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1.
J Biol Chem ; : 101431, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801552

RESUMO

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in ß-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression which might be leveraged to develop more efficacious therapies.

2.
J Biol Chem ; 297(1): 100881, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34144038

RESUMO

GPR17 is a G-protein-coupled receptor (GPCR) implicated in the regulation of glucose metabolism and energy homeostasis. Such evidence is primarily drawn from mouse knockout studies and suggests GPR17 as a potential novel therapeutic target for the treatment of metabolic diseases. However, links between human GPR17 genetic variants, downstream cellular signaling, and metabolic diseases have yet to be reported. Here, we analyzed GPR17 coding sequences from control and disease cohorts consisting of individuals with adverse clinical metabolic deficits including severe insulin resistance, hypercholesterolemia, and obesity. We identified 18 nonsynonymous GPR17 variants, including eight variants that were exclusive to the disease cohort. We characterized the protein expression levels, membrane localization, and downstream signaling profiles of nine GPR17 variants (F43L, V96M, V103M, D105N, A131T, G136S, R248Q, R301H, and G354V). These nine GPR17 variants had similar protein expression and subcellular localization as wild-type GPR17; however, they showed diverse downstream signaling profiles. GPR17-G136S lost the capacity for agonist-mediated cAMP, Ca2+, and ß-arrestin signaling. GPR17-V96M retained cAMP inhibition similar to GPR17-WT, but showed impaired Ca2+ and ß-arrestin signaling. GPR17-D105N displayed impaired cAMP and Ca2+ signaling, but unaffected agonist-stimulated ß-arrestin recruitment. The identification and functional profiling of naturally occurring human GPR17 variants from individuals with metabolic diseases revealed receptor variants with diverse signaling profiles, including differential signaling perturbations that resulted in GPCR signaling bias. Our findings provide a framework for structure-function relationship studies of GPR17 signaling and metabolic disease.


Assuntos
Síndrome Metabólica/genética , Mutação de Sentido Incorreto , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Cálcio/metabolismo , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Transporte Proteico , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/metabolismo
3.
Nutrients ; 12(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003412

RESUMO

High-fat diet (HFD) has been shown to accelerate Alzheimer's disease (AD) pathology, but the exact molecular and cellular mechanisms remain incompletely understood. Moreover, it is unknown whether AD mice are more susceptible to HFD-induced metabolic dysfunctions. To address these questions, we used 5xFAD mice as an Alzheimer's disease model to study the physiological and molecular underpinning between HFD-induced metabolic defects and AD pathology. We systematically profiled the metabolic parameters, the gut microbiome composition, and hippocampal gene expression in 5xFAD and wild type (WT) mice fed normal chow diet and HFD. HFD feeding impaired energy metabolism in male 5xFAD mice, leading to increased locomotor activity, energy expenditure, and food intake. 5xFAD mice on HFD had elevated circulating lipids and worsened glucose intolerance. HFD caused profound changes in gut microbiome compositions, though no difference between genotype was detected. We measured hippocampal mRNAs related to AD neuropathology and neuroinflammation and showed that HFD elevated the expression of apoptotic, microglial, and amyloidogenic genes in 5xFAD mice. Pathway analysis revealed that differentially regulated genes were involved in insulin signaling, cytokine signaling, cellular stress, and neurotransmission. Collectively, our results showed that 5xFAD mice were more susceptible to HFD-induced metabolic dysregulation and suggest that targeting metabolic dysfunctions can ameliorate AD symptoms via effects on insulin signaling and neuroinflammation in the hippocampus.


