Characterization of Proteoglycan and Hyaluronan in Hot Water Extract from Salmon Cartilage.
Ontology highlight
ABSTRACT:
SUBMITTER: Kakizaki I
PROVIDER: S-EPMC8056930 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Proteoglycan (PG) extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community.
| S-EPMC3767651 | biostudies-literature
Project description:BackgroundRheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. The autoimmune character of RA is underscored by prominent production of autoantibodies such as those against IgG (rheumatoid factor), and a broad array of joint tissue-specific and other endogenous citrullinated proteins. Anti-citrullinated protein antibodies (ACPA) can be detected in the sera and synovial fluids of RA patients and ACPA seropositivity is one of the diagnostic criteria of RA. Studies have demonstrated that RA T cells respond to citrullinated peptides (epitopes) of proteoglycan (PG) aggrecan, which is one of the most abundant macromolecules of articular cartilage. However, it is not known if the PG molecule is citrullinated in vivo in human cartilage, and if so, whether citrulline-containing neoepitopes of PG (CitPG) can contribute to autoimmunity in RA.MethodsCitPG was detected in human cartilage extracts using ACPA+ RA sera in dot blot and Western blot. Citrullination status of in vitro citrullinated recombinant G1 domain of human PG (rhG1) was confirmed by antibody-based and chemical methods, and potential sites of citrullination in rhG1 were explored by molecular modeling. CitPG-specific serum autoantibodies were quantified by enzyme-linked immunosorbent assays, and CitPG was localized in osteoarthritic (OA) and RA cartilage using immunohistochemistry.FindingsSera from ACPA+ RA patients reacted with PG purified from normal human cartilage specimens. PG fragments (mainly those containing the G1 domain) from OA or RA cartilage extracts were recognized by ACPA+ sera but not by serum from ACPA- individuals. ACPA+ sera also reacted with in vitro citrullinated rhG1 and G3 domain-containing fragment(s) of PG. Molecular modeling suggested multiple sites of potential citrullination within the G1 domain. The immunohistochemical localization of CitPG was different in OA and RA cartilage.ConclusionsCitPG is a new member of citrullinated proteins identified in human joints. CitPG could be found in both normal and diseased cartilage specimens. Antibodies against CitPG may trigger or augment arthritis by forming immune complexes with this autoantigen in the joints of ACPA+ RA patients.
| S-EPMC4778950 | biostudies-literature
Project description:Pancreatic cancer is one of the most aggressive human malignancies with 7.1% five-year survival rate due to late-stage diagnosis and lack of effective treatment. A novel active compound to be useful for treating pancreatic cancer is absolutely demanded. Agaricus blazei (A. blazei) Murrill has been shown to have an anti-cancer activity, however, its specific efficacy and underlying mechanism is poorly understood. Here, we demonstrated that A. blazei hot water extract (AbE) showed significant growth inhibition of cultured pancreatic cancer cells with less suppressive effect on the normal human pancreatic duct epithelial cells. The pancreatic cancer cells committed G0/G1 cell cycle arrest and caspase-dependent apoptosis. Moreover, we uncovered significant alterations of global gene expression in the pancreatic cancer cells by AbE treatment. Signature of alteration of gene expression indicated that AbE induced repression of genes associated with kinetochore function, spindle formation, centromere maintenance, and cyclins and cyclin dependent kinases, which were essential for cell cycle progression. The gene expression analysis also showed upregulation of proapoptotic genes. These results indicate that AbE could be useful for treatment of pancreatic cancer and a good candidate to isolate potent active compound for development of novel drug for pancreatic cancer.
2018-10-31 | GSE89396 | GEO
Project description:To explore the effect of pretreatment of neuroblastoma cells with hot water extract of Korean ginseng on MNNG-induced parthanatos and its mechanism. Neuroblastoma SH-SY5Y cells were pretreated with 1 mg/L hot water extract of Korean ginseng before induction with 250 ?mol/L MNNG for 1 h or 4 h. CCK-8 and cell flow cytometry were used to detect cell survival rate. Western blotting was used to detect the changes in poly(ADP-ribose) (PAR) expression in the treated cells. Immunofluorescence assay was used to detect nuclear distribution of apoptosis-inducing factor (AIF), and flow cytometry was used to detect the level of reactive oxygen species (ROS) in the cells. Compared with the blank control cells, MNNG-treated SH-SY5Y cells showed significantly decreased survival rate as the concentration of MNNG and the stimulation time increased (P < 0.05). Stimulation with MNNG also resulted in significantly increased expression of PAR protein in the cells (P < 0.05). Pretreatment of the cells with hot water extract of Korean ginseng obviously inhibited MNNG-induced cell death and significantly reduced AIF expression and nucleation in the cells (P < 0.05). MNNG stimulation significantly increased ROS level in the cells, which was decreased significantly by pretreatment of the cells with the extract (P < 0.05). Pretreatment with hot water extract of Korean ginseng reduces MNNG-induced parthanatos and ROS production in SH-SY5Y cells.
