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Neuromuscular Physiology
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
Outer membrane. The outer membrane encompasses the mitochondria and embedded proteins primarily function as transport molecules (125, 127). The transport proteins allow molecules of 10 kilodaltons (kD) or less to pass freely into the intermembrane space but carefully regulate larger molecules. The outer membrane also contains various enzymes that are involved in diverse activities such as fatty acid synthesis (chain elongation), oxidation of epinephrine, and the degradation of tryptophan (37). Outer membrane disruption membrane permits proteins contained in the intermembrane space to leak into the sarcoplasm, leading to cell death (37).
Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
All the cellular processes that proceed in a controlled environment within the cytoplasm are in isolation from the disruptive influences of the external environment. This is attributable to the protective qualities of the cells’ outer membrane. The plasma membrane is crucial to the cell because it maintains the internal environment within the cytoplasm and separates the operating systems of the cell from the extracellular environment, which is essential for the sensitive biochemical processes that are the habitual conduct of the cell. The plasma membrane enables selective passage of substances into and out of the cell to sustain the delicate chemical system within. Structures inside the cell, called organelles, are also comprised of a plasma membrane. Among these membrane-bound organelles are the Golgi apparatus, endoplasmic reticulum, mitochondria, as well as the cell nucleus; all of which play a crucial role in sustaining the dynamic operating systems inside the cell. The contents within these organelles, related to their specific function, are characteristically different to the rest of the cytoplasm; maintained by the plasma membrane that keeps these systems separated.
Models and Paradigms for Assessment of Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
There are several methods by which the anti-inflammatory effects of herbs are evaluated. One of the most common techniques is to gauge the ability of substances to attenuate lipopolysaccharide-induced inflammation. The lipopolysaccharide can be administered to intact animals, or placed into cultured peripheral immune cells, microglia, or neuron-like pheochromocytoma cell lines. Lipopolysaccharide is a major molecular component of the outer membrane of gram-negative bacteria, and is the primary activator of the evolutionarily ancient innate immunity system. Lipopolysaccharide activates the toll-like receptor type4 (TLR4) that then initiates the intracellular inflammatory cascade. The translocation of NF-kβ to the nucleus enhances synthesis of the inflammatory cytokines TNF-α and IL-1β, as well as prostaglandins, leukotrienes, and Reduced Oxygen Species. In T-lymphocytes, NK cells and many other cell types, the release of IL-12 or IL-18 induces release of IFN-γ. The IFN-γ hypersensitizes mononuclear phagocytes to lipopolysaccharide, thus amplifying the inflammatory process.7 In some cases, the mechanism by which herbs interfere with the lipopolysaccharide-induced inflammatory cascade are explored, such as antagonism of TLR4, or prevention of translocation of NF-kβ. In most cases, the anti-inflammatory effects are established by assessing the degree to which the levels of the inflammatory cytokines are contained.
Synthesis and antimicrobial activity of aminoalkyl resveratrol derivatives inspired by cationic peptides
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Rubén Cebrián, Ricardo Lucas, María Victoria Fernández-Cantos, Koen Slot, Pablo Peñalver, Marta Martínez-García, Antonio Párraga-Leo, María Violante de Paz, Federico García, Oscar P. Kuipers, Juan Carlos Morales
Cationic antimicrobials are well known for their ability to bind to negatively charged bacterial membranes. Thus, we decided to analyse in depth the effect of the best candidate (5) in both Gram-negative and Gram-positive bacterial membranes. The outer membrane in Gram-negative bacteria acts as a permeability barrier that impairs antibiotics to reach their target inside the cell.4 Several cationic antimicrobial drugs are characterised to be amphipathic, with a positively charged hydrophilic domain and a hydrophobic domain. As a consequence, these drugs can bind through electrostatic interactions with the negatively charged bacterial surface. Subsequently, the hydrophobic domain can be inserted into the membrane, forming stable and disruptive pores that produce the leaking of the intracellular content and, therefore, cell death by lysis38,39. Alternatively, they can disrupt the membranes inducing an alteration in their permeability40. To understand the effect of amino RES 5 against Gram-negative bacteria, we explored its activity in the outer membrane using E. coli LMG 8224 as a model. We measured the outer membrane permeability under different concentrations of amino RES 5 using the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN) and polymyxin B as a positive control41. A dose-related response was observed for amino RES 5, indicating a perturbation/disruption in the membrane while no effect was observed for RES (Figure 4(A)).
A comprehensive systematic review of the effectiveness of Akkermansia muciniphila, a member of the gut microbiome, for the management of obesity and associated metabolic disorders
Published in Archives of Physiology and Biochemistry, 2023
Neda Roshanravan, Sepideh Bastani, Helda Tutunchi, Behnam Kafil, Omid Nikpayam, Naimeh Mesri Alamdari, Amir Hadi, Simin Sotoudeh, Samad Ghaffari, Alireza Ostadrahimi
Another proposed mechanism behind the favourable effects of Akkermansia may be through mediating metabolic endotoxemia. LPS, lipoglycans, and endotoxins are now well-known components that contribute to the inflammation. They constitute the outer membrane of most exogenous Gram-negative bacteria (Li et al.2016). After the exogenous bacteria or pathogen agents die, LPS is released, crosses the GI barrier, and flows into the bloodstream, known as endotoxemia (d’Hennezel et al.2017). Circulating LPS binds LPS-Binding Protein (LBP). These binding proteins consist of 456 amino acid residues, are synthesised by hepatocytes and intestinal epithelial cells, and are present in the serum (Vreugdenhil et al.1999). These proteins interact with the macrophage receptor, trigger the secretion of inflammatory cytokines (e.g. TNF-α, IL-1), and aggravate the oxidative stress observed in obesity status. Recent data have shown that obesity increases gut permeability and is associated with metabolic endotoxemia (subclinical increases in circulating LPS levels) and meta- inflammation (Cani et al.2007, 2009). However, evidence supports a role for A. muciniphila administration to reinforce gut integrity, modulate gut microbiota profile, and eventually reduce plasma LPS (Everard et al.2013, Li et al.2016, Depommier et al.2019).
Exosomes: from biology to immunotherapy in infectious diseases
Published in Infectious Diseases, 2023
Velia Verónica Rangel-Ramírez, Hilda Minerva González-Sánchez, César Lucio-García
Outer-membrane vesicles can also aid in bacterial survival under stress conditions and nutrient acquisition. They can provide envelope stress relief through the disposal of misfolded proteins, peptidoglycan fragments, or lipopolysaccharide [318–320]. Moreover, vesiculation increases during oxidative stress [318–321]. Furthermore, these vesicles are also proposed to have a role in bacterial community formation and provide nutrients during colonization. For example, the outer-membrane vesicles from Borrelia burgdorferi contain enolase which is essential to bacterial glycolysis and may contribute to colonization [17,218]. Several bacterial species release outer-membrane vesicles containing iron acquisition proteins and receptors for haem groups, such as FetA and FetB47 (iron transporter components) present in the vesicles of N. meningitidis [272]; IhtB, HmuY and gingipains released by Porphyromonas gingivalis [278]; as well as CopB, the haem chaperone CcmE and the surface receptor transferrin-binding protein B from Moraxella catarrhalis [322–324]. In addition, the zinc acquisition proteins ZnuA and ZnuD47 have also been detected in the outer-membrane vesicles of N. meningitidis showing that metal acquisition through these vesicles is not only restricted to iron [272].