Assuntos
Doença de Alzheimer/metabolismo , Proteínas Amiloidogênicas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação Neurogênica/metabolismo , Transdução de Sinais/fisiologia , Doença de Alzheimer/etiologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Microbioma Gastrointestinal/genética , Expressão Gênica , Genótipo , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Hipocampo/metabolismo , Inflamação , Insulina/metabolismo , Lipídeos/sangue , Locomoção/fisiologia , Masculino , Camundongos , Microglia/metabolismo , Inflamação Neurogênica/etiologia , RNA Mensageiro/metabolismo , Fatores de Risco , Transmissão Sináptica/genética
4.
Mikrochim Acta ; 187(9): 515, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839875

RESUMO

To early effectively detect amyloid-beta (Aß) oligomers, a label-free reusable aptasensor was designed. This aptasensor based on a luminescent nanoscale lanthanum-based metal-organic framework (L-MOF)-armored single-stranded DNA antibody (MOF-armored-anti-DNA antibody) as signal tags and aptamer bound to magnetic beads (Apt-MB) as capture probe. The reusable aptasensor combines signal tag and capture probe with antigen-antibody interaction. When the reusable aptasensor is formed, the strong fluorescence intensity of L-MOF will "turn off" by photo-induced electron transfer from excited states to an unfilled d shell of iron cations on the nanoparticle surface. Upon the presence of Aß oligomers in serum samples, they can be especially distinguished with the Aß oligomers aptamer in capture probes and then signal tags are released into the solution for developing the fluorescence aptasensor under excitation/emission 365 nm/430 nm. Meanwhile, the aptamer was recovered from the complex of Aß oligomers/Apt-MB by heat treatment. When the temperature returns to room temperature, the recovered aptamer in the capture probe can once again bound to the MOF-armored-anti-DNA antibody for reuse. The label-free reusable aptasensor system detection has high sensitivity and selectivity toward Aß oligomers (LOD = 0.4 pg/mL) and an excellent linear range (0.001-100 ng/mL). This strategy is a fruitful step for the development of reusable aptasensor and may turn on new avenues for the applications of Aß oligomer detection in clinical diagnosis.Graphical abstract.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Peptídeos beta-Amiloides/química , Anticorpos Imobilizados/imunologia , Aptâmeros de Nucleotídeos/imunologia , DNA de Cadeia Simples/química , DNA de Cadeia Simples/imunologia , Corantes Fluorescentes/química , Humanos , Separação Imunomagnética , Lantânio/química , Limite de Detecção , Nanopartículas de Magnetita/química , Estruturas Metalorgânicas/química , Estrutura Quaternária de Proteína , Espectrometria de Fluorescência
5.
J Org Chem ; 85(14): 9290-9300, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32583669

RESUMO

A new enantioselective Michael addition between 3-(3-hydroxy-1H-pyrazol-1-yl)oxindole, a new synthon generated from isatin N,N'-cyclic azomethine imine 1,3-dipole, and ß-nitrostyrene has been disclosed. A series of chiral 3-(3-oxo-2,3-dihydro-1H-pyrazol-1-yl) disubstituted oxindoles were obtained in excellent results (up to 97% yield, up to 94% ee) with moderate to good diastereoselectivities (up to 4.3:1 dr).

6.
Pediatr Surg Int ; 36(6): 711-718, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32367198

RESUMO

AIM: We evaluated the demographic of biliary atresia (BA) children from twins family and aimed to investigated what it can add to the twins' literature and our understanding of the disease. METHODS: This study contains 11 medical centers in mainland China and the medical record of twins with BA was retrospectively analyzed from January 2012 to December 2018. Follow-up was carried out by out-patient review and questionnaire. RESULTS: The study included 19 twin pairs in whom there was discordance for BA. Sixteen (84.2%) affected twin underwent Kasai Procedure (KP); median age at KP was 78 (49-168) days. There were ten affected twins that became jaundice-free at 3 months post-KP, and eight occurred with different degrees of cholangitis post-KP. Six affected twins received Liver Transplantation (LT) successfully. The 2 year native liver survival rate and the 2 year overall survival rate of affected twins were 61.1 and 94.4%, respectively. There were three affected monozygotic (MZ) twins and one healthy co-twin with BA-associated congenital malformations, all of which were cardiac malformations. The number of virus infection of affected MZ twins was significantly more (p = 0.04) than affected dizygotic (DZ) twin. CONCLUSIONS: Discordance for BA in 19 pairs of twins supported that BA may be related to genetic phenotype or penetrance. The difference in genetic background between MZ and DZ affects the susceptibility of the host to virus infection. High acceptance of KP (84.2%) in our study implied a high motivation for treatment for twins with BA. Delays of KP (78 days) in affected twin may be related to the postnatal gradual onset and the late diagnosis.


