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High load-bearing capacity is one of the crucial indicators for liquid superlubricants to move toward practicality. However, some of the current emerging systems not only have low contact pressures but also are highly susceptible to further degradation due to water adsorption and even superlubricity failure. Herein, a novel choline chloride-based ionic liquid analogues (ILAs) of a superlubricant with triethanolamine (TEOA) as the H-bond donor is reported for the first time; it obtains an ultralow coefficient of friction (0.005) and high load-bearing capacity (360 MPa, more than 2 times that of similar systems) due to adsorption of a small amount of water (<5 wt %) from the air. In situ Raman combined with 1H NMR and FTIR techniques reveals that adsorbed water competes with the hydroxyl group of TEOA for coordination with Cl-, leading to the conversion of some strong H-bonds to weak H-bonds in ILAs; the localized strong H-bonds and weak H-bonds endow the ILAs with high load-bearing capacity and the formation of ultralow shear-resistance sliding interfaces, respectively, under the shear motion. This study proposes a strategy to modulate the interactions between liquid species using adsorbed water from air as a competing ligand, which provides new insights into the design of ILA-based macroscopic liquid superlubricants with a high load-bearing capacity.
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Podosomes play crucial roles in macrophage adhesion and migration. Wiskott-Aldrich syndrome protein (WASP; also known as WAS)-mediated actin polymerization is one of the key events initiating podosome formation. Nevertheless, membrane signals to trigger WASP activation at macrophage podosomes remain unclear. Here, we show that phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] lipids are enriched at the podosome and stably recruit WASP rather than the WASP-5KE mutant. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit ß (PIK3CB) is spatially located at the podosome core. Inhibition of PIK3CB and overexpression of phosphatase and tensin homolog (PTEN) impede F-actin polymerization of the podosome. PIK3CB activation is regulated by Abl1 and Src family kinases. At the podosome core, Src and Hck promote the phosphorylation of Tyr488 in the consensus Y-x-x-M motif of Abl1, which enables the association of phosphoinositide 3-kinase (PI3K) regulatory subunits. Knockdown of Abl1 rather than Abl2 suppresses the PI3K/Akt pathway, regardless of Src and Hck activities. Reintroduction of wild-type Abl1 rather than the Abl1-Y488F mutant rescues PI3KR1 recruitment and PI3K activation. When PIK3CB, Abl1 or Src/Hck is suppressed, macrophage podosome formation, matrix degradation and chemotactic migration are inhibited. Thus, Src/Hck-mediated phosphorylation of Abl1 Tyr488 triggers PIK3CB-dependent PI(3,4,5)P3 production and orchestrates the assembly and function of macrophage podosomes.
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Podossomos , Actinas/genética , Actinas/metabolismo , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Podossomos/metabolismoRESUMO
The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.
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Apoptose , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Movimento Celular , Glioma/metabolismo , Glioma/patologia , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
Chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21 and it is amplified in many solid tumors. In this study, we intended to investigate the clinical significance of CHD1L expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that CHD1L was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of CHD1L was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan-Meier curve indicated that high expression of CHD1L may result in poor prognosis of glioma patients. Accordingly, suppression of CHD1L in glioma cells was shown to induce cell cycle arrest and increase apoptosis. In addition, knockdown of CHD1L significantly accelerated migration and invasion ability of glioma cells. Together our findings suggest that CHD1L is involved in the progression of glioma and may be a novel target for further therapy.
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Apoptose , Neoplasias Encefálicas/patologia , Ciclo Celular , Movimento Celular , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glioma/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Fase G1 , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Fase SRESUMO
The objective of the present study was to determine the effect of dietary oxidized konjac glucomannan (OKGM) and its acidolysis products (L-OKGM) on the immune parameters and the gene expression profile of some inflammatory-related cytokines from Schizothorax prenanti during the early stages of injection with Aeromonas hydrophila. Fish were orally administered with seven different diets containing 0 g kg(-1) (control diet), 8.0, 16.0 and 32.0 g kg(-1) OKGM and L-OKGM diets for 60 days prior to injection. After 60 days, the control and the treated fish were intraperitoneally injected with 0.2 ml PBS or 2 × 10(7) cfu/ml bacteria per fish and sampled at time 6 h post-injection. The results showed that the serum lysozyme activity and complement C3 level of fish fed 8.0 g kg(-1) L-OKGM was significantly increased after bacterial infection. Moreover, the injection with A. hydrophila generally up-regulated the expression of all measured genes when compared to their corresponding controls. When compared with the control group, the expression of TLR22, TNF-α and IL-1ß was significantly increased in fish fed OKGM and L-OKGM diet after bacterial injection. Furthermore, the L-OKGM diet showed higher activity to trigger the immune response against bacteria, especially the low dosage L-OKGM diet. The results suggested that both of OKGM and L-OKGM are promising feed additive for S. prenanti in aquaculture.
