Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Clin Cardiol ; 47(4): e24269, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634453

RESUMO

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.


Assuntos
Neoplasias da Mama , Cardiopatias , Humanos , Pessoa de Meia-Idade , Feminino , Incidência
2.
J Am Heart Assoc ; 13(3): e030132, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38293950

RESUMO

BACKGROUND: An association between variability of cardiovascular risk factors and cardiovascular events has been reported. We examined whether intensive lifestyle intervention (ILI) for weight loss decreased variability of cardiovascular risk factors with a view to additional cardiometabolic benefits. METHODS AND RESULTS: This study was a post hoc secondary analysis of the Look AHEAD (Action for Health in Diabetes) study. Cardiovascular risk factors were measured at 1-year intervals for 4 years in 4249 adults with overweight or obesity and type 2 diabetes who were randomly assigned to ILI or diabetes support and education. Long-term variability was defined as the SD of cardiovascular risk factors during 4-year follow-up. At multiple linear regression analysis, compared with the diabetes support and education group, the ILI group was associated with reduced variability of fasting blood glucose (ß=-1.49 [95% CI, -2.39 to -0.59]), total cholesterol (ß=-1.12 [95% CI, -1.75 to -0.48]), and low-density lipoprotein cholesterol (ß=-1.04 [95% CI, -1.59 to -0.49]), as well as increased variability of systolic blood pressure (ß=0.27 [95% CI, 0.00-0.54]). No significant effect of ILI was found on the variability of diastolic blood pressure (ß=-0.08 [95% CI, -0.22 to 0.05]). CONCLUSIONS: Among adults with overweight or obesity and type 2 diabetes, ILI may reduce long-term variability of fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Our results support that ILI should be recommended to individuals with diabetes as part of management of long-term glycemic and blood lipid control.


Assuntos
Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Humanos , Sobrepeso/complicações , Sobrepeso/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Glicemia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Estilo de Vida , Lipoproteínas LDL , Colesterol , Fatores de Risco
3.
Mol Genet Genomic Med ; 12(1): e2290, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37787490

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH). METHODS: Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants. RESULTS: Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals. CONCLUSION: The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.


Assuntos
Cardiomiopatia Hipertrófica , Síndrome de Noonan , Humanos , Adulto Jovem , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , China , Morte Súbita Cardíaca/etiologia , Mutação , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Proteínas Proto-Oncogênicas c-raf/genética
4.
J Cardiovasc Dev Dis ; 10(10)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37887862

RESUMO

Although fibronectin has been associated with the pathogenesis of atherosclerosis, little is currently known about the relationship between plasma fibronectin and coronary heart disease (CHD). This retrospective study aimed to determine the predictive value of plasma fibronectin for CHD and its severity. A total of 1644 consecutive patients who underwent selective coronary angiography were recruited into the present study. The characteristics and results of the clinical examination of all patients were collected. Logistic regression analyses were performed to determine the predictive value of plasma fibronectin for the presence and severity of CHD. Compared with non-CHD patients, the CHD patients showed significantly higher plasma levels of troponin I and creatine kinase isoenzyme, along with lower plasma levels of fibronectin. However, no significant differences were detected in plasma fibronectin among patients with different grades of CHD. The logistic regression model showed that plasma fibronectin remained an independent predictor of CHD after adjustment with a 1.39-fold increased risk for every 1 SD decrease in plasma fibronectin. Nevertheless, plasma fibronectin could not predict the severity of CHD determined by the number of stenosed vessels and the modified Gensini score. This study demonstrated that lower plasma fibronectin might be an independent predictor of CHD, but it may be of no value in predicting the severity of CHD.

