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1.
Genomics ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33894310

RESUMO

This study aimed to investigate the function of OCT3/4 on tumor immune escape in bladder cancer. Initially, the expression of OCT3/4, TET1, NRF2 and MDM2 was quantified in tumor tissues and cells, followed by gain- or loss-of-function studies to define their roles in cell migration, invasion and apoptosis and tumorigenicity in nude mice. Bladder cancer presented with abundant expression levels of OCT3/4, TET1, NRF2 and MDM2. We found that OCT3/4 promoted TET1 expression via binding to its promoter and that TET1 recruited MLL protein to NRF2 promoter and upregulated its expression, while NRF2 enhanced MDM2 expression. Upregulated MDM2 accelerated tumor immune escape in bladder cancer in mice. OCT3/4 knockdown suppressed the cell migration and invasion while inducing apoptosis, and consequently prevented tumor growth and immune escape in mice. Collectively, OCT3/4 may promote the progression of tumor immune escape in bladder cancer through acting as a promoter of the TET1/NRF2/MDM2 axis.

2.
Circ J ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33504712

RESUMO

BACKGROUND: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture. CONCLUSIONS: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

3.
Ann Transl Med ; 8(16): 1011, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953811

RESUMO

Background: Cardiovascular disease (CVD) poses a serious threat to human health. Research shows that ABO blood groups, especially non-O blood types, are closely related to the incidence of cardiovascular diseases (CVDs). This study aimed to determine the associations of blood types with non-culprit coronary plaque characteristics using optical coherence tomography (OCT). Methods: A total of 257 acute coronary syndrome (ACS) patients (average age, 59.39±10.08 years, 80% male) who underwent OCT of 3 vessels were identified. Subjects were divided into 2 groups: the O blood group (71 patients with 121 plaques) and the non-O group (186 patients with 329 plaques). The non-culprit coronary plaque features of the two groups were compared using OCT. Results: The non-type O group had larger lipid arcs, thinner fibrous caps, and a greater number of thin-cap fibro atheromas (TCFAs). The type A, B, and AB blood groups had larger lipid arcs than the type O blood group, as well as thinner fibrous caps and more TCFAs. The type A blood group had thinner fibrous caps and a greater number of TCFAs than the type B and AB blood groups. Conclusions: ACS patients with type non-O blood had more non-culprit plaques. Patients with type A blood, in particular, had more vulnerable characteristics than those with type O blood.

4.
Channels (Austin) ; 14(1): 246-256, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32752916

RESUMO

The elevated intracellular Ca2+ and oxidative stress are well-reported mechanisms behind renal tubular epithelial injury initiated by various insults. Given that TRPV4 and connexin43 (Cx43) channels are activated by a wide range of stimuli and regulate both intracellular Ca2+ and redox status, we speculated an involvement of these channels in renal tubular cell injury. Here, we tested this possibility and explored the potential underlying mechanisms. Our results demonstrated that exposure of renal tubular epithelial cells to aminoglycoside G418 led to cell death, which was attenuated by both TRPV4 and gap junction (Gj) inhibitor. Activation of TRPV4 caused cell damage, which was associated with an early increase in Cx43 expression and function. Inhibition of Cx43 with chemical inhibitor or siRNA largely prevented TRPV4 activation-induced cell damage. Further analysis revealed that TRPV4 agonists elicited a rise in intracellular Ca2+ and caused a Ca2+-dependent elevation in TXNIP (a negative regulator of the antioxidant thioredoxin). In the presence of Gj inhibitor, however, these effects of TRPV4 were largely prevented. The depletion of intracellular Ca2+ with Ca2+ chelator BAPTA-AM or downregulation of TXNIP with siRNA significantly alleviated TRPV4 activation-initiated cell injury. Collectively, our results point to a critical involvement of TRPV4/Cx43 channel interaction in renal tubular cell injury through mechanisms involving a synergetic induction of intracellular Ca2+ and oxidative stress. Channel interactions could be an important mechanism underlying cell injury. Targeting channels could have therapeutic potential for the treatment of acute tubular cell injury.

