RESUMEN
Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.
Asunto(s)
ADN Glicosilasas , Cardiomiopatías Diabéticas , Resistencia a la Insulina , Animales , ADN Glicosilasas/metabolismo , ADN Glicosilasas/genética , ADN Glicosilasas/deficiencia , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/patología , Ratones , Masculino , PPAR gamma/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Miocardio/patología , Modelos Animales de Enfermedad , Glucólisis , Humanos , Ratones Endogámicos C57BLRESUMEN
Background: Thyroid autoimmunity is one of the most prevalent autoimmune diseases. However, its association with extra-thyroid diseases and mortality risk in the general population remains uncertain. Our study aims to evaluate the association of thyroid autoimmunity with extra-thyroid disease and the risk of mortality. Methods: A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) with participants from 2007-2008, 2009-2010, and 2011-2012, tracking their mortality until 2019. Associations between thyroid autoimmunity, which was defined as having positive thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb), and extra-thyroid disease including diabetes, hypertension, cardiovascular disease, chronic lung disease, arthritis, cancer and chronic renal disease and the risk of mortality were investigated. Results: A total of 7431 participants were included in this study. Positive The prevalence of positive TgAb was 7.54%, and positive TPOAb prevalence was 11.48%. TgAb was significantly associated with diabetes (Model 1: OR=1.64, 95% CI:1.08-2.50; Model 2: OR=1.93, 95% CI: 1.21-3.08) and hypertension (Model 1: OR=0.67, 95% CI: 0.49-0.91; Model 2: OR=0.62, 95% CI: 0.44-0.88). TPOAb was associated with a lower prevalence of chronic lung disease (model 1: OR=0.71, 95% CI: 0.54-0.95; model 2: OR=0.71, 95% CI: 0.53-0.95). No associations were observed between TgAb, TPOAb and other extra-thyroid diseases. Neither TgAb nor TPOAb were associated with all-cause mortality or heart disease mortality. Conclusion: TgAb was linked to a higher prevalence of diabetes and a lower prevalence of hypertension, while TPOAb was associated with a decreased prevalence of chronic lung disease. However, neither TgAb nor TPOAb posed a risk for all-cause mortality or heart disease mortality.
Asunto(s)
Enfermedades Autoinmunes , Diabetes Mellitus , Cardiopatías , Hipertensión , Enfermedades Pulmonares , Enfermedades de la Tiroides , Adulto , Humanos , Autoinmunidad , Encuestas Nutricionales , Estudios Prospectivos , Yoduro Peroxidasa , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/epidemiología , Diabetes Mellitus/epidemiología , Hipertensión/epidemiologíaRESUMEN
Background: The role of prophylactic central lymph node dissection (pCLND) for papillary thyroid cancer (PTC) remains contentious, and the impact of pCLND on long-term patient outcomes is unclear. Methods: A retrospective analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients diagnosed with PTC who did not undergo pCLND between 2004 and 2015 were included in this study, and patients with pN0 PTC who underwent CLND were included as the control group. The researchers calculated the subdistribution hazard ratio (SHR) using the Fine-Gray model and the hazard ratio (HR) using the Cox proportional hazards regression to compare Thyroid cancer-specific survival (TCSS) and overall survival (OS) of the different groups. Results: A total of 38,205 T1-2cN0 PTC patients without pCLND were eligible for the study entry, and 24,157 patients with T1-2pN0 PTC patients who had received CLND were included as the control group. The actuarial 10-year TCSS and OS rates of patients without pCLND were 99.53% and 92.77%, respectively. Patients without pCLND had similar TCSS compared with the control group after adjusting for age, sex, race, tumor stage, multifocality, thyroid surgery, and radiation (SHR = 1.35, 95% CI: 0.95 - 1.93). However, patients without pCLND had a significantly poorer OS than the control group (HR = 1.38, 95% CI: 1.26 - 1.51). Conclusions: Patients without pCLND had similar TCSS compared with the control group after adjusting for confounders but had significantly poorer OS. Whether the OS disparities were attributed to pCLND or other factors still needs further study.