| S-EPMC7544575 | biostudies-literature
Project description:BackgroundAlthough proteoglycan (PG) is one of the major components of cartilage matrices, its biological function is not fully elucidated.MethodsThe objectives of this study were to investigate the proliferation and differentiation of chondrocytes embedded in atelocollagen gel with exogenous cartilage PG (PG-atelocollagen gel) in vitro, and also to evaluate the repair of cartilage defects by PG-atelocollagen gel in vivo. In the in vitro study, rabbit chondrocytes were cultured in the PG-atelocollagen gel. Cell proliferation and mRNA expression levels were measured, and gels were histologically evaluated. In the in vivo study, cultured PG-atelocollagen gel containing chondrocytes were transplanted into full-thickness articular cartilage defects in rabbit knees, and evaluated macroscopically and histologically.ResultsFor the in vitro study, chondrocyte proliferation in 5.0 mg/ml PG-atelocollagen gel was enhanced, and the gene expression of Col2a1 and Aggrecan were decreased. In contrast, chondrocyte proliferation in 0.1 and 1.0 mg/ml PG-atelocollagen gel was not enhanced. The gene expression of Aggrecan in 0.1 and 1.0 mg/ml PG-atelocollagen gel was increased. For the in vivo study, the histological average total score of the 0.1 mg/ml PG-atelocollagen gel was significantly better than that of the group without PG.ConclusionsAlthough the appropriate concentration of PG has not been defined, this study suggests the efficacy of PG for cartilage repair.
| S-EPMC3311805 | biostudies-literature
Project description:Purpose: One of the essential requirements in maintaining the normal joint motor function is the perfect tribological property of the articular cartilage. Many cartilage regeneration strategies have been developed for treatment in early stages of osteoarthritis, but there is little information on how repaired articular cartilage regains durability. The identification of biomarkers that can predict wear resistant property is critical to advancing the success of cartilage regeneration therapies. Proteoglycan 4 (PRG4) is a macromolecule distributing on the chondrocyte surface that contributes to lubrication. In this study, we investigate if PRG4 expression is associated with tribological properties of regenerated cartilage, and is able to predict its wear resistant status. Methods: Two different strategies including bone marrow enrichment plus microfracture (B/BME-MFX) and microfracture alone (B-MFX) of cartilage repair in sheep were used. PRG4 expression and a series of tribological parameters on regenerated cartilage were rigorously examined and compared. Results: Highly and continuously expression of PRG4 in regenerated cartilage surface was negatively correlated with each tribological parameter (P<0.0001, respectively). Multivariate analysis showed that PRG4 expression was the key predictor that contributed to the promotion of cartilage wear resistance. Conclusion: Higher PRG4 expression in regenerated cartilage is significantly associated with wear resistance improvement. PRG4 may be useful for predicting the wear resistant status of regenerated cartilage and determining the optimal cartilage repair strategy.
| S-EPMC7052906 | biostudies-literature
Project description:Malignant gliomas have a distinctive ability to infiltrate the brain parenchyma and disrupt the neural extracellular matrix that inhibits motility of axons and normal neural cells. Chondroitin sulfate proteoglycans (CSPGs) are among the major inhibitory components in the neural matrix, but surprisingly, some are up-regulated in gliomas and act as pro-invasive signals. In the normal brain, CSPGs are thought to associate with hyaluronic acid and glycoproteins such as the tenascins and link proteins to form the matrix scaffold. Here, we examined for the first time the expression of link proteins in human brain and malignant gliomas. Our results indicate that HAPLN4 and HAPLN2 are the predominant members of this family in the adult human brain but are strongly reduced in the tumor parenchyma. To test if their absence was related to a pro-invasive gain of function of CSPGs, we expressed HAPLN4 in glioma cells in combination with the CSPG brevican. Surprisingly, HAPLN4 increased glioma cell adhesion and migration and even potentiated the motogenic effect of brevican. Further characterization revealed that HAPLN4 expressed in glioma cells was largely soluble and did not reproduce the strong, hyaluronan-independent association of the native protein to brain subcellular membranes. Taken together, our results suggest that the tumor parenchyma is rich in CSPGs that are not associated to HAPLNs and could instead interact with other extracellular matrix proteins produced by glioma cells. This dissociation may contribute to changes in the matrix scaffold caused by invasive glioma cells.
