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1.
Org Biomol Chem ; 22(5): 965-969, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38205855

RESUMO

A visible-light-induced decarboxylative cascade reaction of acryloylbenzamides with alkyl N-hydroxyphthalimide (NHP) esters for the synthesis of various 4-alkyl isoquinolinediones mediated by triphenylphosphine (PPh3) and sodium iodide (NaI) was developed. This operationally simple protocol proceeded via the photoactivation of electron donor-acceptor (EDA) complexes between N-hydroxyphthalimide esters and NaI/PPh3, resulting in multiple carbon-carbon bond formations without the use of precious metal complexes or synthetically elaborate organic dyes, which provided an alternative practical approach to synthesize diverse isoquinoline-1,3(2H,4H)-dione derivatives.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 791-799, 2023 Aug 15.
Artigo em Zh | MEDLINE | ID: mdl-37668025

RESUMO

OBJECTIVES: To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 (MyD88) and Toll-like receptor adaptor molecule 1 (TICAM1) and their interactions with community-acquired pneumonia (CAP) in children. METHODS: Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children. RESULTS: The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children (P<0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP (P<0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP (P<0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure (P<0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children (P<0.05). CONCLUSIONS: The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Infecções Comunitárias Adquiridas , Fator 88 de Diferenciação Mieloide , Pneumonia , Criança , Humanos , Proteínas Adaptadoras de Transporte Vesicular/genética , Infecções Comunitárias Adquiridas/genética , Fator 88 de Diferenciação Mieloide/genética , Pneumonia/genética , Polimorfismo de Nucleotídeo Único , Sepse
3.
J Org Chem ; 87(21): 14965-14969, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36279475

RESUMO

Herein, we reported a practical and efficient strategy combining photoredox and enzyme catalysis for the construction of 3-aminoalkyl chromones from o-hydroxyaryl enaminones and N-arylglycine esters. A variety of 3-aminoalkyl chromones were synthesized with good yields under mild conditions in one pot. This synthetic protocol consists of sequential enzymatic hydrolysis and photoredox decarboxylation of N-arylglycine esters, oxidation of aminoalkyl radicals, Mannich reaction, and intramolecular nucleophilic cyclization, which affords a convenient pathway for the preparation of various 3-substituted chromones.


Assuntos
Cromonas , Ésteres , Catálise , Ciclização , Oxirredução
4.
J Org Chem ; 85(23): 15062-15071, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33135893

RESUMO

A new and efficient visible-light-promoted dehydrogenative cross-coupling reaction of imidazo[1,2-a]pyridines with α-amino carbonyl compounds toward imidoyl imidazo[1,2-a]pyridines is developed. A diverse range of imidazo[1,2-a]pyridines undergoes the dehydrogenative imidoylation smoothly with α-amino carbonyl compounds to access the corresponding products in satisfactory yields. We have also proposed the possible reaction mechanism based on preliminary mechanistic studies. The synthetic method has the advantages of wide substrate scope, good functional tolerance, and mild reaction conditions, which make this transformation more practical and sustainable.

5.
Genet Sel Evol ; 52(1): 35, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611306

RESUMO

Base editing has the potential to improve important economic traits in agriculture and can precisely convert single nucleotides in DNA or RNA sequences into minimal double-strand DNA breaks (DSB). Adenine base editors (ABE) have recently emerged as a base editing tool for the conversion of targeted A:T to G:C, but have not yet been used in sheep. ABEmax is one of the latest versions of ABE, which consists of a catalytically-impaired nuclease and a laboratory-evolved DNA-adenosine deaminase. The Booroola fecundity (FecBB) mutation (g.A746G, p.Q249R) in the bone morphogenetic protein receptor 1B (BMPR1B) gene influences fecundity in many sheep breeds. In this study, by using ABEmax we successfully obtained lambs with defined point mutations that result in an amino acid substitution (p.Gln249Arg). The efficiency of the defined point mutations was 75% in newborn lambs, since six lambs were heterozygous at the FecBB mutation site (g.A746G, p.Q249R), and two lambs were wild-type. We did not detect off-target mutations in the eight edited lambs. Here, we report the validation of the first gene-edited sheep generated by ABE and highlight its potential to improve economically important traits in livestock.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Fertilidade/genética , Edição de Genes/métodos , Adenina/metabolismo , Adenosina Desaminase/metabolismo , Adenosina Desaminase/fisiologia , Animais , Cruzamento , Feminino , Engenharia Genética/métodos , Genótipo , Heterozigoto , Tamanho da Ninhada de Vivíparos/genética , Masculino , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Ovinos/genética
6.
Bioorg Chem ; 101: 103949, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32531507