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Aeromonas hydrophila/imunologia , Cyprinidae , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata , Mananas/imunologia , Animais , Aquicultura , Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Mananas/química , Oxirredução , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In the present study, KGM was degraded by H2O2 and HCl to obtain two products with different molecular weights: oxidized konjac glucomannan (OKGM, 4.7 × 10(5) Da) and low-molecular-weight oxidized konjac glucomannan (L-OKGM, 9.2 × 10(3) Da). The effects of the two OKGM products on IL-1ß, TNF-α, and TLR22 gene expression, and immune parameters and the resistance to Aeromonas hydrophila of Schizothorax prenanti were determined. The results showed that the lysozyme activity was significantly enhanced by the L-OKGM diets. The SOD activity was significantly increased by both OKGM and L-OKGM diets. The MDA level of fish fed the OKGM and L-OKGM diets was significantly lower than the control group. IL-1ß mRNA level in the spleen significantly increased in all L-OKGM fed groups. The 8.0 g kg(-1) L-OKGM diet also significantly up-regulated IL-1ß gene expression in the head kidney. In the gut, IL-1ß mRNA levels were significantly higher in fish fed with the 8.0 g kg(-1) OKGM and 16.0 g kg(-1) L-OKGM diets. The TNF-α mRNA level of L-OKGM group significantly increased in the spleen, head kidney and gut. High dosing of OKGM significantly up-regulated TNF-α transcription in the head kidney, while only the 8.0 g kg(-1) OKGM group showed significantly higher TNF-α mRNA expression in the mesonephros. Fish fed the L-OKGM diets showed significantly higher expression of TLR22 in the spleen, head kidney and mesonephros. After the injection of A. hydrophila, the 8.0 g kg(-1) L-OKGM group showed a significantly higher survival rate than did the control group. Present study suggests that OKGM and L-OKGM can up-regulate immune-related gene expression and enhance disease resistance in S. prenanti, and L-OKGM exhibits higher immunomodulatory activity.
Assuntos
Cyprinidae , Suplementos Nutricionais , Mananas/farmacologia , Aeromonas hydrophila , Animais , Cyprinidae/sangue , Cyprinidae/genética , Cyprinidae/imunologia , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Rim Cefálico/metabolismo , Interleucina-1beta/genética , Mucosa Intestinal/metabolismo , Malondialdeído/sangue , Mananas/química , Muramidase/sangue , RNA Mensageiro/metabolismo , Baço/metabolismo , Superóxido Dismutase/metabolismo , Receptores Toll-Like/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
The low concentration of water-based lubricants and the high chemical inertness of the additives involved are often regarded as basic norms in the design of liquid lubricants. Herein, a novel liquid superlubricant of an aqueous solution containing a relatively high concentration of salt, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), is reported for the first time, and the superlubricity stability and load-bearing capacity of the optimized system (MgO0.10/LiTFSI10) are effectively strengthened by the addition of only trace (0.10 wt %) water-chemically active MgO additives. It demonstrates higher applicable loads, lower COF (â¼0.004), and stability relative to the base solution. Only a trace amount of MgO additive is needed for the superlubricity, which makes up for the cost and environmental deficiencies of LiTFSI10. The weak interaction region between free water and the outer-layer water of Li+ hydration shells becomes a possible ultralow shear resistance sliding interface; the Mg(OH)2 layer, generated by the reaction of MgO with water, further creates additional weakly interacting interfaces, leading to the formation of an asymmetric contact between the clusters/particles within the hydrodynamic film by moderating the competition between interfacial water and free water, thus achieving high load-bearing macroscopic superlubricity. This study deepens the contribution of electrolyte concentration to ionic hydration and superlubricity due to the low shear slip layer formed by interfacial water competition with water-activated solid additives, providing new insights into the next generation of high load-bearing water-based liquid superlubricity systems.
