scholarly journals Repurposing Market Drugs to Target Epigenetic Enzymes in Human Diseases

2021 ◽  
Author(s):  
Aishat Motolani ◽  
Matthew Martin ◽  
Steven Sun ◽  
Tao Lu
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
The United States ◽  
Human Diseases ◽  
Marketing Approval ◽  
Repurposed Drugs ◽  
Novel Strategy ◽  
Approved Drugs ◽  
Shed Light

Drug discovery is an exciting yet highly costly endeavor. In the United States, developing a new prescription medicine that gains marketing approval takes near a decade and costs drugmakers for near 3 billion. More challengingly, the success rate of a compound entering phase I trials is just slightly under 10%. Because of these mounting hurdles, repurposing market approved drugs to new clinical indications has been a new trend on the rise. Another merit to this approach is the already confirmed toxicity profiles of the drugs and their possession of drug-like features. Thus, repurposed drugs can reach the market approved stage in a much faster, cheaper, and more efficient way. Notably, epigenetic enzymes play a critical role in the etiology and progression of different diseases. Researchers are now assessing the possibilities of using market approved drugs to target epigenetic enzymes as a novel strategy to curtail disease progression. Thus, in this book chapter, we will provide an outlook on repurposing market drugs to target epigenetic enzymes in various diseases. Consequently, this book chapter will not only provide the readers with current knowledge in this specific field, but also will shed light on the pathway forward for repurposing market drugs to target epigenetic enzymes in human diseases.

scholarly journals In Silico Screening of Potential Phytocompounds from Several Herbs against SARS-CoV-2 Indian Delta Variant B.1.617.2 to Inhibit the Spike Glycoprotein Trimer

2022 ◽  
Vol 12 (2) ◽  
pp. 665
Author(s):  
Muruganantham Bharathi ◽  
Bhagavathi Sundaram Sivamaruthi ◽  
Periyanaina Kesika ◽  
Subramanian Thangaleela ◽  
Chaiyavat Chaiyasut
Keyword(s):  
The United States ◽  
Inhibitory Effect ◽  
Binding Affinities ◽  
Standard Drug ◽  
Houttuynia Cordata ◽  
Future Drug ◽  
Strong Inhibitory Effect ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Shed Light

In October 2020, the SARS-CoV-2 B.1.617 lineage was discovered in India. It has since become a prominent variant in several Indian regions and 156 countries, including the United States of America. The lineage B.1.617.2 is termed the delta variant, harboring diverse spike mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD), which may heighten its immune evasion potentiality and cause it to be more transmissible than other variants. As a result, it has sparked substantial scientific investigation into the development of effective vaccinations and anti-viral drugs. Several efforts have been made to examine ancient medicinal herbs known for their health benefits and immune-boosting action against SARS-CoV-2, including repurposing existing FDA-approved anti-viral drugs. No efficient anti-viral drugs are available against the SARS-CoV-2 Indian delta variant B.1.617.2. In this study, efforts were made to shed light on the potential of 603 phytocompounds from 22 plant species to inhibit the Indian delta variant B.1.617.2. We also compared these compounds with the standard drug ceftriaxone, which was already suggested as a beneficial drug in COVID-19 treatment; these compounds were compared with other FDA-approved drugs: remdesivir, chloroquine, hydroxy-chloroquine, lopinavir, and ritonavir. From the analysis, the identified phytocompounds acteoside (−7.3 kcal/mol) and verbascoside (−7.1 kcal/mol), from the plants Clerodendrum serratum and Houttuynia cordata, evidenced a strong inhibitory effect against the mutated NTD (MT-NTD). In addition, the phytocompounds kanzonol V (−6.8 kcal/mol), progeldanamycin (−6.4 kcal/mol), and rhodoxanthin (−7.5 kcal/mol), from the plant Houttuynia cordata, manifested significant prohibition against RBD. Nevertheless, the standard drug, ceftriaxone, signals less inhibitory effect against MT-NTD and RBD with binding affinities of −6.3 kcal/mol and −6.5 kcal/mol, respectively. In this study, we also emphasized the pharmacological properties of the plants, which contain the screened phytocompounds. Our research could be used as a lead for future drug design to develop anti-viral drugs, as well as for preening the Siddha formulation to control the Indian delta variant B.1.617.2 and other future SARS-CoV-2 variants.

