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1.
Plants (Basel) ; 9(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255501

RESUMO

The signaling pathways induced by Pseudomonas putida in rice plants at the early plant-rhizobacteria interaction stages, with and without inoculation of Xanthomonas oryzae pv. oryzae, were studied. In the absence of pathogen, P. putida reduced ethylene (ET) production, and promoted root and stem elongation. Interestingly, gene OsHDA702, which plays an important role in root formation, was found significantly up-regulated in the presence of the rhizobacterium. Although X. oryzae pv. oryzae inoculation enhanced ET production in rice plants, P. putida treatment repressed ET-, jasmonic acid (JA)- and salicylic acid (SA)-mediated defense pathways, and induced the biosynthesis of abscisic acid (ABA), and the overexpression of OsHDA705 and some pathogenesis-related proteins (PRs), which in turn increased the susceptibility of the rice plants against the pathogen. Collectively, this is the first work on the defense signaling induced by plant growth-promoting rhizobacteria in plants at the early interaction stages, and suggests that rhizobacteria stimulate an alternative defense mechanism in plants based on ABA accumulation and OsHDA705 signaling.

2.
Eur J Nutr ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32979077

RESUMO

PURPOSE: Docosahexaenoic acid (DHA) plays an essential role in brain, and its status is dependent on dietary intakes. School-aged children in rural China, who consume diets low in omega-3 polyunsaturated fatty acids, may benefit from DHA supplementation. Therefore, this trial was performed to examine the effect of 6-month DHA supplementation on executive functions (EFs) among healthy school-aged children in rural China. METHODS: A randomized, double-blind, placebo-controlled trial was conducted among 106 primary school children aged 7-12 years in rural China. Participants were randomized to receive either 300 mg/d DHA or placebo for 6 months. EFs including working memory and cognitive flexibility were evaluated at baseline, at 3 months and at 6 months, using Digit Span Backwards and Wisconsin card sorting test, respectively. Socio-demographic data were collected at baseline, and erythrocyte membrane fatty acids and serum neurotransmitters were measured at baseline and after 6-month intervention. RESULTS: Ninety-four children (88.7%) completed the study according to the protocol. Changes in erythrocyte membrane fatty acids indicated good compliance of the participants. There was no significant intervention effect on serum neurotransmitters. In two-factor ANCOVA, both groups showed a significant improvement in the Digit Span Backwards and the Wisconsin card sorting test from baseline to endpoint. However, no significant intervention effect was found on any EF scores. Linear regression analysis suggested no significant association between changes in erythrocyte DHA level with changes in any EF scores. CONCLUSIONS: Supplementation with 300 mg/d DHA for 6 months had no benefit on EFs including working memory and cognitive flexibility among healthy school-aged children. This trial was registered at clinicaltrials.gov as NCT02308930 on December 5, 2014.

3.
Blood Adv ; 4(13): 3180-3190, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32663298

RESUMO

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

4.
Blood ; 136(5): 623-626, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32518950

RESUMO

We developed a risk score to predict event-free survival (EFS) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n = 1425) was randomly split into training (n = 1070) and validation (n = 355) cohorts. Risk factors were identified and validated via Cox regression models. Two risk factors of 9 evaluated were predictive for EFS: age at transplantation and donor type. On the basis of the training cohort, patients age 12 years or younger with an HLA-matched sibling donor were at the lowest risk with a 3-year EFS of 92% (score, 0). Patients age 13 years or older with an HLA-matched sibling donor or age 12 years or younger with an HLA-matched unrelated donor were at intermediate risk (3-year EFS, 87%; score, 1). All other groups, including patients of any age with a haploidentical relative or HLA-mismatched unrelated donor and patients age 13 years or older with an HLA-matched unrelated donor were high risk (3-year EFS, 57%; score, 2 or 3). These findings were confirmed in the validation cohort. This simple risk score may guide patients with sickle cell disease and hematologists who are considering allogeneic transplantation as a curative treatment relative to other available contemporary treatments.

