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1.
BMC Pregnancy Childbirth ; 24(1): 601, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285345

RESUMO

BACKGROUND: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. METHODS: This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11-14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. RESULTS: FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. CONCLUSION: The combination of FPG and IGFBP-2 at early gestation (11-14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.


Assuntos
Biomarcadores , Diabetes Gestacional , Aprendizado de Máquina , Primeiro Trimestre da Gravidez , Humanos , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Gravidez , Estudos de Casos e Controles , Biomarcadores/sangue , Adulto , Primeiro Trimestre da Gravidez/sangue , China/epidemiologia , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Globulina de Ligação a Hormônio Sexual/análise , Proteína C-Reativa/análise , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Fibronectinas/sangue , Adiponectina/sangue , Glicemia/análise , Valor Preditivo dos Testes , Curva ROC , Modelos Logísticos
2.
Food Chem X ; 23: 101642, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39113743

RESUMO

Panax notoginseng and Panax quinquefolium are important economic plants that utilize dried roots for medicinal and food dual purposes; there is still insufficient research of their stems and leaves, which also contain triterpenoid saponins. The extraction process was developed with a total saponin content of 12.30 ± 0.34% and 12.19 ± 0.64% for P. notoginseng leaves (PNL) and P. quinquefolium leaves (PQL) extracts, respectively. PNL and PQL saponin extracts showed good antioxidant, antihypertensive, hypoglycemic, and anti-inflammatory properties in vitro and RAW264.7 cells. A total of 699 metabolites were identified in PNL and PQL saponin extracts, with the majority being triterpenoid saponins, flavonoids and amino acids. Fourteen ginsenosides, 18 flavonoids or alkaloids, and 16 amino acids were enriched in both saponin extracts. Overall, the utilization of saponins from medicinal plants PNL and PQL has been developed to facilitate systematic research in the functional food and natural product industries.

3.
Shock ; 62(3): 319-326, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38888506

RESUMO

ABSTRACT: Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO 2 35-45 mm Hg (group N) or 46-55 mm Hg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO 2 , cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for 3 postoperative days. Results: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO 2 and rSO 2 during surgery ( P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 ( P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV ( P < 0.05). Group H had lower pH and higher OI at T2-4 ( P < 0.05). CRP and CAR levels rose less in group H on the first day and 1 week later ( P < 0.05). Conclusions: Maintaining PaCO 2 at 46-55 mm Hg reduces POD incidence, possibly by enhancing rSO 2 levels and stabilizing intraoperative respiration/circulation.


Assuntos
Esofagectomia , Hipercapnia , Laparoscopia , Complicações Pós-Operatórias , Toracoscopia , Humanos , Masculino , Idoso , Feminino , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Delírio/etiologia , Delírio/sangue , Neoplasias Esofágicas/cirurgia
4.
Front Plant Sci ; 14: 1138893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056503

RESUMO

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

5.
Cancer Rep (Hoboken) ; 5(9): e1561, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34553845

RESUMO

BACKGROUND: Pyroptosis plays a dual role in the development of cancer and malignancy; as such, it may potentially be a new target for cancer treatment. However, the inflammatory response to pyroptosis may have adverse effects on the body. The roles of gasdermin E (GSDME), caspases, and related proteins associated with pyroptosis in cancer remain controversial. AIM: The goal of this study was to determine whether the expression levels of caspase-3 and GSDME affect the clinical stage, pathological grade, or survival prognosis of patients with lung cancer. METHODS: We examined the protein levels of GSDME, caspase-3, caspase-8, and caspase-9 in lung tissue samples from 100 patients with lung cancer by using immunohistochemistry. RESULTS: We found that GSDME, caspase-3, and caspase-8 were more highly expressed in tumor tissues than in adjacent normal tissues. Moreover, we found that GSDME could serve as a prognostic factor as there was a positive correlation between its expression level and the postoperative survival rate of patients with lung cancer. CONCLUSIONS: GSDME may be an independent factor affecting the prognosis of patients with lung cancer. However, the role of GSDME and its related proteins in cancer requires further research.


