International Journal of Drug Discovery and Pharmacology

The Application of Artificial Intelligence in the Research and Development of Traditional Chinese Medicine

Mon, 18 Mar 2024 00:00:00 +0800

Review

The Application of Artificial Intelligence in the Research and Development of Traditional Chinese Medicine

Zhipeng Ke ^1,2, Minxuan Liu ^1,2,3, Jing Liu ^1,2, Zhenzhen Su ^1,2, Lu Li ^1,2, Mengyu Qian ^1,2, Xinzhuang Zhang ^1,2, Tuanjie Wang ^1,2, Liang Cao ^1,2, Zhenzhong Wang ^1,2, and Wei Xiao ^{1,2, *}

¹National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Lianyungang 222106, China

²Jiangsu Kanion Pharmaceutical Co., Ltd, Lianyungang 222104, China

³ ‍School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210009, China

^* Correspondence: xw_kanion@163.com

Received: 4 September 2023

Accepted: 4 November 2023

Published: 18 March 2024

Abstract: With the accumulation of data in the pharmaceutical industry and the development of artificial intelligence technology, various artificial intelligence methods have been successfully employed in the drug discovery process. The integration of artificial intelligence in Traditional Chinese medicine has also gained momentum, encompassing quality control of Chinese patent medicines, prescriptions optimization, discovery of effective substances, and prediction of side effects. However, artificial intelligence also faces challenges and limitations in Traditional Chinese medicine development, such as data scarcity and complexity, lack of interdisciplinary professionals, black-box models, etc. Therefore, more research and collaboration are needed to address these issues and explore the best ways to integrate artificial intelligence and Traditional Chinese medicine to improve human health.

Mkk7 Protects Against Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction

Mon, 18 Mar 2024 00:00:00 +0800

Article

Mkk7 Protects Against Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction

Tayyiba Azam ^{1, *}, Hongyuan Zhang ¹, Susanne S. Hille ², Elizabeth J. Cartwright ¹, Oliver J. Müller ², and Xin Wang ^{1, *}

¹ Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, M13 9PT, Manchester, UK

² Department of Internal Medicine III, University of Kiel, Germany; German Centre for Cardiovascular Research (DZHK), 24105 Partner Site Hamburg/Kiel/Lübeck, Germany

^* Correspondence: xin.wang@manchester.ac.uk (Xin Wang); tayyiba.azam@manchester.ac.uk (Tayyiba Azam)

Received: 12 June 2023

Accepted: 25 September 2023

Published: 18 March 2024

Abstract: Shifts in epidemiological patterns foretell a rapid increase in the number of patients with heart failure (HF) globally, representing a significant health and economic burden. Heart failure with preserved ejection (HFpEF) is now considered the prevailing subtype of HF, with no effective treatment available to combat this syndrome. Previous studies have highlighted the cardioprotective role of MKK7 during cardiac pathology, however, no extensive research has been performed to examine MKK7 in the context of HFpEF. This study aimed to address this shortcoming by using adeno-associated virus (AAV) 9 to overexpress MKK7 in the two-hit clinically relevant HFpEF mouse model. We report that cardiomyocyte-specific overexpression of MKK7 improved the HFpEF phenotype in mice, by impeding cardiac diastolic dysfunction and myocardial fibrosis. Mechanistically, it was found that MKK7 ameliorated ER stress by maintaining IRE1-XBP1 signalling and blunted CHOP increase in the myocardium. To summarise, MKK7 overexpression holds the ability to protect the myocardium from HFpEF associated pathologies.

Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases

Zijie Liu, Tianyu Song, Liping Xie — Mon, 18 Mar 2024 00:00:00 +0800

Review

Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases

Zijie Liu ^1,2, Tianyu Song ³, and Liping Xie ^{1,2,3, *}

¹ Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China

² School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China

³ ‍Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211166, China

^* Correspondence: lipingxie@njmu.edu.cn

Received: 16 October 2023

Accepted: 20 November 2023

Published: 18 March 2024

Abstract: The transforming growth factor β (TGF-‍β) signaling pathway is crucial for preserving the structural homeostasis of the aorta and promoting aortic development. This pathway encompasses both SMAD-dependent canonical pathway and SMAD-independent non-canonical signaling pathway. Heritable thoracic aortic aneurysms and dissection are highly correlated with genetic alterations in TGF-‍β canonical signaling-related genes. However, depending on the stage of the disease, the TGF-‍β signaling pathway can have either inhibitory or aggravation effects, making its roles in aortic disease complex and occasionally contradictory. This review aims to elucidate the biological mechanisms underlying the TGF-‍β signaling pathway in the most common aortic diseases, namely acute aortic syndromes and aortic aneurysms, and to evaluate the potential clinical application of TGF-β-targeting therapies in aortic diseases.

Development of Proteasome Inhibitors for Cancer Therapy

Xu Chen, Xuan Wu, Linyan Li, Xiaoming Zhu — Mon, 18 Mar 2024 00:00:00 +0800

Review

Development of Proteasome Inhibitors for Cancer Therapy

Xu Chen ^†, Xuan Wu ^†, Linyan Li, and Xiaoming Zhu ^*

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China

^* Correspondence: xmzhu@must.edu.mo

† These authors contributed equally to this work.

Received: 12 January 2024

Accepted: 19 February 2024

Published: 18 March 2024

Abstract: The ubiquitin proteasome system (UPS) is considered a crucial degradation machinery in cellular processes of protein quality control and homeostasis. Dysregulation of the UPS is closely associated with many diseases. The proteasome is a key core component of the UPS, which can prevent the accumulation of misfolded proteins and regulate various cellular processes such as cell cycle, apoptosis, and immune responses. In the past two decades, a total of three proteasome inhibitors have been approved for the treatment of hematological malignancies, including bortezomib, carfilzomib, and ixazomib. Additionally, accumulating reports have suggested that some natural product-derived proteasome inhibitors have been developed as anti-cancer drug candidates. In this review, we summarize the development of proteasome inhibitors as well as the mechanisms involved, clinical application progress, and drug resistance. The natural products of proteasome inhibitors and their future perspectives will also be discussed.

Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases

Hongyuan Zhang, Minxing Zhao, Yanrong Liu — Mon, 18 Mar 2024 00:00:00 +0800

Review

Breaking Boundaries: Novel Effects of Levosimendan in Various Diseases

Hongyuan Zhang¹, Minxing Zhao², and Yanrong Liu^1,3,*

¹Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, M139PT Manchester, UK.

²Loreto High School, Chorlt on, M217SW Manchester, UK.

³The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing, China.

* Correspondence: yanrong.liu@manchester.ac.uk

Received: 6 February 2024

Accepted: 23 February 2024

Published: 18 March 2024

Abstract: Levosimendan, an inodilator that has been applied in clinical use for over two decades, has transcended its initial indication in the management of acutely decompensated chronic heart failure. Over the years, it has been adopted in septic shock, perioperative use of cardiac surgery, advanced end-stage heart failure, and has shown potential for inhaled administration, highlighting its versatility. Levosimendan has diverse mechanisms of action which mediate its non-traditional uses. Ongoing research aims to expand our understanding and develop personalized treatment strategies for the use of levosimendan. The significance of levosimendan in acute decompensated heart failure and cardiogenic shock, highlights its evolving role in contemporary cardiovascular medicine. This comprehensive review explores its pharmacodynamics, effects, and the challenges and opportunities it presents in various clinical settings. We describe levosimedan’s expanding usage, ranging from septic shock, intermittent intravenous in advanced heart failure, perioperative cardiac surgery and pulmonary hypertension management by inhaled levosimendan as well as its future prospects.