Assuntos
Atresia Biliar/cirurgia , Portoenterostomia Hepática/métodos , Gêmeos Monozigóticos , Atresia Biliar/epidemiologia , China/epidemiologia , Doenças em Gêmeos , Feminino , Humanos , Recém-Nascido , Transplante de Fígado , Masculino , Morbidade/tendências , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
7.
Mikrochim Acta ; 187(2): 114, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919722

RESUMO

Amyloid-beta (Aß) oligomers causing neuron damage are regarded as potential therapeutic targets and diagnostic markers for Alzheimer's disease (AD). A homogeneous turn-on fluorometric aptasensor is described for Aß oligomers. It is highly selective and non-invasive and based on (a) the use of a luminescent metal-organic framework carrying aptamer-modified AuNPs (L-MOF/Apt-Au) as tracking agent, and (b) enzyme-assisted target recycling signal amplification. The tracking agent does not emit fluoresce by fluorescence resonance energy transfer (FRET) between the luminescent MOF as donor and Apt-Au as the acceptor under the excitation wavelength of 466 nm. When Aß oligomers are added to the tracking agent solution, the Apt-Au on tracking agent can preferentially bind with Aß oligomers and then be released. This turns the "off" signal of the luminescent MOF tracer to the "on" state. The enzyme (Rec Jf exonuclease) added into the supernatant further improves sensitivity due to enzyme-assisted target-recycling signal amplification. The assay has an excellent linear response to Aß oligomers from 1.0 pM to 10 nM, with a detection limit of 0.3 pM. This homogeneous turn-on fluorometric method is expected to have potential and applications in clinical diagnosis. Graphical abstractSchematic representation of fluorometric assay for amyloid-ß oligomers based on luminescence metal-organic framework nanocomposites as tracking agent with exonuclease-assisted target recycling.


Assuntos
Peptídeos beta-Amiloides/análise , Aptâmeros de Nucleotídeos , Fluorometria/métodos , Estruturas Metalorgânicas/química , Reciclagem/métodos , Doença de Alzheimer/diagnóstico , Técnicas Biossensoriais/métodos , Exonucleases , Ouro , Humanos , Limite de Detecção , Nanopartículas Metálicas/química
8.
J Org Chem ; 85(5): 3921-3928, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-31944112

RESUMO

An abnormal [3 + 2]-cycloaddition and highly effective and convenient one-step preparation of tetracyclic bispirooxindoles containing two all-carbon quaternary spirocenters from isatin N,N'-cyclic azomethine imine 1,3-dipole and 3-methyleneoxindole in the presence of catalytic organic base has been disclosed. A variety of bispirooxindoles bearing a dinitrogen heterocycle with four adjacent cycles have been obtained in excellent yields (up to 95%) and diastereoselectivities (>99:1) under mild conditions.