RESUMO

A one-pot efficient biocatalytic strategy for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones was developed in a circulating microwave reactor selecting α-chymotrypsin as the promiscuous biocatalyst. In the circulating reaction system, the combination of microwave heating and external cooling could avoid the denaturation and inactivation of enzyme, and greatly improved the radiation power of microwave, thus improving the specific effects of microwave. During the reaction process, the microwave radiation power was automatically adjusted by adjusting the speed of the reaction mixture circulation. When the microwave power was maintained at 110 W, the best results could be obtained with the highest yield of 96% at 55 °C in 50 min, and the reaction had a wide range of substrates. But no obvious product was detected in a tank microwave reactor at 55 °C for 100 min, under this condition, the microwave power was maintained at about 3 W. As a contrast, the reaction only obtained 63% yield in 55 °C oil bath for 96 h.


Assuntos
Reatores Biológicos , Micro-Ondas , Animais , Biocatálise , Bovinos , Quimotripsina/metabolismo
7.
J Org Chem ; 84(1): 435-442, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30540464

RESUMO

A novel and efficient direct oxidative phosphonylation of α-amino ketones and α-amino acid derivatives with dialkyl phosphites by the catalysis of a cobalt salt under air is disclosed. A variety of α-amino ketones and α-amino acid derivatives underwent the reaction well with dialkyl phosphites to produce the desired α-aminophosphonates. This protocol not only provides an alternative synthetic route for the preparation of diverse α-aminophosphonates but also avoids the use of potentially explosive peroxide agents.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 789-795, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31416504

RESUMO

OBJECTIVE: To study the association of interleukin-10 (IL-10) -1082A/G, -819C/T, and -592C/A polymorphisms with IL-10 level and the severity of enterovirus 71 (EV71) infection in children. METHODS: A total of 137 children with hand-foot-mouth disease due to EV71 infection were enrolled as EV71 infection group, which was further divided into mild group with 91 children and severe group with 46 children, and 122 healthy children who underwent physical examination were enrolled as healthy control group. Related clinical data were collected. ELISA was used to measure the serum level of IL-10, and polymerase chain reaction-restriction fragment length polymorphism was used to analyze IL-10 -1082A/G, -819C/T and -592C/A polymorphisms. RESULTS: Compared with the healthy control group, the children with EV71 infection had significantly higher frequency of -1082 AA genotype and A allele (P<0.05). Among the children with EV71 infection, the severe group had significantly higher frequency of -1082 AA genotype and A allele than the mild group (P<0.05), while there was no significant difference in the distribution of IL-10 -819C/T and IL-10 -592C/A polymorphisms between the two groups (P>0.05). The severe group had a significantly higher serum level of IL-10 than the mild group and the healthy control group. IL-10 -1082 AA genotype, -819 TT genotype, and -592 AA genotype were associated with the low expression of IL-10 (P<0.05). As for haplotype, the EV71 infection group had a significantly lower frequency of GCC haplotype than the healthy control group (P<0.05). In the severe group, the children with ATA haplotype had a significantly lower IL-10 level than those with other haplotypes, and the children with GCC haplotype had a significantly higher IL-10 level than those with other haplotypes (P<0.05). There was no significant difference in IL-10 level between children with different haplotypes in the mild group and the healthy control group (P>0.05). CONCLUSIONS: IL-10 gene polymorphisms are associated with IL-10 expression and the severity of EV71 infection in children.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Interleucina-10/genética , Criança , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
9.
J Magn Reson Imaging ; 48(6): 1508-1517, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29537670