RESUMEN
Background: Many conclusions have been reached in renal function studies in direct smokers. Aim: This study aimed to determine the relationship between smoking and decreased renal function to ensure that reduced chronic kidney disease incidence can be achieved by limiting smoking, we assessed the relationship between cigarette smoking and renal function. Methods: We recruited 10,267 people from the National Health and Nutrition Program Testing Survey (NHANES) aged over 20 years from 2013 to 2018 to assess smoking exposure by serum cotinine. We estimated the glomerular filtration rate (eGFR) and used multivariate linear regression models and smooth curve fittings to assess the relationship between smoking and renal function. Results: We found an inverse relationship between serum cotinine and the eGFR. In a subgroup analysis, we found a non-linear relationship between serum cotinine and the eGFR in different ethnic groups or in different sexes. In a subgroup analysis of sex, we found inflection points between men and women for the relationship between serum cotinine and the eGFR (men 183 ng/ml and 465 ng/ml; women 227 ng/ml and 412 ng/ml). However, in a subgroup analysis by age, we found that serum cotinine showed a clear negative correlation with the eGFR in people aged 20-39 years, but in people older than 40 years, a weak correlation was shown. In stratified analysis by ethnicity, we found significant negative associations in Mexican American and Other Hispanic individuals and weaker associations in Non-Hispanic White and Non-Hispanic Black individuals. Conclusion: Through the negative correlation between serum cotinine and the eGFR, we can conclude that as the smoking quantity increases, smoking leads to a decrease in renal function. The results of the subgroup analysis indicate that in young people, by advocating smoking cessation early, we can very effectively prevent kidney disease in this population and thus reduce the incidence of chronic kidney disease. Smoking should be included as an independent risk factor for chronic kidney disease.
RESUMEN
BACKGROUND: Metabolic syndrome (MetS) was a risk factor for papillary thyroid cancer (PTC). Whether MetS impacts the aggressiveness of PTC is still unclear. We carried out this study to clarify this issue. METHODS: We evaluated 745 consecutive PTC patients treated with surgery. Patients were divided into three groups based on their number of MetS components: patients without any MetS components, patients with 1-2 MetS components, and patients with 3-5 MetS components. The clinical features and histological aggressiveness of PTC at the time of diagnosis were evaluated. RESULTS: A total of 745 patients were included in this study. And, 145 patients had three or more metabolic components and were diagnosed as MetS. MetS was a risk factor for larger tumors (OR = 2.29, 95% CI: 1.31-4.03), more lymph node metastasis (OR = 1.97, 95% CI: 1.11-3.51), and later clinical stage (OR = 7.92, 95% CI: 1.59-39.34) after correction for age, sex, and thyroid-stimulating hormone (TSH) level and body mass index (BMI). CONCLUSION: In our hospital-based cohort study MetS was associated with the aggressiveness of PTC. This association was still significant after adjusting for age, sex, TSH, and BMI.
Asunto(s)
Síndrome Metabólico , Neoplasias de la Tiroides , Índice de Masa Corporal , Estudios de Cohortes , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Estudios Retrospectivos , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Diterpene Ginkgolides Meglumine Injection (DGMI) is made of extracts from Ginkgo biloba L, including Ginkgolides A, B, and K and some other contents, and has been widely used as the treatment of cerebral ischemic stroke in clinic. It can be learned from the "Compendium of Materia Medica" that Ginkgo possesses the effect of "dispersing toxin". The ancient Chinese phrase "dispersing toxin" is now explained as elimination of inflammation and oxidative state in human body. And it led to the original ideas for today's anti-oxidation studies of Ginkgo in apoptosis induced by optic nerve crush injury. AIM OF THE STUDY: To investigate the underlying molecular mechanism of the DGMI in retinal ganglion cells (RGCs) apoptosis. MATERIALS AND METHODS: TUNEL staining was used to observe the anti-apoptotic effects of DGMI on the adult rat optic nerve injury (ONC) model, and flow cytometry and hoechst 33,342 staining were used to observe the anti-apoptotic effects of DGMI on the oxygen glucose deprivation (OGD) induced RGC-5 cells injury model. The regulation of apoptosis and MAPKs pathways were investigated with Immunohistochemistry and Western blotting. RESULTS: This study demonstrated that DGMI is able to decrease the conduction time of F-VEP and ameliorate histological features induced by optic nerve crush injury in rats. Immunohistochemistry and TUNEL staining results indicated that DGMI can also inhibit cell apoptosis via modulating MAPKs signaling pathways. In addition, treatment with DGMI markedly improved the morphological structures and decreased the apoptotic index in RGC-5 cells. Mechanistically, DGMI could significantly inhibit cell apoptosis by inhibiting p38, JNK and Erk1/2 activation. CONCLUSION: The study shows that DGMI and ginkgolides inhibit RGCs apoptosis by impeding the activation of MAPKs signaling pathways in vivo and in vitro. Therefore, the present study provided scientific evidence for the underlying mechanism of DGMI and ginkgolides on optic nerve crush injury.