10.
Nutr Diabetes ; 9(1): 29, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611548

RESUMO

BACKGROUND: Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) control energy homeostasis by sensing hormonal and nutrient cues and activating secondary melanocortin sensing neurons. We identified the expression of a G protein-coupled receptor, Gpr17, in the ARH and hypothesized that it contributes to the regulatory function of POMC neurons on metabolism. METHODS: In order to test this hypothesis, we generated POMC neuron-specific Gpr17 knockout (PGKO) mice and determined their energy and glucose metabolic phenotypes on normal chow diet (NCD) and high-fat diet (HFD). RESULTS: Adult PGKO mice on NCD displayed comparable body composition and metabolic features measured by indirect calorimetry. By contrast, PGKO mice on HFD demonstrated a sexually dimorphic phenotype with female PGKO mice displaying better metabolic homeostasis. Notably, female PGKO mice gained significantly less body weight and adiposity (p < 0.01), which was associated with increased energy expenditure, locomotor activity, and respiratory quotient, while males did not have an overt change in energy homeostasis. Though PGKO mice of both sexes had comparable glucose and insulin tolerance, detailed analyses of liver gene expression and serum metabolites indicate that PGKO mice could have reduced gluconeogenesis and increased lipid utilization on HFD. To elucidate the central-based mechanism(s) underlying the better-preserved energy and glucose homeostasis in PGKO mice on HFD, we examined the electrophysiological properties of POMC neurons and found Gpr17 deficiency led to increased spontaneous action potentials. Moreover, PGKO mice, especially female knockouts, had increased POMC-derived alpha-melanocyte stimulating hormone and beta-endorphin despite a comparable level of prohormone POMC in their hypothalamic extracts. CONCLUSIONS: Gpr17 deficiency in POMC neurons protects metabolic homeostasis in a sex-dependent manner during dietary and aging challenges, suggesting that Gpr17 could be an effective anti-obesity target in specific populations with poor metabolic control.


Assuntos
Peso Corporal/fisiologia , Encéfalo/metabolismo , Resistência à Insulina/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Pró-Opiomelanocortina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Envelhecimento/metabolismo , Animais , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Feminino , Homeostase/fisiologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/genética , Receptores Acoplados a Proteínas G/genética , Fatores Sexuais
11.
Angew Chem Int Ed Engl ; 58(47): 16800-16805, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31486209

RESUMO

Surface recombination at the photoanode/electrolyte junction seriously impedes photoelectrochemical (PEC) performance. Through coating of photoanodes with oxygen evolution catalysts, the photocurrent can be enhanced; however, current systems for water splitting still suffer from high recombination. We describe herein a novel charge transfer system designed with BiVO4 as a prototype. In this system, porphyrins act as an interfacial-charge-transfer mediator, like a volleyball setter, to efficiently suppress surface recombination through higher hole-transfer kinetics rather than as a traditional photosensitizer. Furthermore, we found that the introduction of a "setter" can ensure a long lifetime of charge carriers at the photoanode/electrolyte interface. This simple interface charge-modulation system exhibits increased photocurrent density from 0.68 to 4.75 mA cm-2 and provides a promising design strategy for efficient photogenerated charge separation to improve PEC performance.

12.
Mikrochim Acta ; 186(8): 515, 2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31280384

RESUMO

A visualization strategy is described for the detection of clenbuterol (CLB). It is using of antibody against dsDNA and G-quadruplex/hemin labeled on a metal organic framework of type MIL-101(Fe) (G-quadruplex/hemin-anti-DNA/MIL-101) acting as a peroxidase mimetic, and magnetic beads modified with aptamer and complementary DNA (MB/Apt-cDNA) as capture probes. The detection reagent was prepared via the reactions between the double stranded DNA (Apt-cDNA) in capture probes and anti-DNA in peroxidase mimetic. In the presence of CLB, the aptamer on the magnetic beads preferentially binds CLB, and the peroxidase mimetic is released to the supernatant after magnetic separation. The released peroxidase mimetic can catalyze the TMB/H2O2 chromogenic system under mild conditions. This leads to the development of a blue-green coloration whose absorbance is measured at 650 nm. The detection limit is as low as 34 fM of CLB. The method was applied to the determination of CLB in pork samples and gave results that were consistent with data obtained with an ELISA kit. Graphical abstract A visualization strategy is described for the detection of clenbuterol. The selectivity of detection system for clenbuterol is excellent compared with other interferents. The method was applied to the determination of CLB in pork samples.


