Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.619
Filtrar
1.
New Phytol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705812

RESUMO

Some medicinal plants of the Solanaceae produce pharmaceutical tropane alkaloids (TAs), such as hyoscyamine and scopolamine. Littorine is a key biosynthetic intermediate in the hyoscyamine and scopolamine biosynthetic pathways. However, the mechanism underlying littorine formation from the precursors phenyllactate and tropine is not completely understood. Here, we report the elucidation of littorine biosynthesis through a functional genomics approach and functional identification of two novel biosynthesis genes that encode phenyllactate UDP-glycosyltransferase (UGT1) and littorine synthase (LS). UGT1 and LS are highly and specifically expressed in Atropa belladonna secondary roots. Suppression of either UGT1 or LS disrupted the biosynthesis of littorine and its TA derivatives (hyoscyamine and scopolamine). Purified His-tagged UGT1 catalysed phenyllactate glycosylation to form phenyllactylglucose. UGT1 and LS co-expression in tobacco leaves led to littorine synthesis if tropine and phenyllactate were added. This identification of UGT1 and LS provides the missing link in littorine biosynthesis. The results pave the way for producing hyoscyamine and scopolamine for medical use by metabolic engineering or synthetic biology.

2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(10): 1224-1230, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31771719

RESUMO

OBJECTIVE: To evaluate the application of heparin-binding protein (HBP) in diagnosis of sepsis in adult patients. METHODS: An extensive search for the Chinese and English literatures from the PubMed, Embase, the Cochrane Library, Wanfang data, CNKI and VIP up to July 2019 was performed. The articles regarding HBP for the diagnosing of sepsis in adult patients were enrolled. Two researchers independently extracted related literature. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-Disc 1.4 and STATA 12.0 were used for Meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to evaluate the diagnostic performance of HBP for sepsis. Deek funnel plot was used to detect publication bias. RESULTS: A total of 10 studies with 1 884 patients were included in this Meta-analysis. The quality of the literature was relatively moderate. HBP in plasma were detected by enzyme linked immunosorbent assay (ELISA) in all studies. The studies showed substantial heterogeneity, and random effect model was used for Meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.80 [95% confidence interval (95%CI) was 0.77-0.83], 0.80 (95%CI was 0.78-0.82), 3.96 (95%CI was 2.45-6.41), 0.28 (95%CI was 0.20-0.39) and 14.63 (95%CI was 6.83-31.30) respectively. The pooled AUC was 0.86 and the Cochran-Q was 0.79. To explore the potential sources of heterogeneity, subgroup analyses were performed based on the severity of the disease, diagnostic criteria and region. However, the results indicated that no methodological covariates affected the diagnostic accuracy of HBP, indicating that there was still unexplained heterogeneity. In addition, the sensitivity analysis by removing individual studies were performed. No outlier study was identified and the results were relatively stable and reliable. Deek funnel plot showed little publication bias. CONCLUSIONS: There is preferable value of HBP for diagnosis of sepsis in adult patients. However, it needs to be further confirmed by large multicenter studies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31741370

RESUMO

Monoclinic BiVO4 (BiV) is a good photoanode for water oxidation but a poor photocatalyst for organic oxidation because of slow O2 reduction. In this work, a well-crystallized BiV microdecahedron (1-2 µm) has been deposited with a poorly crystallized cubic CuFe2O4 (CF) nanosphere (100 nm). For phenol oxidation and O2 reduction to H2O2 in aqueous suspension under visible light, 1 wt % CF/BiV was more active than BiV by approximately factors of 14 and 7, respectively, while CF was almost not active. A (photo)electrochemical measurement showed that CF/BiV was more active than BiV not only for phenol and water oxidation under visible light but also for O2 reduction and water oxidation in the dark. Moreover, as compared to BiV, CF/BiV was more efficient in the charge transfer to a solution species but less efficient either in the light-on electron generation or in the light-off electron disappearance. Based on the solid band edge potentials measured by ultraviolet photoelectron spectroscopy, a possible Z scheme mechanism is proposed involving charge recombination at the CF/BiV interfaces followed by the increased O2 reduction on CF and the increased phenol oxidation on BiV.

