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1.
Am J Hum Genet ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31668705

RESUMO

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.

2.
Am J Hum Genet ; 105(4): 706-718, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564435

RESUMO

Hemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in individuals with diabetes. However, nonglycemic determinants, including genetic variation, may influence how accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics, and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K and/or FN3KRP in Europeans, and G6PD in African-Americans and Hispanics) and we identified an African-ancestry-specific low-frequency variant (rs1039215 in HBG2 and HBE1, minor allele frequency (MAF) = 0.03). The most associated G6PD variant (rs1050828-T, p.Val98Met, MAF = 12% in African-Americans, MAF = 2% in Hispanics) lowered HbA1c (-0.88% in hemizygous males, -0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693, p.Leu353Pro, MAF = 0.5%; -0.98% in hemizygous males, -0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African American cohorts, and we replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.

3.
Ecotoxicol Environ Saf ; 187: 109830, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31648074

RESUMO

A second intracellular copper/zinc superoxide dismutase (icCuZnSOD2) and manganese SOD (MnSOD) were cloned and characterized in Oxya chinensis. The open reading frame (ORF) of OcicCuZnSOD2 and OcMnSOD are 462 and 672 bp encoding 153 and 223 amino acids, respectively. OcicCuZnSOD2 contains two signature sequences, one potential N-glycosylation site, and seven copper/zinc binding sites. OcMnSOD includes a mitochondria targeting sequence of 7 amino acids at N-terminal, one signature sequence, two N-glycosylation sites, and four manganese binding sites. The secondary structure and homology model of OcicCuZnSOD2 include nine ß sheets, two Greek-key motifs, and one electrostatic loop. OcMnSOD contains nine α-helices and three ß-sheets. Phylogenetic analysis shows that OcMnSOD is evolutionarily conserved while OcicCuZnSOD2 may be gene duplication and is paralogous to OcicCuZnSOD1. OcMnSOD expressed widely in all tissues and developmental stages. OcicCuZnSOD2 showed testis-specific expression and expressed highest in the 5th-instar nymph and the adult. The optimum temperatures and pH values of the recombinant OcicCuZnSOD2 and OcMnSOD were 40 °C and 8.0. They were stable at 25-55 °C and at pH 5.0-12.0 and pH 6.0-12.0, respectively. The activity and mRNA expression of each OcSOD were assayed after chlorpyrifos treatments. Total SOD and CuZnSOD activities first increased then declined under chlorpyrifos stress. Chlorpyrifos induced the mRNA expression and activity of OcMnSOD as a dose-dependent manner and inhibited OcicCuZnSOD2 transcription. The role of each OcSOD gene in chlorpyrifos stress was investigated using RNAi and disc diffusion assay with Escherichia coli overexpressing OcSOD proteins. Silencing of OcMnSOD significantly increased ROS content in chlorpyrifos-exposed grasshoppers. Disc diffusion assay showed that the plates with E. coli overexpressing OcMnSOD had the smaller inhibition zones around the chlorpyrifos-soaked filter discs. These results implied that OcMnSOD played a significant role in defense chlorpyrifos-induced oxidative stress.

4.
Epigenomics ; 11(13): 1487-1500, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

5.
J Mol Cell Cardiol ; 136: 27-41, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505198

RESUMO

Coronary heart disease (CHD) is a common heart disease and the leading cause of cardiovascular death. Apoptosis and autophagy are two forms of programmed cell deaths which participate in the pathogenesis, development and prognosis of CHD. They are activated by several different pathways respectively and can interact with each other through the Beclin 1-Bcl-2/Bcl-xL complex, mTOR, TRAIL, TNF-α, ER stress and nucleus p53 pathways. Excessive apoptosis can promote myocardial ischemia, ischemia/reperfusion (I/R) injury, post-ischemia cardiac remodeling and coronary atherosclerosis except for VSMC-induced atherosclerosis progress. In contrast, activated autophagy protects heart from myocardial ischemia injury and post-ischemia cardiac remodeling, but can exert controversial effects on I/R injury and coronary atherosclerosis. Therefore, considering the pathological significance and mechanisms of apoptosis and autophagy underlying CHD, therapeutic implication of targeting apoptosis and autophagy is obvious. Fortunately, some therapeutic drugs and pharmacologic compounds involving mTOR inhibitor and AMPK activator have been reported to regulate apoptosis and autophagy. Although recent studies are limited and insufficient, they have pointed out the complex interplay between apoptosis and autophagy and further provided treatment concept for CHD by balancing the switch between the two responses.

6.
BMC Med Genomics ; 12(1): 124, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443660

RESUMO

BACKGROUND: Non-coding RNA has been shown to participate in numerous biological and pathological processes and has attracted increasing attention in recent years. Recent studies have demonstrated that long non-coding RNA and micro RNA can interact through various mechanisms to regulate mRNA. Yet the gene-gene interaction has not been investigated in coronary heart disease (CHD). METHODS: High throughput sequencing were used to identify differentially expressed (DE) lncRNA, miRNA, and mRNA profiles between CHD and healthy control. Gene Oncology (GO), KEGG enrichment analysis were performed. Gene-gene interaction network were constructed and pivotal genes were screened out. Lentivirus-induced shRNA infection and qRT-PCR were performed to validated the gene-gene interactions. RESULTS: A total of 62 lncRNAs, 332 miRNAs and 366 mRNAs were differentially expressed between CHD and healthy control. GO and KEGG analysis show that immune related molecular mechanisms and biological processes play a role in CHD. The gene-gene interaction network were constructed and visualized based on Pearson correlation coefficients and starBase database. 6 miRNAs in the network were significantly correlated to left ventricular ejection fraction, total choleterol and homocysteine. 2 lncRNAs (CTA-384D8.35 and CTB-114C7.4 (refseq entry LOC100128059)), 1 miRNA (miR-4497), and 1 mRNA (NR4A1) were the pivotal genes. Lentivirus-induced shRNA infection and qRT-PCR had validated the pivotal gene-gene interactions. CONCLUSIONS: These results have shown the potential of lncRNA, miRNA, and mRNA as clinical biomarkers and in elucidating pathological mechanisms of CHD from a transcriptomic perspective.

7.
Mol Cancer ; 18(1): 123, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399034

RESUMO

Piwi interacting RNAs (piRNAs) constitute novel small non-coding RNA molecules of approximately 24-31 nucleotides in length that often bind to members of the piwi protein family to play regulatory roles. Recently, emerging evidence suggests that in addition to the mammalian germline, piRNAs are also expressed in a tissue-specific manner in a variety of human tissues and modulate key signaling pathways at the transcriptional or post-transcriptional level. In addition, a growing number of studies have shown that piRNA and PIWI proteins, which are abnormally expressed in various cancers, may serve as novel biomarkers and therapeutic targets for tumor diagnostics and treatment. However, the functions of piRNAs in cancer and their underlying mechanisms remain incompletely understood. In this review, we discuss current findings regarding piRNA biogenetic processes, functions, and emerging roles in cancer, providing new insights regarding the potential applications of piRNAs and piwi proteins in cancer diagnosis and clinical treatment.

8.
BMJ Open ; 9(8): e024968, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31399446

RESUMO

INTRODUCTION: As the early stage of coronary heart disease (CHD), borderline coronary lesion (BCL) is defined as a 30%-70% diameter stenosis. Previous studies have demonstrated that BCL may progress to acute coronary syndrome easily. However, routine medications available for the treatments of BCL have some limitations. Xuanbi antong granule (XAG) has been used for the treatment of BCL in China for many years. Previous studies have shown that XAG has effectiveness in improving clinical symptoms and quality of life in patients with CHD. This study aims to evaluate the effectiveness and safety of XAG in patients with BCL. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 300 participants will be randomly assigned to the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with XAG and the placebo group will be treated with XAG placebo. All participants will receive a 6-month treatment and then be followed-up for another 6 months. The primary outcomes are the changes of target plaque characteristics (including target plaque volume, degree of stenosis, CT value and calcification score) measured by dual source CT angiography. The secondary outcomes include blood lipid indicators, efficacy of angina symptoms, Seattle Angina Questionnaire, high-sensitivity C-reactive protein and occurrence of major adverse cardiac events. All the data will be recorded in electronic case report forms and analysed by SPSS V.20.0. ETHICS AND DISSEMINATION: This study has been approved by Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2017-083-KY-01). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17013189; Pre-results.

