Glycoconjugate Journal最新文献

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Determination, expression and characterization of an UDP-N-acetylglucosamine:α-1,3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I (GnT-I) from the Pacific oyster, Crassostrea gigas. 太平洋牡蛎(Crassostrea gigas)中一种 UDP-N-乙酰葡糖胺:α-1,3-D-甘露糖苷 β-1,2-N-乙酰葡糖胺基转移酶 I(GnT-I)的测定、表达和表征。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-04-01 DOI: 10.1007/s10719-024-10148-9
Julia Thoma, Reingard Grabherr, Erika Staudacher
{"title":"Determination, expression and characterization of an UDP-N-acetylglucosamine:α-1,3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I (GnT-I) from the Pacific oyster, Crassostrea gigas.","authors":"Julia Thoma, Reingard Grabherr, Erika Staudacher","doi":"10.1007/s10719-024-10148-9","DOIUrl":"10.1007/s10719-024-10148-9","url":null,"abstract":"<p><p>Molluscs are intermediate hosts for several parasites. The recognition processes, required to evade the host's immune response, depend on carbohydrates. Therefore, the investigation of mollusc glycosylation capacities is of high relevance to understand the interaction of parasites with their host. UDP-N-acetylglucosamine:α-1,3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I (GnT-I) is the key enzyme for the biosynthesis of hybrid and complex type N-glycans catalysing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to the α-1,3 Man antenna of Man<sub>5</sub>GlcNAc<sub>2</sub>. Thereby, the enzyme produces a suitable substrate for further enzymes, such as α-mannosidase II, GlcNAc-transferase II, galactosyltransferases or fucosyltransferases. The sequence of GnT- I from the Pacific oyster, Crassostrea gigas, was obtained by homology search using the corresponding human enzyme as the template. The obtained gene codes for a 445 amino acids long type II transmembrane glycoprotein and shared typical structural elements with enzymes from other species. The enzyme was expressed in insect cells and purified by immunoprecipitation using protein A/G-plus agarose beads linked to monoclonal His-tag antibodies. GnT-I activity was determined towards the substrates Man5-PA, MM-PA and GnM-PA. The enzyme displayed highest activity at pH 7.0 and 30 °C, using Man5-PA as the substrate. Divalent cations were indispensable for the enzyme, with highest activity at 40 mM Mn<sup>2+</sup>, while the addition of EDTA or Cu<sup>2+</sup> abolished the activity completely. The activity was also reduced by the addition of UDP, UTP or galactose. In this study we present the identification, expression and biochemical characterization of the first molluscan UDP-N-acetylglucosamine:α-1,3-D-mannoside β-1,2-N-acetylglucosaminyltransferase I, GnT-I, from the Pacific oyster Crassostrea gigas.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"151-162"},"PeriodicalIF":2.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11065688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of circulating advanced glycation end products and their soluble receptors with cancer risk: A systematic review and meta-analysis of observational studies 循环中的高级糖化终产物及其可溶性受体与癌症风险的关系:观察性研究的系统回顾和荟萃分析
IF 3 4区 生物学
Glycoconjugate Journal Pub Date : 2024-03-18 DOI: 10.1007/s10719-024-10147-w
{"title":"Associations of circulating advanced glycation end products and their soluble receptors with cancer risk: A systematic review and meta-analysis of observational studies","authors":"","doi":"10.1007/s10719-024-10147-w","DOIUrl":"https://doi.org/10.1007/s10719-024-10147-w","url":null,"abstract":"<h3>Abstract</h3> <p>Advanced glycation end products (AGE) in complex with their receptors (RAGE) cause a chronic inflammatory state in the body, which is the major mechanism in cancer development. This study aimed to conduct a systematic review and meta-analysis on the observational studies investigating the association between AGEs / sRAGE and cancer incidence. The PubMed, Scopus, and Web of Science databases were comprehensively searched to identify papers focused on the associations of sRAGE and AGEs with cancer incidence up to May 2023. Eight studies with a total of 7690 participants were included in the analysis to evaluate the association between circulating sRAGE and cancer incidence. The results indicated that circulating sRAGE (per 100 ng/L) had a significant inverse association with cancer incidence (RR 0.977; 95% CI 0.956, 0.999; p = 0.036; <em>I</em> <sup>2</sup> = 73.3%). The association between AGEs and cancer incidence was evaluated in 8 studies with a total of 3718 individuals. Serum concentrations of AGEs (per 100 µg/L) were not associated with the risk of cancer incidence (RR 0.988; 95% CI 0.974, 1.002; p = 0.08; <em>I2</em> = 78.8%). Our findings revealed that a higher circulating sRAGE may have a protective effect against cancer incidence.