5.
Int J Mol Sci ; 21(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098345

RESUMO

Nitrogen (N) is the most important limiting factor for cotton production worldwide. Genotype-dependent ability to cope with N shortage has been only partially explored in cotton, and in this context, the comparison of molecular responses of cotton genotypes with different nitrogen use efficiency (NUE) is of particular interest to dissect the key molecular mechanisms underlying NUE. In this study, we employed Illumina RNA-Sequencing to determine the genotypic difference in transcriptome profile using two cotton genotypes differing in NUE (CCRI-69, N-efficient, and XLZ-30, N-inefficient) under N starvation and resupply treatments. The results showed that a large genetic variation existed in differentially expressed genes (DEGs) related to amino acid, carbon, and nitrogen metabolism between CCRI-69 and XLZ-30. Further analysis of metabolic changes in cotton genotypes under N resupply showed that nitrogen metabolism and aromatic amino acid metabolism pathways were mainly enriched in CCRI-69 by regulating carbon metabolism pathways such as starch and sucrose metabolism, glycolysis/gluconeogenesis, and pentose phosphate pathway. Additionally, we performed an expression network analysis of genes related to amino acid, carbon, and nitrogen metabolism. In total, 75 and 33 genes were identified as hub genes in shoots and roots of cotton genotypes, respectively. In summary, the identified hub genes may provide new insights into coordinating carbon and nitrogen metabolism and improving NUE in cotton.


Assuntos
Carbono/metabolismo , Perfilação da Expressão Gênica/métodos , Genes de Plantas/genética , Gossypium/genética , Redes e Vias Metabólicas/genética , Nitrogênio/metabolismo , Metabolismo Energético/genética , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genótipo , Gossypium/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo
6.
Plants (Basel) ; 9(2)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32075340

RESUMO

Cotton production is highly sensitive to nitrogen (N) fertilization, whose excessive use is responsible for human and environmental problems. Lowering N supply together with the selection of N-efficient genotypes, more able to uptake, utilize, and remobilize the available N, could be a challenge to maintain high cotton production sustainably. The current study aimed to explore the intraspecific variation among four cotton genotypes in response to various N supplies, in order to identify the most distinct N-efficient genotypes and their nitrogen use efficiency (NUE)-related traits in hydroponic culture. On the basis of shoot dry matter, CCRI-69 and XLZ-30 were identified as N-efficient and N-inefficient genotypes, respectively, and these results were confirmed by their contrasting N metabolism, uptake (NUpE), and utilization efficiency (NUtE). Overall, our results indicated the key role of shoot glutamine synthetase (GS) and root total soluble protein in NUtE. Conversely, tissue N concentration and N-metabolizing enzymes were considered as the key traits in conferring high NUpE. The remobilization of N from the shoot to roots by high shoot GS activity may be a strategy to enhance root total soluble protein, which improves root growth for N uptake and NUE. In future, multi-omics studies will be employed to focus on the key genes and pathways involved in N metabolism and their role in improving NUE.

7.
J Sci Food Agric ; 100(6): 2761-2773, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020619

RESUMO

BACKGROUND: Although nitrogen (N) availability is a major determinant of cotton production, little is known about the importance of plants' preference for ammonium versus nitrate for better growth and nitrogen use efficiency (NUE). We aimed to assess the growth, physiology, and NUE of contrasting N-efficient cotton genotypes (Z-1017, N-efficient and GD-89, N-inefficient) supplied with low and high concentrations of ammonium- and nitrate-N. RESULTS: The results revealed that ammonium fed plants showed poor root growth, lower dry biomass, N content, leaf chlorophyll and gas exchange than those under nitrate irrespective of the concentration. However, the highest N uptake and utilization efficiency were obtained with nitrate fed plants, which also resulted in the highest dry biomass, N content, leaf chlorophyll and gas exchange as well as root growth. The results further confirmed that N-efficient (Z-1017) genotype performed better under both N sources, showing more flexibility to contrasting N condition by increasing growth and NUE in either source of N. Moreover, multivariate analysis showed a strong relationship of root morphological traits with N utilization efficiency, suggesting the physiological importance of roots over shoots in response to low nitrate concentration. CONCLUSION: Thus, it was confirmed that nitrate-N is superior to ammonium-N and the use of nitrate and N-efficient genotype is the best option for optimum cotton growth and NUE. Further, field evaluation is required to confirm the hypothesis that nitrate is a preferred N source for better cotton production and NUE. © 2020 Society of Chemical Industry.