9.
Toxicol Appl Pharmacol ; 379: 114615, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31175882

RESUMO

Mercury (Hg) is generally considered as a toxic metal; yet the biological outcomes of Hg-containing compounds are highly dependent upon their chemical forms. We hypothesize that mercury sulfide (HgS) is different from HgCl2 and methylmercury (MeHg) in producing intestinal Hg absorption and disruption of gut microbiome. To test this hypothesis, mice were given orally with HgS (α-HgS, 30 mg/kg), Zuotai (ß-HgS, 30 mg/kg), HgCl2 (33.6 mg/kg, equivalent Hg as HgS), or MeHg (3.1 mg/kg, 1/10 Hg as HgS) for 7 days. Accumulation of Hg in the duodenum and ileum after HgCl2 (30-40 fold) and MeHg (10-15 fold) was higher than HgS and Zuotai (~2-fold). HgCl2 and MeHg decreased intestinal intake peptide transporter-1 and Ost-ß, and increased ileal bile acid binding protein and equilibrative nucleoside transporter-1. The efflux transporters ATP-binding cassette sub-family C member-4 (Abcc4), Abcg2, Abcg5/8, and Abcb1b were increased by HgCl2 and to a lesser extent by MeHg, while HgS and Zuotai had minimal effects. Bacterial DNA was extracted and subjected to 16S rDNA sequencing. Operational taxonomic unit (OTU) results showed that among the 10 phyla, HgS increased Firmicutes, Proteobacteria, while HgCl2 increased Bacteroidetes, Cyanobacteria and decreased Firmicutes; among the 79 families, HgS increased Rikenellaceae, Lactobacillaceae, Helicobacteraceae, and decreased Prevotellaceae, while HgCl2 increased Odoribacteraceae, Porphyromonadaceae, and decreased Lactobacillaceae; among the 232 genus/species, HgS and Zuotai affected gut microbiome quite differently from HgCl2 and MeHg. qPCR analysis with 16S rRNA confirmed sequencing results. Thus, chemical forms of mercury are a major determinant for intestinal Hg accumulation, alterations in transporters and disruption of microbiome.

10.
Int J Mol Sci ; 20(12)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208046

RESUMO

The salt overly sensitive 1 (SOS1) gene encodes the plasma membrane Na+/H+ antiporter, SOS1, that is mainly responsible for extruding Na+ from the cytoplasm and reducing the Na+ content in plants under salt stress and is considered a vital determinant in conferring salt tolerance to the plant. However, studies on the salt tolerance function of the TrSOS1 gene of recretohalophytes, such as Tamarix, are limited. In this work, the effects of salt stress on cotton seedlings transformed with tobacco-rattle-virus-based virus-induced gene silencing (VIGS) of the endogenous GhSOS1 gene, or Agrobacterium rhizogenes strain K599-mediated TrSOS1-transgenic hairy root composite cotton plants exhibiting VIGS of GhSOS1 were first investigated. Then, with Arabidopsis thaliana AtSOS1 as a reference, differences in the complementation effect of TrSOS1 or GhSOS1 in a yeast mutant were compared under salt treatment. Results showed that compared to empty-vector-transformed plants, GhSOS1-VIGS-transformed cotton plants were more sensitive to salt stress and had reduced growth, insufficient root vigor, and increased Na+ content and Na+/K+ ratio in roots, stems, and leaves. Overexpression of TrSOS1 enhanced the salt tolerance of hairy root composite cotton seedlings exhibiting GhSOS1-VIGS by maintaining higher root vigor and leaf relative water content (RWC), and lower Na+ content and Na+/K+ ratio in roots, stems, and leaves. Transformations of TrSOS1, GhSOS1, or AtSOS1 into yeast NHA1 (Na+/H+ antiporter 1) mutant reduced cellular Na+ content and Na+/K+ ratio, increased K+ level under salt stress, and had good growth complementation in saline conditions. In particular, the ability of TrSOS1 or GhSOS1 to complement the yeast mutant was better than that of AtSOS1. This may indicate that TrSOS1 is an effective substitute and confers enhanced salt tolerance to transgenic hairy root composite cotton seedlings, and even the SOS1 gene from salt-tolerant Tamarix or cotton may have higher efficiency than salt-sensitive Arabidopsis in regulating Na+ efflux, maintaining Na+ and K+ homeostasis, and therefore contributing to stronger salt tolerance.

11.
Invest New Drugs ; 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31231786

RESUMO

Objective Apatinib is an oral small molecule anti-angiogenic drug. This phase I study aimed to establish the feasible dose of apatinib in combination with pemetrexed plus carboplatin as first-line therapy for epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) negative stage IV non-squamous non-small cell lung cancer (NSCLC). Methods Using a 3 + 3 dose-reduction design, patients received oral apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day two weeks on/one week off schedule (500 mg schedule 2/1) or 250 mg qd. Pemetrexed (500 mg/m2) plus carboplatin (AUG = 5) was administered every three weeks. Maintenance therapy by apatinib or pemetrexed could be carried on until disease progression or unacceptable toxicity. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. Result A total of twelve patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd dosage of apatinib (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events (AEs) were hematological toxicity, hypertension, hand-foot syndrome, and hepatic transaminases elevation. Partial response was observed in four patients of eleven evaluable patients (objective response rate 36.4%), and six patients exhibited stable disease (disease control rate 90.9%). Conclusion In patients with advanced non-squamous NSCLC, the feasible dose of apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC.

12.
Sleep ; 42(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31139831

RESUMO

STUDY OBJECTIVES: Daytime sleepiness is a consequence of inadequate sleep, sleep-wake control disorder, or other medical conditions. Population variability in prevalence of daytime sleepiness is likely due to genetic and biological factors as well as social and environmental influences. DNA methylation (DNAm) potentially influences multiple health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS). METHODS: We performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 619) and the Cardiovascular Health Study (n = 483), with cross-study replication and meta-analysis. Genetic variants near ESS-associated DNAm were analyzed for methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank. RESULTS: In MESA only, we detected four DNAm-ESS associations: one across all race/ethnic groups; three in African-Americans (AA) only. Two of the MESA AA associations, in genes KCTD5 and RXRA, nominally replicated in CHS (p-value < 0.05). In the AA meta-analysis, we detected 14 DNAm-ESS associations (FDR q-value < 0.05, top association p-value = 4.26 × 10-8). Three DNAm sites mapped to genes (CPLX3, GFAP, and C7orf50) with biological relevance. We also found evidence for associations with DNAm sites in RAI1, a gene associated with sleep and circadian phenotypes. UK Biobank follow-up analyses detected SNPs in RAI1, RXRA, and CPLX3 with nominal sleepiness associations. CONCLUSIONS: We identified methylation sites in multiple genes possibly implicated in daytime sleepiness. Most significant DNAm-ESS associations were specific to AA. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.

13.
Hum Mol Genet ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127295

RESUMO

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

14.
Diabetes ; 68(5): 1073-1083, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936141

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 × 10-6) with replication at Bonferroni-corrected P < 8.6 × 10-4 Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 × 10-4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.

15.
PLoS One ; 14(4): e0214061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973896

RESUMO

BACKGROUND: Gene expression may be an important biological mediator in associations between social factors and health. However, previous studies were limited by small sample sizes and use of differing cell types with heterogeneous expression patterns. We use a large population-based cohort with gene expression measured solely in monocytes to investigate associations between seven social factors and expression of genes previously found to be sensitive to social factors. METHODS: We employ three methodological approaches: 1) omnibus test for the entire gene set (Global ANCOVA), 2) assessment of each association individually (linear regression), and 3) machine learning method that performs variable selection with correlated predictors (elastic net). RESULTS: In global analyses, significant associations with the a priori defined socially sensitive gene set were detected for major or lifetime discrimination and chronic burden (p = 0.019 and p = 0.047, respectively). Marginally significant associations were detected for loneliness and adult socioeconomic status (p = 0.066, p = 0.093, respectively). No associations were significant in linear regression analyses after accounting for multiple testing. However, a small percentage of gene expressions (up to 11%) were associated with at least one social factor using elastic net. CONCLUSION: The Global ANCOVA and elastic net findings suggest that a small percentage of genes may be "socially sensitive," (i.e. demonstrate differential expression by social factor), yet single gene approaches such as linear regression may be ill powered to capture this relationship. Future research should further investigate the biological mechanisms through which social factors act to influence gene expression and how systemic changes in gene expression affect overall health.

16.
PLoS One ; 14(4): e0215616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30986272

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0201136.].

17.
Prep Biochem Biotechnol ; 49(6): 584-589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929563

RESUMO

PGHX is a polymer of ß (1-3)-galactose which posses the gel-forming property. As previously reported in the flask culture experiment, the crude PGHX (24.9 g/L, 48.2% in yield) with the maximum gel strength of 957 g/cm2 can be generated. However, PGHX produced in the stirred bioreactor had no gel-forming property when using the same medium. Hence, the effects of different glycerol concentrations on both the yield and the gel-forming property of PGHX were investigated and the reason for gel-forming property losing was explored. We proposed a new strategy for the production of PGHX with enhanced gel formation in the stirred bioreactor by mediating both the concentration of carbon source and the duration of fermentation. As a result, we managed to obtain the crude PGHX (22 g/L, 42.4% in yield) with the maximum gel strength of 438 g/cm2 at 56 h in the bioreactor. This strategy would help the enhancement of PGHX yield in the industrial production.


