The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionineγ-lyase (CSE) and cystathionineβ-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson’s reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

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Genetic Engineering of Disease and Pest Resistance in Plants: Present State of the Art

Zeitschrift für Naturforschung C ◽

10.1515/znc-1993-9-1001 ◽

1993 ◽

Vol 48 (9-10) ◽

pp. 673-688 ◽

Cited By ~ 19

Author(s):

Günter Strittmatter ◽

Dorothee Wegener

Keyword(s):

Host Plants ◽

Molecular Mechanisms ◽

State Of The Art ◽

Durable Resistance ◽

The Other ◽

Rapid Progress ◽

Pathogenic Viruses ◽

The One ◽

Defence Strategies ◽

Defence Reactions

Abstract Rapid progress in gene technology has allowed, on the one hand, insight to be gained into the complex molecular mechanisms of plant/pathogen recognition and the natural defence strategies of host plants. On the other hand, this technology can also be used for the controlled and efficient generation of genetic variability and for the identification of desirable genotypes, far beyond the possibilities of classical breeding. The first successful attempts have been made to improve resistance against pathogenic viruses, bacteria, fungi and insects by engineering transgenic plants. The majority of these strategies were based on constitutively expressing single proteins that are either toxic to the pathogen/pest, or interfere with its reproductive cycle. More refined strategies, which are at the stage of testing, try to mimic and modify naturally-evolved defence reactions of plants and, thereby, will potentially confer a more durable resistance to a broad range of pathogens

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Psychosocial Stress and Ischaemic Heart Disease: A Response to Tennant

Australian & New Zealand Journal of Psychiatry ◽

10.3109/00048678209161267 ◽

1982 ◽

Vol 16 (4) ◽

pp. 265-278

Author(s):

Bruce Boman

Keyword(s):

Cardiovascular Disease ◽

Heart Disease ◽

World War Ii ◽

Ischaemic Heart Disease ◽

Psychosocial Stress ◽

Military Service ◽

Clinical use of the III generation calcium antagonist Amlotopin the treatment of patients with cardiovascular disease

Cardiosomatics ◽

10.26442/cs45033 ◽

2013 ◽

Vol 4 (4) ◽

pp. 25-32

Author(s):

V. S Zadionchenko ◽

G. G Shehyan ◽

A. A Yalymov

Keyword(s):

Cardiovascular Disease ◽

Calcium Current ◽

Developed Countries ◽

The Other ◽

Prescription Rate ◽

Clinical Use ◽

Tissue Selectivity ◽

The 1960S ◽

The One ◽

New Treatments

Despite the facts, revealing the mechanisms of pathogenesis and enhancing the effectiveness of the treatment of cardiovascular disease (CVD), the latter continues to be the leading cause of death and disability in the population. In this regard, the search for new treatments for CVD remains the most relevant in modern cardiology. In the treatment of CVD many classes of drugs are used, among which are calcium antagonists (AA). This class of drugs has been successfully used in the treatment of patients with arterial hypertension (AH) and coronary heart disease [1-3, 5].CA are a heterogeneous group of drugs that have the similar actionmechanism, but differ in a number of properties, including pharmacokinetics, tissue selectivity, effect on heart rate, etc. The main feature of all is the ability of CA to reversibly inhibit calcium current through the slow calcium channels. These funds are used in cardiology from the end of the 1960s and have since become so widely popular that in most developed countries they hold one of the first places on the prescription rate of drugs used for the treatment of cardiovascular disease. This is due, on the one hand, to the CA high clinical efficacy, and on the other to a relatively small number of contraindications to their purpose and the comparatively small number of side effects. [1, 2, 4, 5].

