Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.018
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Food Chem Toxicol ; 137: 111167, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007468

RESUMO

Chronic exposure to n-hexane could induced serious peripheral nerve impairments. It has been well documented that the metabolic activation from n-hexane to 2,5-hexanedione (2,5-HD) is vital in the pathogenesis. Diallyl sulfide (DAS) is an extract of garlic and able to block the bioactivation of xenobiotic. The current study was designed to investigate whether DAS can attenuate n-hexane induced neuropathy. Male Wistar rats were pretreated with DAS (50 or 100 mg/kg.bw) and then n-hexane (3 g/kg.bw) for 7 weeks. Behavioral performance, biomarker measurement and toxicokinetic studies were performed. Enzymatic methods and western blotting analyses were also conducted to investigate the hepatic phase I enzymes (including cytochrome P450(CYP)2E1, CYP1A1 and CYP2B1) and phase II enzymes (including glutathione S transferase theta 1 (GSTT1) and NA(D)PH dehydrogenase quinone 1 (NQO1)). The results showed that DAS improved the behavioral performance while reducing the toxic metabolite: 2,5-HD and pyrrole adducts. Besides, DAS reduced the expression of CYP2E1 with a proportional decrease in activity, which largely decreased the bioactivation of n-hexane in vivo. The results suggested that DAS decreased the toxic metabolites of n-hexane to attenuate n-hexane-induced peripheral neuropathy.

2.
Microb Pathog ; 142: 104043, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032768

RESUMO

Cherax quadricarinatus is seriously affected by multiple types of pathogens, including bacteria and viruses, and has been widely transplanted around the world. Heat shock proteins (Hsps) are a group of molecular chaperones that play important roles in promoting the proper refolding and blocking the aggregation of denatured proteins. In this study, CqHsp60, CqHsp70 and CqHsp90 from C. quadricarinatus were cloned, and their expression patterns were analysed. The CDS (coding sequence) lengths of the CqHsp60, CqHsp70 and CqHsp90 genes were 1731 bp, 1932 bp and 2199 bp, encoding 576, 643 and 732 amino acids, respectively. CqHsp60 was 99.13%, 98.78% and 88.63% identical to the corresponding sequences of Cherax cainii, Cherax destructor and Eriocheir sinensis, respectively. CqHsp70 showed 99.84%, 92.73% and 91.58% identity to the corresponding sequences of C. cainii, C. destructor and E. sinensis, while CqHsp90 was 98.25%, 98.51% and 91.41% identical with those of C. cainii, C. destructor and E. sinensis, respectively. The expression patterns of the three CqHsps were different between males and females. CqHsp60 and CqHsp70 exhibited the highest expression in the hepatopancreas of males and the gonads of females, and CqHsp90 presented the highest expression in the gonads of males and hepatopancreas of females. After pathogenic inoculation, the death trend of C. quadricarinatus at different time points was the same in association with different pathogens, with most deaths occurring within 6 h post-inoculation. The trend of CqHsp transcription at different time points was the same among the groups treated with Vibrio alginolyticus, Vibrio parahemolyticus and Aeromonas hydrophila, exhibiting upregulation first and then downregulation. The expression of CqHsp60 and CqHsp70 in the gills of living C. quadricarinatus was less than 3.5 times that in the PBS group, but in the gills of dead C. quadricarinatus under A. hydrophila inoculation, its expression was more than 5-9 times that in the PBS group. CqHsp90 expression changed dramatically in the V. alginolyticus, V. parahemolyticus and A. hydrophila groups, in which it exceeded 50 times the level in the PBS group. These results indicated that CqHsps could induce the activation of the immune system within a short time and that CqHsp90 could be used as a more effective molecular biomarker than CqHsp70 and CqHsp60 in a pathogenic bacterium-polluted environment.

