RESUMO
BACKGROUND: Congenital heart disease (CHD) frequently manifests as a complex phenotype and approximately one-third of cases may be caused by genetic factors. BCOR, an X-linked gene encoding the corepressor of BCL6, has been demonstrated to be closely involved in human heart development. However, whether BCOR variants represent the genetic etiology underlying CHD needs further investigation. METHODS: We performed whole exome sequencing on CHD nuclear families and identified a candidate gene, BCOR, by robust bioinformatic analysis and medical literature searches. Targeted DNA sequencing of the candidate gene was conducted and then the association between variants and the risk of developing CHD was analyzed. The effects of BCOR mutations on gene expression, localization, protein interaction, and signaling pathways were evaluated in vitro. RESULTS: We identified a BCOR hemizygous missense variant (c.1448C>T, p.Pro483Leu) in a male proband presented with CHD/heterotaxy. Sanger sequencing confirmed that this variant was inherited from his asymptomatic mother. Interestingly, through literature searches, we observed another novel BCOR hemizygous missense variant (c.1619G>A, p.Arg540Gln) in a CHD patient with heterotaxy, supporting the pathogenic evidence of BCOR variants. Functional experiments conducted in vitro revealed that the variant p.Pro483Leu altered the subcellular localization of BCOR protein, disrupted its interaction with BCL6, and significantly promoted cell proliferation, whereas the variant p.Arg540Gln displayed no obvious effects. Nevertheless, transcriptional analysis revealed that down-regulation of BCOR substantially enhanced the activities of mitogen-activated protein and phosphoinositide 3-kinase-AKT signaling pathways, which are closely attributed to heart development. Targeted sequencing of 932 sporadic CHD patients enriched nine variants of BCOR predicted as likely rare and damaging and a septal defect was present in 81.8% (9/11) of them, including the two probands, which was consistent with the possible phenotype caused by BCOR defects. CONCLUSIONS: The findings of the present study indicate that variants in BCOR may predispose individuals to CHD in the Chinese Han population.
Assuntos
Cardiopatias Congênitas , Defeitos dos Septos Cardíacos , Humanos , Masculino , Genes Ligados ao Cromossomo X , População do Leste Asiático , Fosfatidilinositol 3-Quinases , Cardiopatias Congênitas/genética , Defeitos dos Septos Cardíacos/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genéticaRESUMO
A previously healthy 9-year-old girl was referred to us for the evaluation of a murmur on a routine clinical examination. Routine electrocardiogram and chest x-ray were normal. The cardiac enzymes were normal. Combining ultrasound and CCTA, it was confirmed that the hemodynamics of the heart was a left-to-right shunt and that RVOT stole blood from the left ventricle through the single coronary artery (SCA).
Assuntos
Doença da Artéria Coronariana , Anomalias dos Vasos Coronários , Fístula , Cardiopatias Congênitas , Feminino , Humanos , Criança , Ventrículos do Coração/diagnóstico por imagem , Angiografia Coronária , Fístula/diagnóstico , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagemRESUMO
Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(ß-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 µmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 µmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.
Assuntos
Alcaloides , Corydalis , Humanos , Corydalis/química , Alcaloides/farmacologia , Alcaloides/química , Inflamação , Análise Espectral , Isoquinolinas/farmacologiaRESUMO
Modernization of Chinese medicine is an important development direction of traditional Chinese medical sciences. It is of great significance to understand the mechanism of Chinese medicine with basic research, which can also accelerate the development and utilization of Chinese medicine. Salviae Miltiorrhizae Radix et Rhizoma is one of the most commonly used Chinese medicines in China for the prevention and treatment of cardiovascular and cerebrovascular diseases. It has received key and extensive attention worldwide in the following aspects: main active ingredients and their pharmacological mechanism, function and regulation of their biosynthetic pathway and application of their synthetic biology as well as the clinical preparations. The new and developing chemical analysis, network pharmacology, molecular pharmacognosy and omics make the modernization research of Salviae Miltiorrhizae Radix et Rhizoma comprehensive and in-depth. This study systematically reviewed the modernization research of Salviae Miltiorrhizae Radix et Rhizoma, which focused on its pharmacological effects, preparation research, biosynthesis and regulation mechanism of the active ingredients, and expected to exert the model role of Salviae Miltiorrhizae Radix et Rhizoma in the research of Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Medicina Tradicional Chinesa , Salvia miltiorrhiza/química , Medicamentos de Ervas Chinesas/química , Rizoma/química , Raízes de PlantasRESUMO
Imported medicinal materials are an important part of Chinese medicinal resources. To be specific, about 10% of the around 600 commonly used Chinese medicinal materials are from abroad, and the introduction of foreign medicinal materials has promoted the development of Chinese medicine. Amid the advancement of reform and opening up and the "Belt and Road" Initiative, major headway has been made in the cross-border trade in China, bringing opportunities for the import of medicinal materials from border ports. However, for a long time, there is a lack of systematic investigation on the types of exotic medicinal materials at border ports. In the fourth national census of traditional Chinese medicine resources, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, together with several organizations, investigated the nearly 40 border ports, Chinese medicinal material markets, and border trade markets in 6 provinces/autonomous regions in China for the first time and recorded the types, sources, circulation, and the transaction characteristics of imported medicinal materials. Moreover, they invited experts to identify the origins of the collected 237 medicinal materials. In addition, the status quo and the problems of the medicinal materials were summarized. This study is expected to lay a basis for clarifying the market and origins of imported medicinal materials as well as the scientific research on and supervision of them.
Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , Medicina Tradicional Chinesa , Registros , Censos , ChinaRESUMO
Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.
Assuntos
Isquemia Miocárdica , Extratos Vegetais/farmacologia , Rhus , Animais , Apoptose , Camundongos , Isquemia Miocárdica/tratamento farmacológico , Miocárdio , Miócitos Cardíacos , Proteína X Associada a bcl-2RESUMO
Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.
Assuntos
Apoptose , Miócitos Cardíacos , Hipóxia Celular , Humanos , Miocárdio , Estresse OxidativoRESUMO
To enhance specific or total sophorolipids (SLs) production by Starmerella bombicola for specific application, mutant library consisting of 106 mutants from 7 batches was constructed via atmospheric and room-temperature plasma (ARTP). When compared to the wild strain, 11, 36 and 12 mutants performed increases over 30% in lactonic, acidic or total SLs production. Genetic stability investigation showed that 8, 7, and 4 mutants could maintain the improved SLs production capacity. Mutants of A6-9 and A2-8 were selected out for enhanced specific SLs and total SLs production in fed-batch cultivation in flask. Without optimization, A6-9 obtained the highest reported lactonic SLs production of 51.95 g/l and A2-8 performed comparable acidic and total SLs production of 68.75 g/l and 100.33 g/l with all the reported stains. The structural composition of the obtained SLs was analyzed by HPLC and LC/MS, and the results confirmed the enhancement of SLs and certain SL components. These mutants would be important in industrial applications because the production and purification costs of SLs could be greatly reduced. Besides, the acquisition of these mutants also provided materials for the investigation of regulation mechanism of SLs biosynthesis for further genetic engineering of S. bombicola. Furthermore, critical micelle concentration (CMC), minimum surface tension (STmin) and hydrophilic-lipophilic balance (HLB) of the SLs obtained from the wild and mutant strains were also examined and compared. These results demonstrated the feasibility of obtaining SLs with different properties from different strains and the high efficiency of mutation breeding of S. bombicola by ARTP.
Assuntos
Mutação , Ácidos Oleicos/biossíntese , Gases em Plasma/farmacologia , Saccharomycetales , Ácidos Oleicos/genética , Saccharomycetales/genética , Saccharomycetales/metabolismoRESUMO
The Aspongopus chinensis is an insect of the genus Hemiptera, which can be used both as a medicinal and as a gourmet in the folk. It has a long history as a drug, which has the effect of regulating Qi and relieving pain, and warming the Yang. It is mainly used to treat stomach cold and pain, liver and stomach pain, kidney deficiency and impotence, and waist and knee pain. Modern pharmacological studies have shown that A. chinensis has a variety of pharmacological activities. For example, it can be used to fight tumors, improve reproductive damage, and antibacterial, anti-oxidation, anti-coagulation, anti-ulcer, anti-fatigue and so on. The chemical constituents of A. chinensis currently reported mainly include odorous components, vitamins, fatty acids and proteins, amino acids, and other nutrients, as well as nucleosides and dopamines. This study summarizes and analyzes the related research literatures of A. chinensis in China and abroad, and provides a reference for its further development and research from the aspects of chemical composition, pharmacological action and clinical application.
