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1.
Biomed Pharmacother ; 122: 109777, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918261

RESUMO

Sepsis is a critical illness that contributes a high mortality, while Xijiao Dihuang decoction (XJDHT) has been used in treatment against sepsis for many years by clinical doctors. Clinical studies confirmed a good efficacy of XJDHT against sepsis. The aim of this study is to observe the efficacy of XJDHT in sepsis model rats and macrophages activated by LPS, and to verify the underlying mechanisms. The key components of XJDHT and its targets against sepsis were analyzed and selected by network pharmacology. The potential mechanisms that XJDHT regulates the progress of sepsis were verified in sepsis rats and NR8383 cell lines. XJDHT at a dose of 25 mg/kg was administrated to rats which endured cecal ligation and perforation (CLP). After MTT assay, XJDHT at a dose of 4 mg/mL was selected to treat NR8383 cell lines activated by LPS. In vivo experiment, the survival of the rats was assessed. The content of cytokine in serum were assessed by Enzyme-linked immunosorbent assays (ELISA). Contents of cytokine and key molecules in relative signaling pathway were assessed by immunohistochemical method. The pathway protein expressions were detected by Western blotting. In vitro experiment, immunofluorescence was used to assess the content of cytokine and signaling pathway. A total of 42 targets of XJDHT against sepsis were identified by network pharmacology. After eliminating overlapping compounds and proteins, there were 8 compounds in XJDHT that associating with the 42 sepsis-related targets. NF-κB and HIF-1α signaling pathway were recognized to play important role for XJDHT against sepsis. XJDHT improved survival rate in the XJDHT group compared with the model group. The contents of IL-6 increased in the model group compared with the control group with ELISA and immunohistochemistry, while XJDHT reduced the content of IL-6. The expressions of p65 and HIF-1α reduced significantly in the XJDHT group compared with the model group. In vitro study, the content of IL-6 elevated significantly after LPS stimulation, while XJDHT reduced this increase. Furthermore, expressions of protein of p65 and HIF-1α decreased significantly compared with the LPS group. To conclude, our study demonstrated that XJDHT at a dose of 25 g/kg is capable of improving the survival of sepsis via regulating the NF-κB and HIF-1α signaling pathway.

2.
Environ Pollut ; 257: 113564, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753638

RESUMO

In the context of global warming, an important issue is that many pesticides become more toxic, putting non-target organisms at higher risk of pesticide exposure. Eremias argus (a native Chinese lizard) was selected as animal model in this study. As a kind of poikilothermic vertebrate, E.argus is sensitive to temperature change. The experimental design [(with or without L-Glufosinate-ammonium (L-GLA) pollution × two temperatures (25 and 30 °C)] was used in this study for 90 days to identify the chronic effects of the pesticide-temperature interaction on the lizards' neuroendocrine-regulated reproduction. Survival rate, body weight, clutch characteristics, testicular histopathology, the content of neurotransmitters and related enzyme activity, the level of sex steroid, the expression of Heat shock protein 70 (HSP70), antioxidant system, the accumulation and degradation of L-GLA were examined. Results showed that L-GLA disrupt reproduction of lizards through hypothalamus-pituitary-gonad (HPG) axis. In addition, temperature can not only change the environmental behavior of pesticides, but also alter the physiological characteristics of lizards. Thus, our results emphasized that temperature is an essential abiotic factor that should not be overlooked in ecotoxicological studies.

3.
Sci Total Environ ; 708: 135089, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31806336

RESUMO

In solid wastes, pores provide passages for leachate and biogas flows, and room for microbial activities. In this study, the pores in the solid wastes of synthetic solid wastes were measured using X-ray computed microtomography to explore their structural characteristics during degradation. The synthetic municipal solid waste (MSW) column was inoculated with microorganisms obtained from leachate sampling and X-ray digital images of MSW were taken on the 2nd and 260th days after inoculation. The results show that the porosity dropped sharply, and the volume and path number of the connected pores reduced while those of disconnected pores increased. However, the corresponding characteristics in the blank MSWs changed only slightly. For the probability density distributions of the inoculated column, both the pore size (fitted well by y = 0.49e-0.49x, r2 = 0.96) as well as the throat area (fitted well by y = 0.54e-0.54x, r2 = 0.96) changed, depicting an exponential decay at the primary stage and a unimodal distribution at the degraded stage. The pore path length and coordination number also changed. These indicated that the pore structure of MSWs underwent considerable evolution during degradation; the changes can be attributed primarily to microbial activity instead of physical effects.

