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1.
Front Oncol ; 11: 733595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527595

RESUMO

Background: High glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched. Methods: We analyzed the co-expression of glycolysis-related genes and lncRNAs in The Cancer Genome Atlas (TCGA) database to screen glycolysis-related lncRNAs. Further prognostic analysis and differential expression analysis were performed. We further analyzed the relationship between lncRNAs and tumor immune infiltration. Since WAC antisense RNA 1 (WAC-AS1) had the greatest effect on the prognosis among all screened lncRNAs and had a larger coefficient in the prognostic model, we chose WAC-AS1 for further verification experiments and investigated the function and mechanism of action of WAC-AS1 in hepatocellular carcinoma. Results: We screened 502 lncRNAs that have co-expression relationships with glycolytic genes based on co-expression analysis. Among them, 112 lncRNAs were abnormally expressed in liver cancer, and 40 lncRNAs were related to the prognosis of patients. Eight lncRNAs (WAC-AS1, SNHG3, SNHG12, MSC-AS1, MIR210HG, PTOV1-AS1, AC145207.5 and AL031985.3) were used to established a prognostic model. Independent prognostic analysis (P<0.001), survival analysis (P<0.001), receiver operating characteristic (ROC) curve analysis (AUC=0.779) and clinical correlation analysis (P<0.001) all indicated that the prognostic model has good predictive power and that the risk score can be used as an independent prognostic factor (P<0.001). The risk score and lncRNAs in the model were found to be related to a variety of immune cell infiltration and immune functions. WAC-AS1 was found to affect glycolysis and promote tumor proliferation (P<0.01). WAC-AS1 affected the expression of several glycolysis-related genes (cAMP regulated phosphoprotein 19 (ARPP19), CHST12, MED24 and KIF2A) (P<0.01). Under hypoxic conditions, WAC-AS1 regulated ARPP19 by sponging miR-320d to promote glucose uptake and lactate production (P<0.01). Conclusion: We constructed a model based on glycolysis-related lncRNAs to evaluate the prognostic risk of patients. The risk score and lncRNAs in the model were related to immune cell infiltration. WAC-AS1 can regulate ARPP19 to promote glycolysis and proliferation by sponging miR-320d.

2.
Am J Cancer Res ; 11(3): 916-929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791163

RESUMO

Inhibiting the functioning of PD-1/PD-L1 to activate human immune system and improve the prognosis of pancreatic cancer (PC) would provide a significant boost to handling the disease. One research found the expression level of NSG3 was reduced in pediatric pilocytic astrocytoma, so is PC and we found NSG3 could regulate the expression of PD-L1. So NSG3 could become a new target for enhancing the immune response to PC. The GEPIA website was employed to analyze the prognoses in PC patients with different NSG3 levels. Immunohistochemistry (IHC) analysis was applied to detect different levels of NSG3 in para-PC and PC tissues. Cell biological function tests (in vitro) were performed and a subcutaneous nude mice tumor model (in vivo) was established to verify the effect of NSG3 on PC. Immunoblotting and RT-qPCR were utilized to demonstrate the inhibiting effect of NSG3 on PD-L1 through regulating Erk1/2 phosphorylation. A subcutaneous C57BL/6 tumor mice model was established to assess the possibility of a synergistic effect of NSG3 expression and the use of an anti-PD-L1 antibody on PC. PC tissues had decreased NSG3 expression levels, which led to poor prognosis. Overexpressing NSG3 suppressed proliferation, invasion and migration capacities of PC cells. On the contrary, knocking-down NSG3 prompted PC malignancy whether in vivo or in vitro. Importantly, NSG3 prevented Erk1/2 phosphorylation to inhibit PD-L1 expression. Additionally, NSG3 and an immune checkpoint inhibitor anti-PD-1 antibody acted synergistically, which enhanced the efficacy of the inhibitor. NSG3 inhibited PD-L1 expression by suppressing Erk1/2 phosphorylation to improve the immune response to PC. NSG3 is, therefore, a potential new diagnostic and prognostic marker, particularly useful in immune checkpoint blockade therapy.

