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1.
Pulmonary manifestations in Niemann-Pick type C disease with mutations in NPC2 gene: case report and review of literature.
Sheth, J, Joseph, JJ, Shah, K, Muranjan, M, Mistri, M, Sheth, F
BMC medical genetics. 2017;(1):5
Abstract
BACKGROUND Niemann-Pick disease type C (NPC) is an inherited metabolic disorder; due to defect in cellular cholesterol trafficking. It is clinically a heterogeneous disease with variable age of onset with multiple organ systems being involved. NPC1 gene is involved in 95% cases where as remaining ~5% cases are linked with NPC2 gene. CASE PRESENTATION Case-1, a 14-months-old female presented with recurrent respiratory distress, failure to thrive and hepatosplenomegaly. Lung biopsy was suggestive of alveolar proteinosis and liver biopsy confirmed foamy macrophages. Molecular analysis revealed homozygous mutation c.141C > A in exon 2 of NPC2 gene. Case-2, a 3-year-old male presented with dyspnoea and hepatomegaly noticed at 1 year of age. HRCT-scan of thoracic region showed consolidation with mediastinal lymphadenopathy. Broncho-alveolar lavage revealed moderate amount of foamy macrophages and bone marrow examination detected foam cells. Homozygous T > C transition in intron 1 of the NPC2 gene was identified. CONCLUSION Our study demonstrates that NPC2 can present in early years of life with pulmonary complications like alveolar proteinosis and hepatosplenomegaly or hepatomegaly due to mutation in NPC2 gene. An early suspicion will help clinicians to clinch its diagnosis, management and genetic counselling.
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Protein glycosylation in viral hepatitis-related HCC: Characterization of heterogeneity, biological roles, and clinical implications.
Zhang, S, Cao, X, Gao, Q, Liu, Y
Cancer letters. 2017;:64-70
Abstract
Protein glycosylation is one of the most frequent and well-known posttranslational modifications, playing important roles in physiopathological processes. Glycosylation is catalyzed by enzymatic additions of heterogeneous glycans with specific linkage of monosaccharides and, in a preformed fashion, to specific amino acids within glycoproteins. Altered glycan macroheterogeneity and microheterogeneity have been reported in glycoproteins produced mainly by the liver, facilitating tumorigenesis, progression, and metastasis. Characterizing the heterogeneity and biological functions of glycans in liver diseases would lead to a better understanding of the molecular pathogenesis of liver damage and cancer, providing novel diagnostic, prognostic, and therapeutic clues. Technical advances in glycoproteomics and glycomics have allowed a more comprehensive and deeper understanding of disease-related glycosylation events. Here, we briefly review the structural diversity of glycans in viral hepatitis -related hepatocellular carcinoma, discuss their roles in regulating the initiation and development of liver cancer, and introduce potential clinical applications.
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The plant secretory pathway for the trafficking of cell wall polysaccharides and glycoproteins.
Kim, SJ, Brandizzi, F
Glycobiology. 2016;(9):940-949
Abstract
Plant endomembranes are required for the biosynthesis and secretion of complex cell wall matrix polysaccharides, glycoproteins and proteoglycans. To define the biochemical roadmap that guides the synthesis and deposition of these cell wall components it is first necessary to outline the localization of the biosynthetic and modifying enzymes involved, as well as the distribution of the intermediate and final constituents of the cell wall. Thus far, a comprehensive understanding of cell wall matrix components has been hampered by the multiplicity of trafficking routes in the secretory pathway, and the diverse biosynthetic roles of the endomembrane organelles, which may exhibit tissue and development specific features. However, the recent identification of protein complexes producing matrix polysaccharides, and those supporting the synthesis and distribution of a grass-specific hemicellulose are advancing our understanding of the functional contribution of the plant secretory pathway in cell wall biosynthesis. In this review, we provide an overview of the plant membrane trafficking routes and report on recent exciting accomplishments in the understanding of the mechanisms underlying secretion with focus on cell wall synthesis in plants.
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An update on cell surface proteins containing extensin-motifs.
Borassi, C, Sede, AR, Mecchia, MA, Salgado Salter, JD, Marzol, E, Muschietti, JP, Estevez, JM
Journal of experimental botany. 2016;(2):477-87
Abstract
In recent years it has become clear that there are several molecular links that interconnect the plant cell surface continuum, which is highly important in many biological processes such as plant growth, development, and interaction with the environment. The plant cell surface continuum can be defined as the space that contains and interlinks the cell wall, plasma membrane and cytoskeleton compartments. In this review, we provide an updated view of cell surface proteins that include modular domains with an extensin (EXT)-motif followed by a cytoplasmic kinase-like domain, known as PERKs (for proline-rich extensin-like receptor kinases); with an EXT-motif and an actin binding domain, known as formins; and with extracellular hybrid-EXTs. We focus our attention on the EXT-motifs with the short sequence Ser-Pro(3-5), which is found in several different protein contexts within the same extracellular space, highlighting a putative conserved structural and functional role. A closer understanding of the dynamic regulation of plant cell surface continuum and its relationship with the downstream signalling cascade is a crucial forthcoming challenge.
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5.
Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.
Vanier, MT, Gissen, P, Bauer, P, Coll, MJ, Burlina, A, Hendriksz, CJ, Latour, P, Goizet, C, Welford, RW, Marquardt, T, et al
Molecular genetics and metabolism. 2016;(4):244-54
Abstract
Niemann-Pick disease type C (NP-C) is a neurovisceral lysosomal cholesterol trafficking and lipid storage disorder caused by mutations in one of the two genes, NPC1 or NPC2. Diagnosis has often been a difficult task, due to the wide range in age of onset of NP-C and clinical presentation of the disease, combined with the complexity of the cell biology (filipin) laboratory testing, even in combination with genetic testing. This has led to substantial delays in diagnosis, largely depending on the access to specialist centres and the level of knowledge about NP-C of the physician in the area. In recent years, advances in mass spectrometry has allowed identification of several sensitive plasma biomarkers elevated in NP-C (e.g. cholestane-3β,5α,6β-triol, lysosphingomyelin isoforms and bile acid metabolites), which, together with the concomitant progress in molecular genetic technology, have greatly impacted the strategy of laboratory testing. Specificity of the biomarkers is currently under investigation and other pathologies are being found to also result in elevations. Molecular genetic testing also has its limitations, notably with unidentified mutations and the classification of new variants. This review is intended to increase awareness on the currently available approaches to laboratory diagnosis of NP-C, to provide an up to date, comprehensive and critical evaluation of the various techniques (cell biology, biochemical biomarkers and molecular genetics), and to briefly discuss ongoing/future developments. The use of current tests in proper combination enables a rapid and correct diagnosis in a large majority of cases. However, even with recent progress, definitive diagnosis remains challenging in some patients, for whom combined genetic/biochemical/cytochemical markers do not provide a clear answer. Expertise and reference laboratories thus remain essential, and further work is still required to fulfill unmet needs.
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What's new in hepatitis C virus infections in children?
Pawlowska, M, Domagalski, K, Pniewska, A, Smok, B, Halota, W, Tretyn, A
World journal of gastroenterology. 2015;(38):10783-9
Abstract
The number of hepatitis C virus (HCV) infection cases is relatively low in children. This low number may be connected with the lack of screening tests and the asymptomatic course of infection. Currently, mother-to-infant transmission is the most common cause of HCV infection amongst children in developed countries. It is important to introduce routine screening tests for HCV in pregnant women. The risk of vertical transmission of HCV is estimated at approximately 5% (3%-10%). Currently, we do not have HCV transmission prevention methods. Some factors could potentially be eliminated by elective caesarean section. Currently, the method of prevention of perinatal HCV infection is the early identification and effective treatment of infections in young women in the preconception period. We describe genetic tests (IL-28B single nucleotide polymorphisms) to identify children with an increased chance of spontaneous clearance or sustained virologic response achievement and vitamin D level as a potential predictor of treatment response in children. It is also important to develop non-invasive tests that can predict liver fibrosis. The existence of differences in the mechanisms leading to liver injury between children and adults creates new perspectives of action to reduce liver disease progression in children in the early years of life.
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Does intraoperative ulinastatin improve postoperative clinical outcomes in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.
He, QL, Zhong, F, Ye, F, Wei, M, Liu, WF, Li, MN, Li, QB, Huang, WQ, Sun, LB, Shu, HH
BioMed research international. 2014;:630835
Abstract
INTRODUCTION The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac surgery. METHODS RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints. RESULTS Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery. CONCLUSION Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.
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8.
Colonize, evade, flourish: how glyco-conjugates promote virulence of Helicobacter pylori.
Rubin, EJ, Trent, MS
Gut microbes. 2013;(6):439-53
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Abstract
Helicobacter pylori is an adapted gastric pathogen that colonizes the human stomach, causing severe gastritis and gastric cancer. A hallmark of infection is the ability of this organism to evade detection by the human immune system. H. pylori has evolved a number of features to achieve this, many of which involve glyco-conjugates including the lipopolysaccharide, peptidoglycan layer, glycoproteins, and glucosylated cholesterol. These major bacterial components possess unique features from those of other gram-negative organisms, including differences in structure, assembly, and modification. These defining characteristics of H. pylori glycobiology help the pathogen establish a long-lived infection by providing camouflage, modulating the host immune response, and promoting virulence mechanisms. In this way, glyco-conjugates are essential for H. pylori pathogenicity and survival, allowing it to carve out a niche in the formidable environment of the human stomach.
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Lacritin and the tear proteome as natural replacement therapy for dry eye.
Karnati, R, Laurie, DE, Laurie, GW
Experimental eye research. 2013;:39-52
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Abstract
Tear proteins are potential biomarkers, drug targets, and even biotherapeutics. As a biotherapeutic, a recombinant tear protein might physiologically rescue the ocular surface when a deficiency is detected. Such a strategy pays more attention to the natural prosecretory and protective properties of the tear film and seeks to alleviate symptoms by addressing cause, rather than the current palliative, non-specific and temporary approaches. Only a handful of tear proteins appear to be selectively downregulated in dry eye, the most common eye disease. Lacritin and lipocalin-1 are two tear proteins selectively deficient in dry eye. Both proteins influence ocular surface health. Lacritin is a prosecretory mitogen that promotes basal tearing when applied topically. Levels of active monomeric lacritin are negatively regulated by tear tissue transglutaminase, whose expression is elevated in dry eye with ocular surface inflammation. Lipocalin-1 is the master lipid sponge of the ocular surface, without which residual lipids could interfere with epithelial wetting. It also is a carrier for vitamins and steroid hormones, and is a key endonuclease. Accumulation of DNA in tears is thought to be proinflammatory. Functions of these and other tear proteins may be influenced by protein-protein interactions. Here we discuss new advances in lacritin biology and provide an overview on lipocalin-1, and newly identified members of the tear proteome.
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[Keratinisation disorders: new data].
Dereure, O
Annales de dermatologie et de venereologie. 2013;(2):150-1