5.
Mol Nutr Food Res ; 67(22): e2300332, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37712112

RESUMO

SCOPE: Diabetes is an important risk factor for cardiovascular disease (CVD), which in turn is the most common and serious complication of diabetes. This study analyzes dietary patterns and single nucleotide polymorphisms (SNPs) in 543 diabetes patients with new-onset cardiovascular events and 461 diabetic patients without. METHODS AND RESULTS: SNPs are determined and analyzed using real time PCR and gene chip method. Factor analysis and logistic regression are used to determine dietary patterns and evaluate the level of associations and interaction effects, respectively. The legumes and edible fungi pattern and vegetable pattern show a significant negative correlation with complication risk. ADIPOQ rs37563 and legumes and edible fungi pattern have a significant interactive effect on disease, and patients with a high score of C polymorphism genotype (GC + CC) have a lower risk of disease. 5-10-Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and vegetable pattern have a borderline interaction effect on disease, and those patients with TT genotype have a lower risk of disease. CONCLUSION: These findings provide new insights into the role of the interactive protection of dietary patterns and SNPs. And participants with specific alleles show a lower risk of cardiovascular complications.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Dieta , Fatores de Risco de Doenças Cardíacas , Humanos , Alelos , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , População do Leste Asiático , Predisposição Genética para Doença , Genótipo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/genética
6.
J Am Heart Assoc ; 12(8): e028556, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37042265

RESUMO

Background The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non-CKD population and its associated risks with cardiovascular outcomes. Methods and Results The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group-based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow-up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01-1.23), 1.27 (95% CI, 1.14-1.40), and 1.56 (95% CI, 1.38-1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39-2.21] and 2.19 [95% CI, 1.68-2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected. Conclusions In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high-risk population and inspire future studies on individualized risk management.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Estudos Prospectivos , Fatores de Risco , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Rim/fisiologia , Fatores de Risco de Doenças Cardíacas
7.
Int J Obes (Lond) ; 47(5): 399-405, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36899038

RESUMO

BACKGROUND: Obesity is major cause of cardiovascular diseases. Metabolically healthy obesity (MHO) may increase heart failure risk early in life, and may be reflected in impaired cardiac structure and function. Therefore, we aimed to examine the relationship between MHO in young adulthood and cardiac structure and function. METHODS: A total of 3066 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were included, who completed echocardiography in young adulthood and middle age. The participants were grouped by obesity status (body mass index ≥30 kg/m2) and poor metabolic health (≥2 criteria for metabolic syndrome) into four metabolic phenotypes as follows: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). The associations of the metabolic phenotypes (MHN serving as the reference) with left ventricular (LV) structure and function were evaluated using multiple linear regression models. RESULTS: At baseline, mean age was 25 years, 56.4% were women, and 44.7% were black. After a follow-up 25 years, MUN in young adulthood was associated with worse LV diastolic function (E/é ratio, ß [95% CI], 0.73 [0.18, 1.28]), worse systolic function (global longitudinal strain [GLS], 0.60 [0.08, 1.12]) in comparison with MHN. MHO and MUO were associated with LV hypertrophy (LV mass index, 7.49 g/m2 [4.63, 10.35]; 18.23 g/m2 [12.47, 23.99], respectively), worse diastolic function (E/é ratio, 0.67 [0.31, 1.02]; 1.47 [0.79, 2.14], respectively), and worse systolic function (GLS, 0.72 [0.38, 1.06]; 1.35 [0.64, 2.05], respectively) in comparison with MHN. These results were consistent in several sensitivity analyses. CONCLUSIONS: In this community-based cohort using data from the CARDIA study, obesity in young adulthood was significantly associated with LV hypertrophy, worse systolic and diastolic function regardless of metabolic status. Relationship of Baseline Metabolic Phenotypes with Young Adulthood and Midlife Cardiac Structure and Function. Adjusted for year 0 covariates: age, sex, race, educational level, smoking status, drinking status, and physical activity; metabolically healthy non-obesity was used as a reference category for comparison. † Criteria for metabolic syndrome are listed in Supplementary Table S6. MUN metabolically unhealthy non-obesity, MHO metabolically healthy obesity, LVMi left ventricular mass index, LVEF left ventricular ejection fraction, E/A early to late peak diastolic mitral flow velocity ratio, E/é mitral inflow velocity to early diastolic mitral annular velocity, CI confidence interval.