3.
Neurotoxicology ; 78: 11-20, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045579

RESUMO

n-Hexane has been reported to induce serious peripheral neuropathy in workers. Pyrrole adducts are the unique reaction products of n-hexane in organisms and have been demonstrated to be critical to n-hexane neuropathy. Our previous studies have demonstrated that pyrrole adducts could accumulate in hair and showed high correlation with neuropathy at the end of experiments in rat models. In the present study, we examined the time course of hair pyrrole adducts and behavioral changes in rats exposed to different dosages of n-hexane in both treatment (24 weeks) and recovery phases. Our results showed: 1. After treatment, 1.0, 2.0, and 4.0 g/kg dosage groups all lost weight, but the 0.5 g/kg dosage group showed no impairment; after recovery, all impaired rats regained weight. 2. After treatment, 1.0, 2.0, and 4.0 g/kg dosage groups all showed a rise in gait scores, decreased rotarod latency, and decreased motor nerve conduction velocity, whereas the 0.5 g/kg dosage group showed no impairment; after recovery, all impaired rats were completely rehabilitated. 3. After treatment, levels of pyrrole adducts in serum, urine, and hair of experimental groups increased; after recovery, serum and urine pyrrole adducts showed no difference from the control (P > 0.05), whereas hair pyrrole adducts were significantly different from the control (P < 0.01). 4. The half-lives of serum and urine pyrrole adducts were 47.8-78.0 h and 42.7-52.9 h, while the half-life of hair pyrrole adducts was 14-24 weeks. 5. During treatment and recovery, levels of serum, urine, and hair pyrrole adducts showed high correlation with gait scores (P < 0.01), and hair pyrrole adducts had the largest partial correlation coefficient. In conclusion, hair pyrrole adducts could serve as a stable and reliable biomarker for the prevention of n-hexane intoxication. Furthermore, the no-observed-adverse-effect level of hair pyrrole adducts in rats is 275.2 ±â€¯61.5 nmol/g protein. Further studies are required for the definition of the biological exposure limit in humans.

4.
Int J Hyg Environ Health ; 225: 113481, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058935

RESUMO

Maternal exposures to ambient temperatures during pregnancy may increase the preterm birth (PTB) risk; however, which periods have stronger effects remain controversial. The effects of temperature exposure on PTB in first- and second-born neonate groups may be different during the new baby boom that has followed the Two-child Policy in China. We examined a birth cohort of 4928 pregnant women beginning in 2016 in Guangzhou, China. An inverse distance weighted method was used to estimate the temperature exposure at each individual residential address. A distribution lag non-linear model incorporating a Cox proportional hazard model was employed to estimate the effects of temperature exposure on PTB and test the effects modification of birth order related to the new baby boom. A total of 4101 pregnant women were included, of which 234 (5.7%) experienced PTB. Compared with the mean temperature (23.0 °C), we found a significantly higher risks of PTB associated with high temperatures (i.e, 30 °C [95th centile]) from the 4th to 8th, and 22nd to 27th gestational weeks. A peak effect was found during the 6th week (HR = 1.79, 95% CI: 1.26, 2.54) and 24th week (HR = 1.83, 95% CI: 1.27, 2.62). The risks of PTB were reduced for low temperatures (i.e. 14 °C [5th centile] versus 23.0 °C) from the 2nd to 10th and 20th to 26th gestational weeks, and the negative peak effect was found during the 4th week (HR = 0.43, 95% CI: 0.26, 0.72) and 23rd week (HR = 0.59, 95% CI: 0.43, 0.83). Stratification analyses showed that significant effects of 30 °C versus 23 °C on PTB were observed during the 4th to 8th weeks in the second-born neonate, and the peak effect was found in the 6th week (HR = 2.13, 95% CI: 1.31, 3.47). However, we did not find significant effects of 30 °C during the same weeks in the first-born neonate group. Maternal exposures to higher temperatures during pregnancy may increase the risk of PTB, and lower temperatures may decrease the risk of PTB. Stronger effects of temperature exposures during the first trimester on PTB risk were found among the second-born neonates than among the first-born neonates.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 136-140, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027266

