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1.
BMC Genomics ; 22(1): 653, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511071

RESUMO

BACKGROUND: As non-coding RNA molecules of more than 200 bp in length, long non-coding RNAs (lncRNAs) play a variety of roles in biological processes, including regulating the immune responses to bacterial infections. In recent years, there have been many in-depth studies on mammalian lncRNAs, but the relevant studies in fish are very limited. Meanwhile, since lncRNAs are not conserved among species, it is difficult to apply the existing results directly to unstudied species. RESULTS: To obtain the information of lncRNAs in Megalobrama amblycephala, one of the most economically important freshwater fish in China, also to better understand the biological significance of lncRNAs in the immunity system, the fish liver at 0, 4, 12, 24, and 72 h post Aeromonas hydrophila infection (hpi) were obtained for lncRNA-sequencing (lncRNA-seq). A total of 14,849 lncRNAs were identified, and 2196 lncRNAs showed significant differences at different time points post A. hydrophila infection. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the target genes of the differentially expressed lncRNAs were enriched in several pathways related to immune such as apoptosis, inflammation, and immune response. Time-specific modules were then identified, using weighted correlation network analysis (WGCNA), and 28 modules significantly correlated with different time point after infection were found. Furthermore, four immune-related genes and six lncRNAs in the time-specific modules were subsequently verified by RT-qPCR. CONCLUSIONS: The above findings reveal the discovery of widespread differentially expressed lncRNAs in the M. amblycephala liver post A. hydrophila infection, suggesting that lncRNAs might participate in the regulation of host response to bacterial infection, enriching the information of lncRNAs in teleost and providing a resources basis for further studies on the immune function of lncRNAs.


Assuntos
Cyprinidae , RNA Longo não Codificante , Aeromonas hydrophila , Animais , Cyprinidae/genética , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro/genética
2.
Dev Comp Immunol ; 124: 104185, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34174243

RESUMO

Circular RNAs (circRNAs), a class of non-coding RNAs, play an important role in regulating various biological processes. In the present study, circRNAs from the Megalobrama amblycephala liver were identified at five different time points post Aeromonas hydrophila using RNA-seq technology. A total of 250 circRNAs were identified, of which 106 were differentially expressed (DE) in ten pairwise comparisons. GO and KEGG analyses showed that the parental genes of DE circRNAs were enriched in phagocytosis, complement and coagulation cascades, and Fc gamma R-mediated phagocytosis pathways. According to ceRNA hypothesis, the interaction network of circRNAs, miRNAs and mRNAs was constructed. Moreover, WGCNA was conducted, and five specific modules significantly related to bacterial infection were identified. All the above results reveal the important role of circRNAs in immune response, which enriches the information of circRNAs in teleost, and helps to understand the immune response mechanism of M. amblycephala to A. hydrophila.

3.
BMC Infect Dis ; 21(1): 441, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33985440

RESUMO

OBJECTIVES: We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. METHODS: We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. RESULTS: A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/µL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597-83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. CONCLUSION: The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.


Assuntos
Subpopulações de Linfócitos/citologia , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/mortalidade , Adulto , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Feminino , Humanos , Células Matadoras Naturais/citologia , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
4.
BMC Genomics ; 21(1): 857, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267780

RESUMO

BACKGROUND: Ammonia is one of the most common toxicological environment factors affecting shrimp health. Although ammonia tolerance in shrimp is closely related to successful industrial production, few genetic studies of this trait are available. RESULTS: In this study, we constructed a high-density genetic map of the Pacific white shrimp (Litopenaeus vannamei) using specific length amplified fragment sequencing (SLAF-seq). The constructed genetic map contained 17,338 polymorphic markers spanning 44 linkage groups, with a total distance of 6360.12 centimorgans (cM) and an average distance of 0.37 cM. Using this genetic map, we identified a quantitative trait locus (QTL) that explained 7.41-8.46% of the phenotypic variance in L. vannamei survival time under acute ammonia stress. We then sequenced the transcriptomes of the most ammonia-tolerant and the most ammonia-sensitive individuals from each of four genetically distinct L. vannamei families. We found that 7546 genes were differentially expressed between the ammonia-tolerant and ammonia-sensitive individuals. Using QTL analysis and the transcriptomes, we identified one candidate gene (annotated as an ATP synthase g subunit) associated with ammonia tolerance. CONCLUSIONS: In this study, we constructed a high-density genetic map of L. vannamei and identified a QTL for ammonia tolerance. By combining QTL and transcriptome analyses, we identified a candidate gene associated with ammonia tolerance. Our work provides the basis for future genetic studies focused on molecular marker-assisted selective breeding.