Assuntos
Síndrome Metabólica , Obesidade Metabolicamente Benigna , Feminino , Masculino , Humanos , Função Ventricular Esquerda , Volume Sistólico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Hipertrofia Ventricular Esquerda , Índice de Massa Corporal , Fenótipo
8.
Microb Cell Fact ; 22(1): 46, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890537

RESUMO

BACKGROUND: Resveratrol is a commercially available stilbenoid widely used as dietary supplements, functional food ingredients, and cosmetic ingredients due to its diverse physiological activities. The production of resveratrol in microorganisms provides an ideal source that reduces the cost of resveratrol, but the titer in Saccharomyces cerevisiae was still much lower than that in other hosts. RESULTS: To achieve enhanced production of resveratrol in S. cerevisiae, we constructed a biosynthetic pathway via combining phenylalanine and tyrosine pathways by introducing a bi-functional phenylalanine/tyrosine ammonia lyase from Rhodotorula toruloides. The combination of phenylalanine pathway with tyrosine pathway led to a 462% improvement of resveratrol production in yeast extract peptone dextrose (YPD) medium with 4% glucose, suggesting an alternative strategy for producing p-coumaric acid-derived compounds. Then the strains were further modified by integrating multi-copy biosynthetic pathway genes, improving metabolic flux to aromatic amino acids and malonyl-CoA, and deleting by-pathway genes, which resulted in 1155.0 mg/L resveratrol in shake flasks when cultured in YPD medium. Finally, a non-auxotrophic strain was tailored for resveratrol production in minimal medium without exogenous amino acid addition, and the highest resveratrol titer (4.1 g/L) ever reported was achieved in S. cerevisiae to our knowledge. CONCLUSIONS: This study demonstrates the advantage of employing a bi-functional phenylalanine/tyrosine ammonia lyase in the biosynthetic pathway of resveratrol, suggesting an effective alternative in the production of p-coumaric acid-derived compounds. Moreover, the enhanced production of resveratrol in S. cerevisiae lays a foundation for constructing cell factories for various stilbenoids.


Assuntos
Saccharomyces cerevisiae , Tirosina , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Resveratrol/metabolismo , Tirosina/metabolismo , Fenilalanina/metabolismo , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Engenharia Metabólica/métodos
9.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499387

RESUMO

Both aldosterone and arginine vasopressin (AVP) are produced in the heart and may participate in cardiac fibrosis. However, their relationship remains unknown. This study aims to demonstrate the regulation and role of AVP in aldosterone synthesis in the heart. Rats were subjected to a sham operation or myocardial infarction (MI) by ligating the coronary artery. Cardiac function and fibrosis were assessed using echocardiography and immunohistochemical staining, respectively. In addition, the effects of AVP stimulation on cardiac microvascular endothelial cells (CMECs) were studied using ELISA, real-time PCR, and Western blotting. Compared with the rats having undergone a sham operation, the MI rats had an increased LVMI, type I collagen composition, and concentrations of aldosterone and AVP in the heart but decreased cardiac function. As the MI rats aged, the LVMI, type I collagen, aldosterone, and AVP increased, while the LVMI decreased. Furthermore, AVP time-dependently induced aldosterone secretion and CYP11B2 mRNA expression in CMECs. The p-CREB levels were significantly increased by AVP. Nevertheless, these effects were completely blocked by SR49059 or partially inhibited by KN93. This study demonstrated that AVP could induce the secretion of local cardiac aldosterone, which may involve CaMK and CREB phosphorylation and CYP11B2 upregulation through V1 receptor activation.


Assuntos
Arginina Vasopressina , Infarto do Miocárdio , Ratos , Animais , Arginina Vasopressina/farmacologia , Arginina Vasopressina/metabolismo , Colágeno Tipo I , Células Endoteliais/metabolismo , Coração , Aldosterona/metabolismo , Fibrose
10.
Microb Cell Fact ; 21(1): 230, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335407

