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1.
mSphere ; 5(3)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376702

RESUMO

Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B, indicated to prevent recurrence of C. difficile infection (rCDI) in high-risk adults receiving antibacterial treatment for CDI. An exploratory genome-wide association study investigated whether human genetic variation influences bezlotoxumab response. DNA from 704 participants who achieved initial clinical cure in the phase 3 MODIFY I/II trials was genotyped. Single nucleotide polymorphisms (SNPs) and human leukocyte antigen (HLA) imputation were performed using IMPUTE2 and HIBAG, respectively. A joint test of genotype and genotype-by-treatment interaction in a logistic regression model was used to screen genetic variants associated with response to bezlotoxumab. The SNP rs2516513 and the HLA alleles HLA-DRB1*07:01 and HLA-DQA1*02:01, located in the extended major histocompatibility complex on chromosome 6, were associated with the reduction of rCDI in bezlotoxumab-treated participants. Carriage of a minor allele (homozygous or heterozygous) at any of the identified loci was related to a larger difference in the proportion of participants experiencing rCDI versus placebo; the effect was most prominent in the subgroup at high baseline risk for rCDI. Genotypes associated with an improved bezlotoxumab response showed no association with rCDI in the placebo cohort. These data suggest that a host-driven, immunological mechanism may impact bezlotoxumab response. Trial registration numbers are as follows: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).IMPORTANCE Clostridium difficile infection is associated with significant clinical morbidity and mortality; antibacterial treatments are effective, but recurrence of C. difficile infection is common. In this genome-wide association study, we explored whether host genetic variability affected treatment responses to bezlotoxumab, a human monoclonal antibody that binds C. difficile toxin B and is indicated for the prevention of recurrent C. difficile infection. Using data from the MODIFY I/II phase 3 clinical trials, we identified three genetic variants associated with reduced rates of C. difficile infection recurrence in bezlotoxumab-treated participants. The effects were most pronounced in participants at high risk of C. difficile infection recurrence. All three variants are located in the extended major histocompatibility complex on chromosome 6, suggesting the involvement of a host-driven immunological mechanism in the prevention of C. difficile infection recurrence.

2.
Int J Mol Sci ; 21(9)2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32349427

RESUMO

The quality of Lily cut flower was determined by the quality of bulbs. During the process of vernalization and flower bud differentiation, sugar massively accumulated in the bulb, which influenced the bulb development. However, the details of sugar genes' regulation mechanism for these processes were not fully understood. Here, morphological physiology, transcriptomes and gene engineering technology were used to explore this physiological change. Seventy-two genes of 25 kinds of sugar metabolism-related genes were annotated after re-analyzing transcriptome data of Oriental hybrid lily 'Sorbonne' bulbs, which were generated on Hiseq Illumina 2000. The results showed that these genes were closely related to lily bulb vernalization and development. Combining gene expression pattern with gene co-expression network, five genes (Contig5669, Contig13319, Contig7715, Contig1420 and Contig87292) were considered to be the most potential signals, and the sucrose transporter gene (SUT) was the focus of this study. Carbohydrate transport pathway and genes' regulation mechanism were inferred through a physiological and molecular test. SUT seemed to be the sugar sensor that could sense and regulate sugar concentration, which might have effects on other genes, such as FT, LFY and so on. LoSUT2 and LoSUT4 genes were cloned from Oriental hybrid lily 'Sorbonne' by RACE, which was the first time for these genes in Oriental hybrid lily 'Sorbonne'. The physiological properties of these proteins were analyzed such as hydrophobicity and phosphorylation. In addition, secondary and tertiary structures of proteins were predicted, which indicated the two proteins were membrane proteins. Their cellular locations were verified through positioning the experiment of the fluorescent vector. They were highly expressed in cells around phloem, which illustrated the key role of these genes in sugar transport. Furthermore, transient expression assays showed that overexpressed LoSUT2 and LoSUT4 in Arabidopsis thaliana bloomed significantly earlier than the wild type and the expression of FT, SOC1 and LFY were also affected by LoSUT2 and LoSUT4, which indicated that LoSUT2 and LoSUT4 may regulate plants flowering time.

