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söndag 31 januari 2016

Hyaluronihaposta ( kiinnostuksen kohde silmän lasiainen) - ja valon vaikutukssta

https://www.researchgate.net/publication/260174725_Hyaluronic_acid_production_and_application_A_Review
Article

Hyaluronic acid production and application: A Review

10/2013;
ABSTRACT
Hyaluronic acid is a naturally derived, non - immunogenic, non - adhesive glycosaminoglycan that plays
a prominent role in various wound - healing processes, as it as it is naturally angiogenic when degraded to small fragments.
 Hyaluronic acid promotes early inflammation which is critical for initiating wound
healing, but then moderates later stages of the process, allowing matrix stabilization and reduction of long term inflammation. 
Hyaluronic acid is widely distributed in mammalian cells and tissue but is primarily found in synovial fluid, vitreous humor of the eye and loose connective tissue such as rooster comb, umbilical cord, dermis and arterial wall. It is also found in the capsular component of certain bacterial
such as Streptococcus sp. and Staphylococcus sp. These have been biotechnologically developed and are
now a main source of commercial Hyaluronic acid for pharmaceutical, medical and cosmetic application.

The present review was based on Hyaluronic acid production and application. This review assesses the
following topics: Structural features and properties of Hyaluronic acid, Rheological properties of Hyaluronic acid, Lubricity of Hyaluronic acid, Hydrophilicity of Hyaluronic acid, Hyaluronic acid production by bacterial fermentation, Biosynthesis of Hyaluronic acid in Streptococcus, Enzymes involved in Hyaluronic acid biosynthesis, Optimization and extraction of Hyaluronic acid, Analysis of Hyaluronic acid and Applications of Hyaluronic acid.

Hyaluronihapon fotodegradatio_ Tämä on tiedetty kauan.

 http://www.gpb.sav.sk/1990/1990_04_419.pdf

 

Hyaluronihappo ja etanoli vastavaikuttavat keskenään proteiinisynteesissä.

 Ilmeisesti terve hyaluronihapposynteesi normaalin A-vitmiini aineenvaihdunnan ja sitä tuek,vien luteiini-zeaxantiini etx pitoise ravinnon ohella- verensokerin ollessa  normaali- toimii silmän sisällä kuin tapetin  haavavoide, siis pitää sisältä käsin silmää  hyvässä kunnossa, joten pitää  Katsoa, mikä edistää (siis  mikä ei estä) normaalia hyaluronihapposynteesiä kehossa ja silmässä.  Jos silmä jo ulkoa kuivuu eikä  A-vitamiinitilanteen korjauskaan kosteuta silmää, niin   silmän endogeeni  hyaluronihappotuotanto riippuu jostain muustakin kuin A-vitamiiniaineenvaihdunnan tasapainosta..

Drug Des Devel Ther. 2015 Nov 24;9:6225-33. doi: 10.2147/DDDT.S91968. eCollection 2015.

Hyaluronic acid abrogates ethanol-dependent inhibition of collagen biosynthesis in cultured human fibroblasts.

INTRODUCTION:

The aim of the study was to evaluate the effect of ethanol on collagen biosynthesis in cultured human skin fibroblasts, and the role of hyaluronic acid (HA) in this process. Regarding the mechanism of ethanol action on human skin fibroblasts we investigated: expression of β1 integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), nuclear factor kappa B (NF-κB) transcription factor, cytotoxicity assay and apoptosis, metalloproteinase activity, as well as the influence of HA on these processes.

MATERIALS AND METHODS:

Collagen biosynthesis, activity of prolidase, DNA biosynthesis, and cytotoxicity were measured in confluent human skin fibroblast cultures that have been treated with 25, 50, and 100 mM ethanol and with ethanol and 500 µg/mL HA. Western blot analysis and zymography were performed to evaluate expression of collagen type I, β1 integrin receptor, IGF-IR, NF-κB protein, phospho-Akt protein, kinase MAPK, caspase 9 activity, and matrix metalloproteinases (MMP-9 and MMP-2).