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with cognitive deficit but the exact neural mechanisms remain unclear. PURPOSE: To explore sequential brain activities using functional magnetic resonance imaging (fMRI) during the performance of a decision-making task, and to determine whether serum or clinical markers can reflect the involvement of the brain in SLE. SUBJECTS: Sixteen female SLE patients without overt clinical neuropsychiatric symptoms and 16 healthy controls were included. FIELD STRENGTH/SEQUENCE: 1.5T, T1 -weighted anatomic images, gradient-echo echo-planar imaging sequence, and 3D images. ASSESSMENT: The computer-based Iowa Gambling Task (IGT) for assessing decision-making was performed by SLE patients and 16 matched controls; brain activity was recorded via blood oxygen level-dependent (BOLD) fMRI. The amplitudes of the average BOLD responses were calculated for each individual subject, and activation data from fMRI experiments were compared between the two groups. STATISTICAL TESTS: Two-sample t-test; repeated-measures analysis of variance (ANOVA); linear regression analyses. RESULTS: Imaging revealed activity in a distributed network of brain regions in both groups, including the ventromedial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), the posterior cingulate cortex (PCC), and the striatum, as well as the insular, parietal, and occipital cortices. Compared to controls, SLE patients showed lower activation in a convergence zone and the limbic system, namely, the OFC, vmPFC, ACC, and PCC, but greater activation in memory, emotion, and behavior systems involving the dlPFC, the insular cortex and the striatum. Furthermore, brain activation in the vmPFC was positively correlated with IGT scores (r = 0.63, P < 0.001), but inversely related to disease activity (r = -0.57, P < 0.01). DATA CONCLUSION: The dynamics among the aforementioned neural systems (some hyperfunctioning, others hypofunctioning) may shed some light on the pathologic mechanisms underlying SLE without overt clinical neuropsychiatric symptoms. In addition, disease activity may potentially be used as an effective biomarker reflecting cerebral involvement in SLE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1508-1517.


Assuntos
Encéfalo/diagnóstico por imagem , Tomada de Decisões , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/fisiopatologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Mapeamento Encefálico/métodos , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Humanos , Imageamento Tridimensional , Masculino , Rede Nervosa , Neurônios/patologia , Testes Neuropsicológicos , Córtex Pré-Frontal , Análise de Regressão , Adulto Jovem
10.
Int J Neurosci ; 128(8): 785-790, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29199527

RESUMO

OBJECTIVE: To explore the clinical manifestations and imaging features of neurosyphilis and to discuss the obstacles in the diagnosis and treatment of neurosyphilis. METHODS: We present this case study involving three cases of definite neurosyphilis, focusing on their clinical data. RESULTS: Case 1 is a patient with numb and weak left lower limb. Case 2 showed slow reaction and dementia behaviors including worse memory and the decrease of calculation and orientation ability in this patient. Case 3 is a peripheral incomplete left oculomotor nerve palsy patient. Magnetic resonance imaging findings of three patients are different. And single photon emission computed tomography showed the regional cerebral blood flow was all hypoperfused. There were some difficulties in diagnosing and treating the patients in these three cases. CONCLUSION: The clinical manifestations and imaging findings of neurosyphilis are diverse. Clinicians should pay attention to neurosyphilis. After clear diagnosis, patients would receive norm treatment in time.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neurossífilis/diagnóstico , Neurossífilis/terapia , Tomografia Computadorizada de Emissão de Fóton Único , Testes de Aglutinação , Anticorpos Antibacterianos/metabolismo , Circulação Cerebrovascular , Cisteína/análogos & derivados , Cisteína/farmacocinética , Diagnóstico Diferencial , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Neurossífilis/microbiologia , Neurossífilis/fisiopatologia , Compostos de Organotecnécio/farmacocinética , Treponema pallidum/imunologia , Treponema pallidum/patogenicidade
11.
Arch Virol ; 162(6): 1717-1723, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28190199

RESUMO

Enterovirus 71 (EV71) infection has become one of the major threats to children globally in recent years. Toll-like receptor 3 (TLR3) plays an essential role in host defense against EV71 infection. This study was designed to assess the possible association between the TLR3c.1377C/T polymorphism and disease severity in Chinese children with EV71 infection. The TLR3c.1377C/T gene polymorphism was identified in EV71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78) as well as healthy controls (n = 225), using improved multiplex ligation detection reaction (iMLDR) technology. Serum levels of IFN-γ and IL-4 were measured using enzyme-linked immunosorbent assays. The presence of the TT genotype (p = 0.030) and the T allele (OR, 1.8; 95% CI, 1.2-2.8; p = 0.010) was significantly more frequent in severe cases. The plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower with the TT (102.0 ± 24.2 pg/mL, p < 0.01 and 14.2 ± 2.8, p < 0.001) and CT genotypes (114.1 ± 26.2 pg/mL, p < 0.05 and 18.0 ± 3.1, p < 0.001) than with the CC genotype (135.5 ± 36.8 pg/mL and 24.9 ± 4.7), but the plasma levels of IL-4 with the TT (7.3 ± 1.7 pg/mL, p < 0.01) and CT genotypes (6.4 ± 1.3 pg/mL, p < 0.05) were significantly higher than with the CC genotype (5.5 ±1.3 pg/mL). These findings suggest that the TLR3c.1377T allele is associated with susceptibility to severe EV71 infection in Chinese children.


