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1.
Life Sci ; : 117401, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035931

RESUMO

AIMS: The management of acute liver failure (ALF) is a major challenge worldwide. The current study aimed to determine the therapeutic potential of TNF-α pretreatment of umbilical cord mesenchymal stem cell-derived exosomes (T-Exo) in ALF. MAIN METHODS: Here, we enriched T-Exo and untreated exosomes (Exo), them were measured by nanoparticle tracking analysis (NTA) for particle size detection and identified surface marker by Western blot and flow cytometry. Then the cell proliferation was detected by CCK-8 and the effect of T-Exo on the expression levels of pro-inflammatory cytokines was tested by ELISA. ALF mouse models were induced by LPS and D-GalN. H&E staining, immunohistochemistry, and Western blot were used to detect the effect of T-Exo on the levels of NLRP3 and other inflammation-related pathway proteins. qPCR was used to detect the expression level of microRNA-299-3p in T-Exo and its transfer to macrophages. Laser confocal microscopy was used to detect colocalization of exosomes,Golgi and NLRP3 in macrophages. KEY FINDINGS: Our study shows that T-Exo can reduce serum ALT, AST and proinflammatory cytokines level and inhibit activation of NLRP3 inflammation-associated pathway proteins. T-Exo treatment reduces pathological liver damage caused by ALF. Anti-inflammatory-related miRNA-299-3p is up-regulated in TNF-α-stimulated MSCs and selectively packaged into exosomes for role in exosomal treatment. And conducted preliminary exploration and hypothesis on the specific mechanism of this effect. SIGNIFICANCE: These in vitro and in vivo studies indicate that T-Exo attenuates inflammatory damage caused by ALF and promotes liver tissue repair by inhibiting the activation of the NLRP3 pathway.

2.
Gut Microbes ; : 1-18, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931652

RESUMO

Background: Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we investigated the effects of gut microbiota produced-valeric acid (VA) on radiation-induced injuries.Methods: Mice were exposed to total body irradiation (TBI) or total abdominal irradiation (TAI) to mimic accidental or clinical scenarios. High-performance liquid chromatography (HPLC) was performed to assess short-chain fatty acids (SCFAs) in fecal pellets. Oral gavage with VA was used to mitigate radiation-induced toxicity. Gross examination was performed to assess tissue injuries of thymus, spleen and small intestine. High-throughput sequencing was used to characterize the gut microbiota profile. Isobaric tags for relative and absolute quantitation (iTRAQ) were performed to analyze the difference of protein profile. Hydrodynamic-based gene delivery assay was performed to silence KRT1 in vivo.Results: VA exerted the most significant radioprotection among the SCFAs. In detail, VA replenishment elevated the survival rate of irradiated mice, protected hematogenic organs, improved gastrointestinal (GI) tract function and intestinal epithelial integrity in irradiated mice. High-throughput sequencing and iTRAQ showed that oral gavage of VA restored the enteric bacteria taxonomic proportions, reprogrammed the small intestinal protein profile of mice following TAI exposure. Importantly, keratin 1 (KRT1) played a pivotal role in the radioprotection of VA.Conclusions: Our findings provide new insights into gut microbiota-produced VA and underpin that VA might be employed as a therapeutic option to mitigate radiation injury in pre-clinical settings.

3.
Oncogene ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836847

RESUMO

During malignancy, perturbed O-glycosylation confers global influence on cancer progression. As a hallmark of cancer metastasis, GalNAc-type O-glycosylation initiation is aberrantly raised, but the regulatory mechanism is still mysterious. Here, we show that LAMTOR5 raises abnormal initiation of O-glycosylation in breast cancer metastasis. LAMTOR5 was highly expressed in adenocarcinoma and correlated with Tn antigen, a product of O-glycosylation initiation, in both clinical metastatic breast cancer specimens and secondary metastasis mouse model. LAMTOR5-modulated O-glycosylation initiating enzyme GALNT1 conferred Tn accumulation and predicted poor survival. Mechanistically, LAMTOR5 stimulated transcriptions of GALNT1 through coactivating c-Jun, and triggered dislocation of GALNT1 in the endoplasmic reticulum (ER) via LAMTOR5 dependent-activation of c-Src. This unusual initiation of O-glycosylation resulted in the abundance of Tn modified glycoproteins, such as MUC1 and OPN. Collectively, our findings indicate that LAMTOR5/c-Jun/c-Src axis serves as the upstream regulator of abnormal O-glycosylation initiation and potential therapeutic targets in breast cancer metastasis.