4.
Chemosphere ; 243: 125288, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31743868

RESUMO

The decrease in the population of amphibians all over the world has raised concerns. Adult X. laevis frogs were exposed to 0, 1 and 10 mg/L triadimefon and triadimenol. After 14 or 28 days exposure, we collected male and female specimens to study swimming activity, lactic dehydrogenase (LDH) and antioxidant enzyme activity in blood samples, histopathology of liver and thyroid tissue, thyroid hormone levels and thyroid hormone-related gene expression levels in brains. Our results showed that triadimefon and triadimenol could affect the swimming activity of frogs and that this was distinct at different levels of triadimenol. Moreover, triadimefon and triadimenol exposure produced a greater effect on superoxide dismutase (SOD) in females than in males, which was reverse to the finding for glutathione S-transferase (GST) and catalase (CAT). After 28 days exposure, triadimefon produced more toxic effects on the liver than observed for triadimenol. Besides this, triadimefon and triadimenol exposure exerted a greater effect on liver histology and thyroid hormone levels in male frogs than in the females. Our results also found that the expression of genes related to thyroid hormone in brains depended on the exposure level and time, as well as the sex of the treated individual. This study shed light on the relationships between the toxicity of metabolite products and their parent compounds and provided further understanding of the risk of pesticide use on amphibians.

5.
J Affect Disord ; 260: 728-737, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563072

RESUMO

OBJECTIVES: The aim of this study is to investigate the effectiveness of ACT on depression reduction and further examine the relationship between different follow-up periods, different degree of depression, and different age of patients through subgroup analysis. METHODS: Relevant electronic databases were searched from Jan 2010 to Aug 2018, including CNKI, WANFANG, PubMed, EMBASE, Cochrane Library, PsycINFO. Two reviewers independently screened for eligible studies, extracted data, and assessed risk of bias of the included studies. The Cochrane Collaboration's bias assessment tool was used to evaluate the risk of bias for included studies, and Review Manager 5.3 Software for the meta-analysis RESULTS: 18 studies with 1,088 participants were included in the review. Four studies were rated as high-quality studies, and the remaining 14 studies were rated as moderate quality studies. ACT significantly reduced depression as compared with the control group [SMD = 0.59, 95% CI (0.38, 0.81)]. The subgroup analysis found a significant difference between ACT and control group after post-intervention, three months follow up, mild depression group and adults group, [SMD= 0.62, 95% CI (0.35, 0.90), [SMD= 0.55, 95% CI (0.23, 0.87)], [SMD= 0.65, 95% CI (0.40, 0.91)], [SMD= 0.52, 95% CI (0.33, 0.71)] respectively. LIMITATIONS: The heterogeneity between included studies results in heterogeneity of the results. Most of the specific methods for random sequence generation and allocation concealment were not clear. The search results had limitations since only the published studies in Chinese and English were searched and lacked a search for gray and paper documents. CONCLUSIONS: The current study suggested that ACT was significantly for reducing depressive symptoms compared with the control group, especially at three months of follow-up, adult group and mild depression. More research is needed to investigate the difference effects for minor group, moderate and severe depression and long-term follow-up.

6.
J Med Entomol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751462

RESUMO

Theileria spp. are tick-transmitted, intracellular apicomplexan protozoan parasites that infect a wide range of animals and, as such, can cause significant economic losses. The aim of the present study was to detect and analyze apicomplexan parasites from two different ectoparasites that were collected from Xinjiang Uygur Autonomous Region, China. The PCR-based detection of 18S rRNA indicated that Ornithodoros lahorensis specimens from Kashgar, Xinjiang, and Aksu were positive for Theileria spp., as were Melophagus ovinus specimens from Aksu. Meanwhile, phylogenetic analysis, based on the 18S rRNA gene sequences, revealed that the four amplified Theileria sequences could be attributed to T. ovis. To the best of our knowledge, this is the first study to report the detection of T. ovis DNA in M. ovinus and the first molecular identification study to confirm the detection of T. ovis in O. lahorensis in China. Accordingly, the present study extends the known distribution of T. ovis.

