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The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15539. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Background: Prior observational studies have suggested a potential direct link between psoriasis (PSO) and interstitial lung disease (ILD). Consequently, we applied Mendelian randomization (MR) to further evaluate the bidirectional causal relationships between PSO and its different phenotypes [psoriatic arthritis (PSA)/psoriasis vulgaris (PSV)] and ILD. Methods: Data regarding PSO/PSA/PSV and ILD were sourced from publicly accessible genome-wide association studies (GWAS) databases, focusing on European populations. We used five algorithms— MR Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode— to evaluate the causal relationships between PSO/PSA/PSV and ILD, with a primary emphasis on the IVW method. Results: The analysis indicated a potential association between PSA and an elevated risk of ILD [IVW odds ratio (OR): 1.035 (95% CI 1.008, 1.064; P = 0.012)], with no evidence of a direct relationship between total PSO and PSV with ILD. Conversely, no substantial evidence emerged from the reverse MR analysis to suggest that ILD significantly affects total PSO or the specific PSA/PSV phenotypes. Conclusion: Our findings provide genetic evidence supporting the notion that PSA may be a contributory risk factor for ILD. Further investigations are warranted to explore the underlying mechanisms of this potential causal relationship between PSA and ILD. [ABSTRACT FROM AUTHOR]

As the leading cause of mortality worldwide, cardiovascular disease (CVD) represents a variety of heart diseases and vascular disorders, including atherosclerosis, aneurysm, ischemic injury in the heart and brain, arrythmias, and heart failure. Macrophages, a diverse population of immune cells that can promote or suppress inflammation, have been increasingly recognized as a key regulator in various processes in both healthy and disease states. In healthy conditions, these cells promote the proper clearance of cellular debris, dead and dying cells, and provide a strong innate immune barrier to foreign pathogens. However, macrophages can play a detrimental role in the progression of disease as well, particularly those inflammatory in nature. This review will focus on the current knowledge regarding the role of macrophages in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Aims Damage of the blood–brain barrier (BBB) is a hallmark of brain injury during the early stages of ischemic stroke. The subsequent endothelial hyperpermeability drives the initial pathological changes and aggravates neuronal death. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable nonselective cation channel activated by oxidative stress. However, whether TRPM2 is involved in BBB degradation during ischemic stroke remains unknown. We aimed to investigate the role of TRPM2 in BBB degradation during ischemic stroke and the underlying molecular mechanisms. Methods and results Specific deletion of Trpm2 in endothelial cells using Cdh5 Cre produces a potent protective effect against brain injury in mice subjected to middle cerebral artery occlusion (MCAO), which is characterized by reduced infarction size, mitigated plasma extravasation, suppressed immune cell invasion, and inhibited oxidative stress. In vitro experiments using cultured cerebral endothelial cells (CECs) demonstrated that either Trpm2 deletion or inhibition of TRPM2 activation attenuates oxidative stress, Ca2+ overload, and endothelial hyperpermeability induced by oxygen–glucose deprivation (OGD) and CD36 ligand thrombospondin-1 (TSP1). In transfected HEK293T cells, OGD and TSP1 activate TRPM2 in a CD36-dependent manner. Noticeably, in cultured CECs, deleting Trpm2 or inhibiting TRPM2 activation also suppresses the activation of CD36 and cellular dysfunction induced by OGD or TSP1. Conclusions In conclusion, our data reveal a novel molecular mechanism in which TRPM2 and CD36 promote the activation of each other, which exacerbates endothelial dysfunction during ischemic stroke. Our study suggests that TRPM2 in endothelial cells is a promising target for developing more effective and safer therapies for ischemic stroke. [ABSTRACT FROM AUTHOR]

The vast potential of human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) in preclinical models of cardiac pathologies, precision medicine, and drug screening remains to be fully realized because hiPSC-CMs are immature without adult-like characteristics. Here, we present a method to accelerate hiPSC-CM maturation on a substrate, cardiac mimetic matrix (CMM), mimicking adult human heart matrix ligand chemistry, rigidity, and submicron ultrastructure, which synergistically mature hiPSC-CMs rapidly within 30 days. hiPSC-CMs matured on CMM exhibit systemic transcriptomic maturation toward an adult heart state, are aligned with high strain energy, metabolically rely on oxidative phosphorylation and fatty acid oxidation, and display enhanced redox handling capability, efficient calcium handling, and electrophysiological features of ventricular myocytes. Endothelin-1-induced pathological hypertrophy is mitigated on CMM, highlighting the role of a native cardiac microenvironment in withstanding hypertrophy progression. CMM is a convenient model for accelerated development of ventricular myocytes manifesting highly specialized cardiac-specific functions. [Display omitted] • Rapid iPSC-CM maturation on surfaces mimicking native cardiac microenvironment • Concurrent metabolic and redox maturation on cardiac mimetic matrix (CMM) • Hybrid Steiner tree network identifies intermediaries involved in cardiac maturation • Cardiac ultrastructure moderates hypertrophic disease phenotype Afzal et al. induce physiologically inspired cardiac maturation. The resulting cardiac constructs display features of ventricular myocytes within 30 days including structural alignment, electrophysiological maturation, molecular signature, mitochondrial energetics and fatty acid oxidation, and efficient oxidative stress handling capability, facilitating their use in disease modeling and preclinical drug screening. [ABSTRACT FROM AUTHOR]

