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1.
Int J Obes (Lond) ; 48(4): 584-593, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38219005

RESUMO

OBJECTIVES: We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. METHODS: In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina's MethylationEPIC BeadChip. In women with European (n = 303) and South Asian (n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) (n = 877, mainly European/Norwegian). RESULTS: We identified one CpG site significantly associated with GWG (p 5.8 × 10-8) and five CpG sites associated with BMI at gestational week 28 (p from 4.0 × 10-8 to 2.1 × 10-10). Of these, we were able to replicate three in MoBa-START; cg02786370, cg19758958 and cg10472537. Two sites are located in genes previously associated with blood pressure and BMI. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG (p from 1.2 × 10-8 to 0.04). CONCLUSIONS: We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. Three of the sites were replicated in an independent cohort. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. The identified CpG sites were associated with cardiometabolic traits. GOV REGISTRATION NO: Not applicable.


Assuntos
Doenças Cardiovasculares , Ganho de Peso na Gestação , Feminino , Humanos , Gravidez , Índice de Massa Corporal , Doenças Cardiovasculares/genética , Estudos de Coortes , Metilação de DNA/genética , Epigênese Genética/genética , Epigenoma , População Europeia , Estudo de Associação Genômica Ampla , Ganho de Peso na Gestação/genética , Leucócitos , População do Sul da Ásia , Metanálise como Assunto
2.
J Intern Med ; 285(1): 40-48, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30403316

RESUMO

The Precision Medicine Initiative defines precision medicine as 'an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person'. This approach will facilitate more accurate treatment and prevention strategies in contrast to a one-size-fits-all approach, in which disease treatment and prevention strategies are developed for generalized usage. Diabetes is clearly more heterogeneous than the conventional subclassification into type 1 and type 2 diabetes. Monogenic forms of diabetes like MODY and neonatal diabetes have paved the way for precision medicine in diabetes, as carriers of unique mutations require unique treatment. Diagnosis of diabetes in the past has been dependent upon measuring one metabolite, glucose. By instead including six variables in a clustering analysis, we could break down diabetes into five distinct subgroups, with better prediction of disease progression and outcome. The severe insulin-resistant diabetes (SIRD) cluster showed the highest risk of kidney disease and highest prevalence of nonalcoholic fatty liver disease, whereas patients in the insulin-deficient cluster 2 (SIDD) had the highest risk of retinopathy. In the future, this will certainly be improved and expanded by including genetic, epigenetic and other biomarker to allow better prediction of outcome and choice of more precise treatment.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Medicina de Precisão , Biomarcadores , Progressão da Doença , Humanos , Estilo de Vida
3.
J Intern Med ; 286(2): 192-206, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30919529

RESUMO

OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia. METHODS: Eighty-five GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N = 398, Finnish) and STORK/STORK-G (N = 780, Norwegian). RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women, was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased GDM risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations. CONCLUSIONS: Gestational diabetes mellitus is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences.


Assuntos
Criptocromos/genética , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/genética , Proteínas de Grupo de Alta Mobilidade/genética , Adulto , Alelos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Índia/epidemiologia , Resistência à Insulina , Fenótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Prevalência , Países Escandinavos e Nórdicos/epidemiologia
4.
Diabet Med ; 34(10): 1477-1482, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28731584

RESUMO

AIM: The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian population from Punjab. METHODS: Insulin secretion (HOMA2-B) and insulin action (HOMA2-IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria. RESULTS: Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance. CONCLUSIONS: Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action.


Assuntos
Insulina/metabolismo , Insulina/fisiologia , Gravidez/metabolismo , Adulto , Povo Asiático , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Índia/epidemiologia , Resistência à Insulina , Secreção de Insulina , Fatores de Risco , Adulto Jovem
5.
Bioorg Med Chem Lett ; 27(15): 3370-3373, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28615134

RESUMO

In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a-4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a-4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a-8j and 9a-9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c-9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a-8j exhibited toxicity.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Tioglicosídeos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tioglicosídeos/síntese química , Tioglicosídeos/química
6.
Bioorg Med Chem Lett ; 26(1): 209-12, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26586599

RESUMO

Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8µM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50=15.3-22.4µM) against the four cell lines tested.


