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1.
Bioorg Chem ; 109: 104740, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33626453

RESUMO

Six new non-classical cardenolides (1-6), and seventeen known ones (7-23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM-16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a well-studied HIF-1 inhibitor, and 11, 12, 14, 16 and 19 presented 1.4-15.4 folds stronger HIF-1 inhibition than digoxin. 1 and 11 showed a dose-dependent inhibition on HIF-1α protein, which led to their HIF-1 suppressing effects. Compared with LO2 and H9c2 normal cell lines, both 1 and 11 showed selective cytotoxicity against various cancer cell lines including HCT116, HeLa, HepG2, A549, MCF-7, A2780 and MDA-MB-231. Moreover, a comprehensive structure-activity relationship was concluded for these non-classical cardenolides as HIF-1 inhibitors, which may shed some light on the rational design and development of cardenolide-based anticancer drugs.

2.
Biochem Biophys Res Commun ; 547: 9-14, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33588236

RESUMO

Lactic acid in tumor microenvironment inhibits iNKT cell functions and thus dampens their anti-tumor efficacy. The underlying mechanisms remain unclear. Here, we show that phosphodiesterase-5 inhibitors, sildenafil and tadalafil, promote IFN-γ and IL-4 production in iNKT cells in a cGMP-PKG pathway dependent manner. To favor their cytokine production, iNKT cells reduce Pde5a mRNA lever after activation. In line with the reduction of cytokines caused by lactic acid, lactic acid elevates Pde5a mRNA lever in activated iNKT cells. As a result, phosphodiesterase-5 inhibitor partially restores the cytokine production in lactic acid-treated cells. Our results demonstrate that phosphodiesterase-5 inhibits cytokine production in iNKT cells, and that contributes to the lactic acid-caused dysfunction of iNKT cells.

5.
BMJ Open ; 11(2): e045034, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33550266

RESUMO

OBJECTIVES: This study aimed to investigate the knowledge-attitude-practice (KAP) of Chinese college students regarding COVID-19 and evaluate their psychological status against the background of the COVID-19 outbreak. DESIGN: This was a cross-sectional study. SETTING: This study covered 31 provinces, municipalities and autonomous regions of mainland China. PARTICIPANTS: The participants, who were college students with ordinary full-time status, were surveyed anonymously on their KAP regarding COVID-19 by using self-made questionnaires. In addition, the Self-Rating Anxiety Scale was used to assess the psychological status of the students. METHODS: The online cross-sectional study among Chinese college students was conducted in February 2020. Logistic regression analysis was used to analyse the predictors of anxiety symptoms. PRIMARY OUTCOME MEASURES: The level of KAP and anxiety symptoms. RESULTS: A total of 740 college students from 31 provinces, municipalities and autonomous regions in China were recruited in the survey. Among them, 139 (18.78%) revealed having anxiety. Multivariable logistic regression analysis revealed that female gender was the risk factor for anxiety symptoms with an increased 2.164-fold risk than male gender (OR=2.164, 95% CI=1.279 to 3.662). The knowledge (OR=0.825, 95% CI=0.779 to 0.873) and attitude (OR=0.822, 95% CI=0.762 to 0.887) regarding COVID-19 were protective factors against anxiety symptoms. CONCLUSIONS: The level of KAP regarding COVID-19 was significantly negatively correlated with anxiety symptoms. Thus, understanding the level of KAP among college students during the early stages of major public health emergencies, such as a pandemic, is important. Such understanding plays an important role in adopting targeted health education strategies and reducing the psychological damage caused by these emergencies.


Assuntos
Ansiedade/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Estudantes/psicologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Inquéritos e Questionários , Universidades
6.
Foodborne Pathog Dis ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524305

