scholarly journals Trichuris trichiura egg extract proteome reveals potential diagnostic targets and immunomodulators

2021 ◽  
Vol 15 (3) ◽  
pp. e0009221
Author(s):  
Katalina Cruz ◽  
Antonio Marcilla ◽  
Patrick Kelly ◽  
Michel Vandenplas ◽  
Antonio Osuna ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Immune System ◽  
Tandem Mass Spectrometry ◽  
Lipid Binding ◽  
Trichuris Trichiura ◽  
Future Research ◽  
Tandem Mass ◽  
Proteomic Approach ◽  
Life Years ◽  
Antigenic Profile

Embryonated eggs are the infectious developmental stage of Trichuris trichiura and are the primary stimulus for the immune system of the definitive host. The intestinal-dwelling T. trichiura affects an estimated 465 million people worldwide with an estimated global burden of disease of 640 000 DALYs (Disability Adjusted Life Years). In Latin America and the Caribbean, trichuriasis is the most prevalent soil transmitted helminthiasis in the region (12.3%; 95% CI). The adverse health consequences impair childhood school performance and reduce school attendance resulting in lower future wage-earning capacity. The accumulation of the long-term effects translates into poverty promoting sequelae and a cycle of impoverishment. Each infective T. trichiura egg carries the antigens needed to face the immune system with a wide variety of proteins present in the shell, larvae’s surface, and the accompanying fluid that contains their excretions/secretions. We used a proteomic approach with tandem mass spectrometry to investigate the proteome of soluble non-embryonated egg extracts of T. trichiura obtained from naturally infected African green monkeys (Chlorocebus sabaeus). A total of 231 proteins were identified, 168 of them with known molecular functions. The proteome revealed common proteins families which are known to play roles in energy and metabolism; the cytoskeleton, muscle and motility; proteolysis; signaling; the stress response and detoxification; transcription and translation; and lipid binding and transport. In addition to the study of the T. trichiura non-embryonated egg proteome, the antigenic profile of the T. trichiura non-embryonated egg and female soluble proteins against serum antibodies from C. sabaeus naturally infected with trichuriasis was investigated. We used an immunoproteomic approach by Western blot and tandem mass spectrometry from the corresponding SDS-PAGE gels. Vitellogenin N and VWD and DUF1943 domain containing protein, poly-cysteine and histidine tailed protein isoform 2, heat shock protein 70, glyceraldehyde-3-phosphate dehydrogenase, actin, and enolase, were among the potential immunoactive proteins. To our knowledge, this is the first study on the T. trichiura non-embryonated egg proteome as a novel source of information on potential targets for immunodiagnostics and immunomodulators from a neglected tropical disease. This initial list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) can be used in future research on the immunobiology and pathogenesis of human trichuriasis and the treatment of human intestinal immune-related diseases.

scholarly journals Proteomic Analysis Of Trichuris Trichiura Egg Extract Reveals Potential Immunomodulators And Diagnostic Targets

2020 ◽  
Author(s):  
K. Cruz ◽  
A. Marcilla ◽  
P. Kelly ◽  
M. Vandenplas ◽  
A. Osuna ◽  
...  
Keyword(s):  
Immune System ◽  
Intestinal Parasite ◽  
Lipid Binding ◽  
Trichuris Trichiura ◽  
Proteomic Approach ◽  
Egg Extract ◽  
Sds Page ◽  
Protein Isoform ◽  
Antigenic Profile ◽  
Direct Life Cycle

Abstract Background: Trichuris trichiura embryonated eggs are the infectious developmental stage and the first signal to the immune system of the definitive host. Each infective T. trichiura egg carries the antigens needed to challenge the immune system with a wide variety of proteins present in the shell, larvae’s surface, and the accompanying fluid that contains their excretions/secretions. The parasite eggs constitute the first antigenic stimuli to evoke the host response to this intestinal parasite with direct life cycle and enteric development.Methods: The soluble egg extract of T. trichiura obtained from naturally infected African green monkeys (Chlorocebus sabaeus) was investigated using a proteomic approach by mass spectrometry. The antigenic profile of the egg soluble proteins against sera IgG from C. sabaeus with trichuriasis was also investigated by Western blot and LC-MS/MS from the corresponding SDS-PAGE gel.Results: A total of 231 proteins were accurately identified, 168 with known molecular functions. The proteome of the egg lysate revealed common protein families including energy and metabolism; cytoskeleton, motility and muscle; proteolysis; signaling; stress and detoxification; transcription and translation and; lipid binding and transport. Vitellogenin N and VWD and DUF1943 domain containing protein, Poly-cysteine and histidine tailed protein isoform 2, Heat shock protein 70, Glyceraldehyde-3-phosphate dehydrogenase, Actin and Enolase, were among the potential immunoactive proteins. Conclusions: To our knowledge, this study represents the first attempt to identify the proteome of the T. trichiura egg extract as a novel source of immunomodulators and targets for immunodiagnosis able to contribute to the treatment of human autoimmune diseases and to the control of this neglected disease.