Assuntos
Gossypium/crescimento & desenvolvimento , Gossypium/genética , Nitrogênio/metabolismo , Compostos de Amônio/metabolismo , Genótipo , Gossypium/metabolismo , Nitratos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
8.
Plants (Basel) ; 9(2)2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024197

RESUMO

Drought is one of the most important abiotic stresses and hampers many plant physiological processes under suboptimal nitrogen (N) concentration. Seedling tolerance to drought stress is very important for optimum growth and development, however, the enhancement of plant stress tolerance through N application in cotton is not fully understood. Therefore, this study investigates the role of high N concentration in enhancing drought stress tolerance in cotton. A hydroponic experiment supplying low (0.25 mM) and high (5 mM) N concentrations, followed by 150 g L-1 polyethylene glycol (PEG)-induced stress was conducted in a growth chamber. PEG-induced drought stress inhibited seedling growth, led to oxidative stress from excessive malondialdehyde (MDA) generation, and reduced N metabolism. High N concentrations alleviated oxidative damage and stomatal limitation by increasing antioxidant enzymatic activities, leaf relative water content, and photosynthesis in cotton seedlings under drought stress. The results revealed that the ameliorative effects of high N concentration may be ascribed to the enhancement of N metabolizing enzymes and an increase in the amounts of osmoprotectants like free amino acids and total soluble protein. The present data suggest that relatively high N concentrations may contribute to drought stress tolerance in cotton through N metabolism, antioxidant capacity, and osmotic adjustment.

10.
Pathol Oncol Res ; 26(3): 1583-1594, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31489573

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three over-expressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.

11.
Int J Mol Sci ; 20(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752090

RESUMO

Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43+/+) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43+/-) mouse. Consistently, spleen cells from Cx43+/+ mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43+/+ spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases.


Assuntos
Conexina 43/metabolismo , Imunoglobulina G/metabolismo , Lipopolissacarídeos/efeitos adversos , Baço/citologia , Animais , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunoglobulina G/sangue , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , NADPH Oxidase 2/metabolismo , Estresse Oxidativo , Carbonilação Proteica , Baço/imunologia , Tiorredoxinas/metabolismo
12.
Aging (Albany NY) ; 11(22): 10626-10643, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756170

RESUMO

In this study, we analyzed the role of circular RNAs in the growth and progression of bladder cancer. Direct Sanger sequencing and quantitative RT-PCR analysis showed that circ_0006332 was significantly upregulated in bladder cancer tissues. Sequencing analysis showed that circ_0006332 is generated from splicing of exons 8 and 9 of the MYBL2 transcript. Fluorescence in situ hybridization analysis showed that circ_0006332 was localized to the cytoplasm of bladder cancer cells. Dual luciferase reporter assays showed that miR-143 specifically bound to circ_0006332 and the 3'UTR of MYBL2. High expression of circ_006332 correlated with tumor-node-metastasis stages and muscular invasion in bladder cancer patients. Knockdown of circ_0006332 in bladder cancer cells decreased proliferation, colony formation and invasiveness. Circ_0006332 knockdown increased E-cadherin levels and decreased Vimentin, CCNB1 and P21 protein expression. This suggests that circ_0006332 promotes epithelial-mesenchymal transition and cell cycle progression. In vivo experiments in nude mice showed that circ_0006332 knockdown bladder cancer cells form significantly smaller tumors than the controls. Our study demonstrates that circ_0006332 promotes the growth and progression of bladder cancer by modulating MYBL2 expression by acting as a sponge for miR-143. Circ_0006332 is thus a potential early diagnostic marker of bladder cancer.


Assuntos
Proteínas de Ciclo Celular/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , RNA Circular/genética , Transativadores/biossíntese , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Animais , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Transativadores/genética , Neoplasias da Bexiga Urinária/genética
13.
Atherosclerosis ; 289: 94-100, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487565

RESUMO

BACKGROUND AND AIMS: About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS: 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS: Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ±â€¯1.7 mm2vs. 1.9 ±â€¯1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS: Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.