4.
Bioinformatics ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755899

RESUMO

MOTIVATION: Although genome-wide association studies (GWAS) have deepened our understanding of the genetic architecture of complex traits, the mechanistic links that underlie how genetic variants cause complex traits remains elusive. To advance our understanding of the underlying mechanistic links, various consortia have collected a vast volume of genomic data that enable us to investigate the role that genetic variants play in gene expression regulation. Recently, a collaborative mixed model (CoMM) (Yang et al., 2018a) was proposed to jointly interrogate genome on complex traits by integrating both theGWAS dataset and the expression quantitative trait loci (eQTL) dataset. Although CoMM is a powerful approach that leverages regulatory information while accounting for the uncertainty in using an eQTL dataset, it requires individual-level GWAS data and cannot fully make use of widely available GWAS summary statistics. Therefore, statistically efficient methods that leverages transcriptome information using only summary statistics information from GWAS data are required. RESULTS: In this study, we propose a novel probabilistic model, CoMM-S2, to examine the mechanistic role that genetic variants play, by using only GWAS summary statistics instead of individual-level GWAS data. Similar to CoMM which uses individual-level GWAS data, CoMM-S2 combines two models: the first model examines the relationship between gene expression and genotype, while the second model examines the relationship between the phenotype and the predicted gene expression from the first model. Distinct from CoMM, CoMM-S2 requires only GWAS summary statistics. Using both simulation studies and real data analysis, we demonstrate that even though CoMM-S2 utilizes GWAS summary statistics, it has comparable performance as CoMM, which uses individual-level GWAS data. AVAILABILITY AND IMPLEMENTATION: The implement of CoMM-S2 is included in the CoMM package that can be downloaded from https://github.com/gordonliu810822/CoMM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31740556

RESUMO

Quinolone resistance is increasing in Neisseria meningitidis, with high prevalence in China (>70%), but its origin remains unknown. The aim of this study was to investigate donors of mutation-harboring gyrA alleles in N. meningitidis A total of 198 N. meningitidis and 293 commensal Neisseria isolates were collected between 2005 and 2018 in Shanghai, China. Minimum inhibitory concentrations (MICs) of ciprofloxacin were determined using agar dilution method. Resistance-associated genes gyrA and parC were sequenced for all isolates, while a few isolates were performed Illumina sequencing. The prevalence of quinolone resistance in N. meningitidis and commensal Neisseria was 67.7% (134/198) and 99.3% (291/293), respectively. All 134 quinolone-resistant N. meningitidis isolates possessed mutations in T91 (n=123) and/or D95 (n=12) of GyrA, with 7 isolates also harboring ParC mutations and exhibiting higher MICs. Phylogenetic analysis of the gyrA sequence identified six clusters. Among the 71 mutation-harboring gyrA alleles represented by 221 N. meningitidis isolates and genomes (n=221), 12 alleles (n=103, 46.6%) were included in N. meningitidis cluster, while 20 alleles (n=56) in N. lactamica cluster, 27 alleles (n=49) in N. cinerea cluster, and 9 alleles (n=10) in N. subflava cluster. Genomic analyses identified the exact N. lactimica donors of seven mutation-harboring gyrA alleles (gyrA92, gyrA97, gyrA98, gyrA114, gyrA116, gyrA151, and gyrA230) and the N. subflava donor isolate of gyrA171, with recombinant fragment ranging from 634 to 7499 bp. Transformation of gyrA fragments from these donor strains into a meningococcal isolate increased its ciprofloxacin MIC from 0.004 µg/ml to 0.125 or 0.19 µg/ml, and to 0.5 µg/ml with further transformation of an additional ParC mutation. Over half of quinolone-resistant N. meningitidis isolates acquired resistance by horizontal gene transfer from three commensal Neisseria species. Quinolone resistance in N. meningitidis increases in a stepwise manner.

