Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Filtros adicionais











Intervalo de ano
1.
Pediatr Surg Int ; 35(8): 853-859, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203384

RESUMO

PURPOSE: Hepatic artery thrombosis (HAT) remains a life-threatening complication in liver transplantation. We aim to investigate the risk factors of HAT in deceased donor pediatric liver transplantation. METHODS: 104 recipients from 2014 to 2016 were enrolled; donor and recipient characteristics, surgical variables, graft and recipient survival rate were compared between recipients with or without HAT. Univariate and multivariate analysis were applied to identify the risk factors of HAT. RESULTS: The recipient survival rate was 87.0% and 96.3% at 1 year, and 87.0% and 96.3% at 3 years in HAT and non-HAT groups without significant difference. The graft survival rate was 73.9% and 96.3% at 1 year, and 73.9% and 95.1% at 3 years in HAT and non-HAT groups; significant difference was observed between two groups at both 1 and 3 years. Donor age less than 8.5 months, graft weight less than 190 g and GRWR less than 2.2% were identified as independent risk factors for HAT. Recipients with HAT were associated with higher incidence of post-operative biliary complications. CONCLUSIONS: Young donor age and small liver graft are risk factors for HAT in deceased donor pediatric liver transplantation.

2.
J Exp Clin Cancer Res ; 38(1): 276, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234887

RESUMO

BACKGROUND: The E2A gene, which encodes two basic helix-loop-helix transcription factors, E12 and E47, regulates colorectal cancer progression and epithelial-mesenchymal transition. However, whether E2A regulates the tumor-initiating capacity of colorectal cancer is unclear. Thus, we have studied E2A expression in the initiation of colorectal cancer in vivo and in vitro. METHODS: Immunohistochemistry and immunoblot were performed to determine protein levels of E2A in colorectal cancer specimens and cells. RNAi was employed to downregulate E2A expression, and the subsequent change in protein level was evaluated by immunoblot. Sphere-forming assay and enumeration of liver metastasis in mouse models were used to identify the tumor formation ability of colorectal cancer cells. RESULTS: E2A expression in colorectal cancer clinical specimens was inversely associated with patients' progression-free survival. Functional studies demonstrated that E2A significantly decreased tumor formation in vitro and in vivo. Furthermore, nuclear translocation of beta-catenin and activation of the Wnt/beta-catenin pathway occurred after suppression of E2A in colorectal cancer cells. FoxM1 was identified as a down-stream target by mRNA microarray, implying that FoxM1 plays a main role in determining how E2A regulates the tumor-initiating capacity of colorectal cancer. CONCLUSION: E2A suppresses tumor-initiating capacity by targeting the FoxM1-Wnt/ß-catenin pathway.

3.
J Pediatr Surg ; 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31109730

RESUMO

BACKGROUND: Donors with low-body-weight were previously reported to be related to inferior recipient outcomes in pediatric liver transplantation. However, the scarce availability of age and size-matched organs has encouraged us to re-evaluate the feasibility and safety of using low-body-weight donors. METHODS: We retrospectively analyzed 91 deceased donor pediatric liver transplantation between January 2014 and December 2016, donor weight less than 5 kg was defined as low-body-weight donors. The recipients were divided into two groups according to donor weight. (≤5 kg and 5 kg < to ≤20 kg). Donor and recipient characteristics, perioperative data, postoperative complications as well as graft and recipient survival rate were compared RESULTS: The recipients and grafts recovery after transplantation were comparable between two groups. The recipients receiving low-body-weight donors showed higher risk of hepatic artery thrombosis and small-for-size syndrome, however, these complications can effectively be treated by our strategies. The 2-year patient survival rates were 92.9% and 95.2%, 2-year graft survival rates were 92.9% and 93.7% in Groups 1 and 2, without significant difference. CONCLUSIONS: Our finding suggested that the utility of livers from low-body-weight donors is a potential strategy to increase donor availability in well-selected pediatric recipients. LEVEL OF EVIDENCE: III.