Assuntos
Produtos Biológicos/química , Heterópteros/química , Animais , China , Medicina Tradicional ChinesaRESUMO
Saussurea lappa originates in India, and now mainly grow in Yunnan, Sichuan and other places in China. It is one of the commonly used traditional herbal medicines in Tibet and other minority regions, with effects in regulating qi to relieve pain and invigo-rating spleen to promote food. It has been used in clinic for gastrointestinal diseases, such as Qi stagnation syndrome of spleen and stomach, diarrhea and tenesmus. More than 200 compounds have been identified from S. lappa. Among them, sesquiterpenoids attracted much attention. In terms of the number of compounds, eudesmanetype is dominant, guaiane and germacranetypes have also been reported frequently. Pharmacological studies have involved extracts, volatile oils and monomeric components represented by dehydrocostus lactone. Anti-tumor, anti-inflammatory and anti-bacterial effects on digestive system have attracted great attention. However, due to the complex sources of S. lappa and widely used in clinical practice, there is few research progress on relevant chemical constituents and pharmacological activities. This paper systematically summarizes terpenes and the pharmacological effects of S. lappa, in order to provide basis for further studies and clinical applications.
Assuntos
Saussurea , Sesquiterpenos , China , Extratos Vegetais , Terpenos , TibetRESUMO
OBJECTIVE: To investigate the prevalence of congenital heart disease (CHD) in China based on a large prospective multicenter screening study. STUDY DESIGN: A total of 122 765 consecutive infants born at 18 hospitals throughout China between August 1, 2011, and November 30, 2012, were included. Cases of CHD were identified by echocardiography, clinical assessment, and telephone follow-up. RESULTS: The overall prevalence of CHD was 8.98 per 1000 live births (critical, 1.46; serious, 1.47; significant, 5.00; nonsignificant, 1.07), including 7.15 in male infants and 11.11 in female infants. The most common CHD was ventricular septal defect (3.3), followed by atrial septal defect (1.7), patent ductus arteriosus (0.78), pulmonary stenosis (0.73), tetralogy of Fallot (0.47), and transposition of the great arteries (0.35). Female predominance was observed for all CHD and mild CHD (significant and nonsignificant), and male predominance was observed for the critical CHDs. The proportion of preterm newborns was substantially higher among the major CHD cases (critical and serious) compared with normal newborns. There were appreciably more low birth weight infants among the critical CHD cases compared with normal newborns. Significantly higher rates of ventricular septal defect and atrioventricular septal defect were found in infants born to mothers aged ≥35 years. Extracardiac anomalies were found in 9.3% of CHD cases. The risk of CHD was increased by approximately 3-fold when a first-degree relative had CHD. CONCLUSIONS: Our estimates are concordant with data from Western studies. This screening study may provide more accurate and complete information on the overall prevalence of CHD in China.
Assuntos
Cardiopatias Congênitas/epidemiologia , Triagem Neonatal/métodos , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Nascido Vivo , Masculino , Prevalência , Estudos ProspectivosRESUMO
Osteocalcin is a newly identified type of cytokine secreted by osteoblasts, which has an endocrine function, mediates energy and glycol-lipid metabolism, and is closely related to cardiovascular diseases. In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVEF > 62%, the serum osteocalcin levels were significantly higher than in those with LVEF ≤ 62% (P = 0.042), whereas this difference was absent in the women. Both the serum osteocalcin (ß = 0.095, P = 0.028) and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP; ß = -0.003, P < 0.01) levels remained independently significantly correlated with LVEF in the men but not in the women. Receiver operating characteristic (ROC) analyses of the men revealed that the serum osteocalcin (P = 0.007), serum NT-pro-BNP (P = 0.018) and serum osteocalcin + NT-pro-BNP (P < 0.01) levels were all significant in identifying left ventricular systolic dysfunction at baseline, but the pairwise comparisons of the three areas under the curves (AUCs) were all non-significant. The men in the lower osteocalcin level group at baseline suffered a greater risk of future cardiac death than those in the higher osteocalcin level group, whereas the result for NT-pro-BNP exhibited the opposite pattern. In conclusion, lower serum osteocalcin levels in the men could identify left ventricular systolic dysfunction and cardiac death in a manner that was not inferior to high serum NT-pro-BNP levels.