Assuntos
Caspase 3/metabolismo , Neoplasias Pulmonares , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Receptores de Estrogênio , Caspase 8/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Prognóstico , Receptores de Estrogênio/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6149-6162, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951242

RESUMO

R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.


Assuntos
Erigeron , Genes myb , Proteínas de Plantas , Fatores de Transcrição , Erigeron/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
Front Endocrinol (Lausanne) ; 12: 740902, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621244

RESUMO

Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.


Assuntos
Diabetes Gestacional/metabolismo , Estradiol/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Medula Espinal/metabolismo , Adiponectina/sangue , Estudos de Casos e Controles , Estudos de Coortes , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Recém-Nascido , Leptina/sangue , Masculino , Gravidez , Caracteres Sexuais , Testosterona/sangue
8.
J Occup Environ Med ; 63(7): e408-e415, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34184658

RESUMO

OBJECTIVE: To determine the effect of mitochondrial DNA copy number (mtDNAcn) as a biomarker of benzene exposure. METHODS: A total of 294 benzene-exposed workers and 102 controls were recruited. Biomarkers of mtDNAcn, cytokinesis-block micronucleus (MN) frequency, and peripheral blood white blood cells (WBC) were detected. Eighteen polymorphism sites in DNA damage repair and metabolic genes were analyzed. RESULTS: Benzene exposure increased mtDNAcn and indicated a dose-response relationship (P < 0.001). mtDNAcn was negatively correlated with WBC count and DNA methylation and positively correlated with MN frequency. The AG type in rs1695 interacted with benzene exposure to aggravate mtDNAcn (ß = 0.006, 95% CI: 0, 0.012, P = 0.050). rs13181, rs1695, rs1800975, and GSTM1 null were associated with benzene-induced mtDNAcn. Rs1695 interacted with benzene to increase mitochondrial damage. CONCLUSIONS: Benzene exposure increases mtDNAcn levels in benzene-exposed workers.


Assuntos
Benzeno , Exposição Ocupacional , Benzeno/análise , Benzeno/toxicidade , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Interação Gene-Ambiente , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
9.
Data Brief ; 31: 105869, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32637486

RESUMO

In this paper, we present an occupational dataset to evaluate benzene exposure on the effective biomarkers of genetic damage, indicated as cytokinesis-block micronucleus (MN) frequency, hematotoxicity, indicated as white blood cells (WBC) counts, and molecular marker of telomere length (TL). And we further to eliminate the mechanism of benzene induced damage. Then evaluate the effects of sites polymorphism in environmental response genes, including 18 sites in metabolic and DNA repair genes, and the interaction between gene polymorphism and benzene exposure. This dataset is supplementary to the submitted research by [1] focused on the biomarkers TL, and a detailed description of the subjects sampling, biomarkers detection, data analysis and discussion are discussed in detail.

10.
Clin Neurol Neurosurg ; 196: 105971, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516684

RESUMO

Primary intracranial Rhabdoid meningioma (PIRM) is an uncommon subtype of WHO grade III meningioma. Given its rarity, its risk factors and management strategies are still unclear. Therefore, we aimed to assess the risk factors and outcomes for patients with PIRM and proposed an appropriate treatment. Ovid, Medline, Embase, Pubmed, Web of Science and Cochrane database were used to search for articles published between January 1998 and October 2019. Search terms combined "intracranial", "brain", and "cerebral" with "rhabdoid meningioma" or "WHO grade III meningioma". The entire cohort included 27 males (51.9 %) and 25 females (48.1 %) with an age ranging from 2 to 77 years (median 44 years). The size of tumor ranged from 1.3 to 7.4 cm (mean 4.3 cm). The Ki-67 proliferation index ranged from 1 % to 90 % (mean 15 %). In the whole cohort, gross total resection (GTR) and non-GTR were achieved in 63.5 % (33 cases) and 36.5 % (19 cases) patients, respectively. Twenty-five patients (48.1 %) had the postoperative radiotherapy, and 5 patients (9.6 %) had postoperative chemotherapy. Nineteen patients (39.6 %) developed recurrences, 4 patients (7.7 %) developed distant metastasizes, and 13 patients (25.0 %) died. GTR was associated with favorable overall survival (p = 0.008). The 1-, 3-, and 5-year progression-free survival rates were 84.6 %, 59.4 %, and 49.6 %, respectively; and the 1-, 3- and 5- year overall survival rates in the entire group were 91.4 %, 83.5 % and 68.9 %, respectively. GTR is recommend as the initial treatment option for PIRMs, contributing to acute histological diagnosis and prolonging long-term survival.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Antígeno Ki-67 , Masculino , Neoplasias Meníngeas/mortalidade , Meningioma/mortalidade , Pessoa de Meia-Idade , Índice Mitótico , Gradação de Tumores , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
11.
Chemosphere ; 255: 126841, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416388