4.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

5.
Pediatr Transplant ; 23(5): e13396, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081216

RESUMO

BACKGROUND: The lack of age- and size-matched organs result in higher waiting list mortality in pediatric recipients than adults. Organs from deceased newborns and infants are a valuable source to increase donor pool in pediatric liver transplantation. However, the feasibility and safety of using neonatal donors have not been well evaluated. METHODS: From 2014 to 2016, 48 deceased donor pediatric liver transplantations with donor age younger than 1 year old in our center were enrolled in this study. The recipients were divided into three groups based on the donor age (<1 month, 1 month ≤ to <3 months, and 3 months ≤ to <1 year). Recipient's characteristics, perioperative data, and postoperative complications were compared. RESULTS: Two-year patient survival rates were 87.5%, 94.4%, and 95.5%, and 2-year graft survival rates were 75%, 94.4%, and 95.5%, respectively, without significant difference. The liver grafts from donors younger than 3 months were more advantageous in terms of acute rejection and virus infection, while the young grafts were related to slight higher incidence of hepatic artery thrombosis and SFSS. Those complications could be effectively prevented or treated by our perioperative care strategies. In addition, eight recipients who received neonatal livers achieved comparable outcomes with recipients with older livers. CONCLUSION: Our data revealed that the application of liver grafts from donors younger than 1 year old could achieve excellent outcome. In particular, neonatal donors could be safely used in well-selected patients.

6.
Nat Commun ; 10(1): 746, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765691

RESUMO

Excessive or uncontrolled release of proinflammatory cytokines caused by severe viral infections often results in host tissue injury or even death. Phospholipase C (PLC)s degrade phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) lipids and regulate multiple cellular events. Here, we report that PLCß2 inhibits the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-ß-activated kinase 1 (TAK1) activation. Mechanistically, PI(4,5)P2 lipids directly interact with TAK1 at W241 and N245, and promote its activation. Impairing of PI(4,5)P2's binding affinity or mutation of PIP2-binding sites on TAK1 abolish its activation and the subsequent production of pro-inflammatory cytokines. Moreover, PLCß2-deficient mice exhibit increased expression of proinflammatory cytokines and a higher frequency of death in response to virus infection, while the PLCß2 activator, m-3M3FBS, protects mice from severe Coxsackie virus A 16 (CVA16) infection. Thus, our findings suggest that PLCß2 negatively regulates virus-induced pro-inflammatory responses by inhibiting phosphoinositide-mediated activation of TAK1.


Assuntos
Infecções por Coxsackievirus/metabolismo , Citocinas/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfolipase C beta/metabolismo , Animais , Células Cultivadas , Cercopithecus aethiops , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/virologia , Citocinas/genética , Enterovirus/fisiologia , Ativação Enzimática , Regulação da Expressão Gênica , Células HEK293 , Humanos , MAP Quinase Quinase Quinases/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipase C beta/genética , Ligação Proteica , Células Vero
8.
BMC Geriatr ; 18(1): 265, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400830

RESUMO

BACKGROUND: The relationship between kidney function and depressive symptoms among elderly people has been rarely investigated in settings of the general population. The aim of our study was to examine the association of serum cystatin C (cysC) and impaired kidney function with geriatric depressive symptoms among older people living in a rural community in China. METHODS: This population-based cohort study included 1440 individuals (age ≥ 60 years) who were recruited for the Confucius Hometown Aging Project in 2010-2011; of the 1124 persons who were free of depressive symptoms, 669 (59.5%) were re-examined in 2014-2016. At baseline, data on demographics, lifestyle factors, health conditions, and medical history were collected through interviews, clinical examinations, and laboratory tests. We defined impaired kidney function as the cystatin C-based estimated glomerular filtration rate (eGFRcysC) < 60 ml/min/1.73 m2, and depressive symptoms as a score ≥ 5 on the 15-item Geriatric Depression Scale. Data were analyzed using multiple logistic and Cox proportional-hazards models. RESULTS: Of the 1440 participants, 316 (21.9%) were defined to have geriatric depressive symptoms at baseline. Serum cysC levels of 1.01-1.25 and > 1.25 mg/L (vs. ≤1.00 mg/L) were associated with a multiple-adjusted odds ratio (OR) of 1.41 (95% CI 1.01-1.97) and 3.20 (2.32-4.41), respectively, for having geriatric depressive symptoms (Ptrend < 0.001). Of the 669 people who were free of depressive symptoms at baseline, 157 had incident depressive symptoms at the follow-up examination. The multiple-adjusted hazard ratio (HR) for incident depressive symptoms were 2.16 (95% CI 1.43-3.27) for serum cysC > 1.25 mg/L (vs. < 1.00 mg/L). Impaired kidney function was cross-sectionally (multiple-adjusted OR = 2.95; 95% CI 2.22-3.92) and longitudinally (multiple-adjusted HR 1.54; 95% CI 1.03-2.30) associated with an increased risk of geriatric depressive symptoms. CONCLUSION: Elevated serum cysC levels and impaired kidney function are associated with an increased risk of geriatric depressive symptoms among Chinese older people living in a rural community.