RESUMO

Most outbreaks of Shiga toxin-producing Escherichia coli (STEC) are attributed to consumption of contaminated foodstuffs including beef and dairy products. In this study, we evaluated the prevalence of non-O157 STEC cultured from beef and dairy cattle and collected in Xinjiang Uygur Autonomous Region in China. Results identified 67 non-O157 STEC recovered from the 793 samples including beef cattle (10.28%, 43/418) and dairy cattle (6.40%, 24/375). A total of 67 non-O157 STEC was sequenced allowing for in silico analyses of their serotypes, virulence genes, and identification of the corresponding multilocus sequence types (STs). Twenty-one O serogroups and nine H serotypes were identified and the dominant serotype identified was O22:H8. One stx1 subtype (stx1a) and four stx2 subtypes (2a, 2b, 2c, and 2d) were found in the 67 non-O157 STEC isolates. The results revealed that stx1a+stx2a-positive STEC isolates were predominant (32.83%, 22/67), followed by stx1a+stx2d (29.85%, 20/67) and stx2a alone (17.91%, 12/67). Non-O157 STEC isolates carried virulence genes ehxA (98.51%), subA (53.73%), and cdtB (17.91%). Of the four adherence-associated genes tested, eaeA was absent, whereas lpfA and iha were present in 67 and 55 non-O157 STEC isolates, respectively. The STEC isolates were divided into 48 pulsed-field gel electrophoresis patterns and 10 STs, and ST446 (O22:H8) was the dominant clone (22.38%). Our results revealed that there was a high genetic diversity among non-O157 STEC isolated from beef and dairy cattle, some of which have potential to cause human diseases.

7.
Gynecol Endocrinol ; : 1-10, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33487087

RESUMO

AIMS: To investigate the correlation between hypertriglyceridemic waist circumference (HTWC) phenotype and gestational diabetes mellitus (GDM). METHODS: A total of 1083 patients with gestational age ≤8 weeks were divided into four groups: normal triglyceride and waist circumference group (group A, n = 575), simple abdominal obesity group (group B, n = 317), simple high triglyceride group (group C, n = 125), and HTWC group (group D, n = 66). General information and serum biochemical indicators were measured and recorded. Analysis of variance (ANOVA) and logistic regression analysis were used to evaluate the relationship between HTWC with GDM. RESULTS: The prevalence of GDM in the HTWC group was significantly greater than in the other three groups. After adjustment by multivariate logistic regression analysis, the proportion of GDM in the HTWC group was 1.753 times higher than in group A. CONCLUSION: These findings suggest that there is a significant correlation between HTWC phenotype and GDM, indicating that the HTWC phenotype could be applied as a simple marker for identifying GDM risk factors.

8.
Funct Plant Biol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33487217

RESUMO

In this study, label-free quantitative proteomics were used to study cold stress-related proteins in Dongxiang wild rice (Oryza rufipogon Griff., DWR) and cold sensitive cultivated rice 'Xieqingzao B'(Oryza sativa L. ssp. indica cv., XB). The results demonstrated the presence of 101 and 216 differentially expressed proteins (DEPs) were detected in DWR and XB, respectively, after cold stress. Bioinformatics analysis showed that DWR and XB differed significantly in their ability to scavenge reactive oxygen species (ROS) and regulate energy metabolism. Of the 101 DEPs of DWR, 46 DEPs related to differential expressed genes were also detected by transcriptome analysis. And 13 out of 101 DEPs were located in previous cold related quantitative trait loci (QTL). Quantitative real-time PCR analysis indicated that protein expression and transcription patterns were not similar in XB and DWR. Protein-protein interaction (PPI) network was constituted using the DEPs of DWR and XB, and the following three centre proteins were identified: Q8H3I3, Q9LDN2, and Q2QXR8. Next, we selected a centre protein and two of the 37 DEPs with high levels of differential expression (fold change ≥ 2) were used for cloning and prokaryotic expression. We found that Q5Z9Q8 could significantly improve the cold tolerance of Escherichia coli.

9.
Cell Death Dis ; 12(1): 93, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462187

RESUMO

Necroptosis has emerged as a novel and crucial player in acute and chronic liver diseases. Necroptotic cells lead to the release of DAMPs including S100A9, followed by the development of necroinflammation. We previously have documented the beneficial hepatoprotection conferred by M2-like macrophages in acute-on-chronic liver failure (ACLF) in vitro and in vivo, namely, M2-like macrophages protect hepatocytes against apoptosis. Herein, we integrated necroptosis, S100A9, and necroinflammation into this hepatoprotection, and hypothesized M2-like macrophages exert a hepatoprotective effect through inhibiting necroptosis-S100A9-necroinflammation axis. To testify this hypothesis, control mice were pre-treated with necroptosis or S100A9 inhibitors followed by D-GalN/LPS challenge. The extent of liver injury and M1/M2 macrophage activation was assessed. Necroptosis signaling and S100A9 expression were analysed and compared in control and fibrotic mice with or without acute insult. To document the pivotal role of M2-like macrophages in necroptosis and S100A9 inhibition, loss-of-function and gain-of-function experiments were performed. In addition, necroinflammation and its dependence on necroptosis and S100A9 were analysed. Moreover, the inhibitory effects of M2-like macrophages on necroinflammation were investigated in vivo and in vitro. We found that: firstly, the inhibition of necroptosis signaling and S100A9 expression alleviated D-GalN/LPS-induced hepatic damage, which was accompanied by M2-like macrophage activation; secondly, fibrosis inhibited necroptosis signaling and S100A9 expression, which could be attributed to M2-like macrophage activation; thirdly, S100A9 may function as a downstream player of necroptosis signaling; fourthly, fibrosis suppressed necroptosis- and S100A9-dependent necroinflammation; and finally, M2-like macrophages inhibited NLRP3 inflammasome activation and resultant necroinflammation via IL-10. Therefore, M2-like macrophages exert a beneficial hepatoprotection by inhibiting necroptosis-S100A9-necroinflammation axis in ACLF. Our findings provide novel insight for treating ACLF patients by specially targeting this signaling axis.