4.
Adv Sci (Weinh) ; 6(21): 1901048, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31728280

RESUMO

Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy-associated adverse side effects has ignored the gender-specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation-induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high-fat diet (HFD) elicites explicitly contrary results. High-throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation-altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex-dependent fashion partly based on sex-distinct gut microbiota composition in preclinical settings.

5.
J Clin Transl Hepatol ; 7(3): 249-257, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608217

RESUMO

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

6.
Environ Technol ; : 1-14, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31591947

RESUMO

In this paper, laccase was immobilized with the adsorption-crosslinking method in which biochar was used as the carrier and glutaraldehyde was used as the crosslinking agent. Firstly, the optimal immobilization conditions and optimal operating conditions were investigated, and then the stability of both free laccase and immobilized laccase was compared. Finally, the 2,4-dichlorophenol contaminated soil was remedied with both free laccase and immobilized laccase, and the improvement on the remediation of the contaminated soil by immobilized laccase was analysed through the ecological evaluation. The results showed that in the optimal immobilization condition, the biochar with a particle size of 30 mesh should be selected, and glutaraldehyde with a volume fraction of 4% and 20 mL of laccase solution should be added to complete the 6-hour adsorption operation and 4-hour crosslinking operation. The stability of immobilized laccase was better than that of free laccase, and the thermal deactivation kinetic equation for the free laccase was lnA = -0.7657t + 0.4344 and the thermal deactivation kinetic equation for the immobilized laccase was lnA = -0.1048t + 0.0608, respectively. The degradation ability of immobilized laccase for 2-4 dichlorophenol was better than that of free laccase. The degradation rate of 2,4-dichlorophenol was 44.4% in the free laccase group and 64.6% in the immobilized laccase group. The ecological evaluation showed that the biochar-immobilized laccase had a positive effect on the soil ecological environment in the remediation process of the soil and can improve the remediation of the contaminated soil to some extent.

7.
Cancer Biol Med ; 16(2): 276-287, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31516748

RESUMO

Objective: The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis. Methods: We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer. Results: In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1 (NUSAP1) as one of the target genes of miR-18b. NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b. Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro. Conclusions: Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBx-modulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

8.
Environ Technol ; : 1-10, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31530251

RESUMO

In this paper, ultrasound was used to enhance the degradation effect of laccase for 2,4-dichlorophenol (2,4-DCP) in soil. The degradation effect and mechanism of the ultrasound-enhanced laccase were investigated. From the results, the degradation rate of 2,4-DCP can reach as high as 51.7% under the following conditions: reaction period was 21 h, pH = 5.5, ultrasound power was 240 W, duty cycle was 50%, and moisture content was 50%. Using the ultrasound-enhanced laccase, the degradation rate of 2,4-DCP was significantly higher than that using only laccase or only ultrasound. In addition, when ultrasound was used, the optimum pH for the degradation of 2,4-DCP using laccase was increased, making the degradation technology more practical. The analysis results from high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) revealed the degradation pathway of 2,4-DCP in soil: first, 2,4-DCP gradually became phenol through dechlorination, then the small molecular organic matter was generated from the hydroxyl radical or laccase reaction.

9.
Theranostics ; 9(18): 5227-5245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410212

RESUMO

Rationale: Hepatitis B virus (HBV) is a major risk factor for liver cancer, in which HBV covalently closed circular DNA (cccDNA) plays crucial roles. However, the effect of pseudogene-derived long noncoding RNAs (lncRNAs) acting as functional regulators of their ancestral gene expression on HBV replication and hepatocellular carcinoma (HCC) remains unclear. In this study, we speculated that the pseudogene-derived lncRNA PCNAP1 and its ancestor PCNA might modulate HBV replication and promote hepatocarcinogenesis. Methods: We investigated the roles of lncRNA PCNAP1 in contribution of HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling in hepatocarcinogenesis by using CRISPR/Cas9, Southern blot analysis, confocal assays, et al. in primary human hepatocytes (PHH), HepaRG cells, HepG2-NTCP cells, hepatoma carcinoma cells, human liver-chimeric mice model, transgenetic mice model, in vitro tumorigenicity and clinical patients. Results: Interestingly, the expression levels of PCNAP1 and PCNA were significantly elevated in the liver of HBV-infectious human liver-chimeric mice. Clinically, the mRNA levels of PCNAP1 and PCNA were increased in the liver of HBV-positive/HBV cccDNA-positive HCC patients. Mechanistically, PCNA interacted with HBV cccDNA in a HBc-dependent manner. PCNAP1 enhanced PCNA through sponging miR-154 targeting PCNA mRNA 3'UTR. Functionally, PCNAP1 or PCNA remarkably enhanced HBV replication and accelerated the growth of HCC in vitro and in vivo. Conclusion: We conclude that lncRNA PCNAP1 enhances the HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling and the PCNAP1/PCNA signaling drives the hepatocarcinogenesis. Our finding provides new insights into the mechanism by which lncRNA PCNAP1 enhances HBV replication and hepatocarcinogenesis.