Asunto(s)
Apoptosis/efectos de los fármacos , Lesiones por Aplastamiento/tratamiento farmacológico , Ginkgólidos/farmacología , Traumatismos del Nervio Óptico/tratamiento farmacológico , Animales , Línea Celular , Lesiones por Aplastamiento/patología , Modelos Animales de Enfermedad , Ginkgo biloba/química , Ginkgólidos/administración & dosificación , Ginkgólidos/química , Etiquetado Corte-Fin in Situ , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Meglumina/administración & dosificación , Traumatismos del Nervio Óptico/patología , Ratas , Ratas Sprague-Dawley , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patologíaRESUMEN
The present study was undertaken to identify whether prostaglandin E2 receptor is the potential receptor/binding site for Ginkgolide A, Ginkgolide B, Ginkgolide K, and Bilobalide, the four main ingredients of the Ginkgo biloba L., leaves. Using functional assays, we identified EP4, coupled with Gs protein, as a target of Ginkgolide B. In human neuroblastoma SH-SY5Y cells suffered from oxygen-glucose deprivation/reperfusion, Ginkgolide B-activated PKA, Akt, and ERK1/2 as well as Src-mediated transactivation of epidermal growth factor receptor. These resulted in downstream signaling pathways, which enhanced cell survival and inhibited apoptosis. Knockdown of EP4 prevented Ginkgolide B-mediated Src, epidermal growth factor receptor (EGFR), Akt, and ERK1/2 phosphorylation and neuroprotective effects. Moreover, Src inhibitor prevented Ginkgolide B-mediated EGFR transactivation and the downstream Akt and ERK1/2 activation, while the phosphorylation of PKA induced by Ginkgolide B was not affected, indicating Ginkgolide B might transactivate EGFR in a ligand-independent manner. EP4 knockdown in a rat middle cerebral artery occlusion (MCAO) model prevented Ginkgolide B-mediated infarct size reduction and neurological assessment improvement. At the same time, the increased expressions of p-Akt, p-ERK1/2, p-PKA, p-Src, and p-EGFR and the deceased expression of cleaved capases-3 induced by Ginkgolide B in cerebral cortex were blocked due to EP4 knockdown. In conclusion, Ginkgolide B exerts neuroprotective effects in rat MCAO model through the activation of EP4 and the downstream transactivation of EGFR.
RESUMEN
OBJECTIVE: To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR). METHODS: The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed. RESULTS: After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (Pï¼0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (Pï¼0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (Pï¼0.01). CONCLUSION: The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.
Asunto(s)
Transducción de Señal , Apoptosis , Niño , Daunorrubicina , Humanos , Fosfohidrolasa PTEN , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-aktRESUMEN
Four children (two boys and two girls), aged from 3 years and 7 months to 5 years, had mild or moderate anemia, mild hepatosplenomegaly, jaundice (mainly an increase in indirect bilirubin), an increase in the percentages of reticulocytes and spherical erythrocytes in peripheral blood smear and an increase in erythrocyte osmotic brittleness. High-throughput sequencing found two novel mutations in the SLC4A1 gene, c.37G>A and c.340T>C, in case 1 and case 2 respectively, and these two mutations were predicted to be pathogenic by Mutation Taster. The Polyphen2 scores of these two mutations were 0.87 and 0.83 respectively, which suggested that these mutations were probably damaging. The SIFT scores of these two mutations were 0.008 and 0.09 respectively, suggesting that these mutations were probably damaging. No abnormality in this gene was found in their parents. Two reported heterozygous mutations in the ANK1 gene, c.830A>G and c.985G>C, were found in case 3 and case 4 respectively. Gene detection was not performed for the parents of case 3. The mother of case 4 was diagnosed with hereditary spherocytosis and had a heterozygous mutation of c.985G>C in the ANK1 gene. All four children were diagnosed with hereditary spherocytosis. Case 3 had a hemoglobin level of <80â g/L and underwent splenectomy at the age of 5 years and 6 months, and regular postoperative reexamination showed a hemoglobin level of >105â g/L. Hereditary spherocytosis is a hereditary hemolytic disease caused by abnormality in erythrocyte membrane protein, and gene detection helps to make a confirmed diagnosis.