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Two new species of the "Aequales" of genus Gieysztoria were collected and described from an artificial lake on the Shenzhen University campus. Gieysztoria bimaculata n. sp., is distinguished based on two groups clavate pigmentations dorsally between the pharynx and intestine, and has a sclerotic stylet comprising a proximal girdle with 40-46 distal dagger-shape spines, thus has the maximum number of spines within "Aequales" group. Gieysztoria guangdongensis n. sp. has a sclerotic stylet with a proximal girdle and 18 distal blade-shaped spines. Comparison with similar species based mainly on stylet morphology suggests that Gieysztoria bimaculata n. sp. and Gieysztoria guangdongensis n. sp. are apparently different from the known species of Gieysztoria in this moment. In addition, the stability of the amount of distal spines of "Aequales" species is briefly discussed.
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Platelmintos/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Animais , China , Ecossistema , Feminino , Lagos , Masculino , Platelmintos/anatomia & histologiaRESUMO
Carbonates have great potential for development, but the use of propped hydraulic fracturing or acid fracturing stimulation types alone has limited effectiveness. This study collected four sets of rock samples from three carbonate reservoirs: dolomite, limy dolomite, and limestone. The laboratory analysis focuses on propped hydraulic fracturing, acid fracturing, and acid fracturing plus proppants of these rock types. The aim is to assess acid erosion, proppant embedment depth, and the impact of varying proppant sizes and acid injection on fracture conductivity. The results showed that acid fracturing substantially enhanced the hydraulic conductivity of the three rocks. The embedded depth of the small-sized proppant was greater, but the fracture conductivity of the large-sized proppant was greater. Under the conditions of the actual pressure of formation of 55.2 MPa in the target reservoir, using 70/140 mesh proppant, 20% thickened acid, and an injection rate of 20 mL/min: for the dolomite-type rock, the propped hydraulic fracturing method had the highest fracture conductivity, which reached 151.17 D·cm. For the limy dolomite-type rock, the acid fracturing plus proppant experiment had the highest fracture conductivity, which was 157.26 D·cm. For limestone-type rocks, acid fracturing had the highest fracture conductivity of 210.39 D·cm. This study helps to elucidate the mechanism of different stimulation types and provides useful guidance for the more effective development of carbonate oil and gas reservoirs.
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A high load-carrying capacity is the key to the practicality of liquid superlubricity, but it is difficult to achieve high load and low friction simultaneously by relying solely on a liquid film. Herein, a choline chloride-based ionic liquid analogue (ILA) macroscale superlubricant is first reported by tuning down strong hydrogen bonding in the ILA via introducing 2-10 wt % water, with a high load of 160 MPa and a low coefficient of friction of 0.006-0.008. In situ Raman reveals that competitive exchange between external water and crystalline water induces weak H-bond-dominated incomplete hydration, conferring a low-shear interface and considerable load-carrying capacity inside the lubricant. It is a hydrodynamic lubrication film rather than a tribochemical/physical adsorption film, allowing it to be applied to friction pairs of various materials. This study unveils the principle of water mediation of high-viscosity ILAs and also provides new insights into the design of practical ILA-based superlubrication materials with high load-carrying capacity.
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Concurrent chemoradiotherapy (CRT) is regarded as the standard treatment for inoperable esophageal cancers (EC). It is still controversial whether consolidation chemotherapy (CCT) or induction chemotherapy (IC) is beneficial for the patients who received CRT. Therefore, we carried out a retrospective analysis at our institution. A total of 186 inoperable EC patients from 20 October 2017 to 7 June 2021 who have previously received CRT were included in our study. The patients were divided into IC + CRT (n = 52), CCRT (n = 64), and CRT + CCT (n = 70) groups according to whether they received induction chemotherapy, consolidation chemotherapy, or not. We used Kaplan−Meier statistics to analyze their 1-, 2-, and 3-year OS. The median follow-up time for the whole group was 14.15 months. The 1-, 2-, 3- year overall survival (OS) for the CCRT group were 72.2%, 52.5%, and 29.5%, and 50.9%, 37.5%, and 25% for the IC + CRT group (p > 0.05). For the CRT + CCT group,1-, 2-, and 3-year OS were 89.8%, 59.0%, and 42.5% (p < 0.05). Adverse reactions in the three groups were mainly graded 0−3. The difference between the three groups was not statistically significant (p > 0.05). For non-surgical EC patients who received CRT, CCT after CRT but not IC before CRT can improve 1-, 2-, and 3-year OS with a low incidence of associated severe adverse effects. As a result, the addition of consolidation chemotherapy to chemoradiotherapy has significant prognostic advantages for inoperable EC patients.