10.
Sci Rep ; 9(1): 10876, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350522

RESUMO

The anatomical morphologies of vessel elements and pits of bamboo plants are unique, however, intensive research about vessel elements and pits in bamboo species is very scarce. The vessel elements and pits of four sympodial bamboo species were analyzed by light microscopy and environmental scanning electron microscopy (ESEM). Results show that the length and width of vessel elements were significantly different across bamboo species. The simple (main type), scalariform, and reticulate perforation plates were discovered on the end of vessel elements. The four species also displayed distinct pit forms. Characteristics of vessel elements, perforation plates, and the shape and size of pit apertures were examined separately for their potential relationship of bamboo structure and function.

11.
Cancer Lett ; 454: 158-170, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30981758

RESUMO

Long noncoding RNA HULC is identified and highly expressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is a key driver of liver cancer. In the present study, we found that HULC remarkably elevated the levels of HBeAg, HBsAg, HBcAg, pgRNA, HBx, HBV DNA and covalently closed circular DNA (cccDNA), which activated the HBV replication in HBV-expressing hepatoma cells or de novo HBV-infected cell lines (PHH, HepG2-NTCP and dHepaRG). Mechanistically, HULC enhanced HBV cccDNA stability by down-regulating the APOBEC3B in hepatoma cells. HULC significantly up-regulated microRNA-539, which targeted the 3'UTR of APOBEC3B mRNA. Luciferase reporter gene assays revealed a putative STAT3-binding site located in the upstream of miR-539 promoter. Moreover, we identified that HULC was able to elevate HBx, which co-activated the STAT3 to stimulate the miR-539 promoter. Then, miR-539 down-regulated APOBEC3B and promoted HBV replication. Functionally, HULC enhanced the growth of hepatoma cells by activating HBV in vitro and in vivo, which could be blocked by overexpressing APOBEC3B. In conclusion, HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related HCC.

12.
Front Plant Sci ; 10: 134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30842780

RESUMO

Cotton, a natural fiber producing crop of huge importance, is often prone to attack of Verticillium dahliae. Papain-like cysteine proteases (PLCPs) constitute a large family in plants and were proposed to involve in plant defense against pathogen attack in a number of studies. However, there is no detailed characterization of PLCP genes in cotton against infection of V. dahliae. In this study, we carried out a genome-wide analysis in cotton and identified seventy-eight PLCPs, which were divided into nine subfamilies based on their evolution phylogeny: RD21 (responsive to desiccation 21), CEP (cysteine endopeptidase), XCP (xylem cysteine peptidase), XBCP3 (xylem bark cysteine peptidase 3), THI, SAG12 (senescence-associated gene 12), RD19 (responsive to desiccation 19), ALP (aleurain-like protease) and CTB (cathepsin B-like). Genes in each subfamily exhibit a similar structure and motif composition. The expression patterns of these genes in different organs were examined, and subfamily RD21 was the most abundant in these families. Expression profiles under abiotic stress showed that thirty-five PLCP genes were induced by multiple stresses. Further transcriptome analysis showed that sixteen PLCP genes were up-regulated in response to V. dahliae in cotton. Among those, GhRD21-7 showed a higher transcription level than most other PLCP genes. Additionally, over-expression of GhRD21-7 led to enhanced resistance and RNAi lines were more susceptible to V. dahliae in cotton. Our results provide valuable information for future functional genomic studies of PLCP gene family in cotton.

