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1.
World J Pediatr ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193830

RESUMO

BACKGROUND: Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children. METHODS: We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≥ 3 days. RESULTS: Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed. CONCLUSIONS: Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32170789

RESUMO

This study investigated the effects of lycopene on the gene expression profile and expression of genes related to fat metabolism of Xinghua breeding hens. Seven hundred and twenty healthy breeding hens were randomly assigned to four treatments; each treatment was replicated six times with 30 hens each. Broken rice and soybean meal were adopted for the basal diet and added with 0 (control group), 20, 40 and 80 mg/kg lycopene respectively. Gene expression profile of the liver induced by lycopene and expression of genes related to fat metabolism in hens liver and intestine were analysed after 42-day feeding trial including 7-day pre-feeding period and 35-day formal period. The genes involved in fat metabolism were analysed, and we found that lycopene significantly increased the expression of PGC1α, PPARα, RXRα and RARα in the liver, PPARγ, RXRα and RXRγ in the jejunum, and RARα in the duodenum (p < .05); reduced the expression of FABP1 and FABP10 in the liver, and FATP4 in the jejunum (p < .05). By analysing gene expression profile, 158 differentially expressed genes (DEGs) including 69 up-regulated genes and 89 down-regulated genes were obtained between control group and 40 mg/kg group. KEGG pathway analysis was performed on all DEGs, and 5 pathways were obtained. In conclusion, lycopene can affect the expression of related genes, and this may be one of the reasons that lycopene can regulate fat metabolism.

3.
Gene ; 742: 144550, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32165293

RESUMO

Heat stress has a negative impact on dairy cow productivity. In order to reveal the mechanisms of heat-stress response, the mRNA and miRNA expression profiles of five cows under chronic heat-stress and thermoneutral conditions were assayed in blood by high-throughput sequencing technology. A total of 540 mRNAs and 9 miRNAs were expressed differently under heat-stress and thermoneutral conditions. Functional analyses revealed that MAPK signaling pathway, cellular senescence, circadian entrainment, aldosterone synthesis and secretion, and pathways in cancer were enriched for differently expressed mRNAs; meanwhile cGMP-PKG signaling pathway, thermogenesis, and protein digestion and absorption were enriched for differently expressed miRNAs. In addition, GADD45G, TGFB2, and GNG11 may play roles in the heat stress, and bta-miR-423-5p might be one of the regulators of heat-stress response in cows as potential mediators of chronic heat-stress response. In conclusion, the present study described the mRNA and miRNA expression patterns in blood extracted from cows during the transition from heat-stress to thermoneutral conditions. The results provide new data that could help in identifying mechanisms that mediate cows' response to chronic heat stress.

4.
Mol Ther Nucleic Acids ; 20: 231-241, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32193151

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

5.
Biochem Biophys Res Commun ; 524(3): 689-695, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32033747

RESUMO

Dehydration-responsive element binding (DREB) transcription factors activate the expression of downstream functional genes in combination with a dehydration-responsive element (DRE), and thereby improve the resistance of plants to abiotic stresses such as heat. However, the upstream regulatory mechanism of DREB genes under heat is unclear. A DREBA4 subfamily transcription factor (SlDREBA4), which is heat-responsive and improves heat resistance, was isolated from Solanum lycopersicum 'Microtom'. In this study, promoter truncation experiments were performed to verify changes in ß-glucuronidase (GUS) enzyme activity and GUS gene expression levels in transgenic plants with different lengths of promoter fragments under heat and to identify specific regions in the promoter that respond to heat. Our results showed that the GUS reporter gene was constitutively expressed in tissues of the full-length promoter transgenic 'Microtom' plants, with higher expression in conducting tissues of root, stem, and leaf, as well as sepals of flowers and fruits. Under heat treatment, GUS enzyme activity and GUS gene expression levels in tissues of the full-length promoter transgenic plants increased. Promoter deletion analysis identified two positive regulatory regions (-1095 to -730 bp and -162 to -38 bp) responsible for the promoter's response to heat. These results indicated that the heat shock element (HSE) and MYC recognition sequences may cooperate in heat-induced activation of SlDREBA4 promoter.