9.
Med Sci Monit ; 24: 7689-7696, 2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30368517

RESUMO

BACKGROUND lncRNA GAS5 acts as a tumor-suppressor gene in various types of malignancies, but its involvement in esophageal cancer has not been well studied. MATERIAL AND METHODS A total of 112 patients with esophageal cancer and 55 volunteers with normal physiological conditions were included in this study. Tumor tissues and adjacent healthy tissues were collected from esophageal cancer patients and blood was extracted from patients and controls. Expression of GAS5 in those tissues was detected by qRT-PCR. All patients were followed up for 5 years and diagnostic and prognostic values of serum GAS5 for esophageal cancer were investigated by ROC curve analysis and survival curve analysis, respectively. Effects of GAS5 expression on cell proliferation and migration were investigated by CCK-8 assay and Transwell cell migration assay, respectively. Effects of GAS5 overexpression on expression of PI3K/AKT/mTOR-related proteins were explored by Western blot analysis. RESULTS GAS5 expression level was lower in tumor tissues than in adjacent healthy tissues. Serum level of GAS5 was lower in cancer patients than in healthy controls, and serum level of GAS5 was decreased with increase in stage of primary tumor (T stage). GAS5 overexpression inhibited tumor cell proliferation and migration, while treatment with PI3K activator reduced the inhibitory effects. GAS5 overexpression decreased the expression level of PI3K and phosphorylation levels of Akt and mTOR in esophageal cancer cells, while PI3K activator treatment showed no significant effects on GAS5 expression. CONCLUSIONS GAS5 was downregulated in esophageal cancer patients compared to healthy controls, and GAS5 overexpression suppressed proliferation and migration of esophageal cancer cells by inactivating the PI3K/AKT/mTOR pathway.

10.
Nature ; 563(7729): 131-136, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356214

RESUMO

Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING-IRF3-type I IFN signalling cascade1,2. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response3,4, but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy.

11.
Nat Commun ; 9(1): 4295, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327467

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.

12.
Cell Death Discov ; 4: 17, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29531814

RESUMO

The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer. We screened a series of 80 compounds for the ability to interfere with the EMT and potentially be applied as a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a fluorescent analog of guanosine and adenosine, as a candidate in this screen. Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-ß1-treated A549 lung cancer cells. Moreover, 2-AP can inhibit TGF-ß1-induced metastasis of A549 cells. This compound significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT, and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could inhibit metastasis in vitro by suppressing the TGF-ß1-induced EMT and could attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.

13.
Sheng Wu Gong Cheng Xue Bao ; 33(12): 1945-1954, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29271172

RESUMO

To enrich the resource pool of endophytic fungi from plants which produce taxol, a taxol-producing endophytic fungus TMS-26 was isolated from the stem of Taxus Media. The result of high performance liquid chromatography (HPLC) showed that TMS-26 extract exhibited similar chromatographic peaks and retention time (4.545 min) with authentic taxol. Then mass spectrometry (MS) analysis further confirmed that TMS-26 extracts contained the same mass peaks with authentic taxol ((M+Na)+=876). These indicated that the isolated endophytic fungus TMS-26 can produce taxol. According to the morphological characteristics, the molecular analysis of 18S rDNA and internal transcribed spacer nuclear rDNA gene sequence, the fungus was identified as Aspergillus fumigatus TMS-26.

14.
Plant Cell Physiol ; 58(11): 1953-1962, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016961

RESUMO

MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus × domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence complementation and coimmunoprecipitation assays further verified the interaction between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome pathway. Furthermore, transgenic studies in apple calli and Arabidopsis demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by modulating the degradation of MdMYB1 protein. Taken together, our findings provide a new insight into the molecular mechanism by which MdMIEL1 negatively regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1 protein.


