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1.
Glob Heart ; 19(1): 25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434155

RESUMO

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.


Assuntos
Cálcio , Cardiomiopatia Dilatada , Idoso , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Cardiomiopatia Dilatada/diagnóstico , Mortalidade Hospitalar
2.
Front Cardiovasc Med ; 9: 995899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204589

RESUMO

Background: Previous Study Found That Implantation of a Cardioverter-Defibrillator Likely Caused a Worse Prognosis in Older Patients With non-Ischemic Systolic Heart Failure. This Suggests That More Precise Risk Stratification Is Needed in Elderly Patients. We Conducted a Retrospective Study to Evaluate the Association of α-Hydroxybutyrate Dehydrogenase (α-HBDH) With Mortality During Hospitalization in Elderly Patients With non-Ischemic Dilated Cardiomyopathy (NIDCM). Methods: 1,019 Elderly Patients (age ≥60 Years) Diagnosed With NIDCM Were Retrospectively Enrolled From January 2010 to December 2019. Univariate and Multivariate Analyses Were Showed to Explore the Relationship Between α-HBDH and in- Hospital Death. Results: Patients in elevated α-HBDH group (>182 U/L) had a longer hospital stays and higher in-hospital mortality. Univariate logistics regression analysis showed that elevated α-HBDH was significantly related to mortality (OR: 7.004, 95% CI: 3.583-13.693, p < 0.001). Receiver operator characteristic (ROC) curve analysis reflected that α-HBDH levels had excellent predictive power for in-hospital death (AUC = 0.810, 95% CI: 0.745-0.876, p < 0.001). After adjustment of age, serum creatine, albumin and LVEF, multivariate regression analysis validated the association of elevated α-HBDH with increased risk of in-hospital death (p < 0.05). Conclusions: Elevated α-HBDH level is significantly related to in-hospital mortality in older patients with NIDCM.

3.
J Oncol ; 2022: 9025198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245994

RESUMO

Thyroid cancer is a great part of the endocrine tumor with an increasing incidence. Papillary thyroid carcinoma (PTC) is the most common subtype. With the enormous pace taken in the microarray technology, bioinformatics is applied in data mining more frequently. Weighted gene coexpression network analysis (WGCNA) can perform analysis combining clinic information. We performed WGCNA for prognostic genes associated with PTC. From the GEO profile, we got ten modules. We identified a key module that was closest to patients' survival time. Then, we screened five hub genes (ATRX, BOD1L1, CEP290, DCAF16, and NEK1) from the key module based on the clinical information from TCGA. These five genes not only significantly differ between the normal and tumor groups but have prognostic value. The receiver operating characteristic (ROC) curve indicated that they had the potential to serve as prognostic genes. We performed next-generation sequencing using the PTC tissue to get more convincing evidence. Besides, we established a new signature and verified it through K-M plots and ROC. The signature could be an independent factor for the prognosis of PTC, and we built a nomogram to carry out a quantitative study. In a word, the hub genes we explored in the study deserved more basic and clinical research.

4.
J Inflamm Res ; 15: 5361-5371, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36131782

RESUMO

Background: The serum uric acid/albumin ratio (sUAR), a novel inflammatory marker, effectively predicts acute kidney injury (AKI) and cardiovascular outcomes. However, whether the sUAR predicts post-contrast acute kidney injury (PC-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains uncertain. In this study, we evaluated the association between the sUAR and PC-AKI in patients with STEMI undergoing PCI. Methods: We consecutively recruited patients with STEMI who underwent PCI and stratified them into three groups according to the terciles of the sUAR. The primary outcome was the incidence of PC-AKI. The association between the sUAR and PC-AKI was assessed by multivariate logistic regression analysis. Results: A total of 2861 patients with STEMI were included in this study. The incidence of PC-AKI increased stepwise with increasing sUAR tercile (2.6% vs 4.0% vs 11.6%, p < 0.001), and the incidence of in-hospital major adverse clinical events (MACEs) was highest among patients in the Q3 group. Multivariate logistic regression analysis revealed that the sUAR was also an independent predictor of PC-AKI (continuous sUAR, per 1-unit increase, odds ratio [OR] [95% confidence interval (CI)]: 1.06 [1.02-1.10], p = 0.005; tercile of sUAR, OR [95% CI] for Q2 and Q3: 1.18 [0.69-2.01] and 1.85 [1.12-3.06], respectively, with Q1 as a reference) but not in-hospital MACEs. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of the sUAR for predicting PC-AKI was 0.708 (95% CI: 0.666-0.751), and ROC analysis also showed that the sUAR was superior to uric acid and albumin alone in predicting PC-AKI. Conclusion: Increasing sUAR was significantly associated with a higher risk of PC-AKI but not in-hospital MACEs in patients with STEMI who underwent PCI, suggesting that sUAR had a predictive value for PC-AKI after PCI in patients with STEMI. Further studies are required to confirm this finding.