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PRODUKSI REKOMBINAN SEFALOSPORIN ASILASE SEBAGAI BIOKATALIS UNTUK PRODUKSI ASAM 7-AMINOSEFALOSPORANAT

Jurnal Bioteknologi & Biosains Indonesia (JBBI) ◽

10.29122/jbbi.v4i1.2059 ◽

2017 ◽

Vol 4 (1) ◽

pp. 28 ◽

Cited By ~ 1

Author(s):

Bima Wedana Isdiyono ◽

Dudi Hardianto ◽

Fransiskus Xaverius Ivan

Keyword(s):

Escherichia Coli ◽

Induction Time ◽

Acid Oxidase ◽

Enzymatic Method ◽

Amino Acid Oxidase ◽

Two Stage ◽

E Coli ◽

Escherichia Coli Bl21 ◽

Cephalosporin Acylase ◽

The One

Production of Cephalosporin Acylase Recombinant as Biocatalyst for 7-Aminocephalosporanic Acid Production7-aminocephalosporanic acid (7-ACA) is a precursor for the production of semisynthetic cephalosporin derivatives. The enzymatic 7-ACA production can use two-stage and one-step enzymatic methods. Two-stage enzymatic method uses D-amino acid oxidase (DAAO) enzyme to produce glutaryl-7-aminocephalosporanic acid (GL-7-ACA) in the first stage and glutaryl-7-aminocephalosporanic acid acylase to produce 7-ACA in the second stage. The one-stage enzymatic method using cephalosporin acylase (CPC acylase) converts the CPC to 7-ACA directly. The aim of this research was to produce recombinant CPC acylase in Escherichia coli BL21(DE3). Transformantion culture E. coli BL21(DE3) was induced with concentrations of IPTG 0; 0.25; 0.5; 0.75; 1; 2 mM for 5 hours. The induction time of IPTG was determined at 0, 1, 2, 3, 4, and 5 hours. The results showed that CPC acylase produced by E. coli BL21(DE3) with optimum condition of CPC acylase production was 0.5 mM IPTG and optimal induction time of IPTG was 5 hours.Keywords: Cephalosporin, cephalosporin acylase, 7-ACA, protein expression, Escherichia coli BL21(DE3) ABSTRAKAsam 7-aminosefalosporanat (7-ACA) merupakan prekursor untuk produksi turunan sefalosporin semisintetik. Produksi 7-ACA secara enzimatik dapat menggunakan metode dua tahap dan satu tahap enzimatik. Metode enzimatik secara dua tahap menggunakan enzim asam D-amino oksidase (DAAO) untuk menghasilkan asam glutaril-7-aminosefalosporinat (GL-7-ACA) pada tahap pertama dan menggunakan asam glutaril-7-aminosefalosporinat asilase untuk menghasilkan 7-ACA pada tahap kedua. Metode enzimatik satu tahap dengan sefalosporin asilase (CPC asilase) mengubah CPC menjadi 7-ACA secara langsung. Tujuan penelitian adalah memproduksi rekombinan CPC asilase di dalam sel Escherichia coli BL21(DE3). Kultur Transforman E. coli BL21(DE3) diinduksi dengan konsentrasi IPTG 0; 0,25; 0,5; 0,75; 1; 2 mM selama 5 jam. Waktu induksi IPTG ditentukan pada 0, 1, 2, 3, 4 dan 5 jam. Hasil penelitian menunjukan bahwa CPC asilase diproduksi oleh E. coli BL21(DE3) dengan kondisi optimal produksi CPC asilase adalah konsentrasi IPTG 0,5 mM dan waktu induksi IPTG optimal adalah 5 jam.

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Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase

Nitric Oxide ◽

10.1016/j.niox.2017.01.010 ◽

2017 ◽

Vol 64 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

Luan Kelves M. Souza ◽

Thiago S.L. Araújo ◽

Nayara A. Sousa ◽

Francisca Beatriz M. Sousa ◽

Kerolayne M. Nogueira ◽

...