| S-EPMC2785343 | biostudies-literature
Project description:Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a component of the extracellular matrix (ECM) proteins and involved in the tumor environment in the colon. Transforming growth factor (TGF)-β is a key cytokine that regulates the deposition of ECM proteins in CRC. However, the role of HAPLN1 in TGF-β contributions to CRC remains unknown. We found that the mRNA expression of HAPLN1 was decreased in tumors from CRC patients compared with healthy controls and normal tissue adjacent to the tumor using two existing microarray datasets. This was validated at the protein level by tissue array from CRC patients (n = 59). HAPLN1 protein levels were also reduced in human CRC epithelial cells after 24 h of TGF-β stimulation, and its protein expression correlated with type I collagen alpha-1 (COL1A1) in CRC. Transfection of HAPLN1 overexpression plasmids into these cells increased protein levels but reduced COL1A1 protein, tumor growth, and cancer cell migration. TGF-β stimulation increased Smad2/3, p-Smad2/3, Smad4, and E-adhesion proteins; however, HAPLN1 overexpression restored these proteins to baseline levels in CRC epithelial cells after TGF-β stimulation. These findings suggest that HAPLN1 regulates the TGF-β signaling pathway to control collagen deposition via the TGF-β signaling pathway and mediates E-adhesion to control tumor growth. Thus, treatments that increase HAPLN1 levels may be a novel therapeutic option for CRC.
| S-EPMC8710468 | biostudies-literature
Project description:Cordyceps militaris is a well-known Chinese medicinal fungus that has been used as a nutraceutical food in several Asian countries. Cordycepin (3'-deoxyadenosine), a secondary metabolite produced from Cordyceps militaris, has been demonstrated to exert a wide spectrum of pharmacological activities, such as anti-microbial and antitumor activities. However, the effect of cordycepin on immunomodulation in broilers is poorly investigated. In the current study, we investigated the effect of cordycepin (9.69, 19.38, and 38.76 mg) from Cordyceps militaris hot water extract (CMHW) on growth performance and immunocompetence in broilers. Results showed that CMHW significantly decreased inducible nitric oxide synthase (iNOS) mRNA levels in the bursa of Fabricius after 4 weeks of feeding (P<0.05). CMHW treatment reduced cyclooxygenase-2 (COX-2) mRNA levels in the spleen and bursa of Fabricius after 4 weeks of feeding (P<0.05). Supplementation of CMHW for 3 days after vaccination reduced iNOS mRNA level in the spleen of 14 and 28 day-old broilers (P<0.05). Prior to vaccination, CMHW pretreatment significantly down-regulated COX-2 mRNA levels in the spleen and bursa of Fabricius of 14-day-old broilers (P<0.05). Furthermore, CMHW significantly reduced lipopolysaccharide (LPS)-induced iNOS and COX-2 mRNA levels in the spleen and bursa of Fabricius (P<0.05). CMHW treatment attenuated LPS-induced IFN-γ expression in the spleen and bursa of Fabricius, whereas CMHW induced IL-4 expression in these organs in response to LPS challenge (P<0.05). Taken together, these observations demonstrate that CMHW exerts an immunomodulatory role in broilers. CMHW is a potential novel feed additive with applications in inflammation-related diseases and bacterial infection in broilers.
| S-EPMC7005407 | biostudies-literature
Project description:During endochondral ossification, chondrocytes secrete a proteoglycan (PG)-rich extracellular matrix that can inhibit the process of cartilage maturation, including expression of Ihh and Col10a1. Because bone morphogenetic proteins (BMPs) can promote cartilage maturation, we hypothesized that cartilage PGs normally inhibit BMP signalling. Accordingly, BMP signalling was evaluated in chondrocytes of wild-type and PG mutant (fam20b-/-) zebrafish and inhibited with temporal control using the drug DMH1 or an inducible dominant-negative BMP receptor transgene (dnBMPR). Compared with wild type, phospho-Smad1/5/9, but not phospho-p38, was increased in fam20b-/- chondrocytes, but only after they secreted PGs. Phospho-Smad1/5/9 was decreased in DMH1-treated or dnBMPR-activated wild-type chondrocytes, and DMH1 also decreased phospho-p38 levels. ihha and col10a1a were decreased in DMH1-treated or dnBMPR-activated chondrocytes, and less perichondral bone formed. Finally, early ihha and col10a1a expression and early perichondral bone formation of fam20b mutants were rescued with DMH1 treatment or dnBMPR activation. Therefore, PG inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification, and these results offer hope for the development of growth factor therapies for skeletal defects of PG diseases.
| S-EPMC10820745 | biostudies-literature