RESUMO
Colorectal cancer (CRC) is a common malignancy in both men and women, and the prognosis of CRC patients is still unsatisfactory. We aimed to identify novel effective diagnostic and prognostic targets for CRC. The study design is listed as below: we first confirmed the linear correlation between the expression of disheveled 3 (DVL3) and circular RNA_0101802 (circ_0101802) in CRC tissues, and their functional correlation in CRC cells was verified by rescue assays. Subsequently, bioinformatics databases were used to search the common interacted microRNAs (miRNAs) of DVL3 and circ_0101802, and compensation experiments were conducted to verify the functional correlation between miR-665 and DVL3 in CRC cells. Finally, xenograft tumor model was established to confirm the role of circ_0101802/miR-665/DVL3 axis in tumor growth in vivo. The expression of DVL3 and circ_0101802 was elevated in CRC tissues and cell lines, and high levels of DVL3 and circ_0101802 were closely associated with short survival time of CRC patients. Circ_0101802 silencing restrained the proliferation, migration, and tube formation abilities and induced the apoptosis of CRC cells. Circ_0101802 silencing-induced anti-tumor effects in CRC cells were partly reversed by DVL3 overexpression. miR-665 was an intermediary molecule between circ_0101802 and DVL3, and circ_0101802 could positively regulate DVL3 protein expression by sponging miR-665 in CRC cells. DVL3 overexpression partly overturned miR-665 overexpression-mediated anti-tumor effects in CRC cells. Circ_0101802 knockdown significantly suppressed xenograft tumor growth in vivo. In conclusion, circ_0101802 contributed to CRC progression by targeting miR-665/DVL3 signaling.
Assuntos
Neoplasias Colorretais , Proteínas Desgrenhadas , MicroRNAs , RNA Circular , Feminino , Humanos , Masculino , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Proteínas Desgrenhadas/genética , Proteínas Desgrenhadas/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , AnimaisRESUMO
BACKGROUND: To investigate the effect of albumin infusion on cirrhotic patients admitted for acute gastrointestinal bleeding. METHODS: Medical records of cirrhotic patients who admitted due to acute gastrointestinal bleeding through January 2009 to December 2018 were reviewed. Clinical data and the total amount of albumin and red blood cell used during hospitalization were recorded. For patients with rebleeding, the amount of albumin and red blood cell used before rebleeding was also documented. The primary outcome was the occurrence of rebleeding, and the second outcome was in-hospital mortality. Univariate and multivariate logistic analysis was performed to identify risk factors associated with rebleeding and in-hospital mortality. RESULTS: A total of 1503 cirrhotic patients were included in the analysis. There were 146 episodes of in-patient rebleeding occurred, while 81 patients died. Overall, more red blood cells and albumin were prescribed to patients who suffered rebleeding. In terms of the amount before rebleeding, the red blood cell was higher in patients with rebleeding, but the albumin infusion was similar. In the multivariate model, the albumin infusion before rebleeding was an independent risk factor associated with rebleeding (adjusted OR for ≤40 g vs 0 g, 0.469 [0.269-0.793], p = 0.006; adjusted OR for > 40 g vs 0 g, 0.272 [0.115-0.576], p = 0.001). In Child-Pugh C class patients, the use of albumin more than 40 g during hospitalization associated with a lower risk of in-patient mortality (adjusted OR for > 40 g vs 0 g, 0.136 [0.019-0.741], p = 0.031). CONCLUSIONS: Albumin infusion was associated with a lower risk of rebleeding and in-hospital deaths in cirrhosis admitted for acute gastrointestinal bleeding.
