- Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor NK1/Met Signaling. [Journal Article]
- CPCell Physiol Biochem 2018 Aug 14; 48(4):1480-1491
- CONCLUSIONS: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling.
- Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase. [Journal Article]
- SRSci Rep 2018 Aug 07; 8(1):11832
- Heparan Sulfate (HS) is a cell signaling molecule linked to pathological processes ranging from cancer to viral entry, yet fundamental aspects of its biosynthesis remain incompletely understood. Here...
Heparan Sulfate (HS) is a cell signaling molecule linked to pathological processes ranging from cancer to viral entry, yet fundamental aspects of its biosynthesis remain incompletely understood. Here, the binding preferences of the uronyl 2-O-sulfotransferase (HS2ST) are examined with variably-sulfated hexasaccharides. Surprisingly, heavily sulfated oligosaccharides formed by later-acting sulfotransferases bind more tightly to HS2ST than those corresponding to its natural substrate or product. Inhibition assays also indicate that the IC50 values correlate simply with degree of oligosaccharide sulfation. Structural analysis predicts a mode of inhibition in which 6-O-sulfate groups located on glucosamine residues present in highly-sulfated oligosaccharides occupy the canonical binding site of the nucleotide cofactor. The unexpected finding that oligosaccharides associated with later stages in HS biosynthesis inhibit HS2ST indicates that the enzyme must be separated temporally and/or spatially from downstream products during biosynthesis in vivo, and highlights a challenge for the enzymatic synthesis of lengthy HS chains in vitro.
- Impact of oral osteoarthritis therapy usage among other risk factors on knee replacement: a nested case-control study using the Osteoarthritis Initiative cohort. [Journal Article]
- ARArthritis Res Ther 2018 Aug 07; 20(1):172
- CONCLUSIONS: This study provides evidence that the main risk factors leading to KR are disease severity, symptoms and high BMI. Importantly, exposure to oral OA therapies was not associated with the occurrence of KR.
- Heparan sulfate S-domains and extracellular sulfatases (Sulfs): their possible roles in protein aggregation diseases. [Review]
- GJGlycoconj J 2018 Jul 12
- Highly sulfated domains of heparan sulfate (HS), also known as HS S-domains, consist of repeated trisulfated disaccharide units [iduronic acid (2S)-glucosamine (NS, 6S)-]. The expression of HS S-doma...
Highly sulfated domains of heparan sulfate (HS), also known as HS S-domains, consist of repeated trisulfated disaccharide units [iduronic acid (2S)-glucosamine (NS, 6S)-]. The expression of HS S-domains at the cell surface is determined by two mechanisms: tightly regulated biosynthetic machinery and enzymatic remodeling by extracellular endoglucosamine 6-sulfatases, Sulf-1 and Sulf-2. Intracellular or extracellular deposits of misfolded and aggregated proteins are characteristic of protein aggregation diseases. Although proteins can aggregate alone, deposits of protein aggregates in vivo contain a number of proteinaceous and non-protein components. HS S-domains are one non-protein component of these aggregated deposits. HS S-domains are considered to be critical for signal transduction of several growth factors and several disease conditions, such as tumor progression, but their roles in protein aggregation diseases are not yet fully understood. This review summarizes the current understanding of the possible roles of HS S-domains and Sulfs in the formation and cytotoxicity of protein aggregates.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Glucosamine is an amino-monosaccharide that is either derived from shellfish or synthetically produced. Glucosamine sulfate has no specific lactation-related uses. It is most commonly used to treat o...
Glucosamine is an amino-monosaccharide that is either derived from shellfish or synthetically produced. Glucosamine sulfate has no specific lactation-related uses. It is most commonly used to treat osteoarthritis. A glucosamine derivative, N-acetylglucosamine, is a normal component of human breastmilk. Glucosamine sulfate is well tolerated with occasional gastrointestinal discomfort (e.g., diarrhea, heartburn, nausea, vomiting) reported. Although no studies exist on the use of glucosamine sulfate during breastfeeding, its use by a nursing mother is unlikely to adversely affect the breastfed infant. Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.
- [The rationale for the application of magnetophoresis for the treatment of intra-articular pathology]. [Journal Article]
- VKVopr Kurortol Fizioter Lech Fiz Kult 2018; 95(3):49-56
- The present study was designed to elucidate the influence of the magnetic field on the spectroscopic characteristics of nimesulide and glucosamine sulfate preparations. The secondary objective of the...
