Mango processing generates significant amounts of residues (35-65%) that may represent environmental problems owed to improper disposal. The use of mango byproducts as substrates to produce hyaluronic acid (HA) is an attractive alternative to reduce the cost of substrate. In this study, we evaluated the potential of hydrolyzates from mango peels and seeds to produce HA by Streptococcus equi. subsp. zooepidemicus. The physicochemical characterization of mango residues showed that the seeds contain a higher amount of holocellulose (cellulose and hemicellulose), which amounts 54.2% (w/w) whereas it only represents 15.5% (w/w) in the peels. Mango peels, however, are composed mainly of hot water-extractives (62% w/w, that include sucrose, fructose, glucose and organic acids). A higher concentration of monosaccharides (39.8 g/L) was obtained from the enzymatic hydrolysis (with Macerex) of peels as compared to seeds (24.8 g/L with Celuzyme). From mango peels, hydrolyzates were obtained 0.6 g/L HA, while 0.9 g/L HA were obtained with hydrolyzates from mango seeds. These results demonstrate that mango byproducts have the potential to be used for production of HA.
- Klíčová slova
- Streptococcus zooepidemicus, Enzymatic hydrolyzates, Hyaluronic acid, Mango by-products,
- MeSH
- celulosa metabolismus MeSH
- fermentace MeSH
- hydrolýza MeSH
- kyselina hyaluronová * biosyntéza metabolismus MeSH
- Mangifera * mikrobiologie chemie MeSH
- monosacharidy metabolismus MeSH
- semena rostlinná chemie mikrobiologie metabolismus MeSH
- Streptococcus equi * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- celulosa MeSH
- kyselina hyaluronová * MeSH
- monosacharidy MeSH
In preovulatory follicles, after the endogenous gonadotropin surge, the oocyte-cumulus complexes (OCCs) produce hyaluronan (HA) in a process called "cumulus expansion". During this process, the heavy chains (HCs) of the serum-derived inter-alpha-trypsin inhibitor (IαI) family bind covalently to synthesized HA and form a unique structure of the expanded cumulus HA-rich extracellular matrix. Understanding the biochemical mechanism of the covalent linkage between HA and the HCs of the IαI family is one of the most significant discoveries in reproductive biology, since it explains basis of the cumulus expansion process running in parallel with the oocyte maturation, both essential for ovulation. Two recent studies have supported the above-mentioned findings: in the first, seven components of the extracellular matrix were detected by proteomic, evolutionary, and experimental analyses, and in the second, the essential role of serum in the process of cumulus expansion in vitro was confirmed. We have previously demonstrated the formation of unique structure of the covalent linkage of HA to HCs of IαI in the expanded gonadotropin-stimulated OCC, as well as interactions with several proteins produced by the cumulus cells: tumor necrosis factor-alpha-induced protein 6, pentraxin 3, and versican. Importantly, deletion of these genes in the mice produces female infertility due to defects in the oocyte-cumulus structure.
- Klíčová slova
- cumulus expansion, extracellular matrix, hyaluronan, inter-alpha-trypsin inhibitor,
- MeSH
- alfa-globuliny metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- extracelulární matrix * metabolismus MeSH
- kumulární buňky * metabolismus MeSH
- kyselina hyaluronová * metabolismus MeSH
- lidé MeSH
- myši MeSH
- oocyty * metabolismus MeSH
- ovariální folikul * metabolismus MeSH
- sérový amyloidový protein metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- alfa-globuliny MeSH
- C-reaktivní protein MeSH
- inter-alpha-inhibitor MeSH Prohlížeč
- kyselina hyaluronová * MeSH
- PTX3 protein MeSH Prohlížeč
- sérový amyloidový protein MeSH
Peritoneal adhesions are postsurgical fibrotic complications connected to peritoneal inflammation. The exact mechanism of development is unknown; however, an important role is attributed to activated mesothelial cells (MCs) overproducing macromolecules of extracellular matrix (ECM), including hyaluronic acid (HA). It was suggested that endogenously-produced HA contributes to the regulation of different fibrosis-related pathologies. However, little is known about the role of altered HA production in peritoneal fibrosis. We focused on the consequences of the increased turnover of HA in the murine model of peritoneal adhesions. Changes of HA metabolism were observed in early phases of peritoneal adhesion development in vivo. To study the mechanism, human MCs MeT-5A and murine MCs isolated from the peritoneum of healthy mice were pro-fibrotically activated by transforming growth factor β (TGFβ), and the production of HA was attenuated by two modulators of carbohydrate metabolism, 4-methylumbelliferone (4-MU) and 2-deoxyglucose (2-DG). The attenuation of HA production was mediated by upregulation of HAS2 and downregulation of HYAL2 and connected to the lower expression of pro-fibrotic markers, including fibronectin and α-smooth muscle actin (αSMA). Moreover, the inclination of MCs to form fibrotic clusters was also downregulated, particularly in 2-DG-treated cells. The effects of 2-DG, but not 4-MU, were connected to changes in cellular metabolism. Importantly, the inhibition of AKT phosphorylation was observed after the use of both HA production inhibitors. In summary, we identified endogenous HA as an important regulator of peritoneal fibrosis, not just a passive player during this pathological process.