RESUMO

OBJECTIVE: To analyze the relationship between cytogenetic changes and the progression in the patients with chronic myeloid leukemia (CML) during the treatment with tyrosine kinase inhibitor (TKI). METHODS: The chromosome G banding of 150 patients with CML treated in our hospital, was carried out to analyze the karyotype by the 24 h short-term culture or direct method of bone marrow cells, and the point mutation of the ABL kinase area was detected, the relationship between cytogenetic changes and the evolution of the disease course was analyzed. RESULTS: The indirect fluorescence in situ hybridization showed that the BCR-ABL fusion gene of 150 patients was positive, out of which 142 cases showed positive Philadelphia (Ph) (94.67%), 8 cases with Ph negative (5.33%). Among 142 cases with Ph positive on the first diagnosis, and 14 cases (9.86%) with additional chromosome abnormality (9.86%), 4 cases (2.82%) with mutation translocation with 124 cases (87.32%), standard translocation t (9; 22) (q34; Q11) were found. Out of the 14 patients with additional chromosomal abnormalities, 8 cases with "main pathmay" abnormalities, 2 case with -Y abnormalities, and 4 cases with "secondary pathway" abnormalities were observed. During TKI treatment, additional chromosomal abnormalities were found in 46 patients with standard translocation and abnormal number of chromosomes, and the incidence of disease progression and point mutation were higher (P<0.05). Compared with patients with the standard translocation, the disease-free survival rate of the patients diagnosed as CML at 1st visit and with additional chromosome abnormality was significantly decreased (P<0.05), but the overall survival rate showed no significantly different (P>0.05). Compared with patients without additional cvtogenetic aberrations, the disease free and overall survival rate of the patients with additional cytogenetic aberrations during the TKI treatment of CML in chronic phase were significantly decreased (P<0.05). CONCLUSION: Some CML patients may have additional chromosomal abnormalities during the onset and development of the disease, and these patients are at higher risk of disease progression.

6.
Sci Total Environ ; 711: 135098, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000339

RESUMO

Diabetes is a major public health problem globally, and heat exposure may be a potential risk factor for death among diabetes. This study examines the association between heat and diabetes mortality in different regions of Thailand and investigates whether heat effects are modified by regional greenness. Daily temperature and daily diabetes deaths data were obtained for 60 provinces of Thailand during 2000-2008. A case-crossover analysis was conducted to quantify the odds of heat-related death among diabetes. Meta-regression was then used to examine potential modification effects of regional greenness (as represented by the Normalized Difference Vegetation Index) on heat-related mortality. A strong association between heat and diabetes mortality was found in Thailand, with important regional variations. Nationally, the pooled odds ratio of diabetes mortality was 1.10 (95% confidence interval (CI): 1.06-1.14) for heat (90th percentile of temperature) and 1.20 (95% CI: 1.10-1.30) for extreme heat (99th percentile of temperature) compared with the minimum mortality temperature, across lag 0-1 days. Central and northeast Thailand were the most vulnerable regions. Regional greenness modified the effects of heat, with lower mortality impacts in areas of higher levels of greenness. In conclusion, heat exposure increases mortality risk in diabetes, with large geographical variations in risk suggesting the need for region-specific public health strategies. Increasing greenness levels may help to reduce the burden of heat on diabetes in Thailand against the backdrop of a warming climate.