Assuntos
Aminoácidos/química , Aminoácidos/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Ácidos Oleicos/química , Ácidos Oleicos/farmacologia , Aminoácidos/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácidos Oleicos/síntese química , Relação Estrutura-Atividade , Tioglicolatos/química
7.
Bioorg Med Chem Lett ; 26(2): 613-617, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26646219

RESUMO

A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60°C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride to form the corresponding amine. The synthesized derivatives were further subjected to biological evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3, MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was observed that the carboxylated quinolone derivatives with hexanoic (8a), octanoic (8b), lauric (8d) and myristic (8e) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a) exhibited promising activity against both bacterial and fungal strains and significant antibacterial activity was observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9µg/mL). The compound 8a also showed excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with MIC values of 2.1 and 4.6µg/mL, respectively.


Assuntos
4-Quinolonas/química , Anti-Infecciosos/química , Antineoplásicos/química , Antioxidantes/química , 4-Quinolonas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Linhagem Celular Tumoral , Fungos/efeitos dos fármacos , Halogenação , Humanos , Micoses/tratamento farmacológico , Neoplasias/tratamento farmacológico
8.
Bioorg Med Chem Lett ; 26(21): 5198-5202, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27707604

RESUMO

A series of novel ricinoleic acid based lipoamino acid derivatives were synthesized from (Z)-methyl-12-aminooctadec-9-enoate and different l-amino acids (glycine, alanine, phenyl alanine, valine, leucine, isoleucine, proline and tryptophan). The structures of all the prepared compounds were characterized by 1H NMR, 13C NMR and mass spectral studies. The title compounds were evaluated for their antimicrobial and anti-biofilm activities. Among all the derivatives, compound 7a (Z)-methyl-12-(2-aminoacetamido)octadec-9-enoate exhibited promising antibacterial activity (MIC, 3.9-7.8µg/mL) and compounds 7b (Z)-methyl 12-(2-aminopropanamido)octadec-9-enoate and 7g (Z)-methyl-12-(pyrrolidine-2-carboxamido)octadec-9-enoate exhibited moderate activity (MIC, 7.8-31.2µg/mL) selectively against four different Gram-positive bacterial strains such as Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, S. aureus MLS-16 MTCC 2940, Micrococcus luteus MTCC 2470. These compounds also exhibited excellent antifungal activity against studied fungal strains. Further, the compounds 7a, 7b and 7g were also screened for anti-biofilm activity. Among these lipoamino acid derivatives, compound 7a exhibited good anti-biofilm activity (IC50, 1.9-4.1µg/mL) against four Gram-positive bacterial strains.


Assuntos
Aminoácidos/química , Antibacterianos/farmacologia , Ácidos Ricinoleicos/síntese química , Ácidos Ricinoleicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Ácidos Ricinoleicos/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
9.
J Food Sci Technol ; 52(8): 4905-14, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26243910

RESUMO

Lipase catalyzed interesterification of rice bran oil (RBO) with hydrogenated cottonseed oil (HCSO) was carried out for producing a low trans free fat. The interesterification reaction was performed by varying parameters such as weight proportions of RBO and HCSO, reaction temperatures, time period and lipase concentration. Both non specific and specific lipases namely Novozym 435 and Lipozyme TL IM were employed for this study. Based on the data generated, the optimum reaction conditions were found to be: weight proportion of RBO and HCSO, 80:20; lipase concentration, 5 % (w/w) of substrates; reaction temperature, 60 °C; reaction time, 4 h for Lipozyme TL IM and 5 h for Novozym 435. The degree of interesterification, calculated based on the results of solid fat characteristics was used for comparing the catalytic activity of Novozym 435 and Lipozyme TL IM. It was observed that the degree of interesterification (DI) reached a near 100 % at the 4th hour for reaction employing Lipozyme TL IM with a rate constant of 0.191 h(-1) while Novozym 435 catalyzed reaction reached a near 100 % degree of interesterification at the 5th hour with a rate constant of 0.187 h(-1), suggesting that Lipozyme TL IM has a faster catalytic activity.

10.
Bioorg Med Chem Lett ; 24(22): 5224-7, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25304897

RESUMO

A novel library of Schiff base analogues (5a-q) were synthesized by the condensation of methyl-12-aminooctadec-9-enoate and different substituted aromatic aldehydes. The synthesized compounds were thoroughly characterized by spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, ESI-MS and HRMS). The Schiff base analogues with different substitutions were screened for in vitro antibacterial activity against 7 different bacterial strains. Among these, the compounds with electron withdrawing substituent, namely chlorine (5a) and electron donating substituents, namely hydroxy (5 n) and methoxy (5 o), were found to exhibit excellent to good antimicrobial activities (MIC value 9-18 µM) against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS-16 MTCC 2940 and Bacillus subtilis MTCC 121. The products were also screened for anti-biofilm and MBC (Minimum Bactericidal Concentration) activities which exhibited promising activities.