</p> <span> <h3>Graphical Abstract</h3> <p> <span> <span> <img alt=\"\" src=\"https://static-content.springer.com/image/MediaObjects/10719_2024_10147_Figa_HTML.png\"/> </span> </span></p> </span>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":"2 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140146950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serotype-specific quantification of residual free polysaccharide in multivalent pneumococcal conjugate vaccines. 多价肺炎球菌结合疫苗中残留游离多糖的血清型特异性定量。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-02-01 Epub Date: 2024-01-15 DOI: 10.1007/s10719-023-10143-6
Milica Grozdanovic, Rachelle Samuel, Brendan Grau, Frances Ansbro
{"title":"Serotype-specific quantification of residual free polysaccharide in multivalent pneumococcal conjugate vaccines.","authors":"Milica Grozdanovic, Rachelle Samuel, Brendan Grau, Frances Ansbro","doi":"10.1007/s10719-023-10143-6","DOIUrl":"10.1007/s10719-023-10143-6","url":null,"abstract":"<p><p>The Streptococcus pneumoniae bacteria has over 100 known serotypes that display a continuous change in prevalence by patients' age and geographical location and therefore necessitate continued efforts toward development of new vaccines with broader protection. Glycoconjugate vaccines have been instrumental in reducing global morbidity and mortality caused by Streptococcus pneumoniae infections. In these vaccines, the bacterial polysaccharide is conjugated to a carrier protein to enhance immunogenicity. To ensure well defined immunogenicity and stability of conjugated vaccines, reliable quantification of non-conjugated (free) polysaccharide is a critical, albeit challenging step during vaccine clinical dosing, release and stability monitoring. Multivalent preparations of Cross-reactive material 197 (CRM197)- conjugated pneumococcal polysaccharide materials often contain only nanogram levels of each individual free polysaccharide at final container concentrations. We have developed a novel method for the separation of free polysaccharides from conjugated material that requires no sample derivatization, employing instead an approach of quantitative immunoprecipitation of CRM197 with 3 different monoclonal antibodies and magnetic beads. A mix of antibodies against both linear and conformational epitopes enables successful removal of conjugates regardless of the protein folded state. The remaining free polysaccharide is subsequently measured in a serotype-specific ELISA.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"47-55"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural elucidation of a non-starch polysaccharides from Lilii Bulbus and its protective effects against corticosterone-induced neurotoxicity in PC12 cells. 莉莉牛非淀粉多糖的结构鉴定及其对皮质酮诱导的 PC12 细胞神经毒性的保护作用
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-02-01 Epub Date: 2023-12-28 DOI: 10.1007/s10719-023-10145-4
Yili Zheng, Xueying Li, Danna Lin, Jian Wu, Yufei Tian, Hongyuan Chen, Wen Rui
{"title":"Structural elucidation of a non-starch polysaccharides from Lilii Bulbus and its protective effects against corticosterone-induced neurotoxicity in PC12 cells.","authors":"Yili Zheng, Xueying Li, Danna Lin, Jian Wu, Yufei Tian, Hongyuan Chen, Wen Rui","doi":"10.1007/s10719-023-10145-4","DOIUrl":"10.1007/s10719-023-10145-4","url":null,"abstract":"<p><p>Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"57-65"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regular moderate physical exercise decreases Glycan Age index of biological age and reduces inflammatory potential of Immunoglobulin G. 经常进行适度的体育锻炼可降低生物年龄的糖化年龄指数,并降低免疫球蛋白 G 的炎症潜能。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-02-01 Epub Date: 2023-12-26 DOI: 10.1007/s10719-023-10144-5