5.
Genome Biol ; 21(1): 120, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423473

RESUMO

BACKGROUND: Vertebrate early embryogenesis is initially directed by a set of maternal RNAs and proteins, yet the mechanisms controlling this program remain largely unknown. Recent transcriptome-wide studies on RNA structure have revealed its pervasive and crucial roles in RNA processing and functions, but whether and how RNA structure regulates the fate of the maternal transcriptome have yet to be determined. RESULTS: Here we establish the global map of four nucleotide-based mRNA structures by icSHAPE during zebrafish early embryogenesis. Strikingly, we observe that RNA structurally variable regions are enriched in the 3' UTR and contain cis-regulatory elements important for maternal-to-zygotic transition (MZT). We find that the RNA-binding protein Elavl1a stabilizes maternal mRNAs by binding to the cis-elements. Conversely, RNA structure formation suppresses Elavl1a's binding leading to the decay of its maternal targets. CONCLUSIONS: Our study finds that RNA structurally variable regions are enriched in mRNA 3' UTRs and contain cis-regulatory elements during zebrafish early embryogenesis. We reveal that Elavl1a regulates maternal RNA stability in an RNA structure-dependent fashion. Overall, our findings reveal a broad and fundamental role of RNA structure-based regulation in vertebrate early embryogenesis.

6.
Biol Blood Marrow Transplant ; 26(7): e161-e166, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389803

RESUMO

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/métodos , Infecções por Coronavirus/epidemiologia , Criopreservação/métodos , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Pneumonia Viral/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Estados Unidos/epidemiologia , Doadores não Relacionados
7.
J Cell Physiol ; 235(12): 9370-9377, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32346889

RESUMO

The aim is to investigate the correlation between computed tomography (CT) features and insulin resistance levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). Nearly, 268 untreated PTB patients complicated with T2DM were divided into two groups according to the optimal cutoff value of HOMA-IR score for the Chinese population: HOMA-IR ≤ 2.69 (Group I: 74 patients), >2.69 (Group II: 194 patients). The basic characteristics and changes of CT manifestations were analyzed. In the two groups, the detection rate of large segmented leafy shadow was 39.2% and 78.9%; the air bronchogram sign detection rate was 40.5% and 80.9%; the discovery rate of mouth-eaten cavity was 33.8% and 73.7%; the thin-walled cavity detection rate was 2.7% and 16.0%; the rate of multiple cavities was 35.1% and 69.6%; and bronchial tuberculosis was found in 4.1% and 35.6%, respectively. The detection rates of lesions in Group II were significantly higher than in Group I (p < .05). HOMA-IR was found independently associated with large segmented leafy shadow, air bronchial sign, thin-walled cavity, and bronchial tuberculosis. The level of insulin resistance can effectively reflect the severity of PTB patients with T2DM. CT scan can directly provide image information in clinics. These two examinations can guide clinicians to accurately formulate subsequent treatment plans.

8.
Dev Cell ; 53(3): 272-286.e7, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275888

RESUMO

Extreme weather events can cause heat stress that decreases crop production. Recent studies have demonstrated that protein degradation and rRNA homeostasis as well as transcription factors are involved in the thermoresponse in plants. However, how RNA modifications contribute to temperature stress response in plant remains largely unknown. Herein, we identified OsNSUN2 as an RNA 5-methylcytosine (m5C) methyltransferase in rice. osnsun2 mutant displayed severe temperature- and light-dependent lesion-mimic phenotypes and heat-stress hypersensitivity. Heat stress enhanced the OsNSUN2-dependent m5C modification of mRNAs involved in photosynthesis and detoxification systems, such as ß-OsLCY, OsHO2, OsPAL1, and OsGLYI4, which increased protein synthesis. Furthermore, the photosystem of osnsun2 mutant was vulnerable to high ambient temperature and failed to undergo repair under tolerable heat stress. Thus, OsNSUN2 mutation reduced photosynthesis efficiency and accumulated excessive reactive oxygen species upon heat treatment. Our findings demonstrate an important mechanism of mRNA m5C-dependent heat acclimation in rice.