Assuntos
Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Albuminas , Hemorragia Gastrointestinal/etiologia , Mortalidade Hospitalar , Hospitalização , Humanos , Cirrose Hepática/complicações , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: With the follow-up extending to 5 years, the outcomes of SYNTAX (Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) trial were comparable between coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in left-main (LM) patients with intermediate SYNTAX scores of 23-32. A subdivision depending on SYNTAX score will help to identify unsuitable LM patients with intermediate SYNTAX scores to receive PCI treatment. METHODS: Between January 2011 and June 2013, 104 patients with LM Coronary Artery Disease (CAD) undergoing PCI were selected retrospectively. We compared clinical outcomes in patients with SYNTAX score <27 and ≥27. The follow-up time was 25.23 ± 7.92 months. Kaplan-Meier survival analyses and Cox proportional hazards models were used to compare various outcomes between two groups. RESULTS: Higher rates of repeated revascularization (18.2% versus 4.2%, P = .027) and major adverse cerebro-cardiovascular events (MACCE) (24.2% versus 7.0%, P = .014) were shown in patients with SYNTAX score ≥ 27. After multivariate adjustment, a significant higher risk of repeated revascularization (hazard ratio: 6.25, 95% confidence interval: 1.48 to 26.37, P = .013) and MACCE (hazard ratio: 4.49, 95% confidence interval: 1.41 to 14.35, P = .011) were also found in patients with SYNTAX score ≥ 27. CONCLUSIONS: Based on the higher rate of repeated revascularization and MACCE, patients with LM CAD and intermediate SYNTAX scores will need a subdivision to identity the one not benefit from PCI. CABG is still the standard treatment method for patients of LM CAD with a SYNTAX score of ≥ 27.
Assuntos
Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment.
Assuntos
Neoplasias Colorretais/patologia , MicroRNAs/fisiologia , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/genética , Neoplasias Colorretais/genética , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Severe erosion wear is found on valve spools, which threatens the safety and reliability of these units. The use of the plasma beam spraying surfacing method can significantly improve the corrosion resistance and sealing performance of hydraulic valve spools, reduce material waste, and reduce maintenance costs. The effects of the co-addition of CeO2 and SiC particles on the morphology, surface cracks, microstructure, precipitated phases, and wear property of plasma-beam-sprayed Fe55-based coatings on 1025 steel were investigated using OM, EDS, ultra-deep field microscopy, and a wet sand rubber wheel friction tester, respectively. The dendrite exhibited a directional growth pattern perpendicular to the substrate and the transitional states of the microstructure with the co-addition of CeO2 and SiC particles. CeO2 or SiC reduced the liquid phase diffusion coefficient DL of Cr and C and resulted in a decrease in the G/R ratio. The dendrites changed into equiaxed grains. The main phase composition of the Fe55 welding layer was Cr7C3, γ-Fe. The martensite in the surfacing layer and the carbides formed Cr7C3, which can improve the hardness of the surfacing layer. The grain boundaries consisted mainly of a reticular eutectic structure. The uniform distribution of the Cr7C3 hard phase in the Fe55+1.5 wt% SiC+0.01 wt% CeO2 resulted in a uniformly worn surface. The sub-wear mechanisms during the friction process were micro-ploughing and micro-cutting. The hardness and toughness of Fe55+1.5 wt% SiC+0.01 wt% CeO2 were well-matched, avoiding excessive micro-cutting and microplastic deformation. A low content of CeO2 could lead to the formation of equiaxed grain and effectively improve the uniformity of the microstructure. The wear-resistant layer of Fe55+1.5 wt% SiC+0.01 wt% CeO2 can effectively improve the service life and long-term sealing performance of the valve spools.
RESUMO
In this study, niobium was added into grain-oriented silicon steels, four Nb-bearing hot-rolled bands with Nb content range from 0-0.025 wt% were prepared and a detailed study of the micro characterization (microstructure, texture and precipitates) of hot-rolled bands was carried out by various analysis methods, such as EBSD and TEM. The results indicate that the precipitates in Nb-free steel are MnS and AlN; however, in the Nb-bearing steel they are MnS, AlN and Nb(C, N). The precipitates are finer and more dispersed in Nb-bearing steel, and a stronger pining force was obtained, which contributes to the finer microstructure and less recrystallization fractions of the hot-rolled bands. A larger volume fraction and stronger intensity of Goss texture is presented in steel with 0.025 wt% Nb due to the effective inhibiting effect. However, it has little effect on the changes of microstructure and texture when the Nb content is more than 0.009 wt%.
RESUMO
This study investigates the strengthening mechanism and carbide precipitation behavior of medium Mn steel with Nb-Mo microalloy after cyclic quenching and austenite reverse transformation treatment. The results show that the Nb/Mo element not only precipitates (Nb,Mo)C in the grains, hindering the movement of dislocations and increases the strength, but also segregates at the austenite/ferrite grain boundary, thus delaying the transformation from austenite to ferrite. In addition, a large amount of nano-scale cementite is retained after cyclic quenching and austenite reverse transformation, which has a positive effect on the proportion of retained austenite in medium Mn steel. Moreover, the carbides with small size and low Mn content are dissolved, and the decomposed C and Mn content are beneficial to the nucleation of austenite during the intercritical annealing process at a temperature of 690 °C.