6.
Mol Med Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746399

RESUMO

Bone marrow mesenchymal stem cells (BM­MSCs) are important for postnatal angiogenesis and are suitable for use in construction of blood vessels by tissue engineering. The present study aimed to investigate the influence of recombination signal binding protein for immunoglobulin kappa J region (RBP­JK) on the differentiation of BM­MSCs into vascular endothelial cells, and to assess the underlying mechanisms. BM­MSCs were isolated and identified by flow cytometry. Lentiviral vectors encoding RBP­JK shRNA (shRBPJK) were constructed to knockdown RBP­JK expression and endothelial differentiation of BM­MSCs was induced. The experimental groups were treated with: empty lentiviral vector (vector group), growth factors (bFGF and VEGF; induced group), shRBPJK (shRBPJK group), and growth factors + shRBPJK (induced + shRBPJK group). The expression of endothelial markers, vascular endothelial growth factor receptor 2 (Flk­1), and von Willebrand factor (vWF) were detected by immunofluorescence. Additionally, in vitro blood vessel formation and phagocytosis were assessed using acetylated LDL, Dil complex and the underlying molecular mechanisms evaluated by western blotting. BM­MSCs were separated and transduced with shRBPJK to reduce RBP­JK expression. Compared with the vector group, the expression of the endothelial cell markers, Flk­1 and vWF, in vitro tubule formation, and phagocytosis ability increased, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were significantly decreased (P<0.05) in the induced, shRBPJK, and induced + shRBPJK groups. Compared with the induced group, the expression of Flk­1 and vWF, the number of tubules, and phagocytosis were higher in the induced + shRBPJK group, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were lower (P<0.05). Collectively, the present data indicated that silencing of RBP­JK promotes the differentiation of MSCs into vascular endothelial cells, and this process is likely regulated by AKT/NF­κB signaling.

7.
Eur J Surg Oncol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31677940

RESUMO

BACKGROUND: Both radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) are minimally invasive approach for hepatocellular carcinoma (HCC) at early stage. This study aimed to compare the efficacy of RFA and LH for treating HCC with a large cohort. METHODS: From March 2014 to July 2016, 477 patients who underwent RFA (n = 314) or LH (n = 163) for HCC tumors meeting the criteria were included. Overall survival (OS) and recurrence-free survival (RFS) were compared. Propensity score matching (PSM) was performed to balance for the factors that may affect the choice of treatment. RESULTS: Collectively, the 1-, 2- and 3-year OS rates were significantly greater after LH than RFA, as well the corresponding RFS rates, before and after PSM by 2:1. However, the RFA group had fewer major complications (P=0.004), shorter postoperative stays (P=0.023) and lower hospital charges (P<0.001) than the LH group. In the subgroup analysis, RFA demonstrated comparable RFS in treating less than 3 cm tumor (P=0.22) located in noncentral bisection (SII, SIII, SVI, SVII) and tumor between 3 cm and 5 cm (P=0.07) located in central bisections (SIV, SV, SVIII). The female, HBV infection, and RFA are factors of worse OS, and the latter two factors also indicated higher RFS. CONCLUSIONS: Though, LH possessed superior intrahepatic control rate than RFA in most condition of tumor smaller than 5 cm, the RFA could be an optimal approach achieved comparable outcomes in patients with centrally located HCC, with fewer major complications, shorter postoperative stays and lower hospital charges.

8.
Math Biosci Eng ; 16(6): 7921-7933, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31698647

RESUMO

Background: An increasing number of patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and develop progressive disease after receiving conventional treatments. In recent years, several novel therapies have been approved for later lines of therapy of previously treated NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as the second-line therapy for pre-treated patients. However, the use of erlotinib has been reported to represent different clinical effects and adverse effects. Objectives: The current study was aim to investigate the efficacy and safety of erlotinib versus chemotherapy in pre-treated patients with advanced NSCLC. Methods: Electronic databases were searched for eligible literatures updated on June 2018. Randomized-controlled trials assessing the efficacy and safety of erlotinib in pre-treated NSCLC were included, of which the main outcomes were ORR (objective response rate), PFS (progression-free survival), OS (overall survival) and AEs (adverse events). All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. Results: A total of 11 randomized controlled trials were included in this analysis. The group of erlotinib did not achieved benefit in progression-free survival (OR = 0.61, 95%CI = 0.33-1.12, P = 0.11), overall survival (OR = 0.98, 95%CI = 0.84-1.15, P = 0.81) as well with the objective response rate (OR = 0.77, 95%CI = 0.36-1.63, P = 0.49), respectively. In the results of subgroup analysis among the patients with EGFR wild-type, there is also no significant differences in overall survival with erlotinib (OR = 0.90, 95%CI = 0.78-1.04, P = 0.15) and progression-free survival (OR = 0.33, 95%CI = 0.09-1.18, P = 0.09). The most common treatment-related adverse events in the erlotinib group is rash (OR = 5.79, 95%CI = 2.12-15.77, P = 0.0006), and neutropenia (OR = 0.02, 95%CI = 0.01-0.10, P ≤ 0.00001) is more found in the control group. In addition, fatigue (P = 0.09) and diarrhea (P = 0.52), the difference between the two groups had no statistical significance. Conclusions: There was no significant difference noted with regard to efficacy and safety between erlotinib vs. chemotherapy as the later-line therapy for previously treated patients with NSCLC, even with subgroup patients who have wild-type EGFR tumors. While, erlotinib might increase the risk of rash, and decrease the risk of neutropenia, compared with the chemotherapy. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.

