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2.
Cell Discov ; 7(1): 62, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373445

RESUMO

Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.

3.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-33737494

RESUMO

It has been well investigated that circular RNAs (circRNAs) play important roles in various cancers. The function of circ_0002711 and its underlying mechanisms in ovarian cancer (OC) remain unknown. qRT-PCR and western blot were performed to detect the expressions of circ_0002711, microRNA-1244 (miR-1244), and Rho kinase 1 (ROCK1) in OC tissues and cells. MTT assay and colony formation assay were employed to evaluate cell proliferation. Detection of lactate production, glucose uptake, and ATP level and oxygen consumption were used to determine Warburg effect. Western blot was used to examine glycolysis or proliferationrelated genes. Dual-luciferase reporter assay and RIP pull down assay were used to address the relationship among circ_0002711, miR-1244, and ROCK1. In vivo tumor growth was evaluated in nude mice. Circ_0002711 was upregulated in OC tissues and cell lines. Circ_0002711 downregulation inhibited cell viability, colony formation ability and aerobic glycolysis. Circ_0002711 contained binding sites with miR1244. Moreover, loss of miR-1244 undermined circ_0002711 downregulation-mediated function. ROCK1 contained binding sites with miR-1244. MiR-1244 upregulation suppressed cell proliferation and aerobic glycolysis, which was rescued by enhanced expression of ROCK1. Circ_0002711 knockdown hampered ROCK1 expression by upregulating miR-1244 expression. Finally, decreased expression of circ_0002711 inhibited tumor growth in vivo. Circ_0002711/miR-1244/ROCK1 axis regulated Warburg effect and tumor growth in vivo.


Assuntos
Glicólise/genética , MicroRNAs/genética , Neoplasias Ovarianas/patologia , RNA Circular/genética , Quinases Associadas a rho/genética , Aerobiose , Animais , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33729889

RESUMO

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Assuntos
COVID-19 , Medição de Risco/métodos , COVID-19/epidemiologia , COVID-19/mortalidade , China , Hospitalização/estatística & dados numéricos , Humanos , Itália , Fatores de Risco
5.
Cell Metab ; 31(6): 1068-1077.e3, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32369736

RESUMO

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.


Assuntos
Glicemia/análise , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico/fisiologia , Hiperglicemia/sangue , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/mortalidade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
6.
Biomed Res Int ; 2019: 2035682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737654

RESUMO

Selenium has remained a controversial character in cancer research. While its antitumor effects have been widely demonstrated, further evidence is required to establish it as a robust treatment regime. Sodium selenite (SS), an inorganic selenium, reportedly affected the proliferation and redifferentiation of gastric cancer cells, but whether it could act as a complement to conventional chemotherapeutic drugs for combination therapy is uncertain. Herein, SGC-7901 and MGC-803 gastric cancer cells were treated with PADM (Ac-Phe-Lys-PABC-ADM), a prodrug of doxorubicin/adriamycin (ADM), and the combined antitumor effects of the two drugs were evaluated. Characterization after treatment revealed that although PADM exhibited antitumor effects individually by inhibiting the proliferation and migration of gastric cancer cells and inducing apoptosis, the addition of SS significantly amplified these effects. Furthermore, gastric cancer cell apoptosis triggered by the combined treatment of SS and PADM may involve the participation of mitochondrial apoptosis, as evidenced by the changes in mitochondrial morphology and occurrence of mitochondrial fission. Collectively, SS could be a strong complementary drug that accentuates the therapeutic potential of PADM in gastric cancer treatment and management, and its significance could contribute to unique and innovative anticancer strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Doxorrubicina/farmacologia , Pró-Fármacos/farmacologia , Selenito de Sódio/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Humanos , Mitocôndrias/efeitos dos fármacos
7.
Biomed Res Int ; 2019: 2486783, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531348

RESUMO

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacologia , Xenoenxertos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pró-Fármacos/farmacologia , Selenito de Sódio/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Xenoenxertos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Cancer Manag Res ; 10: 4145-4153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323670

RESUMO

Background: Colon cancer (CC) patients with early relapse usually have a poor prognosis. In this study, we aimed to identify a novel signature to improve the prediction of relapse-free survival (RFS) in CC. Methods: Four microarray datasets were merged into a training set (n=1,045), and one RNA-sequencing dataset was used as a validation set (n=384). In the training set, microarray meta-analysis screened out 596 common RFS-related genes across datasets, which were used to construct 177,310 gene pairs. Then, the LASSO penalized generalized linear model identified 16 RFS-related gene pairs, and a risk score was calculated for each sample according to the model coefficients. Results: The risk score demonstrated a good ability in predicting RFS (area under the curve [AUC] at 5 years: 0.724; concordance index [C-index]: 0.642, 95% CI: 0.615-0.669). High-risk patients showed a poorer prognosis than low-risk patients (HR: 3.519, 95% CI: 2.870-4.314). Subgroup analysis reached consistent results when considering multiple confounders. In the validation set, the risk score had a similar performance (AUC at 5 years: 0.697; C-index: 0.696, 95% CI: 0.627-0.766; HR: 2.926, 95% CI: 1.892-4.527). When compared with a 13-gene signature, a 15-gene signature, and TNM stage, the score showed a better performance (P<0.0001; P=0.0004; P=0.0125), especially for the patients with a longer follow-up (R2=0.988, P<0.0001). When the follow-up was >5 years (n=314), the score demonstrated an excellent performance (C-index: 0.869, 95% CI: 0.816-0.922; HR: 13.55, 95% CI: 7.409-24.78). Conclusion: Our study identified a novel gene-pair signature for prediction of RFS in CC.

