scholarly journals Treatment of Cardiovascular Disease by Traditional Chinese Medicine against Pregnane X Receptor

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Kuen-Bao Chen ◽  
Hsin-Yi Chen ◽  
Kuan-Chung Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Cardiovascular Disease ◽  
Drug Development ◽  
Circulatory System ◽  
Docking Simulation ◽  
Pregnane X Receptor ◽  
Md Simulations ◽  
Positive Control ◽  
Hazardous Substances ◽  
Lead Compounds ◽  
Circulatory System Diseases

Recently, cardiovascular disease, also known as loop circulatory system diseases or disorders, is one of the serious diseases including heart disease, stroke, atherosclerosis, myocardial infarction, hypertension, hypotension, and thrombosis. Human pregnane X receptor, PXR, plays a crucial role in exogenous and endobiotic metabolism for rabbit, rat, mouse, and human. The PXR activation can protect the blood vessels from damage of hazardous substances. In this study we aim to investigate the potent lead compounds as PXR receptor agonist against cardiovascular disease. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as PXR agonists from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, bis(4-hydroxybenzyl) ether mono-β-D-glucopyranoside (BEMG), ixerisoside, and tangshenoside II, have displayed higher potent binding affinities than the positive control, PNU-142721, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and PXR protein under dynamic conditions, top TCM compounds, BEMG and tangshenoside II, maintain most of interactions with PXR protein, which keep the ligand binding stable in the binding domain. Hence, we propose BEMG and tangshenoside II as potential lead compounds for further study in drug development process with the PXR protein.

scholarly journals Potential Smoothened Inhibitor from Traditional Chinese Medicine against the Disease of Diabetes, Obesity, and Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Mao-Feng Sun ◽  
Hsin-Yi Chen ◽  
Cheng-Chun Lee ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Drug Development ◽  
Hedgehog Signaling ◽  
Docking Simulation ◽  
Md Simulations ◽  
Positive Control ◽  
Lead Compounds ◽  
Oncology Clinical Trials ◽  
Body Patterning ◽  
The Stability ◽  
Smo Inhibitor

Nowadays, obesity becomes a serious global problem, which can induce a series of diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease, metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog signaling pathway plays an important role in body patterning during embryogenesis. For this reason, smoothened homologue (Smo) protein had been indicated as the drug target. In addition, the small-molecule Smo inhibitor had also been used in oncology clinical trials. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as Smo inhibitor from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities than the positive control, LY2940680, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and Smo protein under dynamic conditions, top three TCM compounds maintain most of interactions with Smo protein, which keep the ligand binding stable in the binding domain. Hence, we propose precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead compounds for further study in drug development process with the Smo protein.

scholarly journals In SilicoInvestigation of Potential Pyruvate Kinase M2 Regulators from Traditional Chinese Medicine against Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Kuen-Bao Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Virtual Screening ◽  
Drug Development ◽  
Pyruvate Kinase ◽  
Md Simulation ◽  
Docking Simulation ◽  
Target Protein ◽  
Binding Affinities ◽  
Pyruvate Kinase M2 ◽  
Lead Compounds ◽  
The Stability

A recent research in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted fromLycium chinenseMill. andAbrus precatoriusL., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.

scholarly journals Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

BMJ ◽  
2019 ◽  
pp. l1580 ◽  
Author(s):  
Yan Xie ◽  
Benjamin Bowe ◽  
Yan Yan ◽  
Hong Xian ◽  
Tingting Li ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gastrointestinal Cancer ◽  
Circulatory System ◽  
Upper Gastrointestinal Cancer ◽  
Circulatory System Diseases ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Upper Gastrointestinal

AbstractObjectiveTo estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).DesignLongitudinal observational cohort study.SettingUS Department of Veterans Affairs.ParticipantsNew users of PPIs (n=157 625) or H2 blockers (n=56 842).Main outcome measuresAll cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).ResultsThere were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).ConclusionsTaking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

scholarly journals Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Stress Responses ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Human Tumor ◽  
Docking Simulation ◽  
Md Simulations ◽  
Tumor Promoter ◽  
Dynamic Conditions ◽  
Lead Compounds ◽  
Phosphatase 2A

Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A-αprotein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A-αprotein.