7.
PLoS One ; 14(11): e0224892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31697766

RESUMO

Environmental exposure to metals is ubiquitous, but its relation to androgen hormone levels is not well understood, especially in children and adolescents. This study aimed to explore the relationship between blood metal concentrations (lead, cadmium, total mercury, selenium, and manganese) and serum total testosterone (TT) levels in 6-19-year-old children and adolescents in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Weighted multivariable linear regression models using NHANES sampling weights were employed to evaluate the association between log-transformed serum TT and each metal categories in male and female children (age 6-11years) and adolescents (age 12-19 years). We established that blood cadmium and manganese levels were associated with significantly higher serum TT levels in the female adolescents. Additionally, the blood selenium levels in male adolescents were related to significantly higher serum TT. No significant associations between blood lead or total mercury levels and TT were observed in children or adolescents of either sex. These findings suggest that environmental exposure to certain metals could affect serum TT levels in adolescents, which might have important implications for the health of adolescents. Further research is required to confirm and extend our present findings.

8.
Sci Rep ; 9(1): 16151, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695117

RESUMO

Literature on familial risk of carcinomas in situ (CISs) is limited because many cancer registries do not collect information on CIS. In Sweden CISs are collected, and we used these data to analyze familial relative risks (RRs) for concordant (CIS-CIS) types of anogenital (cervical, other female and male genital and anal) and skin squamous cell CIS; additionally RRs were assessed between CIS types and between CIS and invasive forms. RRs were calculated for the offspring generations when family members were diagnosed CIS. Case numbers for CIS ranged from 330 in anal to 177,285 in cervical CIS. Significant concordant CIS-CIS RRs were 2.74 for female genital, 1.77 for cervical and 2.29 for SCC skin CISs. The CIS forms associated also with each other, except for cervical and skin CIS types. RRs for concordant CIS-invasive cancer associations were lower than CIS-CIS associations. Cervical CIS associated with non-Hodgkin CIS which may suggest immune dysfunction as a contributing factors. The results for anogenital CIS types suggest that life style related human papilloma virus infections contributed to the observed familial associations. Lower risks for CIS-invasive cancer than CIS-CIS suggest that CIS and invasive cancers share only partially risk factors that underlie familial clustering.

9.
Oncol Lett ; 18(4): 4064-4073, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579069

RESUMO

Colorectal cancer (CRC) is one of most common malignancies worldwide. 5-fluorouracil (5-FU) is a mainstay of CRC treatment, particularly in patients with advanced stages of the disease; however, 5-FU-based chemotherapy is not always effective and may result in progression of the disease. The present study investigated several candidate microRNAs (miRs) in parental and 5-FU-resistant HCT116 and HT29 cells, and identified miR-361 as a novel regulator of chemosensitivity. Overexpression of miR-361 enhanced the 5-FU susceptibility of parental and resistant HCT116 and HT29 cells in vitro. Impaired colony formation capacity and increased cell apoptosis (as determined via flow cytometry) was observed in resistant HCT116 and HT29 cells. Furthermore, forkhead box M1 (FOXM1) was identified as a target gene of miR-361 using a dual-luciferase reporter assay, western blotting and reverse transcription-quantitative PCR. Additionally, FOXM1 knockdown improved the cytotoxicity of 5-FU in resistant CRC. ATP binding cassette subfamily C members 5 and 10 (ABCC5/10) were found to be downstream effectors of miR-361. In conclusion, miR-361 increased chemosensitivity, at least in part, via modulation of FOXM1-ABCC5/10. miR-361 may serve as a potential therapeutic target for patients with CRC.