Asunto(s)
Esferocitosis Hereditaria , Ancirinas , Niño , Preescolar , Eritrocitos , Femenino , Heterocigoto , Humanos , Masculino , MutaciónRESUMEN
In this study, we aimed to investigate the effects of diterpene ginkgolides meglumine injection (DGMI) on paraquat (PQ)-induced lung injury and pulmonary fibrosis in rats. Male SD rats were challenged by PQ (20?mg/kg, i.p.) with or without either DGMI (1.25, 2.5, 5?mg/kg, i.p.) or Edaravone (EDA, 6?mg/kg, i.p.) posttreatment 2?h after PQ administration. Lung tissues were removed for biochemical analyses and pathological examinations on day 1, day 3, day 7, day 14 and day 21. Results showed that the administration of DGMI significantly increased the survival of PQ-challenged rats. At the same time, DGMI reversed the increase of Malondialdehyde (MDA) level and the decrease of Super Oxide Dismutase (SOD) level in lung tissues. Moreover, lung to body weight ratio, Interleukin-1beta (IL-1?), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-?) levels in lung tissues were reduced compared with the model group. H&E and Masson staining revealed that DGMI (5?mg/kg) alleviated histological injury and pulmonary fibrosis, and EDA (6?mg/kg) exerted approximate effects. Immunohistochemistry staining presented that the benefit effects of DGMI were associated with its ability to activate Akt-Nrf-2 pathway. In conclusion, these results suggest that DGMI possesses potential role in future therapies for PQ-induced lung injury and pulmonary fibrosis.
Asunto(s)
Ginkgólidos/farmacología , Meglumina/farmacología , Edema Pulmonar/prevención & control , Fibrosis Pulmonar/prevención & control , Lesión Pulmonar Aguda , Animales , Antipirina/análogos & derivados , Antipirina/farmacología , Relación Dosis-Respuesta a Droga , Edaravona , Ginkgólidos/administración & dosificación , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdehído/metabolismo , Meglumina/administración & dosificación , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons. METHODS: A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG. RESULTS: After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group (6.4±2.6â g vs 2.3±0.5â g; P<0.001). The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared with the ND group, the HFD group had significant increases in the TRPV1 current intensity and number of action potentials in the DRG (P<0.05). CONCLUSIONS: High-fat diet induces a significant increase in body weight and leads to high expression of TRPV1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.
Asunto(s)
Dieta Alta en Grasa , Ganglios Espinales/química , Sistema Respiratorio/química , Canales Catiónicos TRPV/análisis , Potenciales de Acción , Animales , Peso Corporal , Masculino , Ratones , Ratones Endogámicos C57BL , Canales Catiónicos TRPV/fisiologíaRESUMEN
Aflatoxin B1 (AFB1) develops various toxic effects in the liver by impairing mitochondrial function, inducing cell apoptosis. However, little is focused on its toxicity to broiler cardiomyocytes (BCMs). Here, the mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, cardiac troponin T (cTnT) location, apoptosis induced by AFB1, and antioxidative genes were investigated in BCMs. It was found that AFB1 evoked intracellular ROS generation, and induced apoptosis in BCMs. AFB1 treatment resulted in increased percentage of apoptotic cells, increased location range of cTnT in cytoplasm, upregulated messenger RNA (mRNA) expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and downregulated mRNA expressions of Mn-superoxide dismutase in BCMs. These findings suggested AFB1 treatment caused significant cardiomyocyte damage and cardiotoxicity, impairment of mitochondrial functions, activated ROS generation, and induced apoptosis, and probably was involved in the Nrf2 signal pathway in BCMs.