Assuntos
Amônia , Locos de Características Quantitativas , Amônia/toxicidade , Animais , Mapeamento Cromossômico , Ligação Genética , Marcadores Genéticos , Humanos
5.
Front Genet ; 11: 571880, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193676

RESUMO

Nitrite is a major environmental toxin in aquaculture systems that disrupts multiple physiological functions in aquatic animals. Although nitrite tolerance in shrimp is closely related to successful industrial production, few genetic studies of this trait are available. In this study, we constructed a high-density genetic map of Litopenaeus vannamei with 17,242 single nucleotide polymorphism markers spanning 6,828.06 centimorgans (cM), with an average distance of 0.4 cM between adjacent markers on 44 linkage groups (LGs). Using this genetic map, we identified two markers associated with nitrite tolerance. We then sequenced the transcriptomes of the most nitrite-tolerant and nitrite-sensitive individuals from each of four genetically distinct L. vannamei families (LV-I-4). We found 2,002, 1,983, 1,954, and 1,867 differentially expressed genes in families LV-1, LV-2, LV-3, and LV-4, respectively. By integrating QTL and transcriptomics analyses, we identified a candidate gene associated with nitrite tolerance. This gene was annotated as solute carrier family 26 member 6 (SLC26A6). RNA interference (RNAi) analysis demonstrated that SLC26A6 was critical for nitrite tolerance in L. vannamei. The present study increases our understanding of the molecular mechanisms underlying nitrite tolerance in shrimp and provides a basis for molecular-marker-assisted shrimp breeding.

7.
FASEB J ; 34(8): 11257-11271, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32648265

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is the most economically important infectious disease of pigs worldwide. Our previous study revealed that Tongcheng (TC) pigs display higher resistance to PRRS than Largewhite (LW) pigs, but the genetic mechanism remains unknown. Here, we first confirmed that CXCL14 was downregulated in lungs and porcine alveolar macrophages (PAMs) responding to PRRS virus (PRRSV) infection, but the decline in LW pigs was more obvious than that in TC pigs. Then, we found that the overexpression of CXCL14 activated type-I interferon (IFN-I) signaling by upregulating interferon beta (IFNB), which plays a major role in the antiviral effect. To further decipher the mechanism underlying its differential expression, we characterized the core promoter of CXCL14 as being located from -145 to 276 bp of the transcription start site (TSS) and identified two main haplotypes that displayed significant differential transcriptional activities. We further identified two coupled point mutations that altered the binding status of CEBPB and were responsible for the differential expression in TC and LW pigs. The regulatory effect of CEBPB on CXCL14 was further confirmed by RNA interference (RNAi) and chromatin immunoprecipitation (ChIP), providing crucial clues for deciphering the mechanism of CXCL14 downregulation in unusual conditions. The present study revealed the potential antiviral effect of CXCL14, occurring via activation of interferon signaling, and suggested that CXCL14 contributes to the PRRS resistance of TC pigs.