Assuntos
Agonistas Adrenérgicos beta/análise , Clembuterol/análise , Contaminação de Alimentos/análise , Carne Vermelha/análise , Suínos , Agonistas Adrenérgicos beta/química , Animais , Anticorpos/química , Aptâmeros de Nucleotídeos/química , Biomimética , Clembuterol/química , Colorimetria , DNA/química , DNA/imunologia , Quadruplex G , Hemina/química , Ferro/química , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Peroxidase/química
13.
BMC Med Genomics ; 12(Suppl 6): 108, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345219

RESUMO

BACKGROUND: Genetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene. RESULTS: We identified LoFs in 433 genes significantly associated with at least one of 10 major CVD traits. Next, we used RNA-sequence data from the STARNET study to validate 115 of the 433 LoF harboring-genes in that their expression levels were concordantly associated with corresponding CVD traits. Together with the documented hepatic lipid-lowering gene, APOC3, the expression levels of six additional liver LoF-genes were positively associated with levels of plasma lipids in STARNET. Candidate LoF-genes were subjected to gene silencing in HepG2 cells with marked overall effects on cellular LDLR, levels of triglycerides and on secreted APOB100 and PCSK9. In addition, we identified novel LoFs in DGAT2 associated with lower plasma cholesterol and glucose levels in BioMe that were also confirmed in STARNET, and showed a selective DGAT2-inhibitor in C57BL/6 mice not only significantly lowered fasting glucose levels but also affected body weight. CONCLUSION: In sum, by integrating genetic and electronic medical record data, and leveraging one of the world's largest human RNA-sequence datasets (STARNET), we identified known and novel CVD-trait related genes that may serve as targets for CVD therapeutics and as such merit further investigation.


Assuntos
Doenças Cardiovasculares/genética , Genômica , Mutação , Doenças Cardiovasculares/sangue , Colesterol/sangue , Genótipo , Humanos , Triglicerídeos/sangue
14.
Endocrinology ; 160(9): 2038-2048, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199472

RESUMO

Insulin signaling in the central nervous system influences satiety, counterregulation, and peripheral insulin sensitivity. Neurons expressing the Glut4 glucose transporter influence peripheral insulin sensitivity. Here, we analyzed the effects of insulin receptor (IR) signaling in hypothalamic Glut4 neurons on glucose sensing as well as leptin and amino acid signaling. By measuring electrophysiological responses to low glucose conditions, we found that the majority of Glut4 neurons in the ventromedial hypothalamus (VMH) were glucose excitatory neurons. GLUT4-Cre-driven insulin receptor knockout mice with a combined ablation of IR in Glut4-expressing tissues showed increased counterregulatory response to either 2-deoxyglucose-induced neuroglycopenia or systemic insulin-induced hypoglycemia. The latter response was recapitulated in mice with decreased VMH IR expression, suggesting that the effects on the counterregulatory response are likely mediated through the deletion of IRs on Glut4 neurons in the VMH. Using immunohistochemistry in fluorescently labeled hypothalamic Glut4 neurons, we showed that IR signaling promoted hypothalamic cellular signaling responses to the rise of insulin, leptin, and amino acids associated with feeding. We concluded that hypothalamic Glut4 neurons modulated the glucagon counterregulatory response and that IR signaling in Glut4 neurons was required to integrate hormonal and nutritional cues for the regulation of glucose metabolism.


Assuntos
Transportador de Glucose Tipo 4/fisiologia , Receptor de Insulina/fisiologia , Núcleo Hipotalâmico Ventromedial/fisiologia , Animais , Glucagon/sangue , Glucose/metabolismo , Hipoglicemia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Dalton Trans ; 47(20): 6986-6994, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29736509

RESUMO

Three new manganese 4'-(3,5-dicarboxyphenyl)-2,2':6',2'''-terpyridine (H2DATP) metal-organic framework materials have been generated through regulating the ratios of a binary solvent mixture (DMA/H2O) under solvothermal conditions. Compound 1 {[Mn2(DATP)(HDATP)(H2O)4](OH)·10H2O}n displaying a one-dimensional (1D) chainlike structure was crystallized from the DMA/H2O mixture with a molar ratio of 1 : 1, while the two-dimensional (2D) layer species, {[Mn(DATP)(H2O)]·2H2O}n (2) was produced by increasing the ratio of DMA/H2O to 5 : 1. Interestingly, the crystallization in pure DMA yields a three-dimensional (3D) interpenetrating network {[Mn(DATP)]·4H2O}n (3), featuring higher solvent stability and pH stability than compounds 1 and 2. It is proved that solvent not only influences the structural transformation process of crystals but also has a significant effect on their properties. These three compounds present different catalytic performances in the CO2 cycloaddition to epoxides with various substituent groups into corresponding cyclic carbonates, and only 3 can serve as an efficient and recyclable catalyst at mild temperature.