Asunto(s)
Aflatoxina B1/toxicidad , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Antioxidantes/metabolismo , Células Cultivadas , Pollos , Citoplasma/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Expresión Génica , Miocitos Cardíacos/citología , Factor de Transcripción NF-E2/genética , Factor de Transcripción NF-E2/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Troponina T/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the clinical features of Diamond-Blackfan anemia (DBA) and related pathogenic genes. METHODS: A retrospective analysis was performed for the clinical data of two children with DBA, and related literature was reviewed. RESULTS: The two children with DBA (2-3 months old) manifested with severe normochromic normocytic anemia, decreased reticulocyte count, and increased serum iron and serum ferritin. Normal white blood cell and platelet counts were noted in the two patients. Bone marrow examination showed a decreased percentage of erythrocytes and rare normoblasts in the two patients. Gene screening showed a reported pathogenic heterozygous mutation in RPS19 gene, c.212G>A (p. Gly71Glu), in one patient, and there were no mutations in his parents. In the other patient, gene screening showed a heterozygous mutation in RPL5 gene, c.740T>C (p. I247L), which had not been reported in literature, and there were no mutations in her parents. A bioinformatic analysis showed that this might be a pathogenic mutation. CONCLUSIONS: The onset age of DBA is early infancy in most children, with a manifestation of erythroid deficiency. RPS19 and RPL5 gene mutations are common causes of this disease. Molecular detection helps with the early diagnosis of DBA.
Asunto(s)
Anemia de Diamond-Blackfan/genética , Proteínas Ribosómicas/genética , Biología Computacional , Humanos , Lactante , Masculino , MutaciónRESUMEN
This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.
Asunto(s)
Asma/complicaciones , Obesidad/etiología , Humanos , Leptina/fisiología , Factor de Crecimiento Nervioso/fisiología , Neurotransmisores/fisiología , Inhibidor 1 de Activador Plasminogénico/fisiologíaRESUMEN
Reactive oxygen species are damaging to cardiomyocytes. H9c2 cardiomyocytes are commonly used to study the cellular mechanisms and signal transduction in cardiomyocytes, and to evaluate the cardioprotective effects of drugs following oxidative damage. The present study developed a robust, automated high throughput screening (HTS) assay to identify cardioprotective agents from a traditional Chinese medicine (TCM) library using a H2O2induced oxidative damage model in H9c2 cells. Using this HTS format, several hits were identified as cardioprotective by detecting changes to cell viability using the cell counting kit (CCK)8 assay. Two TCM extracts, KY0520 and KY0538, were further investigated. The results of the present study demonstrated that treatment of oxidatively damaged cells with KY0520 or KY0538 markedly increased the cell viability and superoxide dismutase activity, decreased lactate dehydrogenase activity and malondialdehyde levels, and inhibited early growth response1 (Egr1) protein expression. The present study also demonstrated that KY0520 or KY0538 treatment protected H9c2 cells from H2O2induced apoptosis by altering the Bcl-2/Bax protein expression ratio, and decreasing the levels of cleaved caspase3. In addition, KY0520 and KY0538 reduced the phosphorylation of ERK1/2 and p38MAPK proteins, and inhibited the translocation of Egr1 from the cytoplasm to nucleus in H2O2-treated H9c2 cells. These findings suggested that oxidatively damaged H9c2 cells can be used for the identification of cardioprotective agents that reduce oxidative stress by measuring cell viabilities using CCK8 in an HTS format. The underlying mechanism of the cardioprotective activities of KY0520 and KY0538 may be attributed to their antioxidative activity, regulation of Egr1 and apoptosisassociated proteins, and the inhibition of ERK1/2, p38-MAPK and Egr-1 signaling pathways.
Asunto(s)
Cardiotónicos/farmacología , Descubrimiento de Drogas/métodos , Medicamentos Herbarios Chinos/farmacología , Estrés Oxidativo/efectos de los fármacos , Línea Celular Tumoral , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Peróxido de Hidrógeno/farmacología , Lactato Deshidrogenasas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Malondialdehído/metabolismo , Medicina Tradicional China , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reproducibilidad de los Resultados , Superóxido Dismutasa/metabolismoRESUMEN
The Ate1 arginyltransferase (R-transferase) is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. Ate1 arginylates N-terminal Asp, Glu, or (oxidized) Cys. The resulting N-terminal Arg is recognized by ubiquitin ligases of the N-end rule pathway. In the yeastSaccharomyces cerevisiae, the separase-mediated cleavage of the Scc1/Rad21/Mcd1 cohesin subunit generates a C-terminal fragment that bears N-terminal Arg and is destroyed by the N-end rule pathway without a requirement for arginylation. In contrast, the separase-mediated cleavage of Rec8, the mammalian meiotic cohesin subunit, yields a fragment bearing N-terminal Glu, a substrate of the Ate1 R-transferase. Here we constructed and used a germ cell-confinedAte1(-/-)mouse strain to analyze the separase-generated C-terminal fragment of Rec8. We show that this fragment is a short-lived N-end rule substrate, that its degradation requires N-terminal arginylation, and that maleAte1(-/-)mice are nearly infertile, due to massive apoptotic death ofAte1(-/-)spermatocytes during the metaphase of meiosis I. These effects ofAte1ablation are inferred to be caused, at least in part, by the failure to destroy the C-terminal fragment of Rec8 in the absence of N-terminal arginylation.