3.
Vaccine ; 38(20): 3665-3670, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32245644

RESUMO

BACKGROUND: Middle school students are recommended as the primary target population for human papillomavirus (HPV) vaccination. This study aimed to assess HPV and HPV vaccine knowledge, and to evaluate the effect of a school-based educational intervention, immediately and one year later, on HPV knowledge and vaccine acceptability among adolescents in mainland China. METHODS: A school-based interventional follow-up study was conducted in seven representative cities in mainland China from May 2015 to May 2017. "Train-the-trainer" strategy was employed to educate school teachers in this study. Students aged 13 to 14 years old were assigned to intervention classes and control classes. All students were required to complete the baseline questionnaire. Students in the intervention classes were given a 45-minute lecture regarding HPV and HPV vaccine knowledge and were then asked to complete a post-education questionnaire. One year later, all students were asked to complete the post-education questionnaire again. RESULTS: Baseline HPV knowledge was low among Chinese adolescents, with only 12.6% and 15.7% of students having heard of HPV and HPV vaccines, respectively. After the intervention, the level of HPV-related knowledge increased immediately, and students with higher knowledge levels of HPV and HPV vaccines were more willing to get vaccinated. One year after the intervention, the knowledge of HPV and HPV vaccines was dramatically diminished. However, knowledge was significantly higher in intervention classes compared to control classes. CONCLUSIONS: Knowledge and awareness of HPV and vaccination are generally deficient among Chinese adolescents. School-based health education was very effective in improving awareness and positive attitudes about HPV and HPV vaccines within a short time. Integrating health education on HPV into the existing school-based sexual health curriculum could be an effective way to increase HPV vaccination coverage and help to eliminate preventable HPV-associated cancers in China.

4.
J Clin Lab Anal ; : e23340, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32320103

RESUMO

OBJECTIVE: This study aimed to investigate the tumor circular RNA_0018289 (circ_0018289) expression and its correlation with clinical characteristics as well as survival profiles in cervical cancer patients. METHODS: A hundred and ninety-two cervical cancer patients who received surgical resection were recruited in this prospective study. Tumor tissue and paired adjacent tissue were obtained during the surgery, in which circ_0018289 expression was detected by reverse transcription quantitative polymerase chain reaction. Disease-free survival (DFS) and overall survival (OS) were recorded. RESULTS: Circ_0018289 expression was upregulated in tumor tissue compared with paired adjacent tissue (P < .001), and receiver operative characteristic curve disclosed its good value for separating tumor tissue from adjacent tissue with an area under curve of 0.907 (95% CI: 0.879-0.935). Additionally, tumor circ_0018289 expression was positively associated with tumor size (P = .009), lymph node metastasis (P = .005) and Federation International of Gynecology and Obstetrics stage (P = .005). The DFS (P = .005) and OS (P = .015) were both worse in patients with circ_0018289 high expression compared to patients with circ_0018289 low expression. Meanwhile, in patients with circ_0018289 high expression, DFS and OS were the longest in patients with high+ expression followed by patients with high++ expression, and the shortest in patients with high+++ expression. Moreover, circ_0018289 high expression could independently predict worse DFS in the total cervical cancer patients (P = .042). CONCLUSION: Circ_0018289 could serve as a potential disease monitoring and prognostic biomarker in cervical cancer patients.

5.
Sci Rep ; 10(1): 5250, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251355

RESUMO

Fungal plant pathogens remain a serious threat to the sustainable agriculture and forestry, despite the extensive efforts undertaken to control their spread. White root rot disease is threatening rubber tree (Hevea brasiliensis) plantations throughout South and Southeast Asia and Western Africa, causing tree mortality and severe yield losses. Here, we report the complete genome sequence of the basidiomycete fungus Rigidoporus microporus, a causative agent of the disease. Our phylogenetic analysis confirmed the position of R. microporus among the members of Hymenochaetales, an understudied group of basidiomycetes. Our analysis further identified pathogen's genes with a predicted role in the decay of plant cell wall polymers, in the utilization of latex components and in interspecific interactions between the pathogen and other fungi. We also detected putative horizontal gene transfer events in the genome of R. microporus. The reported first genome sequence of a tropical rubber tree pathogen R. microporus should contribute to the better understanding of how the fungus is able to facilitate wood decay and nutrient cycling as well as tolerate latex and utilize resinous extractives.