RESUMO

Benzene is a globally occurring environmental and occupational pollutant that causes leukemia. To better understand telomere length (TL) as a function of benzene toxicity, we recruited 294 shoe-making workers and 102 controls from Wenzhou, China in 2011. Biomarkers of TL, cytokinesis-block micronucleus (MN) frequency, and white blood cells (WBC) were measured. In total, 18 polymorphic sites in environmental response genes, including metabolic and DNA repair genes, were analyzed. Results indicate that benzene exposure led to a longer TL at a threshold of 32 mg/m3-year of cumulative exposure dose (CED). Furthermore, the TL was longer in members of the damaged group, when evaluated for MN frequency (P < 0.001) and reduced WBC (P < 0.001), than in those of the normal group. Workers carrying genotype TT (ß = 0.32, P = 0.042) in rs3212986 of ERCC1 and genotype TC (ß = 0.24, P = 0.082) in rs1051740 of mEH exon3 were associated with a longer TL as compared to the wild-type group. TA (ß = -0.53, P < 0.001) in rs6413432 of CYP2E1 was associated with a shorter TL. Benzene exposure interacted with the TA type in rs6413432 (ß = 0.003, 95% CI: 0, 0.006, P = 0.042) and the CC type in rs1051740 (ß = 0.007, 95% CI: 0.001, 0.013, P = 0.015) after adjusting for confounding factors. Our results indicate that benzene induces an increase in TL at a threshold of CED ≥32mg/m3-year. Rs1051740, rs3212986, and rs6413432 were found to be involved in benzene-induced telomere growth; in particular, rs1051740 and rs6413432 interacted with the benzene exposure, resulting in an extended TL.


Assuntos
Poluentes Ocupacionais do Ar/análise , Benzeno/análise , Exposição Ocupacional/análise , Telômero , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Benzeno/toxicidade , China , Citocromo P-450 CYP2E1/genética , Feminino , Genótipo , Humanos , Masculino , Polimorfismo Genético , Sapatos
12.
Environ Mol Mutagen ; 61(8): 786-796, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32329128

RESUMO

Benzene is a global pollutant and has been established to cause leukemia. To better understand the role of DNA methylation in benzene toxicity, peripheral blood mononuclear cells were collected from six benzene-poisoning patients and six matched controls for genome-wide DNA methylation screening by Illumina Infinium Methylation 450 BeadChip. The Gene Chip Human Gene 2.0 ST Array (Affymetrix) was used to analyze global mRNA expression. Compared with the corresponding sites of controls, 442 sites in patients were hypermethylated, corresponding to 253 genes, and 237 sites were hypomethylated, corresponding to 130 genes. The promoter methylation and mRNA expression of CSF3R, CREB5, and F2R were selected for verification by bisulfite sequencing and real-time PCR in a larger data set with 21 cases and 23 controls. The results indicated that promoter methylation of CSF3R (p = .005) and F2R (p = .015) was significantly higher in cases than in controls. Correlation analysis showed that the promoter methylation of CSF3R (p < .001) and F2R (p < .001) was highly correlated with its mRNA expression. In the poisoning cases, neutrophil percentage was significantly different among the high, middle, and low CSF3R-methylation groups (p = .002). In particular, the neutrophil percentage in the high CSF3R-methylation group (48.10 ± 9.63%) was significantly lower than that in the low CSF3R-methylation group (59.30 ± 6.26%) (p = .012). The correlation coefficient between promoter methylation in CSF3R and the neutrophil percentage was -0.445 (p = .020) in cases and - 0.398 (p = .060) in controls. These results imply that hypermethylation occurs in the CSF3R promoter due to benzene exposure and is significantly associated with a reduction in neutrophils.


