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1.
Genomics ; 116(3): 110851, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692440

RESUMO

Skeletal muscle satellite cells (SMSCs) play an important role in regulating muscle growth and regeneration. Chromatin accessibility allows physical interactions that synergistically regulate gene expression through enhancers, promoters, insulators, and chromatin binding factors. However, the chromatin accessibility altas and its regulatory role in ovine myoblast differentiation is still unclear. Therefore, ATAC-seq and RNA-seq analysis were performed on ovine SMSCs at the proliferation stage (SCG) and differentiation stage (SCD). 17,460 DARs (differential accessibility regions) and 3732 DEGs (differentially expressed genes) were identified. Based on joint analysis of ATAC-seq and RNA-seq, we revealed that PI3K-Akt, TGF-ß and other signaling pathways regulated SMSCs differentiation. We identified two novel candidate genes, FZD5 and MAP2K6, which may affect the proliferation and differentiation of SMSCs. Our data identify potential cis regulatory elements of ovine SMSCs. This study can provide a reference for exploring the mechanisms of the differentiation and regeneration of SMSCs in the future.


Assuntos
Diferenciação Celular , Desenvolvimento Muscular , Células Satélites de Músculo Esquelético , Animais , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/citologia , Ovinos/genética , Desenvolvimento Muscular/genética , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , RNA-Seq , Transdução de Sinais , Células Cultivadas , Sequenciamento de Cromatina por Imunoprecipitação , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proliferação de Células
2.
J Biol Chem ; 299(6): 104749, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37100284

RESUMO

The recent SARS-CoV-2 and mpox outbreaks have highlighted the need to expand our arsenal of broad-spectrum antiviral agents for future pandemic preparedness. Host-directed antivirals are an important tool to accomplish this as they typically offer protection against a broader range of viruses than direct-acting antivirals and have a lower susceptibility to viral mutations that cause drug resistance. In this study, we investigate the exchange protein activated by cAMP (EPAC) as a target for broad-spectrum antiviral therapy. We find that the EPAC-selective inhibitor, ESI-09, provides robust protection against a variety of viruses, including SARS-CoV-2 and Vaccinia (VACV)-an orthopox virus from the same family as mpox. We show, using a series of immunofluorescence experiments, that ESI-09 remodels the actin cytoskeleton through Rac1/Cdc42 GTPases and the Arp2/3 complex, impairing internalization of viruses that use clathrin-mediated endocytosis (e.g. VSV) or micropinocytosis (e.g. VACV). Additionally, we find that ESI-09 disrupts syncytia formation and inhibits cell-to-cell transmission of viruses such as measles and VACV. When administered to immune-deficient mice in an intranasal challenge model, ESI-09 protects mice from lethal doses of VACV and prevents formation of pox lesions. Altogether, our finding shows that EPAC antagonists such as ESI-09 are promising candidates for broad-spectrum antiviral therapy that can aid in the fight against ongoing and future viral outbreaks.


Assuntos
Antivirais , COVID-19 , Mpox , Vacínia , Animais , Camundongos , Antivirais/farmacologia , Mpox/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Vacínia/tratamento farmacológico , Vaccinia virus/efeitos dos fármacos
3.
Environ Sci Technol ; 58(17): 7445-7456, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38622030

RESUMO

The tandem application of CO2 electrolysis with syngas fermentation holds promise for achieving heightened production rates and improved product quality. However, the significant impact of syngas composition on mixed culture-based microbial chain elongation remains unclear. Additionally, effective methods for generating syngas with an adjustable composition from acidic CO2 electrolysis are currently lacking. This study successfully demonstrated the production of medium-chain fatty acids from CO2 through tandem acidic electrolysis with syngas fermentation. CO could serve as the sole energy source or as the electron donor (when cofed with acetate) for caproate generation. Furthermore, the results of gas diffusion electrode structure engineering highlighted that the use of carbon black, either alone or in combination with graphite, enabled consistent syngas generation with an adjustable composition from acidic CO2 electrolysis (pH 1). The carbon black layer significantly improved the CO selectivity, increasing from 0% to 43.5% (0.05 M K+) and further to 92.4% (0.5 M K+). This enhancement in performance was attributed to the promotion of K+ accumulation, stabilizing catalytically active sites, rather than creating a localized alkaline environment for CO2-to-CO conversion. This research contributes to the advancement of hybrid technology for sustainable CO2 reduction and chemical production.