3.
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
4.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421384

RESUMO

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Linfócitos/citologia , Neutrófilos/citologia , Corticosteroides/efeitos adversos , Área Sob a Curva , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Tempo de Internação , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
5.
Med (N Y) ; 2(1): 38-48.e2, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33043313

RESUMO

Background: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. Methods: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. Findings: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. Conclusions: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. Funding: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

6.
Cell Metab ; 32(2): 176-187.e4, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592657

RESUMO

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/efeitos dos fármacos , COVID-19 , Comorbidade , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2
8.
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
9.
Sensors (Basel) ; 19(24)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835681

RESUMO

This paper investigates the performance of a full-duplex (FD) relaying-enabled satellite sensor network under residual loop interference, where the satellite uplink and the downlink transmissions simultaneously occur over the same frequency band. Specifically, the closed-form expressions for the outage probability and ergodic capacity of the FD relaying satellite sensor network are derived by considering residual loop interference, channel statistical property, propagation loss, geometric satellite antenna pattern, and terminal elevation angle. Simulation results show the achieved performance gains of a full-duplex relaying satellite sensor network over traditional half-duplex relaying, and highlight the impact of key system parameters on the performance of the considered FD relaying satellite sensor network.

10.
Zhonghua Yi Xue Za Zhi ; 87(6): 409-13, 2007 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-17456384

RESUMO

OBJECTIVE: To investigate the effects of lipiodol-hydroxyapatite nanoparticle (lipi-nHAP) on the growth, necrosis, apoptosis, proliferation, and angiogenesis of hepatic tumor. METHODS: Ultrasound-emulsification was used to make lipi-nHAP Eighty New Zealand white rabbits underwent implantation of carcinoma cells of the line VX2 into the left lobe of liver. Two weeks later the rabbits underwent catheterization into the gastroduodenal artery so that, and then the rabbits were randomly divided into four equal groups to receive infusion via the hepatic artery of different drugs: physiological saline (Group A), lipiodol (Group B), adriamycin + lipiodol (Group C), and lipi-nHAP (Group D). Seven and 14 days after the treatment the size of tumor was observed by spiral CT scan, and the volume and growth rate of tumor were calculated. Two weeks after the treatment 8 rabbits from each group were killed and their liver tumors were taken out and the survival rates of remaining rabbits were observed. The necrosis rate of the liver tumor was assessed by measuring the area of the tumor and the necrosis. The apoptotic rate was examined by TUNEL method. Mcrovessel density (MVD) was examined by immunohistochemistry anti-CD31 antibody. Anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used to detect the expression of PCNA so as to calculate the proliferation index of the cells. RESULTS: The tumor volume and growth rate of Group D 7 and 14 days after treatment were both significantly lower than those of other groups (all P < 0.05) and the necrosis rate and apoptotic index of Group D were both significantly higher than those of other groups (all P < 0.05). The values of MVD were higher in Groups C and D compared with those of Group A. Compared with those in other groups, the values of MVD and expression level of PCNA were significantly lower in group D (all P < 0.05). The survival time of Group D was longer than those of other groups (all P < 0.05). CONCLUSION: lipi-nHAP can suppress the growth of tumor, increase the tumor's necrosis rate and apoptotic index, inhibit the development of neovascularization, decrease the expression level of PCNA of residual tumor, and prolong the surviving time of the animals with hepatic tumor. It may become an effective embolization material to treat liver cancer.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Durapatita/uso terapêutico , Óleo Iodado/uso terapêutico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Animais , Durapatita/administração & dosagem , Feminino , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Óleo Iodado/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais/irrigação sanguínea , Neoplasias Hepáticas Experimentais/patologia , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Inoculação de Neoplasia , Neovascularização Patológica/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Antígeno Nuclear de Célula em Proliferação/análise , Antígeno Nuclear de Célula em Proliferação/biossíntese , Coelhos , Distribuição Aleatória , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
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