6.
World J Gastroenterol ; 26(12): 1242-1261, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32256014

RESUMO

Inflammatory bowel disease (IBD) is a complex disease with multiple pathogenic factors. Although the pathogenesis of IBD is still unclear, a current hypothesis suggests that genetic susceptibility, environmental factors, a dysfunctional immune system, the microbiome, and the interactions of these factors substantially contribute to the occurrence and development of IBD. Although existing and emerging drugs have been proven to be effective in treating IBD, none can cure IBD permanently. G protein-coupled receptors (GPCRs) are critical signaling molecules implicated in the immune response, cell proliferation, inflammation regulation and intestinal barrier maintenance. Breakthroughs in the understanding of the structures and functions of GPCRs have provided a driving force for exploring the roles of GPCRs in the pathogenesis of diseases, thereby leading to the development of GPCR-targeted medication. To date, a number of GPCRs have been shown to be associated with IBD, significantly advancing the drug discovery process for IBD. The associations between GPCRs and disease activity, disease severity, and disease phenotypes have also paved new avenues for the precise management of patients with IBD. In this review, we mainly focus on the roles of the most studied proton-sensing GPCRs, cannabinoid receptors, and estrogen-related GPCRs in the pathogenesis of IBD and their potential clinical values in IBD and some other diseases.

7.
BMC Genomics ; 21(1): 196, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126975

RESUMO

BACKGROUND: Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. RESULTS: Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon. CONCLUSIONS: This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.

8.
Addict Behav ; 106: 106392, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32193072

RESUMO

INTRODUCTION: The study tested the psychometric properties of two Chinese version Internet Gaming Disorder scales (IGDSs): a dichotomous IGDS with yes/no type of response and a polytomous IGDS with a 0-5 Likert-type response. METHODS: The reliability and validity of two scales were tested separately, among two population-based samples of Chinese adolescents and adults (351 for dichotomous IGDS and 378 for polytomous IGDS). The diagnostic accuracy of the dichotomous IGDS was assessed in an independent sample of 114 gamers (56 disordered gamers and 58 average gamers) using Receiver Operating Characteristic (ROC) analysis. RESULTS: The results demonstrated good internal consistency (αdichotomous = 0.80 and αpolytomous = 0.89) and test-retest reliability (rdichotomous = 0.83 and rpolytomous = 0.84) for both scales. Both scales showed sound validity, as indicated by significant correlations with measurements of internet addiction, aggression, impulsivity, craving for gaming and time spent playing games. Factor analysis demonstrated that both Chinese IGDSs have a similar single-component structure to the original scales. The ROC analysis indicated an excellent diagnostic accuracy of the dichotomous IGDS. When apply the five or more cutoff points, the prevalence of IGD was 7.41% in the population-based sample. CONCLUSION: This study demonstrated robust psychometric properties of the Chinese version dichotomous IGDS and polytomous IGDS, and suggests that these scales are valid tools that suitable for clinical and research purposes.

9.
J Antimicrob Chemother ; 75(6): 1546-1553, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32211756

RESUMO

OBJECTIVES: Ceftolozane/tazobactam is approved for hospital-acquired/ventilator-associated bacterial pneumonia at double the dose (i.e. 2 g/1 g) recommended for other indications. We evaluated the bronchopulmonary pharmacokinetic/pharmacodynamic profile of this 3 g ceftolozane/tazobactam regimen in ventilated pneumonia patients. METHODS: This was an open-label, multicentre, Phase 1 trial (clinicaltrials.gov: NCT02387372). Mechanically ventilated patients with proven/suspected pneumonia received four to six doses of 3 g of ceftolozane/tazobactam (adjusted for renal function) q8h. Serial plasma samples were collected after the first and last doses. One bronchoalveolar lavage sample per patient was collected at 1, 2, 4, 6 or 8 h after the last dose and epithelial lining fluid (ELF) drug concentrations were determined. Pharmacokinetic parameters were estimated by non-compartmental analysis and pharmacodynamic analyses were conducted to graphically evaluate achievement of target exposures (plasma and ELF ceftolozane concentrations >4 mg/L and tazobactam concentrations >1 mg/L; target in plasma: ≥30% and ≥20% of the dosing interval, respectively). RESULTS: Twenty-six patients received four to six doses of study drug; 22 were included in the ELF analyses. Ceftolozane and tazobactam Tmax (6 and 2 h, respectively) were delayed in ELF compared with plasma (1 h). Lung penetration, expressed as the ratio of mean drug exposure (AUC) in ELF to plasma, was 50% (ceftolozane) and 62% (tazobactam). Mean ceftolozane and tazobactam ELF concentrations remained >4 mg/L and >1 mg/L, respectively, for 100% of the dosing interval. There were no deaths or adverse event-related study discontinuations. CONCLUSIONS: In ventilated pneumonia patients, 3 g of ceftolozane/tazobactam q8h yielded ELF exposures considered adequate to cover ceftolozane/tazobactam-susceptible respiratory pathogens.