9.
Food Chem ; 320: 126642, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32217432

RESUMO

Melatonin (MLT) is a versatile biological signal that is involved in a number of plant processes, including germination, development, flowering, photosynthesis and defence. The need to develop new methodologies for enhancing crop yields and extending fruit postharvest preservation, together with the beneficial effects of dietary MLT, have stimulated the study of the availability and biological roles of MLT in fruit. Here, we are reviewing for the first time the effects of endogenous and exogenous MLT on fruit production and postharvest preservation. The signalling pathways implicated in MLT response and the applications of MLT in fruit decay, abiotic stress and pathogen infection have been traced in order to provide new insights on the biological significance of MLT in fruit.


Assuntos
Conservação de Alimentos , Melatonina/química , Plantas/química , Frutas/química , Frutas/metabolismo , Melatonina/metabolismo , Plantas/metabolismo , Preservação Biológica
10.
Haematologica ; 105(5): 1329-1338, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31558669

RESUMO

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

11.
Asian J Surg ; 43(1): 347-353, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31229360

RESUMO

OBJECTIVE: To compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology regarding intra- and post-operative outcomes. METHODS: A retrospective study was performed on consecutive patients with gynecologic oncology from February 2014 to October 2017 at Gansu Provincial Hospital, China. Multivariable linear and logistic regression models were performed to explore the difference between two surgeries in the surgical outcomes after adjusting for potential confounders. RESULTS: 276 women were included in this study: 153 robot-assisted surgeries and 123 conventional laparoscopies. The multivariable linear regression model showed that robot-assisted surgery was longer operative time [coefficient (coef), 33.76; 95% CI, 12.47, 55.05; P = 0.002) ], higher lymph node yield (coef, 10.41; 95% CI, 7.47, 13.35; P < 0.001), shorter time to early post-operative feeding (coef, -1.09; 95% CI, -1.33, -0.84; P < 0.001) and less post-operative drainage volume (coef, -368.77; 95% CI, -542.46, -195.09; P < 0.001) than conventional laparoscopy. However, no difference was observed between the two surgeries regarding the estimated blood loss (P > 0.05). The multivariable logistic regression model showed that post-operative complications were similar between robot-assisted surgery and conventional laparoscopy (P > 0.05). CONCLUSION: Robot-assisted surgery was superior to conventional laparoscopy regarding intra- and post-operative outcomes for gynecologic oncology.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/métodos , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Feminino , Humanos , Período Intraoperatório , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
12.
Huan Jing Ke Xue ; 40(8): 3568-3576, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854762

RESUMO

To clarify the spatial distribution characteristics of zooplankton communities and the relationship between zooplankton and water environmental factors, 81 samples from 28 rivers and lakes in Beijing were collected in September 2017. A total of 68 species of zooplankton were identified, including 17 species of protozoa (25%), 36 species of rotifers (53%), 13 species of cladocera (19%), and copepods (3%, which were mainly copepodids and nauplii). Among 15 dominant species, 12 were copepods and rotifers. Zooplankton communities varied between the different rivers:The zooplankton in rivers in mountainous areas were mainly protozoa and copepods; in suburban areas, communities were dominated by copepods; and in urban areas, rotifers were dominant. A comprehensive water quality index, the Shannon-Wiener index, the Pielou evenness index, and the Margalef richness index were also calculated. Results showed that the water quality of the rivers in mountainous areas was generally better than in urban areas, which was better than in suburban areas. TN was found to be the main form of pollution using the single factor water quality index. Principal component analysis (PCA) and canonical correspondence analysis (CCA) identified that NH4+-N, BOD5, and COD had a significant effect on zooplankton community characteristics.