Assuntos
Dióxido de Carbono , Eletrólise , Ácidos Graxos , Fermentação , Dióxido de Carbono/química , Ácidos Graxos/metabolismo
4.
Hemoglobin ; : 1-6, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693050

RESUMO

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and ß-globin chains and consequently cause clinical symptoms of ß-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with ß thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous ß0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of ß-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.

5.
Mol Ther ; 30(5): 1885-1896, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34687845

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines.


Assuntos
COVID-19 , Vacinas , Animais , Camundongos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunidade , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Linfócitos T
6.
Ecotoxicol Environ Saf ; 257: 114914, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37084658

RESUMO

Ingestion of arsenic interferes with spermatogenesis and increases the risk of male infertility, but the underlying mechanism remines unclear. In this study, we investigated spermatogenic injury with a focus on blood-testis barrier (BTB) disruption by administrating 5 mg/L and 15 mg/L arsenic orally to adult male mice for 60 d. Our results showed that arsenic exposure reduced sperm quality, altered testicular architecture, and impaired Sertoli cell junctions at the BTB. Analysis of BTB junctional proteins revealed that arsenic intake downregulated Claudin-11 expression and increased protein levels of ß-catenin, N-cadherin, and Connexin-43. Aberrant localization of these membrane proteins was also observed in arsenic-treated mice. Meanwhile, arsenic exposure altered the components of Rictor/mTORC2 pathway in mouse testis, including inhibition of Rictor expression, reduced phosphorylation of protein kinase Cα (PKCα) and protein kinase B (PKB), and elevated matrix metalloproteinase-9 (MMP-9) levels. Furthermore, arsenic also induced testicular lipid peroxidative damage, inhibited antioxidant enzyme (T-SOD) activity, and caused glutathione (GSH) depletion. Our findings suggest that disruption of BTB integrity is one of the main factors responsible for the decline in sperm quality caused by arsenic. PKCα-mediated rearrangement of actin filaments and PKB/MMP-9-increased barrier permeability jointly contribute to arsenic-induced BTB disruption.


Assuntos
Arsênio , Camundongos , Masculino , Animais , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Arsênio/toxicidade , Arsênio/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase C-alfa/metabolismo , Barreira Hematotesticular/metabolismo , Sêmen , Testículo/metabolismo , Espermatogênese , Fatores de Transcrição/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo
7.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36768334

RESUMO

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells.


Assuntos
Diacilglicerol O-Aciltransferase , Lipogênese , Proteínas de Membrana , Triglicerídeos , Animais , Feminino , Humanos , Aciltransferases/genética , Aciltransferases/metabolismo , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Lipogênese/genética , Lipogênese/fisiologia , Mamíferos/metabolismo , Triglicerídeos/biossíntese , Triglicerídeos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
8.
BMC Genomics ; 23(1): 535, 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35870881

RESUMO

BACKGROUND: Phosphatidylethanolamine-binding protein (PEBP) is widely present in animals, plants, and microorganisms. Plant PEBP genes are mainly involved in flowering transition and nutritional growth. These genes have been studied in several plants; however, to the best of our knowledge, no studies have explored them in Brassica juncea var. tumida. This study identified and characterized the entire PEBP gene family of Brassica juncea var. tumida. RESULTS: A total of 21 PEBP genes were identified from Brassica juncea var. tumida. Through phylogenetic analysis, the 21 corresponding proteins were classified into the following four clusters: TERMINAL FLOWER 1 (TFL1)-like proteins (n = 8), MOTHER OF FT AND TFL1 (MFT)-like proteins (n = 5), FLOWERING LOCUS T (FT)-like proteins (n = 6), and ybhB-like proteins (n = 2). A total of 18 genes contained four exons and had similar gene structures in each subfamily except BjMFT1, BjPYBHB1, and Arabidopsis thaliana CENTRORADIALIS homolog of Brassica juncea var. tumida (BjATC1). In the analysis of conserved motif composition, the BjPEBP genes exhibited similar characteristics, except for BjFT3, BjMFT1, BjPYBHB1, BjPYBHB2, and BjATC1. The BjPEBP promoter includes multiple cis-acting elements such as the G-box and I-box elements that respond to light, ABRE and GARE-motif elements that respond to hormones, and MBSI and CAT-box elements that are associated with plant growth and development. Analysis of RNA-Seq data revealed that the expression of a few BjPEBP genes may be associated with the development of a tumorous stem. The results of qRT-PCR showed that BjTFL1 and BjPYBHB1 were highly expressed in the flower tissue, BjFT1 and BjATC1 were mainly expressed in the root, and BjMFT4 were highly detected in the stem. The results of yeast two-hybrid screening suggested that BjFT interacts with Bj14-3-3. These results indicate that BjFT is involved in flowering regulation. CONCLUSIONS: To the best of our knowledge, this study is the first to perform a genome-wide analysis of PEBP genes family in Brassica juncea var. tumida. The findings of this study may help improve the yield and molecular breeding of Brassica juncea var. tumida.