6.
Medicine (Baltimore) ; 99(8): e19316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080148

RESUMO

OBJECTIVE: To investigate the effect of edaravone on depression relief in symptomatic patients with intracranial stenosis and its relationship with the expression of sex hormones. METHODS: We recruited 112 patients with symptomatic intracranial arterial stenosis from Renmin Hospital, Wuhan University, between October 2014 and October 2017. All patients were divided into the traditional or experimental (traditional treatment + intravenous infusion of edaravone 30 mg twice a day for 14 days) treatment groups. The general clinical data were collected, and neurological functional recovery using the Modified Rankin Scale (mRS) and National Institute of Health stroke scale (NIHSS) scores were recorded. Symptom Checklist 90 (SCL-90) was used to assess the general psychological changes of the patient, followed by the 24 Hamilton Depression Scale (HAMD) to examine the incidence of post-stroke depression (PSD). This divided the patients into the mild, moderate, and severe depression groups. Next, we measured the serum protein expression of the sex hormones estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), prolactin (PRL), and luteinizing hormone (LH). RESULTS: The mRS and NIHSS scores were significantly lower in the experimental group than in the control group (P < .05). There was no significant difference in SCL90 score before intervention (P > .05); the scores were significantly lower in the experimental group after intervention (P < .05). There was a significant difference in SCL-90 and HAMD scores between groups before treatment (P < .05), with significantly lower scores in the experimental group post-treatment (P < .05). The incidence of depression was significantly reduced in the experimental group post-treatment. Furthermore, the expression of E2 and FSH was significantly higher (P < .01) and lower (P < .001), respectively, in women than in men in the experimental group post-treatment. Interestingly, the expression of T was significantly lower in men in the experimental group post-treatment (P < .001). CONCLUSION: Edaravone significantly improved the clinical efficacy of stent implantation in intracranial artery stenosis treatment by alleviating depression and reducing the incidence of PSD.


Assuntos
Arteriopatias Oclusivas/terapia , Encéfalo/irrigação sanguínea , Depressão/tratamento farmacológico , Edaravone/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Stents , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Índice de Gravidade de Doença , Testosterona/sangue
7.
Pharmacol Res ; 155: 104690, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057894

RESUMO

The innate immune system drives inflammatory joint damage in osteoarthritis (OA) and regulates cartilage repair. Berberine chloride (BBR) is an isoquinoline alkaloid that shows immunomodulatory activity in a variety of cell lines. However, the immunomodulatory mechanisms of BBR in chondrocytes during OA are largely unknown. Herein, we assessed the ability of BBR to mediate chondroprotection through its effects on innate immunity. We found that BBR up-regulated the expression of surfactant protein D (SP-D) in OA cartilage, a key regulator of inflammation and innate immunity both in the airways and extrapulmonary tissues, including joint cartilage. To further explore these findings, we used recombinant adeno-associated virus (rAAV)-mediated knockdown of SP-D. Silencing was assessed in rat model of surgically-induced OA in the presence or absence of BBR treatment, 10 weeks post-surgery. We observed a clear improvement in histological scores of BBR-treated animals compared to those treated with BBR and the rAAV-SP-D vector. In addition, animals co-treated with BBR + recombinant human SP-D (rhSP-D) exhibited significantly lower histological scores than those treated with BBR alone. BBR treatment led to significantly reduced immune cell infiltration mediated through TLR4, F4/80, CD68 and CD34, whilst SP-D silencing reversed this improvement. In contrast, rhSP-D treatment enhanced the protective phenotype. We further explored how BBR influences SP-D and other OA-associated genes in vitro. We observed an up-regulation of SP-D and a marked decline in TRAF6, TLR4, MD-2 and MyD88 expression, as well as NF-κB p65 and IκBα phosphorylation in chondrocytes treated with sodium nitroprusside. siRNAs specific for SP-D were able to partially reverse this phenotype, whilst both rhSP-D and the TLR4 inhibitor TAK-242 enhanced the effects. Together, these results are consistent with a model wherein SP-D has therapeutic potential for OA treatment. Concomitantly, BBR modulates immune responses and decreases cartilage degradation. These findings suggest that BBR achieves this function through releasing SP-D from MD2/SP-D complexes and through the inhibition of TLR4/NF-κB signaling.