9.
Medicine (Baltimore) ; 95(35): e4592, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27583873

RESUMO

BACKGROUND: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. METHODS: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. RESULTS: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. CONCLUSION: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/genética , Neoplasias Bucais/genética , Neoplasias Nasofaríngeas/genética , Proteínas de Ligação a Selênio/genética , Neoplasias Tonsilares/genética , Carcinoma de Células Escamosas/química , Intervalo Livre de Doença , Regulação para Baixo , Seguimentos , Expressão Gênica , Humanos , Neoplasias Hipofaríngeas/química , Neoplasias Hipofaríngeas/patologia , Hipofaringe/química , Neoplasias Laríngeas/química , Neoplasias Laríngeas/patologia , Laringe/química , Boca/química , Neoplasias Bucais/química , Neoplasias Bucais/patologia , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/patologia , Nasofaringe/química , Gradação de Tumores , Estadiamento de Neoplasias , Tonsila Palatina/química , Proteínas de Ligação a Selênio/análise , Taxa de Sobrevida , Neoplasias Tonsilares/química , Neoplasias Tonsilares/patologia
10.
Mol Med Rep ; 11(6): 4645-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25634687

RESUMO

Aberrant microRNA (miRNA) expression has been linked to cancer development. In this study, we aimed to investigate whether the anti­cancer effect of miRNA­299­3p on laryngeal cancer Hep­2 cells is mediated through targeting human telomerase reverse transcriptase (hTERT). The expression of miR­299­3p in laryngeal cancer Hep­2 cells and human osteosarcoma U2OS cells was quantified by stem­loop­mediated reverse transcription quantitative polymerase chain reaction. miR­299­3p mimic was transfected into Hep­2 cells to induce overexpression of miR­299­3p. A CCK­8 assay was performed to identify the effects of miR­299­3p overexpression on the proliferation of Hep­2 cells. Western blot analysis was carried out to determine the expression of hTERT protein. A significant decrease was noted in the expression of miR­299­3p in Hep­2 cells compared with that of U2OS cells (P<0.05). Overexpression of miR­299­3p resulted in a notable inhibition of cellular proliferation (P<0.05), as well as downregulation of hTERT mRNA and protein in Hep­2 cells (P>0.05). The expression of miR­299­3p is downregulated in human laryngeal cancer Hep­2 cells. Overexpression of miR­299­3p inhibits Hep­2 cell growth by targeting the 3'­untranslated region of hTERT mRNA.


Assuntos
MicroRNAs/metabolismo , Telomerase/metabolismo , Regiões 3' não Traduzidas , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Células HeLa , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Oligonucleotídeos Antissenso/metabolismo , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Telomerase/química , Telomerase/genética
11.
Cancer Biother Radiopharm ; 29(7): 289-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25153197

RESUMO

Global DNA hypomethylation, in particular that of the gene promoter sequence in gene hypermethylation, is a well-known characteristic of human cancer. Subtelomeres are enriched CpG islands; methylation is believed to be a potential epigenetic regulator. However, regulation on the telomere length remains largely unknown. To demonstrate this correlation, four nasopharyngeal carcinoma cell lines (CNE, CNE1, CNE2, 5-8F) were treated for 72 hours with 0, 1, or 2.5 µM of the demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC). Subtelomeric (D4Z4) level methylation was evaluated with a bisulfite assay, the human telomerase catalytic subunit (hTERT) expression was assayed by reverse transcription-polymerase chain reaction, the telomerase activity was detected using a telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot terminal restriction fragment analysis. There was significant demethylation following 5-aza-dC treatment, and a strongly repressed hTERT expression decreased the telomerase activity and remarkably shortened telomeres. Thus, partial subtelomeric methylation does not repress hTERT expression; conversely, demethylation may downregulate hTERT expression and shorten telomeres.


Assuntos
Metilação de DNA/genética , Neoplasias Nasofaríngeas/genética , Telomerase/genética , Telômero/genética , Carcinoma , Linhagem Celular Tumoral , Ilhas de CpG/genética , Proteínas de Ligação a DNA/genética , Regulação para Baixo/genética , Humanos , Carcinoma Nasofaríngeo , Regiões Promotoras Genéticas/genética
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