Assuntos
Angiografia Coronária , Coração/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroglicerina/farmacologia , Estudos Prospectivos , Fatores de Risco
14.
J Enzyme Inhib Med Chem ; 34(1): 1380-1387, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401884

RESUMO

Novel sulfonamide-dithiocarbamate hybrids were designed and synthesised via the molecular hybridisation strategy. Among them, compound 13d displayed a potent activity with IC50 values of 0.9, 0.7, 1.9 and 2.6 µM against UM-UC-3, RT-112, RT4 and T24. Compound 13d inhibited the migration and regulated the migration-related markers (E-cadherin, N-cadherin, Vimentin, Snail and Slung) against RT-112 cells in a concentration dependent manner. By the tubulin polymerisation assay in vitro and immunostaining assay, compound 13d was identified as a novel tubulin polymerisation inhibitor. Intragastric administration of compound 13d could inhibit the growth of RT-112 cells in vivo in a xenograft mouse model with the low toxicity, indicating that it may be a leading candidate with antitumor properties to treat bladder cancer.


Assuntos
Antineoplásicos/farmacologia , Sulfonamidas/farmacologia , Moduladores de Tubulina/farmacologia , Neoplasias da Bexiga Urinária/patologia , Animais , Antineoplásicos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectrometria de Massas , Camundongos , Camundongos Nus , Espectroscopia de Prótons por Ressonância Magnética , Sulfonamidas/química , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Antioxid Redox Signal ; 31(16): 1194-1212, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319679

RESUMO

Aims: Inflammasome activation plays a pivotal role in many inflammatory diseases. Given that connexin (Cx) channels regulate numerous cellular events leading to inflammasome activation, we determined whether and how connexin affected inflammasome activation and inflammatory cell injury. Results: Exposure of mouse peritoneal macrophages (PMs) to lipopolysaccharide (LPS) plus ATP caused NLRP3 inflammasome activation, together with an increased connexin43 (Cx43). Inhibition of Cx43 blunted inflammasome activation. Consistently, PMs from the Cx43 heterozygous mouse (Cx43+/-) exhibited weak inflammasome activation, in comparison with those from the Cx43+/+ mouse. Further analysis revealed that inflammasome activation was preceded by an increased reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 2 (NOX2), protein carbonylation, and mitogen-activated protein kinase (MAPK) activation. Suppression of ROS with antioxidant, downregulation of NOX2 with small interfering RNA (siRNA), or inhibition of NADPH oxidase or MAPKs with inhibitors blocked Cx43 elevation and inflammasome activation. Intriguingly, suppression of Cx43 also blunted NOX2 expression, protein carbonylation, p38 phosphorylation, and inflammasome activation. In a model of acute renal injury induced by LPS, the Cx43+/- mouse exhibited a significantly lower level of blood interleukin-1ß (IL-1ß), blood urea nitrogen, and urinary protein, together with milder renal pathological changes and renal expression of NLRP3 and NOX4, as compared with the Cx43+/+ mouse. Moreover, inhibition of gap junctions suppressed IL-1ß- and tumor necrosis factor-α-induced expression of NOX4 in glomerular podocytes and tubular epithelial cells. Innovation and Conclusion: Our study indicates that Cx43 contributes to inflammasome activation and the progression of renal inflammatory cell injury through modulation of intracellular redox status. Cx43 could be a novel target for the treatment of certain inflammatory diseases.


Assuntos
Lesão Renal Aguda/metabolismo , Conexina 43/metabolismo , Inflamassomos/metabolismo , Espaço Intracelular/metabolismo , Lipopolissacarídeos , Estresse Oxidativo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Ânions/análise , Ânions/metabolismo , Linhagem Celular , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/análise , Superóxidos/metabolismo
16.
Biomed Res Int ; 2019: 9681863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984788