Nina Šimunić-Briški, Vedran Dukarić, Mateja Očić, Tomislav Madžar, Martina Vinicki, Azra Frkatović-Hodžić, Damir Knjaz, Gordan Lauc
{"title":"Regular moderate physical exercise decreases Glycan Age index of biological age and reduces inflammatory potential of Immunoglobulin G.","authors":"Nina Šimunić-Briški, Vedran Dukarić, Mateja Očić, Tomislav Madžar, Martina Vinicki, Azra Frkatović-Hodžić, Damir Knjaz, Gordan Lauc","doi":"10.1007/s10719-023-10144-5","DOIUrl":"10.1007/s10719-023-10144-5","url":null,"abstract":"<p><p>Physical inactivity and obesity are growing concerns, negatively impacting the general population. Moderate physical activity is known to have a beneficial anti-inflammatory effect. N-glycosylation of immunoglobulin G (IgG) reflects changes in the inflammatory potential of IgG. In this study, GlycanAge index of biological age (GlycanAge), one of the first commercially used biomarkers of aging, was employed to assess effects of exercise intensity in three different groups of athletes: professional competing athletes, regularly moderate active individuals and newly involved recreational individuals, compared to the group of inactive individuals. GlycanAge was significantly lower in the active group compared to the inactive group (β = -7.437, p.adj = 7.85E-03), and nominally significant and increased in professional athletes compared to the active group (β = 7.546, p = 3.20E-02). Competing female athletes had significantly higher GlycanAge comparing to active females exercising moderately (β = 20.206, p.adj = 2.71E-02), while the latter had significantly lower GlycanAge when compared with the inactive counterparts (β = -9.762, p.adj = 4.68E-02). Regular, life-long moderate exercise has an anti-inflammatory effect in both female and male population, demonstrated by lower GlycanAge index, and it has great potential to mitigate growing issues related to obesity and a sedentary lifestyle, which are relentlessly increasing world-wide.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"67-76"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Regular moderate physical exercise decreases Glycan Age index of biological age and reduces inflammatory potential of Immunoglobulin G. 更正为经常进行适度体育锻炼可降低生物年龄的糖龄指数,并降低免疫球蛋白 G 的炎症潜能。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-02-01 DOI: 10.1007/s10719-024-10146-x
Nina Šimunić-Briški, Vedran Dukarić, Mateja Očić, Tomislav Madžar, Martina Vinicki, Azra Frkatović-Hodžić, Damir Knjaz, Gordan Lauc
{"title":"Correction to: Regular moderate physical exercise decreases Glycan Age index of biological age and reduces inflammatory potential of Immunoglobulin G.","authors":"Nina Šimunić-Briški, Vedran Dukarić, Mateja Očić, Tomislav Madžar, Martina Vinicki, Azra Frkatović-Hodžić, Damir Knjaz, Gordan Lauc","doi":"10.1007/s10719-024-10146-x","DOIUrl":"10.1007/s10719-024-10146-x","url":null,"abstract":"","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"77-78"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mannose-specific plant and microbial lectins as antiviral agents: A review 作为抗病毒剂的甘露糖特异性植物和微生物凝集素:综述
IF 3 4区 生物学
Glycoconjugate Journal Pub Date : 2024-01-20 DOI: 10.1007/s10719-023-10142-7
Ankita Gupta, Kusum Yadav, Anurag Yadav, Rumana Ahmad, Aditi Srivastava, Dileep Kumar, Mohammad Amir Khan, U. N. Dwivedi
{"title":"Mannose-specific plant and microbial lectins as antiviral agents: A review","authors":"Ankita Gupta, Kusum Yadav, Anurag Yadav, Rumana Ahmad, Aditi Srivastava, Dileep Kumar, Mohammad Amir Khan, U. N. Dwivedi","doi":"10.1007/s10719-023-10142-7","DOIUrl":"https://doi.org/10.1007/s10719-023-10142-7","url":null,"abstract":"<p>Lectins are non-immunological carbohydrate-binding proteins classified on the basis of their structure, origin, and sugar specificity. The binding specificity of such proteins with the surface glycan moiety determines their activity and clinical applications. Thus, lectins hold great potential as diagnostic and drug discovery agents and as novel biopharmaceutical products. In recent years, significant advancements have been made in understanding plant and microbial lectins as therapeutic agents against various viral diseases. Among them, mannose-specific lectins have being proven as promising antiviral agents against a variety of viruses, such as