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Medicinal Mushrooms
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Temitope A. Oyedepo, Adetoun E. Morakinyo
More than 380 species of mushrooms have been documented to possess medicinal properties and this as a result of their high content of prebiotics (Geurts et al., 2014). Mushrooms prebiotics are known to improve the antioxidant status as a result of alterations in the composition of gut microbiota. Mushrooms play a vital role in immune response during the treatment of respiratory diseases, atherosclerosis, cancer, and other metabolic diseases (Koyyalamudi et al., 2009a, 2009b; Varshney et al., 2013). Prebiotics from mushrooms also have hypocholesterolemia properties that help reduce lipogenic gene expression (Hmgcr, Fasn, Srebp1c, and Acaca) and genes responsible for reverse cholesterol transport (Abcg5 and Abcg8) significantly, as well as an increase in Low Density Lipoprotein Receptor gene expression in the liver (Meneses et al., 2016). Ganoderma lucidium is a mushroom that has been documented to reduce obesity in mice by altering the composition of gut microbiota (Xu and Zhang, 2015).
Lipoproteins for Biomedical Applications: Medical Imaging and Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Pratap C. Naha, Stephen E. Henrich, David P. Cormode, C. Shad Thaxton
In addition to their widely recognized role in reverse cholesterol transport, HDL plays major roles as systemic delivery agents. In the native setting, HDL species (which are 7–13 nm in diameter) harbor and deliver a diverse set of cargoes including circulating miRNAs [128], endogenous lipids [55], proteins [129, 130], and small hydrophobic metabolites and signaling molecules. This versatility has made HDL extremely attractive as a drug delivery platform, particularly for cancer and inflammation. One property of HDLs which makes them ideal candidates for delivery of anti-cancer agents is their ability to target tumor cells. While a majority of chemotherapeutics are indiscriminately uptaken by healthy and malignant tissues, HDLs are capable of targeting tumor tissue both actively and passively. First, nanoparticles such as HDL are often preferentially uptaken by the leaky, fenestrated vasculature of tumor tissue. Due to impaired lymphatic drainage and the resultant elevated hydrostatic pressures, particles of this size are also more likely to be retained in tumor tissues once they have extravasated. These phenomena together are known as the enhanced permeability and retention (EPR) effect [131], although the strength of this effect is variable between tumor types as well as between tumors of the same type [131, 132]. Since both HDL and LDL are within the right size range (i.e., ~5–200 nm) and have long circulation half-lives, they can deliver substantial drug payloads via the EPR effect. Beyond the EPR effect, HDL also may actively target tumors via specific HDL receptors, as mentioned above [133–137]. Cargo delivered by HDLs to tumor cells also avoids the endolysosomal pathway [65, 138], which offers a distinct advantage over many competing delivery systems, especially for nucleic acid cargo [74], as most drug-loaded nanoparticles which enter the endolysosomal pathway undergo degradation in lysosomes before interacting with the intended target.
Site-Specific Antibody Conjugation for ADC and Beyond
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
The site-specific antibody conjugation has been applied for preparing immunoconjugates against other diseases such as autoimmune diseases and atherosclerosis. A highly potent phosphodiesterase 4 (PDE4) inhibitor, GSK256066, was site-specifically coupled to a human anti-CD11a through an unnatural amino acid, pAcF, introduced at HC-A122 with DAR at ~2 [69]. PDE4 is a cAMP phosphodiesterase widely expressed in a variety of cells and some small molecule PDE4 inhibitors showed wide-ranging preclinical efficacy in autoimmune diseases with a few being approved by regulatory agencies for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects have impeded their broader therapeutic application. The site-specific conjugation of pan-immune cell targeting human anti-CD11a with GSK256066 resulted in an immunoconjugate that was rapidly internalized into immune cells and suppressed lipopolysaccharide (LPS)-induced TNFa secretion in primary human monocytes. In another study, a liver X receptor (LXR) agonist was site-specifically conjugated to pAcF at HC-A122 of anti-CD11a [70]. Liver X receptor agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been limited by on-target adverse effects in the liver mediated by excessive lipogenesis after the interaction of the ligand with LXR-a. To prevent the adverse effect, the aminoooxy-modified LXR agonist was coupled to pAcF in anti-CD11a for selective delivery of the agonist to monocytes/macrophages while sparing hepatocytes. The anti-CD11a IgG-LXR agonist immunoconjugate induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro with EC50 at nM range, but had no significant effect in hepatocytes, indicating that the payload delivery was CD11a-mediated. This approach represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.
Effect of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a high-sugar meal breakfast the following day in postmenopausal women: a randomized cross-over study
Published in Journal of Sports Sciences, 2022
Meena Shah, Adam Gloeckner, Sarah Bailey, Beverley Adams-Huet, Andreas Kreutzer, Dennis Cheek, Jada L Willis, Joel Mitchell
There was an increase in T-HDLP but no change in LB-HDL 2b during the postprandial period compared to the respective baseline value in both the EX and NE conditions. This indicates that the rise in T-HDLP was due to increase in small dense HDLP which do not have the same cardio-protective properties as the LB-HDL 2b. This is further confirmed by the fact that T-HDLP – LB-HDL 2b (mostly made up of small dense HDLP) increased whereas the ratio of LB-HDL 2b:T-HDLP decreased during the postprandial period. Williams et al. (Williams et al., 1995) reported that replacing some of the dietary fat with carbohydrates reduced HDL mean diameter. Compared to large HDL, small HDL particles have reduced capacity to engage in reverse cholesterol transport where HDL picks up cholesterol from peripheral tissues and takes it to the liver for removal through biliary secretion (Barter & Kastelein, 2006; Curtiss et al., 2006). Apo A also dissociates from small HDL particle more easily and may be lost through renal clearance (Barter & Kastelein, 2006; Curtiss et al., 2006). Voros et al. (Voros et al., 2013) found that smaller, lipid‐poor HDL particles, were associated with higher plaque volume in patients with suggestive myocardial ischaemia or a high probability of coronary artery disease.