scholarly journals Repurposed Drugs Block Toxin-Driven Platelet Clearance by the Hepatic Ashwell-Morell Receptor to Clear Staphylococcus aureus Bacteremia

2020 ◽  
Author(s):  
Josh Sun ◽  
Satoshi Uchiyama ◽  
Joshua Olson ◽  
Yosuke Morodomi ◽  
Ingrid Cornax ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Critical Role ◽  
Bloodstream Infections ◽  
Therapeutic Benefit ◽  
High Morbidity ◽  
Staphylococcus Aureus Bacteremia ◽  
Sialidase Inhibitor ◽  
Repurposed Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs

ABSTRACTStaphylococcus aureus (SA) bloodstream infections cause high morbidity and mortality (20-30%) despite modern supportive care. In a human bacteremia cohort, development of thrombocytopenia was correlated to increased mortality and increased α-toxin expression by the pathogen. Platelet-derived antibacterial peptides are important in bloodstream defense against SA, but α-toxin decreased platelet viability, induced platelet sialidase to cause desialylation of platelet glycoproteins, and accelerated platelet clearance by the hepatic Ashwell-Morell receptor (AMR). Ticagrelor (Brilinta®), a commonly prescribed P2Y12 receptor inhibitor used post-myocardial infarction, blocked α-toxin-mediated platelet injury and resulting thrombocytopenia, thus providing protection from lethal SA infection in a murine intravenous challenge model. Genetic deletion or pharmacological inhibition of AMR stabilized platelet counts and enhanced resistance to SA infection, and the anti-influenza sialidase inhibitor oseltamivir (Tamiflu®) provided similar therapeutic benefit. Thus a “toxin-platelet-AMR” regulatory pathway plays a critical role in the pathogenesis of SA bloodstream infection, and its elucidation provides proof-of-concept for repurposing two FDA-approved drugs as adjunctive therapies to improve patient outcomes.

Bilingual and Monolingual Students' Perceptions of the CSD Major: A Qualitative Study

2015 ◽  
Vol 18 (1) ◽  
pp. 16-31 ◽  
Author(s):  
Flora Keshishian ◽  
Rebecca Wiseheart
Keyword(s):  
Qualitative Study ◽  
Undergraduate Students ◽  
Critical Role ◽  
School Setting ◽  
The United States ◽  
Bilingual Students ◽  
Speech Language Pathology ◽  
Diverse Environment ◽  
Language Pathology ◽  
Areas Of Interest

There is a growing demand for bilingual services in speech-language pathology and audiology. To meet this growing demand, and given their critical role in the recruitment of more bilingual professionals, higher education institutions need to know more about bilingual students' impression of Communication Sciences and Disorders (CSD) as a major. The purpose of this qualitative study was to investigate bilingual and monolingual undergraduate students' perceptions of the CSD major. One hundred and twenty-two students from a large university located in a highly multicultural metropolitan area responded to four open-ended questions aimed at discovering students' major areas of interest (and disinterest) as well as their motivations for pursuing a degree in CSD. Consistent with similar reports conducted outside the United States, students from this culturally diverse environment indicated choosing the major for altruistic reasons. A large percentage of participants were motivated by a desire to work with children, but not in a school setting. Although 42% of the participants were bilingual, few indicated an interest in taking an additional course in bilingual studies. Implications of these findings as well as practical suggestions for the recruitment of bilingual students are discussed.

