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      Bioactive Lipids and Their Derivatives in Biomedical Applications

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          Abstract

          Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

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          From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

          A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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            Membrane lipids: where they are and how they behave.

            Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?
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              Doxil®--the first FDA-approved nano-drug: lessons learned.

              Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Biomol Ther (Seoul)
                Biomol Ther (Seoul)
                Biomolecules & Therapeutics
                The Korean Society of Applied Pharmacology
                1976-9148
                2005-4483
                1 September 2021
                1 September 2021
                1 September 2021
                : 29
                : 5
                : 465-482
                Affiliations
                [1]College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
                Author notes
                [* ] Corresponding Authors E-mail: lqviet.pharm@ 123456gmail.com (Le QV), ohyk@ 123456snu.ac.kr (Oh YK), Tel: +82-2-880-2493 (Le QV), +82-2-880-2493 (Oh YK), Fax: +82-2-882-2493 (Le QV), +82-2-882-2493 (Oh YK)
                Article
                bt-29-5-465
                10.4062/biomolther.2021.107
                8411027
                34462378
                c8ab3a76-cef3-4b98-80ed-2196bd16e22c
                Copyright © 2021, The Korean Society of Applied Pharmacology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 June 2021
                : 10 July 2021
                : 14 July 2021
                Categories
                Review

                lipids,fatty acids,glycerolipids,phospholipids,biomedical applications

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