- Klíčová slova
- fibrosis, hyaluronic acid, mesothelial cells, metabolism, peritoneal adhesions,
- MeSH
- deoxyglukosa MeSH
- extracelulární matrix genetika metabolismus MeSH
- kyselina hyaluronová * metabolismus MeSH
- lidé MeSH
- myši MeSH
- peritoneální fibróza * genetika metabolismus MeSH
- transformující růstový faktor beta metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- deoxyglukosa MeSH
- kyselina hyaluronová * MeSH
- transformující růstový faktor beta MeSH
Hyaluronan (HA) is a naturally occurring polysaccharide widely used in medicine and cosmetics. To further broaden its potential, various HA derivatives have been developed with the aim of reducing solubility, slowing degradation, or providing other beneficial properties. However, for most medical applications, these derivatives must be processed into suitable forms. Here we present water-insoluble fibres prepared from lauroyl-modified HA using a wet spinning process. Important properties of the fibres, such as swelling or the degradation rate, can be fine-tuned by adjusting the degree of HA modification. Due to their mechanical properties, the lauroyl HA fibres can be easily processed into threads and subsequently into fabrics of various sizes, shapes, and degrees of porosity. In addition, in vitro cytotoxicity testing of the fibres showed that they were non-cytotoxic. Overall, our results suggest that lauroyl HA fibres are a promising material that could be used to develop a variety of medical devices.
- Klíčová slova
- Fibre, Lauroyl hyaluronan, Wet spinning,
- MeSH
- kyselina hyaluronová * metabolismus MeSH
- poréznost MeSH
- voda * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina hyaluronová * MeSH
- voda * MeSH
4-methylumbelliferone (4MU) has been suggested as a potential therapeutic agent for a wide range of neurological diseases. The current study aimed to evaluate the physiological changes and potential side effects after 10 weeks of 4MU treatment at a dose of 1.2 g/kg/day in healthy rats, and after 2 months of a wash-out period. Our findings revealed downregulation of hyaluronan (HA) and chondroitin sulphate proteoglycans throughout the body, significantly increased bile acids in blood samples in weeks 4 and 7 of the 4MU treatment, as well as increased blood sugars and proteins a few weeks after 4MU administration, and significantly increased interleukins IL10, IL12p70 and IFN gamma after 10 weeks of 4MU treatment. These effects, however, were reversed and no significant difference was observed between control treated and 4MU-treated animals after a 9-week wash-out period.
- Klíčová slova
- 4-methylumbelliferone, chondroitin sulphates, hyaluronan, neuroplasticity,
- MeSH
- hymekromon * škodlivé účinky terapeutické užití MeSH
- interleukin-12 MeSH
- krysa rodu Rattus MeSH
- kyselina hyaluronová * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hymekromon * MeSH
- interleukin-12 MeSH
- kyselina hyaluronová * MeSH
Hyaluronan (HA) is a core constituent of perineuronal nets (PNNs) that surround subpopulations of neurones. The PNNs control synaptic stabilization in both the developing and adult central nervous system, and disruption of PNNs has shown to reactivate neuroplasticity. We investigated the possibility of memory prolongation by attenuating PNN formation using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis. Adult C57BL/6 mice were fed with chow containing 5% (w/w) 4-MU for 6 months, at a dose ~6.7 mg/g/day. The oral administration of 4-MU reduced the glycosaminoglycan level in the brain to 72% and the spinal cord to 50% when compared to the controls. Spontaneous object recognition test (SOR) performed at 2, 3, 6 and 7 months showed a significant increase in SOR score in the 6-months treatment group 24 h after object presentation. The effect however did not persist in the washout group (1-month post treatment). Immunohistochemistry confirmed a reduction of PNNs, with shorter and less arborization of aggrecan staining around dendrites in hippocampus after 6 months of 4-MU treatment. Histopathological examination revealed mild atrophy in articular cartilage but it did not affect the motor performance as demonstrated in rotarod test. In conclusion, systemic oral administration of 4-MU for 6 months reduced PNN formation around neurons and enhanced memory retention in mice. However, the memory enhancement was not sustained despite the reduction of PNNs, possibly due to the lack of memory enhancement training during the washout period. Our results suggest that 4-MU treatment might offer a strategy for PNN modulation in memory enhancement.