Assuntos
Benzeno/toxicidade , Metilação de DNA , Neutrófilos/efeitos dos fármacos , Regiões Promotoras Genéticas , Receptores de Fator Estimulador de Colônias/genética , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Exposição Ocupacional
13.
PLoS One ; 14(8): e0220500, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381583

RESUMO

Aberrant DNA methylation patterns are common in cancers and environmental pollutant exposed subjects. Up to date, few studies have examined the aberrant DNA methylation patterns in benzene exposed workers. We recruited 141 benzene-exposed workers, including 83 benzene-exposed workers from a shoe factory in Wenzhou and 58 workers from a painting workshop in Wuhu, 35 workers in Wuhu were followed from 2009 to 2013, and 48 indoor workers as controls from Wenzhou. We used high-resolution melting (HRM) to quantitate human samples of DNA methylation in long interspersed nuclear element-1 (LINE-1), (6)-methylguanine-DNA methyltransferase (MGMT), and DNA mismatch repair gene human mutator L homologue 1 (hMLH1). AML-5 cells were treated with benzoquinone (BQ) and hydroquinone (HQ), and the promoter methylation of MGMT and hMLH1 was detected using the bisulfite sequencing PCR method. The degree of LINE-1 methylation in benzene-exposed workers was significantly lower than that of the controls (p<0.001), and the degree of MGMT (p<0.001) and hMLH1 (p = 0.01) methylation was significantly higher than that of the controls. The in vitro study validated the aberrant hypermethylation of hMLH1 after treatment with BQ. Among the cohort workers who were followed from 2009 to 2013, the LINE1 methylation elevated in 2013 than 2009 (p = 0.004), and premotor methylation in hMLH1 reduced in 2013 than 2009 (p = 0.045) with the reduction of the benzene exposure. This study provides evidence that benzene exposure can induce LINE-1 hypomethylation and DNA repair gene hypermethylation.


Assuntos
Benzeno/efeitos adversos , Metilação de DNA/efeitos dos fármacos , Poluentes Ambientais/efeitos adversos , Exposição Ocupacional/efeitos adversos , Regiões Promotoras Genéticas/efeitos dos fármacos , Adolescente , Adulto , Idoso , Linhagem Celular , Feminino , Humanos , Elementos Nucleotídeos Longos e Dispersos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , O(6)-Metilguanina-DNA Metiltransferase/genética , Exposição Ocupacional/análise , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-30744808

RESUMO

OBJECTIVE: The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. METHODS: Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. RESULTS: Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p < 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (ß=-0.20, 95% CI: -0.42, 0.03, p = 0.045). CONCLUSION: In benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation.


Assuntos
Benzeno/efeitos adversos , Biomarcadores/análise , Dano ao DNA , Metilação de DNA , Reparo do DNA , Exposição Ocupacional/efeitos adversos , Polimorfismo de Nucleotídeo Único , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/metabolismo , Adulto , Estudos de Casos e Controles , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Genoma Humano , Haplótipos , Humanos , Masculino , Testes para Micronúcleos , Proteínas Nucleares/genética , Prognóstico , Fatores de Transcrição/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Proteína de Xeroderma Pigmentoso Grupo A/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética
15.
Physiol Plant ; 167(4): 597-612, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30548605

RESUMO

Panax notoginseng (Burk) F.H. Chen is an economically and medicinally important plant of the family Araliacease, with seed dormancy being a key factor limiting the extended cultivation of P. notoginseng. The seeds belong to the morphophysiological dormancy (MPD) group, and it has also been described as the recalcitrant seed. To date, the molecular mechanism of dormancy release in the recalcitrant seed of P. notoginseng is unknown. In the present study, the transcript profiles of seeds from different after-ripening stages (0, 20, 40 and 60 days) were investigated using Illumina Hiseq 2500 technology. 91 979 946 clean reads were generated, and 81 575 unigenes were annotated in at least one database. In addition, the differentially expressed genes (DEGs) were identified by the pairwise comparisons. We screened out 2483 DEGs by the three key groups of 20 days vs 0 d, 40 d vs 0 d and 60 d vs 0 d. The DEGs were analyzed by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation. Meanwhile, we obtained 78 DEGs related to seeds dormancy release at different after-ripening stages of P. notoginseng, of which 15 DEGs were associated with abscisic acid and gibberellin. 26 DEGs that encode late embryogenesis abundant protein and antioxidant enzyme were correlated with desiccation tolerance in seeds. In summary, the results obtained here showed that PECTINESTERASE-2-LIKE, GA-INSENSITIVE, ENT-KAURENE SYNTHASE, PROTEIN PHOSPHATASE 2C, GIBBERELLIN 2-BETA-DIOXYGENASE, SUPEROXIDE DISMUTASE, L-ASCORBATE PEROXIDASE, CATALASE, LATE EMBRYOGENESIS ABUNDANT PROTEIN DC3 and DEHYDRIN 9 were potentially involved in dormancy release and desiccation sensitivity of P. notoginseng seeds. The data might provide a basis for researches on MPD.


Assuntos
Panax notoginseng/genética , Dormência de Plantas , Sementes/genética , Transcriptoma , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Germinação
16.
Environ Mol Mutagen ; 60(4): 361-367, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30578676

RESUMO

Vinyl chloride monomer (VCM) is a confirmed carcinogen. The effects of VCM on telomeres and the gene expression of telomere complex proteins, shelterin, have not been well studied but could be of potential relevance to the carcinogenic mechanism of VCM and the health surveillance of VCM-exposed workers. A group of 241 VCM-exposed workers and 101 internal controls from the same plant in Shandong, China were recruited and quantitative polymerase chain reaction was preformed to measure relative telomere length (RTL) and gene expression of shelterin proteins. VCM cumulative exposure dose (CED) was estimated for the exposed workers. The differences in RTL and gene expression between groups were compared by Wald test fitted with robust regression. Shorter RTL was observed in VCM-exposed workers than in the controls (P < 0.001) and was related to CED of VCM. Shortened RTL was also significantly related to increasing age (P = 0.012) and high blood pressure (P = 0.056). Levels of gene expression of shelterin components in exposed workers were all lower than in controls except increased TIN2 expression, and the gene expression differences in TIN2 and POT1 among exposed and control groups were significant (P = 0.014 for TIN2 and P < 0.001 for POT1, respectively). VCM exposure is found associated with altered telomere length and gene expression of shelterin components. This provides new insights into the potential carcinogenic mechanisms of VCM and could be helpful for the health surveillance for VCM-exposed workers. Environ. Mol. Mutagen. 60:361-367, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Carcinógenos/toxicidade , Exposição Ocupacional/efeitos adversos , Homeostase do Telômero/efeitos dos fármacos , Proteínas de Ligação a Telômeros/genética , Cloreto de Vinil/toxicidade , Adulto , China , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Shelterina , Encurtamento do Telômero/efeitos dos fármacos
17.
PLoS One ; 13(11): e0202848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30500823