Assuntos
Antibacterianos/síntese química , Bacillus subtilis/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Extratos Vegetais/síntese química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bacillus subtilis/fisiologia , Biofilmes/crescimento & desenvolvimento , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ricinus , Bases de Schiff/síntese química , Bases de Schiff/isolamento & purificação , Bases de Schiff/farmacologia , Staphylococcus aureus/fisiologia
11.
Lett Appl Microbiol ; 57(4): 295-302, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23725061

RESUMO

UNLABELLED: Hypnea musciformis red seaweed is popularly known to produce carrageenan was collected from the Gulf of Mannar, India. Strain HMGM-7 [MTCC 11712] was isolated from the surface of this seaweed, which was capable of producing an extracellular black-coloured polymeric pigment. Based on phenotypic characterization and 16S rDNA sequencing, the strain HMGM-7 was identified as Pseudomonas stutzeri. Biophysical characterization by UV-visible, FT-IR, EPR and XRD spectroscopic studies confirmed the pigment as melanin. Further chemical characterization showed that it was acid-resistant, alkali-soluble and alkali-insoluble in most of the organic solvents and distilled water. To our knowledge, this is a first report on a marine Pseudomonas stutzeri strain producing significant amounts of melanin of about 6·7 g l(-1) without L-tyrosine supplementation in the sea-water production medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This investigation reports a marine Pseudomonas stutzeri strain HMGM-7 [MTCC 11712] that produces significant quantities of melanin (6·7 g l(-1) ) in sea-water medium without the supplementation of L-tyrosine. The confirmation of the produced melanin was carried out by various chemical and physical characterization studies. The isolated melanin may find potential application for use in cosmetic and/or pharmaceutical industries.


Assuntos
Melaninas/biossíntese , Pseudomonas stutzeri/isolamento & purificação , Pseudomonas stutzeri/metabolismo , Alga Marinha/microbiologia , Linhagem Celular Tumoral , Humanos , Índia , Melaninas/química , Pseudomonas stutzeri/genética , Água do Mar/microbiologia , Espectroscopia de Infravermelho com Transformada de Fourier , Tirosina/metabolismo
12.
Bioorg Med Chem Lett ; 22(14): 4678-80, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22704888

RESUMO

We report the total synthesis of (2S,3R)-2-aminododecan-3-ol has been achieved starting from commercially available 10-undecenoic acid. The key steps involved are Sharpless asymmetric epoxidation, Miyashita's boron-directed C-2 regioselective azidolysis, generated the asymmetric centers and in situ detosylation and reduction of azido tosylate. The antifungal activity of the synthesized (2S,3R)-2-aminododecan-3-ol was evaluated on several Candida strains and was comparable to miconazole, a standard drug.


Assuntos
Antifúngicos/síntese química , Dodecanol/análogos & derivados , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Dodecanol/síntese química , Dodecanol/farmacologia , Estrutura Molecular
13.
Br Poult Sci ; 52(6): 769-74, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22221243

RESUMO

1. Rice bran lysolecithin (RBL) was evaluated in broiler chicken diets. In the first experiment, RBL was included in diet at 0, 0·5, 2, 8 and 32 g/kg and fed to 250 broiler chickens from 0 to 42 d of age. In the second experiment, RBL was fed at 0, 25 and 50 g/kg diet to 405 day-old broiler chickens until 21 d of age, while during the finisher phase (22-35 d of age) chickens receiving each concentration of RBL were given all three concentrations of RBL in a 3 × 3 factorial manner. The diets were isocaloric. 2. Body weight, food consumption and food conversion efficiency were unaffected by feeding RBL, while the weight of pancreas increased at ≥2 g/kg of RBL in diet (experiment 1). In experiment 2, body weight was greater in the chickens receiving RBL at either 25 or 50 g/kg (21 d) and 50 g/kg (35 d of age). At 21 d of age, food consumption was greater at 25 or 50 g RBL/kg diet, while food conversion efficiency improved with 50 g RBL/kg diet. 3. Fat digestibility increased with RBL at 32 g/kg (experiment 1) and ≤25 g/kg (experiment 2). Rice bran lysolecithin increased ready to cook weight at 50 g/kg during starter phase and decreased abdominal fat at 25 and 50 g/kg during finisher phase (experiment 2). Liver and meat fat content were not affected. 4. It is concluded that lysolecithin from rice bran oil could be used as energy supplement in broiler chicken diet.


Assuntos
Galinhas/metabolismo , Lisofosfatidilcolinas/administração & dosagem , Carne/normas , Óleos de Plantas/administração & dosagem , Tecido Adiposo/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal/fisiologia , Ingestão de Energia/fisiologia , Feminino , Fígado/metabolismo , Masculino , Tamanho do Órgão/fisiologia , Distribuição Aleatória , Óleo de Farelo de Arroz
14.
Mol Cell Endocrinol ; 521: 111107, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33309639

RESUMO

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3ß-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica/genética , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Imunoprecipitação da Cromatina , Citoplasma/genética , Citoplasma/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Imuno-Histoquímica , Insulina/genética , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Análise de Célula Única , Fatores de Transcrição/genética
15.
Mol Cell Endocrinol ; 511: 110835, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32371087

RESUMO

It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Grelina/sangue , Grelina/farmacologia , Secreção de Insulina , Ilhotas Pancreáticas/patologia , Contagem de Células , Jejum/sangue , Glucose/metabolismo , Humanos , Secreção de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Fenótipo , RNA-Seq , Doadores de Tecidos
16.
Food Chem ; 248: 210-216, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29329846

RESUMO

An enzymatic process was developed for the preparation of a nutritionally enriched 1,3-diacylglycerol(DAG)-rich oil from a blend of refined sunflower and rice bran oils. The process involves hydrolysis of vegetable oil blend using Candida cylindracea followed by esterification with glycerol using Lipozyme RM1M. The resultant DAG-rich oil contains 84% of DAG (66% of 1,3-DAG, 18% of 1,2-DAG) and 16% of triacylglycerol (TAG) along with micro nutrients like γ-oryzanol, tocotrienols, tocopherols and phytosterols. Nutritional studies of the DAG-rich oil were conducted in Wistar rats and compared with sunflower oil (SFO). The calorific value of the DAG-rich oil was estimated to be 6.45 Kcals/g as against 9.25 Kcals/g for SFO. The serum and liver cholesterol and TAG levels in rats fed with 1,3-DAG-rich oil were found to be significantly reduced as compared to rats fed diet containing SFO. We conclude that 1,3-DAG-rich oil is a low calorie fat and exhibits hypolipidemic effects.


Assuntos
Diglicerídeos/química , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Óleo de Farelo de Arroz/química , Óleo de Girassol/química , Animais , Restrição Calórica , Candida , Colesterol/sangue , Colesterol/metabolismo , Esterificação , Lipase/química , Lipase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fitosteróis/análise , Ratos , Ratos Wistar , Tocoferóis/análise , Triglicerídeos/análise , Triglicerídeos/metabolismo
17.
Bioresour Technol ; 98(6): 1260-4, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16822671

RESUMO

Ethyl acetate was explored as an acyl acceptor for immobilized lipase-catalyzed preparation of biodiesel from the crude oils of Jatropha curcas (jatropha), Pongamia pinnata (karanj) and Helianthus annuus (sunflower). The optimum reaction conditions for interesterification of the oils with ethyl acetate were 10% of Novozym-435 (immobilized Candida antarctica lipase B) based on oil weight, ethyl acetate to oil molar ratio of 11:1 and the reaction period of 12h at 50 degrees C. The maximum yield of ethyl esters was 91.3%, 90% and 92.7% with crude jatropha, karanj and sunflower oils, respectively under the above optimum conditions. Reusability of the lipase over repeated cycles in interesterification and ethanolysis was also investigated under standard reaction conditions. The relative activity of lipase could be well maintained over twelve repeated cycles with ethyl acetate while it reached to zero by 6th cycle when ethanol was used as an acyl acceptor.


Assuntos
Acetatos/química , Lipase/química , Óleos de Plantas/química , Candida/enzimologia , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Esterificação , Cromatografia Gasosa-Espectrometria de Massas
18.
Food Chem ; 221: 664-672, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27979256