Asunto(s)
Apoptosis , Metafase , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Proteolisis , Separasa/metabolismo , Espermatocitos/metabolismo , Aminoaciltransferasas/genética , Aminoaciltransferasas/metabolismo , Animales , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Masculino , Ratones , Ratones Noqueados , Proteínas Nucleares/genética , Fosfoproteínas/genética , Separasa/genéticaRESUMEN
This paper summarized the recent 30 years research progress of the chemical constituents from Notopterygii Rhizoma et Radix. The chemical constituents from Notopterygii Rhizoma et Radix mainly consist of coumarins, polyene-polyacetylenes, sesquiterpenes, phenolic acids, while steroids and flavonoids were less reported. All constituents were confirmed and corrected through SciFinder. We also checked the Chinese name and English name and listed the CAS number of each compound. It can provide some guidelines for the research, development and utilization of Notopterygii Rhizoma et Radix in the future. Whether there is columbianin in the Notopterygii Rhizoma et Radix need to be further researched.
Asunto(s)
Apiaceae/química , Medicamentos Herbarios Chinos/análisis , Rizoma/químicaRESUMEN
OBJECTIVE: To investigate the association between single nucleotide polymorphism (SNP) (rs17166050) in RAD50 gene and acute lymphoid leukemia (ALL) in children. METHODS: A total of 177 ALL children from Wuhan and surrounding areas and 232 healthy children were selected. The numbers of standard-risk, medium-risk, and high-risk children were 66, 69, and 42, respectively. The genotypes of SNP in RAD50 gene were determined using PCR-RFLP, and the relationship of the RAD50 polymorphism with ALL susceptibility and clinical risk was analyzed. RESULTS: The genotype (AA, GA, and GG) distribution of SNP in RAD50 gene showed significant differences between the ALL and control groups (P=0.038), and G allele was significantly associated with ALL susceptibility (OR=1.459, 95% CI: 1.034-2.057, P=0.031). However, the SNP was not associated with the risk stratification of ALL. CONCLUSIONS: The SNP (rs17166050) in RAD50 gene is associated with the susceptibility to ALL in children, but is not associated with the risk stratification of ALL.
Asunto(s)
Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Ácido Anhídrido Hidrolasas , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , RiesgoRESUMEN
OBJECTIVE: To study the role of Helicobacter pylori (H. pylori) infection in newly diagnosed childhood immune thrombocytopenia (ITP). METHODS: A total of 495 children with newly diagnosed ITP who were hospitalized for the first time between January 2011 and December 2013 were included as the case group. A total of 123 children with common respiratory tract infection (not ITP or other diseases of blood system) were randomly selected as the control group. All patients were divided into four groups by age: <1 year group, 1-3 years group, 3-7 years group, and 7-14 years group. The incidence of H. pylori infection in all age groups and the clinical outcomes of ITP children with or without H. pylori infection were retrospectively analyzed. RESULTS: The incidence rate of H. pylori infection in the case group increased with increasing age. There was no significant difference in the incidence rate of H. pylori infection between the case and the control groups among subjects of the same age (P>0.05). All the ITP patients were not given anti-H. pylori treatment and only received the treatment (glucocorticoid and/or immunoglobulin) for ITP, and their remission rate declined with increasing age. There was no significant difference in the remission rate between the ITP children with H. pylori infection and those without H. pylori infection in the same age group (P>0.05). CONCLUSIONS: H. pylori infection may not be a major cause of ITP in children, and the clinical outcomes of children with acute ITP are not affected by receiving anti-H. pylori treatment or not.