Assuntos
Antivirais/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Quimiocinas CXC/metabolismo , Interferon beta/metabolismo , Mutação/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Regiões Promotoras Genéticas/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Quimiocinas CXC/genética , Regulação para Baixo/genética , Pulmão/metabolismo , Pulmão/virologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologia , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Ligação Proteica/genética , Ligação Proteica/fisiologia , Interferência de RNA/fisiologia , Transdução de Sinais/genética , Suínos , Sítio de Iniciação de Transcrição/fisiologia , Ativação Transcricional/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-32200130

RESUMO

MicroRNAs (miRNAs), as important regulators of post-transcriptional gene expression, play important roles in the occurrence and function of organs. In this study, morpholino (MO) knockdown of miR-462/miR-731 was used to investigate the potential mechanisms of the miR-462-731 cluster during zebrafish liver development. The results showed significant reduction of digestive organs, especially liver and exocrine pancreas after the miR-462/miR-731 knockdown, and those phenotypes could be partially rescued by corresponding miRNA duplex. Acinar cells of the exocrine pancreas were also severely affected with pancreatic insufficiency. In particular, knockdown of miR-462 caused pancreas morphogenesis abnormity with specific bilateral exocrine pancreas. Additionally, it was found that miR-731 played a role in liver and exocrine pancreas development by directly targeting dkk3b, instead of the down-regulation of Wnt/ß-catenin signaling. These findings contribute significantly to our understanding of molecular mechanisms of miR-462-731 cluster in development of digestive organs.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/genética , Pâncreas Exócrino/embriologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Pâncreas Exócrino/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
10.
Sci Total Environ ; 711: 134416, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000302

RESUMO

Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei.


Assuntos
Metabolômica , Penaeidae , Transcriptoma , Animais , Hepatopâncreas , Nitritos , Estresse Fisiológico
11.
Front Immunol ; 11: 584808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584649

RESUMO

Chinese horseshoe crab, Tachypleus tridentatus, is an ancient marine arthropod with a long evolutionary history. As a kind of living fossil species, the pathogen defenses of horseshoe crabs entirely depend on the innate immune system. Although, there are abundant immune molecules found in the horseshoe crab hemolymph, the biological mechanisms underlying their abilities of distinguishing and defending against invading microbes are still unclear. In this study, we used high-throughput sequencing at mRNA and protein levels and bioinformatics analysis methods to systematically analyze the innate immune response to Gram-negative bacteria in hemolymph of Chinese horseshoe crab. These results showed that many genes in the complement and coagulation cascades, Toll, NF-κB, C-type lectin receptor, JAK-STAT, and MAPK signaling pathways, and antimicrobial substances were activated at 12 and 24 h post-infection, suggesting that Gram-negative bacteria could activate the hemolymph coagulation cascade and antibacterial substances release via the above pathways. In addition, we conjectured that Toll and NF-κB signaling pathway were most likely to participate in the immune response to Gram-negative bacteria in hemolymph of horseshoe crab through an integral signal cascade. These findings will provide a useful reference for exploring the ancient original innate immune mechanism.


Assuntos
Bactérias Gram-Negativas/imunologia , Hemolinfa/imunologia , Hemolinfa/microbiologia , Caranguejos Ferradura/imunologia , Caranguejos Ferradura/microbiologia , Animais , China , Imunidade Inata/imunologia , Lectinas/imunologia , Transdução de Sinais/imunologia
12.
Int J Infect Dis ; 88: 141-148, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442630

RESUMO

OBJECTIVES: The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. METHODS: We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. RESULTS: A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens. CONCLUSION: High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/administração & dosagem , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , beta-Glucanas/sangue , Adulto , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/fisiologia , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Fatores de Risco
13.
Ecotoxicol Environ Saf ; 180: 491-500, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31121556

RESUMO

Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.


Assuntos
Amônia/toxicidade , Metabolismo Energético/efeitos dos fármacos , Penaeidae/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Tolerância a Medicamentos , Perfilação da Expressão Gênica , Metabolômica , Penaeidae/genética , Penaeidae/metabolismo
14.
Fish Shellfish Immunol ; 89: 43-51, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30890434