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Quimioterapia de Consolidação , Neoplasias Esofágicas , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Quimioterapia de Indução , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Radiotherapy (RT) is the main treatment for unoperated esophageal cancer (EC) patients. It is controversial whether adding chemotherapy (CT) to RT is beneficial for elderly EC patients. The purpose of our study was to compare the efficacy of chemoradiotherapy (CRT) with RT alone for non-surgical elderly esophageal cancer patients. METHODS: A total of 7,101 eligible EC patients older than 65 years diagnosed between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. All the samples were divided into the radiotherapy group and the chemoradiotherapy group. After being matched by propensity score matching (PSM) at a 1:1 ratio, 3,020 patients were included in our analysis. The Kaplan-Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). RESULTS: After PSM, the clinical characteristics of patients between the RT and CRT groups were comparable. For EC patients older than 65 years, the 3-year OS and CSS in the CRT group were 21.8% and 27.4%, and the 5-year OS and CSS in the CRT group were 12.7% and 19.8%, respectively. The 3-year OS and CSS in the RT group were 6.4% and 10.4%, and the 5-year OS and CSS in the RT group were 3.5% and 7.2%, respectively. Next, these patients were divided into five subgroups based on the age stratification (ages 65-69; 70-74; 75-79; 80-84; ≥85). In each subgroup analysis, the 3- and 5-year OS and CSS showed significant benefits in the CRT group rather than in the RT group (all p < 0.05). We were unable to assess toxicities between the two groups due to a lack of correlated information. CONCLUSIONS: CRT could improve OS and CSS for non-surgical EC patients older than 65 years. Adding chemotherapy to radiation showed a significant prognostic advantage for elderly esophageal cancer patients.
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To combine the advantages of micelles and biomimetic silica materials, biomimetic micellar mesoporous silica xerogel (BM-SX) was initially established, biomimetic silica xerogel (B-SX) was also studied as control and nitrendipine (NDP) was taken as model drug. The content mainly focused on drug dissolution, systemic stability and cellular transmembrane transport of NDP loaded B-SX and NDP loaded BM-SX. With extra mesopores formed due to HPMC E50 micelles, the mean pore diameter, surface area and pore volume of BM-SX were all larger than B-SX. After loading NDP into the two carriers, crystal NDP changed to amorphous phase, leading to enhanced NDP dissolution. BM-SX presented superior abilities not only for its higher drug dissolution compared to B-SX but also for its capacity in remaining high amorphous drug phase and therefore no drug dissolution reduction can be observed. The dynamic contact angle result confirmed the strong power of HPMC E50 micelles in maintaining amorphous NDP in the carrier to improve high systemic stability. Both B-SX and BM-SX could increase drug absorption permeability and exert function as drug efflux inhibitor to inhibit the efflux effect of p-gp drug pump and promote NDP absorption and transport, and BM-SX was superior owing to micelles in the system.
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Nitrendipino , Dióxido de Silício , Biomimética , Portadores de Fármacos , Micelas , Porosidade , SolubilidadeRESUMO
The applicability of sludge biochar catalyst (SBC) coupling with ultrasound (US) irradiation for the simultaneous removal of Pb(II) and phenol was firstly investigated in this study. Results indicate that Pb(II) removal of SBC/US process was superior to that of SBC without US. The inhibitory order of the coexisting anions on Pb(II) removal was PO43- > HCO3- > NO3- > F- > SO42- > Cl-. Also, several coexisting metals ions inculding Cr(VI), Ni(II) and Cu(II) could be removed in a simultaneous manner with Pb(II). A high removal performance of Pb(II) by SBC/US process and its synergism with phenol oxidation had been successfully achieved. The simultaneous removal efficiencies of Pb(II) and phenol were high up to 95% within 60 min at optimum reaction conditions. Four kinds of Pb species inculding Pb0, PbCO3, PbO and Pb(OH)2 were formed during the reaction, whereas five kinds of transformation compounds of phenol such as 1,4-benzoquinone, acetic acid, formic acid, maleic acid and propionic acid were detected. Both HO and O2- contributed to the oxidation of phenol by SBC/US process, but HO was dominant radical. A reaction mechanism for the synergistic removal of Pb(II) and phenol by SBC/US process involving in four stages-namely adsorption, precipitation, reduction and Fenton-like oxidation processes was proposed. This study demonstrates that SBC/US process could be considered as a potential candidate for the remediation of real wastewaters containing Pb(II) and phenol.