10.
Ecotoxicol Environ Saf ; 185: 109691, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31563746

RESUMO

The rational use and the environmental safety of chiral pesticides have attracted significant research interest. Here, enantioselective toxic effects and the selective toxic mechanism of triticonazole (TRZ) against the aquatic microalgae Chlorella pyrenoidosa were studied. The 96h-EC50 values of rac-, (R)-(-)-, and (S)-(+)-TRZ were 1.939, 0.853, and 22.002 mg/L, respectively. At a concentration of 1 mg/L, the contents of photosynthetic pigments of C. pyrenoidosa exposed to (R)-(-)-TRZ were lower than if exposed to S-(+)-form and racemate. Transmission electron microscopic images showed that the R-(-)-form compromised the integrity of cells and disrupted the chloroplast structure. R-(-)-TRZ stimulated vast reactive oxygen species (ROS) and significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content. For lipid accumulation experiments, nicotinamide adenine dinucleotide (NADH) and triacylglycerol (TAG) accumulations in algal cells treated with R-(-)-TRZ were 171.50% and 280.76%, respectively, compared with the control group. This far exceeded levels of algal cells treated with S-(+)- and rac-TRZ. Based on these data, R-(-)-TRZ was concluded to selectively affect the photosynthetic system, antioxidant system, and lipid synthesis of algal cells, thus causing enantioselective toxic effects of TRZ against C. pyrenoidosa, which indicating that the use of racemate may cause unpredictable environmental harm. Therefore, to reduce the hidden dangers of chiral pesticides for the ecological environment, the environmental risk of TRZ should be evaluated at the stereoselective level.


Assuntos
Chlorella/efeitos dos fármacos , Ciclopentanos/toxicidade , Fungicidas Industriais/toxicidade , Microalgas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Antioxidantes/metabolismo , Chlorella/metabolismo , Chlorella/ultraestrutura , Cloroplastos/efeitos dos fármacos , Cloroplastos/metabolismo , Ciclopentanos/química , Fungicidas Industriais/química , Malondialdeído/farmacologia , Microalgas/metabolismo , Microalgas/ultraestrutura , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo , Superóxido Dismutase/metabolismo , Triazóis/química , Poluentes Químicos da Água/química
11.
Sci Rep ; 9(1): 11804, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413311

RESUMO

Data on familial risks in penile and vulvar/vaginal cancers and in second primary cancers (SPCs) following these cancers are limited. We used the Swedish Family-Cancer Database from years 1958 through 2015 to identify 3641 penile and 8856 vulvar/vaginal cancers and to calculate relative risks (RRs) and 95% confidence intervals (CIs) for these cancers according to site-specific cancer in family members; additionally risk for SPCs was calculated. The familial RR for concordant (same) penile cancer was 3.22 (1.34-7.74), and it was 2.72 (1.69-4.39) for vulvar/vaginal cancer; RRs were increased for vulvar/vaginal cancer in families of anal cancer patients. RR for second penile cancer after penile cancers was 11.68 (7.95-17.18), while that for concordant vulvar/vaginal cancer was 9.03 (7.31-11.15). SPCs were diagnosed in 16.8% of penile cancer patients and in them 45.9% of deaths were caused by SPC (other than penile cancer). In vulvar/vaginal cancer patients with SPC, 36.4% of deaths were due to SPC. The results showed that these genital cancers might run in families and as SPCs are associated with human papilloma virus and smoking related cancers. Risk for these genital and anal SPCs are high and a follow-up plan should be agreed at diagnosis of these cancers.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31447403

RESUMO

In order to better assess the health of the human body and protect people from disease, this study designs a wearable glasses system based on pulse signal preprocessing algorithm, pulse rate calculation algorithm and motion recognition algorithm. The pulse data before and after exercise are used to analyze the health status of the human body. Finally, the performance in various aspects of the system was verified by relevant experiments. The results show that the system is feasible. It can be seen that the system can be used for the assessment of human health conditions, and it is expected to serve people well in the future and make people live a healthier life.