10.
Nanoscale Res Lett ; 16(1): 8, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411061

RESUMO

Periodical silver nanoparticle (NP) arrays were fabricated by magnetron sputtering method with anodic aluminum oxide templates to enhance the UV light emission from ZnO by the surface plasmon resonance effect. Theoretical simulations indicated that the surface plasmon resonance wavelength depended on the diameter and space of Ag NP arrays. By introducing Ag NP arrays with the diameter of 40 nm and space of 100 nm, the photoluminescence intensity of the near band-edge emission from ZnO was twofold enhanced. Time-resolved photoluminescence measurement and energy band analysis indicated that the UV light emission enhancement was attributed to the coupling between the surface plasmons in Ag NP arrays and the excitons in ZnO with the improved spontaneous emission rate and enhanced local electromagnetic fields.

11.
Arch Microbiol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398398

RESUMO

The composition of microorganisms in the gastrointestinal tract is closely related to the intestinal microenvironments and the exterior growth environments of host. In this study, 16S rDNA sequencing technology was adopted to investigate the influence of fermentation bed on the cecum microorganisms of ducks. Two feeding density treatment groups were set up, including group A (n = 4brids/m2) and group B (n = 6brids/m2). Samples were collected from the intermediate core fermentation layer (10-20 cm) of the fermented mattress materials and from the intestinal contents of ducks at 4, 6 and 8 weeks, respectively. Results showed that Bacteroidetes (20.12-27.17%) and Ruminococcaceae UCG-014 (2.97-10.1%) were the predominant microorganisms in duck cecum, while the Truepera (5.08-6.29%), Pricia (4.44-5.44%) and Luteimonas (3.62-4.99%) were the dominant microorganisms in fermentation mattress material. The cecum bacteria exhibited great difference among different growth periods of the ducks. Increasing the stocking density of ducks had a negative effect on the beneficial bacteria in the cecum. The microbial populations in fermentation mattress material were very different from that in the cecal. In summary, our findings can provide a scientific data for the rational use of fermentation bed feeding mode in poultry production.

12.
J Dairy Sci ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33455743

RESUMO

The activities of ß-galactosidases from bacteria and molds are affected by temperature, pH, and other factors in the processing of dairy products, limiting their application, so it is necessary to find alternative lactases. In this study, the ß-galactosidase gene from Bacillus coagulans T242 was cloned, co-expressed with a molecular chaperone in Escherichia coli BL21, and subjected to bioinformatic and kinetic analyses and lactase characterization. The results show that the enzyme is a novel thermostable neutral lactase with optimum hydrolytic activity at pH 6.8 and 50°C. The thermal stability and increased lactose hydrolysis activity of ß-galactosidase in the presence of Ca2+ indicated its potential application in the dairy industry.

13.
Appetite ; 160: 105092, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387589

RESUMO

In China, approximately half of total food waste is generated from the foodservice sector, which largely results from irresponsible consumer behavior when ordering food. Therefore, the purpose of this study was to better understand and intervene in Chinese consumers' ordering behavior in restaurants, ultimately contributing to minimizing food waste in China. Thus, the current study proposed a comprehensive model which incorporated habitual processes (individual ordering habits) and situational constraints (interventions from waiters) into the original theory of planned behavior (TPB) and the norm-activation (NAM) theoretical framework. This comprehensive model was tested on a sample of 527 consumers from Mainland China and was compared with the more mature models: TPB, NAM, and a combined model of both. Results showed that the comprehensive model explained the highest degree of variation in over-ordering behavior. Individual ordering habits and interventions from the waiter were proven to be crucial in understanding the complicated decision-making process of ordering foods in restaurants. Based on the model, implications for research and practice are also discussed.