- Klíčová slova
- Extracellular matrix, Hyaluronan, Memory, Neuroplasticity, Perineuronal net,
- MeSH
- agrekany účinky léků MeSH
- aplikace orální MeSH
- centrální nervový systém účinky léků MeSH
- chování zvířat účinky léků MeSH
- extracelulární matrix účinky léků MeSH
- hymekromon aplikace a dávkování farmakologie MeSH
- kyselina hyaluronová metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuroplasticita účinky léků MeSH
- oligodendroglie účinky léků MeSH
- rozpoznávání (psychologie) účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- agrekany MeSH
- hymekromon MeSH
- kyselina hyaluronová MeSH
Photoaged skin exhibits signs of inflammation, DNA damage and changes in morphology that are visible at the macroscopic and microscopic levels. Photoaging also affects the extracellular matrix (ECM) including hyaluronan (HA), the main polysaccharide component thereof. HA is a structurally simple but biologically complex molecule that serves as a water-retaining component and provides both a scaffold for a number of the proteins of the ECM and the ligand for cellular receptors. The study provides an overview of the literature concerning the changes in HA amount, size and metabolism, and the potential role of HA in photoaging. We also suggest novel HA contributions to photoaging based on our knowledge of the role of HA in other pathological processes, including the senescence and inflammation-triggered ECM reorganization. Moreover, we discuss potential direct or indirect intervention to mitigate photoaging that targets the hyaluronan metabolism, as well as supplementation.
- Klíčová slova
- ECM, UV radiation, hyaluronan, inflammation, senescence,
- MeSH
- antigeny CD44 metabolismus MeSH
- kůže metabolismus MeSH
- kyselina hyaluronová metabolismus MeSH
- lidé MeSH
- proteiny metabolismus MeSH
- stárnutí kůže * MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antigeny CD44 MeSH
- kyselina hyaluronová MeSH
- proteiny MeSH
Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs-mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.
- Klíčová slova
- fibrosis, hyaluronan, inflammation, mesothelial cell, mesothelial-to-mesenchymal transition, metabolism, peritoneal adhesion,
- MeSH
- epitel MeSH
- fibroblasty fyziologie MeSH
- kyselina hyaluronová * metabolismus MeSH
- myofibroblasty metabolismus MeSH
- peritoneum * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kyselina hyaluronová * MeSH
There is inconsistent information regarding the size effects of exogenously given hyaluronan on its in vivo fate. The data are often biased by the poor quality of hyaluronan and non-ideal labelling strategies used for resolving exogenous/endogenous hyaluronan, which only monitor the label and not hyaluronan itself. To overcome these drawbacks and establish the pharmacokinetics of intravenous hyaluronan in relation to its Mw, 13C-labelled HA of five Mws from 13.6-1562 kDa was prepared and administered to mice at doses 25-50 mg kg-1. The elimination efficiency increased with decreasing Mw. Low Mw hyaluronan was rapidly eliminated as small hyaluronan fragments in urine, while high Mw hyaluronan exhibited saturable kinetics and complete metabolization within 48 h. All tested Mws exhibited a similar uptake by liver cells and metabolization into activated sugars. 13C-labelling combined with LC-MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.
- Klíčová slova
- Hyaluronan, Metabolism, Molecular weight, Pharmacokinetics, Stable isotope,
- MeSH
- cesty eliminace léčiva MeSH
- chrupavka metabolismus MeSH
- cyklická ADP-ribosa metabolismus MeSH
- intravenózní podání MeSH
- izotopové značení metody MeSH
- izotopy uhlíku chemie metabolismus farmakokinetika MeSH
- kosti a kostní tkáň metabolismus MeSH
- kyselina hyaluronová chemie metabolismus farmakokinetika MeSH
- molekulová hmotnost MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- tkáňová distribuce MeSH
- uridindifosfát-N-acetylglukosamin metabolismus MeSH
- uridindifosfátglukosa metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Carbon-13 MeSH Prohlížeč
- cyklická ADP-ribosa MeSH
- izotopy uhlíku MeSH
- kyselina hyaluronová MeSH
- uridindifosfát-N-acetylglukosamin MeSH
- uridindifosfátglukosa MeSH
It is generally known that hyaluronic acid (HA) is a biocompatible and biodegradable glycosaminoglycan distributed widely throughout epithelial, connective and neural tissues. HA is one of the chief components of the extracellular matrix. Lack of immunogenicity is one of the biggest advantages of the therapeutic use of HA, but it also prevents the production of specific anti-HA antibodies. Contrary to this, there are still several studies performing HA detection by immunohistochemical or immunohistofluorescent method using an anti-HA antibody. Therefore, this short study discusses whether the anti-HA antibody is specific for HA. To verify the specificity of the HA staining the hyaluronidase treatment of histological samples was performed and the ability of anti-HA antibody and biotinylated HA binding protein (bHABP)-based probe to bind to their targets was evaluated. Additionally, the competitive binding assay with short HA oligosaccharides and subsequent histological staining was performed. Both assays showed that the anti-HA antibody is not sufficiently specific for HA and that the bHABP probe is a reliable method for HA detection in histological samples. The conclusion made by previous investigators based on using HA antibodies should be reevaluated and future use of anti-HA antibody should be avoided.
- Klíčová slova
- IFC, IHC, anti-HA antibody, hyaluronan, hyaluronic acid binding protein, hyaluronidase,
- MeSH
- hyaluronoglukosaminidasa metabolismus MeSH
- kyselina hyaluronová metabolismus MeSH
- lidé MeSH
- protilátky metabolismus MeSH
- skot MeSH
- Streptomyces enzymologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hyaluronoglukosaminidasa MeSH
- kyselina hyaluronová MeSH
- protilátky MeSH