RESUMO

Complement factor D (Df) is a serine protease, which can activate the alternative pathway by cleaving complement factor B, and involves in the innate defense against pathogens infection in teleost. In this study, we cloned, characterized the Df gene from blunt snout bream (Megalobrama amblycephala) (Mamdf), and examined its expression pattern and antimicrobial activity. The open reading frame (ORF) of Mamdf was 753 bp, encoding 250 amino acids with a molecular mass of 27.2 kDa. Mamdf consisted of a single serine protease trypsin superfamily domain, 3 substrate binding sites and 3 active sites, but no potential N-glycosylation site. Pairwise alignment showed that Mamdf shared the highest identity (94%) with grass carp (Ctenopharyngodon idellus). Phylogenetic analysis indicated that Mamdf and other vertebrate Df had a common ancestral origin. Mamdf structured with 4 introns and 5 exons. The Mamdf mRNA expressed relatively high at the intestine appearance stage during early development and constitutively expressed in various tissues with the highest expression in the kidney in healthy adults. After challenged with Aeromonas hydrophila, significant changes of Mamdf at both mRNA and protein levels in the kidney, spleen, liver and head-kidney were observed. The recombinant Mamdf protein showed antimicrobial activity against both gram-positive bacteria and gram-negative bacteria. The above results suggested the immune function of Mamdf, and would benefit further detailed Df function research in the immune process in teleost.


Assuntos
Fator D do Complemento/genética , Fator D do Complemento/imunologia , Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Fator D do Complemento/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/veterinária , Filogenia , Distribuição Aleatória , Alinhamento de Sequência/veterinária
15.
Int J Infect Dis ; 81: 17-24, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30641204

RESUMO

OBJECTIVE: The aim of this study was to conduct a systematic review to better understand the epidemiological and clinical characteristics of listeriosis patients in mainland China. METHODS: The six most widely used Chinese and English language databases were searched. The records of patients with listeriosis in mainland China reported during the years 2011-2017 were extracted. The clinical data of patients and information on clinical isolates of Listeria were collected and analyzed. RESULTS: In total, 136 records were identified, reporting 562 patients with listeriosis. The number of patients was much higher than that reported in the previous decade. The 227 non-perinatal listeriosis patients included had a mortality rate of 23.78%. Of the 231 perinatal listeriosis patients, 32.68% resulted in abortion and/or newborn death. All listeriosis cases were reported as being sporadic. The listeriosis was traced to infection via a meat product in only three patients, while 33.12% were healthcare-associated infections. CONCLUSIONS: The number of patients with listeriosis in mainland China may have been underestimated previously. Perinatal cases in mainland China account for a much higher proportion than is usually described. Considering the high number of listeriosis patients in China, a comprehensive monitoring system for Listeria is urgently needed.


Assuntos
Listeria monocytogenes/isolamento & purificação , Listeriose/epidemiologia , Listeriose/microbiologia , China/epidemiologia , Humanos
16.
Cell Death Differ ; 26(8): 1531-1544, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30459392

RESUMO

MicroRNAs (miRNAs) play significant roles in both embryonic hematopoiesis and hematological malignancy. Zebrafish miR-462-731 cluster is orthologous of miR-191-425 in human which regulates proliferation and tumorigenesis. In our previous work, miR-462-731 was found highly and ubiquitously expressed during early embryogenesis. In this study, by loss-of-function analysis (morpholino knockdown combined with CRISRP/Cas9 knockout) and mRNA profiling, we suggest that miR-462-731 is required for normal embryonic development by regulating cell survival. We found that loss of miR-462/miR-731 caused a remarkable decrease in the number of erythroid cells as well as an ectopic myeloid cell expansion at 48 hpf, suggesting a skewing of myeloid-erythroid lineage differentiation. Mechanistically, miR-462-731 provides an instructive input for pu.1-dependent primitive myelopoiesis through regulating etsrp/scl signaling combined with a novel pu.1/miR-462-731 feedback loop. On the other hand, morpholino (MO) knockdown of miR-462/miR-731 resulted in an expansion of posterior blood islands at 24 hpf, which is a mild ventralization phenotype resulted from elevation of BMP signaling. Rescue experiments with both BMP type I receptor inhibitor dorsomorphin and alk8 MO indicate that miR-462-731 acts upstream of alk8 within the BMP/Smad signaling pathway and functions as a novel endogenous BMP antagonist. Besides, an impairment of angiogenesis was observed in miR-462/miR-731 morphants. The specification of arteries and veins was also perturbed, as characterized by the irregular patterning of efnb2a and flt4 expression. Our study unveils a previously unrecognized role of miR-462-731 in BMP/Smad signaling mediated hematopoietic specification of mesodermal progenitors and demonstrates a miR-462-731 mediated regulatory mechanism driving primitive myelopoiesis in the ALPM. We also show a requirement for miR-462-731 in regulating arterial-venous specification and definitive hematopoietic stem cell (HSC) production. The current findings might provide further insights into the molecular mechanistic basis of miRNA regulation of embryonic hematopoiesis and hematological malignancy.