8.
Int J Biol Macromol ; 148: 333-341, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954783

RESUMO

Deacetyl-7-aminocephalosporanic acid (D-7-ACA) is required for producing of many semisynthetic ß-lactam antibiotics; therefore, enzymes capable of converting 7-aminocephalosporanic acid (7-ACA) to D-7-ACA present a valuable resource to the pharmaceutical industry. In the present study, a putative acetylesterase, EstZY, was identified and characterized from a thermophilic bacterium Alicyclobacillus tengchongensis. Sequence alignment showed that EstZY was an acetylesterase which belonged to carbohydrate esterase family 7 (CE7), with substrate preference for short-chain acyl esters p-NPC2 to p-NPC8. Maximum enzyme activity was recorded at pH 9.0 and 50 °C, where Km and Vmax were calculated as 1.9 ± 0.23 mM and 258 ± 18.5 µM min-1, respectively. The residues Ser185, Asp274, and His303 were identified as the putative catalytic triad by homology modelling, site-directed mutagenesis and molecular docking. Moreover, EstZY can remove the acetyl group at C3' position of 7-ACA to form D-7-ACA; this is the first report of a 7-ACA deacetylase from CE7 family in A. tengchongensis and may represent a new enzyme with industrial values.

9.
Mikrochim Acta ; 187(2): 146, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970525

RESUMO

An optical fiber nanoprobe is presented for fluorometric determination of copper(II). The method based on the use of water-dispersible AgInZnS quantum dots (QDs) deposited at the end of an optical fiber in a poly(vinyl alcohol) matrix. The fluorescnece of the QDs, best measured at excitation/emisssion wavelengths of 365/570 nm, is quenched by Cu(II) due to both static and electron transfer from the QDs to Cu(II). This is experimentally confirmed by photoluminescence and UV-vis absorption spectra, and measurement of luminescence lifetimes. The probe is highly selective and possesses a linear detection range that extends from 2.5 to 800 nM. Graphical abstractSchematic representation of an optical fiber nanoprobe based on hydrophilic AgInZnS quantum dots for fluorometric determination of copper(II). The fluorescence is quenched by Cu(II) due to static quenching and dynamic quenching. It has a detection range of 2.5-800 nM.

10.
J Antibiot (Tokyo) ; 73(4): 260-264, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31925390

RESUMO

A systematic study of the secondary metabolites of the wild granaticin-producing strain Streptomyces vietnamensis GIMV4.0001 led to the isolation of six known early shunt products related to actinorhodin, SEK34 (3), SEK34b (4), mutactin (5), dehydromutactin (7), EM18 (8) and GTRI-02 (9). While the other shunt products were minor or trace products, the production ratio of SEK34 (3) and SEK34b (4) to granaticins was strikingly high. Nearly 64% of the intermediate with the first ring closed went to the SEK34/SEK34b aberrant pathway. The high level of the aberrant metabolic flow toward the early shunt products SEK34 and SEK34b indicated that the second ring closure of the granaticin (1) biosynthesis is a key limiting step in the granaticin biosynthetic machinery of S. vietnamensis GIMV4.0001.

11.
Reprod Domest Anim ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31960497

RESUMO

Fecundity improvement is one of the most important objectives for goat breeders as it can considerably greatly increase production efficiency. The molecular mechanisms underlying fecundity in goats remain largely unknown. To explore the molecular and genetic mechanisms related to the fecundities and prolificacies in Chuanzhong black goats, we performed high-throughput RNA sequencing to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs (DElncRNAs and DEmRNAs, respectively) the ovaries of high-fecundity and low-fecundity goats; furthermore, we conducted functional annotation analyses to identify pathways of interest. Overall, 1,353 DEmRNAs and 168 DElncRNAs were identified. Quantitative real-time PCR (qRT-PCR) was performed to validate some randomly selected DElncRNAs and DEmRNAs. We found that two DElncRNAs ENSCHIT00000005909 and ENSCHIT00000005910 might positively influence the expression of the corresponding gene IL1R2 (upregulated in high-fecundity group), exerting co-regulative effects on the ovarian function, through which litter size might show variations. KEGG pathway analysis indicated that the DEmRNAs SRD5A2, LOC102191297 and LOC102171967 were significantly enriched in steroid hormone biosynthesis-this pathway was related to animal reproduction. To summarize, our findings expand the understanding pertaining to the biological functions of lncRNAs and contribute to the annotation of the goat genome; moreover, they should be helpful for further studying the role of lncRNAs in ovulation and lambing.