Assuntos
Rios , Zooplâncton , Animais , Pequim , Estações do Ano , Qualidade da Água
13.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3502-3511, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602915

RESUMO

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/administração & dosagem , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Relação Dose-Resposta a Droga , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
14.
Mol Cell ; 75(6): 1188-1202.e11, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31399345

RESUMO

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.


Assuntos
5-Metilcitosina/metabolismo , Embrião não Mamífero/embriologia , Desenvolvimento Embrionário/fisiologia , Estabilidade de RNA/fisiologia , RNA Mensageiro Estocado/metabolismo , Peixe-Zebra/embriologia , Animais , Células HeLa , Humanos , Camundongos , RNA Mensageiro Estocado/genética , Peixe-Zebra/genética
15.
Nat Cell Biol ; 21(8): 978-990, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31358969

RESUMO

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.


Assuntos
5-Metilcitosina/metabolismo , Regulação da Expressão Gênica/genética , Metiltransferases/genética , Neoplasias da Bexiga Urinária/genética , Proteína 1 de Ligação a Y-Box/genética , Animais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Humanos , Camundongos , RNA Mensageiro/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
16.
Blood Adv ; 3(12): 1826-1836, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31201170

RESUMO

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico/efeitos adversos , Adolescente , Adulto , Idoso , Doadores de Sangue/estatística & dados numéricos , Doadores de Sangue/provisão & distribução , Transplante de Medula Óssea/estatística & dados numéricos , Inibidores de Calcineurina/uso terapêutico , Doença Crônica , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Incidência , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etnologia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/estatística & dados numéricos , Transplante Haploidêntico/métodos , Adulto Jovem
17.
Huan Jing Ke Xue ; 40(3): 1152-1162, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087961

RESUMO

Volatile organic compounds (VOCs)are important air pollutants in China, and control of their emission is an important subject of air pollution prevention and control.Architectural coatings play a significant role as sources of atmospheric VOCs in China.Due to recent economic development and increase in the levels of urbanization, the building of residences and other buildings is ongoing all the time, which results in increasing demand for architectural coatings and the VOCs pollution caused by painting operations.However, there are few studies of the VOCs emission factors and VOCs emissions due to architectural coatings.In this paper, a set of bottom-up VOCs emission inventory estimation methods for architectural coatings in China was established.The architectural coatings VOCs emission factors were gotten by actual measurement of VOCs in architectural coatings and by summarizing studies of VOCs contents in architectural coatings.Combining these results with the consumption of architectural coating sources, a VOCs emission inventory of architectural coatings in China from 2013 to 2016 was established.The results showed the following.① VOCs emission factors were 24.63 g·kg-1 for water-based interior wall coatings; 17.5 g·kg-1 and 298.8 g·kg-1 for water-based and solvent-based exterior wall coatings, respectively. They were 2.75, 87.86, and 400 g·kg-1 for water-based, reaction-type, and solvent-based waterproof coatings, respectively. For water-based, solventless, and solvent-based floor coatings, they were 86.2, 25.24, and 317 g·kg-1, respectively; and 31.95 g·kg-1 and 464.61 g·kg-1 for water-based and solvent-based anticorrosive coatings respectively. The emission factors were 59.7 g·kg-1 and 347.2 g·kg-1 for water-based and solvent-based fire retardant coatings, respectively. ② VOCs emissions from the use of architectural coatings were 255900 t, 287500 t, 319700 t, and 348000 t from 2013 to 2016 in China, with an upward trend. ③ Total VOCs emissions from architectural coatings was 348000 t in 2016, and the VOCs emissions from floor coatings was 78700 t, accounting for 22.61% with the maximum contribution rate. The VOCs emissions from exterior wall coatings were 64900 t, accounting for 18.65% (second place), and the VOCs emissions from fire retardant coatings and anticorrosive coatings (functional coatings) were 64500 t and 50800 t, accounting for 18.53% and 14.6% respectively. The VOCs emissions from waterproof coatings and interior wall coatings were 46100 t and 43000 t, accounting for 13.25% and 12.36%, respectively. ④ The consumption of water-based architectural coatings reached a total of 4889400 t in 2016 with VOCs emissions of 97900 t and average VOCs emissions factor of 20.02 g·kg-1; however, the consumption of solvent-based architectural coatings totaled 636500 t with VOCs emissions of 227200 t and average VOCs emission factor of 356.95 g·kg-1. Reducing the consumption of solvent-based coatings would be favorable for reduction of VOCs emissions. ⑤ As for the spatial distribution, architectural coating-related VOCs emissions were mainly concentrated in Shandong, Jiangsu, Zhejiang, Henan, Sichuan, Guangdong, and Hebei provinces, which have large populations. The province with the highest VOCs emissions was Shandong, with a percentage of 9.36%, and the second was Jiangsu, with a percentage of 8.54%.