James Bryce and the Australian Constitution

2015 ◽  
Vol 43 (2) ◽  
pp. 177-200
Author(s):  
Stephen Gageler
Keyword(s):  
United States ◽  
Judicial Review ◽  
Constitutional Law ◽  
The United States ◽  
United States Constitution ◽  
Constitutional Development ◽  
Practical Operation ◽  
Responsible Government ◽  
Shed Light

James Bryce was a contemporary of Albert Venn Dicey. Bryce published in 1888 The American Commonwealth. Its detailed description of the practical operation of the United States Constitution was influential in the framing of the Australian Constitution in the 1890s. The project of this article is to shed light on that influence. The article compares and contrasts the views of Bryce and of Dicey; Bryce's views, unlike those of Dicey, having been largely unexplored in contemporary analyses of our constitutional development. It examines the importance of Bryce's views on two particular constitutional mechanisms – responsible government and judicial review – to the development of our constitutional structure. The ongoing theoretical implications of The American Commonwealth for Australian constitutional law remain to be pondered.

Building America

2019 ◽  
Author(s):  
Jean H. Baker
Keyword(s):  
United States ◽  
Early Republic ◽  
Critical Role ◽  
Water System ◽  
The United States ◽  
Primary Sources ◽  
Early American ◽  
Transatlantic Exchange ◽  
The Us ◽  
Private Homes

Building America: The Life of Benjamin Henry Latrobe is a biography of America’s first professionally trained architect and engineer. Born in 1764, Latrobe was raised in Moravian communities in England and Germany. His parents expected him to follow his father and brother into the ministry, but he rebelled against the church. Moved to London, he studied architecture and engineering. In 1795 he emigrated to the United States and became part of the period’s Transatlantic Exchange. Latrobe soon was famous for his neoclassical architecture, designing important buildings, including the US Capitol and Baltimore Basilica as well as private homes. Carpenters and millwrights who built structures more cheaply and less permanently than Latrobe challenged his efforts to establish architecture as a profession. Rarely during his twenty-five years in the United States was he financially secure, and when he was, he speculated on risky ventures that lost money. He declared bankruptcy in 1817 and moved to New Orleans, the sixth American city that he lived in, hoping to recoup his finances by installing a municipal water system. He died there of yellow fever in 1820. The themes that emerge in this biography are the critical role Latrobe played in the culture of the early republic through his buildings and his genius in neoclassical design. Like the nation’s political founders, Latrobe was committed to creating an exceptional nation, expressed in his case by buildings and internal improvements. Additionally, given the extensive primary sources available for this biography, an examination of his life reveals early American attitudes toward class, family, and religion.

Disparities in Health Between Black and White Americans: Current Knowledge and Directions for Future Research

2018 ◽  
pp. 456-478
Author(s):  
Thomas E. Fuller-Rowell ◽  
David S. Curtis ◽  
Adrienne M. Duke
Keyword(s):  
Health Disparities ◽  
Current Knowledge ◽  
Public Investment ◽  
The United States ◽  
Future Research ◽  
Sociocultural Factors ◽  
White Americans ◽  
Biological Mechanisms ◽  
Black And White ◽  
Racial Ethnic

Conceptual frameworks for racial/ethnic health disparities are abundant, but many have received insufficient empirical attention. As a result, there are substantial gaps in scientific knowledge and a range of untested hypotheses. Particularly lacking is specificity in behavioral and biological mechanisms for such disparities and their underlying social determinants. Alongside lack of political will and public investment, insufficient clarity in mechanisms has stymied efforts to address racial health disparities. Capitalizing on emergent findings from the Midlife in the United States (MIDUS) study and other longitudinal studies of aging, this chapter evaluates research on health disparities between black and white US adults. Attention is given to candidate behavioral and biological mechanisms as precursors to group differences in morbidity and mortality and to environmental and sociocultural factors that may underlie these mechanisms. Future research topics are discussed, emphasizing those that offer promise with respect to illuminating practical solutions to racial/ethnic health disparities.

scholarly journals Remedying the Mitochondria to Cure Human Diseases by Natural Products