12.
Life Sci ; 243: 117288, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926246

RESUMO

AIMS: Intervertebral disc degeneration (IDD) was associated with microRNA (miRNA) dysregulation. Therefore, we verified the hypothesis that miRNAs modulated IDD by affecting the insulin-like growth factor-binding protein 5 (IGFBP5)/extracellular signal-regulated kinase (ERK) signaling pathway. MATERIALS AND METHODS: The miRNA expression profiles in nucleus pulposus (NP) cells were compared between patients with IDD and controls, and miRNA microarray and quantitative real-time PCR (RT-qPCR) assays were utilized. Luciferase reporter and Western blotting assays were performed to detect the miRNA targets. KEY FINDINGS: RT-qPCR confirmed that the expression level of miR-24-3p was significantly increased in degenerative NP cells. Moreover, the miR-24-3p level was positively correlated with the disc degeneration grade, and miR-24-3p significantly induced NP cell apoptosis. IGFBP5 was determined as a target of miR-24-3p, and IGFBP5 knockdown induced effects on NP cells similar to those induced by miR-24-3p. Compared with control cells, NP cells presented with miR-24-3p overexpression or IGFBP5 downregulation via shRNAs had significantly increased p-ERK and Bax expression levels. Furthermore, in vivo analysis on IDD rat model showed that the downregulation of miR-24-3p could effectively suspend IDD. SIGNIFICANCE: These results demonstrated that miR-24-3p upregulation could promote IDD through IGFBP5 and the ERK signaling pathway.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Degeneração do Disco Intervertebral/fisiopatologia , MicroRNAs/fisiologia , Transdução de Sinais , Animais , Apoptose , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima
13.
Biomed Chromatogr ; 34(3): e4769, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31808565

RESUMO

This study was designed to investigate the metabolic and transcriptional alterations in seminal fluid caused by asthenozoospermia (AS). To address these issues, a method of metabonomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and real-time quantitative PCR (RT-qPCR) was performed to identify some crucial biomarkers and transcription levels of the enzymes in seminal fluid. Seminal fluid samples were collected from 87 AS patients and 73 healthy males with normozoospermia. The quantitative analysis by UPLC-MS/MS showed that 19 metabolites in seminal plasma were associated with AS, and they were involved in several metabolic pathways, such as energy metabolism, purine metabolism, methionine cycle, and branched chain amino acid metabolism. Among these metabolites, the levels of citric acid, malic acid, succinic acid, and pyruvic acid, which are related to energy metabolism, were collectively reduced in the AS group, whereas the lactic acid level was enhanced. These results indicated that lesser energy source (adenosine triphosphate) was produced through the anaerobic glycolysis pathway rather than via aerobic catabolism of suger and tricarboxylic acid cycle, resulting in reduced power of sperms. Meanwhile, partial least squares discriminant analysis showed significant differences in metabolic profiles between the AS and control groups. In addition, RT-qPCR results revealed that the expression levels of four genes encoding fructokinase citrate synthase, succinate dehydrogenase, and spermine synthase, which were related to energy metabolism, were decreased in the AS group. The 23 descriptors with differential expression in AS may be valuable for the diagnosis and sequential study on AS. These results will help highlight the role of sperm inactivity in AS pathogenesis.

14.
J Wildl Dis ; 56(1): 93-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31329525

RESUMO

The only known outbreak of foot-and-mouth disease (FMD) in wildlife in the US occurred in mule deer (Odocoileus hemionus) in California in 1924-25. There is little recorded information on the pathogenesis and epidemiology of the disease in deer in that outbreak. In this experimental study, we compared the susceptibility of mule deer to FMD virus (FMDV) serotype O to that of cattle (Bos taurus). We also determined the potential for intra- and interspecies transmission of FMDV serotype O in mule deer and cattle, and assessed conventional laboratory tests in their ability to detect FMDV in mule deer. Two mule deer and one steer were each infected by intraepithelial tongue inoculation with 10,000 bovine tongue infective doses of FMDV, strain O1 Manisa. The inoculated steer and deer were kept in the same room with contact animals of both species. Exposed contact animals were moved to rooms with unexposed animals after becoming febrile. All mule deer (n=14) and cattle (n=6) developed clinical signs and lesions consistent with FMDV infection. Deer had a high prevalence of myocarditis and high mortality. Virus was transmitted between mule deer, from cattle to mule deer, and from mule deer to cattle. Virus and antibodies against nonstructural FMDV proteins in mule deer and cattle were detected by conventional laboratory tests. Virus shedding was detected by PCR and virus isolation up to 9 d postexposure in deer.