9.
Cell Rep ; 29(7): 1862-1877.e7, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31722203

RESUMO

Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.

10.
Hepatology ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677282

RESUMO

Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. We included 1031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort (GLCC) enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer (BCLC) stage, and cancer treatment. The multivariable-adjusted HRs in the highest vs. lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend=0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend=0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CONCLUSION: Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31705277

RESUMO

PURPOSE: The relationships among PSG findings, OSA symptoms, and tonsil and adenoid size are not clear. In this study, we aimed to investigate the associations between pediatric OSA and tonsil and adenoid size using subjective (OSA-18 questionnaire) and objective (PSG) measurements. METHODS: 101 consecutive patients aged from 2 to 12 years (mean age, 5.4 ± 2.2 years; boys, 72.3%) diagnosed with OSA were enrolled in two age groups (2-6 years group and 7-12 years group) and underwent PSG and lateral cephalometric radiography. Tonsil size and the adenoid-nasopharyngeal (A/N) ratio were determined. Quality of life and sleep symptoms were measured using the Chinese version OSA-18 questionnaire. Demographic and clinical data were obtained. RESULTS: 75 and 26 patients were separately enrolled in 2-6 years group and 7-12 years group. In 2-6 years group, the multiple linear regression revealed that tonsil size and A/N ratio were associated with log apnea-hypopnea index (AHI), and the Spearman's rank correlation reflected a positive correlation between log AHI and the OSA-18 sleep disturbance score (r = 0.362, P = 0.001). Log OSA-18 score was correlated with tonsil size (r = 0.349, P = 0.002) but not the A/N ratio in 2-6 years group. Finally, no significant associations were observed between log OSA-18 scores and log AHI in all patients. CONCLUSION: As PSG stays the golden standard for diagnoses of pediatric OSA, physical examinations and quality-of-life assessments are needed to fully assess the impact of OSA on children.

12.
Medicine (Baltimore) ; 98(46): e17403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725603

RESUMO

Studies investigating the association between gene variants and depression susceptibility found inconsistent data. The present study aimed to clarify whether CNR1rs1049353, CNR1 AAT triplet repeat, and CNR2rs2501432 polymorphisms confer higher risk for depressive disorder.Literature from PubMed, Medline, Embase, Scopus, Cochrance Library, and Wanfang databases was searched (up to August 20, 2018). Seven case-control studies with various comorbidities were eligible. We targeted CNR single-nucleotide polymorphisms (SNPs) that have been reported by 2 or more studies to be involved in the current meta-analysis, resulting in a final list of 3 SNPs: CNR1rs1049353, CNR1 AAT triplet repeat polymorphism, and CNR2rs2501432. Odds ratios (ORs) and 95% confidence intervals (CIs) for allele and homozygote comparisons, dominant and recessive models, and triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5) were assessed using a random effect model as measures of association. Heterogeneity among included studies was analyzed using sensitivity test. Publication bias was also explored by Egger and rank correlation test.overall, no significant association was found between depression and CNR1rs1049353 (G vs A: OR [95% CI] = 1.09 [0.61-1.95]; GG vs AA: 1.29 [0.73-2.26]; GG vs GA+AA: 1.10 [0.57-2.10]; GG+GA vs AA: 1.25 [0.72-2.18]; and AAT triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5): 1.92 [0.59-6.27]. In contrast, a significant association between CNR2rs2501432 and depression was detected, and the ORs and 95% CIs are as follows: allele contrast (OR = 1.39, 95% CI = [1.12-1.72], P = .003); homozygous (OR = 2.19, 95% CI = [1.34-3.59], P = .002); dominant (OR = 1.93,95% CI = [1.23-3.04], P = .005); and recessive (OR = 1.41, 95% CI = [1.04-1.92], P = .03).This meta-analysis revealed that CNR1rs1049353 or AAT triplet repeat polymorphism had no association with susceptibility to depression, while CNR2rs2501432 polymorphism was a remarkable mark for depression patients.