10.
Nat Commun ; 11(1): 1427, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188862

RESUMO

Anthropogenic environments have been implicated in enrichment and exchange of antibiotic resistance genes and bacteria. Here we study the impact of confined and controlled swine farm environments on temporal changes in the gut microbiome and resistome of veterinary students with occupational exposure for 3 months. By analyzing 16S rRNA and whole metagenome shotgun sequencing data in tandem with culture-based methods, we show that farm exposure shapes the gut microbiome of students, resulting in enrichment of potentially pathogenic taxa and antimicrobial resistance genes. Comparison of students' gut microbiomes and resistomes to farm workers' and environmental samples revealed extensive sharing of resistance genes and bacteria following exposure and after three months of their visit. Notably, antibiotic resistance genes were found in similar genetic contexts in student samples and farm environmental samples. Dynamic Bayesian network modeling predicted that the observed changes partially reverse over a 4-6 month period. Our results indicate that acute changes in a human's living environment can persistently shape their gut microbiota and antibiotic resistome.

11.
J Food Biochem ; 44(5): e13187, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185800

RESUMO

The anti-inflammatory and anti-asthmatic effects of rubusoside (Rbs) were investigated in the ovalbumin (OVA)-induced asthmatic mice, followed by effective attenuation of Rbs treatment on the airway hyperresponsiveness and reduction of inflammatory cells inside the bronchoalveolar lavage fluid (BALF). The mitigation of inflammatory infiltration as a result of Rbs treatment was histologically observed in these mice lungs. Rbs contributed to the decrease of inflammatory cytokines (TNF-α, IL-13, IL-6, IL-5, and IL-4) inside the BALF of mice with asthma. A decline of OVA-dependent IgE and IgG1 inside the serum was also noticed in these mice. Rbs was proved to enhance the mRNA level of Foxp3 inside the mice lung affected with asthma while decrease that of IL-17A, IL-23, and RORγt. NF-κB pathway activation elicited by OVA was suppressed by Rbs inside the pulmonary tissues. Rbs played significantly in the reduction of airway inflammation induced by OVA which with modulating NF-κB pathway activation. PRACTICAL APPLICATIONS: Simultaneous therapy with medicine and food is strategically significant for disease prevention and treatment in traditional Chinese medicine. Rbs is a diterpene glycoside isolated from Rubus suavissimus. The anti-inflammatory and anti-asthmatic mechanism dependent of Rbs need further study clinically. The goal of current investigation is to explore the anti-inflammatory as well as anti-asthmatic activity of Rbs in mouse models of OVA-induced experimental allergic asthma. Results of the present study are scientifically supportive for the use of Rbs as an adjunctive reagent for clinical treatment of allergic asthma.

12.
Cell Death Dis ; 11(2): 118, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051399

RESUMO

Recent studies suggest that Src family kinase (SFK) plays important roles in systemic sclerosis and pulmonary fibrosis. However, how SFKs contributed to the pathogenesis of liver fibrosis remains largely unknown. Here, we investigated the role of Fyn, a member of SFK, in hepatic stellate cell (HSC) activation and liver fibrosis, and evaluated the anti-fibrotic effects of Saracatinib, a clinically proven safe Fyn inhibitor. Fyn activation was examined in human normal and fibrotic liver tissues. The roles of Fyn in HSC activation and liver fibrosis were evaluated in HSC cell lines by using Fyn siRNA and in Fyn knockout mice. The effects of Saracatinib on HSC activation and liver fibrosis were determined in primary HSCs and CCl4 induced liver fibrosis model. We showed that the Fyn was activated in the liver of human fibrosis patients. TGF-ß induced the activation of Fyn in HSC cell lines. Knockdown of Fyn significantly blocked HSC activation, proliferation, and migration. Fyn deficient mice were resistant to CCl4 induced liver fibrosis. Saracatinib treatment abolished the activation of Fyn, downregulated the Fyn/FAK/N-WASP signaling in HSCs, and subsequently prevented the activation of HSCs. Saracatinib treatment significantly reduced the severity liver fibrosis induced by CCl4 in mice. In conclusions, our findings supported the critical role of Fyn in HSC activation and development of liver fibrosis. Fyn could serve as a promising drug target for liver fibrosis treatment. Fyn inhibitor Saracatinib significantly inhibited HSC activation and attenuated liver fibrosis in mouse model.