15.
Huan Jing Ke Xue ; 41(1): 166-172, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854917

RESUMO

We use 84 rainfall samples collected during June to September 2017 from the Dongkemadi basin, source region of the Yangtze River, China, to analyze the characteristics and influencing factors of stable isotopes in groundwater, and further discuss the groundwater recharge sources. The results showed that the range of groundwater δ18 O values in this permafrost region varied from -15.3‰ to -12.5‰ (mean -14.0‰). The range of δD values in groundwater varied from -108.9‰ to -91.7‰ (mean -100.2‰). Compared with local atmospheric precipitation, groundwater isotopes were relatively enriched. The slope and intercept of the groundwater line (GL) in the study area were both lower than of those of the global and local meteoric water lines (GMWL and LMWL), thus indicating that groundwater in the study area was subjected to evaporation during rainfall recharge of groundwater. The d-excess values of groundwater varied from 4.9‰ to 25.0‰ (mean 11.6‰), which was close to the average d-excess value determined for global average rainfall (10‰), but lower than that of rainfall in the study area (15.1‰). The influencing factors on the composition and variation of groundwater isotopes were different in different periods. The permafrost active layer was relatively thin during periods of increasing air temperature, and groundwater isotopes were significantly affected by air temperature. A temperature decrease during the latter part of the sampling period, when the thickness of the permafrost active layer was still increasing, further increased the retention time of infiltrating rainfall in the soil, thereby eventually leading to evaporation that strengthened the enrichment of heavy isotopes in the groundwater. According to the topographic characteristics of the Dongkemadi basin, the isotopic characteristics of the groundwater, and the factors influencing the isotopic composition, we conclude that rainfall was the main source of groundwater recharge. The results of this study provide a scientific basis for studying water cycle processes in the permafrost regions of the source region of the Yangtze River.

16.
Phys Rev Lett ; 123(20): 206601, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31809106

RESUMO

Recently discovered Dirac semimetals (DSMs) with two Dirac nodes, such as Na_{3}Bi and Cd_{2}As_{3}, are regarded as carrying the Z_{2} topological charge in addition to the chiral charge. We study the Floquet phase transition of Z_{2} topological DSMs subjected to a beam of circularly polarized light. Owing to the resulting interplay of the chiral and Z_{2} charges, the Weyl nodes are not only chirality dependent but also spin dependent, which constrains the behavior in creation and annihilation of the pair of Weyl nodes. Interestingly, we find a novel phase: One spin band is in the Weyl semimetal phase while the other is in the insulator phase, and we dub it the Weyl half-metal (WHM) phase. We further study the spin-dependent transport in a Dirac-Weyl semimetal junction and find a spin filter effect as a fingerprint of the existence of the WHM phase. The proposed spin filter effect, based on the WHM bulk band, is highly tunable in a broad parameter regime and robust against magnetic disorder, which is expected to overcome the shortcomings of the previously proposed spin filter based on the topological edge or surface states. Our results offer a unique opportunity to explore the potential applications of topological DSMs in spintronics.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1574-1579, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607314

RESUMO

OBJECTIVE: To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms (MPN). METHODS: The exon 9 of TET2 gene was amplified by RT-PCR, and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing. The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden. The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed. RESULTS: TET2 gene rs3733609 C/T heterozygosity (normal T/T) could be detected in 19 cases of 85 cases of JAK2V617F positive MPN (22.4%) patients, while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers, and the incidence was only 8.5% (9/106). Compared with the negative group (TET2 rs3733609 T/T), there was no significant difference in the median age, hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609 (CT/TC) positive, but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased. In JAK2V617F high allele burden group, TET2 gene SNP rs3733609 was positive in 7 cases (36.8%, 7/19), the ratio was higher than that in the low allele burden group(18.2%, 12/66). CONCLUSION: TET2 SNP rs3733609 C/T may be a new susceptible allelee, which affects the clinical characteristics and clonal evolution of MPN patients.