The present study was designed to elucidate the influence of the magnetic field on the spectroscopic characteristics of nimesulide and glucosamine sulfate preparations. The secondary objective of the study was to evaluate the clinical effectiveness of the combined application of magnetotherapy and transdermal forms containing a non-steroidal anti-inflammatory preparation and a chondroprotector with the use of magnetophoresis. For this purpose, we analyzed the samples exposed to the running magnetic field in an infrared spectrometer to elucidate the changes in the optical characteristics of the preparations of interest. The clinical effectiveness of the combined application of magnetophoresis was estimated in 83 patients presenting with knee osteoarthritis. The use of the infrared spectroscopic technique in the combination with the Fourier analysis made it possible to visualize the absence of coarse optical defects and structural changes in the test samples under the influence of the physical factors which provides the basis for their physiophoretic administration. The clinical studies conducted with the application of the combined physio-pharmacological treatment have demonstrated the feasibility and high effectiveness of this approach for the management of the patients presenting with articular pathology. The rehabilitative measures accelerated the earlier appearance of the pronounced analgesic effect and promoted the restoration of the joint function. Moreover, they reduced the drug load and improved the quality of life of the patients.
- Molecular characterization of a novel chitinase CmChi1 from Chitinolyticbacter meiyuanensis SYBC-H1 and its use in N-acetyl-d-glucosamine production. [Journal Article]
- BBBiotechnol Biofuels 2018; 11:179
- CONCLUSIONS: The hydrolytic properties and good environmental adaptions indicate that CmChi1 has excellent potential in commercial GlcNAc production. This is the first report on exo-acting, endo-acting and N-acetyl-β-d-glucosaminidase activities from Chitinolyticbacter species.
- Impacts of glycation and transglutaminase-catalyzed glycosylation with glucosamine on the conformational structure and allergenicity of bovine β-lactoglobulin. [Journal Article]
- FFFood Funct 2018 Jul 17; 9(7):3944-3955
- β-Lactoglobulin (β-LG) is recognized as the major milk allergen. In this study, the effects of transglutaminase (TGase) and glucosamine (GlcN)-catalyzed glycosylation and glycation on the conformatio...
β-Lactoglobulin (β-LG) is recognized as the major milk allergen. In this study, the effects of transglutaminase (TGase) and glucosamine (GlcN)-catalyzed glycosylation and glycation on the conformational structure and allergenicity of β-LG were investigated. The formations of cross-linked peptides were demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and GlcN-conjugated modification was identified using matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Structural analysis revealed that glycosylation and glycation of β-LG induced unfolding of the primary protein structure followed by a loss of the secondary structure. As revealed by circular dichroism (CD) spectroscopy, glycosylated β-LG exhibited the highest increase in the β-sheets from 32.6% to 40.4% (25 °C) and 44.2% (37 °C), and the percentage of α-helices decreased from 17.7% to 14.4% (25 °C) and 12.3% (37 °C), respectively. The tertiary and quaternary structures of β-LG also changed significantly during glycosylation and glycation, along with reduced free amino groups and variation in surface hydrophobicity. Immunoblotting and indirect enzyme-linked immuno sorbent assay (ELISA) analyses demonstrated that the lowest IgG- and IgE-binding capacities of β-LG were obtained following glycosylation at 37 °C, which were 52.7% and 56.3% lower than that of the native protein, respectively. The reduction in the antigenicity and potential allergenicity of glycosylated β-LG was more pronounced compared to TGase treated- and glycated β-LG, which correlated well with the structural changes. These results suggest that TGase-catalyzed glycosylation has more potential compared to glycation for mitigating the allergenic potential of milk products.
- Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. [Review]
- RIRheumatol Int 2018; 38(8):1413-1428
- Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systema...
Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.
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- Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character. [Journal Article]
- BCBMC Cancer 2018 Jun 25; 18(1):687
- CONCLUSIONS: We evidenced alterations in the expression of HSPGs, including the expression of cell surface core proteins, many glycosiltransferases and some enzymes that modify the GAG chains in LSCRCs, but this was dependent on the metastatic nature of the tumor. Some of these alterations are shared with RSCRCs, while others, focused on specific gene groups, are dependent on tumor localization.