13.
Bioinformatics ; 35(20): 4029-4037, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30918942

RESUMO

MOTIVATION: Multiview clustering has attracted much attention in recent years. Several models and algorithms have been proposed for finding the clusters. However, these methods are developed either to find the consistent/common clusters across different views, or to identify the differential clusters among different views. In reality, both consistent and differential clusters may exist in multiview datasets. Thus, development of simultaneous clustering methods such that both the consistent and the differential clusters can be identified is of great importance. RESULTS: In this paper, we proposed one method for simultaneous clustering of multiview data based on manifold optimization. The binary optimization model for finding the clusters is relaxed to a real value optimization problem on the Stiefel manifold, which is solved by the line-search algorithm on manifold. We applied the proposed method to both simulation data and four real datasets from TCGA. Both studies show that when the underlying clusters are consistent, our method performs competitive to the state-of-the-art algorithms. When there are differential clusters, our method performs much better. In the real data study, we performed experiments on cancer stratification and differential cluster (module) identification across multiple cancer subtypes. For the patients of different subtypes, both consistent clusters and differential clusters are identified at the same time. The proposed method identifies more clusters that are enriched by gene ontology and KEGG pathways. The differential clusters could be used to explain the different mechanisms for the cancer development in the patients of different subtypes. AVAILABILITY AND IMPLEMENTATION: Codes can be downloaded from: http://homepage.fudan.edu.cn/sqzhang/files/2018/12/MVCMOcode.zip. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

14.
Opt Lett ; 44(3): 570-573, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30702681

RESUMO

A passively mode-locked fiber laser with controllable pulse width is demonstrated by use of an all-fiber saturable absorber based on a hybrid no-core fiber (NCF)-graded index multimode fiber (GIMF) structure incorporated into an Er-doped fiber ring cavity. Such a hybrid NCF-GIMF structure has a tunable intracavity filtering effect. As a result, the mode-locking operation is achieved with controllable pulse width and spectral bandwidth in the normal dispersion regime by only stretching the fiber device. Soliton pulses with the pulse width of 7.7-23 ps are generated, and bound solitons with variable widths are also experimentally demonstrated. The results obtained reveal the versatility and flexibility of the NCF-GIMF structured device in controlling the pulse dynamics for different experimental requirements.

15.
Biochem Biophys Res Commun ; 508(3): 735-741, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30528233

RESUMO

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) play an important role in the regulation of the immune system and inflammatory responses; however, their role in acute liver failure (ALF) and related pathological conditions is unclear. In this study, we found that hUCMSC-EXOs can reduce the expression of the NLRP3 inflammasome and downstream inflammatory factors in acute liver failure. Western blot and ELISA results showed that hUCMSC-EXOs decreased the expression of NLRP3, caspase-1, IL-1ß and IL-6 in LPS-stimulated RAW 264.7 macrophages. In vivo, the hUCMSC-EXOs repaired damaged liver tissue and decreased the expression of the NLRP3 inflammasome and the levels of ALT and AST in a mouse ALF model. The results of this study provide a new strategy for the application of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of ALF.


Assuntos
Exossomos/transplante , Inflamassomos/metabolismo , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/terapia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/citologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cordão Umbilical/citologia , Animais , Modelos Animais de Doenças , Humanos , Recém-Nascido , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7
16.
Toxicol Appl Pharmacol ; 364: 12-21, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30529626

RESUMO

Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells. On the basis of anti-tumor properties of cordycepin, we examined the effects of cordycepin on sensitizing breast cancer cells toward radiotherapy. Cordycepin administration promoted G2/M arrest and apoptosis of MCF-7 and MDA-MB-231 cells resulting in restraining the proliferation of the cells in vitro and in vivo following irradiation. Mechanistic investigations showed that the breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species (ROS) and incremental numbers of γ-H2AX foci after irradiation exposure. Importantly, cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor (Nrf2) and a series of downstream genes, such as heme oxygenase-1 (HO-1), to enhance ROS in breast cancer cells exposed to irradiation. Together, our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis. Thus, our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiotherapy, and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting.


Assuntos
Neoplasias da Mama/radioterapia , Desoxiadenosinas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Dano ao DNA , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Heme Oxigenase-1/metabolismo , Histonas/metabolismo , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
17.
BMC Plant Biol ; 18(1): 150, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041622

RESUMO

BACKGROUND: Transcription factors operate as important switches of transcription networks, and NAC (NAM, ATAF, and CUC) transcription factors are a plant-specific family involved in multiple biological processes. However, this gene family has not been systematically characterized in cotton. RESULTS: Here we identify a large number of genes with conservative NAC domains in four cotton species, with 147 found in Gossypium arboreum, 149 in G. raimondii, 267 in G. barbadense and 283 in G. hirsutum. Predicted membrane-bound NAC genes were also identified. Phylogenetic analysis showed that cotton NAC proteins clustered into seven subfamilies and homologous protein pairs showed similar characteristics. Evolutionary property analysis revealed that purifying selection of NAC genes occurred between diploid and polyploid cotton species, and variation analysis showed GhNAC genes may have been subjected to selection and domestication. NAC proteins showed extensive transactivation and this was dependent on the C-terminus. Some development and stress related cis-elements were enriched in the promoters of GhNAC genes. Comprehensive expression analysis indicated that 38 GhNAC genes were candidates for involvement in fiber development, and 120 in stress responses. Gene co-expression network analysis revealed relationships between fiber-associated NAC genes and secondary cell wall (SCW) biosynthesis genes. CONCLUSIONS: NAC genes were identified in diploid and tetraploid cotton, revealing new insights into their evolution, variation and homology relationships. Transcriptome analysis and co-expression network indicated roles for GhNAC genes in cotton fiber development and stress response, and NAC genes may prove useful in molecular breeding programmes.