7.
BMC Complement Med Ther ; 20(1): 41, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046689

RESUMO

BACKGROUND: Most randomized controlled trials (RCTs) of traditional medicine (such as traditional Chinese medicine (TCM), psychotherapy or behavioral therapy, and dietary interventions, etc.) have reported that they could not provide convincing evidence to support the efficacy because of the low quality of their studies. Here, we aimed to determine the underlying problems of the study quality using standards of evidence-based medicine (EBM) to evaluate the efficacy of traditional medicine. METHODS: We conducted an example of meta-analysis to evaluate the efficacy of acupuncture, a classical treatment of TCM, for treatment of intracerebral hemorrhage (ICH). The quality of the included studies was evaluated by using a Jadad score. RESULTS: A total of 24 Chinese RCTs that enrolled 1815 patients with ICH were included. Although the results suggested that acupuncture had good efficacy for relief of neurological deficits and improvement of the activities of daily living despite the high heterogeneity of the included studies, the low quality of the included literature reduced the worthiness of the evidence. Two systematic problems (lack of blinding and allocation concealment and high heterogeneity) and one non-systematic problem (lack of reports on adverse events and follow-up) of the TCM studies were found in this illustrational meta-analysis. We believed that other interventions of traditional medicine also suffer from these problems. CONCLUSIONS: Non-systematic problems can be improved by perfecting the experimental design, educating the researcher, and improving the reporting system. However, systematic problems are derived from the characteristics of traditional medicine that are difficult to be corrected. We propose that adoption of objective indexes might be a better solution to improve the systematic problems of traditional medicine. We summarized the problems and the underlying solutions, which may contribute to improve the study quality of systematic review in traditional medicine, strictly complying with the principles of EBM.

8.
BMC Plant Biol ; 20(1): 63, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028891

RESUMO

BACKGROUND: Microbes isolated from hyperaccumulating plants have been reported to be effective in achieving higher phytoextraction efficiency. The plant growth-promoting bacteria (PGPB) SaMR12 from the cadmium (Cd)/zinc hyperaccumulator Sedum alfredii Hance could promote the growth of a non-host plant, oilseed rape, under Cd stress. However, the effect of SaMR12 on Brasscia juncea antioxidative response under Cd exposure was still unclear. RESULTS: A hydroponic experiment was conducted to study the effects of Sphingomonas SaMR12 on its non-host plant Brassica juncea (L.) Czern. under four different Cd treatments. The results showed that SaMR12 could colonize and aggregate in the roots and then move to the shoots. SaMR12 inoculation promoted plant growth by up to 71% in aboveground biomass and 81% in root biomass over that of the non-inoculated plants. SaMR12-inoculated plants significantly enhanced root Cd accumulation in the 10 and 20 µM Cd treatments, with 1.72- and 0.86-fold increases, respectively, over that of the non-inoculated plants. SaMR12 inoculation not only decreased shoot hydrogen peroxide (H2O2) content by up to 38% and malondialdehyde (MDA) content by up to 60% but also reduced proline content by 7-30% in shoots and 17-32% in roots compared to the levels in non-inoculated plants. Additionally, SaMR12 inoculation promoted the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and facilitated the relative gene expression levels of dehydroascorbate reductase (DHAR) and glutathione reductase (GR) involved in the glutathione (GSH)-ascorbic acid (AsA) cycle. CONCLUSIONS: The results demonstrated that, under Cd stress, SaMR12 inoculation could activate the antioxidative response of B. juncea by decreasing the concentrations of H2O2, MDA and proline, increasing the activities of antioxidative enzymes, and regulating the GSH-AsA cycle. These results provide a theoretical foundation for the potential application of hyperaccumulator endophytic bacteria as remediating agents to improve heavy metal tolerance within non-host plant species, which could further improve phytoextraction efficiency.

9.
Org Lett ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009410

RESUMO

A simple imine-based covalent organic framework (COF) as heterogeneous ligand for PdII-promoted Heck reaction is reported. Good regioselectivity for a wide range of electronically unbiased olefins is obtained (linear/branched >100:1 in most cases). Related tests and density functional theory calculations are used to explore the reason underlying the high selectivity. This research opens a route for COF as an intriguing platform to control regioselectivity catalysis.

10.
Nat Commun ; 11(1): 310, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964862

RESUMO

Regulations currently in force enable to claim that the lead content in perovskite solar cells is low enough to be safe, or no more dangerous, than other electronics also containing lead. However, the actual environmental impact of lead from perovskite is unknown. Here we show that the lead from perovskite leaking into the ground can enter plants, and consequently the food cycle, ten times more effectively than other lead contaminants already present as the result of the human activities. We further demonstrate that replacing lead with tin represents an environmentally-safer option. Our data suggest that we need to treat the lead from perovskite with exceptional care. In particular, we point out that the safety level for lead content in perovskite-based needs to be lower than other lead-containing electronics. We encourage replacing lead completely with more inert metals to deliver safe perovskite technologies.