13.
Artif Cells Nanomed Biotechnol ; 48(1): 683-686, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32088997

RESUMO

Background: Involvements of microRNA-22 (miR-22) in cancer have attracted much attention, but its role in diagnosis of hepatocellular carcinoma (HCC) is still largely unknown. Therefore, the aim of this study was to investigate the expression level and the prognostic value of miR-22 in HCC patients.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate serum level of miR-22 in 108 HCC patients and 67 healthy controls. The relationship between miR-22 expression level and clinicopathologic characteristics was analysed via chi-square test. Receiver operating characteristic (ROC) curve was built to estimate the diagnostic value of serum miR-22 in HCC.Results: miR-22 expression was significantly down-regulated in HCC compared to that in healthy controls (p < .05). And the low miR-22 expression was significantly associated with vein invasion (p = .002), TNM stage (p = .013) and high serum levels of AFP (α-fetoprotein), ALT (alanine aminotransferase), AST (aspartate aminotransferase) and ALP (alkaline phosphatase. miR-22 had a high diagnostic value with area under the curve of 0.866 corresponding with a sensitivity of 89.3% and a specificity of 68.9%, respectively.Conclusion: miR-22 expression was down-regulated in HCC patients. Serum miR-22 might be a novel diagnostic marker in HCC.

14.
Medicine (Baltimore) ; 99(5): e18738, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000377

RESUMO

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.


Assuntos
Carcinoma/terapia , Quimiorradioterapia , Histerectomia , Neoplasias do Colo do Útero/terapia , Feminino , Humanos
15.
Eur J Med Genet ; 63(5): 103855, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31972369

RESUMO

We report a genetic assessment of autosomal dominant, nonsyndromic, progressive sensorineural hearing loss in a Chinese family, combining whole-exome sequencing and genome-wide linkage analysis. A novel missense mutation, c.626G > C, in the SCD5 gene was identified in this family. The heterozygous missense mutation could segregate hearing loss cases among family members, and was predicted to be deleterious by Polyphen-2, LRT and Mutation Taster. SCD5 is an endoplasmic reticulum enzyme, catalyzing the formation of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). It plays a crucial role in regulating lipid metabolism. The SCD5 protein is expressed in inner and outer hair cells of the organ of Corti, the stria vascularis, cells of the lateral cochlear wall behind the spiral prominence, and more strongly in spiral ganglion cells of guinea pig and human fetal cochleas. SCD5 protein was also expressed in the brain, consistent with the hearing loss feature: the patients had a poor speech discrimination score at young age and mild hearing loss as evaluated by pure tone audiometry. In summary, we identified SCD5 as a novel gene responsible for autosomal dominant nonsyndromic deafness.

16.
Sci Rep ; 10(1): 984, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969614

RESUMO

El Niño-Southern Oscillation (ENSO) is the dominant interseasonal-interannual variability in the tropical Pacific and substantial efforts have been dedicated to predicting its occurrence and variability because of its extensive global impacts. However, ENSO predictability has been reduced in the 21st century, and the impact of extratropical atmosphere on the tropics has intensified during the past 2 decades, making the ENSO more complicated and harder to predict. Here, by combining tropical preconditions/ocean-atmosphere interaction with extratropical precursors, we provide a novel approach to noticeably increase the ENSO prediction skill beyond the spring predictability barrier. The success of increasing the prediction skill results mainly from the longer lead-time of the extratropical-tropical ocean-to-atmosphere interaction process, especially for the first 2 decades of the 21st century.

17.
Medicine (Baltimore) ; 99(1): e18596, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895808

RESUMO

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Because the molecular mechanisms of DKD are not fully understood, exploration of hub genes and the mechanisms underlying this disease are essential for elucidating the pathogenesis and progression of DKD. Accordingly, in this study, we performed an analysis of gene expression in DKD. The differentially expressed genes (DEGs) included 39 upregulated genes and 113 downregulated genes in the GSE30528 dataset and 127 upregulated genes and 18 downregulated genes in the GSE30529 dataset. Additionally, functional analyses were performed to determine the roles of DEGs using glomeruli samples from patients with DKD and healthy controls from the GSE30528 dataset and using tubule samples from patients with DKD and healthy controls from the GSE30529 dataset. These DEGs were enriched in pathways such as the Wnt signaling pathway, metabolic pathways, and the mammalian target of rapamycin signaling pathway in the GSE30528 dataset and the longevity regulating pathway and Ras signaling pathway in the GSE30529 dataset. Moreover, a protein-protein interaction network was constructed using the identified DEGs, and hub gene analysis was performed. Furthermore, correlation analyses between key genes and pathological characteristics of DKD indicated that CCR4, NTNG1, HGF and ISL1 are related to DKD, and NTNG1 and HGF may server as diagnostic biomarkers in DKD using the receiver-operator characteristic (ROC) curve. Collectively, our findings established 2 reliable biomarkers for DKD.