Assuntos
Antocianinas/metabolismo , Malus/metabolismo , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/genética , Malus/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Proteólise , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
15.
Plant Physiol Biochem ; 108: 24-31, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27404131

RESUMO

The basic helix-loop-helix (bHLH) Leu zipper transcription factor MYC2 is an important regulator in the Jasmonic acid (JA) signaling pathway. In this study, the apple MdMYC2 gene was isolated and cloned on the basis of its homology with Arabidopsis thaliana MYC2. Quantitative real time PCR (qRT-PCR) analysis demonstrated that MdMYC2 transcripts were induced by Methyl Jasmonate (MeJA) treatment and wounding. The MdMYC2 protein interacted with itself and bound the G-Box motif of the AtJAZ3 gene. MdMYC2 interacted with the MdJAZ2 protein, which is a repressor protein in the JA signaling pathway. Furthermore, we obtained transgenic apple calli that either overexpressed or suppressed the MdMYC2 gene. Expression analysis with qRT-PCR demonstrated that the transcript levels of JA-regulated anthocyanin biosynthetic genes, such as MdDFR, MdUF3GT, MdF3H and MdCHS, were markedly up-regulated in the MdMYC2 overexpressing calli and down-regulated in the suppressing calli compared with the WT control. As a result, the overexpressing calli produced more anthocyanin, and the suppressing calli produced less. Finally, the MdMYC2 gene was ectopically expressed in Arabidopsis. Both phenotypic investigation and expression analysis demonstrated that the MdMYC2 transgenic Arabidopsis lines were more sensitive to MeJA than the WT control. Together, these results indicate that the apple MdMYC2 gene plays a vital role in the JA response.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Malus/genética , Proteínas de Plantas/genética , Acetatos/metabolismo , Acetatos/farmacologia , Antocianinas/metabolismo , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Sítios de Ligação , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas , Malus/efeitos dos fármacos , Malus/metabolismo , Motivos de Nucleotídeos , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Complexo de Endopeptidases do Proteassoma/metabolismo , Estabilidade Proteica
16.
Anal Chim Acta ; 912: 85-96, 2016 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-26920776

RESUMO

A novel multistage MS approach, insource collision-induced dissociation (CID) combined with Time Aligned Parallel (TAP) fragmentation, was established to study the fragmentation behavior of polycyclic polyprenylated acylphloroglucinols (PPAPs), which could provide a more reliable fragmentation relationship between precursor and daughter ions. The diagnostic ions for different subtypes of PPAPs and their fragmentation behaviors have been summarized. Moreover, a new and reliable multidimensional analytical workflow that combines ultrahigh performance liquid chromatography (UHPLC), data-independent mass spectrometry (MS(E)), and tandem MS with ion mobility (IM) has been optimized and established for the analysis of PPAPs in the plant Garcinia oblongifolia by diagnostic filtering. Diagnostic fragment ions were used to selectively screen PPAPs from extracts, whereas IM coupled to MS was used to maximize the peak capacity. Under the optimized UHPLC-IM-MS(E) and UHPLC-IM-MS/MS method, 140 PPAPs were detected from the crude extract of G. oblongifolia, and 10 of them were unambiguously identified by comparing them to the reference compounds. Among those PPAPs, 7 pairs of coeluting isobaric PPAPs that were indistinguishable by conventional UHPLC-HRMS alone, were further resolved using UHPLC-IM-MS. It is anticipated that the proposed method will be extended to the rapid screening and characterization of the other targeted or untargeted compounds, especially these coeluting isomers in complex samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Garcinia/química , Floroglucinol/análise , Espectrometria de Massas em Tandem/métodos
17.
Rev Sci Instrum ; 83(1): 013101, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22299923

RESUMO

Polarization flipping accompanying with intensity transfer between two eigenstates of one laser mode happens when waveplate is placed in external cavity. The position of polarization flipping of two eigenstates is a function of phase retardation of waveplate. Phase retardation of waveplate is measured through analyzing the position of polarization flipping of two eigenstates. The measurement accuracy of phase retardation is 0.22°. A new structure of optical cement tray which can eliminate stress birefringence from optical cement process is invented. The accuracy of waveplate manufacture can be improved greatly based on the work of this article.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA