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Ultra-Orphan drug development for GNE Myopathy: A synthetic literature review and meta-analysis.

GNE myopathy is an autosomal recessive hereditary muscle disorder that has the following clinical characteristics: develops in early adulthood, gradually progresses from the distal muscles, and is relatively sparing of quadriceps until the advanced stages of the disease. With further progression, patients become non-ambulatory and need a wheelchair. There is growing concern about extra-muscular presentations such as thrombocytopenia, respiratory dysfunction, and sleep apnea syndrome. Pathologically, rimmed vacuoles and tubulofilamentous inclusions are observed in affected muscles. The cause of

Influenza A Virus Binding to α,2-3- and α,2-8-Linked Sialo-Gangliosides Reconstituted in Phase-Separated Vesicles.

We investigated the binding of influenza A viruses (IAVs) to gangliosides containing either α,2-3- or α,2-8-linked sialic acid residues, or … interactions modulate the ability of viruses to establish multivalent contacts with membrane-bound sialic acids. Taken together, our findings demonstrate that electrostatic repulsion, glycosidic linkage, and lipid packing collectively govern influenza binding to phase-separated membranes. These results suggest that the commonly discussed preferential binding …

A study of the influence of mouth-breathing in some parameters of unstimulated and stimulated whole saliva of adolescents.

OBJECTIVE: The aim of this study was to analyze some standard parameters of the unstimulated and stimulated whole saliva of mouth-breathers and a control group to determine if these variables present any difference in mouth-breathers compared to control group, since these parameters of saliva can influence the oral health. METHODS: Saliva samples were collected from 61 adolescents aged 10-19 years; 30 were mouth-breathers and 31 were nose-breathers. The unstimulated salivary specimen was collected, followed by collection of the stimulated saliva. Soon after collecting the salivary sample, the

Sialylation: an Avenue to Target Cancer Cells.

Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoprotei … ses mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is gover …

Non-specific accumulation of glycosphingolipids in GNE myopathy.

BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) is a bifunctional enzyme responsible for the first committed steps in the synthesis of sialic acid, a common terminal monosaccharide in both protein and lipid glycosylation. GNE mutations are responsible for a rare autosomal recessive neuromuscular disorder, GNE myopathy (also called hereditary inclusion body myopathy). The connection between the impairment of sialic acid synthesis and muscle pathology in GNE myopathy remains poorly understood. METHODS: Glycosphingolipid (GSL) analysis was performed by HPLC in multiple models of GNE myo

UDP-GlcNAc2-epimerase regulates cell surface sialylation and cell adhesion to extracellular matrix in Burkitt's lymphoma.

Alteration of cell surface glycoconjugates plays a crucial role in many biological phenomenon, including invasion and metastasis. In the present study, we investigated the relationship between cell surface sialylation and the adhesive properties of two clones (3G3 and 3D2) of a human Burkitt's lymphoma cell line, HBL-8 to extracellular matrix. By flow cytometric analysis we found that the cell surface of 3G3 clone was highly sialylated and that of the 3D2 clone were hyposialylated. Moreover, cell surface sialic acid content was significantly greater in the 3G3 clone than in the 3D2 clone. In v

[Effects of experimental varicocele on the apoptosis of epididymis epithelium and synthesizing function of the epididymis in rats].

OBJECTIVE: To study the relationships of experimental varicocele to the apoptosis of epididymis epithelium and changes of the contents of alpha-1,4-glucosidase and sialic acid from the unilateral epididymis in adolescent rats, and to investigate the effects of varicocele on the unilateral epididymis epithelium. METHODS: Experimental left varicocele models of 16 adult male Sprague-Dawley rats were obtained by partial ligation of the left renal vein. The epididymides were collected for detecting the apoptosis of epididymis epithelium and the contents of alpha-1,4-glucosidase and sialic acid by

Visualization of carbohydrate chains in rabbit salivary glands by means of enzymatic degradation and plant lectins.

We investigated the structure of glycoconjugates contained within the secretory end-pieces and ductal segments in the rabbit submandibular and sublingual glands. Glycosidic sequences were examined by means of enzymatic degradation with specific glycosidases (sialidase, alpha-fucosidase, beta-galactosidase, alpha-mannosidase) followed by lectin binding with PNL-HRP, WPL-HRP, WGL-HRP, SBL-HRP, Con A-HRP. It was found that this procedure represents a valid tool for studying carbohydrates, in so far as their characterization and localization were based only on colour reactions. In particular, this

Fusobacterium nucleatum Lipopolysaccharides Disrupt the Interaction of Siglec‑7 to Sialoglycans Expressed on Mammalian Cells.

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are key immune receptors that bind to cell surface sialic acids, leading to modulation of the immune system. Interrupting the Siglec-sialoglycan binding in cancer has been proposed as a potential antitumor response strategy. We previously showed that colon-cancer-associated Fusobacterium nucleatum (Fn) ATCC 51191 interacts with Siglec-7 via its lipopolysaccharide (LPS), revealing Fn LPS as a new ligand for Siglec-7. Here, we used glycoengineered cells carrying sialic acid variants to investigate the capacity of LPS isolated from F. nucl…

Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation.

Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the "mixing vessel theory". Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimen…

Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model.

In order to combat invading pathogens neutrophils can release neutrophil extracellular traps (NETs). However, since NETs can also damage end … uclei and membrane perforation was prevented. However, the inhibitory effects were diminished, when sialic acids were released under acidic conditions. Comparable results were achieved, when sialic acids were targeted by neuraminidase digestion, indicating a sialic acid dependent inhibition of NET release. Thus, bovine cervical mucins have an anti-inflammatory …

[Function of glycochains in virus infection].

Influenza A virus (IAV) has two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acids at the terminals of glycochains on the host cell surface as virus receptors. NA shows sialidase activity, which cleaves sialic acids from the terminals of glycochains. A new subtype (antigenicities of HA and NA) of IAV for humans has pandemic potential. We investigated the functions of HA and NA in IAV replication and pandemic potential in terms of glycoscience. We found that the sialidase activity of pandemic IAV had low pH stability, which enhanced IAV replication. It i…

Synthesis and glycosylation of fibronectin in hepatocytes from vitamin A-deficient rats.

Recent work from our laboratory (Kim and Wolf, J Biol Chem 262:365-371, 1987) has shown increased uptake of labeled amino acids into fibrone … y oligosaccharide structures. Selective enzymatic removal of sialic acid showed that +A.FN had both sialic acids in an alpha 2----3 linkage, whereas -A.FN apparently had one alpha 2----3 and one alpha 2----6-linked sialic acid. The borotritide experiments allowed us to calculate that +A.FN appeared to have 5 oligosaccharide chains per FN monomer, whereas the - …

Novel biallelic GNE variants identified in a patient with chronic thrombocytopenia without any symptoms of myopathy.

GNE encodes a rate-limiting enzyme that regulates the biosynthesis of a sialic acid precursor. As sialic acids are critical for the platelet membrane and muscle fibers, GNE variants cause GNE-related thrombocytopenia and GNE-related myopathy. Here, we report a neonate with thrombocytopenia that initially met the criteria for neonatal allo-immune thrombocytopenia (NAIT) but was resistant to treatments and then revealed novel biallelic heterozygous GNE variants without any symptoms of myopathy when diagnosed. NAIT was initially diagnosed due to alloantibodies against HPA5 and its mismatch betwee…

Spatial localization of avian and human influenza A virus receptors in male and female bovine reproductive tissues.

Highly pathogenic avian influenza virus (HPAIV) of the H5N1 type has recently emerged as a major concern in livestock, with widespread outbreaks now confirmed in U.S. dairy cattle. This raises critical questions about the susceptibility of bovine reproductive tissues to viral entry, replication, and potential transmission. Influenza A viruses (IAV) initiate infection through hemagglutinin (HA) binding to host cell surface sialic acid residues, avian-adapted strains preferentially bind α2,3-linked sialic acids, while human-adapted strains bind α2,6-linked residues. This study aimed to character…

Полисиозная кислота сдерживает воспалительное созревание моноцитов.

Сиалистические кислоты широко распределены моносакаридами в центральной нервной системе (СНС), где они в основном встречаются в качестве конечной сиалевой кислоты, а также в ди-, олиго- и полисиалистических формах на гликокаликсе, что в совокупности способствует развитию, устойчивости и долгосрочной целостности СНК. Было продемонстрировано, что для модуляции иммунной реакции иммуноглобулиновых рецепторов (Siglec) с помощью α2,8-связанных полисиаловых кислот, используется сиалистическая кислота, связывающая иммунную реакцию. В этом исследовании мюрин и моноциты человека подвергались воздействию

Совпадение в аннотации оригинала
Sialic acids are widely distributed monosaccharides in the central nervous system (CNS), where they are predominantly found as terminal sialic acid residues, as well as in di-, oligo-, and polysialic forms on the glycocalyx, collectively contributing to the development, resilience, and long-term integrity of the CNS. Harnessing sialic acid-binding immunoglob…

Progressive multifocal leukoencephalopathy (PML) development is associated with mutations in JC virus capsid protein VP1 that change its receptor specificity.

Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-deriv

Specific Analysis of α-2,3-Sialylated N-Glycan Linkage Isomers by Microchip Capillary Electrophoresis-Mass Spectrometry.

Sialylated N-glycan isomers with α-2,3 and α-2,6 linkages play crucial and distinctive roles in diverse physiological and pathological processes. Changes of α-2,3-linked sialic acids in sialylated N-glycans are especially important in monitoring the initiation and progression of diseases. However, the specific analysis of α-2,3-sialylated N-glycan linkage isomers remains challenging due to their extremely low abundance and technical limitations in separation and detection. Herein, we designed an integrated strategy that combines linkage-specific derivatization and a charge-sensitive separation…

Alterations in surface carbohydrates and in some functional properties of liver lysosomal membrane in vitamin A-deficient rat.

A significant decrease in total carbohydrates and particularly in mannose, galactose and sialic acid has been observed in vitamin A-deficient rat liver lysosomal membrane. These alterations adversely affect the membrane permeability and structure-linked latency of the lysosomal enzymes. Significant reduction in the pH-dependent in vitro binding of the lysosomal arylsulfatase B to the highly purified membrane has been observed in vitamin A deficiency. This is attributed to the decrease in electro-negativity, mainly due to the observed reduction in negatively-charged sialic acid residues on the

Syrian hamster is a valuable animal model for evaluating the transmissibility of emerging influenza viruses.

Multiple influenza virus subtypes actively circulate in nature, and assessing their transmissibility provides crucial information for predicting their pandemic potential and for pandemic preparedness. Here, we evaluated the receptor-binding preferences, replication, and transmission of five different influenza viruses (i.e. CA/07-H1N1, GX/18-H1N1, CK/S2283-H3N8, CK/SD007-H9N2, and DK/35-H5N1) in Syrian hamsters. Receptor-binding analysis using biolayer interferometry revealed that four of these viruses preferentially bound α2,6-linked sialic acid receptors, whereas the H5N1 virus bound to α2,3