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The Potential of Microbial Mediated Fermentation Products of Herbal Material in Anti-Aging Cosmetics
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Type III collagen comprises approximately 20% of the total collagen in the skin, concentrated in the mesh-like papillary dermis, while the remaining 80% is comprised of type-I collagen, concentrated in the reticular dermis. Structurally, type III collagen is a homotrimer of α1(III) chains and type I, a heterotrimer of two α1(I) chains and one α2(I) chain arranged in an anti-parallel conformation to produce more dense fibers (Cole et al., 2018). These fibers are enzymatically cross linked following the secretion of procollagen and its maturation to confer resistance to proteolytic cleavage. The proteolytic removal of C and N terminal pro-peptides facilitates the maturation of procollagen into mature collagen fibers. For instance, in type-I collagen various intracellular lysine residues containing α1(I) and α2(I) chains are converted to hydroxylysine through the action of lysyl hydroxylase, while extracellular lysine and hydroxylysine residues are converted to aldehydes through the action of lysyl oxidase. This process enables spontaneous, non-reducible inter- and intra-peptide crosslinking. The action of lysyl oxidase is crucial in facilitating matrix deposition of elastin fibers and prevention of excessive elasticity (Cole et al., 2018).
Stroke and Transient Ischemic Attacks of the Brain and Eye
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Ehlers–Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). It is a rare connective tissue disorder inherited as an autosomal dominant trait, characterized mainly by arterial dissection, intracranial aneurysm, and the spontaneous rupture of large- and medium-sized arteries, and a gravid uterus or intestines. Carotid intima media thickness is one-third lower and circumferential wall stress 40% higher than in matched controls. The higher circumferential wall stress is probably a major risk factor for the dissection and rupture of fragile arterial tissue.
Introduction and Review of Biological Background
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Collagen structure begins with synthesis of procollagen chains. Procollagen chains are unique to each type of collagen, but are approximately 1055 amino acids in length. Three procollagen chains form a triple helix, which is the basic unit of collagen. Because of the amino acid sequence of collagen, which is mostly a trimer of glycine, a variable amino acid (usually lysine) and proline, each polypeptide chain forms a left-handed helix which can be intertwined with two other chains to form a right-handed triple superhelix (tropocollagen). Tropocollagen is 300 nm in length and around 285,000 Da. Extensive posttranslational modifications ensue, which are dependent on adequate nutrient status, as will be detailed in subsequent chapters. Collagen is glycosylated, and modified proline and lysine residues provide stabilization of the triple helix structure. Cross-linking with other collagen molecules forms collagen microfibrils. Collagen fibrils are formed from further cross-linking of large numbers of microfibrils. Finally, collagen fibers are formed by aggregation of collagen fibrils, which by now are macroscopic in size. Thus, simple chains of amino acids can be amplified into large physical structures.
Severe foveal hypoplasia and macular degeneration in Stickler syndrome caused by missense mutation in COL2A1 gene
Published in Ophthalmic Genetics, 2022
Mamika Asano, Katsuhiko Yokoyama, Kazuma Oku, Itsuka Matsushita, Kenichi Kimoto, Toshiaki Kubota, Hiroyuki Kondo
Mutations in the procollagen genes, COL2A1, COL11A1, COL11A2, COL9A1, COL9A2 and COL9A3 cause Stickler syndrome, and the COL2A1, COL11A1 and COL11A2 genes are responsible for autosomal dominant Stickler syndrome (4). Mutations in the COL2A1 gene are the most common cause of Stickler syndrome, and more than 80% of the mutations are truncation mutations, i.e., nonsense, insertion, deletion, and splicing mutations that lead to haploinsufficiency (Human Gene Mutation Database, HGMD; https://my.qiagendigitalinsights.com/bbp/view/hgmd/pro/start.php). Patients with truncation mutations in the COL2A1 gene show characteristic membranous structures in the vitreous (5,6). On the other hand, some of the missense mutations in the COL2A1 gene have been reported to cause specific alterations of the vitreous due to dominant-negative effects (5). As best we know, there are no reports on whether eyes with missense mutations have specific retinal findings.
Emerging drugs for the treatment of idiopathic pulmonary fibrosis: 2020 phase II clinical trials
Published in Expert Opinion on Emerging Drugs, 2021
Giacomo Sgalla, Marialessia Lerede, Luca Richeldi
ND-L02-s020 (Development code: BMS-986,263) is a lipid nanoparticle encapsulating a short-interfering RNA (siRNA), which prevents translation of heat shock protein 47 (HSP47). This protein has a crucial role in fibrosis development as it acts a collagen molecular chaperone, modulating procollagen cleavage. In vitro and in vivo studies using murine models of BLM-induced lung fibrosis showed a HSP47 overexpression involving lung myofibroblasts and a positive effect of HSP47 siRNA carried through liposomes on BAL cellularity, hydroxyproline levels (measure of collagen formation), reduction in lung weight and fibrosis scores [49,50]. The JUNIPER study (ClinicalTrials.gov Identifier: NCT03538301) is a phase II, randomized clinical trial currently recruiting IPF patients with mild-to-moderate functional impairment aimed to assess safety, tolerability, biological activity and pharmacokinetics of ND-L02-s020. It is composed of two active arms of treatment (intravenous administration of the study drug at two different dosages every 2 weeks) compared to placebo. Eligible subjects are being stratified based on their baseline antifibrotic treatment. Study completion is expected in September 2021.
Glimpses into the molecular pathogenesis of Peyronie’s disease
Published in The Aging Male, 2020
Evert-Jan P. M. ten Dam, Mels F. van Driel, Igle Jan de Jong, Paul M. N. Werker, Ruud A. Bank
Collagen synthesis is a complex process, and many enzymes are involved. Chaperones assist in folding of the procollagen molecules and propeptidases cleave off the propeptides to convert procollagen into collagen. Conversion of proline into 3-hydroxyproline or 4-hydroxyproline is catalyzed by prolyl hydroxylases, conversion of lysine (Lys) into 4-hydroxylysine (Hyl) by lysyl hydroxylases, and cross-linking is initiated by lysyl oxidases [47]. We used a low-density array (Table 2 andFigure 3) to quantify the expression of these enzymes, to clarify whether there were possible aberrations in (pro)collagen processing. An important post-translational modification of collagen is the conversion of triple helical lysine (Lys) into hydroxylysine (Hyl), and the addition of sugars to Hyl, resulting in the glycosylated residues galactosylhydroxylysine (Gal–Hyl) and glucosylgalactosylhydroxylysine (Glc–Gal–Hyl) [26]. It has now been established that the conversion of triple helical Lys into Hyl is catalyzed by lysyl hydroxylase 1 (encoded by PLOD1) and lysyl hydroxylase 3 (encoded by PLOD3), and that the formation of Glc–Gal–Hyl (but not Gal-Hyl) is catalyzed by lysyl hydroxylase 3 [26]. We have observed no differences in mRNA levels of PLOD1 between plaque and control tissue, but there was a major increase in mRNA levels of PLOD3 in plaque tissue. Therefore, an overhydroxylation of Lys in PD tissue is expected, as well as increased levels of Glc–Gal–Hyl. A Lys overhydroxylation and a Hyl overglycosylation have been reported for affected DD tissues [37,40,41].