultural interventions that focus on cognitive factors have much promise with this issue. CONCLUSIONS: Interventions are needed that effectively and efficiently target the personal motivation of at-risk Asian women to seek out and engage in breast cancer prevention. Concerning implications, personal motivation to seek out and engage in individual preventive actions for breast cancer prevention among Asian women is a timely, high priority target with practical implications for community development and health promotion. Further studies using qualitative, anthropologic approaches shaped for implementation in multi-ethnic Asian settings are needed to inform and guide these interventions.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/psicologia , Comportamentos Relacionados com a Saúde , Ásia , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/psicologia , Feminino , Humanos , Motivação
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