Keyword(s):

Hydrogen Sulfide ◽

Amino Acid ◽

Gastric Damage ◽

Acid Oxidase ◽

Amino Acid Oxidase

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Angioregulatory microRNAs in Colorectal Cancer

Cancers ◽

10.3390/cancers12010071 ◽

2019 ◽

Vol 12 (1) ◽

pp. 71 ◽

Cited By ~ 8

Author(s):

Mohammad Hasan Soheilifar ◽

Michael Grusch ◽

Hoda Keshmiri Neghab ◽

Razieh Amini ◽

Hamid Maadi ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Tumor Cells ◽

Molecular Mechanisms ◽

The Other ◽

Angiogenic Response ◽

Rate Determining Step ◽

Antiangiogenic Factors ◽

The One ◽

Tumor Suppressor Mirnas

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

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Lipid-Induced Mechanisms of Metabolic Syndrome

Journal of Obesity ◽

10.1155/2020/5762395 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Yulia K. Denisenko ◽

Oxana Yu Kytikova ◽

Tatyana P. Novgorodtseva ◽

Marina V. Antonyuk ◽

Tatyana A. Gvozdenko ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fatty Acids ◽

Inflammatory Process ◽

Molecular Mechanisms ◽

Insulin Response ◽

The Body ◽

Diagnostic Methods ◽

The Other ◽

Prevention And Treatment ◽

The One

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

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Harnessing the Benefits of Endogenous Hydrogen Sulfide to Reduce Cardiovascular Disease

Antioxidants ◽

10.3390/antiox10030383 ◽

2021 ◽

Vol 10 (3) ◽

pp. 383

Author(s):

Kevin M. Casin ◽

John W. Calvert

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Hydrogen Sulfide ◽

Research Area ◽

Therapeutic Interventions ◽

Intermittent Fasting ◽

Beneficial Impact ◽

Mercaptopyruvate Sulfurtransferase ◽

H2s Production ◽

The U.S

Cardiovascular disease is the leading cause of death in the U.S. While various studies have shown the beneficial impact of exogenous hydrogen sulfide (H2S)-releasing drugs, few have demonstrated the influence of endogenous H2S production. Modulating the predominant enzymatic sources of H2S—cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase—is an emerging and promising research area. This review frames the discussion of harnessing endogenous H2S within the context of a non-ischemic form of cardiomyopathy, termed diabetic cardiomyopathy, and heart failure. Also, we examine the current literature around therapeutic interventions, such as intermittent fasting and exercise, that stimulate H2S production.

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Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.734550 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qingyan Huang ◽

Yuhong Gan ◽

Zhikang Yu ◽

Heming Wu ◽

Zhixiong Zhong

Keyword(s):

Molecular Mechanisms ◽

Plaque Formation ◽

The Other ◽

High Morbidity ◽

Endothelial Cell Dysfunction ◽

Mesenchymal Transition ◽

Substantial Body ◽

Cell Dysfunction ◽

Endothelial To Mesenchymal Transition ◽

The One

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.

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MOLECULAR MECHANISMS OF FORMATION OF BLOOD EOSINOPHILIA UNDER PULMONARY TUBERCULOSIS

Annals of the Russian academy of medical sciences ◽

10.15690/vramn.v67i5.276 ◽

2012 ◽

Vol 67 (5) ◽

pp. 58-62 ◽

Cited By ~ 1

Author(s):

Yu. V. Kolobovnikova ◽

O. I. Urazova ◽

V. V. Novitskii ◽

K. O. Mikheeva ◽

M. D. Goncharov

Keyword(s):

Plasma Concentration ◽

Pulmonary Tuberculosis ◽

Vascular Endothelium ◽

Molecular Mechanisms ◽

Granulomatous Inflammation ◽

The Other ◽

Blood Eosinophilia ◽

Mechanisms Of Formation ◽

The One

Molecular factors of pathogenesis of the eosinophilic blood reaction under pulmonary tuberculosis are analyzed in the article. It has been established that the key cytokine providing the development of hemic eosinophilia in patients with pulmonary tuberculosis is IL-5. IL-5 plasma concentration turned out to be increased only in patients with eosinophilia. Increase of eotaxin was determined in patients with tuberculosis despite of the presense of eosinophilia. One-directional nature of the defined changes in eotaxin concentration might be explained by dual properties of this chemokine: on the one hand, eotaxin mediates long-term presence of eosinophils in blood; on the other hand, it initiates the process of adhesion of eosinophilic leucocytes to vascular endothelium with their further migration to the focus of granulomatous inflammation. The established increase in number of IL-5R-positive eosinophils presents one more mechanism which explains the basis of long-term presence of eosinophils in peripheral blood in patients with pulmonary tuberculosis.

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