Hyperuricemia and Cardiovascular Disease

2019 ◽  
Vol 25 (6) ◽  
pp. 700-709 ◽  
Author(s):  
Shuangshuang Zhang ◽  
Yong Wang ◽  
Jinsong Cheng ◽  
Ning Huangfu ◽  
Ruochi Zhao ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Kidney Stones ◽  
Treatment Plan ◽  
Circulatory System ◽  
Special Focus ◽  
Positive Effects

Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is believed to be linked to the development of gout and kidney stones. Hyperuricemia is closely correlated with cardiovascular disease, metabolic syndrome, and chronic kidney disease, as attested by the epidemiological and empirical research. In this review, we summarize the recent knowledge about hyperuricemia, with a special focus on its physiology, epidemiology, and correlation with cardiovascular disease. This review also discusses the possible positive effects of treatment to reduce urate levels in patients with cardiovascular disease and hyperuricemia, which may lead to an improved clinical treatment plan.

scholarly journals Changes in Six-Month Prevalence of Circulatory System Diseases among People Aged 20 Years and Older between 2013 and 2018 in Hunan, China

2021 ◽  
Vol 18 (5) ◽  
pp. 2599
Author(s):  
Zhenzhen Rao ◽  
Junjie Hua ◽  
Ruotong Li ◽  
Yanhong Fu ◽  
Jie Li ◽  
...  
Keyword(s):  
Age Groups ◽  
Circulatory System ◽  
Population Based ◽  
Hunan Province ◽  
Rural Residents ◽  
Chi Square ◽  
Circulatory System Diseases ◽  
Chi Square Test ◽  
Urban Rural ◽  
Socio Demographic Factors

Recent changes in population-based prevalence for circulatory system diseases (CSDs) remain unreported either nationally or locally for China. Data were from the two-round health service household interview survey of Hunan Province, China, in 2013 and 2018. A Rao–Scott chi-square test was performed to examine prevalence differences across socio-demographic variables. The overall age-standardized prevalence of CSDs increased substantially between 2013 and 2018 for inhabitants aged 20 years and older (14.25% vs. 21.25%; adjusted odds ratio (OR) = 1.59, 95% CI: 1.24–2.04). Hypertensive disease was the most prevalent type of CSD, accounting for 87.24% and 83.83% of all CSDs in 2013 and in 2018, respectively. After controlling for other socio-demographic factors, the prevalence of CSDs was significantly higher in 2018 (adjusted OR = 1.40), urban residents (adjusted OR = 1.43), females (adjusted OR = 1.12) and older age groups (adjusted OR = 5.36 for 50–59 years, 9.51 for 60–69 years, 15.19 for 70–79 years, and 12.90 for 80 years and older) than in 2013, rural residents, males and the youngest age group (20–49 years). The recent increase in the overall age-standardized CSD prevalence and the large prevalence disparities across urban/rural residents, sex and age groups merit the attention of policymakers and researchers. Further prevention efforts are needed to curb the increasing tendency and to reduce the prevalence of disparities across socio-demographic groups.

scholarly journals Potential Mitochondrial Isocitrate Dehydrogenase R140Q Mutant Inhibitor from Traditional Chinese Medicine against Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-Yuan Lee ◽  
Kuan-Chung Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Point Mutations ◽  
Docking Simulation ◽  
Myelogenous Leukemia ◽  
Mutant Protein ◽  
Binding Affinities ◽  
Isocitrate Dehydrogenase 1 ◽  
Lead Compounds ◽  
Arginine Residues ◽  
Acute Myelogenous

A recent research of cancer has indicated that the mutant of isocitrate dehydrogenase 1 and 2 (IDH1and2) genes will induce various cancers, including chondrosarcoma, cholangiocarcinomas, and acute myelogenous leukemia due to the effect of point mutations in the active-site arginine residues of isocitrate dehydrogenase (IDH), such as IDH1/R132, IDH2/R140, and IDH2/R172. As the inhibition for those tumor-associated mutant IDH proteins may induce differentiation of those cancer cells, these tumor-associated mutant IDH proteins can be treated as a drug target proteins for a differentiation therapy against cancers. In this study, we aim to identify the potent TCM compounds from the TCM Database@Taiwan as lead compounds of IDH2 R140Q mutant inhibitor. Comparing to the IDH2 R140Q mutant protein inhibitor, AGI-6780, the top two TCM compounds, precatorine and abrine, have higher binding affinities with target protein in docking simulation. After MD simulation, the top two TCM compounds remain as the same docking poses under dynamic conditions. In addition, precatorine is extracted fromAbrus precatoriusL., which represents the cytotoxic and proapoptotic effects for breast cancer and several tumor lines. Hence, we propose the TCM compounds, precatorine and abrine, as potential candidates as lead compounds for further study in drug development process with the IDH2 R140Q mutant protein against cancer.

Sign in / Sign up

Export Citation Format

Share Document