Assuntos
Morte Súbita Cardíaca/patologia , Osteocalcina/sangue , Disfunção Ventricular Esquerda/metabolismo , Idoso , China , Feminino , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Disfunção Ventricular Esquerda/sangueRESUMO
There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (ß = 0.151, P = 0.035) and HOMA-IR (ß = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.
Assuntos
Jejum , Hiperglicemia/classificação , Hiperglicemia/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/metabolismo , Feminino , Humanos , Masculino , Manose/metabolismo , Metabolômica/métodos , Pessoa de Meia-Idade , Ribonucleotídeos/metabolismoRESUMO
BACKGROUND: Challenges remain in the judgement of pathological murmurs in newborns at maternity hospitals, and there are still many simple major CHD patients in developing countries who are not diagnosed in a timely fashion. This study aimed to evaluate the accuracy of cardiac auscultation on neonatal CHD by general paediatricians. METHODS: We conducted a prospective study at three hospitals. All asymptomatic newborns underwent auscultation, pulse oximetry monitoring, and echocardiography. Major CHD was classified and confirmed through follow-up. We evaluated the accuracy of various degrees of murmurs for detecting major CHD to determine the most appropriate standards and time of auscultation. RESULTS: A total of 6750 newborns were included. The median age of auscultation was 43 hours. Cardiac murmurs were identified in 6.6% of newborns. For all CHD, 44.4% had varying degrees of murmurs. A murmur of grade ≥2 used as a reference standard for major CHD had a sensitivity of 89.58%. The false positive rate of murmurs of grade ≥2 for detecting major CHD was significantly negatively related to auscultation time, with 84.4% of false positives requiring follow-up for non-major CHD cardiac issues. Auscultation after 27 hours of life could reduce the false positive rate of major CHD from 2.7 to 0.9%. CONCLUSIONS: With appropriate training, maternity hospital's paediatricians can detect major CHD with high detection rates with an acceptable false positive rate.
Assuntos
Auscultação Cardíaca , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Triagem Neonatal/métodos , China/epidemiologia , Reações Falso-Positivas , Feminino , Sopros Cardíacos/diagnóstico , Humanos , Recém-Nascido , Masculino , Oximetria , Pediatras/educação , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
The distribution and diastereomeric profiles of hexabromocyclododecanes (HBCDs, identified as persistent organic pollutants) in soil-vegetable system of open fields remain unknown. In this study, three main HBCD diastereoisomers (α-, ß-, and γ-HBCDs) were analyzed in paired soil and vegetable samples from vegetable farms in four cities (Guangzhou, Jiangmen, Huizhou, Foshan) of the Pearl River Delta region, Southern China. The sum concentrations of the three diastereoisomers (∑HBCDs) in soils varied from 0.99 to 18.4â¯ng/g (dry weight) with a mean of 5.77â¯ng/g, decreasing in the order of Jiangmenâ¯>â¯Guangzhouâ¯>â¯Huizhouâ¯>â¯Foshan. The distributions of HBCDs in both soil and vegetable were diastereomer-specific, with γ-HBCD being predominant. The ∑HBCDs in vegetables ranged from 0.87 to 32.7â¯ng/g (dry weight) with a mean of 16.6â¯ng/g, generally higher than those of the corresponding soils. Thus bioconcentration factors (BCFs, the ratio of contaminant concentration in vegetable to that in soil) of HBCDs were generally greater than 1.0, implying higher accumulation in vegetable. The estimated daily intake (EDI) of ΣHBCDs via consumption of vegetables varied from 0.26 to 9.35â¯ng/kgâ¯bw/day with a mean of 3.60â¯ng/kgâ¯bw/day for adults and from 0.32 to 11.5â¯ng/kgâ¯bw/day with a mean of 4.41â¯ng/kgâ¯bw/day for Children, far lower than the oral reference dose (RfD, 2â¯×â¯105â¯ng/kgâ¯bw/day) proposed by US National Research Council. These results suggest that HBCD in the vegetables posed low health risk for the local population. These data are the first report on HBCD occurrence and health risk in soil-vegetable system of open fields.
Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Criança , China , Cidades , Monitoramento Ambiental , Humanos , Solo , VerdurasRESUMO
Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculataï¼with a variety of pharmacological activityï¼widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this studyï¼the coding sequence of A. paniculata CPR was screened and cloned by homologous alignmentï¼named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression. After isolation and purificationï¼the enzyme activity was identified in vitro. The results showed that ApCPR4 could reduce the cytochrome c and ferricyanide in NADPH-dependent manner. In order to verify its in vivo functionï¼ApCPR4 and CYP76AH1 were co-transformed into yeast engineering bacteria. The results showed that ApCPR4 could help CYP76AH1 catalyze the formation of rustols in yeast. Real-time quantitative PCR results showed that the expression of ApCPR4 increased gradually in leaves treated with methyl jasmonate (MeJA). The expression pattern was consistent with the trend of induction and accumulation of andrographolide by MeJAï¼suggesting that ApCPR4 was associated with biosynthesis of andrographolide.
Assuntos
Andrographis/enzimologia , NADPH-Ferri-Hemoproteína Redutase/genética , Proteínas de Plantas/genética , Acetatos , Andrographis/genética , Vias Biossintéticas , Clonagem Molecular , Ciclopentanos , Diterpenos/metabolismo , Oxilipinas , Folhas de Planta/enzimologiaRESUMO
To observe the protective effect of scutellarin ethyl ester on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats(MCAOR), and explore its mechanism. Totally 84 male SD rats were randomly divided into seven groupsï¼ sham-operated group, model group,positive drug group(niomdipine,12 mgâ¢kg⻹), Brevisapin tablets group(48 mgâ¢kg⻹), and high, middle and low-dose scutellarin ethyl ester groups(100, 50, 25 mgâ¢kg⻹). The MCAOR model was prepared by using thread embolism method to observe the neurological function of rats, the area of cerebral infarction was measured with TTC, and the levels of MDA, SOD and NO in serum were detected with semiautomatic biochemistry analyzer.Ox-LDL and TNF-α cell injury models was established by treating HUVECs with 200 mgâ¢L⻹ ox-LDL and 100 µgâ¢L⻹ TNF-α,and the levels of MDA, SOD, NO, ET, 6-keto-PGF1α,TXB2, IL-1, IL-6, IL-8, ICAM-1 and PECAM-1 in the cell supernatant were determined. The results showed that scutellarin ethyl ester could effectively improve the neurological function of MCAOR rats, and significantly reduce the area of cerebral infarction. Compared with the model group, activities of SOD and NO in serum increased, while content of MDA decreased. In the cell supernatant, activities of SOD, 6-keto-PGF1α and NO increased, content of IL-1, IL-6, IL-8, ICAM-1, PECAM-1, TXB2, ET and MDA decreased, which indicated that scutellarin ethyl ester has a certain protective effect on focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats, and its mechanism may be related to antioxidative stress, improvement of endothelial function and reduction in inflammatory reaction.
Assuntos
Apigenina/farmacologia , Isquemia Encefálica/tratamento farmacológico , Glucuronatos/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Animais , Masculino , Artéria Cerebral Média , Ratos , Ratos Sprague-Dawley , Traumatismo por ReperfusãoRESUMO
Protein complexes are involved in the synthesis of multiple secondary metabolites in plants, and their separation is essential to elucidate plant secondary metabolism and improve in vitro catalytic efficiency. In this study, the transgenic hairy roots of CYP76AH1, a key enzyme of tanshinone synthesis pathway, was constructed and the transgenic hairy roots of Danshen overexpressing CYP76AH1 protein were screened by Western blotting and used as a tissue culture material for the subsequent extraction of protein complex in tanshinone synthesis pathway. By optimizing the type and concentration of the detergent in the protein extraction buffer, the buffer containing 0.5% Triton X-100 was selected as the best extraction buffer, and a relatively large amount of soluble CYP76AH1 protein was isolated. This study lays the foundation for the further separation and purification of protein complexes interacting with CYP76AH1, and provides the idea for deep analysis of tanshinone metabolic pathway.
Assuntos
Família 7 do Citocromo P450/genética , Raízes de Plantas/enzimologia , Salvia miltiorrhiza/enzimologia , Abietanos/biossíntese , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Salvia miltiorrhiza/genéticaRESUMO
BACKGROUND: The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery. METHODS: A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via PHASE V.2.1 software. RESULTS: The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes. CONCLUSIONS: PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR * 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery. TRIAL REGISTRATION: The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.