11.
Environ Health Perspect ; 128(1): 17006, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31909654

RESUMO

BACKGROUND: Both extreme heat and air pollution exposure during pregnancy have been associated with preterm birth; however, their combined effects are unclear. OBJECTIVES: Our goal was to estimate the independent and joint effects of heatwaves and fine particulate matter [PM <2.5µm in aerodynamic diameter (PM2.5)], exposure during the final gestational week on preterm birth. METHODS: Using birth registry data from Guangzhou, China, we included 215,059 singleton live births in the warm season (1 May-31 October) between January 2015 and July 2017. Daily meteorological variables from 5 monitoring stations and PM2.5 concentrations from 11 sites were used to estimate district-specific exposures. A series of cut off temperature thresholds and durations (2, 3, and 4 consecutive d) were used to define 15 different heatwaves. Cox proportional hazard models were used to estimate the effects of heatwaves and PM2.5 exposures during the final week on preterm birth, and departures from additive joint effects were assessed using the relative excess risk due to interaction (RERI). RESULTS: Numbers of preterm births increased in association with heatwave exposures during the final gestational week. Depending on the heatwave definition used, hazard ratios (HRs) ranged from 1.10 (95% CI: 1.01, 1.20) to 1.92 (1.39, 2.64). Associations were stronger for more intense heatwaves. Combined effects of PM2.5 exposures and heatwaves appeared to be synergistic (RERIs>0) for less extreme heatwaves (i.e., shorter or with relatively low temperature thresholds) but were less than additive (RERIs<0) for more intense heatwaves. CONCLUSIONS: Our research strengthens the evidence that exposure to heatwaves during the final gestational week can independently trigger preterm birth. Moderate heatwaves may also act synergistically with PM2.5 exposure to increase risk of preterm birth, which adds new evidence to the current understanding of combined effects of air pollution and meteorological variables on adverse birth outcomes. https://doi.org/10.1289/EHP5117.

12.
J Immunother Cancer ; 8(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31959726

RESUMO

BACKGROUND: Although clear cell renal cell carcinoma (ccRCC) is well known as a highly immunogenic tumor, only a small subset of patients could benefit from current immunotherapy, which might be due to the heterogeneity of immune microenvironment in ccRCC. So, it is meaningful to explore novel immunotherapy or combination therapy for improving therapeutic efficacy. HHLA2, a newly discovered B7 family member, is prevalently expressed in numerous tumors, including ccRCC. This study aimed to investigate the prognostic impact of HHLA2/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs). METHODS: The expression levels of HHLA2, PD-L1, CD8, and CD4 in cancer tissues from cases (206 in the training cohort and 197 in the validation cohort) with surgically resectable primary ccRCC were evaluated by immunohistochemistry. RESULTS: The positive rates of HHLA2 were much higher than those of PD-L1 in ccRCC tissues. HHLA2-positive expression was significantly associated with necrosis, microvascular invasion, advanced Fuhrman nuclear, and TNM stage and indicated a shorter progression-free survival (PFS) and overall survival (OS) in both cohorts. Moreover, patients with HHLA2/PD-L1 co-expression suffered the highest risk of disease progression and death by a significant margin. Besides, HHLA2/PD-L1 co-expression was significantly associated with a high density of CD8+ and CD4+ TILs. Notably, a new immune classification, based on HHLA2/PD-L1 co-expression and TILs, successfully stratified PFS and OS, especially in patients with TILs positivity. CONCLUSIONS: The expression of HHLA2 is more frequent than PD-L1 in ccRCC. HHLA2/PD-L1 co-expression had an adverse impact on the prognoses of patients with ccRCC; this finding provides a rationale for combination immunotherapy with anti-HHLA2 and PD-L1 blockage for patients with ccRCC in the future.