Assuntos
Enterovirus Humano A/fisiologia , Infecções por Enterovirus/genética , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Alelos , Povo Asiático/genética , Criança , Pré-Escolar , China , Infecções por Enterovirus/sangue , Infecções por Enterovirus/virologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Interferon gama/sangue , Interleucina-4/sangue , Masculino
12.
PLoS Genet ; 10(2): e1004124, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24550737

RESUMO

Obesity is one of the largest health problems facing the world today. Although twin and family studies suggest about two-thirds of obesity is caused by genetic factors, only a small fraction of this variance has been unraveled. There are still large numbers of genes to be identified that cause variations in body fatness and the associated diseases encompassed in the metabolic syndrome (MetS). A locus near a sequence tagged site (STS) marker D6S1009 has been linked to obesity or body mass index (BMI). However, its genetic entity is unknown. D6S1009 is located in the intergenic region between SLC35D3 and NHEG1. Here we report that the ros mutant mice harboring a recessive mutation in the Slc35d3 gene show obesity and MetS and reduced membrane dopamine receptor D1 (D1R) with impaired dopamine signaling in striatal neurons. SLC35D3 is localized to both endoplasmic reticulum (ER) and early endosomes and interacts with D1R. In ros striatal D1 neurons, lack of SLC35D3 causes the accumulation of D1R on the ER to impair its ER exit. The MetS phenotype is reversible by the administration of D1R agonist to the ros mutant. In addition, we identified two mutations in the SLC35D3 gene in patients with MetS, which alter the subcellular localization of SLC35D3. Our results suggest that the SLC35D3 gene, close to the D6S1009 locus, is a candidate gene for MetS, which is involved in metabolic control in the central nervous system by regulating dopamine signaling.


Assuntos
Dopamina/genética , Síndrome Metabólica/genética , Proteínas de Transporte de Monossacarídeos/genética , Obesidade/genética , Animais , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Dopamina/metabolismo , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Proteínas de Transporte de Monossacarídeos/metabolismo , Mutação , Neurônios/metabolismo , Neurônios/patologia , Obesidade/metabolismo , Obesidade/patologia , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Transdução de Sinais , Córtex Visual/metabolismo , Córtex Visual/patologia
13.
Molecules ; 22(5)2017 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-28481323

RESUMO

An efficient, convenient, and eco-friendly biocatalytic approach was developed for the synthesis of quinoline derivatives via the α-chymotrypsin-catalyzed Friedländer reaction. Interestingly, α-chymotrypsin exhibited higher catalytic activity in an ionic liquid (IL) aqueous solution as compared to that observed in our previous relevant study, which was conducted using an organic solvent, and a series of substrates gave similar excellent yields at lower reaction temperature and under reduced enzyme-loading conditions.


Assuntos
Quimotripsina/química , Líquidos Iônicos/química , Quinolinas/química , Quinolinas/síntese química , Catálise
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(1): 39-43, 2017 Jan.
Artigo em Zh | MEDLINE | ID: mdl-28100320