RESUMO

Marsdenia tenacissima is a well-known anti-cancer medicinal plant used in traditional Chinese medicine, which often grows on the karst landform and the water conservation capacity of land is very poorly and drought occurrences frequently. We found M. tenacissima has strong drought resistance because of continuousdrought16 d, the leaves of M. tenacissima were fully curly and dying. But the leaves were fully almost recovering after re-watering 24h. The activity of SOD and POD were almost doubled under drought stress. The content of osmotic regulating substance proline and soluble sugar were three times than control group. But after re-watering, these indexes were declined rapidly. Three cDNA libraries of control, drought stress, and re-watering treatments were constructed. There were 43,129,228, 47,116,844, and 42,815,454 clean reads with Q20 values of 98.06, 98.04, and 97.88respectively.SRA accession number of raw data was PRJNA498187 on NCBI. A total of 8672, 6043, and 6537 differentially expressed genes (DEGs) were identified in control vs drought stress, control vs re-watering, and drought stress vs re-watering, respectively. In addition, 1039, 1016, and 980 transcription factors (TFs) were identified, respectively. Among them, 363, 267, and 299 TFs were identified as DEGs in drought stress, re-watering, and drought stress and re-watering, respectively. These differentially expressed TFs mainly belonged to the bHLH, bZIP, C2H2, ERF, MYB, MYB-related, and NAC families. A comparative analysis found that 1174 genes were up-regulated and 2344 were down-regulated under drought stress and this pattern was the opposite to that found after re-watering. Among the up-regulated genes, 64 genes were homologous to known functional genes that directly protect plants against drought stress. Furthermore, 44 protein kinases and 38 TFs with opposite expression patterns under drought stress and re-watering were identified, which are possibly candidate regulators for drought stress resistance in M. tenacissima. Our study is the first to characterize the M. tenacissima transcriptome in response to drought stress, and will serve as a useful resource for future studies on the functions of candidate protein kinases and TFs involved in M. tenacissima drought stress resistance.


Assuntos
Resistência à Doença/genética , Marsdenia , Proteínas de Plantas , RNA de Plantas , Estresse Fisiológico , Fatores de Transcrição , Desidratação/genética , Desidratação/metabolismo , Regulação da Expressão Gênica de Plantas , Marsdenia/genética , Marsdenia/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , RNA de Plantas/biossíntese , RNA de Plantas/genética , Análise de Sequência de RNA , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Transcriptoma
18.
Ying Yong Sheng Tai Xue Bao ; 29(1): 193-204, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29692028

RESUMO

To explore the effects of light intensity on photosynthetic characteristics and light adaptation of the shade-demanding species Panax notoginseng, the responses of photosynthesis to photosynthetic photon flux density, CO2 and sunflecks in the two-year-old Panax notoginseng were investigated under different levels of light intensity (29.8%, 9.6%, 5.0%, 1.4% and 0.2% of full sunlight). Meanwhile, chlorophyll a fluorescence parameter and light energy partitioning were also recorded and calculated in the responsive process. P. notoginseng grown under 29.8% full sunlight (FL) had a lower apparent quantum yield (AQY), potential photochemical quantum yield (Fv/Fm) and potential photochemical activity (Fv/Fo), however, it had a higher maximum net photosynthetic rate (Pn max), maximum electron transport rate (Jmax), F/Fm', electron transport rate (ETR), photochemical quenching (qP) and the proportion of light energy allocated to photochemistry dissipation (ΦPS2), but the non-photochemical quenching (NPQ) was not the highest. There were no significant differences in Pn max, light compensation point (LCP), light saturation point (LSP), dark respiration rate (Rd) among 9.6%FL and 5.0% FL treatments, but these treatments had relatively higher values of NPQ, AQY, carboxylation efficiency (CE), maximum carboxylation rate (Vc max), Fv/Fm and Fv/Fo. In addition, the Pn max, CE, Vc max, Jmax, ETR,F/Fm', qP, NPQ and ΦPSII decreased with the decrease in light intensity from 5.0%FL to 0.2%FL, and the proportion of light energy allocated to fluorescent dissipation (Φf,d) were increased. Under 500 µmol·m-2·s-1 light-flecks inducting, the ΦPSⅡof P. notoginseng increased slowly with the extension of time except for the treatment of less than 5.0%FL, and under the circumstance of 1.4%FL and 0.2%FL, ΦPSⅡreached significantly a perfect result, moreover, Φf,dincreased rapidly. These results suggested that the enhancement in photosynthetic electron transport to use the light energy and the moderate photoinhibition of PS2 might avoid the irreversible oxidative damage of photosynthetic organization in P. notoginseng under high levels of light intensity. Moderate shading was beneficial to maintain its higher non-photochemical quenching ability. However, its photosynthetic capacity depressed and the proportion of light energy allocated to non-photochemical pathway increased obviously in excessive shading, and it easily caused a light oxidative damage.