Assuntos
Agrobacterium/metabolismo , Galactanos/biossíntese , Glicerol/metabolismo , Aminoácidos/análise , Biomassa , Reatores Biológicos , Fermentação/efeitos dos fármacos , Galactanos/química , Géis
18.
Chemistry ; 25(13): 3343-3351, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30721542

RESUMO

Biomimetic straw-like bundles of Co-doped Fe2 O3 (SCF), with Co2+ incorporated into the lattice of α-Fe2 O3 , was fabricated through a cost-effective hydrothermal process and used as the anode material for lithium-ion batteries (LIBs). The SCF exhibited ultrahigh initial discharge specific capacity (1760.7 mA h-1 g-1 at 200 mA g-1 ) and cycling stability (with the capacity retention of 1268.3 mA h-1 g-1 after 350 cycles at 200 mA g-1 ). In addition, a superior rate capacity of 376.1 mA h-1 g-1 was obtained at a high current density of 4000 mA g-1 . The remarkable electrochemical lithium storage of SCF is attributed to the Co-doping, which increases the unit cell volume and affects the whole structure. It makes the Li+ insertion-extraction process more flexible. Meanwhile, the distinctive straw-like bundle structure can accelerate Li ion diffusion and alleviate the huge volume expansion upon cycling.

19.
Lung Cancer ; 127: 1-5, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30642536

RESUMO

OBJECTIVE: To evaluate the influence of a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment on the clinical features of leptomeningeal metastasis (LM) progression and outcome in advanced non-small cell lung cancer (NSCLC) patients. METHODS: We retrospectively evaluated advanced NSCLC patients receiving effective first-generation EGFR TKI treatment (e.g., treatment > 6 months) at our institution between January 2008 and February 2014. Incidence, time to progression, and treatment outcome of LM were examined. RESULTS: In our cohort, 29/420 patients (6.9%) developed LM. Among the patients harboring L858R or deletion of exon 19 in EGFR, the incidence of LM was 10.7% (21/197) and 3.4% (7/203), respectively (P = 0.006). The median time to LM progression was 16.5 months (95% confidence interval (CI), 11.9-20.8). The median overall survival (OS) after LM diagnosis was 5.2 months (95% CI, 3.2-7.2). In a subgroup analysis, OS was improved in patients with performance status (PS) ≤ 2 vs. PS > 2 (14.2 months vs. 2.3 months, respectively; P < 0.001). OS was also improved among patients who received, rather than did not receive, anti-tumor treatment (6.0 months vs. 1.9 months, respectively; P < 0.001) or whole brain radiotherapy (WBRT) (6.0 months vs. 3.9 months, respectively; P = 0.038). Multivariate analysis indicated that WBRT is a good prognostic factor (P = 0.048), whereas best support care (P = 0.033) and PS > 2 (P = 0.034) were poor prognostic factors. CONCLUSION: A greater incidence of LM was observed in NSCLC patients harboring EGFR mutations after effective EGFR TKI treatment. In particular, the primary mutation, L858R, potentially predicts a higher risk of LM compared with deletion of exon 19. These results highlight the importance of determining mutation status when evaluating the biological behavior of LM in NSCLC patients who positively respond to EGFR TKI treatment.

20.
Ecotoxicol Environ Saf ; 168: 27-34, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30384164

RESUMO

Lead (Pb) is known to be toxic to many organisms. Oxidative stress is a major mechanism of its toxicity. This research aims to investigate the effects of Pb on hydrogen peroxide (H2O2) and malonedialdehyde (MDA) contents, activities and mRNA levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) after Oxya chinensis were acutely treated with lead acetate for 24 h. The results showed that the LD50-24 h value of lead acetate to O. chinensis was 1541.89 (1431.19-1655.77) µg g-1 body H2O2 and MDA contents were elevated after Pb administration, which suggested that Pb induced the overproduction of ROS and caused oxidative stress. SOD activities were significantly inhibited 40.42% of the control by 280 µg µL-1 Pb. CAT activities were increased while GPx activities had no significant changes. Different types of antioxidant-related genes had various responses to Pb stress. The transcriptions of icCuZnSOD2 and ecCuZnSOD2 were significantly inhibited by different concentrations of Pb. MnSOD mRNA levels showed the concentration-dependent rise with the Pb concentrations increase. The expressions of ecCuZnSOD1, CAT1, and GPx were significantly up-regulated while the transcriptions of icCuZnSOD1 and CAT2 had no significant changes. Alteration of activities and mRNA expressions of antioxidant enzymes implied that Pb-induced antioxidant defenses were related to modifications at enzymatic and transcriptional levels. The profiles of antioxidant enzymes and H2O2 and MDA contents and relationships among the parameters indicated that the cooperation of multiple antioxidants rather than a single factor might be responsible for the antioxidant defenses against Pb stress.


Assuntos
Gafanhotos/fisiologia , Chumbo/metabolismo , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Chumbo/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Regulação para Cima/fisiologia
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