RESUMO

OBJECTIVE: To investigate the association of gene polymorphisms of Toll-like receptor 3 (TLR3)-1377C/T and expression of TLR3 with the susceptibility to enterovirus 71 (EV71) encephalitis in children. METHODS: A total of 187 children with EV71 infection (59 children in the encephalitis group and 128 in the non-encephalitis group) and 232 children who underwent physical examination were enrolled in the case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the TLR3-1377C/T gene polymorphisms. ELISA was used to measure the serum level of TLR3. RESULTS: There were no significant differences in the genotype and allele frequencies of TLR3-1377C/T between the non-encephalitis group and the encephalitis group. Compared with the control group, the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 (P<0.05), and the non-encephalitis group had the highest level (P<0.05). The encephalitis group had a significantly higher EV71 viral load than the non-encephalitis group (P<0.01). The children aged <1 year or ≥1 year in the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 compared with their counterparts in the control group (P<0.05), and the children aged <1 year or ≥1 year in the non-encephalitis group had a significantly higher serum level of TLR3 than those in the encephalitis group (P<0.05). In the encephalitis group, the children aged ≥1 year had a significantly higher TLR3 concentration than those aged <1 year (P<0.05), and there were no significant differences in the TLR3 concentration between the children aged ≥1 year and <1 year in the non-encephalitis group and the control group. In the encephalitis group, the proportion of children aged <1 year was significantly higher than those aged ≥1 year (P<0.05). CONCLUSIONS: The TLR3-1377C/T gene polymorphisms are not significantly associated with the development of EV71 encephalitis. Low expression of TLR3 might weaken the inhibitory effect on virus replication and promote the development of EV71 encephalitis. The deficiency in the expression of TLR3 in serum after EV71 infection might be an important factor for the development of encephalitis in infants.


Assuntos
Encefalite Viral/genética , Enterovirus Humano A , Infecções por Enterovirus/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
15.
J Magn Reson Imaging ; 43(1): 75-87, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26094886

RESUMO

PURPOSE: To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. RESULTS: The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. CONCLUSION: Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hipocampo/fisiopatologia , Transtornos da Memória/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Transtornos Cognitivos/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Memória de Curto Prazo , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
J Org Chem ; 81(19): 9449-9454, 2016 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-27617488

RESUMO

An efficient copper-catalyzed cascade cyclization reaction for the preparation of polysubstituted 1,4-dihydropyridines between N-arylglycine esters and 1,3-dicarbonyl compounds using molecular oxygen as the terminal oxidant has been described. Various N-arylglycine esters 1 and 1,3-dicarbonyl compounds 2 were able to undergo the cascade reaction smoothly to afford the desired products 3 in satisfactory yields. The cascade reaction has the advantages of good functional group tolerance and mild reaction conditions. A possible mechanism has also been proposed on the basis of control experiments.

17.
Bioorg Med Chem Lett ; 26(10): 2413-2417, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27072907

RESUMO

As our continuing research on antifungal dihydroisoquinolin-2-ium salts, forty 2-aryl-8-OR-3,4-dihydroisoquinolin-2-ium bromides were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activity against three plant pathogenic fungi and structure-activity relationships (SAR) were derived. The vast majority of the compounds displayed the medium to high activity with inhibition rates of 50-100% at 150µM. About half of the compounds were more active than their natural model compounds sanguinarine and chelerythrine for all the fungi, and part or most of them were more active than positive drugs thiabendazole and azoxystrobin. SAR analysis showed that both substitution patterns of the C-ring and the type of 8-OR group significantly influenced the activity. Thus, a series of new title compounds with excellent antifungal potency emerged.


Assuntos
Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade , Benzofenantridinas/química , Benzofenantridinas/farmacologia , Técnicas de Química Sintética , Avaliação Pré-Clínica de Medicamentos/métodos , Fungicidas Industriais/síntese química , Isoquinolinas/química , Isoquinolinas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Tiabendazol/farmacologia
18.
Arch Virol ; 160(4): 1035-42, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25666199

RESUMO

Enterovirus 71 (EV71) has caused many outbreaks of diseases among children worldwide since it was first reported in 1974, but its mechanism of pathogenesis remains unclear. This study was designed to investigate the possible association of the IL-4 -589C/T gene polymorphism with severity of EV71 infection in Chinese children. The IL-4 -589C/T gene polymorphism was detected in EV71-infected subjects (n = 185), including those with mild cases (n = 102) and severe cases (n = 83) as well as healthy controls (n = 234), using an improved multiplex ligation detection reaction (iMLDR) technique. The plasma levels of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assays. The presence of the CC genotype (p = 0.022) and the C allele (OR, 2.1; 95 % CI, 1.3-3.6; p = 0.004) was significantly higher in severe cases. Furthermore, the CC genotype and C allele were also more frequently found in cases of EV71 encephalitis (p < 0.05). The plasma levels of IL-4 of the CC (7.9 ± 1.3 pg/mL, p < 0.001) and CT genotype (6.8 ± 2.1 pg/mL, p < 0.01) were significantly elevated compared to those of the TT genotype, but the plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower for the CC and CT genotypes than for the TT genotype (p < 0.05). These findings suggest that the IL-4 -589C allele could be a susceptibility factor in the development of EV71 disease in Chinese children.


Assuntos
Povo Asiático/genética , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/genética , Predisposição Genética para Doença , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Alelos , Criança , Pré-Escolar , China , Enterovirus Humano A/genética , Infecções por Enterovirus/sangue , Infecções por Enterovirus/virologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Interferon gama/sangue , Interleucina-4/sangue , Masculino
19.
Inflamm Res ; 63(7): 549-56, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24609754

RESUMO

OBJECTIVE: The goal of this study was to examine the relationship between CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphism and severity of Enterovirus 71 (EV71) infection in a Chinese population. METHODS: A case-control study was conducted to compare the distribution of genotype and genetic frequency of the CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphisms among EV71-infected patients (n = 186), including mild cases (n = 103), severe cases (n = 83) and healthy control subjects (n = 233) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and analyzed the relationship between the CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphism and the susceptibility to EV71 infection. RESULTS: No significant differences were found in the distribution of genotype CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T between the healthy control group and EV71-infected patients. However, three SNPs were associated with severity of EV71 infection: the G allele (genotypes AG or GG) in the CCL2-2518A/G (OR 2.34, 95 % CI 1.50-3.65, P < 0.001), the A allele (genotypes AA or AG) in the CXCL10-201A/G (OR 3.60, 95 % CI 1.73-7.47, P < 0.001), and the C allele (genotypes CC or CT) in the IL8+781C/T (OR 2.63, 95 % CI 1.67-4.13, P < 0.001) were more frequent in patients with severe EV71 infection. No significant difference was observed between EV71 encephalitis and severe cases. At the same time, there were significant differences in fever days, WBC, CRP and BG concentration, and CCL2, CXCL10 and IL-8 levels according to the three SNPs among 186 EV71-infected patients, but no significant differences were observed in gender, age, ALT, AST, CK-MB, and CSF evaluations. CONCLUSION: The G carrier of the CCL2-2518A/G, the A carrier of the CXCL10-201A/G, and the C carrier of the IL8+781C/T were found to be associated with severity of EV71 infection, and could be susceptibility factors in the development of EV71 infection in the Chinese population.


Assuntos
Quimiocina CCL2/genética , Quimiocina CXCL10/genética , Infecções por Enterovirus/genética , Predisposição Genética para Doença , Interleucina-8/genética , Povo Asiático/genética , Quimiocina CCL2/sangue , Quimiocina CXCL10/sangue , Pré-Escolar , Enterovirus Humano A , Infecções por Enterovirus/sangue , Feminino , Humanos , Interleucina-8/sangue , Masculino , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença
20.
Arch Virol ; 159(9): 2503-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24788844

RESUMO

The study was performed in 36 Chinese patients with enterovirus 71 (EV71) encephalitis and 141 patients with EV71-related hand, foot and mouth disease (HFMD) without encephalitis. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. Patients with EV71 encephalitis had a significantly higher frequency of the CCL2-2510GG genotypes when compared to patients with EV71-related HFMD without encephalitis (66.7% vs. 41.8%, p=0.028). The frequency of CCL2-2510G alleles was also significantly higher among the patients with EV71 encephalitis than among patients with EV71-related HFMD without encephalitis (79.2% vs. 64.9%, OR=2.1, 95% CI=1.1-3.8, P=0.023). Significant differences were found in gender, age, fever days, white blood cell count, C-reactive protein level, blood glucose concentration, and CCL2 level among genotypes of CCL2-2510A/G in EV71-infected patients, but no significant differences were found in alanine aminotransferase, aspartate aminotransferase, or creatine kinase myocardial isozyme levels or in cerebrospinal fluid evaluations (except monocytes) in patients with EV71 encephalitis. These findings suggest that the CCL2-2510G allele is associated with susceptibility to EV71 encephalitis in Chinese patients.


Assuntos
Quimiocina CCL2/genética , Encefalite Viral/genética , Enterovirus Humano A/imunologia , Infecções por Enterovirus/genética , Predisposição Genética para Doença , Polimorfismo Genético , Criança , Pré-Escolar , China , Encefalite Viral/imunologia , Infecções por Enterovirus/imunologia , Feminino , Frequência do Gene , Técnicas de Genotipagem , Humanos , Lactente , Masculino , Polimorfismo de Fragmento de Restrição
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