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1.
A Promising Candidate: Heparin-Binding Protein Steps onto the Stage of Sepsis Prediction.
Yang, Y, Liu, G, He, Q, Shen, J, Xu, L, Zhu, P, Zhao, M
Journal of immunology research. 2019;:7515346
Abstract
Sepsis is a systemic inflammatory response syndrome caused by infection. With high morbidity and mortality of this disease, there is a need to find early effective diagnosis and assessment methods to improve the prognosis of patients. Heparin-binding protein (HBP) is a granular protein derived from polynuclear neutrophils. The biosynthetic HBP in neutrophils is rapidly released under the stimulation of bacteria, resulting in increased vascular permeability and edema. It is reasonable to speculate that the HBP in plasma may serve as a novel diagnostic marker for sepsis, bacterial skin infection, acute bacterial meningitis, leptospirosis, protozoan parasites, and even some noncommunicable diseases. It implies that in the detection and diagnosis of sepsis, it will be possible to make relevant diagnosis through this new indicator in the future. In this review, we summarize the typical biological function of HBP and its latest research progress to provide theoretical basis for clinical prediction and diagnosis of sepsis.
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2.
Quantitative proteomic analyses in blood: A window to human health and disease.
Whittaker, K, Burgess, R, Jones, V, Yang, Y, Zhou, W, Luo, S, Wilson, J, Huang, RP
Journal of leukocyte biology. 2019;(3):759-775
Abstract
This review discusses how the measurement of proteins in blood and its components via quantitative proteomics analyses can inform health status. Various external and internal factors such as environmental conditions, genetic background, nutrition, diet, and lifestyle, chronic pathological conditions, disease state, or therapeutic intervention will be investigated and their effects on the protein profile will be shown. The resulting changes to ones' health and how this protein expression information can be used in early screening/diagnostic applications, drug discovery, precision treatment, patient management, and monitoring overall health status will also be presented.
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3.
Blood-based protein biomarkers for stroke differentiation: A systematic review.
Misra, S, Kumar, A, Kumar, P, Yadav, AK, Mohania, D, Pandit, AK, Prasad, K, Vibha, D
Proteomics. Clinical applications. 2017;(9-10)
Abstract
Computed tomography (CT) scan is the mainstay for diagnosis of stroke; but the facility of CT scan is not easily available. A blood-based biomarker approach is required to distinguish ischemic stroke (IS) from hemorrhagic stroke (HS) in pre-hospital settings.To conduct a systematic review of diagnostic utility of blood biomarkers for differential diagnosis of stroke.A comprehensive literature search was carried out till March 7, 2017 in PubMed, Cochrane, Medline, OVID, and Google Scholar databases. Methodological quality of each study was assessed using the modified Quality Assessment of Diagnostic Accuracy Studies questionnaire.Eighteen studies were identified relevant to our systematic review. Ten single biomarkers and seven panels of different biomarkers were identified which showed potential for differentiating IS and HS. Activated Protein C- Protein C Inhibitor Complex (APC-PCI) (sensitivity-96%), Glial Fibrillary Acidic Protein (GFAP) (specificity-100%) and a panel of APC-PCI & GFAP (sensitivity- 71%) and Retinol Binding Protein 4 (RBP4) & GFAP (specificity- 100%) were found to have high sensitivity and specificity for differentiating the two stroke types.Our systematic review does not recommend the use of any blood biomarker for clinical purposes yet based on the studies conducted till date.
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4.
Quality specifications for the extra-analytical phase of laboratory testing: Reference intervals and decision limits.