15.
Ann Thorac Surg ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33482166

RESUMO

In patients with myocardial bridges (MB) and insufficient medical management, the optimal surgical strategy remains undetermined. Based on computer simulations, we developed a novel procedure, MB bypass graft (MBBG), which showed better hemodynamics compared with CABG in a simulation study. In this novel procedure, the left internal mammary artery was used to connect the proximal and distal ends of the MB. For the first time, we used MBBG to treat a patient with extensive MB. The patient recovered smoothly after surgery and the LIMA graft remained patent 3 months postoperatively.

16.
Bioresour Technol ; 323: 124616, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387711

RESUMO

Biochar was prepared by torrefaction of ammonium persulphate pretreated bamboo (labeled as APBC) and applied into elimination of Pb(II) from water solutions. APBC was characterized by N2 adsorption-desorption isotherms, elemental and Zeta potential analyses, SEM-EDS, XPS, and FTIR. Abundant N- and O-containing groups appeared atop APBC. Batch sorption assays revealed that APBC had high affinity and strong sorption ability towards Pb(II). The high Pb(II) adsorbing ability was attributed to the high contents of N- and O-containing functional groups of APBC. The adsorption mechanism mainly occurred by inner-sphere surface complexation. Hence, torrefaction of ammonium persulphate pretreated bamboo is a promising strategy for producing efficient biochar that is applicable for industrial wastewater treatment.


Assuntos
Chumbo , Poluentes Químicos da Água , Adsorção , Sulfato de Amônio , Carvão Vegetal , Poluentes Químicos da Água/análise
17.
Pediatrics ; 147(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33376211

RESUMO

BACKGROUND: Health administrative data offer a vital source of data on maternal prenatal opioid exposure (POE). The impact of different methods to estimate POE, especially combining maternal and newborn records, is not known. METHODS: This population-based cross-sectional study included 454 746 hospital births with linked administrative data in Ontario, Canada, in 2014-2017. POE ascertainment included 3 sources: (1) prenatal opioid prescriptions, (2) maternal opioid-related hospital records, and (3) newborn hospital records with neonatal abstinence syndrome (NAS). Positive percent agreement was calculated comparing cases identified by source, and a comprehensive method was developed combining all 3 sources. We replicated common definitions of POE and NAS from existing literature and compared both number of cases ascertained and maternal socio-demographics and medical history using the comprehensive method. RESULTS: Using all 3 data sources, there were 9624 cases with POE (21.2 per 1000 births). Among these, positive percent agreement (95% confidence interval) was 79.0% (78.2-79.8) for prenatal opioid prescriptions, 19.0% (18.2-19.8) for maternal opioid-related hospital records, and 44.7% (43.7-45.7) for newborn NAS. Compared with other definitions, our comprehensive method identified up to 523% additional cases. Contrasting ascertainment with maternal opioid-related hospital records, newborn NAS, and prenatal opioid prescriptions respective rates of maternal low income were 57%, 48%, and 39%; mental health hospitalization history was 33%, 28%, and 17%; and infant discharge to social services was 8%, 13%, and 5%. CONCLUSIONS: Combining prenatal opioid prescriptions and maternal and newborn opioid-related hospital codes improves identification of a broader population of mothers and infants with POE.