18.
Leukemia ; 33(11): 2599-2609, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31073153

RESUMO

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60-77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) (n = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials (n = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p < 0.001), but more frequently had high-risk AML (high WBC, secondary AML, and unfavorable cytogenetics). Overall survival (OS) was worse in alloHCT during the first 9 months after CR1 (HR = 1.52, p = 0.02), but was significantly better thereafter (HR = 0.53, p < 0.0001) relative to CT. Treatment-related mortality (TRM) following HCT was worse in the first 9 months (HR = 2.8, 95% CI: 1.5-5.2, p = 0.0009), while post-HCT relapse was significantly less frequent beyond 9 months (HR = 0.42, 95% CI: 0.29-0.61, p < 0.0001). Despite higher early TRM, alloHCT recipients had superior long-term OS [29% (24-34%) versus CT 13.8% (9-21%) at 5 years]. Although this is a retrospective analysis with potential biases, it indicates that alloHCT led to heightened early risks from TRM, yet reduced relapse and superior long-term survival relative to CT in older AML patients in CR1.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Estados Unidos
19.
Mol Neurobiol ; 56(9): 6586-6593, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30903531

RESUMO

Glaucoma is a chronic optic neuropathy that could lead to permanent vision loss. Primary open-angle glaucoma (POAG) is the most common type of glaucoma, with elevated intraocular pressure (IOP) as a major risk factor. IOP is mainly regulated by trabecular meshwork (TM), an important component of the conventional aqueous humor (AH) outflow pathway. TM cells are constantly subjected to oxidative stress. Long-term exposure to oxidative stress has been shown to cause elevation of AH outflow resistance, leading to higher IOP. In this study, we induced chronic oxidative stress in human trabecular meshwork (TM-1) cells with 1 µM rotenone and investigated the levels of reactive oxygen species (ROS), autophagy, and mitochondrial functions. Protective effects of rapamycin, an inducer of autophagy, were also investigated. Our data indicated that rotenone significantly increased oxidative stress, but not autophagy, in TM-1 cells. Rapamycin at 10 nM effectively suppressed the rotenone-induced cell apoptosis, as well as the ROS elevation. The protective effects of rapamycin could be associated to the induction of autophagy and removal of damaged mitochondria in TM-1 cells. Our results suggest autophagy has important roles in protecting TM-1 cells from oxidative stress, which could be further developed into a novel treatment to POAG.


Assuntos
Citoproteção/efeitos dos fármacos , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Sirolimo/farmacologia , Malha Trabecular/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Proteínas do Citoesqueleto/metabolismo , Dexametasona/farmacologia , Proteínas do Olho/metabolismo , Glicoproteínas/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Rotenona/toxicidade , Regulação para Cima/efeitos dos fármacos
20.
Blood Adv ; 3(4): 670-680, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808685

RESUMO

Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.


Assuntos
Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
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