HIV, Influenza, Herpes, Ebola, Hepatitis, Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and most recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The binding of mannose-binding lectins (MBLs) from plants and microbes to high-mannose containing N-glycans (which may be simple or complex) of glycoproteins found on the surface of viruses has been found to be highly specific and mainly responsible for their antiviral activity. MBLs target various steps in the viral life cycle, including viral attachment, entry and replication. The present review discusses the brief classification and structure of lectins along with antiviral activity of various mannose-specific lectins from plants and microbial sources and their diagnostic and therapeutic applications against viral diseases.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GM1 structural requirements to mediate neuronal functions 介导神经元功能的 GM1 结构要求
IF 3 4区 生物学
Glycoconjugate Journal Pub Date : 2023-12-15 DOI: 10.1007/s10719-023-10141-8
Maria Fazzari, Giulia Lunghi, Erika Di Biase, Margherita Maggioni, Emma Veronica Carsana, Laura Cioccarelli, Laura Vigani, Nicoletta Loberto, Massimo Aureli, Laura Mauri, Maria Grazia Ciampa, Manuela Valsecchi, Koichi Takato, Akihiro Imamura, Hideharu Ishida, Omar Ben Mariem, Simona Saporiti, Luca Palazzolo, Elena Chiricozzi, Ivano Eberini, Sandro Sonnino
{"title":"GM1 structural requirements to mediate neuronal functions","authors":"Maria Fazzari, Giulia Lunghi, Erika Di Biase, Margherita Maggioni, Emma Veronica Carsana, Laura Cioccarelli, Laura Vigani, Nicoletta Loberto, Massimo Aureli, Laura Mauri, Maria Grazia Ciampa, Manuela Valsecchi, Koichi Takato, Akihiro Imamura, Hideharu Ishida, Omar Ben Mariem, Simona Saporiti, Luca Palazzolo, Elena Chiricozzi, Ivano Eberini, Sandro Sonnino","doi":"10.1007/s10719-023-10141-8","DOIUrl":"https://doi.org/10.1007/s10719-023-10141-8","url":null,"abstract":"<p>Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc. Here we detailed the minimum structural requirements of the oligosaccharide portion of GM1 for mediating the TrkA dependent neuritogenic processing. By <i>in vitro</i> and <i>in silico</i> biochemical approaches, we demonstrated that the minimal portion of GM1 required for the TrkA activation is the inner core of the ganglioside’s oligosaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal. The addition of a sialic acid residue at position 3 of the outer galactose of the GM1 oligosaccharide, which forms the oligosaccharide of GD1a, prevented the interaction with TrkA and the resulting neuritogenesis. On the contrary, the addition of a fucose residue at position 2 of the outer galactose, forming the Fucosyl-GM1 oligosaccharide, did not prevent the TrkA-mediated neuritogenesis.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":"10 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lysosomal sialidase NEU1, its intracellular properties, deficiency, and use as a therapeutic agent. 溶酶体硅糖苷酶 NEU1、其细胞内特性、缺乏症和作为治疗剂的用途。
IF 3 4区 生物学
Glycoconjugate Journal Pub Date : 2023-12-01 Epub Date: 2023-12-26 DOI: 10.1007/s10719-023-10135-6
Kohji Itoh, Jun Tsukimoto
{"title":"Lysosomal sialidase NEU1, its intracellular properties, deficiency, and use as a therapeutic agent.","authors":"Kohji Itoh, Jun Tsukimoto","doi":"10.1007/s10719-023-10135-6","DOIUrl":"10.1007/s10719-023-10135-6","url":null,"abstract":"<p><p>Neuraminidase 1 (NEU1) is a lysosomal sialidase that cleaves terminal α-linked sialic acid residues from sialylglycans. NEU1 is biosynthesized in the rough endoplasmic reticulum (RER) lumen as an N-glycosylated protein to associate with its protective protein/cathepsin A (CTSA) and then form a lysosomal multienzyme complex (LMC) also containing β-galactosidase 1 (GLB1). Unlike other mammalian sialidases, including NEU2 to NEU4, NEU1 transport to lysosomes requires association of NEU1 with CTSA, binding of the CTSA carrying terminal mannose 6-phosphate (M6P)-type N-glycan with M6P receptor (M6PR), and intralysosomal NEU1 activation at acidic pH. In contrast, overexpression of the single NEU1 gene in mammalian cells causes intracellular NEU1 protein crystallization in the RER due to self-aggregation when intracellular CTSA is reduced to a relatively low level. Sialidosis (SiD) and galactosialidosis (GS) are autosomal recessive