scholarly journals The Proteomic Signature of Intestinal Acute Rejection in the Mouse

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 23
Author(s):  
Mihai Oltean ◽  
Jasmine Bagge ◽  
George Dindelegan ◽  
Diarmuid Kenny ◽  
Antonio Molinaro ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Intestinal Transplantation ◽  
Clinical Value ◽  
Post Transplantation ◽  
Altered Expression ◽  
Non Invasive ◽  
Or Groups ◽  
Tissue Homogenates ◽  
Proteome Changes ◽  
Alteration Pattern

Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.

scholarly journals Measurements Methods for the Development of MicroRNA-Based Tests for Cancer Diagnosis

2021 ◽  
Vol 22 (3) ◽  
pp. 1176
Author(s):  
Francesca Precazzini ◽  
Simone Detassis ◽  
Andrea Selenito Imperatori ◽  
Michela Alessandra Denti ◽  
Paola Campomenosi
Keyword(s):  
Expression Profiling ◽  
Clinical Stage ◽  
Response To Therapy ◽  
Clinical Settings ◽  
Molecular Tools ◽  
Altered Expression ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Mirna Expression Profiling ◽  
Technological Limitations

Studies investigating microRNAs as potential biomarkers for cancer, immune-related diseases, or cardiac pathogenic diseases, among others, have exponentially increased in the last years. In particular, altered expression of specific miRNAs correlates with the occurrence of several diseases, making these molecules potential molecular tools for non-invasive diagnosis, prognosis, and response to therapy. Nonetheless, microRNAs are not in clinical use yet, due to inconsistencies in the literature regarding the specific miRNAs identified as biomarkers for a specific disease, which in turn can be attributed to several reasons, including lack of assay standardization and reproducibility. Technological limitations in circulating microRNAs measurement have been, to date, the biggest challenge for using these molecules in clinical settings. In this review we will discuss pre-analytical, analytical, and post-analytical challenges to address the potential technical biases and patient-related parameters that can have an influence and should be improved to translate miRNA biomarkers to the clinical stage. Moreover, we will describe the currently available methods for circulating miRNA expression profiling and measurement, underlining their advantages and potential pitfalls.

Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation

2016 ◽  
Vol 36 ◽  
pp. 32-41 ◽  
Author(s):  
Ane Miren Andres ◽  
Monica Santamaria ◽  
Francisco Hernandez-Oliveros ◽  
Laura Guerra ◽  
Sergio Lopez ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Intestinal Transplantation

The most useful and commonly available acute rejection surveillance strategies are routine monitoring of myocardial function and donor-specific anti-HLA Abs monitoring

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Acute Rejection ◽  
Cell Function ◽  
Clinical Symptoms ◽  
Contractile Function ◽  
Therapy Monitoring ◽  
Genomic Medicine ◽  
Non Invasive ◽  
Monitoring Tools ◽  
Immune Mediated ◽  
Routine Monitoring

Given the complexity of acute rejection (AR) pathogenesis and its vast spectrum of clinical symptoms, no methodology (invasive or non-invasive) can provide all the information needed to identify functionally and prognostically relevant AR, treatment selection, and therapy monitoring early. Only the use of EMBs in combination with non-invasive technologies and methods to detect subclinical changes in myocardial contractile function (e.g., TDI and STE), to detect alloimmune activation (e.g., IM assay, assessment of complement-activating donor-specific anti-HLA Abs (DSAbs), screening of circulating cfdDNA), and to predict the imminent risk of immune-mediated injury (e.g., assessment of complement-activating DSAbs).Searching for both ACR and AMR in all EMBs is a key prerequisite for accurate diagnosis and decision-making in individuals suspected of AR. Close non-invasive allograft surveillance to detect patients at high risk of AR, along with properly planned EMBs (depending on the particular risk profile of the patient), can improve AR surveillance while decreasing rsEMBs. Because rsEMBs are less prevalent after the first post-HTx year and largely symptom-driven diagnostic EMBs, ongoing development of comprehensive, non-invasive technology to monitor both ACR and AMR is of significant importance. This is especially helpful for detecting late subclinical AMR, which would otherwise go unreported.The most useful and commonly available AR surveillance strategies are routine monitoring of myocardial functions utilizing sensitive ECHO techniques (TDI and STE for acute subclinical dysfunction diagnosis) and DSAb monitoring. As a result, early and late use of HTx is strongly suggested. New IM technologies such as T-cell function assays and genomic medicine approaches such as GEP, circulating dd-cfdDNA screening and microRNA assessment are promising non-invasive monitoring tools for future clinical use, but it is still necessary to test the practical value of their individual or combined use for AR detection (including both ACR and AMR), not just for ACR.