RESUMO

BACKGROUND: Ginsenosides are Panax plant-derived triterpenoid with wide applications in cardiovascular protection and immunity-boosting. However, the saponins content of Panax plants is fairly low, making it time-consuming and unsustainable by direct extraction. Protopanaxadiol (PPD) is a common precursor of dammarane-type saponins, and its sufficient supply is necessary for the efficient synthesis of ginsenoside. RESULTS: In this study, a combinational strategy was used for the construction of an efficient yeast cell factory for PPD production. Firstly, a PPD-producing strain was successfully constructed by modular engineering in Saccharomyces cerevisiae BY4742 at the multi-copy sites. Then, the INO2 gene, encoding a transcriptional activator of the phospholipid biosynthesis, was fine-tuned to promote the endoplasmic reticulum (ER) proliferation and improve the catalytic efficiency of ER-localized enzymes. To increase the metabolic flux of PPD, dynamic control, based on a carbon-source regulated promoter PHXT1, was introduced to repress the competition of sterols. Furthermore, the global transcription factor UPC2-1 was introduced to sterol homeostasis and up-regulate the MVA pathway, and the resulting strain BY-V achieved a PPD production of 78.13 ± 0.38 mg/g DCW (563.60 ± 1.65 mg/L). Finally, sugarcane molasses was used as an inexpensive substrate for the first time in PPD synthesis. The PPD titers reached 1.55 ± 0.02 and 15.88 ± 0.65 g/L in shake flasks and a 5-L bioreactor, respectively. To the best of our knowledge, these results were new records on PPD production. CONCLUSION: The high-level of PPD production in this study and the successful comprehensive utilization of low-cost carbon source -sugarcane molassesindicate that the constructed yeast cell factory is an excellent candidate strain for the production of high-value-added PPD and its derivativeswith great industrial potential.


Assuntos
Ginsenosídeos , Saccharum , Saponinas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharum/genética , Saccharum/metabolismo , Engenharia Metabólica/métodos , Melaço , Saponinas/metabolismo , Carbono/metabolismo
11.
Nutrients ; 14(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35565681

RESUMO

The evidence regarding the impact of the scores on healthy eating indices on the risk of cardiovascular events among patients with type 2 diabetes (T2D) is limited. As such, in this study, we examined the associations of adherence to the Chinese and American dietary guidelines and the risk of cardiovascular disease (CVD) among Chinese individuals with T2D. We conducted a 1:1 age- and sex-matched case−control study based on a Chinese population. We used a structured questionnaire and a validated 79-item food-frequency questionnaire to collect general information and dietary intake information, and calculated the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015). As participants, we enrolled a total of 419 pairs of hospital-based CVD cases and controls, all of whom had T2D. We found a significant inverse association between diet quality scores on the CHEI and HEI-2015 and the risk of CVD. The adjusted odds ratios (95% confidence interval) per five-score increment were 0.68 (0.61, 0.76) in the CHEI and 0.60 (0.52, 0.70) in the HEI-2015. In stratified analyses, the protective associations remained significant in the subgroups of sex, BMI, smoking status, tea-drinking, hypertension state, dyslipidemia state, T2D duration, and medical nutrition therapy knowledge (all p < 0.05). These findings suggest that a higher CHEI or HEI-2015 score, representing a higher-quality diet relative to the most recent Chinese or American dietary guidelines, was associated with a decreased risk of CVD among Chinese patients with T2D.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Dieta/efeitos adversos , Humanos , Política Nutricional
12.
Oxid Med Cell Longev ; 2022: 8332825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340217

RESUMO

Mounting evidence demonstrates uncontrolled endoplasmic reticulum (ER) stress responses can activate the inflammasome, which generally results in endothelial dysfunction, a major pathogenetic factor of chronic inflammatory diseases such as atherosclerosis. Salvianolic acid B (SalB), produced by Radix Salviae, exerts antioxidative and anti-inflammatory activities in multiple cell types. However, SalB's effects on ER stress-related inflammasome and endothelial dysfunction remain unknown. Here, we showed SalB substantially abrogated ER stress-induced cell death and reduction in capillary tube formation, with declined intracellular reactive oxygen species (ROS) amounts and restored mitochondrial membrane potential (MMP), as well as increased expression of HO-1 and SOD2 in bone marrow-derived endothelial progenitor cells (BM-EPCs). ER stress suppression by CHOP or caspase-4 siRNA transfection attenuated the protective effect of SalB. Additionally, SalB alleviated ER stress-mediated pyroptotic cell death via the suppression of TXNIP/NLRP3 inflammasome, as evidenced by reduced cleavage of caspase-1 and interleukin- (IL-) 1ß and IL-18 secretion levels. Furthermore, this study provided a mechanistic basis that AMPK/FoxO4/KLF2 and Syndecan-4/Rac1/ATF2 signaling pathway modulation by SalB substantially prevented BM-EPCs damage associated with ER stress by decreasing intracellular ROS amounts and inducing NLRP3-dependent pyroptosis. In summary, our findings identify that ER stress triggered mitochondrial ROS release and NLRP3 generation in BM-EPCs, while SalB inhibits NLRP3 inflammasome-mediated pyroptotic cell death by regulating the AMPK/FoxO4/KLF2 and Syndecan-4/Rac1/ATF2 pathways. The current findings reveal SalB as a potential new candidate for the treatment of atherosclerotic heart disease.


Assuntos
Células Progenitoras Endoteliais , Inflamassomos , Proteínas Quinases Ativadas por AMP/metabolismo , Benzofuranos , Proteínas de Ciclo Celular/metabolismo , Células Progenitoras Endoteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Transdução de Sinais , Sindecana-4/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
13.
ACS Synth Biol ; 11(2): 770-779, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35107265

RESUMO

UDP-glycosyltransferase (UGT)-mediated glycosylation is a common modification in triterpene saponins, which exhibit a wide range of bioactivities and important pharmacological effects. However, few UGTs involved in saponin biosynthesis have been identified, limiting the biosynthesis of saponins. In this study, an efficient heterologous expression system was established for evaluating the UGT-mediated glycosylation process of triterpene saponins. Six UGTs (UGTPn17, UGTPn42, UGTPn35, UGTPn87, UGTPn19, and UGTPn12) from Panax notoginseng were predicted and found to be responsible for efficient and direct enzymatic biotransformation of 21 triterpenoid saponins via 26 various glycosylation reactions. Among them, UGTPn87 exhibited promiscuous sugar-donor specificity of UDP-glucose (UDP-Glc) and UDP-xylose (UDP-Xyl) by catalyzing the elongation of the second sugar chain at the C3 or/and C20 sites of protopanaxadiol-type saponins with a UDP-Glc or UDP-Xyl donor, as well as at the C20 site of protopanaxadiol-type saponins with a UDP-Glc donor. Two new saponins, Fd-Xyl and Fe-Xyl, were generated by catalyzing the C3-O-Glc xylosylations of notoginsenoside Fd and notoginsenoside Fe when incubated with UGTPn87. Moreover, the complete biosynthetic pathways of 17 saponins were elucidated, among which notoginsenoside L, vinaginsenoside R16, gypenoside LXXV, and gypenoside XVII were revealed in Panax for the first time. A yeast cell factory was constructed with a yield of Rh2 at 354.69 mg/L and a glycosylation ratio of 60.40% in flasks. Our results reveal the biosynthetic pathway of a group of saponins in P. notoginseng and provide a theoretical basis for producing rare and valuable saponins, promoting their industrial application in medicine and functional foods.


Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Saponinas , Triterpenos , Ginsenosídeos/metabolismo , Glicosiltransferases/metabolismo , Panax/metabolismo , Panax notoginseng/metabolismo , Difosfato de Uridina/metabolismo
14.
Clin Cardiol ; 42(10): 860-865, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31339592

