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      Polyamines: Functions, Metabolism, and Role in Human Disease Management

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          Abstract

          Putrescine, spermine, and spermidine are the important polyamines (PAs), found in all living organisms. PAs are formed by the decarboxylation of amino acids, and they facilitate cell growth and development via different cellular responses. PAs are the integrated part of the cellular and genetic metabolism and help in transcription, translation, signaling, and post-translational modifications. At the cellular level, PA concentration may influence the condition of various diseases in the body. For instance, a high PA level is detrimental to patients suffering from aging, cognitive impairment, and cancer. The levels of PAs decline with age in humans, which is associated with different health disorders. On the other hand, PAs reduce the risk of many cardiovascular diseases and increase longevity, when taken in an optimum quantity. Therefore, a controlled diet is an easy way to maintain the level of PAs in the body. Based on the nutritional intake of PAs, healthy cell functioning can be maintained. Moreover, several diseases can also be controlled to a higher extend via maintaining the metabolism of PAs. The present review discusses the types, important functions, and metabolism of PAs in humans. It also highlights the nutritional role of PAs in the prevention of various diseases.

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          A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.

          Over the past decade, myocardial structure, cardiomyocyte function, and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) a high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease, and salt-sensitive hypertension induce a systemic proinflammatory state; 2) a systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) coronary microvascular endothelial inflammation reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) low PKG activity favors hypertrophy development and increases resting tension because of hypophosphorylation of titin; and 5) both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and heart failure development. The new HFPEF paradigm shifts emphasis from LV afterload excess to coronary microvascular inflammation. This shift is supported by a favorable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction, in which remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation, or vascular hyperemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            TFEB links autophagy to lysosomal biogenesis.

            Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. During starvation, the cell expands both compartments to enhance degradation processes. We found that starvation activates a transcriptional program that controls major steps of the autophagic pathway, including autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. Nuclear localization and activity of TFEB were regulated by serine phosphorylation mediated by the extracellular signal-regulated kinase 2, whose activity was tuned by the levels of extracellular nutrients. Thus, a mitogen-activated protein kinase-dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles.
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              The intersection between aging and cardiovascular disease.

              The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will continue to increase. Aging is an inevitable part of life and unfortunately poses the largest risk factor for cardiovascular disease. Although numerous studies in the cardiovascular field have considered both young and aged humans, there are still many unanswered questions as to how the genetic pathways that regulate aging in model organisms influence cardiovascular aging. Likewise, in the molecular biology of aging field, few studies fully assess the role of these aging pathways in cardiovascular health. Fortunately, this gap is beginning to close, and these two fields are merging together. We provide an overview of some of the key genes involved in regulating lifespan and health span, including sirtuins, AMP-activated protein kinase, mammalian target of rapamycin, and insulin-like growth factor 1 and their roles regulating cardiovascular health. We then discuss a series of review articles that will appear in succession and provide a more comprehensive analysis of studies carried out linking genes of aging and cardiovascular health, and perspectives of future directions of these two intimately linked fields.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Med Sci (Basel)
                Med Sci (Basel)
                medsci
                Medical Sciences
                MDPI
                2076-3271
                09 June 2021
                June 2021
                : 9
                : 2
                : 44
                Affiliations
                [1 ]Department of Agriculture and Environmental Sciences, National Institute of Food Technology Entrepreneurship and Management, Kundli, Sonepat 131028, Haryana, India
                [2 ]Food Microbiology Lab, Division of Livestock Products Technology, ICAR-Indian Veterinary Research Institute, Izatnagar 243122, Uttar Pradesh, India
                [3 ]Department of Radiodiagnosis and Imaging, All India Institute of Medical Science, Rishikesh 249203, Uttarakhand, India; dr.tarafdarswarnava@ 123456gmail.com
                [4 ]Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India; surbhiagarwal171990@ 123456gmail.com
                [5 ]Livestock Production and Management Section, ICAR-Indian Veterinary Research Institute, Izatnagar 243122, Uttar Pradesh, India; ayontarafdar@ 123456gmail.com
                Author notes
                [* ]Correspondence: narashans.alok@ 123456gmail.com (N.A.S.); sharma.agribiotechnology@ 123456gmail.com (S.S.); Tel.: +91-82-2183-3995 (N.A.S.); +91-81-9901-8295 (S.S.)
                Author information
                https://orcid.org/0000-0002-1507-6118
                https://orcid.org/0000-0003-3582-8871
                https://orcid.org/0000-0002-4769-3145
                Article
                medsci-09-00044
                10.3390/medsci9020044
                8293435
                34207607
                f8687722-85df-42d2-a0c2-d2e44a0c0a3c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 03 May 2021
                : 07 June 2021
                Categories
                Review

                polyamines,biosynthesis,nutritional role,human health,disease prevention

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