scholarly journals Non-invasive electrophysiological imaging of acute rejection in a transplanted heart

EP Europace ◽  
2013 ◽  
Vol 15 (11) ◽  
pp. 1614-1614 ◽  
Author(s):  
K. A. Desouza ◽  
S. M. Joseph ◽  
Y. Rudy
Keyword(s):  
Acute Rejection ◽  
Non Invasive

MicroRNA expression in infertile men: its alterations and effects

Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 263-271 ◽  
Author(s):  
Maryam Kiani ◽  
Mohammad Salehi ◽  
Asghar Mogheiseh
Keyword(s):  
Male Infertility ◽  
Testicular Biopsy ◽  
Transcriptional Gene Silencing ◽  
Mirna Regulation ◽  
Altered Expression ◽  
Diagnostic Biomarkers ◽  
Rna Molecules ◽  
Non Invasive ◽  
Post Transcriptional Gene Silencing ◽  
Different Types

SummaryInfertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.

MO921PROGNOSTIC OUTCOMES OF TRANSPLANTED KIDNEY USING SOLUBLE  CD30 AND Β2- MICROGLOBULIN

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ahmed Abo omar ◽  
Gamal Saadi
Keyword(s):  
Acute Rejection ◽  
Graft Survival ◽  
Patient Group ◽  
The Other ◽  
Kidney Graft ◽  
Post Transplantation ◽  
Β2 Microglobulin ◽  
Transplanted Kidney ◽  
Successful Transplantation

Abstract Background and Aims Transplantation is the first successful modality of renal replacement therapy (RRT) for irreversible chronic kidney disease (CKD; stage 5). Identifying additional factors associated with poor long-term prognosis after transplantation may provide clues regarding the pathophysiological mechanisms involved in allograft failure and identify high-risk patients who may benefit from additional monitoring or interventions. Successful kidney transplantation results in a substantial decrease in β2M levels, but a delayed decrease or increasing levels after transplantation may serve as a marker of acute rejection or inflammation. Several reports show that elevated sCD30 levels, pre and post transplantation are associated with a poor prognosis for long term kidney graft survival. These studies found higher CD30 levels in allograft recipients and a good predictor of impending acute rejection. The aim of the work is to study the prognostic outcomes of transplanted kidney using CD30 and β2-Microglobulin Method prospective study was conducted in nephrology unit –internal medicine department at Tanta and Kasr El Ainy university ,over 1 year.20 patients subjected to primary Tx.participated in this study.Cd30 and β2M.at day -1,2weeks and 3 months,with clinical follow up after 1 year to detect graft survival Results At day -1,level of cd30 was higher in rejection group than the other patient group.2 weeks post transplantation ,level of cd30 was higher in rejection group than the other patient group and at 3 monthes post transplantation level of cd30 was higher in rejection group than the other patient group,and these differences are statistically highly significant.(p values :0.003 ,0.005 and 0.002 respectively) Successful transplantation leads to significant decrease in serum cd30 at 2 weeks post tx.(P1 <0.005) and at 3 monthes post tx. (P1<0.001) although in rejection group, significant decrease in cd30 was at 2 weeks post tx.only(P1<0.005) and at 3 monthes serum cd30 began to rise again with( P1 0.157). At day -1,level of β2microglobulin was higher in rejection group than the other patient groupwith statistically significant difference (p. 0.01).2 weeks post transplantation ,level of β2microglobulin was higher in rejection group than the other patient groupbut statistically not significant(p. 0.18 ) and at 3 monthes post transplantation level of β2microglobulin was higher in rejection group than the other patient group but statistically non significant(p. 0.18 ). Successful transplantation leads to significant decrease in serum β2microglobulin at 2 weeks post tx.(P1 <0.002) and at 3 monthes post tx. (P1<0.001) although in rejection group ,significant decrease in β2microglobulin was at 3 monthes post tx.only(P1<0.005) and at 2 weeks no significant decrease(p1 0.15) Conclusion pre transplantation high Cd30 and β2M is associated with poor outcome.failure of decrease of cd30 and β2M post Tx. also associated with poor outcome or infection. Successful transplantation leads to significant decrease in serum cd30 and β2M. which can be used as predictors of graft survival with better sensitivity and specificity than serum creatinin.

Sign in / Sign up

Export Citation Format

Share Document