Assuntos
Arabidopsis , Mostardeira , Arabidopsis/genética , Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Mostardeira/genética , Filogenia , Proteínas de Plantas/metabolismo , Plantas/genética
9.
J Cell Mol Med ; 24(2): 1906-1916, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31840411

RESUMO

Meckel syndrome (MKS) is a pre- or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo-occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35-years-old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715* ) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild-type CEP290 protein of 290 KD. Hence, it is a loss-of-function variant. We also found that the mutant cilium appears longer in length than the wild-type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population.


Assuntos
Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular/genética , Transtornos da Motilidade Ciliar/genética , Proteínas do Citoesqueleto/genética , Encefalocele/genética , Sequenciamento do Exoma , Mutação/genética , Doenças Renais Policísticas/genética , Retinose Pigmentar/genética , Adulto , Povo Asiático/genética , Sequência de Bases , Encefalocele/patologia , Feminino , Feto/diagnóstico por imagem , Homozigoto , Humanos , Rim/patologia , Masculino , Linhagem , Ultrassonografia Pré-Natal
10.
BMC Genomics ; 21(1): 800, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203382

RESUMO

BACKGROUND: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. RESULTS: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. CONCLUSIONS: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.


Assuntos
Tecido Adiposo , Cruzamento , Fator de Crescimento Derivado de Plaquetas/genética , Cauda , Animais , Genômica , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Ovinos/genética
11.
J Cell Biochem ; 121(2): 1463-1474, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31599078

RESUMO

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.


Assuntos
Artrite Experimental , Edaravone/farmacologia , Animais , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Proteínas de Ciclo Celular/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo
12.
Mol Biol Evol ; 36(11): 2591-2603, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31273382

RESUMO

High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski's horses added for comparison. We find that Tibetan horses do not descend from Przewalski's horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

13.
Appl Microbiol Biotechnol ; 104(22): 9749-9757, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32989515

RESUMO

Cadmium (Cd) contamination has resulted in serious environmental pollution and threatens human health and ecosystems. Our recent studies have demonstrated that Pseudomonas chenduensis strain MBR can decrease Cd bio-availability and reduce Cd accumulation in rice; however, the transcriptional mechanisms underlying the bacterial response during and particularly after Cd bioremediation are still unclear. In this study, we used RNA-Seq to investigate the transcriptional profiles of strain MBR during and after Cd bioremediation. During Cd bioremediation, MBR removed all Cd2+ ions in solution within 24 h, accompanied by 564 upregulated and 363 downregulated expressed genes compared with that of the control (without Cd supplementation). Specifically, under Cd stress, the upregulation of czc (czcA, czcB, and czcC) and mer (merA, merT, merC, and merP) genes enabled Cd efflux from the cytoplasm and conferred resistance of MBR to Cd toxicity. The upregulation of genes (algK, algX, and alg44) related to biofilm formation enabled Cd absorption and contributed to Cd bioremediation. After Cd bioremediation, MBR was transferred to non-Cd medium, and the genes related to histidine metabolism and flagellar assembly still showed similar expression patterns as those during bioremediation (defined as Cd legacy effects). However, the genes involved in Cd resistance and bioremediation were not influenced by Cd legacy effects. This study provides new and thorough insights into the molecular mechanisms underlying Cd bioremediation by a functional microbe. KEY POINTS: • The upregulation of czc and mer genes is responsible for MBR resistance to Cd. • The upregulation of genes related to biofilm formation contributes to Cd bioremediation. • Cd effects on genes involved in histidine metabolism and flagellar assembly are long-lasting.