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Esgotos , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Chumbo , Fenol , Fenóis/análise , Poluentes Químicos da Água/análiseRESUMO
The purpose of this study was to facilely develop biomimetic amino modified mesoporous silica xerogel (AMSX) and study how AMSX regulated loading and in vitro sustained delivery of carboxyl-containing drug levorotary ofloxacin (LOFL). Characteristics of AMSX, including morphology, porous structure, elements and crystalline state were investigated and pharmaceutical performance of AMSX for the delivery of LOFL was studied. The result showed that AMSX was accumulational spherical nanoparticles with mesoporous structure. Hydrogen bonding force was formed between carboxylic groups of LOFL and amino groups grafted on the surface of AMSX. Furthermore, a three-level three-factorial Box-Behnken experimental design was applied to optimize the amount of major agent for synthesizing AMSX with expected drug loading capacity and also to figure out how AMSX regulated in vitro delivery of LOFL. It is believed that the present work will provide novel insights for designing mesoporous silica as drug carrier and favored the development of sustained release system.
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Géis/química , Ofloxacino/química , Dióxido de Silício/química , Portadores de Fármacos/química , Ligação de Hidrogênio , Nanopartículas/química , Ofloxacino/metabolismo , Porosidade , MolhabilidadeRESUMO
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for nonsurgical esophageal cancer (EC). However, esophageal cancer patients receiving CCRT alone are still unsatisfactory in terms of local control and overall survival (OS) benefit. Clinicians generally add consolidation chemotherapy (CCT) after CCRT. It remains controversial whether CCT following CCRT is beneficial for esophageal cancer. We, therefore, undertook a meta-analysis to assess the need for CCT in inoperable esophageal cancer. MATERIALS AND METHODS: We combed PubMed, Embase, Cochrane Library, Web of Science, and CNKI for relevant published articles up to July 2020 that compared CCRT plus CCT to CCRT alone for patients with nonsurgical EC. Our primary endpoint was OS and progression-free survival (PFS), and the secondary endpoint was treatment toxicity. We analyzed the hazard ratio (HR) to estimate the time-to-event data and the odds ratio (OR) to compare the treatment-related effect. To assess heterogeneity, we performed the I2 test and examined publication bias using funnel plots analysis. RESULTS: The 11 retrospective studies involved 2008 patients. Of these 2008 patients, 1018 received CCRT plus CCT, and 990 received CCRT. Compared to CCRT alone, CCT after CCRT did not improve disease control rate (DCR) (OR 1.66; 95% CI 0.53-5.15, p=0.384) and objective response rate (ORR) (OR 1.44; 95% CI 0.62-3.35, p=0.393). However, OS (HR 0.72; 95% CI 0.59-0.86, p < 0.001) and PFS (HR 0.61; 95% CI 0.44-0.84, p=0.003) did increase. Our results show that CCT plus CCRT had a clear survival advantage over CCRT alone. The risk of treatment toxicity did not increase for EC patients who received CCT. CONCLUSION: CCT after CCRT significantly increases OS and PFS in patients with nonsurgical EC and could provide them remarkable survival benefits. The results provide an evidence-based framework for the use of CCT after CCRT.
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Tripartite motif 33 (TRIM33), a member of the transcription intermediate factor 1 (TIF1) family of transcription cofactors, mediates transforming growth factor-beta (TGF-ß) signaling through its PHD-Bromo cassette in mesendoderm differentiation during early mouse embryonic development. However, the role of the TRIM33 RING domain in embryonic differentiation is less clear. Here, we report that TRIM33 mediates Wnt signaling by directly regulating the expression of a specific subset of Wnt target genes, and this action is independent of its RING domain. We show that TRIM33 interacts with ß-catenin, a central player in Wnt signaling in mouse embryonic stem cells (mESCs). In contrast to previous reports in cancer cell lines, the RING domain does not appear to function as the E3 ligase for ß-catenin, since neither knockout nor overexpression of TRIM33 had an effect on ß-catenin protein levels in mESCs. Furthermore, we show that although TRIM33 seems to be dispensable for Wnt signaling through a reporter assay, loss of TRIM33 significantly impairs the expression of a subset of Wnt target genes, including Mixl1, in a Wnt signaling-dependent manner. Together, our results indicate that TRIM33 regulates Wnt signaling independent of the E3 ligase activity of its RING domain for ß-catenin in mESCs.