Ceriotti, F
Clinical biochemistry. 2017;(10-11):595-598
Abstract
Reference intervals and decision limits are a critical part of the clinical laboratory report. The evaluation of their correct use represents a tool to verify the post analytical quality. Four elements are identified as indicators. 1. The use of decision limits for lipids and glycated hemoglobin. 2. The use, whenever possible, of common reference values. 3. The presence of gender-related reference intervals for at least the following common serum measurands (besides obviously the fertility relate hormones): alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatine kinase (CK), creatinine, gamma-glutamyl transferase (GGT), IgM, ferritin, iron, transferrin, urate, red blood cells (RBC), hemoglobin (Hb) and hematocrit (Hct). 4. The presence of age-related reference intervals. The problem of specific reference intervals for elderly people is discussed, but their use is not recommended; on the contrary it is necessary the presence of pediatric age-related reference intervals at least for the following common serum measurands: ALP, amylase, creatinine, inorganic phosphate, lactate dehydrogenase, aspartate aminotransferase, urate, insulin like growth factor 1, white blood cells, RBC, Hb, Hct, alfa-fetoprotein and fertility related hormones. The lack of such reference intervals may imply significant risks for the patients.
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5.
Ceruloplasmin and other copper binding components of blood plasma and their functions: an update.
Linder, MC
Metallomics : integrated biometal science. 2016;(9):887-905
Abstract
We know that blood plasma contains many proteins and also other components that bind copper. The largest contributor to copper in the plasma is ceruloplasmin, which accounts for 40-70 percent. Apart from ceruloplasmin and albumin, most of these components have not been studied extensively, and even for ceruloplasmin and albumin, much remains to be discovered. New components with new functions, and new functions of known components are emerging, some warranting reconsideration of earlier findings. The author's laboratory has been actively involved in research on this topic. This review summarizes and updates our knowledge of the nature and functions of ceruloplasmin and the other known and emerging copper-containing molecules (principally proteins) in this fluid, to better understand how they contribute to copper homeostasis and consider their potential significance to health and disease.
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6.
Overcoming inactivation of the lung surfactant by serum proteins: a potential role for fluorocarbons?
Krafft, MP
Soft matter. 2015;(30):5982-94
Abstract
In many pulmonary conditions serum proteins interfere with the normal adsorption of components of the lung surfactant to the surface of the alveoli, resulting in lung surfactant inactivation, with potentially serious untoward consequences. Here, we review the strategies that have recently been designed in order to counteract the biophysical mechanisms of inactivation of the surfactant. One approach includes protein analogues or peptides that mimic the native proteins responsible for innate resistance to inactivation. Another perspective uses water-soluble additives, such as electrolytes and hydrophilic polymers that are prone to enhance adsorption of phospholipids. An alternative, more recent approach consists of using fluorocarbons, that is, highly hydrophobic inert compounds that were investigated for partial liquid ventilation, that modify interfacial properties and can act as carriers of exogenous lung surfactant. The latter approach that allows fluidisation of phospholipid monolayers while maintaining capacity to reach near-zero surface tension definitely warrants further investigation.
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7.
Three new players in energy regulation: preptin, adropin and irisin.
Aydin, S
Peptides. 2014;:94-110
Abstract
Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.
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8.
The composition and metabolism of large and small LDL.
Diffenderfer, MR, Schaefer, EJ
Current opinion in lipidology. 2014;(3):221-6
Abstract
PURPOSE OF REVIEW Decreased size and increased density of LDL have been associated with increased coronary heart disease (CHD) risk. Elevated plasma concentrations of small dense LDL (sdLDL) correlate with high plasma triglycerides and low HDL cholesterol levels. This review highlights recent findings about the metabolism and composition of LDL subfractions. RECENT FINDINGS The development of an automated assay has recently made possible the assessment of the CHD risk associated with sdLDL in large clinical trials and has demonstrated convincingly that sdLDL cholesterol levels are a more significant independent determinant of CHD risk than total LDL cholesterol. Metabolic studies have revealed that sdLDL particles originate through the delipidation of larger atherogenic VLDL and large LDL and from direct de novo production by the liver. Proteins associated with LDL, in addition to apolipoprotein (apo) B, include the C apolipoproteins, apoA-I, apoA-IV, apoD, apoE, apoF, apoH, apoJ, apoL-1, apoM, α-1 antitrypsin, migration inhibitory factor-related protein 8, lysosome C, prenylcysteine oxidase 1, paraoxonase 1, transthyretin, serum amyloid A4, and fibrinogen α chain. The role of the increasing number of LDL-associated proteins remains unclear; however, the data do indicate that LDL particles not only transport lipids but also carry proteins involved in inflammation and thrombosis. The sdLDL proteome in diabetic individuals differs significantly from that of larger LDL, being enriched in apoC-III. SUMMARY Progress in our understanding of the composition and metabolism of LDL subfractions strengthens the association between sdLDL and CHD risk.