RESULTS:

Ethanol in a dose-dependent manner lead to the impairment of collagen biosynthesis in fibroblast cultures through decreasing prolidase activity and expression of β1 integrin and IGF-IR. This was accompanied by an increased cytotoxicity, apoptosis and lowered expression of the signaling pathway proteins induced by β1 integrin and IGF-IR, that is, MAPK (ERK1/2) kinases. The lowered amount of synthesized collagen and prolidase activity disturbance may also be due to the activation of NF-κB transcription factor, which inhibits collagen gene expression. It suggests that the decrease in fibroblast collagen production may be caused by the disturbance in its biosynthesis but not degradation. The application of HA has a protective effect on disturbances caused by the examined substances. It seems that regulatory mechanism of ethanol-induced collagen aberration take place at the level of collagen biosynthesis, since no effect of ethanol and HA was found on process of collagen degradation by MMP-2 and MMP-9.

CONCLUSION:

This study provides evidence that ethanol impairs collagen metabolism in human skin fibroblasts, leading to a significant decrease in the amount of produced protein. This mechanism probably is due to downregulation of prolidase activity, expression of β1 integrin and IGF-IR receptors, and the signaling pathway proteins induced by these receptors.

KEYWORDS:

collagen; ethanol; fibroblast; hyaluronic acid
PMID:
26648698
[PubMed - in process]

PMCID:
PMC4664499

Free PMC Article

A-vitamiinin ja lasiasnesteen keskeinen vuorovaikutus?

http://www.ncbi.nlm.nih.gov/pubmed/?term=A+vitamin+and++vitreous+humour

Tsitol Genet. 2010 Nov-Dec;44(6):15-21.

Investigating the effects of vitreous humour (crude extract) on growth and differentiation of rat mesenchymal stem cells (rMSCs) and human NTERA2 cells.


Abstract

Two main characteristics of all types of stem cells are their potency for differentiation and self renewal capacity. There is a lot of interest to find the conditions and factors, which govern these behaviours of stem cells. It is very well documented that retinoic acid (RA) reduces growth rate by induction of cell differentiation in certain conditions and cell lines. On the other hand, hyaluronic acid (HA) is known for its growth induction on cultured cells. A natural source of HA, rabbit vitreous humour (VH), was previously shown to promote wound repair in model animals. In search for its possible mechanisms, VH extract was tested on the cultured mesenchymal stem cells and NTERA2 as human embryonal carcinoma cells in the presence of RA. Changes in some cellular and molecular markers (A2B5, Oct4, Sox2) showed that VH and possibly HA interfere with differentiating effects of RA. Therefore, this reagent may affect cell proliferation 

Normaali lasiainen on kirkas , geelimäinen.

Mediators Inflamm. 2012;2012:148039. doi: 10.1155/2012/148039. Epub 2012 Aug 29.

Proteomic analyses of the vitreous humour.

Abstract

The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. In the last decade, proteomics analyses have been performed to characterise the proteome of the human VH and explore networks of functionally related proteins, providing insight into the aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent proteomic studies on the VH from animal models of autoimmune uveitis have identified new signalling pathways associated to autoimmune triggers and intravitreal inflammation. This paper aims to guide biological scientists through the different proteomic techniques that have been used to analyse the VH and present future perspectives for the study of intravitreal inflammation using proteomic analyses.
Free PMC Article
Lasiaisneste, vitreous humor,  Corpus vitreum, glaskropp

Sokeri ja silmän särveiskalvo proteiiniaineenvaihdunta

http://www.ncbi.nlm.nih.gov/pubmed/16954709

Ophthalmologica. 2006;220(5):317-22.
Effect of high glucose concentration on corneal collagen biosynthesis.

Abstract
The effect of high glucose concentration (3 g/l) on bovine corneal total protein and collagen biosynthesis was studied, using 3H-proline incorporation in explant cultures with protein and collagen determinations. The high glucose concentration increased the incorporation of 3H-proline in total corneal proteins as well as in collagens. The specific radioactivity of stromal collagens was strongly increased in these conditions. Mannitol was used to control the osmotic effect of the high glucose concentration, both at 1 and 3 g/l concentrations. Mannitol did not increase the incorporation of 3H-proline in total proteins or collagens, but on the contrary decreased it. The high glucose concentration decreased the excretion of neosynthesized proteins and collagens in the culture medium, but did not affect the total protein or collagen content of the corneas. The strong increase in the specific radioactivity of corneal collagens in the presence of 3 g/l glucose suggests an increased turnover of collagens in diabetic corneas. The increased biosynthesis of collagens together with their decreased elimination in the extracellular compartment can create the conditions for the formation and accumulation of advanced glycation endproducts by the Maillard reaction. This can induce and stimulate the liquefaction of the vitreous body leading to sight-threatening disorders such as diabetic retinopathy, retinal detachment, glaucoma, cataract formation and age-related macular degeneration (ARMD).
Copyright 2006 S. Karger AG, Basel.
PMID:
16954709
[PubMed - indexed for MEDLINE] 
 