Assuntos
Nefropatias Diabéticas/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Rim/metabolismo , Netrinas/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proteínas Ligadas por GPI/metabolismo , Humanos
18.
Food Chem ; 311: 125875, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753680

RESUMO

Camellia gymnogyna Chang (CgC), a wild tea plant, was discovered on Dayao Mountain, China. However, research regarding this tea plant is limited. Our study found that CgC contains theobromine, caffeine, and theacrine, among which theobromine content was the highest (14.37-39.72 mg/g). In addition, theobromine synthase (TS) was partially purified from CgC leaves, up to 35.87-fold, with consecutive chromatography, and its molecular weight was found to be approximately 62 kDa. The optimum reaction time, pH, and temperature for theobromine synthase from 7-methylxanthine was found to be 6 h, 4, and 45 °C, respectively. TS expression at both mRNA and protein stages was higher in the first than in the fourth leaf (P < 0.05). Subcellular localization of TS indicated that it was localized in the nucleus. These results indicate that CgC can be of scientific value and could lead to efficient utilization of this rare wild tea germplasm.

19.
Anaerobe ; 61: 102137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846705

RESUMO

BACKGROUND: Bezlotoxumab has been shown to prevent Clostridium difficile infection recurrence (rCDI) in high-risk patients. METHODS: We used whole genome sequencing to estimate the impact of bezlotoxumab on same-strain relapse or new-strain reinfection in MODIFY I/II trials. Reinfection with a new strain and relapse with the same strain were differentiated by the comparison of ribotype (RT) and pair-wise single-nucleotide whole genome sequencing (WGS) variations (PWSNV). Relapse was assigned if the baseline RT and the RT isolated during rCDI were the same, and if PWSNVs were ≤ 2. Reinfection was assigned if the baseline RT and the RT isolated during rCDI were different, or if the RT was the same but PWSNVs were > 10. Unknown status was assigned if the RT was the same but PWSNVs were 3-10. RESULTS: 259 rCDI events were evaluable (50 [19.3%] reinfection; 198 [76.4%] relapse). The proportion of relapses was higher for ribotype 027 (84.5%) compared with other ribotypes (74.1%). Cumulative incidence of relapse was significantly lower for bezlotoxumab versus no bezlotoxumab (p < 0.0001), with a non-significant trend towards reduction for reinfection (p = 0.14). CONCLUSION: Bezlotoxumab treatment significantly reduced the rate of CDI relapse versus a regimen without bezlotoxumab. (NCT01241552/NCT01513239).

20.
PLoS Genet ; 15(12): e1008414, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830031

RESUMO

Human nondisjunction errors in oocytes are the leading cause of pregnancy loss, and for pregnancies that continue to term, the leading cause of intellectual disabilities and birth defects. For the first time, we have conducted a candidate gene and genome-wide association study to identify genes associated with maternal nondisjunction of chromosome 21 as a first step to understand predisposing factors. A total of 2,186 study participants were genotyped on the HumanOmniExpressExome-8v1-2 array. These participants included 749 live birth offspring with standard trisomy 21 and 1,437 parents. Genotypes from the parents and child were then used to identify mothers with nondisjunction errors derived in the oocyte and to establish the type of error (meiosis I or meiosis II). We performed a unique set of subgroup comparisons designed to leverage our previous work suggesting that the etiologies of meiosis I and meiosis II nondisjunction differ for trisomy 21. For the candidate gene analysis, we selected genes associated with chromosome dynamics early in meiosis and genes associated with human global recombination counts. Several candidate genes showed strong associations with maternal nondisjunction of chromosome 21, demonstrating that genetic variants associated with normal variation in meiotic processes can be risk factors for nondisjunction. The genome-wide analysis also suggested several new potentially associated loci, although follow-up studies using independent samples are required.

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