lysosomal storage diseases caused by the gene mutations of NEU1 and CTSA, respectively. These incurable diseases associate with the NEU1 deficiency, excessive accumulation of sialylglycans in neurovisceral organs, and systemic manifestations. We established a novel GS model mouse carrying homozygotic Ctsa IVS6 + 1 g/a mutation causing partial exon 6 skipping with simultaneous deficiency of Ctsa and Neu1. Symptoms developed in the GS mice like those in juvenile/adult GS patients, such as myoclonic seizures, suppressed behavior, gargoyle-like face, edema, proctoptosis due to Neu1 deficiency, and sialylglycan accumulation associated with neurovisceral inflammation. We developed a modified NEU1 (modNEU1), which does not form protein crystals but is transported to lysosomes by co-expressed CTSA. In vivo gene therapy for GS and SiD utilizing a single adeno-associated virus (AAV) carrying modNEU1 and CTSA genes under dual promoter control will be created.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"611-619"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated concentrations of Neu5Ac and Neu5,9Ac2 in human plasma: potential biomarkers of cardiovascular disease. 人血浆中Neu5Ac和neu5,9ac2浓度升高:心血管疾病的潜在生物标志物
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2023-12-01 Epub Date: 2023-11-22 DOI: 10.1007/s10719-023-10138-3
Jack Cheeseman, Concepcion Badia, Georgia Elgood-Hunt, Richard A Gardner, Duong N Trinh, Marco P Monopoli, Gunter Kuhnle, Daniel I R Spencer, Helen M I Osborn
{"title":"Elevated concentrations of Neu5Ac and Neu5,9Ac<sub>2</sub> in human plasma: potential biomarkers of cardiovascular disease.","authors":"Jack Cheeseman, Concepcion Badia, Georgia Elgood-Hunt, Richard A Gardner, Duong N Trinh, Marco P Monopoli, Gunter Kuhnle, Daniel I R Spencer, Helen M I Osborn","doi":"10.1007/s10719-023-10138-3","DOIUrl":"10.1007/s10719-023-10138-3","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is a group of health conditions affecting the heart and vascular system with very high prevalence and mortality rates. The presence of CVD is characterised by high levels of inflammation which have previously been associated with increased plasma concentrations of N-acetyl neuraminic acid (Neu5Ac). While Neu5Ac has been studied in the context of CVD, Neu5,9Ac<sub>2</sub> has not, despite being the second most abundant sialic acid in human plasma. A small-scale pilot study of thirty plasma samples from patients with diagnosed CVD, and thirty age and sex-matched healthy controls, was designed to gain insight into sialic acids as biomarkers for CVD and potential future areas of study. Each sample was assayed for Neu5Ac and Neu5,9Ac<sub>2</sub> concentrations. Mean Neu5Ac and Neu5,9Ac<sub>2</sub> concentrations were significantly elevated in patients with CVD compared to healthy controls (Neu5Ac: P < 0.001; Neu5,9Ac<sub>2</sub>: P < 0.04). Receiver operator curve (ROC) analysis indicated that both Neu5Ac and Neu5,9Ac<sub>2</sub> have reasonable predictive power for the presence of CVD (Neu5Ac AUC: 0.86; Neu5,9Ac<sub>2</sub> AUC: 0.71). However, while Neu5Ac had both good sensitivity (0.82) and specificity (0.81), Neu5,9Ac<sub>2</sub> had equivalent specificity (0.81) but very poor sensitivity (0.44). A combination marker of Neu5Ac + Neu5,9Ac<sub>2</sub> showed improvement over Neu5Ac alone in terms of predictive power (AUC: 0.93), sensitivity (0.87), and specificity (0.90). Comparison to a known inflammatory marker, high sensitivity c-reactive protein (hs-CRP: P-value: NS, ROC:0.50) was carried out, showing that both Neu5Ac and Neu5,9Ac<sub>2</sub> outperformed this marker. Further to this, hs-CRP values were combined with the three different sialic acid markers to determine any effect on the AUC values. A slight improvement in AUC was noted for each of the combinations, with Neu5Ac + Neu5,9Ac<sub>2</sub> + hs-CRP giving the best AUC of 0.97 overall. Thus, Neu5Ac would appear to offer good potential as a predictive marker for the presence of CVD, which the addition of Neu5,9Ac<sub>2</sub> predictive power improves, with further improvement seen by the addition of hs-CRP.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"645-654"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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