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9.
Removal of protein-bound uraemic toxins by haemodialysis.
Niwa, T
Blood purification. 2013;:20-5
Abstract
Accumulating evidence suggests that protein-bound uraemic toxins play an important role in uraemic complications, especially in cardiovascular disease. Notably, protein-bound uraemic toxins such as indoxyl sulphate, p-cresyl sulphate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) have emerged as important targets of therapeutic removal. Indoxyl sulphate stimulates reactive oxygen species production in human umbilical vein endothelial cells (HUVEC) most intensely, followed by CMPF. Indoxyl sulphate and CMPF inhibit cell growth of HUVEC. Haemodialysis (HD) even with a high-flux membrane cannot efficiently remove the protein-bound uraemic toxins because of their high albumin-binding property. Especially, indoxyl sulphate, p-cresyl sulphate, and CMPF showed high protein-binding ratios (more than 95%) and low reduction rates by HD (less than 35%). Removal of indoxyl sulphate and p-cresyl sulphate can be improved to some extent by increasing the diffusion of the free forms with super-flux membrane HD, increasing the dialyzer mass transfer area coefficient and dialysate flow, haemodiafiltration, daily HD, and addition of a sorbent to dialysate. However, CMPF is more strongly bound to albumin (with a binding ratio of 99-100%) than indoxyl sulphate and p-cresyl sulphate, and cannot be removed at all by conventional HD. Uraemic toxins strongly or covalently bound to albumin such that CMPF can be removed by protein-leaking HD. Protein-leaking HD with a polymethylmethacrylate membrane BK-F dialyzer can reduce serum levels of CMPF with improvement of anaemia as well as reduce plasma levels of homocysteine, pentosidine, and inflammatory cytokines.
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10.
Nondialyzable uremic toxins.
Piroddi, M, Bartolini, D, Ciffolilli, S, Galli, F
Blood purification. 2013;:30-41
Abstract
Nondialyzable uremic toxins can be defined as solutes producing adverse biological effects that consequently to peculiar physicochemical features (mainly their large size and hydrophobic character) cannot leave the blood stream through a dialysis membrane. These are the subject of great interest for the scientific community, in that emerging evidence suggests that such uremic retention solutes may contribute a main role to the complex inflammatory and vascular comorbidity of the uremic syndrome. Treatments based on most efficient diffusive or convective protocols of dialysis and pharmacological therapies cannot prevent nor correct such clinical symptoms. Protein-bound solutes and other proteinaceous components present in excess in the uremic milieu are thus natural candidates for explaining the resistance of uremic toxicity to current regimens of therapy. Intense research is in progress to identify molecular species and mechanisms of toxicity, but the real challenge of our times is to develop innovative clinical protocols that may remove or prevent the formation/toxicity of nondialyzable uremic solutes. These include high-efficacy protein-leaking dialyzers, adsorption techniques, frequent dialysis, and pharmacological therapies. These aspects are examined in this review paper, paying particular attention to covalent posttranslational modifications of plasma proteins produced as a consequence of oxidative, nitrosative and carbonyl stress. These represent an emerging trait in the pathobiology of inflammatory and age-related disorders, deserving further consideration in chronic kidney disease.