5.
J Geriatr Cardiol ; 19(7): 487-497, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35975020

RESUMO

OBJECTIVE: To investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI). METHODS: This observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTS: Of patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONS: Compared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.

7.
Fetal Pediatr Pathol ; 41(3): 355-370, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32901528

RESUMO

Aim: This study investigated the effect of FoxM1 on the biological behavior of neuroblastoma (NB) cells in vitro and the association between FoxM1 and PI3K/AKT pathways in NB cell lines. Materials and methods: Recombinant plasmid pcDNA3.1 (+)-FoxM1 and FoxM1-specific small interfering RNA (siRNA) were transfected into IMR-32 cells by liposome transfection. The expression of FoxM1, AKT and PI3K were determined by qRT-PCR and western blotting. The effect of FoxM1 and PI3K/AKT pathways on the cell cycles and apoptosis were analyzed by flow cytometry. Cell viability and proliferation ability were assessed by CCK8 and colony formation assay. Results: Knockdown of FoxM1 promoted NB cell apoptosis and G1-phase cell cycle arrest significantly, increased the expression of apoptosis-related proteins, and suppressed the phospho-activation of PI3K and AKT. Over-expression of FoxM1 had the opposite effects. Conclusion: FoxM1 knockdown inhibited NB cell proliferation and induced apoptosis through inhibiting activation of PI3K and AKT.


Assuntos
Proteína Forkhead Box M1 , Neuroblastoma , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Humanos , Neuroblastoma/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
8.
Clin Pharmacol Ther ; 110(4): 1119-1126, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34287856

RESUMO

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Anticoagulantes/administração & dosagem , Fondaparinux/administração & dosagem , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Mortalidade Hospitalar , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , China , Terapia Antiplaquetária Dupla , Feminino , Heparina/administração & dosagem , Humanos , Infusões Parenterais , Injeções , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Recidiva
9.
Bioorg Chem ; 114: 105080, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34225164

RESUMO

Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure-activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.


Assuntos
Antioxidantes/farmacologia , Curcumina/farmacologia , Química Verde , Infarto da Artéria Cerebral Média/tratamento farmacológico , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/síntese química , Antioxidantes/química , Células Cultivadas , Curcumina/análogos & derivados , Curcumina/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Substâncias Protetoras/síntese química , Substâncias Protetoras/química , Ratos , Traumatismo por Reperfusão/patologia , Relação Estrutura-Atividade
10.
Int J Biol Macromol ; 183: 340-345, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33932411

RESUMO

Yellowhead catfish (Tachysurus fulvidraco) is an important aquaculture fish species in China with a high market value. Infectious diseases pose serious threats in farmed fish species, and although vaccines can prevent certain infections, they rely on potent adjuvants. In this study, we analyzed the transcriptomic profiles of spleens from poly (I:C)-treated T. fulvidraco. We obtained 46,362,922 reads corresponding to 490,926 transcripts and 318,059 genes. Gene annotation using different databases and subsequent differential gene expression analyses led to the identification of 5587 differentially expressed genes (DEGs), of which 2473 were up-regulated and 3114 were down-regulated in poly (I:C)-treated fish. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs revealed the significant dysregulation of immune- and cancer-related genes in the spleens of poly (I:C)-treated fish. Notably, several components of JAK-STAT, MAPK, and p53 signaling pathways were significantly dysregulated in response to poly (I:C) treatment. Quantitative real-time PCR (qRT-PCR) analysis of 11 randomly selected immune response genes confirmed the reliability of our findings. In conclusion, our findings provide novel insight into the immune responses of T. fulvidraco and suggest that poly (I:C) may represent a promising adjuvant of fish vaccines.


Assuntos
Poli I-C/química , Animais , Peixes-Gato , Perfilação da Expressão Gênica , Transcriptoma/genética
11.
BMC Cardiovasc Disord ; 21(1): 202, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882836

RESUMO

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.


Assuntos
Doença da Artéria Coronariana/terapia , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Eur J Clin Pharmacol ; 76(12): 1755-1763, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32700000

RESUMO

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.


Assuntos
Síndrome Coronariana Aguda/terapia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Síndrome Coronariana Aguda/mortalidade , Idoso , Atorvastatina/administração & dosagem , Causas de Morte , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos
13.
Int J Nanomedicine ; 14: 8627-8645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806961

RESUMO

BACKGROUND AND PURPOSE: Systemic lupus erythematous (SLE) is an autoimmune disease caused by many factors. Lupus nephritis (LN) is a common complication of SLE and represents a major cause of morbidity and mortality. Previous studies have shown the advantages of multi-targeted therapy for LN and that TLR4 signaling is a target of anti-LN drugs. High-mobility group box 1 (HMGB1), a nuclear protein with a proinflammatory cytokine activity, binds specifically to TLR4 to induce inflammation. We aimed to develop PEGylated TAT peptide-cationic liposomes (TAT-CLs) to deliver anti-HMGB1 siRNA and dihydroartemisinin (DHA) to increase LN therapeutic efficiency and explore their treatment mechanism. METHODS: We constructed the TAT-CLs-DHA/siRNA delivery system using the thin film hydration method. The uptake and localization of Cy3-labeled siRNA were detected by confocal microscopy and flow cytometry. MTT assays were used to detect glomerular mesangial cell proliferation. Real-time PCR, Western blot analysis, and ELISA evaluated the anti-inflammatory mechanism of TAT-CLs-DHA/siRNA. RESULTS: We constructed the TAT-CLs-DHA/siRNA delivery system measuring approximately 140 nm with superior storage and serum stabilities. In vitro, it showed significantly greater uptake compared with unmodified liposomes and significant inhibition of glomerular mesangial cell proliferation. TAT-CLs-DHA/siRNA inhibited NF-κB activation in a concentration-dependent manner. Real-time PCR and Western blot analysis showed that TAT-CLs-DHA/siRNA downregulated expression of HMGB1 mRNA and protein. TAT-CLs-DHA/siRNA markedly diminished Toll-like receptor 4 (TLR4) expression and subsequent activation of MyD88, IRAK4, and NF-κB. CONCLUSION: TAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.


Assuntos
Artemisininas/administração & dosagem , Produtos do Gene tat/genética , Proteína HMGB1/genética , Lipossomos/administração & dosagem , Nefrite Lúpica/terapia , RNA Interferente Pequeno/administração & dosagem , Receptor 4 Toll-Like/metabolismo , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipossomos/química , Lipossomos/farmacologia , Nefrite Lúpica/metabolismo , NF-kappa B/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Int Urol Nephrol ; 51(12): 2267-2272, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31641999

RESUMO

PURPOSE: Trimetazidine has been shown to prevent the risk of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing percutaneous coronary intervention (PCI). However, the effect of trimetazidine on CIN in unselected patients is unknown. We aimed to evaluate the effect of trimetazidine on preventing CIN in unselected patients treated with PCI. METHODS: 2154 consecutive patients were enrolled and divided into the trimetazidine (n = 529) and non-trimetazidine group (n = 1625). Patients in the trimetazidine group received trimetazidine 20 mg thrice daily starting at least 24 h before the procedure and continuing until discharge. The primary outcome was CIN. RESULTS: CIN was observed in 197 (9.2%) patients. The incidence of CIN was similar between two groups (9.1% vs. 9.2%, P = 0.947). After adjusting for other potential risk factors, trimetazidine did not significantly reduce the risk of CIN (OR = 0.70, 95% CI 0.46-1.08, P = 0.104). The results remained similar when using the alternate definitions of CIN and different subgroup analysis based on diabetes or chronic kidney disease. In additional, no significant difference between two groups was found with respect to in-hospital major adverse clinical events (1.89% vs. 1.66%, P > 0.05). CONCLUSIONS: Trimetazidine did not exert significant renal protective effect on preventing CIN and in hosptial major adverse clinical events in unselected patients undergoing PCI.


Assuntos
Cateterismo Cardíaco , Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Intervenção Coronária Percutânea , Trimetazidina/uso terapêutico , Idoso , Cateterismo Cardíaco/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
ACS Chem Neurosci ; 10(11): 4545-4557, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31491086

RESUMO

The supplementation of exogenous antioxidants to scavenge excessive reactive oxygen species (ROS) is an effective treatment for cerebral ischemia-reperfusion injury (CIRI) in stroke. Piperlongumine (PL), a natural alkaloid, has a great potential as a neuroprotective agent, but it also has obvious toxicity. Moreover, its neuroprotective effects remain to be improved. In this study, we designed a series of novel PL analogs by hybridizing the screened low-toxicity diketene skeleton with antioxidant effect and the 3,4,5-trimethoxyphenyl group, which may increase the antioxidant activity of PL. The intermediate was synthesized by a novel green synthesis method, and 34 compounds were obtained. The compounds without obvious cytotoxicity have remarkable antioxidant effects, especially compared with diketene skeletons and PL. The cytoprotection of the active compound decreased significantly by reduction of the carbon-carbon double bonds of the Michael acceptor in the diketene skeleton. More importantly, further study revealed that compound A9, which has the best activity, can confer protection for cells against oxidative stress and attenuate brain injury in vivo. Overall, this study provided a promising drug candidate for the treatment of CIRI and guided the further development of drug research in oxidative stress-mediated diseases.


Assuntos
Antioxidantes/síntese química , Isquemia Encefálica/tratamento farmacológico , Dioxolanos/síntese química , Desenho de Fármacos , Química Verde/métodos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Sobrevivência Celular , Dioxolanos/farmacologia , Dioxolanos/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo
17.
J Nat Prod ; 82(6): 1714-1718, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31095383

RESUMO

Five new diterpenes, including an unprecedented 5,5,6,6,5-pentacyclic diterpene, sponalactone (1), two new spongian diterpenes, 17- O-acetylepispongiatriol (2) and 17- O-acetylspongiatriol (3), and two new spongian diterpene artifacts, 15α,16α-dimethoxy-15,16-dihydroepispongiatriol (4) and 15α-ethoxyepispongiatriol-16(15 H)-one (5), were isolated from a South China Sea collection of the marine sponge Spongia officinalis, together with three known analogues (6-8). The structures of the new diterpenes were elucidated by extensive spectroscopic analysis. The absolute configurations were established on the basis of ECD data. Compounds 1-5 and 7 exhibited moderate inhibition against LPS-induced NO production in RAW264.7 macrophages with IC50 values of 12-32 µM.


Assuntos
Diterpenos/farmacologia , Macrófagos/efeitos dos fármacos , Poríferos/química , Animais , China , Diterpenos/química , Diterpenos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular
18.
Acta Pharm Sin B ; 9(2): 335-350, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30972281

RESUMO

Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

19.
Fish Shellfish Immunol ; 87: 43-50, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30590169

RESUMO

Because of the high protein content and rich meat quality of crayfish Procambarus clarkii, it has become widely popular in China in recent years and has a high economic value. When P. clarkii is stimulated by heavy metals, it reacts to oxidation. P. clarkii has evolved antioxidant defense systems, including antioxidant enzymes such as catalase (CAT). The hexavalent form of Cr (VI) is a pathogenic factor that is of particular concern in aqueous systems because of its great toxicity to living organisms. In this study, we characterized the transcriptome of P. clarkii using a RNA sequencing method and performed a comparison between K2Cr2O7-treated samples and controls. In total, 34,237 unigenes were annotated. We identified 5098 significantly differentially expressed genes (DEGs), including 2536 and 2562 were significantly up-regulated and down-regulated, respectively. In addition, quantitative real time-PCR (qRT-PCR) confirmed the up-regulation of a random selection of DEGs. Our results contribute to a more comprehensive understanding of the antioxidant defense system used by P. clarkii in response to heavy metal stress.


Assuntos
Astacoidea/efeitos dos fármacos , Cromatos/toxicidade , Compostos de Potássio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Astacoidea/genética , Astacoidea/metabolismo , Perfilação da Expressão Gênica , Transcriptoma
20.
Fish Shellfish Immunol ; 86: 311-318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30465916

RESUMO

Procambarus clarkii is one of the most economically important species in Chinese aquaculture, and is widely cultured. Infection of P. clarkii populations with bacterial pathogens causes high mortality and great economic loss, therefore disease control is of significant economic importance. P. clarkii is a model system for studying immune responses in invertebrates, and its immune system consists solely of the innate response. In the present study, we examined gene expression related to immune function in P. clarkii in response to pathogen challenge. The transcriptome of hepatopancreas tissue from P. clarkii challenged with peptidoclycan (PGN) was analyzed and compared to control specimens. After assembly and annotation, 48,661 unigenes were identified with an average length of 671.54 bp. A total of 2533 differentially expressed genes (DEGs) were obtained, including 765 significantly up-regulated unigenes and 1757 significantly down-regulated unigenes. Gene ontology (GO) analysis demonstrated 19 biological process subcategories, 16 cellular component subcategories, and 17 molecular function subcategories that were enriched among these DEGs. Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed enrichment among immune responses pathways. Taken together, this study not only enriches the existing P. clarkii transcriptome database, but also elucidates immune responses of crayfish that are activated in response to PGN challenge.


Assuntos
Astacoidea/genética , Perfilação da Expressão Gênica , Hepatopâncreas/efeitos dos fármacos , Peptidoglicano/farmacologia , Animais , Astacoidea/imunologia , Ontologia Genética , Hepatopâncreas/imunologia
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