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Stem Cell Engineering Using Bioactive Molecules for Bone-Regenerative Medicine
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Adenosine is an endogenous signaling nucleoside composed of an adenine molecule attached to a ribose sugar (MW: 267.2 Da). Adenosine, like many other mediators of angiogenesis, also contributes to bone-related signaling. Agonists of all four adenosine receptors (A1, A2a A2b, and A3) enhance proliferation of human primary osteoblast cells in vitro, while associated antagonists abrogate these effects.125 Agonism of the A2a receptor inhibits macrophage colony–stimulating factor (M-CSF)/RANKL-induced osteoclast differentiation as measured by cathepsin K, NFATc1, and OPN. Adenosine can be converted to cyclic adenosine monophosphate (cAMP) through a series of biochemical synthesis reactions that ends with the conversion of adenosine triphosphate to cAMP by adenylyl cyclase. While adenosine has been associated with both angiogenic and osteogenic effects, cAMP has been mostly explored as a means for enhancing bone formation. Codelivery of dibutyryl cAMP (dbcAMP), a cell-permeable cAMP analogue, with BMP-4 to mouse stromal cells results in enhanced expression of ALP in a dbcAMP dose-dependent manner. Another cAMP analogue, 6-Bnz-cAMP, was recently used to enhance osteogenic differentiation of mouse osteoblast-like cells, while enhancing RUNX2 expression, ALP activity, osteocalcin and OPN expression, and calcium mineralization.126
Marine Algae in Diabetes and Its Complications
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Fucoidans are commonly sulfated marine polysaccharides that have a wide spectrum of bioactivities. Ecklonia cava, Fucus vesiculosus, and Cladosiphon okamuranus were the most widely studied species for fucoidans (Wijesinghe and Jeon, 2012). Fucoidans are a group of fucans, i.e., sulfated polysaccharides extracted from brown seaweeds and are characterized by fucose-rich sulfated groups. Other examples of fucans are ascophyllans (xylofucoglycuronan and xylofucomanuronan) and sargassans (glycuronofucogalactan). The position of sulfate groups in marine sulfated polysaccharides has a significant impact on their beneficial biological effects. Fucoidans isolated from various seaweed species have diverse bioactive capabilities depending on their compositional structure, charge density, distribution, and bonding of the sulfate substitution (Ale et al., 2011). Fucoidans isolated from brown seaweeds had potential beneficial effects on diabetes. Fucoidans from Ascophyllum nodosum and Turbinaria ornate displayed α-amylase inhibition activities (Kim et al., 2015; Lakshmanasenthil et al., 2014). In addition, fucoidans have been verified to provide pancreatic protection. Fucoidan from Acaudina molpadioides protected pancreatic islet cells against apoptosis via inhibition of inflammation in type 2 diabetic mice (Wang et al., 2016). In streptozotocin-treated β-cells and mice, fucoidan ameliorated pancreatic β-cell death and impaired insulin synthesis via the Sirt-1-dependent pathway (Yu et al., 2017). It stimulated insulin secretion and provided pancreatic protection via the cyclic adenosine monophosphate (cAMP) signaling pathway (Jiang et al., 2015). Additionally, insulin sensitivity was enhanced by increasing the expression of diabetes-related genes in 3T3-L1 adipocytes (Kim et al., 2007). Low-molecular-weight fucoidan also improved the action of insulin via adenosine-activated protein kinase (AMPK) stimulation (Jeong et al., 2013).
Hyperlipidemia and male infertility
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Zainab Bubakr Hamad Zubi, Hamad Abdulsalam Hamad Alfarisi
Mammalian sperm cell membrane has a lipid bilayer consists of phospholipids and cholesterol. During passage of sperm from the testes to the female genital tract, sperm membrane undergoes several modifications. Membrane lipids particularly cholesterol are responsible for the physiological alterations in the membrane fluidity and cell responsiveness to the environment [40]. Cholesterol of sperm plasma membrane regulates membrane permeability, lateral mobility of integral proteins and functional receptors within the membrane. Loss of cholesterol from the membrane is responsible for destabilization of the membrane during capacitation [44]. Capacitation is the functional maturation of the sperm which takes place within the female genital tract. It is essential for the sperm ability to fertilize an egg. It involves changes in the sperm head and flagellum including the ability of sperm to undergo acrosomal reaction and acquisition of motility hyperactivation [45]. The initial step toward the capacitation is the removal of sperm external coating-proteins that protect the sperm on its path to oocyte and prevent early occurrence of acrosomal reaction [44]. Cholesterol efflux from the sperm membrane causes a decrease in the cholesterol/phospholipid ratio which leads to changes in the membrane fluidity and causes membrane protein redistribution that required for capacitation [46]. It is also important for signaling mechanisms that regulate capacitation process. Signaling mechanisms can be initiated through the cholesterol loss via two mechanisms: 1) an interaction between membrane proteins which occurs as a subsequent to the increase in the membrane fluidity and 2) freeing of certain signaling molecules from their interaction with cavolin giving them the ability to form specific signaling complexes [47]. Cholesterol efflux is an early event in the capacitation followed by a reduction in the cholesterol/phospholipid ratio which changes the membrane dynamics and increases its permeability to bicarbonate and calcium ions. This is followed by the activation of adenylyl cyclase and increase production of cyclic adenosine monophosphate (cAMP). A signal cascade initiated through activation of protein kinase A (PKA) which phosphorylates sperm protein tyrosine residue. Finally, the sperm acquire hyperactive motility and the ability to bind to zona pellucida to undergo the acrosomal reaction [48]. Hypercholesterolemia alters the concentration and distribution of cholesterol of sperm plasma membrane and subsequently reduces the acrosomal reaction and capacitation [40,41]. High cholesterol level inhibits capacitation either through its direct effect on certain surface proteins that have roles in signaling transduction, or indirectly via restricting the conformational changes of sperm surface proteins and consequently decreases their activity [47].