scholarly journals Chemical Contaminants in Raw and Pasteurized Human Milk

2018 ◽  
Vol 34 (2) ◽  
pp. 340-349 ◽  
Author(s):  
Jennifer C. Hartle ◽  
Ronald S. Cohen ◽  
Pauline Sakamoto ◽  
Dana Boyd Barr ◽  
Suzan L. Carmichael
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Human Milk ◽  
Polybrominated Diphenyl Ethers ◽  
Future Research ◽  
Tandem Mass ◽  
Chemical Contamination ◽  
Chemical Contaminants ◽  
Chromatography Tandem Mass Spectrometry ◽  
Phthalate Metabolite

Background: Environmental contaminants ranging from legacy chemicals like p,p’-dichlorodiphenyltrichloroethane (DDT) to emerging chemicals like phthalates are ubiquitous. Research aims/questions: This research aims to examine the presence and co-occurrence of contaminants in human milk and effects of pasteurization on human milk chemical contaminants. Methods: We analyzed human milk donated by 21 women to a milk bank for 23 chemicals, including the persistent organic pollutants (POPs) polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) isomers that are known to sequester in adipose tissue, along with the current-use and nonpersistent pesticides chlorpyrifos and permethrin, phthalates, and bisphenol A (BPA). Human milk was analyzed raw and pasteurized for these chemicals using gas chromatography–tandem mass spectrometry for the POPs and high-performance liquid chromatography–tandem mass spectrometry for non-POPs. Results: Within the different chemical classes, PBDE47, PCB153, ppDDE, and MEHHP (phthalate metabolite) had the highest median concentrations and were observed in all samples. We also observed chlorpyrifos and BPA in all samples and permethrin in 90% of the samples tested. Only two chemicals, chlorpyrifos and permethrin, were susceptible to substantial degradation from pasteurization, a standard method for processing donated human milk. Conclusion: We detected 19 of 23 chemicals in all of our prepasteurized milk and 18 of 23 chemicals in all of our pasteurized milk. Pasteurization did not affect the presence of most of the chemicals. Future research should continue to explore human milk for potential chemical contamination and as a means to surveil exposures among women and children.

scholarly journals Protein profiling of sickle cell versus control RBC core membrane skeletons by ICAT technology and tandem mass spectrometry

2006 ◽  
Vol 11 (3) ◽  
Author(s):  
Jose Chou ◽  
Pankaj Choudhary ◽  
Steven Goodman
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Sickle Cell ◽  
Membrane Skeleton ◽  
Protein Profiling ◽  
Tandem Mass ◽  
Proteomic Approach ◽  
Significant Difference ◽  
The Mean ◽  
Cell Versus

AbstractA proteomic approach using a cleavable ICAT reagent and nano-LC ESI tandem mass spectrometry was used to perform protein profiling of core RBC membrane skeleton proteins between sickle cell patients (SS) and controls (AA), and determine the efficacy of this technology. The data was validated through Peptide/Protein Prophet and protein ratios were calculated through ASAPratio. Through an ANOVA test, it was determined that there is no significant difference in the mean ratios from control populations (AA1/AA2) and sickle cell versus control populations (AA/SS). The mean ratios were not significantly different from 1.0 in either comparison for the core skeleton proteins (α spectrin, β spectrin, band 4.1 and actin). On the natural-log scale, the variation (standard deviation) of the method was determined to be 14.1% and the variation contributed by the samples was 13.8% which together give a total variation of 19.7% in the ratios.

Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: Outcome and cost–utility analysis

2021 ◽  
pp. 096914132110216
Author(s):  
Zixuan Zhao ◽  
Chi Chen ◽  
Xueshan Sun ◽  
Duo Zhou ◽  
Xinwen Huang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Metabolic Diseases ◽  
Cost Benefit Analysis ◽  
Cost Utility ◽  
Acid Oxidation ◽  
Cost Ratio ◽  
Tandem Mass ◽  
Life Years

Objectives Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit–cost ratio (BCR), cost–utility ratio (CUR) and incremental cost–utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. Methods The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009–2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost–benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. Results Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders ( n = 276), then fatty acid oxidation disorders ( n = 248), followed by organic acidaemias ( n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ –768,428.76/QALY, and the BCR was 6.09. Conclusions NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.

scholarly journals Proteomics Profiles of CD34+ Cells in Bone Marrow of Patients with Severe Aplastic Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5159-5159 ◽  
Author(s):  
Zonghong Shao ◽  
Weiwei Qi ◽  
Rong Fu
Keyword(s):  
Mass Spectrometry ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Immune System ◽  
Tandem Mass Spectrometry ◽  
Protein Modification ◽  
Tandem Mass ◽  
Cd34 Cells ◽  
Ubiquitin Proteasome ◽  
Normal Controls

Abstract Objective Application of isobaric tags for relative and absolute quantification (iTRAQ) technology, the proteins of CD34+ cells in bone marrow for patients with severe aplastic anemia (SAA) and normal controls were analyzed. To obtain differential proteomics profiles of CD34+ cells in bone marrow for SAA specificity. To preliminary screen the autoantigen which may cause immune system hyperfunction in SAA, providing a theoretical basis for further elucidating the immune pathogenesis of SAA. Methods Untreated SAA patients, remission SAA patients, as well as normal controls in Tianjin Medical University General Hospital from 2013.1 to 2014.2 were enrolled in this study. CD34+ cells in bone marrow for 29 cases of recovery SAA patients and 10 normal human were purified by immunomagnetic cell sorting, total protein were extracted and were processed enzymolysis, labeled sample by iTRAQ reagent, then analyzed the protein of sample by multidimensional liquid chromatography tandem mass spectrometry of Q Exactive, identified proteins by application of database, compared the different expression of proteins between SAA patients and normal controls, to preliminary screen the autoantigen which may cause immune system hyperfunction in SAA. Results Expression of differential proteomic profiles for CD34+ cells in SAA bone marrow were obtained. The protein confidence > 95% and identification of peptide protein false positive rate < 1% were limited, 15120 peptides and 3208 protein were identified. The Ratio of different proteins (SAA group/ normal group) greater than 2.794 and less than 0.323 and the confidence limit greater than 95% were limited , 157 different proteins with high confidence were identified, of which 54 up-regulated proteins, 103 down regulated proteins. The physiological function of proteins involved cell apoptosis, cell cycle, RNA splicing and metabolism, protein modification and transfer, the ubiquitin proteasome mediated protein degradation. Conclusions The proteome profiles of CD34+ cells in SAA bone marrow were obtained successfully, and it was proved that iTRAQ marker tandem mass spectrometry for proteome of bone marrow cells for patients with SAA was an effective method. It was found that 157 abnormal expression proteins of CD34+ cells in SAA bone marrow, the function of proteins mainly involved apoptosis, cell cycle, protein modification and transport, RNA processing and splicing, the ubiquitin proteasome system. We preliminary predicted autoantigen which may cause SAA immune "waterfall" activation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Economics of tandem mass spectrometry screening of neonatal inherited disorders

2006 ◽  
Vol 22 (3) ◽  
pp. 321-326 ◽  
Author(s):  
Abdullah Pandor ◽  
Joe Eastham ◽  
James Chilcott ◽  
Suzy Paisley ◽  
Catherine Beverley
Keyword(s):  
Mass Spectrometry ◽  
Cost Effectiveness ◽  
Tandem Mass Spectrometry ◽  
Neonatal Screening ◽  
Screening Program ◽  
Tandem Ms ◽  
Tandem Mass ◽  
Mcad Deficiency ◽  
Life Years ◽  
Neonatal Screening Program

Objectives:The aim of this study was to evaluate the cost-effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS).Methods:A systematic review of clinical efficacy evidence and cost-effectiveness modeling of screening in newborn infants within a UK National Health Service perspective was performed. Marginal costs, life-years gained, and cost-effectiveness acceptability curves are presented.Results:Substituting the use of tandem MS for existing technologies for the screening of PKU increases costs with no increase in health outcomes. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS, with an operational range of 50,000 to 60,000 specimens per system per year, would result in a mean incremental cost of −£17,298 (−£129,174, £66,434) for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 57.3 (28.0, 91.4) life-years.Conclusions:Cost-effectiveness analysis using economic modeling indicates that substituting the use of tandem MS for existing technologies for the screening of PKU alone is not economically justified. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS would be economically attractive.

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