KOMMENTTI:  Näkökyvylle on tärkeä pitää verensokeri normaalina.  
Miksi?  Tietysti korkeat sokeripiikit voi saada verenkierrosta  esim liikuntaa lisäämällä tasoittumaan veren puolella ja lihaksista, mutta piikeistä jää kohonnutta  glukoosia ja  aineenvaihduntavaikutusta silmään. 
 Näistä  merkityksellisintä lienee se energia-aineen glukoosin  aiheuttama induktio, jonka glukoosi tekee: sarveiskalvon  kollageenibiosynteesiin. Se  lisääntyy mutta extrasellulaarista aitioista  tapahtuu samalla  huonompaa   eliminaatiota, joten  turn over- prosessi, joka kiihtyy diabeteksessa ,, on yksipuolinen, ontuva,  aiheuttaen  lopulta  glykaatiotuotteiden kertymistä  ja se taas  aiheuttaa lasiaisen vetistymistä ja näköhäiriöitä,  diabeettista retinopatiaa, retinan irtoamista,  viherkaihia, kaihin muodostusta ja iästä riippuvaa keltaisen täplän degeneraatiota (AMD.
AMD:n suhteen  verensokerin normaalina pitäminen on joka päivä  kautta vuorokauden tärkeä seikka.. Jo kauan on tiedetty että jos veren puolella on  sokeri 9 mmol/L se on silmän puolella 11. Siis  enemmän kuin veressä. 

onsdag 27 januari 2016

Beta-solujen kehittämisestä

Muistiin uutisista. tänään 27.1. 2016. LÄHDE: 
Trends Endocrinol Metab. 2016 Jan 22. pii: S1043-2760(16)00015-1. doi: 10.1016/j.tem.2016.01.002. [Epub ahead of print]

Lineage Reprogramming: A Promising Road for Pancreatic β Cell Regeneration.

TIIVISTELMÄ, Abstract

Solusiirtoterapia on lupaava metodi  haiman beta-solujen funktion palauttamiseksi  ja täten diabeettisen ainenvaihdunnan korjaamiseksi ei-diabeettiseksi.  Toisilleen kaukaiset solut kuten fibroblastit, keratinosyytit ja lihassolut sekä kehityksellisesti  toisiaan lähellä olevat solut  kuten maksasolut, mahasuolikanavan solut ja exokriiniset haimasolut on onnistuttu ohjelmoimaan uudestaan beta-soluiksi koeputkessa ja  kehossa. Kuitenkin kun jotkut uudelleen programmoidut beta-solut omaavat samankaltaisuuksia  oikeitten beta-solujen kanssa, niin toiset eivät  kehity kunnolla toimiviksi betasoluiksi.

Cell replacement therapy is a promising method to restore pancreatic β cell function and cure diabetes. Distantly related cells (fibroblasts, keratinocytes, and muscle cells) and developmentally related cells (hepatocytes, gastrointestinal, and pancreatic exocrine cells) have been successfully reprogrammed into β cells in vitro and in vivo. However, while some reprogrammed β cells bear similarities to bona fide β cells, others do not develop into fully functional β cells. 

Tässä artikkelissa tehdään katsausta nykyään käytetyistä stratgegioista  betasolujen uudelleen ohjelmoimisessa. näitä ovat 
  • betasolusaarekkeen kehitykseen liittyvien transkriptiotekijoiden  ektooppinen ilmentäminen 
  • isäntäsoluja ylläpitävien tekijöiden repressoiminen
  • epigeneettisen modifikaation säätely
  • mikromiljöön vaihtelut  
 Täysin toimivien  betasolujen kehittämisessä solusiirtoterapiaaan
annetaan etusija ykkinkertaisten ja tehokkaitten uudelleenohjelmoivien metodien kehittelemiselle.  

Here we review various strategies currently used for β cell reprogramming, including ectopic expression of specific transcription factors associated with islet development, repression of maintenance factors of host cells, regulation of epigenetic modifications, and microenvironmental changes. Development of simple and efficient reprogramming methods is a key priority for developing fully functional β cells suitable for cell replacement therapy.
Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS:

cell replacement therapy; cell reprogramming; diabetes mellitus; pancreatic β cells; transdifferentiation