Assuntos
Cádmio , Oryza , Biodegradação Ambiental , Cádmio/análise , Cádmio/toxicidade , Ecossistema , Humanos , Oryza/genética , Pseudomonas/genética
14.
Clin Lab ; 66(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32776744

RESUMO

BACKGROUND: The aim of the study is to evaluate the significance of the Architect anti-HCV signal to cutoff (S/CO) ratios for predicting hepatitis C viremia and determine the optimal S/Co ratio value for Architect anti-HCV assay. METHODS: The results of patients who underwent HCV RNA quantitative assays because of positive anti-HCV from January 2015 to August 2019 were retrospectively analyzed, including S/Co ratio values, HCV RNA quantitative results, alanine aminotransferase (ALT), and aspartate transaminase (AST) values. Binary logistic regression and Spearman's correlation coefficient were used to analyze the collected data. Receiver-operating characteristics curve (ROC) was applied to analyze the predicting values of the indexes. RESULTS: In total, 811 patients were included in our study and HCV viremia was detected in 342 (42.1%) patients. There is no correlation between anti-HCV S/CO ratio and HCV RNA level. The samples with an S/Co ratio between 1 and 4 (271/271, 100%) were all HCV RNA negative. The area under the ROC curve of anti-HCV S/CO ratio was 0.8714 and the maximal Youden index was 0.681 at an optimal cutoff S/CO ratio value of 8.99. CONCLUSIONS: With the cutoff value of 1.0, the Architect anti-HCV assay showed excellent sensitivity but poor specificity in predicting HCV viremia. An S/Co ratio of 8.99 was optimal for further confirmation testing of HCV viremia.


Assuntos
Hepatite C , Viremia , Hepacivirus/genética , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C , Humanos , RNA Viral/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Viremia/diagnóstico
15.
Acta Obstet Gynecol Scand ; 99(6): 731-743, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32166736

RESUMO

INTRODUCTION: The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of NIPT by combining our cohort study results with published studies in a systematic meta-analysis. MATERIAL AND METHODS: A cohort study was carried out in the First Affiliated Hospital of Sun Yat-sen University and Kanghua Hospital. Meanwhile, searches of PubMed, EMBASE, The Cochrane Library and Web of Science for all relevant peer-reviewed articles were performed with a restriction to English language publication before 15 June 2019. Quality assessments were conducted with the Quality Assessment Tool for Diagnostic Accuracy Studies-2 checklist. Data analysis, heterogeneity, subgroup analysis and publication bias were carried out using META-DISC 1.4 and STATA 12.0. RESULTS: In all, 141 twin pregnancies included in our cohort study; confirmation revealed one true-positive case for trisomy 21 and 140 true-negative cases. The sensitivity and specificity for trisomy 21 by NIPT were both 100%. Twenty-two eligible studies were enrolled in this meta-analysis together with our study. There were 199 cases of trisomy 21, 58 cases of trisomy 18, 14 cases of trisomy 13 and 6347 cases of euploids in total. For trisomy 21, NIPT showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.99, 1.00, 145.81, 0.06 and 1714.09, respectively. For trisomy 18, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.88, 1.00, 200.98, 0.19 and 483.68, respectively. CONCLUSIONS: The performance of NIPT for trisomy 21 in twin pregnancy was excellent and it was similar to that reported in singleton pregnancy. However, due to publication bias (trisomy 18) and small number of cases (trisomy 13), accurate assessment of the predictive performance of NIPT for trisomies 18 and 13 could not be achieved.