13.
PLoS One ; 15(1): e0226718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910437

RESUMO

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early prediction of HT in acute cerebral infarction contributes not only to the selections of therapeutic regimen but also, more importantly, to the improvement of prognosis of acute cerebral infarction. The purpose of this study was to develop and validate a model to predict a patient's risk of HT within 30 days of initial ischemic stroke. METHODS: We utilized a retrospective multicenter observational cohort study design to develop a Lasso Logistic Regression prediction model with a large, US Electronic Health Record dataset which structured to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). To examine clinical transportability, the model was externally validated across 10 additional real-world healthcare datasets include EHR records for patients from America, Europe and Asia. RESULTS: In the database the model was developed, the target population cohort contained 621,178 patients with ischemic stroke, of which 5,624 patients had HT within 30 days following initial ischemic stroke. 612 risk predictors, including the distance a patient travels in an ambulance to get to care for a HT, were identified. An area under the receiver operating characteristic curve (AUC) of 0.75 was achieved in the internal validation of the risk model. External validation was performed across 10 databases totaling 5,515,508 patients with ischemic stroke, of which 86,401 patients had HT within 30 days following initial ischemic stroke. The mean external AUC was 0.71 and ranged between 0.60-0.78. CONCLUSIONS: A HT prognostic predict model was developed with Lasso Logistic Regression based on routinely collected EMR data. This model can identify patients who have a higher risk of HT than the population average with an AUC of 0.78. It shows the OMOP CDM is an appropriate data standard for EMR secondary use in clinical multicenter research for prognostic prediction model development and validation. In the future, combining this model with clinical information systems will assist clinicians to make the right therapy decision for patients with acute ischemic stroke.

15.
Nat Commun ; 11(1): 17, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911615

RESUMO

Mutation of o2 doubles maize endosperm lysine content, but it causes an inferior kernel phenotype. Developing quality protein maize (QPM) by introgressing o2 modifiers (Mo2s) into the o2 mutant benefits millions of people in developing countries where maize is a primary protein source. Here, we report genome sequence and annotation of a South African QPM line K0326Y, which is assembled from single-molecule, real-time shotgun sequencing reads collinear with an optical map. We achieve a N50 contig length of 7.7 million bases (Mb) directly from long-read assembly, compared to those of 1.04 Mb for B73 and 1.48 Mb for Mo17. To characterize Mo2s, we map QTLs to chromosomes 1, 6, 7, and 9 using an F2 population derived from crossing K0326Y and W64Ao2. RNA-seq analysis of QPM and o2 endosperms reveals a group of differentially expressed genes that coincide with Mo2 QTLs, suggesting a potential role in vitreous endosperm formation.

16.
Nature ; 577(7791): 566-571, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31915377

RESUMO

Epithelial-to-mesenchymal transitions (EMTs) are phenotypic plasticity processes that confer migratory and invasive properties to epithelial cells during development, wound-healing, fibrosis and cancer1-4. EMTs are driven by SNAIL, ZEB and TWIST transcription factors5,6 together with microRNAs that balance this regulatory network7,8. Transforming growth factor ß (TGF-ß) is a potent inducer of developmental and fibrogenic EMTs4,9,10. Aberrant TGF-ß signalling and EMT are implicated in the pathogenesis of renal fibrosis, alcoholic liver disease, non-alcoholic steatohepatitis, pulmonary fibrosis and cancer4,11. TGF-ß depends on RAS and mitogen-activated protein kinase (MAPK) pathway inputs for the induction of EMTs12-19. Here we show how these signals coordinately trigger EMTs and integrate them with broader pathophysiological processes. We identify RAS-responsive element binding protein 1 (RREB1), a RAS transcriptional effector20,21, as a key partner of TGF-ß-activated SMAD transcription factors in EMT. MAPK-activated RREB1 recruits TGF-ß-activated SMAD factors to SNAIL. Context-dependent chromatin accessibility dictates the ability of RREB1 and SMAD to activate additional genes that determine the nature of the resulting EMT. In carcinoma cells, TGF-ß-SMAD and RREB1 directly drive expression of SNAIL and fibrogenic factors stimulating myofibroblasts, promoting intratumoral fibrosis and supporting tumour growth. In mouse epiblast progenitors, Nodal-SMAD and RREB1 combine to induce expression of SNAIL and mesendoderm-differentiation genes that drive gastrulation. Thus, RREB1 provides a molecular link between RAS and TGF-ß pathways for coordinated induction of developmental and fibrogenic EMTs. These insights increase our understanding of the regulation of epithelial plasticity and its pathophysiological consequences in development, fibrosis and cancer.