Glutamate excitotoxicity is a central mechanism contributing to cellular dysfunction and death in various neurological disorders and diseases, such as stroke, traumatic brain injury, epilepsy, schizophrenia, addiction, mood disorders, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, pathologic pain, and even normal aging-related changes. This detrimental effect emerges from glutamate binding to glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, N-methyl-d-aspartate receptors, kainate receptors, and GluD receptors. Thus, excitotoxicity could be prevented by targeting glutamate receptors and their downstream signaling pathways. However, almost all the glutamate receptor antagonists failed to attenuate excitotoxicity in human patients, mainly due to the limited understanding of the underlying mechanisms regulating excitotoxicity. Transient receptor potential (TRP) channels serve as ancient cellular sensors capable of detecting and responding to both external and internal stimuli. The study of human TRP channels has flourished in recent decades since the initial discovery of mammalian TRP in 1995. These channels have been found to play pivotal roles in numerous pathologic conditions, including excitotoxicity. In this review, our focus centers on exploring the intricate interactions between TRP channels and glutamate receptors in excitotoxicity. [ABSTRACT FROM AUTHOR]

Viral pneumonia (VP) is known for its wide transmission and severe pathological damage. ninety cases of VP patients were rolled into an experimental group (group E, methylprednisolone + advanced antibiotics + antiviral drugs) and a control group (group C, methylprednisolone), with 45 cases in each group. General information about the patients, inflammatory factors, serum immunoglobulins, T lymphocyte subsets, and treatment outcomes (efficiency rate, conversion rate to negative) were compared. In group E, interleukin-6 (IL-6) (0.18±0.07) ng/L was inferior to in group C (0.33±0.09) ng/L, p<0.05; tumor necrosis factor-alpha (TNF-α) (17.22±4.13) ng/L was inferior to group C (26.07±4.08) ng/L, p<0.05; lgA (0.81±0.22) g/L was superior to in group C (0.68±0.17) g/L, P<0.05; lgM (1.62±0.13) g/L was superior to group C (1.09±0.03) g/L, p<0.05; lgE (0.19±0.02) g/L was inferior to group C (0.23±0.03) g/L, p<0.05; CD4+/CD8+ ratio (1.71±0.33) was superior to group C (1.24±0.43), p<0.05; the total efficiency rate in group C (77.78%) was inferior to group E (97.78%), p<0.05; the conversion rate to negative of viral antigens in group E (91.11%) was superior to in group C (64.44%), p<0.05. methylprednisolone in combination with advanced antibiotics and antiviral drugs is an effective treatment approach for VP.

Objective: To accurately and effectively identify the most critical needs of extracorporeal membrane oxygenation (ECMO) treatment for patients with severe cardiopulmonary diseases, and to better carry out continuous improvement of medical service quality an patients' satisfaction., Methods: Patients who underwent ECMO and transferred from 56 medical institutions in the Henan Provincial People's Hospital Critical Care Medicine Specialist Alliance [the patients who were transported before applying quality function deployment (QFD) from June 2017 to May 2018 were enrolled as the control group, and patients who were transported after applying QFD from June 2018 to May 2019 were the observation group], medical staff in the alliance hospitals, ECMO transfer teams and transfer driver teams were enrolled as the subjects of the survey. QFD was applied to convert the collected requirements into quality improvement elements for targeted improvement measures., Results: A total of 125 questionnaires were distributed in this survey, and 116 valid questionnaires were collected, including 91 from patients (including 27 from the control group and 64 from the observation group), 10 from the medical staff of the alliance hospitals, 10 from the ECMO transport teams and 5 from the transport driver teams. The questionnaire recovery rate was 92.8%. The improvement elements of ECMO treatment for patients with critical cardiopulmonary diseases were ranked according to the importance, and the top five were as follows: the accuracy of the first diagnosis, the specialization of ECMO team, the guarantee of vehicle safety, the seamless responses, and the smooth coordinated rescue protocol., Conclusions: The top five improvement elements should be prioritized in ECMO treatment of patients with critical cardiopulmonary disease in all hospitals of the Alliance to ensure more accurate and timely treatment.