This Special Issue attributes to the 2017 China-Canada-USA Pharmacology/Physiology Conference (CCUPPC), one of the initiatives of promoting scientific exchanges and research collaborations in the field of pharmacology, physiology and drug development. The conference brought scientists from China, Canada, and USA together, and created a new platform for international collaboration.
The conference took place at the University of Toronto, known as the birthplace for insulin and the alma mater of Dr. Norman Bethune, and is also one of the world's top research-intensive universities, from June 25 to June 30, 2017. The conference was sponsored by the University of Toronto (Faculties of Medicine and Pharmacy; Departments of Physiology, and Pharmacology and Toxicology) and was co-organized with the Chinese Pharmacological Society, the Canadian Physiological Society, the Canadian Society of Pharmacology and Therapeutics, and the North American Chinese Pharmacological Association. The conference was also supported by the Guangdong Pharmacological Society, the North American Chapter Chinese Pharmacological Society, Acta Pharmacologica Sinica, the Toronto Chinese Professors Association, and Society of Chinese Bioscientists in America Toronto Chapter.
In this special issue, all articles have been peer-reviewed and provide the current views on critical topics in pharmacology and drug development that have been extensively discussed at the conference.
Stroke has been one of the leading causes of death worldwide, and threatened the health of the aging population. However, the mechanism leading to ischemic and hypoxic brain damage in stroke and related disorders remains not fully understood, thus hindering the development of efficient treatment and prevention of stroke. Tymianski's group from the University of Toronto emphasized that stroke creates a complex interplay of multiple pathways, and discussed the discovery of NA-1 as a potential neuroprotectant in acute stroke1. Jiangang Shen group from Hong Kong University highlighted the important role of reactive nitrogen species/caveoline-1/matrix metalloproteinase signalling cascades in ischemic stroke injury, and discussed the potential of a few natural compounds in stroke treatment by targeting the pathways2. Hong-Shuo Sun and Zhong-Ping Feng groups from the University of Toronto summarized the current progresses of drug uses to promote stem-cell-based therapy following stroke3. The Sun and Feng groups also discussed the role of a number of ion channels, including KATP4, TRPM25 and Cl channels6, and the effects of their modulators in ischemic and hypoxic brain injury in adult and neonatal models. Shirley Wu group from the University of Toronto further discussed the advances of nanotechnology in efficient drug delivery for brain disorders7.
Mental health and other neurodegenerative disorders have been the main focuses in neuropharmacological studies. Albert Wong group from the Centre for Addition and Mental Health and the University of Toronto discussed potential drug targets for schizophrenia8 and anxiety-related behaviour9. Yufeng Tong group from the Structural Genomics Consortium at the University of Toronto reviewed that dysfunction of ubiquitylation system that plays an integral role in proteostasis is progressive in Huntington's disease and unravelling the molecular mechanisms the pathogenesis of proteostasis provided insight in new potential therapeutic avenues in the disease10. Michael Jackson group from University of Manitoba highlighted the current advances of TRPM 2 channels as a drug target in a number of neurological diseases including Alzhemer disease, Parkinson disease, and bipolar disorder11.
Phoenixin is a newly discovered novel peptide released from reproductive glands. Jin Jun Luo group from Lewis Katz School of Medicine at Temple University and Denise Belsham group from the University of Toronto independently reviewed the discovery of the peptide. Denise Belsham group emphasized the functions and mechanisms of action underlying effects of phoenixin12, whereas Jin Jun Luo group stressed the possible role of the peptide in the “itch sensation” that transmits from the skin to brain13.
Another major research topic in pharmacology is to better understand the mechanisms of action underlying effects of natural products. For instance, Tianru Jin from the University of Toronto pointed out that the curry compound, curcumin, has been drawing the most attention from bio-medical researchers and drug developers, and discussed how curcumin and dietary polyphenol research has enriched our knowledge of insulin signalling14. Catherine Chan group from University of Alberta showed that epicatechin, an ingredient of dark chocolate, exhibited pro-glucose-stimulated insulin secretion independent on antioxidant activity15. Zhong Zuo group from the Chinese University of Hong Kong provided a comprehensive overview of the anti-inflammatory effects, pharmacokinetic properties, and clinical efficacy of arctigenin and arctiin from Arctium lappa L16.
