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Digestion of human milk fat in healthy infants.
He, X, McClorry, S, Hernell, O, Lönnerdal, B, Slupsky, CM
Nutrition research (New York, N.Y.). 2020;:15-29
Abstract
Lipid digestion is critical for infant development, and yet, the interconnection between lipid digestion and the microbiota is largely understudied. This review focuses on digestion of the human milk fat globule and summarizes the current understanding of the mechanisms underlying this process in infants. We first discuss the partial hydrolysis of milk fat in the stomach, which leads to rearrangement of lipid droplets, creating a lipid-water interface necessary for duodenal lipolysis. In the first few months of life, secretion of pancreatic triglyceride lipase, phospholipase A2, and bile salts is immature. The dominant lipases aiding fat digestion in the newborn small intestine are therefore pancreatic lipase-related protein 2 and bile salt-stimulated lipase from both the exocrine pancreas and milk. We summarize the interaction between ionic fatty acids and cations to form insoluble fatty acid soaps and how it is influenced by various factors, including cation availability, pH, and bile salt concentration, as well as saturation and chain length of fatty acids. We further argue that the formation of the soap complex does not contribute to lipid bioavailability. Next, the possible roles that the gut microbiota plays in lipid digestion and absorption are discussed. Finally, we provide a perspective on how the manufacturing process of infant formula and dairy products may alter the physical properties and structure of lipid droplets, thereby altering the rate of lipolysis.
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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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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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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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Protein secretion and the endoplasmic reticulum.
Benham, AM
Cold Spring Harbor perspectives in biology. 2012;(8):a012872
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In a complex multicellular organism, different cell types engage in specialist functions, and as a result, the secretory output of cells and tissues varies widely. Whereas some quiescent cell types secrete minor amounts of proteins, tissues like the pancreas, producing insulin and other hormones, and mature B cells, producing antibodies, place a great demand on their endoplasmic reticulum (ER). Our understanding of how protein secretion in general is controlled in the ER is now quite sophisticated. However, there remain gaps in our knowledge, particularly when applying insight gained from model systems to the more complex situations found in vivo. This article describes recent advances in our understanding of the ER and its role in preparing proteins for secretion, with an emphasis on glycoprotein quality control and pathways of disulfide bond formation.
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Myocilin polymorphisms and primary open-angle glaucoma: a systematic review and meta-analysis.
Cheng, JW, Cheng, SW, Ma, XY, Cai, JP, Li, Y, Lu, GC, Wei, RL
PloS one. 2012;(9):e46632
Abstract
BACKGROUND Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations. METHODS A meta-analysis of 32 published genetic association case-control studies, which examined the relation between POAG and the R46X, R76K, Y347Y, T353I, and Q368X polymorphisms of the myocilin gene, was carried out. RESULTS In meta-analysis, significant associations were observed between POAG risk and two myocilin polymorphisms with summarized odds ratio of 4.68 (95%CI, 2.02-10.85) for Q368X and 2.17 (95% CI, 1.32-3.57) for T353I. Both Q368X and T353I were significantly associated with high-tension glaucoma, with summarized odds ratio of 4.26 (1.69, 10.73) and 2.26 (1.37-3.72). In Westerners, significant association was observed for Q368X mutation (odds ratio, 5.17; 95% CI, 2.16-12.40). However, in Asians it was for T353I (odds ratio, 2.17; 95% CI, 1.32-3.57). CONCLUSIONS There is strong evidence that myocilin polymorphisms are associated with POAG susceptibility, and the prevalence of myocilin mutations might be ethnicity-dependent in Caucasians for Q368X and in Asians for T353I.
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Mass spectrometry based targeted protein quantification: methods and applications.
Pan, S, Aebersold, R, Chen, R, Rush, J, Goodlett, DR, McIntosh, MW, Zhang, J, Brentnall, TA
Journal of proteome research. 2009;(2):787-97
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The recent advance in technology for mass spectrometry-based targeted protein quantification has opened new avenues for a broad range of proteomic applications in clinical research. The major breakthroughs are highlighted by the capability of using a "universal" approach to perform quantitative assays for a wide spectrum of proteins with minimum restrictions and the ease of assembling multiplex detections in a single measurement. The quantitative approach relies on the use of synthetic stable isotope labeled peptides or proteins, which precisely mimic their endogenous counterparts and act as internal standards to quantify the corresponding candidate proteins. This report reviews recently developed platform technologies for emerging applications of clinical proteomics and biomarker development.