18.
J BUON ; 25(5): 2205-2214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33277837

RESUMO

PURPOSE: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1-214 transcript (PVT1-214) is a notable lncRNA involved in gastric cancer and colorectal cancer (CRC) so far. Nowadays, the biological function of PVT1-214 on the response of CRC to chemotherapy is still unclear. We aimed to explore the molecular mechanism of PVT1-214 and its regulatory mechanism in advanced CRC. METHODS: The levels of PVT1-214, microRNA (miR)-128, and interferon regulatory factor-1 (IRF-1) in CRC tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Log-rank test was applied to evaluate the role of high PVT1-214 levels in shortening the overall survival of CRC patients. Chi-square test was to assess the relation between PVT1-214 expression and clinicopathological features of CRC patients. CCK8 assays tested the cell proliferation of oxaliplatin-resistant CRC cells (HCT116/Oxa and SW480/Oxa) with PVT1-214 knockdown. The underlying regulatory mechanism between PVT1-214 and miR-128 was predicted by bioinformatics and verified by RNA transfection, qRT-PCR and western blotting. Chromatin immunoprecipitation (ChIP) assay was done to examine the relationship between or IRF-1 and the PVT1-214 gene. RESULTS: High levels of PVT1-214 expression were more likely to be present in patients with late-stage (IV), chemotherapy resistance, and inferior overall survival. PVT1-214 was aberrantly elevated in oxaliplatin-resistant CRC tissues and cell lines (HCT116/Oxa and SW480/Oxa). PVT1-214 knockdown reduced cell proliferation, migration and invasion of oxaliplatin-resistant CRC cells in vitro. Moreover, IRF-1 was found to be a negative transcription regulator of PVT1-214 and decreased PVT1-214 levels in oxaliplatin-resistant CRC cells. Besides, PVT1-214 repressed miR-128 function by binding to the complementary sites of miR-128. CONCLUSIONS: IRF-1/PVT1-214 may markedly boost the oxaliplatin-resistance of CRC, resulting in the late TNM stage and poor survival. These findings suggest that the IRF-1/PVT1-214 axis may be a helpful target for intervention in CRC.

19.
PLoS One ; 15(12): e0244487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373398

RESUMO

BACKGROUND: In pancreatic cancer, toxicities associated with current chemotherapeutic regimens remain concerning. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as the first-line treatment for newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma patients. METHODS: GSL was administered every 2 weeks-intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7. We retrospectively analyzed the feasibility of GSL and patient outcomes in three medical centers in Taiwan. RESULTS: Overall, 49 patients received GSL with a median follow-up of 24.9 months from May 2015 to March 2019. The median patient age was 68 years (range, 47-83 years), with a marginally higher number of females (57.1%). Among the 44 patients who underwent image evaluation, 13 demonstrated a partial response (29.5%) and 17 presented with stable disease (38.6%). The partial response rate and stable disease rate was 26.5% and 34.7%, respectively, in the intent-to-treat analysis. The median time-to-treatment failure was 5.79 months (95% C.I., 2.63-8.94), progression-free survival was 6.94 months (95% C.I., 5.55-8.33), and overall survival time was 11.53 months (95% C.I., 9.94-13.13). For GSL treatment, the most common grade 3 or worse toxicities were anemia (18.3%), neutropenia (6.1%), nausea (4.1%), and mucositis (4.1%). Treatment discontinuation was mostly due to disease progression (65.3%). CONCLUSIONS: The modified GSL therapy can be a promising and affordable treatment for patients with advanced and metastatic pancreatic cancer in Taiwan. A prospective trial of modified GSL for elderly patients is currently ongoing in Taiwan.

20.
Pest Manag Sci ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33336552

RESUMO

BACKGROUND: Carboxylesterase (CarE) is a major class of enzyme involved in the detoxification of toxic xenobiotics in various insect species. Previous work has shown that the carboxylesterase gene CarE001G found in Helicoverpa armigera is more active and can metabolize synthesized pyrethroids, such as ß-cypermethrin, one of the commonly used commercial insecticides for lepidopteran pest control. In addition, CarE001G is very special as it has a very specific glycine-rich region located adjacent to its C-terminal. But whether mutations in this unique sequence can change the biochemistry and function of CarE001G are unknown. RESULTS: In this study, four variants of CarE001G with different deletions in the glycine-rich region were obtained and functionally expressed in Escherichia coli. The recombinant proteins were purified and confirmed by Western blot and mass spectrometry analyses. These mutant enzymes showed high catalytic efficiency toward the model substrate α-naphthyl acetate. Inhibition study showed that ß-cypermethrin had relatively strong inhibition on CarE activities. In vitro metabolism assay showed that the mutant enzymes significantly enhanced their metabolic activities toward ß-cypermethrin with specific activities between 4.0 and 5.6 nmol L-1 min-1 mg-1 protein. Molecular docking analyses consistently demonstrated that deletion mutations in the glycine-rich region may facilitate the anchoring of the ß-cypermethrin molecule in the active binding pocket of the mutant enzymes. CONCLUSION: The data show that deletion mutations can cause qualitative change in the capacity of CarEs in the detoxification of ß-cypermethrin. This indicates that deletion mutations in the glycine-rich region may have the potential to cause synthesized pyrethroid (SP) resistance in H. armigera in the future.

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