Assuntos
Síndrome de Down/diagnóstico , Teste Pré-Natal não Invasivo , Gravidez de Gêmeos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Funções Verossimilhança , Gravidez , Sensibilidade e Especificidade , Adulto Jovem
16.
Ecotoxicol Environ Saf ; 198: 110655, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32361136

RESUMO

Microbial treatment of heavy metal-polluted sites is considered an environmentally friendly bioremediation technology with high potential. This study shows that Pseudomonas chengduensis strain MBR, a bacterium that can potentially be applied in the treatment of heavy metal pollution, is most affected by Cd(II) stress at the beginning of its growth. Up to 100% of total Cd(II) adsorption occurs in the first 48 h after treatment of stationary phase cells with Cd(II). A biofilm forms on the cell surface, Cd(II) adsorbs, and is reduced to Cd (0) in the form of nanoscale particles. The genome of strain MBR was sequenced, annotated and analyzed. We identified various genes potentially related to cadmium resistance, transport and metabolism. Analysis of the strain MBR genome is helpful to explore the mechanism of Cd(II) resistance, and can provide new ideas for cadmium pollution control.


Assuntos
Cádmio/toxicidade , DNA Bacteriano/genética , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Pseudomonas/efeitos dos fármacos , Adsorção , Biodegradação Ambiental , Biotransformação , Cádmio/metabolismo , Poluentes Ambientais/metabolismo , Biblioteca Genômica , Genômica , Estresse Oxidativo/genética , Pseudomonas/genética , Pseudomonas/metabolismo
17.
Exp Cell Res ; 371(1): 83-91, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30059665

RESUMO

SIRT1 is a protein deacetylase with a broad range of biological functions, many of which are known to be important in carcinogenesis, however much of the literature regarding the role of SIRT1 in cancer remains conflicting. In this study we assessed the effect of SIRT1 on the initiation and progression of thymic T cell lymphomas. We employed mouse strains in which SIRT1 activity was absent or could be reversibly modulated in conjunction with thymic lymphoma induction using either the N-nitroso-N-methylurea (NMU) carcinogenesis or the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) transgene. Decreased SIRT1 activity reduced the development of thymic lymphomas in the NMU-treated mice but was permissive for the formation of lung adenomas. Conversely, in the NPM-ALK transgenic mice, decreased SIRT1 activity had a modest promoting effect in the development of thymic lymphomas. The results of the work presented here add to the growing body of evidence that sirt1 is neither an outright oncogene nor a tumor suppressor. These opposing results in two models of the same disease suggest that the influence of sirt1 on carcinogenesis may lie in a role in tumor surveillance.


Assuntos
Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Linfoma de Células T/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Sirtuína 1/genética , Neoplasias do Timo/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/etiologia , Adenocarcinoma de Pulmão/mortalidade , Administração Oral , Animais , Antineoplásicos Hormonais/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/etiologia , Linfoma de Células T/mortalidade , Masculino , Metilnitrosoureia/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Fusão Oncogênica/metabolismo , Especificidade de Órgãos , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Análise de Sobrevida , Tamoxifeno/farmacologia , Timo/efeitos dos fármacos , Timo/metabolismo , Timo/patologia , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/etiologia , Neoplasias do Timo/mortalidade , Transfecção
18.
Appl Microbiol Biotechnol ; 103(19): 8203-8214, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396678

RESUMO

Microbial bioremediation of heavy metal-contaminated soil is a potential technique to reduce heavy metals in crop plants. However, the dynamics and roles of the local microbiota in bioremediation of heavy metal-contaminated soil following microbial application are rarely reported. In this study, we used Pseudomonas chenduensis strain MBR for bioremediation of Cd-contaminated paddy soil and investigated its effects on the dynamics of the local soil bacterial community and Cd accumulation in rice. Cd accumulation in rice grains and roots were significantly reduced by the addition of the strain MBR. The addition of the strain MBR caused greater changes in bacterial communities in rhizosphere soil than in bulk soil. MBR enhanced the roles of microbial communities in transformation of Cd fractions, especially in rhizosphere soil. The strain MBR likely regulated abundant subcommunities more than rare subcommunities to improve Cd bioremediation, especially in rhizosphere soil. Consequently, the dynamics and functional roles of the local microbial communities differed significantly during bioremediation between abundant and rare subcommunities and between rhizosphere soil and bulk soil. This study provides new insight into the microbiota-related mechanisms underlying bioremediation.