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Diferenciação Celular/genética , Células-Tronco Embrionárias Murinas/metabolismo , Fatores de Transcrição/genética , Via de Sinalização Wnt/genética , Animais , Linhagem Celular , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Ligação Proteica , Fatores de Transcrição/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Gliomas are the most common primary brain tumors of the central nervous system (CNS). Due to the poor prognosis of glioma patients, it is urgent to develop more effective therapies. Deltex-3-like (DTX3L), also known as B-lymphoma and BAL-associated protein (BBAP), has been reported to play an important role in the progression of many tumors. This study aimed to investigate the clinical significance and biological function of DTX3L in human glioma. Clinically, the protein expression level of DTX3L is increased in glioma tissues compared with that observed in normal brain tissues. Immunohistochemical analysis demonstrated that DTX3L was highly expressed in the glioma tissues and its level was correlated with the grade of malignancy. Multivariate analysis revealed the association between high expression of DTX3L and the poor prognosis of glioma patients. In addition, knockdown of DTX3L by siRNA transfection increased glioma cell apoptosis. Moreover, suppression of DTX3L expression was shown to significantly inhibit the migration and invasion of glioma cells. These data indicate that DTX3L plays an important role in the pathogenic process of glioma, suggesting that DTX3L could be a potential prognostic biomarker for glioma.
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Neoplasias Encefálicas/genética , Glioma/genética , Ubiquitina-Proteína Ligases/genética , Regulação para Cima , Apoptose , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Glioma/diagnóstico , Glioma/patologia , Humanos , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/genética , Ubiquitina-Proteína Ligases/análiseRESUMO
RBQ3, also known as RBBP5 (RB-binding protein 5), was an RB-binding protein. Besides, it was one of core components of MLL1 (mixed lineage leukemia 1), which were required for H3K4 methyltransferase activity. MLL1 dysfunction was found to be associated with the progression of some cancers such as acute leukemias. However, the precise role of RBQ3 in tumor progression remains obscure. In this study, we explored the expression and clinical role of RBQ3 in gliomas. Our results showed that RBQ3 was significantly upregulated in clinical glioma specimens by Western blot and immunohistochemistry. Moreover, its level was significantly associated with the pathology grades. High RBQ3 expression was suggested to be an independent prognostic factor for glioma patients' survival by univariate and multivariate analyses. Serum starvation and refeeding assay indicated that the expression of RBQ3 increased 8h after serum-stimulation, together with percentage of cells at S phase. In addition, knockdown of RBQ inhibited U87-MG cell proliferation with CCK8 kit, flow cytometry assays and colony formation analyses; while the depletion of RBQ3 induced the apoptosis of U87-MG cells. All the findings suggested that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents.
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Neoplasias Encefálicas/patologia , Encéfalo/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Proteínas Nucleares/metabolismo , Adulto , Apoptose/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura Livres de Soro/farmacologia , Proteínas de Ligação a DNA , Feminino , Glioma/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Sincalida/metabolismo , TransfecçãoRESUMO
OBJECTIVE: To investigate changes in the expression of sarcoplamic reticular Ca(2+)-ATPase (SERCA) and IP(3)-I receptors (IP(3)R(1)) mRNA in patients with atrial fibrillation. METHODS: Thirty-eight patients with mitral stenosis undergoing open heart surgery were studied. 100 mg of atrial tissue was obtained during surgery from the right appendage and the right atrium. The amount of messenger ribonucleic acid (mRNA) amount of SERCA and IP(3)R(1) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). RESULTS: Levels of mRNA expression of SERCA in patients with AF, as compared with subjects in sinus rhythm, was lower and that of IP(3)R(1) was higher. The longer AF was sustained, the higher the levels of mRNA. There was no significant difference between right atrial free wall and right appendage. CONCLUSIONS: The expression changes of SERCA and IP3R mRNA may correlate with the initiation or maintenance of AF.