RESUMO

Novel phenoylated phosphatidylcholines were synthesized from 1,2-dipalmitoyl phosphatidylcholine/egg 1,2-diacyl phosphatidylcholine and phenolic acids such as ferulic, sinapic, vanillic and syringic acids. The structures of phenoylated phosphatidylcholines were confirmed by spectral analysis. 2-acyl-1-lyso phosphatidylcholine was synthesized from phosphatidylcholine via regioselective enzymatic hydrolysis and was reacted with hydroxyl protected phenolic acids to produce corresponding phenoylated phosphatidylcholines in 48-56% yields. Deprotection of protected phenoylated phosphatidylcholines resulted in phenoylated phosphatidylcholines in 87-94% yields. The prepared compounds were evaluated for their preliminary in vitro antimicrobial and antioxidant activities. Among the active derivatives, compound 1-(4-hydroxy-3,5-dimethoxy) cinnamoyl-2-acyl-sn-glycero-3-phosphocholine exhibited excellent antioxidant activity with EC50 value of 16.43µg/mL. Compounds 1-(4-hydroxy-3-methoxy) cinnamoyl-2-acyl-sn-glycero-3-phosphocholine and 1-(4-hydroxy-3,5-dimethoxy) cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine exhibited good antioxidant activity with EC50 values of 36.05 and 33.35µg/mL respectively. Compound 1-(4-hydroxy-3-methoxy) cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine exhibited good antibacterial activity against Klebsiella planticola with MIC of 15.6µg/mL and compound 1-(4-hydroxy-3-methoxy) benzoyl-2-acyl-sn-glycero-3-phosphocholine exhibited good antifungal activity against Candida albicans with MIC of 15.6µg/mL.


Assuntos
Anti-Infecciosos/uso terapêutico , Antioxidantes/uso terapêutico , Hidroxibenzoatos/química , Hidroxibenzoatos/síntese química , Fosfatidilcolinas/química , Fosfatidilcolinas/síntese química
19.
Colloids Surf B Biointerfaces ; 152: 133-142, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28103530

RESUMO

Development of safe non-viral carrier systems for efficient intra-cellular delivery of drugs and genes hold promise in the area of translational research. Liposome based delivery systems have emerged as one of the attractive strategies for efficient delivery of drugs and nucleic acids. To this end, number of investigations was carried on liposomal formulations using lipids for achieving higher efficiency in transfection with lower cytotoxicities. In our efforts to develop safer and efficient liposomal delivery systems, we synthesized a novel anti-oxidant lipid, α-lipoyl, oleyl-sn-phosphatidylcholine (LOPC) and used as a helper lipid in combination with a cationic amphiphile, Di-Stearyl Dihydroxy Ethyl Ammonium Chloride (DSDEAC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at varying concentrations of LOPC. DNA binding properties of the liposomal formulations (DS, DS LA1, DS LA2 and DS LA3) revealed that increasing the percentage of single aliphatic chain lipid LOPC, did not affect the DNA binding properties. But, transfection profiles of these liposomal formulations in 3 different cell lines (HeLa, HEK 293 and MCF7) showed difference in their efficacies. Results showed that optimal percentage of LOPC i.e. 25% in DSDEAC and DOPC at 1:1 molar ratio (DS LA1) enhanced transfection as compared to DSDEAC:DOPC alone. The endosomal escape studies with NBD labelled lysotracker and Rhodamine labelled liposomal formulations revealed that DS LA1 and DS LA2 facilitated the release of genetic cargo with a better efficiency than their counter parts. Reactive Oxygen Species (ROS), a key modulator of necroptosis were lowered with the treatment of DS LA1 than other liposomal formulations. Here in, we present a novel liposomal formulation using DSDEAC and DOPC at 1:1 molar ratio doped with 25-50% (mole ratio) LOPC as an efficient delivery system for enhanced transfection with quenching of ROS levels compared to formulations without LOPC.


Assuntos
Antioxidantes/química , Lipossomos/química , Fosfatidilcolinas/química , Ácido Tióctico/química , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Transfecção
20.
J Oleo Sci ; 65(12): 1023-1031, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27829607

RESUMO

A series of novel fatty substituted 4-methyl-2H-chromen-2-one (coumarins) were synthesized by employing cross metathesis, a key step in the synthesis. The antioxidant activities of the title compounds were compared with the commercial antioxidants, namely butylated hydroxy toluene (BHT) and α-tocopherol, glycosidic and other substituted 4-methyl-2H-chromen-2-ones. Among the different 4-methyl-2H-chromen-2-ones, the glycosidic substituted 4-methyl-2H-chromen-2-ones was excellent, while those with aliphatic fatty acid chain and hydroxyl substitutents were good. Among the substituted 4-methyl-2H-chromen-2-ones, glycosidic, hydroxyl and cyano containing 4-methyl-2H-chromen-2-ones exhibited good, while fatty substituted exhibited moderate anticancer activities against the four different cancer cell lines tested, namely DU145 (Prostate carcinoma cancer cell), HepG2 (Hepato cellular carcinoma cancer cell), SKOV3 (Ovarian cancer cell) and MDA-MB 231 (Human breast cancer cell). The study reveals that these substituted coumarins can be potential candidates in a number of food and pharmaceutical formulations.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
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