RESUMO

Abnormal expression of noncoding RNA molecules such as circRNA plays an important role in the development of malignant tumors. circRNAs are stable in structure and can be useful as ideal tumor markers. Advanced bladder cancer has poor treatment options and prognosis. Thus, we examined circRNAs to further understand the pathogenesis and development of bladder cancer and to identify molecular markers for the early diagnosis of bladder carcinoma. We found that hsa_circ_0018069 was differentially expressed in our RNA sequencing data. We used qRT-PCR to detect its expression in T24 and Biu-87 cell lines and in 41 paired samples of bladder cancer and adjacent normal tissue and analyzed the correlation between expression of hsa_circ_0018069 and the clinical characteristics of patients with bladder cancer. We then performed a bioinformatics analysis to reveal the mechanism of hsa_circ_0018069 in tumorigenesis of bladder cancer. The expression of hsa_circ_0018069 was significantly reduced in T24 and Biu-87 cells and was also significantly downregulated in bladder cancer tissues. Decreased expression of hsa_circ_0018069 was related to the grade stage (P=0.024), T stage (P=0.027), and muscular invasion depth (P=0.022) of bladder cancer. Bioinformatics analysis showed that hsa_circ_0018069 was coexpressed with protein-coding mRNAs that participate in cytoskeletal protein binding and cell-substrate junction assembly and play an anticancer role through focal adhesion and calcium signaling pathways. ceRNA analysis showed that hsa_circ_0018069 functions in ErbB, Ras, FoxO, and the focal adhesion signaling pathway by harboring miR-23c, miR-34a-5p, miR-181b-5p, miR-454-3p, and miR-3666. hsa_circ_0018069 may thus play an important role in the occurrence and progression of bladder cancer and serve as a valuable biomarker for the early diagnosis of this disease.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , RNA/genética , Neoplasias da Bexiga Urinária/sangue , Idoso , Biomarcadores Tumorais/genética , Sinalização do Cálcio , Carcinoma/genética , Carcinoma/patologia , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA/sangue , RNA Circular , RNA Mensageiro/sangue , Análise de Sequência de RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
17.
Oncol Lett ; 17(4): 3874-3880, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30881506

RESUMO

Long non-coding RNAs (lncRNAs) may serve an important role in cancer development and may also be suitable for use as prognostic biomarkers. At present, the role of lncRNAs in bladder cancer remains unclear. The present study examined the potential involvement of lncRNA LINC00460 in bladder urothelial carcinoma using data from The Caner Genome Atlas (TCGA) and cell line experiments. The results indicated that LINC00460 expression levels were increased in bladder urothelial carcinoma tissues and bladder cancer 5637 and T24 cell lines compared with corresponding normal controls (P<0.05). TCGA data indicated that LINC00460 expression was negatively correlated with a positive prognosis in patients with bladder urothelial carcinoma (P<0.05). Consistently, the downregulation of LINC00460 with short hairpin RNA significantly suppressed 5637 and T24 cell proliferation and migration. Therefore, it was suggested that strategies that target LINC00460 may be developed as novel therapeutic approaches for the treatment of bladder cancer. In addition, the expression level of androgen receptor (AR) was downregulated in bladder urothelial carcinoma tissues and exhibited a negative correlation with the expression level of LINC00460 (r=-0.43; P<0.0001), based on the data from TCGA. We hypothesized that LINC00460 may serve an oncogenic role by regulating the expression of AR.

18.
Free Radic Biol Med ; 134: 190-199, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30639567

RESUMO

Hydrogen sulfide (H2S) is a gaseous mediator with multifaceted biological activities. It has anti-inflammatory and anti-oxidative effects. Currently, the mechanisms are not fully understood. Given that Trx/ASK1/P38 signaling pathway mediates many oxidative cell responses, we tested whether and how H2S affected this pathway. Exposure of podocytes to Adriamycin (ADR), an antitumor drug, led to a P38-mediated oxidative cell injury, as evidenced by the increased protein carbonylation, oxidative activation of P38, and prevention of the cell death by antioxidants, NADPH oxidase inhibitor and P38 inhibitor. In the presence of H2S donor NaHS, however, the podocyte injury was largely prevented. NaHS also significantly prevented cell death elicited by H2O2, menadione, and thioredoxin (Trx) inhibitors. These effects of H2S were also associated with a potent inhibition of P38. Further analysis revealed that H2S did not affect the protein level of TXNIP and Trx, two pivotal regulators of ASK1/P38 activation, but it promoted the dissociation of Trx from TXNIP. Moreover, it disrupted the H2O2-initiated polymerization of Trx and converted Trx from the oxidized to the reduced form. In HepG2 cells, inhibition of H2S-producing enzyme cystathionine γ-lyase (CSE) increased Trx oxidation, promoted Trx binding to TXNIP and exaggerated cell injury caused by Trx inhibition. Collectively, our results indicate that H2S exerted its antioxidative effects through the regulation of the redox state of Trx and interference with Trx/ASK1/P38 signaling pathway. Given the importance of the pathway in the mediation of multiple oxidative cell responses, our study thus provides novel mechanistic insight into the action of H2S.