Assuntos
Luz , Panax notoginseng/fisiologia , Fotossíntese , Clorofila , Clorofila A , Folhas de Planta
19.
Onco Targets Ther ; 11: 1447-1456, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29588599

RESUMO

OBJECTIVE: The objective of this paper was to assess the effects of hydatid cyst fluid (HCF) of Echinococcus granulosus on melanoma A375 cell proliferation and apoptosis. METHODS: A375 cells were classified into five groups by in vitro culture: normal group, control group, 10% HCF group, 20% HCF group and 30% HCF group. Trypan blue staining method was employed to detect the toxicity of HCF. Effects of different concentrations of HCF on melanoma A375 cell proliferation at different time points were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and propidium iodide (PI) staining were used to detect cell cycle, and Annexin-V/PI double staining method was used to determine A375 cell apoptotic rate. Western blotting was applied to detect the expression of phosphorylated extracellular regulated protein kinases, proliferating cell nuclear antigen (PCNA), cell-cycle-related proteins (cyclin A, cyclin B1, cyclin D1 and cyclin E) and apoptosis-related proteins (Bcl-2, Bax and caspase-3). RESULTS: HCF with a high concentration was considered as atoxic to A375 cells. HCF promoted A375 cell proliferation, and the effects got stronger with an increase in concentrations but was retarded after reaching a certain range of concentrations. HCF increased phosphorylation level and expression of extracellular regulated protein kinase, as well as PCNA expression. HCF also promoted the transferring progression of A375 cells from the G0/G1 phase to the S phase to increase the cell number in S phase and increased the expression of cyclin A, cyclin D1 and cyclin E. HCF increased the expression of procaspase-3 (the precursor of apoptosis-related protein caspase-3) and antiapoptotic protein-Bcl-2, and decreased the expression of proapoptotic factor Bax, thereby inhibiting cell apoptosis. CONCLUSION: As a result, this study confirmed that HCF promotes proliferation and inhibits apoptosis of melanoma A375 cells.

20.
J Occup Environ Med ; 60(4): e188-e192, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29370017

RESUMO

OBJECTIVE AND METHODS: To analyze the association between global DNA methylation and single-nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR). MTHFR polymorphisms rs1801133 and rs1801131 were detected using the restriction fragment length polymorphism method, and cytokinesis-block micronucleus (MN) frequency and global DNA methylation was measured in workers from 410 shoe factories. RESULTS: A multilinear regression analysis demonstrated that DNA methylation of the TT variant allele of rs1801133 was lower than that of the CC wild type allele (Exp(ß) [95% CI], 0.76 [0.56, 1.02], P = 0.071), with a P-value approaching significance. A significantly increased MN frequency was observed for carriers of the TT genotype (frequency ratio = 1.27, 95% CI: 1.07-1.51, P < 0.01). CONCLUSION: The results imply that the TT genotype in rs1801133 is associated with global DNA hypomethylation, which may influence the induction of MN following exposure to benzene.


Assuntos
Benzeno/efeitos adversos , Metilação de DNA/genética , Indústria Manufatureira , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Exposição Ocupacional/efeitos adversos , Polimorfismo de Nucleotídeo Único , Adulto , China , Feminino , Genótipo , Humanos , Masculino , Testes para Micronúcleos , Polimorfismo de Fragmento de Restrição , Sapatos
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