Assuntos
Cádmio/metabolismo , Consórcios Microbianos , Pseudomonas/metabolismo , Poluentes do Solo/metabolismo , Biodegradação Ambiental , Cádmio/análise , Oryza/química , Raízes de Plantas/química , Pseudomonas/crescimento & desenvolvimento , Sementes/química
19.
Ecotoxicol Environ Saf ; 185: 109685, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31541947

RESUMO

Food security and human health can be seriously affected by heavy metal and metalloid (HM) pollution of soil. In this study, the risks posed by HMs and microbial community responses to HM pollution of agricultural soil in southwestern China were investigated. The C, N, P, and S (nutrients) concentrations were 12040.7-15912.7, 1298.06-1832.01, 750.91-2050.35, and 269.17-2115.52 mg/kg, respectively. The As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn concentrations were 3.11-8.20, 1.85-6.56, 22.83-43.96, 11.21-23.30, 0.08-0.81, 11.02-22.97, 24.07-42.96, and 193.63-698.39 mg/kg, respectively. Interpolation analysis indicated that the nutrient and HM concentrations varied spatially rather strongly. The concentrations of all of the elements were higher in soil from the northern sampling sites than in soil from the other sites. HMs in soil were found to pose high levels of risk (RI 898.85, i.e., >600). Cd contributed more than the other HMs to the risk assessment values (ErCd 293.72-1031.94), so was the most serious contaminant. Microbial diversity decreased over time in soil with high HM concentrations (plot S2) and was lower than in soil with low HM concentrations (plot S8). The nutrient and HM concentrations correlated with the microbial community characteristics. Proteobacteria, Acidobacteria, and Chloroflexi were (in decreasing order) the dominant bacterial phyla. We speculate that these phyla may be strongly resistant to HMs. The fourth most common phylum was Actinobacteria. Bacteria in this phylum could be used as biological indicators of the HM pollution status. Soil micro-ecosystems can self-regulate. HM stress will affect the evolution of soil microorganisms and relevant functional genes. The spatiotemporal variability in the microbial community responses to HMs and the spatial analysis and ecological risk assessment results will be useful reference data for the remediation of HM-polluted soil.


Assuntos
Monitoramento Ambiental/métodos , Fazendas , Metaloides/análise , Metais Pesados/análise , Microbiota/efeitos dos fármacos , Poluentes do Solo/análise , Agricultura , China , Humanos , Medição de Risco , Solo/química , Microbiologia do Solo/normas , Análise Espacial
20.
BMC Genomics ; 19(1): 495, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29940837

RESUMO

BACKGROUND: Long intergenic noncoding RNAs (lincRNAs) have been recognized in recent years as key regulators of biological processes. However, lincRNAs in goat remain poorly characterized both across various tissues and during different developmental stages in goat (Capra hircus). RESULTS: We performed the genome-wide discovery of the lincRNAs in goat by combining the RNA-seq dataset that were generated from 28 cashmere goat skin samples and the 12 datasets of goat tissues downloaded from the NCBI database. We identified a total of 5546 potential lincRNA transcripts that overlapped 3641 lincRNA genes. These lincRNAs exhibited a tissue-specific pattern. Specifically, there are 584 lincRNAs expressed exclusively in only one tissue, and 91 were highly expressed in hair follicle (HF). In addition, 2350 protein-coding genes and 492 lincRNAs were differentially expressed in the skin of goat. The majority exhibited the remarkable differential expression during the transition of the goat skin from the May-June to August-October time point, which covered the different seasons. Fundamental biological processes, such as skin development, were significantly enriched in these genes. Furthermore, we identified several lincRNAs highly expressed in the HF, which exhibited not only the co-expression pattern with the key factors to the HF development but also the activated expression in the August to October time point. Intriguingly, one of spatiotemporal lincRNAs, linc-chig1598 could be a potential regulator of distal-less homeobox 3 expression during the secondary hair follicle growth. CONCLUSIONS: This study will facilitate future studies aimed at unravelling the function of lincRNAs in hair follicle development.


Assuntos
Folículo Piloso/fisiologia , RNA Longo não Codificante/fisiologia , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Cabras , Folículo Piloso/metabolismo , RNA Longo não Codificante/genética , Transcriptoma/genética
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