Assuntos
Hematopoese , MicroRNAs/metabolismo , Mielopoese , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismo , Animais , Células-Tronco Hematopoéticas/metabolismo , MicroRNAs/genética , Peixe-Zebra
17.
Heredity (Edinb) ; 121(4): 319-326, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30093666

RESUMO

Sex reversal in insects, amphibians, reptiles, and fishes is a complicated and interesting biological phenomenon. Sex reversal changes the sex ratio of populations and may complicate breeding schemes. In the Chinese tongue sole (Cynoglossus semilaevis), genetic females may change into pseudomales, thereby increasing aquaculture costs because of the lower growth rate of the males than that of the females. Here we identify a new locus associated with sex reversal; this single nucleotide polymorphism (SNP) is located in the third intron of the doublesex and mab-3 related transcription factor 1 (Dmrt1) gene on the Z chromosome (named Cyn_Z_8564889) and has two alleles, A and G. Cyn_Z_8564889 regulates sex reversal interactively with our previously detected SNP (Cyn_Z_6676874), with the genetic females simultaneously carrying the T allele of Cyn_Z_6676874 and the A allele of Cyn_Z_8564889 changing into pseudomales. Other Dmrt1 polymorphisms were detected, which formed two haplotypes. Two SNPs in the second exon of Dmrt1 result in amino acid changes, suggesting that Dmrt1 is essential in sex reversal. We also verified that pseudomales produce no or little W sperm. The interaction and linkage between Cyn_Z_6676874 and Cyn_Z_8564889 and the absence of W sperm from pseudomales unravel the genetic architecture of sex reversal in C. semilaevis.


Assuntos
Peixes/genética , Estudos de Associação Genética , Loci Gênicos , Fenótipo , Caracteres Sexuais , Alelos , Animais , Epistasia Genética , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Polimorfismo de Nucleotídeo Único , Espermatogênese/genética
18.
Gene ; 678: 219-225, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30086363

RESUMO

HIF prolyl hydroxylase 1 (PHD1) functions in prolyl hydroxylation on mammal hypoxia-inducible factors (HIF), important transcription factors involved in hypoxia, however the roles of Phd1 in fish remain unclear. In this study, the full-length cDNA and promoter sequences of blunt snout bream (Megalobrama amblycephala) phd1 gene were isolated by a modified RACE strategy. The phd1 cDNA was 2672 bp for encoding 481 amino acid residues. In silico assays indicated that phd1 had 5 exons, and a 348 bp CpG island in the exon1, and several transcription factor binding sites (CAAT box, HRE, ARNT, FOX, etc) were also found on the promoter. The quantitative real-time PCR results suggested that phd1 mRNA was constitutively expressed in all detected tissues, and higher in the blood, brain and heart in normoxia, but significantly decreased after hypoxia in all detected tissues except for gill. Western blot assays indicated that two Phd1 isoforms were generated by alternative translation initiation. Moreover, these two isoforms were both localized in the nucleus, therein only the senior isoform promoted cell proliferation. Taken together, the present study firstly describes the functions of M. amblycephala two Phd1 isoforms in hypoxia and cell proliferation.


Assuntos
Cyprinidae/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Processamento Alternativo , Animais , Núcleo Celular/metabolismo , Clonagem Molecular , Cyprinidae/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Distribuição Tecidual
20.
Medicine (Baltimore) ; 97(9): e9854, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29489682

RESUMO

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20-81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Imunofenotipagem , Contagem de Linfócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , China , Doença Crônica , Infecções por Vírus Epstein-Barr/sangue , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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