International Journal of Drug Discovery and Pharmacology

Brief Version of Chinese Society of Cardiology Guidelines on the Diagnosis and Treatment of Adult Fulminant Myocarditis

Hongyang Shu, Chen Chen, Luyun Wang, Jiangang Jiang, Daowen Wang — Tue, 20 Aug 2024 00:00:00 +0800

Review

Brief Version of Chinese Society of Cardiology Guidelines on the Diagnosis and Treatment of Adult Fulminant Myocarditis

Hongyang Shu, Chen Chen, Luyun Wang, Jiangang Jiang and Daowen Wang *

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

* Correspondence: dwwang@tjh.tjmu.edu.cn

Received: 3 April 2024; Revised: 6 June 2024; Accepted: 25 June 2024; Published: 20 August 2024

Abstract: Fulminant myocarditis is an acute and severe diffuse inflammatory disease of the heart with a high mortality rate. Its pathogenesis is driven by overactivation of the innate immunity and inflammatory storms. Based on China’s practical experience, the clinical guidelines for the management of the disease recommend adoption of a “life support-based comprehensive treatment regimen” which comprises mechanical circulatory support and immunomodulatory therapy at optimized doses of glucocorticoids and immunoglobin rather than immunosuppression to improve survival rates and long-term prognosis. The application experience of this treatment regimen in China provides evidence upon which the guidelines are formulated. This regimen emphasizes the importance of early identification, diagnosis, prediction, and treatment in patients with fulminant myocarditis. This is a brief introduction of the guidelines.

Cell Proliferation and Cytotoxicity Assays, The Fundamentals for Drug Discovery

Jingyi Niu, Minai Li, Ying Wang — Tue, 20 Aug 2024 00:00:00 +0800

Review

Cell Proliferation and Cytotoxicity Assays, The Fundamentals for Drug Discovery

Jingyi Niu ^†, Minai Li ^† and Ying Wang *

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao 999078, China

* Correspondence: emilyywang@um.edu.mo

† These authors contributed equally to this work

Received: 6 May 2024; Revised: 19 June 2024; Accepted: 21 June 2024; Published: 20 August 2024

Abstract: Cell proliferation and cytotoxicity assays are fundamental to drug discovery. This review summarizes prevalent methodologies for assessing cell proliferation and cytotoxicity, including direct cell count, metabolic activity, luminescent labeling, and tri-color viability imaging. The critical determinants that can significantly impact these assay outcomes, such as cellular doubling time, transitional states like quiescence and autophagy, cell cycle stages, metabolic enzyme functions, and genetic variability, are also explored. It is necessary to integrate the commonly used assays with additional analytical techniques to achieve precision in drug discovery. A multi-tiered approach that combines cellular assays with molecular analyses can improve screening processes, reduce false negatives, and increase confidence in the therapeutic potential of lead compounds.

Detoxification of Paraquat: Scooping up the Moon from the Water?

Yanyan Zhu, Xiuping Chen — Fri, 23 Aug 2024 00:00:00 +0800

Review

Detoxification of Paraquat: Scooping up the Moon from the Water?

Yanyan Zhu and Xiuping Chen *

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 519000, China

* Correspondence: xpchen@um.edu.mo; Tel.: +853-88224679

Received: 9 May 2024; Revised: 6 June 2024; Accepted: 12 June 2024; Published: 23 August 2024

Abstract: Paraquat poisoning is a global public health problem, particularly in the Asia-Pacific region. Ingestion of even small amounts of paraquat can be life-threatening. However, there is no specific antidote for this pesticide, which has a low lethal dose and high lethality in humans. Paraquat poisoning causes systemic toxicity with the primary target organ being the lungs, resulting in acute alveolitis and pulmonary fibrosis. It can also lead to multiple organ failure. This review summarizes the current clinical management of patients with paraquat poisoning and the potentially effective compounds reported in the literature and patents for the treatment of paraquat poisoning. It also summarizes future directions for antidote development based on reports of available potential antidotes and provides ideas for paraquat antidote development.

Proteolysis Targeting Chimeras (PROTACs): An Innovative Strategy for Targeted Protein Degradation and Disease Treatment

Jun Xia, James K.S. Norris, May-Li MacKinnon, Sam Butterworth — Mon, 26 Aug 2024 00:00:00 +0800

Review

Proteolysis Targeting Chimeras (PROTACs): An Innovative Strategy for Targeted Protein Degradation and Disease Treatment

Jun Xia, James K.S. Norris, May-Li MacKinnon and Sam Butterworth *

Division of Pharmacy and Optometry, Faculty of Biology Medicine and Health, The University of Manchester, Manchester M13 9PL, UK

* Correspondence: sam.butterworth@manchester.ac.uk

Received: 18 May 2024; Revised: 9 July 2024; Accepted: 9 July 2024; Published: 26 August 2024

Abstract: Protein ubiquitination is a highly conserved post-translational modification through which cells initiate the proteasomal degradation of undesired, aberrant, or damaged proteins. Protein ubiquitination plays a crucial role in protein homeostasis and regulates a wide range of essential physiological processes including DNA repair, immunological response, cell survival and apoptosis. Dysregulation of ubiquitination is associated with various pathologies including cancers, neurodegenerative diseases, and immune disorders. The ubiquitin-proteasome system (UPS) machinery has been utilized in therapeutic research as it can be manipulated to induce the degradation of undruggable proteins in a superior manner to traditional drug modalities. One such a method of specific protein degradation is the use of heterobifunctional molecules such as proteolysis targeting chimeras (PROTACs). This literature review will focus on the composition, mechanism of action and developmental milestones of PROTACs, comparing these against traditional drug discovery and treatment approaches. In addition, the potential benefits of PROTAC usage will be highlighted by analyzing their practical applications in drug therapies.

Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection

Tue, 27 Aug 2024 00:00:00 +0800

Review

Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection

Lionel Chong, Nicholas Dushaj, Ani Rakoubian, Johnathan Yarbro, Satoru Kobayashi and Qiangrong Liang *

Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY 11568-8000, USA

* Correspondence: qliang03@nyit.edu; Tel.: +1-516-686-1331; Fax: +1-516-686-3832

Received: 23 April 2024; Revised: 31 May 2024; Accepted: 3 June 2024; Published: 27 August 2024

Abstract: Cardiomyocytes are highly dependent on oxygen for optimal function. Disruption of oxygen availability, as in the case of ischemic heart disease, can significantly impair heart function. Moreover, comorbidities like diabetes, hyperlipidemia, and hypertension can exacerbate ischemic cardiac injury. However, cardiomyocytes possess inherent protective mechanisms that can be activated to enhance myocardial survival under such conditions. Understanding the functions and regulatory mechanisms of these cardioprotective genes is crucial for advancing our knowledge of cardiovascular health and for developing therapeutic strategies. This review examines the intricate mechanisms of cardioprotection, with a focus on key genes and proteins, including hypoxia-inducible factor-1 (HIF-1), heme oxygenase-1 (HO-1), glucose transporter 1 (GLUT-1), and GLUT-4. In addition, the review explores the roles and regulation of these factors in the heart under ischemic stress, shedding light on their relevance in conditions like diabetes, hypertension, and hyperlipidemia/atherosclerosis. Moreover, it highlights the complex interplay among their mechanisms and suggests opportunities for developing targeted therapiesfor the treatment of ischemic heart disease, hypertension, and hyperlipidemia.

Human Cardiac Organoids: Quantification and Qualification in Cardiovascular Studies

Yingjuan Liu, Sabu Abraham, Honglin Xu — Thu, 29 Aug 2024 00:00:00 +0800

Review

Human Cardiac Organoids: Quantification and Qualification in Cardiovascular Studies

Yingjuan Liu, Sabu Abraham, and Honglin Xu *

Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK.

* Correspondence: honglin.xu@postgrad.manchester.ac.uk

Received: 4 April 2024; Revised: 29 May 2024; Accepted: 29 May 2024; Published: 29 August 2024

Abstract: The human cardiac organoids (hCOs) represent a three-dimensional (3D) tissue model that mirrors in vivo cardiac conditions. Recent advancements underscore the immense potential of hCOs in several areas including studying early cardiogenesis, modeling heart diseases, screening potential drugs, and even exploring possibilities for cardiac regeneration. Recognizing the pivotal role hCOs play across various applications, this review examines the evolution of key metrics and tools for assessing cardiac organoids tailored for diverse research objectives. Moreover, it deliberates on the limitations of cardiac organoids and outlines the prospective avenues for future research applications of hCOs.

Molecular and cellular contributors of Rheumatoid Arthritis

Qingxin Bang, Weihua Song, Xiaomeng Wang — Thu, 29 Aug 2024 00:00:00 +0800

Review

Molecular and Cellular Contributors of Rheumatoid Arthritis

Qingxin Bang¹, Weihua Song², and Xiaomeng Wang^1,3,4,*

¹ Centre for Vision Research, Duke NUS Medical School, 8 College Road, Singapore 169857, Singapore
² Innoland Biosciences, 400 East Building, 6 West Beijing Road, Taicang 215414, China
³ Singapore Eye Research Institute (SERI) The Academia, 20 College Road, Level 6 Discovery Tower, Singapore 169856, Singapore
⁴ Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Dr, Singapore 138673, Singapore

* Correspondence: xiaomeng.wang@duke-nus.edu.sg

Received: 7 March 2024; Revised: 17 May 2024; Accepted: 18 May 2024; Published: 29 August 2024

Abstract: Rheumatoid arthritis (RA) is a chronic immune-mediated condition affecting about 1% of the world population. Persistent synovial inflammation (synovitis) triggers the hyperplastic transformation of the synovium which eventually destroys juxta-articular bones and articular cartilage. As the disease progresses, RA patients may present systemic and extra-articular manifestations. Particularly, RA patients are at an increased risk of developing cardiovascular events and mortality as compared to individuals without RA. Recent advances in understanding the molecular and cellular mechanisms of RA led to the development of disease-modifying drugs and reliable assessment tools that have significantly improved the management of RA. This review focuses on the current understanding of RA pathogenesis and treatment strategies.