Salvia miltiorrhiza Burge (Danshen) is an eminent medicinal herb and used broadly in cardiovascular and cerebrovascular disorders. Pei-qing Liu group from Sun Yat-Sen University provided a systematic up-to-date review on the cardiovascular actions and therapeutic potential of the major bioactive constituents of Danshen17. Yao-ming Du and Guan-lei Wang groups from Guangdong Academy of Medical Sciences and Sun Yat-Sen University, respectively, reported a novel marine compound, Xyloketal B, isolated from mangrove fungus Xylaria sp. exhibiting antihypertensive effects via both endothelial NO-sGC-cGMP pathway and smooth muscle calcium signalling18. Chunxiang Zhang group from the University of Alabama at Birmingham further revealed the microRNA expression profile and demonstrated that miR-145 mediated a critical signalling pathway in serum-induced contact inhibition disruption. They concluded that the contact inhibition of vascular smooth muscle cells may represent a novel therapeutic approach for vascular disease19. In addition, Mingyao Liu group from the University of Toronto reviewed the history and current progress of organ preservation, and discussed the future directions of the most effective therapy for patients with end-stage diseases to meet the increased demands in medical practice20.
We would like to thank the editorial staffs of Acta Pharmacologica Sinica for their support for and assistance during the process of the issue production. We look forward to furthering the international collaboration in future research endeavours.
Ballarin B, Tymianski M . Discovery and development of NA-1 for the treatment of acute ischemic stroke. Acta Pharmacol Sin 2018; 39: 661–8.
Chen HS, Chen X, Li WT, Shen JG . Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery. Acta Pharmacol Sin 2018; 39: 669–82.
Zhu SZ, Szeto V, Bao MH, Sun HS, Feng ZP . Pharmacological approaches promoting stem cellbased therapy following ischemic stroke insults. Acta Pharmacol Sin 2018; 39: 695–712.
Szeto V, Chen NH, Sun HS, Feng ZP . The role of KATP channels in cerebral ischemic stroke. Acta Pharmacol Sin 2018; 39: 683–94.
Turlova E, Feng ZP, Sun HS . The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia. Acta Pharmacol Sin 2018; 39: 713–21.
Wong R, Abussaud A, Leung JW, Xu BF, Li FY, Huang S, et al. Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo . Acta Pharmacol Sin 2018; 39: 858–65.
Zhang RX, Li J, Zhang T, Amini MA, He C, Lu B, et al. Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy-an illustration with firsthand examples. Acta Pharmacol Sin 2018; 39: 825–44.
Xu MY, Wong AHC . GABAergic inhibitory neurons as therapeutic targets. Acta Pharmacol Sin 2018; 39: 733–53.
Wang DY, Kosowan J, Samsom J, Leung L, Zhang KL, Li YX, et al. Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice. Acta Pharmacol Sin 2018; 39: 866–74.
Harding RJ, Tong YF . Proteostasis in Huntington's disease. Acta Pharmacol Sin 2018; 39: 754–69.
Belrose JC, Jackson MF . TRPM2: a candidate therapeutic target for treating neurological diseases. Acta Pharmacol Sin 2018; 39: 722–32.
McIlwraith EK, Belsham DD . Phoenixin: uncovering its receptor, signaling and functions. Acta Pharmacol Sin 2018; 39: 774–8.
Lyu RM, Cowan A, Zhang Y, Chen YH, Dun SL, Chang JK, et al. Phoenixin: a novel brain-gut-skin peptide with multiple bioactivity. Acta Pharmacol Sin 2018; 39: 770–3.
Jin TR . Curcumin and dietary polyphenol research: beyond drug discovery. Acta Pharmacol Sin 2018; 39: 779–86.
Yang KY, Chan CB . Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity. Acta Pharmacol Sin 2018; 39: 893–902.
Gao Q, Yang M, Zuo Z . Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L. Acta Pharmacol Sin 2018; 39: 787–801.
Liu ZM, Xu SW, Liu PQ . Salvia miltiorrhiza Burge (Danshen): A golden herbal medicine in cardiovascular therapeutics. Acta Pharmacol Sin 2018; 39: 802–24.
Zhao LY, Li J, Huang XQ, Wang GH, Lv XF, Meng WF, et al. Xyloketal B exerts antihypertensive effect in renovascular hypertensive rats via the NO-sGC-cGMP pathway and calcium signaling. Acta Pharmacol Sin 2018; 39: 875–84.
Sun YY, Qin SS, Cheng YH, Wang CY, Liu XJ, Liu Y, et al. MicroRNA expression profile and functional analysis reveal their roles in contact inhibition and its disruption switch of vascular smooth muscle cells. Acta Pharmacol Sin 2018; 39: 885–92.
Jing L, Yao L, Zhao M, Peng LP, Liu MY . Organ preservation: from the past to the future. Acta Pharmacol Sin 2018; 39: 845–57.
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Feng, Zp., Sun, Hs. A new platform for international collaboration on pharmacology and drug development: 2017 China-Canada-USA Pharmacology/Physiology Conference. Acta Pharmacol Sin 39, 659–660 (2018). https://doi.org/10.1038/aps.2018.34