Assuntos
Doxorrubicina/toxicidade , Sulfeto de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tiorredoxinas/química , Animais , Antibióticos Antineoplásicos/toxicidade , Células Cultivadas , Gasotransmissores/farmacologia , Células Hep G2 , Humanos , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , Oxirredução , Podócitos/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Sci Rep ; 9(1): 86, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643161

RESUMO

In recent years, heavy metal pollution has become a more serious global problem, and all countries are actively engaged in finding methods to remediate heavy metal-contaminated soil. We conducted transcriptome sequencing of the roots of cotton grown under three different cadmium concentrations, and analysed the potential strategies for coping with cadmium stress. Through Gene Ontology analysis, we found that most of the genes differentially regulated under cadmium stress were associated with catalytic activity and binding action, especially metal iron binding, and specific metabolic and cellular processes. The genes responsive to cadmium stress were mainly related to membrane and response to stimulus. The KEGG pathways enriched differentially expressed genes were associated with secondary metabolite production, Starch and sucrose metabolism, flavonoid biosynthesis, phenylalanina metalism and biosynthesis, in order to improve the activity of antioxidant system, repair systems and transport system and reduction of cadmium toxicity. There are three main mechanisms by which cotton responds to cadmium stress: thickening of physical barriers, oxidation resistance and detoxification complexation. Meanwhile, identified a potential cotton-specific stress response pathway involving brassinolide, and ethylene signaling pathways. Further investigation is needed to define the specific molecular mechanisms underlying cotton tolerance to cadmium stress. In this study potential coping strategies of cotton root under cadmium stress were revealed. Our findings can guide the selection of cotton breeds that absorb high levels of cadmium.


Assuntos
Cádmio/toxicidade , Gossypium/efeitos dos fármacos , Poluentes do Solo/toxicidade , Estresse Fisiológico , Perfilação da Expressão Gênica , Gossypium/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética
20.
Biomed Pharmacother ; 107: 1093-1103, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30257321

RESUMO

BACKGROUND: As an inorganic compound used to treat various cancers and other diseases, arsenic trioxide (As2O3) has been reported to induce cellular apoptosis in certain kinds of cancers including bladder cancer. The aim of the present study was to elucidate the crucial cooperative role of As2O3 and intravesical bacillus Calmette-Guerin (BCG) immunotherapy and its ability to protect against bladder cancer by targeting the IER3/Nrf2 pathway. METHOD: Initially, an orthotopic bladder cancer model was established in mice by means of intravesical instillation of the human bladder cancer cell line 5637. The expression of IL-6/IL-8 in dendritic cells (DCs) and the proportion of CD4+ cells and ratio of CD4+/CD8+ T cells were subsequently determined. RT-qPCR and Western blot assay methods were employed to determine the expressions of IER3, Nrf2, NQO1, IL-6 and IL-8. Finally, tumor cell apoptosis and the volume and weight of the in vivo tumors were evaluated in an attempt to determine the contributory role of As2O3 in combination with BCG immunotherapy in treating bladder cancer. RESULTS: The additive effect of As2O3 and BCG was demonstrated to promote the expressions of IL-6/IL-8 among DCs. Additionally, the proportion of CD4+ cells, ratio of CD4+/CD8+ T cells and rate of tumor cell apoptosis were all elevated, while decreased in vivo tumor volume and weight were detected. Of importance, we determined the role that ad-shNrf2 (adenoviral vectors expressing shRNA against Nrf2) played in inhibiting the effects of As2O3 on bladder cancer. CONCLUSION: Taken together, the key findings of the present study provide evidence defining the effect of As2O3 on inducing the inhibitory effect of BCG on the development of bladder cancer via the IER3/Nrf2 pathway, highlighting the potential of As2O3 as a treatment option for bladder cancer through its enhancement of intravesical BCG.


Assuntos
Trióxido de Arsênio/administração & dosagem , Vacina BCG/administração & dosagem , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Administração Intravesical , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Trióxido de Arsênio/farmacologia , Vacina BCG/imunologia , Western Blotting , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C3H , Fator 2 Relacionado a NF-E2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Bexiga Urinária/imunologia
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