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      Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids

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          Abstract

          Cardiotonic steroids (CTS) are a group of compounds existing in animals and plants. CTS are commonly referred to cardiac glycosides (CGs) which are composed of sugar residues, unsaturated lactone rings and steroid cores. Their traditional mechanism of action is to inhibit sodium-potassium ATPase to strengthen the heart and regulate heart rate, so it is currently widely used in the treatment of cardiovascular diseases such as heart failure and tachyarrhythmia. It is worth noticing that recent studies have found an avalanche of inestimable values of CTS applications in many fields such as anti-tumor, anti-virus, neuroprotection, and immune regulation through multi-molecular mechanisms. Thus, the pharmacological activities and applications of CTS have extensive prospects, which would provide a direction for new drug research and development. Here, we review the potential applications of CTS in cardiovascular system and other systems. We also provide suggestions for new clinical practical strategies of CTS, for many diseases. Four main themes will be discussed, in relation to the impact of CTS, on 1) tumors, 2) viral infections, 3) nervous system diseases and 4) immune-inflammation-related diseases.

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          Most cited references129

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          Cancer Statistics, 2021

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            How neuroinflammation contributes to neurodegeneration.

            Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions such as signal transmission and network integration in the central nervous system and are the main targets of neurodegenerative disease. In this Review, I address how the neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests with supportive cells termed glia and the blood-brain barrier. Accumulating evidence suggests that neurodegeneration occurs in part because the environment is affected during disease in a cascade of processes collectively termed neuroinflammation. These observations indicate that therapies targeting glial cells might provide benefit for those afflicted by neurodegenerative disorders.
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              Cardiac excitation-contraction coupling.

              Of the ions involved in the intricate workings of the heart, calcium is considered perhaps the most important. It is crucial to the very process that enables the chambers of the heart to contract and relax, a process called excitation-contraction coupling. It is important to understand in quantitative detail exactly how calcium is moved around the various organelles of the myocyte in order to bring about excitation-contraction coupling if we are to understand the basic physiology of heart function. Furthermore, spatial microdomains within the cell are important in localizing the molecular players that orchestrate cardiac function.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                02 June 2022
                2022
                : 13
                : 902459
                Affiliations
                [1] 1 Key Laboratory of Cardiovascular Medicine Research , Department of Pharmacology , Ministry of Education , Harbin Medical University , Harbin, China
                [2] 2 Thyroid Surgery , Affiliated Cancer Hospital , Harbin Medical University , Harbin, China
                [3] 3 Department of Pharmacy , The Fourth Affiliated Hospital of Harbin Medical University , Harbin, China
                Author notes

                Edited by: Antonio Carlos Campos De Carvalho, Federal University of Rio de Janeiro, Brazil

                Reviewed by: Luis Eduardo M. Quintas, Federal University of Rio de Janeiro, Brazil

                Emiliano Medei, Federal University of Rio de Janeiro, Brazil

                This article was submitted to Cardiovascular and Smooth Muscle Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                902459
                10.3389/fphar.2022.902459
                9205219
                35721110
                f0df7d9f-09e5-483a-8828-5452bb370050
                Copyright © 2022 Ren, Gao, Guo, Wang and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2022
                : 11 May 2022
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                cardiotonic steroids (cts),antitumor,antiviral,neuroprotection,immune regulation

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