13.
PLoS One ; 14(8): e0221435, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430353

RESUMO

Melophagus ovinus (sheep ked) is a blood-sucking ectoparasite that is parasitic primarily on sheep. It is widely distributed in different geographical regions worldwide. In China, it has been mainly found in Xinjiang, Gansu, and Tibet in recent years. In addition to causing direct damage to the animal hosts, M. ovinus also carries pathogens and serves as a vector for disease transmission. Border disease virus (BDV) is a positive-sense, single-stranded RNA pestivirus that mainly infects and causes border disease (BD) in sheep and goats worldwide. Since 2012, this disease has been reported in 4 provinces in China. In the present study, we investigated the presence of BDV in M. ovinus from Xinjiang and Gansu. Frozen M. ovinus collected during 2017 and 2018 from Xinjiang and Gansu and preserved in our laboratory were studied. First, total RNA of M. ovinus was extracted, followed by reverse transcription, PCR (RT-PCR) amplification of the 5'-UTR of BDV, and sequencing of the amplified products. Finally, the sequencing results were analyzed using DNAStar, MEGA 5.0 molecular biology software, and the BLAST online platform. The results from RT-PCR and sequencing analyses showed that among the samples included in the study, only the M. ovinus collected from Qinghe County in Alta, Xinjiang in 2018 tested positive for BDV. BLAST analysis showed that the viral strain with the most similar nucleotide identity to the sequence of the China/BDV/2018 fragment was the goat-derived BDV strain AH12-02 collected in Anhui, China, in 2012. A phylogenetic-tree analysis showed the strain to exhibit a BDV-3 genotype. This is the first report globally on BDV detected in M. ovinus and is also the first report of BDV discovered in Xinjiang, China. This study reconfirms the presence of BDV in China.

14.
J Virol ; 93(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31167905

RESUMO

Super-enhancers (SEs) are clusters of enhancers marked by extraordinarily high and broad chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) signals for H3K27ac or other transcription factors (TFs). SEs play pivotal roles in development and oncogenesis. Epstein-Barr virus (EBV) super-enhancers (ESEs) are co-occupied by all essential EBV oncogenes and EBV-activated NF-κB subunits. Perturbation of ESEs stops lymphoblastoid cell line (LCL) growth. To further characterize ESEs and identify proteins critical for ESE function, MYC ESEs were cloned upstream of a green fluorescent protein (GFP) reporter. Reporters driven by MYC ESEs 525 kb and 428 kb upstream of MYC (525ESE and 428ESE) had very high activities in LCLs but not in EBV-negative BJAB cells. EBNA2 activated MYC ESE-driven luciferase reporters. CRISPRi targeting 525ESE significantly decreased MYC expression. Genome-wide CRISPR screens identified factors essential for ESE activity. TBP-associated factor (TAF) family proteins, including TAF8, TAF11, and TAF3, were essential for the activity of the integrated 525ESE-driven reporter in LCLs. TAF8 and TAF11 knockout significantly decreased 525ESE activity and MYC transcription. MEF2C was also identified to be essential for 525ESE activity. Depletion of MEF2C decreased 525ESE reporter activity, MYC expression, and LCL growth. MEF2C cDNA resistant to CRIPSR cutting rescued MEF2C knockout and restored 525ESE reporter activity and MYC expression. MEF2C depletion decreased IRF4, EBNA2, and SPI1 binding to 525ESE in LCLs. MEF2C depletion also affected the expression of other ESE target genes, including the ETS1 and BCL2 genes. These data indicated that in addition to EBNA2, TAF family members and MEF2C are essential for ESE activity, MYC expression, and LCL growth.IMPORTANCE SEs play critical roles in cancer development. Since SEs assemble much bigger protein complexes on enhancers than typical enhancers (TEs), they are more sensitive than TEs to perturbations. Understanding the protein composition of SEs that are linked to key oncogenes may identify novel therapeutic targets. A genome-wide CRISPR screen specifically identified proteins essential for MYC ESE activity but not simian virus 40 (SV40) enhancer. These proteins not only were essential for the reporter activity but also were also important for MYC expression and LCL growth. Targeting these proteins may lead to new therapies for EBV-associated cancers.

15.
Ecotoxicol Environ Saf ; 181: 370-380, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212185

RESUMO

Cigarette smoke can cause follicle destruction and oocyte dysfunction and increase the risks of spontaneous abortion, stillbirth, and tubal ectopic pregnancy, affecting female reproductive health. Third-hand smoke (THS) is residual tobacco smoke existing in the environment long after cigarettes are extinguished, which can react with other compounds in the environment to produce secondary pollutants. However, the effects of THS on the female reproductive system, particularly the maturation of the oocyte, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a component of THS, is a logical biomarker of THS exposure. Thus, this study aims to investigate the toxic effects of NNA on the maturation of murine oocytes and subsequent developmental competence. Herein, murine oocytes were exposed to 0 (control group), 0.1, 1.0, 10, and 50 µM NNA for 24 h. Our results showed that NNA exposure reduced the polar body extrusion rate by causing 8-oxo-deoxyguanosine (8-OHdG) to increase and disrupting the meiotic spindle morphology by inhibiting ERK1/2 activation during in vitro maturation. Additionally, NNA exposure resulted in cleavage and blastocyst rate reduction by altering DNA and histone methylations by reducing 5 mC and H3K4me2 levels and by inducing apoptosis caused by mitochondrial dysfunction and reactive oxygen species accumulation, as shown by the increased superoxide dismutase mRNA level and by the decreased Bcl-x mRNA level. Collectively, our results demonstrate that NNA exposure reduces the maturation and developmental capability of murine oocytes by increasing the risk of DNA damage and abnormal spindle morphology, altering epigenetic modifications, and inducing apoptosis, suggesting the toxic effect of NNA on mammalian productive health.


Assuntos
Aldeídos/toxicidade , Poluentes Ambientais/toxicidade , Nitrosaminas/toxicidade , Oócitos/efeitos dos fármacos , Piridinas/toxicidade , Animais , Apoptose , Dano ao DNA , Epigênese Genética , Feminino , Camundongos , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fuso Acromático/efeitos dos fármacos
16.
Microorganisms ; 7(6)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141917

RESUMO

The inactivation of Escherichia coli O157:H7 (E. coli) in physiological saline and lotus roots by high hydrostatic pressure (HHP) in combination with CO2 or N2 was studied. Changes in the morphology, cellular structure, and membrane permeability of the cells in physiological saline after treatments were investigated using scanning electron microscopy, transmission electron microscopy, and flow cytometry, respectively. It was shown that after HHP treatments at 150-550 MPa, CO2-packed E. coli cells had higher inactivation than the N2-packed and vacuum-packed cells, and no significant difference was observed in the latter two groups. Further, both the morphology and intracellular structure of CO2-packed E.coli cells were strongly destroyed by high hydrostatic pressure. However, serious damage to the intracellular structures occurred in only the N2-packed E. coli cells. During HHP treatments, the presence of CO2 caused more disruptions in the membrane of E. coli cells than in the N2-packed and vacuum-packed cells. These results indicate that the combined treatment of HHP and CO2 had a strong synergistic bactericidal effect, whereas N2 did not have synergistic effects with HHP. Although these two combined treatments had different effects on the inactivation of E. coli cells, the inactivation mechanisms might be similar. During both treatments, E. coli cells were inactivated by cell damage induced to the cellular structure through the membrane components and the extracellular morphology, unlike the independent HHP treatment.

17.
J Biol Chem ; 294(25): 9734-9745, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31073033

RESUMO

Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult because of a lack of specific symptoms. Many patients have advanced disease at diagnosis, and these patients respond poorly to treatment. New treatments are therefore needed to improve the outcome of NPC. To better understand the molecular pathogenesis of NPC, here we used an NPC cell line in a genome-wide CRISPR-based knockout screen to identify the cellular factors and pathways essential for NPC (i.e. dependence factors). This screen identified the Moz, Ybf2/Sas3, Sas2, Tip60 histone acetyl transferase complex, NF-κB signaling, purine synthesis, and linear ubiquitination pathways; and MDM2 proto-oncogene as NPC dependence factors/pathways. Using gene knock out, complementary DNA rescue, and inhibitor assays, we found that perturbation of these pathways greatly reduces the growth of NPC cell lines but does not affect growth of SV40-immortalized normal nasopharyngeal epithelial cells. These results suggest that targeting these pathways/proteins may hold promise for achieving better treatment of patients with NPC.

18.
Sci Total Environ ; 673: 424-434, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30991332

RESUMO

To investigate photochemical ozone (O3) pollution over the South China Sea (SCS), an intensive sampling campaign was conducted from August to November simultaneously at a continental site (Tung Chung, TC) and a marine site (Wan Shan Island, WSI). It was found that when continental air masses intruded the SCS, O3 episodes often occurred subsequently. To discover the causes, a photochemical trajectory model (PTM) coupled with the near-explicit Master Chemical Mechanism (MCM) was adopted, and the photochemical processes of air masses during the transport from TC to WSI were investigated. The simulated O3 and its precursors (i.e. NOx and VOCs) showed a reasonably good agreement with the observations at both TC and WSI, indicating that the PTM was capable of simulating O3 formation for air masses traveling from TC to WSI. The modeling results revealed that during the transport of air masses from TC to WSI, both VOC and NOx decreased in the morning while O3 increased significantly, mainly due to rapid chemical reactions with elevated radicals over the SCS. The elevated radicals over the SCS were attributable to the fact that higher NOx at TC consumed more radicals, whereas the concentration of radicals increased from TC to WSI because of NOx dilution and destruction. Subsequently, the photochemical cycling of radicals accelerated, leading to high O3 mixing ratios over the SCS. Furthermore, based on the source profiles of the emission inventory used, the contributions of six sources, i.e. gasoline vehicle exhaust, diesel vehicle exhaust, gasoline evaporation and LPG usage, solvent usage, biomass and coal burning, and biogenic emissions, to maritime O3 formation were evaluated. The results suggested that gasoline vehicles exhaust and solvent usage largely contributed the O3 formation over the SCS (about 5.2 and 3.8 ppbv, respectively). This is the first time that the contribution of continental VOC sources to the maritime O3 formation was quantified.

19.
J Virol ; 93(13)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31019051

RESUMO

Epstein-Barr virus (EBV) infection of human primary resting B lymphocytes (RBLs) leads to the establishment of lymphoblastoid cell lines (LCLs) that can grow indefinitely in vitro EBV transforms RBLs through the expression of viral latency genes, and these genes alter host transcription programs. To globally measure the transcriptome changes during EBV transformation, primary human resting B lymphocytes (RBLs) were infected with B95.8 EBV for 0, 2, 4, 7, 14, 21, and 28 days, and poly(A) plus RNAs were analyzed by transcriptome sequencing (RNA-seq). Analyses of variance (ANOVAs) found 3,669 protein-coding genes that were differentially expressed (false-discovery rate [FDR] < 0.01). Ninety-four percent of LCL genes that are essential for LCL growth and survival were differentially expressed. Pathway analyses identified a significant enrichment of pathways involved in cell proliferation, DNA repair, metabolism, and antiviral responses. RNA-seq also identified long noncoding RNAs (lncRNAs) differentially expressed during EBV infection. Clustered regularly interspaced short palindromic repeat (CRISPR) interference (CRISPRi) and CRISPR activation (CRISPRa) found that CYTOR and NORAD lncRNAs were important for LCL growth. During EBV infection, type III EBV latency genes were expressed rapidly after infection. Immediately after LCL establishment, EBV lytic genes were also expressed in LCLs, and ∼4% of the LCLs express gp350. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) and POLR2A chromatin interaction analysis followed by paired-end tag sequencing (ChIA-PET) data linked EBV enhancers to 90% of EBV-regulated genes. Many genes were linked to enhancers occupied by multiple EBNAs or NF-κB subunits. Incorporating these assays, we generated a comprehensive EBV regulome in LCLs.IMPORTANCE Epstein-Barr virus (EBV) immortalization of resting B lymphocytes (RBLs) is a useful model system to study EBV oncogenesis. By incorporating transcriptome sequencing (RNA-seq), chromatin immune precipitation followed by deep sequencing (ChIP-seq), chromatin interaction analysis followed by paired-end tag sequencing (ChIA-PET), and genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen, we identified key pathways that EBV usurps to enable B cell growth and transformation. Multiple layers of regulation could be achieved by cooperations between multiple EBV transcription factors binding to the same enhancers. EBV manipulated the expression of most cell genes essential for lymphoblastoid cell line (LCL) growth and survival. In addition to proteins, long noncoding RNAs (lncRNAs) regulated by EBV also contributed to LCL growth and survival. The data presented in this paper not only allowed us to further define the molecular pathogenesis of EBV but also serve as a useful resource to the EBV research community.

20.
Chemosphere ; 226: 817-824, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30965253

RESUMO

Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na+/K+-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance.


Assuntos
Aminobutiratos/toxicidade , Poluição Ambiental/efeitos adversos , Lagartos/metabolismo , Locomoção/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Aminobutiratos/farmacocinética , Aminobutiratos/farmacologia , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Ecotoxicologia , Feminino , Lagartos/fisiologia , Masculino , Síndromes Neurotóxicas/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/metabolismo , Fatores Sexuais
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