Assuntos
Depressão/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Alelos , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco
13.
Int J Biol Sci ; 15(12): 2522-2537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754326

RESUMO

Despite remarkable advancements in our understanding of breast cancer, it remains the leading cause of cancer deaths in women. Distant recurrence and metastasis is the main reason for death due to breast cancer. It is well recognized that the GATA binding protein 3 (GATA3), a transcription factor, is a tumor suppressor in breast cancer. To date, the mechanistic molecular details of GATA3 remain elusive, because, as a transcription factor, it is not a direct executor in physiological and pathological processes. Here, we demonstrate that GATA3 reduces the ATP level in the breast cancer microenvironment and inhibits breast cancer metastasis by up-regulating ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3). The extracellular ATP concentration is significantly higher in tumor tissues than in normal tissues and promotes the migration of cancer cells from the primary site. ENTPD3 hydrolyzes ATP in tumor microenvironment and suppresses breast cancer metastasis. Furthermore, ENTPD3 inhibits epithelial-to-mesenchymal transition, a key program responsible for the development of metastatic disease. These findings provide novel insights into the tumor suppressor activity of GATA3.

14.
Theranostics ; 9(26): 8392-8408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754404

RESUMO

Calcyclin-binding protein (CACYBP) is a multi-ligand protein implicated in the progression of various human cancers. However, its function in hepatocellular carcinoma (HCC) remains unknown. Methods: The expression of CACYBP and RNF41 (RING finger protein 41) in HCC cancer and adjacent non-tumor tissues was detected by immunohistochemistry. CCK-8 assays, colony formation assays, flow cytometry detection and xenograft models were used to evaluate the impact of CACYBP expression on HCC cell growth, apoptosis and cell cycle regulation. Immunoprecipitation and ubiquitination assays were performed to determine how RNF41 regulates CACYBP. The regulatory mechanism of RNF41-CACYBP signaling axis on P27Kip1 was investigated by western blotting and immunofluorescence. Results: CACYBP was highly expressed and associated with poor prognosis in HCC. CACYBP expression was required for HCC cell growth in vitro and in vivo. Moreover, we identified RNF41 as a specific binding partner of CACYBP at exogenous and endogenous levels. RNF41 recruited CACYBP by its C-terminal substrate binding domain, subsequently ubiquitinating CACYBP and promoting its degradation in both proteasome- and lysosome-dependent pathways. In HCC tissues, RNF41 expression was reduced and conferred a negative correlation with CACYBP expression. Mechanistically, CACYBP overexpression stimulated the Ser10, Thr157 and Thr198 phosphorylation of P27Kip1 and its cytoplasmic retention, and RNF41 co-expression attenuated this phenomenon. CACYBP depletion led to decreased levels of cyclin D1, cyclin A2, CDK2 and CDK4, causing a typical cell cycle arrest at G1/S phase and increasing apoptosis in HCC cells. P27Kip1-S10D but not P27Kip1-S10A reconstitution rescued partially the cell cycle function and apoptotic feature after CACYBP depletion. Conclusion: Our findings provide novel insights into the functional role and regulatory mechanism of CACYBP in HCC.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31766587

RESUMO

The effects of hydrodynamics on algae growth have received considerable attention, and flow velocity is one of the most frequently discussed factors. For Euglena gracilis, which aggregates resources and is highly resistant to environmental changes, the mechanism underlying the impact of flow velocity on its growth is poorly understood. Experiments were conducted to examine the response of algae growth to different velocities, and several enzymes were tested to determine their physiological mechanisms. Significant differences in the growth of E. gracilis were found at different flow velocities, and this phenomenon is unique compared to the growth of other algal species. With increasing flow velocity and time, the growth of E. gracilis is gradually inhibited. In particular, we found that the pioneer enzyme is peroxidase (POD) and that the main antioxidant enzyme is catalase (CAT) when E. gracilis experiences flow velocity stress. Hysteresis between total phosphorus (TP) consumption and alkaline phosphatase (AKP) synthesis was observed. Under experimental control conditions, the results indicate that flow velocities above 0.1 m/s may inhibit growth and that E. gracilis prefers a relatively slow or even static flow velocity, and this finding could be beneficial for the control of E. gracilis blooms.

16.
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).

17.
World Neurosurg ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756500

RESUMO

OBJECTIVE: Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased healthcare costs, and mortality. We assessed the effectiveness of a pragmatic risk stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision-making, in reducing the rate of VRIs. METHODS: Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across three hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the three sites from January 2015 to December 2016. RESULTS: The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P=.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = .33). In two sites (Site 1, 2.0% vs. 2.1% vs. 1.9%, and Site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk stratification pathway maintained already low infection rates; in Site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = .06). CONCLUSION: The introduction of a pragmatic evidence-based risk stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multi-site institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.

18.
Mikrochim Acta ; 186(12): 835, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758331

RESUMO

A dual (colorimetric and fluorometric) method is described for sensitive and selective determination of the herbicide glyphosate. It is based on the use of a system composed of polyethylenimine-capped NaGdF4:Yb,Er upconversion nanoparticles (UCNPs), copper(II) ions, hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine. The physicochemical and photophysical properties of the polyethylenimine-capped UCNPs were characterized by various spectroscopic and microscopic techniques. The fluorescence of the UCNPs (with main emission peaks at 548 and 660 nm under 980 nm excitation) is reduced in the presence of Cu(II) because of the formation of a blue oxidation product of 3,3',5,5'-tetramethylbenzidine as a result of the peroxidase mimicking activity of Cu(II). In the presence of glyphosate, its strong affinity for Cu(II) leads to the formation of N-(phosphonomethyl)glycine copper(II) complexes. This inhibits the quenching ability and catalysis activity of Cu(II). Hence, fluorescence is increasingly less reduced. Fluorescence at 660 nm increases linearly in the 0.05 to 125 µg·mL-1 glyphosate concentration range and the detection limit is found 9.8 ng·mL-1. The colorimetric assay (performed at 652 nm) has a detection ranges from 5 to 125 µg·mL-1, and the limit of detection is 1 µg·mL-1. Graphical abstractSchematic representation of UCNP-H2O2-TMB-Cu(II) mixed system for optical determinations of glyphosate.

19.
Neurosci Lett ; : 134640, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759083

RESUMO

Dopaminergic (DAergic) degeneration and abnormal α-synuclein (α-syn) expression, phosphorylation and aggregation are observed in both the nigrostriatal system (NSS) and enteric nervous system (ENS) of patients with Parkinson's disease (PD). Whether these alterations in α-syn and DAergic neurons occur synchronously in the two nervous systems or follow a process that spreads from the gut to the brain remains a subject of debate. Here, in MPTP-intoxicated cynomolgus monkeys, we showed a parallel DAergic degeneration in the colon as well as in the substantia nigra and striatum (SN/STR), as indicated by reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). In addition, we observed a simultaneous increase in the concentrations of total, phosphorylated, and oligomeric α-syn in the colon and SN/STR. Moreover, we identified that the above changes in α-syn were associated with an increase in the expression of polo-like kinase 2 (PLK2), an enzyme that promotes α-syn phosphorylation, and a decrease in the activity of protein phosphatase 2A (PP2A), an enzyme that facilitates α-syn dephosphorylation. Because the colonic ENS can be readily analyzed using routine biopsies, the shared pathological features between the colonic ENS and the brain NSS found in this study provide useful information for assessing and understanding the neuropathology in PD patients using colonic biopsies.

20.
Prenat Diagn ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671222

RESUMO

OBJECTIVE: To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). METHOD: A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. RESULTS: The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. CONCLUSION: Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA