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2.
Eur J Med Chem ; 189: 112038, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945667

RESUMO

Bufadienolides are a type of natural cardiac steroids and originally isolated from the Traditional Chinese Medicine Chan'Su, they have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy with potent anti-tumor activities. Due to their unique molecular structures with unsaturated six-membered lactones attached to the steroid core, bufadienolides have received great attention in the synthetic organic community. This review presents total synthetic efforts to some representative bufadienolides, chemical modification of bufadienolides will also be given to discuss their structure-activity relationship in anti-tumor.

4.
ACS Chem Biol ; 15(1): 44-51, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31860257

RESUMO

Fusidane-type antibiotics are a group of triterpenoid antibiotics. They include helvolic acid, fusidic acid, and cephalosporin P1, among which fusidic acid has been used clinically. We have recently elucidated the biosynthesis of helvolic acid and fusidic acid, which share an early biosynthetic route involving six conserved enzymes. Here, we report two separate gene clusters for cephalosporin P1 biosynthesis. One consists of the six conserved genes, and the other contains three genes encoding a P450 enzyme (CepB4), an acetyltransferase (CepD2), and a short-chain dehydrogenase/reductase (CepC2). Introduction of these three genes into Aspergillus oryzae, which harbors the six conserved genes, produced cephalosporin P1. Stepwise introduction revealed that CepB4 not only catalyzes stereoselective dual oxidation of C6 and C7, but also monooxygenation of C6 or C7. This led to the generation of five new analogues. Using monohydroxylated products as substrates, we demonstrated that CepD2 specifically acetylates C6-OH, although both C6-OH and C7-OH acetylated analogues have been identified in nature.

5.
Appl Opt ; 58(36): 9883-9895, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31873634

RESUMO

Modulation using a rotating waveplate is the most popular way in astronomy to obtain radiation polarization states and thus the physical condition of celestial bodies. Modulation error analysis of the rotating quarter-waveplate polarimeter is presented in this paper. In terms of geometric dimensions, three modulation error sources are analyzed: the waveplate axial error, waveplate rotation axis tip-tilt error (zenithal error), and position error of the waveplate fast axis (azimuthal error). The dispersion deviation, as another dimension of modulator error, is also studied in this paper. In theory, two factors affect the accuracy of polarization measurement using waveplate polarimetry: retardance $ \delta $δand fast axis position $ \theta $θ. The temperature property of the waveplate, which represents the axial error, the waveplate mounting tip-tilt error, which represents the zenithal error, and the wavelength-based retardance characteristic, which represents the dispersion property of the waveplate, belong to the retardance error. The motorized rotary stage home position error and the random sample rotating position error, representing the azimuthal error, belong to the fast axis position error. These factors will be analyzed in detail here. Based on these analyses, the maximum allowable upper limits for each error source under $ 1 \times {10^{ - 4}} $1×10-4 polarization measurement accuracy are presented. Also, feasible solutions are proposed to address these errors.

6.
Gastroenterol Rep (Oxf) ; 7(5): 354-360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31687155

RESUMO

Background: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. Methods: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. Results: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. Conclusions: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

7.
Bioorg Med Chem Lett ; 29(24): 126772, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31711785

RESUMO

Inhibition of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) to prevent brain ß-amyloid (Aß) peptide's formation is a potential effective approach to treat Alzheimer's disease. In this report we described a structure-based optimization of a series of BACE1 inhibitors derived from an iminopyrimidinone scaffold W-41 (IC50 = 7.1 µM) by Wyeth, which had good selectivity and brain permeability but low activity. The results showed that occupying the S3 cavity of BACE1 enzyme could be an effective strategy to increase the biological activity, and five compounds exhibited stronger inhibitory activity and higher liposolubility than W-41, with L-5 was the most potent inhibitor against BACE1 (IC50 = 0.12 µM, logP = 2.49).

8.
Brief Bioinform ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612203

RESUMO

Identification of disease-associated circular RNAs (circRNAs) is of critical importance, especially with the dramatic increase in the amount of circRNAs. However, the availability of experimentally validated disease-associated circRNAs is limited, which restricts the development of effective computational methods. To our knowledge, systematic approaches for the prediction of disease-associated circRNAs are still lacking. In this study, we propose the use of deep forests combined with positive-unlabeled learning methods to predict potential disease-related circRNAs. In particular, a heterogeneous biological network involving 17 961 circRNAs, 469 miRNAs, and 248 diseases was constructed, and then 24 meta-path-based topological features were extracted. We applied 5-fold cross-validation on 15 disease data sets to benchmark the proposed approach and other competitive methods and used Recall@k and PRAUC@k to evaluate their performance. In general, our method performed better than the other methods. In addition, the performance of all methods improved with the accumulation of known positive labels. Our results provided a new framework to investigate the associations between circRNA and disease and might improve our understanding of its functions.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(10): 1022-1027, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31642438

RESUMO

OBJECTIVE: To study the clinical features and etiology of abdominal distension in children with different ages. METHODS: A retrospective analysis was performed for the clinical data of 1 561 children who were admitted due to abdominal distension from January 2013 to October 2016, including clinical manifestations, radiological examination, pathological results, and disease diagnosis. RESULTS: Among the 1 561 children, there were 823 neonates (aged <28 days), 307 infants (aged 28 days to 1 year), 186 toddlers (aged 1-3 years), 120 preschool children (aged 3-6 years), 106 school-aged children (aged 6-12 years), and 19 adolescents (aged 12-17 years). Vomiting was the major associated symptom in neonates, infants, toddlers, and school-aged children, abdominal pain was the major associated symptom in pre-school children, and vomiting and abdominal pain were the major associated symptoms in adolescents. Hypoactive bowel sound was the major accompanying sign in neonates and infants, and abdominal tenderness was the major accompanying sign in the other four age groups. Plain abdominal radiograph showed intestinal inflation in neonates and intestinal inflation with an air-fluid level in the other five age groups. Histopathological examination was performed for 339 children and the pathological results of intestinal tissue showed small, few, or poorly developed submucosal ganglion cells in neonates, intestinal inflammation/bleeding/necrosis in infants, and appendicitis in the other age groups. Necrotizing enterocolitis was the main cause of abdominal distension in neonates (34.4%), and intestinal obstruction was the main cause in infants (36.8%), toddlers (52.2%), pre-school children (51.7%), school-aged children (62.3%), and adolescents (52.6%). CONCLUSIONS: Vomiting is a common symptom in children with abdominal distension in all age groups. Neonates and infants with abdominal distension often present with hypoactive bowel sounds, and children over 1 year old mainly suffer from abdominal tenderness. Necrotizing enterocolitis is the most common cause of neonatal abdominal distension, and abdominal distension in the other age groups is mainly attributed to intestinal obstruction.


Assuntos
Apendicite , Enterocolite Necrosante , Doenças do Recém-Nascido , Enteropatias , Adolescente , Criança , Pré-Escolar , Hemorragia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-31598812

RESUMO

The aim of this study is to analyze the clinical and echocardiographic determinants of functional tricuspid regurgitation (TR) before and after surgical intervention of rheumatic mitral valve disease, with focus on effectiveness of different methods of tricuspid valve annuloplasty (TAP). Three-dimensional echocardiographic images were obtained in 170 patients with mitral valve rheumatic disease before and 1 year after mitral valve replacement, with and without concomitant TAP. Together with standard cardiac chamber quantification, multiplanar reconstruction images of the tricuspid valve (TV) apparatus were analyzed in the septal-lateral and antero-posterior directions, end-diastolic TV annular diameter, TV tenting height and tenting area were measured. By multivariate logistic regression, septal-lateral TV tenting area (p < 0.001) were independently correlated with preoperative FTR severity while postoperative septal-lateral TV annular diameter (p < 0.001) independently determined residual TR at 1-year follow-up. Both ring and suture TAP groups had postoperative reduction of S-L TV diameters, but isolated MVR group had an 11% increase in S-L TV diameters. Compared with TAP of size 26 mm and 28 mm rings group, suture TAP group had more common significant residual TR (29% vs. 3%, p = 0.001). Our study demonstrated that ring annuloplasty could provide effective reduction of the TV annulus and prevent postoperative TR progression, and for rheumatic mitral valve disease patients with mild functional TR, prophylactic TAP concomitant with MVR might be considered to address the postoperative TV annulus dilation.

11.
Microorganisms ; 7(10)2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31546741

RESUMO

A bacterial strain, Streptomyces albogriseolus LBX-2, was isolated from a soil sample in Chengdu, China. S. albogriseolus LBX-2 is an aerobic and Gram-positive microorganism that is capable of using the polyethylene as the sole carbon source. Results of scanning electron microscopy and tensile tests indicated that S. albogriseolus LBX-2 could cause the damages to polyethylene (PE). Suspension culture of LBX-2 resulted in the weight loss in the PE powder over a 15-day period. The bacterial growth curve assay clearly demonstrated the utilization of n-hexadecane and n-octadecane for the strain LBX-2. Phylogenetic analysis showed that it was grouped in the same clade as S. albogriseolus belonging to Streptomyces. The complete genome of strain LBX-2 consists of a chromosome of 7,210,477 bp and a linear plasmid of 336,677 bp. Compared with other strains of Streptomyces, the genome size of S. albogriseolus LBX-2 was smaller than the average but its guanine and cytosine content (72.47%) was higher than the others. The Non-Redundant Protein Database (NR), Kyoto Encyclopedia of Genes and Genomes (KEGG), SwissProt, Gene Ontology (GO) and Clusters of Orthologous Groups (COG) annotations provided information on the specific functions of encoded proteins. A total of 21 monooxygenase and 22 dioxygenase genes were found in its genome. Synteny comparison with the genome of Streptomyces coelicolor A3(2) revealed a low overall genetic diversity between them. This study provides valuable information to reveal the underlying mechanisms on PE degradation by S. albogriseolus LBX-2.

12.
Drug Dev Res ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397505

RESUMO

The proteolytic enzyme ß-secretase (BACE1) plays a central role in the synthesis of the pathogenic ß-amyloid peptides (Aß) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+• ) assay, which could be used as a lead compound for further study.

13.
J Cell Biochem ; 120(11): 18762-18770, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31265172

RESUMO

In human, there are two myxovirus resistance genes-MX1 and MX2, which respectively encode MXA and MXB protein. For MXB, it was traditionally deemed to work in the progression of cell cycle and adjustment of nuclear import. Thus, we speculated that it might play important roles in tumor progression. The purpose of this study was to preliminarily explore the underlying functions and mechanism of the MX2 gene on glioblastoma multiforme. Quantitative reverse transcription polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), and transwell experiments were to detect the relative MX2 mRNA level and its biological functions on glioma cells, respectively. The data displayed that MX2 was obviously downregulated both in glioblastoma (GBM) and GBM cell lines, meanwhile, its overexpression could markedly reduce cell proliferation, migration, and invasion of glioma cells, implying that it was related with glioblastoma progression. In addition, the overall survival of patient with glioblastoma had a negative correlation with the MX2 expression. Then, Western blot indicated the potential mechanism of MX2 in glioblastoma. We found that MX2 overexpression could decrease the relative levels of phosphorylated-ERK1/2 (p-ERK1/2), p-p38, and nuclear factor-κB (NF-κB), while have no effects on extracellular signal-regulated kinase (ERK), p38, and lamin B1. Moreover, the influences of MX2 overexpression on cell proliferation, migration, and invasion could be weakened by the three inhibitors (PD98059, SB203580, and (pyridin-2-ylmethyl) dithiocarbamate [PDTC]). These results implied that MX2 might suppress the proliferation and metastasis of glioma cells by manipulating the ERK/P38/NF-κB signaling pathway. In conclusion, MX2 is potential to be a new marker used for glioblastoma prognosis or a new target for glioblastoma treatments.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(6): 613-618, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31208519

RESUMO

Food allergen-specific immune tolerance is defined as nonresponsiveness of the adaptive immune system to food antigens. Failed development or inhibition of such tolerance may cause food allergy. With the increasing incidence rate of food allergy year by year, more and more studies have found the association between food allergy and various diseases. The development of food allergen-specific immune tolerance in childhood has been taken more and more seriously. In recent years, many studies have shown that the development of food allergen-specific immune tolerance is influenced by various factors, which can be roughly divided into antigens, organisms, and environment. This article reviews the influencing factors for the development of immune tolerance to food allergens in children, in order to provide help for reducing the incidence of food allergy and improving the prognosis of food allergy.


Assuntos
Hipersensibilidade Alimentar , Alérgenos , Criança , Humanos , Tolerância Imunológica , Incidência
15.
Eur J Pharmacol ; 853: 184-192, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30928629

RESUMO

Celastrol exhibits anticancer activity and has a number of potential molecular targets. Among them, the proteasome has attracted particular attention. Although celastrol inhibits multiple myeloma (MM) cell proliferation, the induction of proteasome-inhibitory activity by celastrol in MM cells at the cellular level and in tumors of mice bearing xenografts has not been confirmed. In the present study, we found that celastrol inhibited the caspase-like (ß1), trypsin-like (ß2) and chymotrypsin-like (ß5) proteasome activities of purified human 20S proteasomes, with half-maximal inhibitory concentration (IC50) values of 7.1, 6.3, and 9.3 µmol/L, respectively. Celastrol also inhibited human MM cellular ß1, ß2, and ß5 proteasome activities, with IC50 values of 2.3, 2.1, and 0.9 µmol/L, respectively. After MM cells were treated with celastrol, a population of apoptotic cells and a population of cells in G0/G1 were observed. Celastrol also inhibited proteasome activity and induced apoptosis in tumor tissue. Treatment of MM.1S and RPMI 8226 tumor-bearing severe combined immunodeficiency (SCID) mice with celastrol reduced the tumor volume. In conclusion, our results reveal the effects of celastrol on proteasome activity in MM cells and shed light on the underlying mechanisms of its anticancer activity, providing a basis for developing celastrol as a potential therapeutic agent for MM.


Assuntos
Apoptose/efeitos dos fármacos , Mieloma Múltiplo/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Camundongos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
DNA Cell Biol ; 38(5): 436-442, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810360

RESUMO

Dilated cardiomyopathy (DCM) is a common type of cardiomyopathy. The pathogenesis of DCM remains unclear and involves varied genes. AXIN1 is a crucial gene in regulating various functions in cells, it encodes protein Axin1, which regulates the assembly and disassembly of ß-catenin destruction complex. In addition, Wnt/ß-catenin signaling pathway plays an important role in cardiogenesis. We aimed to detect whether AXIN1 polymorphisms contribute to the susceptibility and prognosis of DCM in a Chinese Han population. A total of 340 DCM patients and 430 controls were enrolled, and patients who had complete contact information were followed up for a median period of 49 months. Polymerase chain reaction-restriction fragment length polymorphism was carried out to genotype the two AXIN1 tag single nucleotide polymorphisms (SNPs) (rs12921862 and rs1805105). All data were analyzed using the statistical software package, SPSS 21.0. The frequencies of allele A in rs12921862 and allele C in rs1805015 were increased in DCM patients compared with healthy controls (p < 0.001). Genotypic frequencies of rs12921862 and rs1805105 were associated with the susceptibility of DCM in codominant, dominant, and overdominant models (p < 0.01). AA/AC and AC genotypes of rs12921862 in the dominant and the overdominant genetic models also presented a correlation with poor prognosis of DCM in both univariate (p < 0.01) and multivariate analyses (p < 0.01) after adjusting for age, gender, left ventricular (LV) end-diastolic diameter, and LV ejection fraction. Our results suggest that AXIN1 polymorphisms are associated with the susceptibility and prognosis of DCM in a Chinese Han population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteína Axina/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Cardiomiopatia Dilatada/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Pediatr Allergy Immunol ; 30(4): 451-461, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30703250

RESUMO

BACKGROUND: The role of atopy patch test (APT) in the diagnosis of food allergy (FA) remains largely controversial. In our meta-analysis, we aimed to evaluate the accuracy of APT for diagnosing FA in children. METHODS: Pubmed, Embase and Cochrane Library were searched for studies regarding the diagnostic value of APT for FA in children compared to oral food challenge (double-blind placebo-controlled food challenge and/or open food challenge). The last search was conducted on November 11, 2017. Two reviewers independently screened relevant studies and assessed the quality by QUADAS-2. Meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), NLR (negative likelihood ratio) with their 95% confidence intervals (CIs). Subgroup analyses were conducted according to different food allergens, atopic dermatitis, gastrointestinal symptoms, and age younger than 3 years. RESULTS: Forty-one studies were included in the meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were 50.30% (95% CI 48.40%-52.30%), 86.60% (95% CI 85.30%-87.80%), 3.405 (95% CI 2.594-4.470), 0.545 (95% CI 0.469-0.634) and 7.528 (95% CI 5.507-11.206), respectively. However, for children with FA-related gastrointestinal symptoms, the pooled sensitivity and specificity were 57.40% (95% CI 52.10%-62.50%) and 91.50% (95% CI 88.30%-94.10%) respectively. CONCLUSIONS: Our findings suggest that APT is specific but not sensitive for diagnosing FA in children, especially in children with FA-related gastrointestinal symptoms.

19.
Beilstein J Org Chem ; 15: 291-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30800179

RESUMO

Herein we report a novel palladium-catalyzed reaction that results in phenanthrene derivatives using aryl iodides, ortho-bromobenzoyl chlorides and norbornadiene in one pot. This dramatic transformation undergoes ortho-C-H activation, decarbonylation and subsequent a retro-Diels-Alder process. Pleasantly, this protocol has a wider substrate range, shorter reaction times and higher yields of products than previously reported methods.

20.
Nat Prod Res ; 33(20): 2925-2931, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30518257

RESUMO

One new indole-type alkaloid, α-L-rhamnopyranosyl-(1→6)-ß-D- glucopyranosyl 6-methoxy-3-indolecarbonate (1), together with three known alkaloids (2-4), one aromatic acid (5) and five known saponins (6-10), was isolated from the roots of Clematis florida var. plena. Their structures were established by NMR spectroscopic analysis and acid hydrolysis. In in vivo anti-inflammatory activity, n-butanol extract was found to be potent against ear edema in mice, with inhibition rate of 48.7% at a dose of 800 mg/kg. Furthermore, compounds 8 and 9 obtained from the n-butanol extract exhibited significant anti-inflammatory activities with inhibition rates of 50.9% and 54.7% at a dose of 200 mg/kg.


Assuntos
Alcaloides/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Clematis/química , Raízes de Plantas/química , Alcaloides/análise , Animais , Edema/etiologia , Florida , Hidrólise , Indóis/isolamento & purificação , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Extratos Vegetais/farmacologia , Saponinas/química , Triterpenos/química
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