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Jian-Kang Mu ◽  
Yan-Qin Li ◽  
Ting-Ting Shi ◽  
Li-Ping Yu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Natural Products ◽  
Mitochondrial Dysfunction ◽  
Mechanism Of Action ◽  
Current Knowledge ◽  
Human Diseases ◽  
Mitochondrial Regulation ◽  
The Relationship

Mitochondria are the ‘engine’ of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products.

scholarly journals Aldose Reductase and the Polyol Pathway in Schwann Cells: Old and New Problems

2021 ◽  
Vol 22 (3) ◽  
pp. 1031
Author(s):  
Naoko Niimi ◽  
Hideji Yako ◽  
Shizuka Takaku ◽  
Sookja K. Chung ◽  
Kazunori Sango
Keyword(s):  
Schwann Cells ◽  
Aldose Reductase ◽  
Critical Role ◽  
Polyol Pathway ◽  
Glucose Flux ◽  
Rate Limiting ◽  
Deficient Mice ◽  
Excess Glucose ◽  
Shed Light ◽  
Immortalized Schwann Cells

Aldose reductase (AR) is a member of the reduced nicotinamide adenosine dinucleotide phosphate (NADPH)-dependent aldo-keto reductase superfamily. It is also the rate-limiting enzyme of the polyol pathway, catalyzing the conversion of glucose to sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase. AR is highly expressed by Schwann cells in the peripheral nervous system (PNS). The excess glucose flux through AR of the polyol pathway under hyperglycemic conditions has been suggested to play a critical role in the development and progression of diabetic peripheral neuropathy (DPN). Despite the intensive basic and clinical studies over the past four decades, the significance of AR over-activation as the pathogenic mechanism of DPN remains to be elucidated. Moreover, the expected efficacy of some AR inhibitors in patients with DPN has been unsatisfactory, which prompted us to further investigate and review the understanding of the physiological and pathological roles of AR in the PNS. Particularly, the investigation of AR and the polyol pathway using immortalized Schwann cells established from normal and AR-deficient mice could shed light on the causal relationship between the metabolic abnormalities of Schwann cells and discordance of axon-Schwann cell interplay in DPN, and led to the development of better therapeutic strategies against DPN.

scholarly journals Impact of mobile stroke units

2021 ◽  
pp. jnnp-2020-324005
Author(s):  
Klaus Fassbender ◽  
Fatma Merzou ◽  
Martin Lesmeister ◽  
Silke Walter ◽  
Iris Quasar Grunwald ◽  
...  
Keyword(s):  
Cost Efficiency ◽  
Current Knowledge ◽  
Vascular Imaging ◽  
Vessel Occlusion ◽  
Stroke Units ◽  
Stroke Treatment ◽  
Stroke Research ◽  
Mobile Stroke Unit ◽  
Novel Strategy

Since its first introduction in clinical practice in 2008, the concept of mobile stroke unit enabling prehospital stroke treatment has rapidly expanded worldwide. This review summarises current knowledge in this young field of stroke research, discussing topics such as benefits in reduction of delay before treatment, vascular imaging-based triage of patients with large-vessel occlusion in the field, differential blood pressure management or prehospital antagonisation of anticoagulants. However, before mobile stroke units can become routine, several questions remain to be answered. Current research, therefore, focuses on safety, long-term medical benefit, best setting and cost-efficiency as crucial determinants for the sustainability of this novel strategy of acute stroke management.

scholarly journals Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanchi Malhotra ◽  
Imran Masood ◽  
Noberto Giglio ◽  
Jay D. Pruetz ◽  
Pia S. Pannaraj
Keyword(s):  
United States ◽  
Differential Diagnosis ◽  
Heart Disease ◽  
Chagas Disease ◽  
Latin American ◽  
Current Knowledge ◽  
Parasitic Infection ◽  
The United States ◽  
Cardiac Complications ◽  
The U.S

Abstract Background Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. Methods We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. Results Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. Conclusions Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

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