17.
Nature ; 578(7793): E11, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31937917

RESUMO

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Transl Oncol ; 13(1): 32-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760267

RESUMO

BACKGROUND: Escaping cell death pathways is an important event during carcinogenesis. We previously identified anti-TNFα-induced apoptosis (ATIA, also known as vasorin) as an antiapoptotic factor that suppresses reactive oxygen species (ROS) production. However, the role of vasorin in lung carcinogenesis has not been investigated. METHODS: Vasorin expression was examined in human lung cancer tissues with immunohistochemistry and database analysis. Genetic and pharmacological approaches were used to manipulate protein expression and autophagy activity in human bronchial epithelial cells (HBECs). ROS generation was measured with fluorescent indicator, apoptosis with release of lactate dehydrogenase, and cell transformation was assessed with colony formation in soft agar. RESULTS: Vasorin expression was increased in human lung cancer tissues and cell lines, which was inversely associated with lung cancer patient survival. Cigarette smoke extract (CSE) and benzo[a]pyrene diol epoxide (BPDE)-induced vasorin expression in HBECs. Vasorin knockdown in HBECs significantly suppressed CSE-induced transformation in association with enhanced ROS accumulation and autophagy. Scavenging ROS attenuated autophagy and cytotoxicity in vasorin knockdown cells, suggesting that vasorin potentiates transformation by impeding ROS-mediated CSE cytotoxicity and improving survival of the premalignant cells. Suppression of autophagy effectively inhibited CSE-induced apoptosis, suggesting that autophagy was pro-apoptotic in CSE-treated cells. Importantly, blocking autophagy strongly potentiated CSE-induced transformation. CONCLUSION: These results suggest that vasorin is a potential lung cancer-promoting factor that facilitates cigarette smoke-induced bronchial epithelial cell transformation by suppressing autophagy-mediated apoptosis, which could be exploited for lung cancer prevention.

19.
Biomed Chromatogr ; 34(2): e4715, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31633829

RESUMO

In the present study, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach was designed to measure the rat plasma levels of verubecestat with diazepam as the internal standard. Acetonitrile-based protein precipitation was applied for sample preparation, then the analyte verubecestat was subjected to gradient elution chromatography with a mobile phase composed of acetonitrile (A) and 0.1% formic acid in water (B). Verubecestat was monitored by m/z 410.1 → 124.0 transition for quantification by multiple reaction monitoring (MRM) in positive ion electrospray ionization (ESI) source. When the concentration of verubecestat ranged from 1 to 2500 ng/mL, the method exhibited good linearity. For verubecestat, the intra- and inter-day precision were determined with the values of 2.9-9.0% and 0.4-6.5%, respectively; and the accuracy ranged from -2.2% to 10.4%. Matrix effect, extraction recovery, and stability data were in line with the standard FDA guidelines for validating a bioanalytical method. The validity of the developed method was confirmed through the pharmacokinetic study.

20.
Diagn Microbiol Infect Dis ; 96(2): 114948, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787408

RESUMO

We characterized a strain of Laribacter hongkongensis isolated from the blood of a patient with fatal sepsis, who had alcoholic cirrhosis with ascites and portal hypertension. L. hongkongensis bacteremia is associated with underlying liver diseases (P < 0.001) and mortality (P < 0.05), whereas L. hongkongensis gastroenteritis is associated with recent travel history (P < 0.05).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA