RESUMO
MOTIVATION: The COVID-19 pandemic has been spreading globally for four years, yet specific drugs that effectively suppress the virus remain elusive. Furthermore, the emergence of complications associated with COVID-19 presents significant challenges, making the development of therapeutics for COVID-19 and its complications an urgent task. However, traditional drug development processes are time-consuming. Drug repurposing, which involves identifying new therapeutic applications for existing drugs, presents a viable alternative. RESULT: In this study, we construct a knowledge graph by retrieving information on genes, drugs, and diseases from databases such as DRUGBANK and GNBR. Next, we employ the TransR knowledge representation learning approach to embed entities and relationships into the knowledge graph. Subsequently, we train the knowledge graph using a graph neural network model based on TransR scoring. This trained knowledge graph is then utilized to predict drugs for the treatment of COVID-19 and its complications. Based on experimental results, we have identified 15 drugs out of the top 30 with the highest success rates associated with treating COVID-19 and its complications. Notably, out of these 15 drugs, 10 specifically aimed at treating COVID-19, such as Torcetrapib and Tocopherol, has not been previously identified in the knowledge graph. This finding highlights the potential of our model in aiding healthcare professionals in drug development and research related to this disease.
Assuntos
COVID-19 , Reposicionamento de Medicamentos , Humanos , Pandemias , Reconhecimento Automatizado de Padrão , Desenvolvimento de MedicamentosRESUMO
The anticancer drug of tyrosine kinase-inhibitors (TKIs) has significantly improved the prognosis of patients with specific leukemia but has also increased the risk of organ adverse reactions. Herein, we present a case of a patient diagnosed with myeloproliferative neoplasms who experienced recurrent chest pain after receiving treatment with Olverembatinib. Electrocardiography and coronary angiography confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries. This case serves as a reminder for clinicians to pay more attention and actively prevent the cardiac adverse reactions of TKIs when using such medications.
Assuntos
Angiografia Coronária , Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Eletrocardiografia , Antineoplásicos/efeitos adversos , Resultado do Tratamento , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/diagnóstico , Cardiotoxicidade , Pessoa de Meia-IdadeRESUMO
Fractional flow reserve (FFR) has been established as a gold standard for functional coronary ischemia. At present, the FFR can be calculated from coronary computed tomography angiography (CCTA) images (CT-FFR). Previous studies have suggested that CT-FFR outperforms CCTA and invasive coronary angiography (ICA) in determining hemodynamic significance of stenoses. Recently, a novel automatical algorithm of CT-FFR called RuiXin-FFR has been developed. The present study is designed to investigate the predictive value of this algorithm and its value in therapeutic decision making. The present study retrospectively included 166 patients with stable coronary artery disease (CAD) who underwent CCTA screening and diagnostic ICA examination at Peking University People's Hospital, in 73 of whom wire-derived FFR was also measured. CT-FFR analyses were performed with a dedicated software. All patients were followed up for at least 1 year. We validated the accuracy of RuiXin-FFR with invasive FFR as the standard of reference, and investigated the role of RuiXin-FFR in predicting treatment strategy and long-term prognosis. The mean age of the patients was 63.3 years with 63.9% male. The CT-FFR showed a moderate correlation with wire-derived FFR (r = 0.542, p < 0.0001) and diagnostic accuracy of 87.6% to predict myocardial ischemia (AUC: 0.839, 95% CI 0.728-0.950), which was significantly higher than CCTA and ICA. In the multivariate logistic regression analysis, CT-FFR ≤ 0.80 was an independent predictor of undergoing coronary revascularization (OR: 45.54, 95% CI 12.03-172.38, p < 0.0001), whereas CT-FFR > 0.80 was an independent predictor of non-obstructive CAD (OR: 14.67, 95% CI 5.42-39.72, p < 0.0001). Reserving ICA and revascularization for vessels with positive CT-FFR could have reduced the rate of ICA by 29.6%, lowered the rate of ICA in vessels without stenosis > 50% by 11.7%, and increased the rate of revascularization in patients receiving ICA by 21.2%. The average follow-up was 23.7 months, and major adverse cardiovascular events (MACE) occurred in 11 patients. The rate of MACE was significantly lower in patients with CT-FFR > 0.80. The new algorithm of CT-FFR can be used to predict the invasive FFR. The RuiXin-FFR can also provide useful information for the screening of patients in whom further ICA is indeed needed and prognosis evaluation.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Isquemia Miocárdica , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Angiografia por Tomografia Computadorizada/métodos , Estudos Retrospectivos , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X , Algoritmos , Valor Preditivo dos TestesRESUMO
OBJECTIVES: To study the distribution, drug resistance, and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) isolated from hospitalized children, providing a reference for the prevention and treatment of CRAB infections in hospitalized children. METHODS: Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction. The drug resistance, biofilm phenotypes, and gene carriage of these two types of strains were compared. RESULTS: Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum ß-lactamases with downregulated outer membrane porins, harboring the VIM, OXA-23, and OXA-51 genes. The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains (P<0.05). Genes related to biofilm formation, including Bap, bfs, OmpA, CsuE, and intI1, were detected in both epidemic and sporadic strains, with a higher detection rate of the intI1 gene in epidemic strains (P<0.05). CONCLUSIONS: CRAB strains are colonized in the hospital, with sporadic strains having a stronger ability to form biofilms, suggesting the potential for forming new clonal transmissions in the hospital. Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Biofilmes , Carbapenêmicos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Biofilmes/efeitos dos fármacos , Carbapenêmicos/farmacologia , Humanos , Criança , Infecções por Acinetobacter/microbiologia , Pré-Escolar , beta-Lactamases/genética , Criança Hospitalizada , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Feminino , Lactente , Masculino , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genéticaRESUMO
Intermediate-scale quantum technologies provide new opportunities for scientific discovery, yet they also pose the challenge of identifying suitable problems that can take advantage of such devices in spite of their present-day limitations. In solid-state materials, fractional quantum Hall phases continue to attract attention as hosts of emergent geometrical excitations analogous to gravitons, resulting from the nonperturbative interactions between the electrons. However, the direct observation of such excitations remains a challenge. Here, we identify a quasi-one-dimensional model that captures the geometric properties and graviton dynamics of fractional quantum Hall states. We then simulate geometric quench and the subsequent graviton dynamics on the IBM quantum computer using an optimally compiled Trotter circuit with bespoke error mitigation. Moreover, we develop an efficient, optimal-control-based variational quantum algorithm that can efficiently simulate graviton dynamics in larger systems. Our results open a new avenue for studying the emergence of gravitons in a new class of tractable models on the existing quantum hardware.
RESUMO
Objectives: The present study is designed to investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on left ventricular performance recovery. Background: IMR has been established as a gold standard for coronary microvascular assessment and a predictor of left ventricular recovery after ST-segment elevation myocardial infarction (STEMI). CaIMR is a novel and accurate alternative of IMR. Methods: The present study retrospectively included 80 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). We offline performed the post-PCI caIMR analysis of the culprit vessel. Echocardiography was performed within the first 24 hours and at 3 months after the index procedure. Left ventricular recovery was defined as the change in left ventricular ejection fraction (LVEF) more than zero. Results: The mean age of the patients was 58.0 years with 80.0% male. The average post-PCI caIMR was 43.2. Overall left ventricular recovery was seen in 41 patients. Post-PCI caIMR (OR: 0.948, 95% CI: 0.916-0.981, p = 0.002), left anterior descending as the culprit vessel (OR: 3.605, 95% CI: 1.23-10.567, p = 0.019), and male (OR: 0.254, 95% CI: 0.066-0.979, p = 0.047) were independent predictors of left ventricular recovery at 3 months follow-up. A predictive model was established with the best cutoff value for the prediction of left ventricular recovery 2.33 (sensitivity 0.610, specificity 0.897, and area under the curve 0.765). In patients with a predictive model score less than 2.33, the LVEF increased significantly at 3 months. Conclusions: The post-PCI caIMR can accurately predict left ventricular functional recovery at 3 months follow-up in patients with STEMI treated by primary PCI, supporting its use in clinical practice.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Angiografia Coronária , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.
Assuntos
Poluição do Ar/efeitos adversos , COVID-19/mortalidade , Exposição por Inalação/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , China/epidemiologia , Cidades/estatística & dados numéricos , Humanos , Exposição por Inalação/análise , Mortalidade , Valor Preditivo dos Testes , SARS-CoV-2RESUMO
BACKGROUND: To compare the effect and outcomes of optical coherence tomography (OCT)-guided rotational atherectomy (RA) with intravascular ultrasound (IVUS)-guided RA in the treatment of calcified coronary lesions. METHODS: Data of calcified coronary lesions treated with RA that underwent OCT-guided or IVUS-guided from January 2016 to December 2019 at a single-center registry were retrospectively analyzed. The effect and outcomes between underwent OCT-guided RA and IVUS-guided RA were compared. RESULTS: A total of 33 lesions in 32 patients received OCT-guided RA and 51 lesions in 47 patients received IVUS-guided RA. There was no significant difference between OCT-guided RA group and IVUS-guided RA group in clinical baselines characteristics. Comparing the procedural and lesions characteristics of the two groups, the contrast volume was larger [(348.8 ± 110.6) ml vs. (275.2 ± 76.8) ml, P = 0.002] and the scoring balloon was more frequently performed (33.3% vs. 3.9%, P = 0.001) after RA and before stenting in the OCT-guided RA group. Comparing the intravascular imaging findings of the two groups, stent expansion was significantly larger in the OCT-guided RA group ([82 ± 8]% vs. [75 ± 9]%, P = 0.001). Both groups achieved procedural success immediately. There were no significantly differences in the incidence of complications. Although there was no statistical difference in the occurrence of MACE at 1 year between OCT-guided RA group and IVUS-guided RA group (3.1% vs. 6.4%, P = 0.517), no cardiovascular death, TVR and stent thrombosis occurred in OCT-guided RA group. CONCLUSIONS: OCT-guided RA compared to IVUS-guided RA for treating calcified coronary lesions resulted in better stent expansion and may have improved prognosis.
Assuntos
Angioplastia Coronária com Balão , Aterectomia Coronária , Doença da Artéria Coronariana/terapia , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção , Calcificação Vascular/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Aterectomia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Stents , Tomografia de Coerência Óptica/efeitos adversos , Resultado do Tratamento , Ultrassonografia de Intervenção/efeitos adversos , Calcificação Vascular/diagnóstico por imagemRESUMO
This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Lactonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacosRESUMO
An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1-7), and the ACE2/angiotensin-(1-7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1-7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1-7)/MAS may help attenuate organ injuries. SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.
Assuntos
Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/enzimologia , Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , PandemiasRESUMO
BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.
Assuntos
Síndrome de Brugada/diagnóstico , Síndrome de Brugada/epidemiologia , Fatores Etários , Idoso , Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Vida Independente , Estudos Longitudinais , Pessoa de Meia-Idade , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Sexuais , Taxa de Sobrevida , Taiwan/epidemiologia , Fatores de TempoRESUMO
This retrospective study was to compare the image quality of right coronary artery (RCA) and effective radiation dose on prospective ECG-gated method between 320 row computed tomography (CT) and 2nd generation (128-slice) dual source CT. A total of 215 candidates underwent CT coronary angiography using prospective ECG-gated method, 120 patients enrolled in 320 row CT group, and 95 patients in dual source CT group. We divided RCA image quality scores as 1/2/3/4, which means excellent/good/adequate/not assessable and heart rates were considered, as well as the radiation dose. There is no statistically significant difference of RCA image quality of Score 1/2 between 320 row CT and 2nd generation dual source CT, but lower heart rate (<70/min) improved RCA image quality. Meanwhile, the 2nd generation dual source CT scan have significant lower radiation dose. For patients with high level heart rate variation, both prospective ECG-gated method of 320 row CT scan (Toshiba) and 2nd generation dual source CT scan (Siemens) basically provided good image quality on RCA. There is an advantage of effective radiation dose reduction in prospective ECG-gated method using the 2nd generation dual source CT scan. After the iodine contrast agent was injected into elbow vein, the threshold triggering method was used to carry out prospective gated scanning, and the acquired fault image was reconstructed by the standard post-processing software of each manufacturer. The radiation dose value is obtained through the dose report automatically generated after each scan.
Assuntos
Vasos Coronários , Eletrocardiografia , Técnicas de Imagem de Sincronização Cardíaca , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Humanos , Estudos Prospectivos , Doses de Radiação , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
In this work, a simple room-temperature phosphorescence (RTP) method was first proposed to detect adriamycin, by using a functional material of Mn doped ZnS quantum dots (Mn-ZnS QDs) composited with poly(diallyldimethylammonium chloride) (PDDA). After PDDA was associated to the Mn-ZnS QDs, the RTP intensity was significantly enhanced. As a result, Mn-ZnS QDs/PDDA nanoassemblies greatly improve the adriamycin detection ability of QDs and provide an important method for developing more effective and sensitive adriamycin detection sensor. The method based upon RTP has a linear range from 0.5 to 64.0 µM with a detection limit (3σ/s) for adriamycin of 0.45 µM. The developed method was further successfully applied to detect adriamycin in human serum samples (diluted 50 times) with satisfactory results, and the recovery ranged from 98.3 to 101.3.
Assuntos
Antibióticos Antineoplásicos/análise , Doxorrubicina/análise , Pontos Quânticos , Sulfetos/química , Compostos de Zinco/química , Humanos , Medições Luminescentes , Manganês , TemperaturaRESUMO
Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 µM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.
Assuntos
Chalconas/uso terapêutico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfolipase C gama/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombose/metabolismo , Trombose/prevenção & controle , Animais , Cálcio/metabolismo , Immunoblotting , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Selectina-P/metabolismo , Agregação Plaquetária/efeitos dos fármacosRESUMO
Cytochrome c oxidase subunit II (COX II) containing a dual core CuA active site is one of the core subunits of mitochondrial Cytochrome c oxidase (Cco), which plays a significant role in the physiological process. In this report, the full-length cDNA of COXII gene was cloned from Sitophilus zeamais, which had an open reading frame (ORF) of 684 bp encoding 227 amino acids residues. The predicted COXII protein had a molecular mass of 26.2 kDa with pI value of 6.37. multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXII had high sequence identity with the COXII of other insect species. The gene was subcloned into the expression vector pET-32a, and induced by isopropyl ß-d-thiogalactopyranoside (IPTG) in E. coli Transetta (DE3) expression system. Finally the recombinant COXII with 6-His tag was purified using affinity chromatography with Ni(2+)-NTA agarose. Western Blotting (WB) showed the recombinant protein was about 44 kD, and the concentration of fusion protein was 50 µg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXII could catalyze the oxidation of substrate Cytochrome C (Cyt c), and influenced by allyl isothiocyanate (AITC). By using molecular docking method, It was found that a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results suggested that tag-free COXII was functional and one of the action sites of AITC, which will be helpful to carry out a point mutation in binding sites for the future research.
Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/genética , Regulação Enzimológica da Expressão Gênica , Proteínas de Insetos/genética , Gorgulhos/genética , Sequência de Aminoácidos , Animais , Biocatálise/efeitos dos fármacos , Western Blotting , Clonagem Molecular , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/classificação , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Escherichia coli/genética , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Isotiocianatos/metabolismo , Isotiocianatos/farmacologia , Simulação de Acoplamento Molecular , Peso Molecular , Oxirredução , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Especificidade por Substrato , Gorgulhos/enzimologiaRESUMO
Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3(') ,4(') -hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20-100 µm) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI-annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2 promoter-binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen-activated protein kinases, including p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen-activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme.
Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Flavonas/farmacologia , Glioma/patologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citrus/química , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Fator de Transcrição E2F1/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
In this work, maltodextrin-grafted-cinnamic acid (MD-g-CA) was synthesised and used as wall material to improve the stability of purple sweet potato anthocyanins (PSPa) via microencapsualtion. MD-g-CA was prepared through esterification in a two-step convenient synthesis procedure and characterised using infra-red (IR) spectroscopy. The IR data indicated the typical ester carbonyl stretching at around 1721 cm-1. Moreover, MD-g-CA could give about 40% inhibition of DPPH radical and present excellent UV-absorption, which were notably better than that of native MD. Maltodextrin (MD) and MD-g-CA were used to prepare PSPa microcapsules by spray drying. The stability of PSPa was evaluated by UV-Vis analysis. The microcapsules produced by MD-g-CA showed a spheres-like appearance with some cracks. Storage tests revealed that the degradation rate of PSPa embedded by MD-g-CA was much lower than that of free PSPa under the same condition. Thus, MD-g-CA could be used as an effective wall material to improve stability of anthocyanins.
Assuntos
Antocianinas/química , Cinamatos , Polissacarídeos , Cápsulas , Cinamatos/síntese química , Cinamatos/química , Estabilidade de Medicamentos , Ipomoea batatas/química , Polissacarídeos/síntese química , Polissacarídeos/químicaRESUMO
AIMS: The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older. METHODS AND RESULTS: The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 ± 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 ± 8 vs. 35 ± 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow-up (log-rank test, P = 0.21, 0.32, respectively). CONCLUSION: The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality.
Assuntos
Síndrome de Brugada/diagnóstico , Síndrome de Brugada/mortalidade , Eletrocardiografia/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Taxa de Sobrevida , Taiwan/epidemiologiaRESUMO
We aimed to examine the association between preoperative use of statins and postoperative acute kidney injury (AKI) in patients undergoing major surgery by performing a systemic review and meta-analysis. MEDLINE and EMBASE, from inception to April 2013, and the reference lists of related articles were searched for relevant studies. Trials comparing preoperative statin therapy with no preoperative statin in patients undergoing major surgery were included. Outcome measures of interest were the risk of cumulative postoperative AKI and postoperative AKI requiring renal replacement therapy (RRT). Fixed or random effect meta-analysis was performed to derive summary effect estimates. In five randomized controlled trials (RCTs) and 19 observational studies, comprising a total of 989 173 patients undergoing major surgery, 112 840 patients (11.41%) received preoperative statin therapy. The specific type, dosage, and duration of statin therapy were not available in most studies. Preoperative statin therapy was associated with a significant risk reduction for cumulative postoperative AKI (weighted summary odds ratio (OR) 0.87, 95% CI 0.79 to 0.95). The effect of risk reduction was also significant when considering postoperative AKI requiring RRT (OR 0.80, 95% CI 0.72 to 0.90). When restricting the analysis to the five RCTs, preoperative statin therapy did not show significant protective effect on postoperative AKI (OR 0.49, 95% CI 0.22 to 1.09). In patients undergoing major surgery, preoperative statin therapy could associate with a reduced risk for postoperative AKI. However, considerable heterogeneity existed among included studies. Future randomized trials were warranted for this critical clinical question.