RESUMO
Ginsenosides from the edible and medicinal plant ginseng have demonstrated various pharmacological activities. However, producing ginsenoside efficiently remains a challenge. Engineering metabolic pathways through protein assembly in yeast is a promising way for ginsenoside production. In the biosynthetic pathway of ginsenosides, dammarenediol-II synthase and squalene epoxidase are two key enzymes that determine the production rate of the dammarane-type ginsenoside precursor dammarenediol-II. In this work, a strategy to enhance the biosynthesis of dammarenediol-II in Pichia pastoris was developed by the self-assembly of the two key enzymes via protein-protein interaction. After being modified by interacting proteins, the two enzymes were successfully co-localized, resulting in a 2.1-fold enhancement in dammarenediol-II yields.
Assuntos
Ginsenosídeos/biossíntese , Pichia/enzimologia , Espectrometria de FluorescênciaRESUMO
Dammarenediol-II is the nucleus of dammarane-type ginsenosides, which are a group of active triterpenoids exhibiting various pharmacological activities. Based on the native triterpene synthetic pathway, a dammarenediol-II synthetic pathway was established in Pichia pastoris by introducing a dammarenediol-II synthase gene (PgDDS) from Panax ginseng, which is responsible for the cyclization of 2,3-oxidosqualene to dammarenediol-II in this study. To enhance productivity, a strategy of "increasing supply and reducing competitive consumption of 2,3-oxidosqualene" was used. To increase the supply of 2,3-oxidosqualene, we augmented expression of the ERG1 gene, which is responsible for 2,3-oxidosqualene synthesis. This significantly improved the yield of dammarenediol-II over 6.7-fold, from 0.030mg/g dry cell weight (DCW) to 0.203mg/g DCW. Subsequently, to reduce competition for 2,3-oxidosqualene from ergosterol biosynthesis without affecting the normal growth of P. pastoris, we targeted the ERG7gene, which is responsible for conversion of 2,3-oxidosqualene to lanosterol. This gene was downregulated by replacing its native promoter with a thiamine-repressible promoter, using a marker-recycling and gene-targeting Cre- lox71/66 system developed for P. pastoris herein. The yield of dammarenediol-II was further increased more than 3.6-fold, to 0.736mg/g DCW. Furthermore, the direct addition of 0.5g/L squalene into the culture medium further enhanced the yield of dammarenediol-II to 1.073mg/g DCW, which was 37.5-fold higher than the yield from the strain with the PgDDS gene introduction only. The P. pastoris strains engineered in this study constitute a good platform for further production of ginsenosides in Pichia species.
Assuntos
Engenharia Metabólica/métodos , Pichia/metabolismo , Saponinas/biossíntese , Vias Biossintéticas , Ergosterol/metabolismo , Genes Fúngicos , Vetores Genéticos/metabolismo , Pichia/genética , Pichia/crescimento & desenvolvimento , Regiões Promotoras Genéticas/genética , Edição de RNA , Esqualeno/análogos & derivados , TriterpenosRESUMO
Although mesenchymal stem cells (MSCs) have been increasingly trialed to treat a variety of diseases, the underlying mechanisms remain still elusive. In this study, human umbilical cord (UC)-derived MSCs were stimulated by hypoxia, and the membrane microvesicles (MVs) in the supernatants were collected by ultracentrifugation, observed under an electron microscope, and the origin was identified with the flow cytometric technique. The results showed that upon hypoxic stimulus, MSCs released a large quantity of MVs of ~100 nm in diameter. The MVs were phenotypically similar to the parent MSCs, except that the majority of them were negative for the receptor of platelet-derived growth factor. DiI-labeling assay revealed that MSC-MVs could be internalized into human UC endothelial cells (UC-ECs) within 8 h after they were added into the culture medium. Carboxyfluorescein succinimidyl ester-labeling technique and MTT test showed that MSC-MVs promoted the proliferation of UC-ECs in a dose-dependent manner. Further, MVs could enhance in vitro capillary network formation of UC-ECs in a Matrigel matrix. In a rat hindlimb ischemia model, both MSCs and MSC-MVs were shown to improve significantly the blood flow recovery compared with the control medium (P<0.0001), as assessed by laser Doppler imaging analysis. These data indicate that MV releasing is one of the major mechanisms underlying the effectiveness of MSC therapy by promoting angiogenesis.