Assuntos
Proteínas de Ligação a DNA/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos , Proteínas Proto-Oncogênicas/genética , Alelos , Éxons , Humanos , Mutação , Transtornos Mieloproliferativos/genética , Neoplasias
18.
J Dig Dis ; 20(11): 589-595, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31574578

RESUMO

To evaluate current diagnosis and treatment of patients with nocturnal gastroesophageal reflux (nGER). METHODS: This multicenter observational study was conducted in 44 hospitals in China from May 2017 to February 2018. Outpatients with nGER were recruited and their relevant data were collected using a questionnaire, including age, gender, body mass index, history of smoking and alcohol consumption, comorbid diseases, lifestyle, self-reported health status, medical history, nGER symptoms and severity, Hospital Anxiety Depression Scale, Pittsburgh Sleep Quality Index, diagnosis and treatment choices. The study was registered on the Chinese Clinical Trial Registry (no. ChiCTR1800017525). RESULTS: The study included 4978 individuals, with valid questionnaires collected from 4448 patients (89.4%). The symptoms of heartburn and regurgitation were more severe at night than during the day (P < 0.05). Age and body mass index were positively correlated with reflux severity at night and during the day (P < 0.05). The severity of nGER was positively associated with lifestyle factors such as smoking, a high-fat diet, carbonated beverage consumption, late supper (later than 9 pm), and snoring (all P < 0.05). Night-time heartburn and regurgitation were related with sleep disorder. CONCLUSIONS: Lifestyle factors are associated with nGER severity, and nGER affects sleep quality. It will be beneficial to popularize and strengthen the diagnosis and treatment of nGER.

19.
Pestic Biochem Physiol ; 160: 154-162, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519250

RESUMO

Sanguinarine (Sang) is a natural alkaloid and distributed in several plants of Papaveraceae. The antitumor, antioxidant, antimicrobial and anti-inflammatory effects of Sang were extensively reported, but its speciality and mechanism against Lepidoptera insects were still unknown. In this study, detailed toxicological parameters of Sang against silkworms, Bombyx mori (B. mori), were determined by a toxicological test. Then, a nuclear magnetic resonance-based (NMR) metabolomics method was adopted to analyze the changes in hemolymph metabolites of silkworms after feeding Sang. The growth of fourth-instar larvae was significantly ceased by the oral administration of 0.05-0.3% Sang and vast deaths appeared in 0.3% Sang group on Day 4 and Day 5. The quantitative analysis of metabolites indicated that trehalose and citrate levels in hemolymph were increased after 24 h of feeding 0.3% Sang, whereas the concentrations of pyruvate, succinate, malate and fumarate were decreased. In addition, the enzymatic determination and reverse transcription quantitative PCR (RT-qPCR) showed that the trehalase (THL) activity and the transcriptional level of one gene coding THL were uniformly weakened by 0.3% Sang. One of the important mechanisms of Sang against silkworms might be interpreted as follows. Sang impaired trehalose hydrolysis, reduced THL activity and transcription, and led to the inhibition of energy metabolism, consequent antigrowth and high lethality in larvae of B. mori. Our findings offered new insights into the insecticidal effect of Sang from the perspective of energy metabolism and provided the basis for the application of Sang in the control of Lepidoptera pests.


Assuntos
Benzofenantridinas/toxicidade , Bombyx/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Isoquinolinas/toxicidade , Larva/efeitos dos fármacos , Animais , Bombyx/crescimento & desenvolvimento , Hemolinfa/metabolismo , Inseticidas/farmacologia , Metabolômica
20.
Mol Reprod Dev ; 86(11): 1758-1770, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31535418

RESUMO

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) is a central regulator of mitochondrial biogenesis and metabolism, and its expression is closely related to embryo development. To gain insights into the possible mechanisms of PPARGC1A during early embryogenesis, the development potential, mitochondrial biogenesis, and the culture medium metabolomics of embryos were evaluated when PPARGC1A overexpressed or suppressed in rabbit zygotes. Results showed that different PPARGC1A levels in rabbit zygotes could affect blastocyst percentage, and the expressions of mitochondrial biogenesis and metabolic-related genes, as well as the glutathione and adenosine triphosphate levels during early embryo development. In addition, compared with the controls, 12 and 10 different metabolites involved in carbohydrate, amino acid, and fatty acid metabolism were screened in the 5 day's spent culture medium of PPARGC1A overexpressed and suppressed embryos by gas chromatography-mass spectrometer, respectively. Consistent with these metabolite changes, the transcriptions of genes encoding glucose transporters and fatty acid biosynthetic proteins in the embryos from different groups were regulated by PPARGC1A during rabbit embryo development. Taken together, these data provide evidence that PPARGC1A may regulate early rabbit embryo development through mitochondrial biogenesis and metabolism.

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