RESUMO

BACKGROUND: Some previous studies explored associations between vascular endothelial growth factor receptor 2 (VEGFR2) polymorphisms and atherosclerotic cardiovascular diseases (ASCVD), with conflicting findings. HYPOTHESIS: We thought that VEGFR2 polymorphisms may influence susceptibility to ASCVD. Here, we aimed to better analyze the relationship between VEGFR2 polymorphisms and ASCVD in a larger combined population by performing a meta-analysis. METHODS: We searched Pubmed, Embase, and Web of Science for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between VEGFR2 polymorphisms and ASCVD. RESULTS: Ten studies were included for this meta-analysis (5474 cases and 8584 controls). VEGFR2 rs1870377 (dominant comparison: 0.81 (0.73-0.89), I2 = 56%; recessive comparison: 1.40 (1.25-1.57), I2 = 34%; allele comparison: 0.81 (0.76-0.87), I2 = 0%), rs2071559 (dominant comparison: 0.83 (0.76-0.91), I2 = 0%; recessive comparison: 1.22 (1.07-1.38), I2 = 0%; allele comparison: 0.86 (0.81-0.92), I2 = 0%) and rs2305948 (dominant comparison: 0.79 (0.72-0.87), I2 = 25%; recessive comparison: 1.44 (1.08-1.92), I2 = 60%; allele comparison: 0.79 (0.68-0.92), I2 = 73%) polymorphisms were all found to be significantly associated with susceptibility to ASCVD in general population. Subgroup analyses by type of disease revealed similar significant findings for rs1870377, rs2071559, and rs2305948 polymorphisms in coronary artery disease (CAD) subgroup. Besides, positive results were also found for rs1870377 polymorphism in ischemic stroke (IS) subgroup. CONCLUSIONS: In summary, this meta-analysis proved that these VEGFR2 polymorphisms could be used to identify individual with elevated susceptibility to ASCVD.


Assuntos
Aterosclerose/genética , Predisposição Genética para Doença , Polimorfismo Genético , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Aterosclerose/metabolismo , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Biosci Rep ; 39(7)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29339422

RESUMO

Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional secreted protein that can be induced by fasting, hypoxia and glucocorticoids. ANGPTL4 has been associated with a variety of diseases; however, the role of ANGPTL4 in cardiac hypertrophy remains poorly understood. In our study, we aimed to explore the effect of ANGPTL4 on phenylephrine-induced cardiomyocyte hypertrophy. Our results showed that knockdown of ANGPTL4 expression significantly exacerbated cardiomyocyte hypertrophy, as demonstrated by increased hypertrophic marker expression, including ANP and cell surface area. Moreover, significantly reduced fatty acid oxidation, as featured by decreased CPT-1 levels, was observed in hypertrophic cardiomyocytes following ANGPTL4 down-regulation. Furthermore, knockdown of ANGPLT4 led to down-regulated expression of peroxisome proliferator-activated receptor α (PPARα), which is the key regulator of cardiac fatty acid oxidation. In addition, ANGPTL4 silencing promoted the activation of JNK1/2, and JNK1/2 signaling blockade could restore the level of PPARα and significantly ameliorate the ANGPTL4 knockdown-induced cardiomyocyte hypertrophy. Therefore, our study demonstrated that ANGPTL4 regulates PPARα through JNK1/2 signaling and is required for the inhibition of cardiomyocyte hypertrophy.


Assuntos
Proteína 4 Semelhante a Angiopoietina/genética , Cardiomegalia/genética , Miócitos Cardíacos/metabolismo , PPAR alfa/genética , Angiopoietina-1/genética , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Proteína Quinase 8 Ativada por Mitógeno/genética , Miócitos Cardíacos/patologia , Oxirredução , Fenilefrina/toxicidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Propriedades de Superfície
16.
Int J Mol Med ; 42(3): 1765, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29845220

RESUMO

Subsequently to the publication of this article, the authors have realized that the address affiliation for the corresponding author, Chengheng Hu, and the authors Longyun Peng and Xinxue Liao appeared incorrectly. These authors' affiliation information should have appeared as follows (the corrected address affiliation is featured in bold): XIAO KE1,2*, JINGFU CHEN3*, LONGYUN PENG4, WEI ZHANG5, YIYING YANG5, XINXUE LIAO4, LIQIU MO6, RUIXIAN GUO7, JIANQIANG FENG6, CHENGHENG HU4 and RUQIONG NIE2 1Department of Cardiology, Shenzhen Sun Yat­sen Cardiovascular Hospital, Shenzhen; 2Department of Cardiology, Sun Yat­sen Memorial Hospital, Sun Yat­sen University, Guangzhou, Guangdong; 3Department of Cardiovascular Medicine and Dongguan Cardiovascular Institute, The Third People's Hospital of Dongguan City, Dongguan; 4Department of Cardiology and Key Laboratory on Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat­sen University; 5Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division of The First Affiliated Hospital, Sun Yat­sen University; 6Department of Anesthesiology, Huangpu Division of The First Affiliated Hospital, Sun Yat­sen University; 7Department of Physiology, Zhongshan School of Medicine, Sun Yat­sen University, Guangzhou, Guangdong, P.R. China *Contributed equally In addition, the address for correspondence in the correspondence box should have appeared as follows: Correspondence to: Professor Chengheng Hu, Department of Cardiology and Key Laboratory on Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat­sen University, Guangdong, 58 Zhongshan 2rd Road, Guangzhou 510080, P.R. China E­mail: huchengheng138@163.com The authors regret this error in the affiliations, and apologize for any inconvenience caused. [the original article was published in the International Journal of Molecular Medicine 39: 1001­1010, 2017; DOI: 10.3892/ijmm.2017.2891].

17.
Int J Mol Med ; 39(4): 1001-1010, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28204829

RESUMO

It has been reported that exogenous hydrogen sulfide (H2S) protects against high glucose (HG)-induced cardiac injury and has a modulatory effect on heat shock protein (HSP) and Akt, which play a cardioprotective role. In this study, we examined whether the HSP90/Akt pathway contributes to the protective effects of exogenous H2S against HG-induced injury to H9c2 cardiac cells. Our results revealed that the exposure of H9c2 cardiac cells to 35 mM glucose (HG) for 1 to 24 h decreased the expression of HSP90 and markedly reduced the expression level of phosphorylated (p)-Akt in a time-dependent manner. Co-exposure of the cells to HG and geldanamycin (GA; an inhibitor of HSP90) aggravated the inhibition of the p-Akt expression level by HG. Of note, treatment of the cells with 400 µM NaHS (a donor of H2S) for 30 min prior to exposure to HG significantly attenuated the HG-induced decrease in the expression levels of both HSP90 and p-Akt, along with inhibition of HG-induced cell injury, as indicated by the increase in cell viability and superoxide dismutase (SOD) activity, and by a decrease in the number of apoptotic cells, reactive oxygen species (ROS) generation, as well as by the decreased dissipation of mitochondrial membrance potential (MMP). Importantly, treatment of the cells with GA or LY294002 (an inhibitor of Akt) prior to exposure to NaHS and HG considerably blocked the cardioprotective effects of NaHS against the HG-induced injury mentioned above. On the whole, the findings of this study demonstrate that the inhibition of the HSP90/Akt pathway may be an important mechanism responsible for HG-induced cardiomyocyte injury. We also provide novel evidence that exogenous H2S protects H9c2 cells against HG-induced injury by activating the HSP90/Akt pathway.


Assuntos
Cardiotônicos/farmacologia , Glucose/efeitos adversos , Proteínas de Choque Térmico HSP90/metabolismo , Sulfeto de Hidrogênio/farmacologia , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Glucose/farmacologia , Morfolinas/farmacologia , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos , Espécies Reativas de Oxigênio/metabolismo
18.
Cardiovasc Ther ; 35(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28039944