Assuntos
Fibra de Algodão , Gossypium/metabolismo , Fatores de Transcrição/fisiologia , Sequência Conservada/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genes de Plantas/fisiologia , Variação Genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Gossypium/genética , Gossypium/crescimento & desenvolvimento , Filogenia , Estresse Fisiológico , Sintenia/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Ativação Transcricional/fisiologia
18.
Ann Hepatol ; 17(3): 392-402, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29735787

RESUMO

INTRODUCTION AND AIM: Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS: We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS: The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION: In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.


Assuntos
Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Antivirais/uso terapêutico , Técnicas de Apoio para a Decisão , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Modelos Biológicos , Nucleosídeos/uso terapêutico , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Antivirais/efeitos adversos , Bilirrubina/sangue , Biomarcadores/sangue , China , Progressão da Doença , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/mortalidade , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeos/efeitos adversos , Escores de Disfunção Orgânica , Valor Preditivo dos Testes , Estudos Prospectivos , Protrombina/metabolismo , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
19.
BMC Syst Biol ; 12(Suppl 1): 8, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29671401

RESUMO

BACKGROUND: Breast cancer and ovarian cancer are hormone driven and are known to have some predisposition genes in common such as the two well known cancer genes BRCA1 and BRCA2. The objective of this study is to compare the coexpression network modules of both cancers, so as to infer the potential cancer-related modules. METHODS: We applied the eigen-decomposition to the matrix that integrates the gene coexpression networks of both breast cancer and ovarian cancer. With hierarchical clustering of the related eigenvectors, we obtained the network modules of both cancers simultaneously. Enrichment analysis on Gene Ontology (GO), KEGG pathway, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA) in the identified modules was performed. RESULTS: We identified 43 modules that are enriched by at least one of the four types of enrichments. 31, 25, and 18 modules are enriched by GO terms, KEGG pathways, and DO terms, respectively. The structure of 29 modules in both cancers is significantly different with p-values less than 0.05, of which 25 modules have larger densities in ovarian cancer. One module was found to be significantly enriched by the terms related to breast cancer from GO, KEGG and DO enrichment. One module was found to be significantly enriched by ovarian cancer related terms. CONCLUSION: Breast cancer and ovarian cancer share some common properties on the module level. Integration of both cancers helps identifying the potential cancer associated modules.


Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Ovarianas/genética , Algoritmos , Análise por Conglomerados , Feminino , Ontologia Genética , Humanos
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(2): 569-575, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29665934

RESUMO

OBJECTIVE: To study the effect and mechanism of mTOR signaling on adipogenesis of bone marrow mesenchymal stem cells(BM-MSCs) from aplastic anemia (AA) patients through regulation of PPARγ. METHODS: BM-MSCs were isolated from 24 newly diagnosed AA patients and 24 healthy controls. The surface antigen expression of BM-MSCs was identified by flow cytometry. The capacity of adipogenic differentiation of BM-MSCs was determined by lipid droplets based on Oil Red O staining and by the expression of FABP4 based on Western blot. Protein levels of mTOR signaling and PPARγ were tested by immunofluorescence and Western blot. RESULTS: AA BM-MSCs displayed an enhanced capacity of differentiating into adipocytes, compared with control BM-MSCs. It was found that mTOR was activated in AA BM-MSCs. Moreover, the expression levels of p-mTOR and PPAR-γ in AA BM-MSCs showed a parallel differentiation-dependent increase during adipogenic differentiation, which were significantly higher than that of control BM-MSCs at the same time point of adipogenic differentiation. mTOR inhibitor rapamycin did not only inhibit the adipogenic differentiation of BM-MSCs from AA pateints at the early-middle stage, but also partly reversed the adipogenic differention of BM-MSCs from AA pateints at the late stage by PPARγ regulation. CONCLUSION: mTOR signaling may play a critical role in the adipogenic differentiation of BM-MSCs from AA patients by positively regulating PPARγ expression.


Assuntos
Anemia Aplástica , Adipogenia , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais , PPAR gama , Transdução de Sinais , Serina-Treonina Quinases TOR
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