16.
Org Biomol Chem ; 16(8): 1297-1304, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29388660

RESUMO

A novel and diastereoselective [3 + 2] annulation of isoindigos and Morita-Baylis-Hillman carbonates has been developed for the highly efficient and one-step preparation of highly steric dispiro[cyclopent-3'-ene]bisoxindoles with two all-carbon quaternary spirocenters and three adjacent cycles in excellent yields (up to >99%) and diastereoselectivities (up to >20 : 1) under mild conditions within a few minutes. A series of dispiro[cyclopent-3'-ene]bisoxindoles were obtained and scale-up experiment was conducted with excellent results demonstrating the potential applications of this protocol.

17.
Org Lett ; 19(12): 3051-3054, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28571319

RESUMO

A new isatin N,N'-cyclic azomethine imine 1,3-dipole was devised, and an unusual Michael addition with ß-nitrostyrene catalyzed by tributylamine under mild conditions has been developed. The new reaction featured the C3 umpolung of oxindole and an unusual formation of double bond. Notably, this new synthon performed as a donor rather than an acceptor. This protocol provided a promising method for the preparation of various 3-aminooxindoles with good yields in moderate diastereoselectivities.

18.
Org Lett ; 19(11): 2805-2808, 2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28497972

RESUMO

An unusual and highly effective asymmetric annulation of nitrosoarenes with hydroxymaleimides catalyzed by a chiral bifunctional amine squaramide catalyst has been disclosed. A wide range of highly fused chiral N-hydroxyindolines with two consecutive quaternary stereocenters and multifunctional groups were directly and effectively prepared in excellent yields (up to >99%) with complete regioselective cyclization and excellent stereoselectivities (up to >99:1 dr and >99% ee). The efficiency and potentials of the new reaction and the target chiral entities were well demonstrated by delicate transformations into a series of new chiral indolines.

19.
BMC Surg ; 17(1): 37, 2017 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-28403863

RESUMO

BACKGROUND: Gastric duplication cysts are rare congenital alimentary tract anomalies and most cases are recognized during childhood. There were few reports about gastric duplication cysts in newborns and even fewer reports about laparoscopic resection of gastric duplication cysts in newborns. CASE PRESENTATION: We report a series of five newborns with gastric duplication cysts which were successfully resected by laparoscopy between January 2010 and April 2015. Case 1, a male newborn was admitted because of severe salivation, choking cough and dyspnea for 30 min after birth. Case 2, a male, was suspected of duodenal ileus by antenatal examination. Case 3, a female was admitted because of vomiting for 5 days. Case 4,a female without significant symptoms simply visited us for the abdominal cyst detected by antenatal examination. Case 5, a male was admitted because of vomiting for 4 days. All patients were performed with a surgery after assistant examinations. Case 1 was died of respiratory failure and the other patients recovered uneventfully. CONCLUSION: Gastric duplication cysts in newborns are very rare. Laparoscopic surgery play an important role on the diagnosis and treatment. Our experience and practice indicate that laparoscopic resection of gastric duplication cysts in newborns is viable and there is also a need to increase sample size to prove its safety and effectiveness.


Assuntos
Cistos/cirurgia , Laparoscopia/métodos , Vômito/etiologia , Feminino , Humanos , Íleus/cirurgia , Recém-Nascido , Masculino
20.
Chirality ; 29(7): 369-375, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28418612

RESUMO

Chiral diamine catalysts 11a-e derived from α,α-diphenyl prolinol were prepared and successfully applied to the Michael addition of aromatic oximes to α,ß-unsaturated aldehydes in mediocre to good yields (up to 78%) and good to high enantioselectivities (up to 93% ee).

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