RESUMO

AIMS: Our previous study indicates that hydrochlorothiazide inhibits transforming growth factor (TGF)-ß/Smad signaling pathway, improves cardiac function and reduces fibrosis. We determined whether these effects were common among the diuretics and whether angiotensin II receptor type 1 (AT1) signaling pathway played a role in these effects. METHODS: Heart failure was produced by ligating the left anterior descending coronary artery in adult male Sprague Dawley rats. Two weeks after the ligation, 70 rats were randomly divided into five groups: sham-operated group, control group, valsartan group (80 mg/kg/d), hydrochlorothiazide group (12.5 mg/kg/d) and furosemide group (20 mg/kg/d). In addition, neonatal rat ventricular fibroblasts were treated with angiotensin II. RESULTS: After eight-week drug treatment, hydrochlorothiazide group and valsartan group but not furosemide group had improved cardiac function (ejection fraction was 49.4±2.1%, 49.5±1.8% and 39.9±1.9%, respectively, compared with 40.1±2.2% in control group), reduced cardiac interstitial fibrosis and collagen volume fraction (9.7±1.2%, 10.0±1.3% and 14.1±0.8%, respectively, compared with 15.9±1.1% in control group), and decreased expression of AT1, TGF-ß and Smad2 in the cardiac tissues. In addition, hydrochlorothiazide reduced plasma angiotensin II and aldosterone levels. Furthermore, hydrochlorothiazide inhibited angiotensin II-induced TGF-ß1 and Smad2 protein expression in the neonatal rat ventricular fibroblasts. CONCLUSIONS: Our study indicates that the cardiac function and remodeling improvement after ischemic heart failure may not be common among the diuretics. Hydrochlorothiazide may reduce the left ventricular wall stress and angiotensin II signaling pathway to provide these beneficial effects.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Diuréticos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Ventrículos do Coração/efeitos dos fármacos , Hidroclorotiazida/farmacologia , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Aldosterona/sangue , Angiotensina II/sangue , Animais , Animais Recém-Nascidos , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Furosemida/farmacologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Masculino , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Volume Sistólico/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Valsartana/farmacologia
19.
Biochem Biophys Res Commun ; 483(1): 534-540, 2017 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-28011270

RESUMO

Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.


Assuntos
Angiotensina II/metabolismo , Fibrilação Atrial/metabolismo , Sulfeto de Hidrogênio/química , Canal de Potássio Kv1.5/metabolismo , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetofenonas/química , Animais , Células Cultivadas , Cães , Ensaio de Imunoadsorção Enzimática , Átrios do Coração/metabolismo , Masculino , Células Musculares/citologia , NADPH Oxidase 4 , Oniocompostos/química , Reação em Cadeia da Polimerase , RNA Interferente Pequeno/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transfecção , Regulação para Cima
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(6): 681-4, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27491226

RESUMO

OBJECTIVE: To observe the therapeutic effects of Berberine Capsule (BC) on patients with mild hyperlipidemia. METHODS: Totally 102 mild hyperlipemia patients were recruited. All patients were suggested to have proper diet and physical activity as basic therapy for 1 month of run-in period. Totally 97 patients completed it. Then they were randomly assigned to the berberine group (the treatment group, 49 cases) and the placebo group (the control group, 48 cases). Patients in the treatment group took BC 300 mg, while those in the control group took placebo 300 mg, thrice per day for 3 successive months. Then placebos and BC were interrupted for 2 months (as washout period). All subjects received only diet control and physical activity during washout period. After washout period, placebos and BC were re-administered to all patients in the same way for 3 months. Body mass index (BMI), fasting plasma glucose (FPG), TG, TC, LDL-C, and HDL-C were assessed after run-in period, washout period, at month 1, 2, 3 after the first therapy, at month 1, 2, 3 after second treatment, respectively. RESULTS: Compared with the end of run-in period, TG, TC, and LDL-C decreased, and HDL-C increased in the treatment group (P < 0.05) after first 3 months of treatment. Compared with 3 months after the first therapy, TG, TC, and LDL-C increased and HDL-C decreased in the treatment group after washout period (P < 0.05). Compared with the end of wash- out period, TC and LDL-C decreased in the treatment group at month 2 after second treatment (P < 0.05); TG, TC, and LDL-C decreased (P < 0.01, P < 0.05), and HDL-C increased (P < 0.05) at month 3 after second treatment. Compared with the control group at month 3 after second treatment, TG, TC, and LDL-C all decreased, and HDL-C increased in the treatment group (all P < 0.05). CONCLUSION: BC was effective in improving blood lipid level in mild hyperlipidemia patients.


Assuntos
Berberina/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Glicemia/análise , Índice de Massa Corporal , Cápsulas , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...