scholarly journals Serum miR-155, miR-223, miR-17, miR-200a, miR-205, Interleukin 6, and Prostaglandins as Novel Diagnostic Markers for Endometritis in Arabian Mares

Author(s):  
Sally Ibrahim ◽  
Mohamed Hedia ◽  
Mohamed O. Taqi ◽  
Mohamed K. Derbala ◽  
karima mahmoud ◽  
...  

Abstract Background: So far the intimate link between serum microRNA (miRNA) and uterine inflammation in mares is unknown. We aimed (I) to investigate the expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 (II) and to measure the concentrations of interleukin 6 (IL-6), and prostaglandins (PGF2α& PGE2) in serum of Arabian mares with healthy and abnormal uterine status (endometritis).Methods and Results: This study was conducted on 80 Arabian mares; young (4-7 years), and old (8-14 years). These animals were divided into 48 sub-fertile including 16 young and 32 old mares suspected of endometritis and 32 fertile as control (24 young and 8 old) at stud farms. Serum samples were collected for measuring IL-6, PGF2α, and PGE2 concentrations, as well as serum miRNA isolation and qRT-PCR. Serum concentrations of IL-6, PGE2, and PGF2α were higher (P≤0.001) in mares with endometritis (young and old) compared to the control ones. Age of mares had a remarkable effect(0.001≤P≤0.01) onIL-6, PGE2, and PGF2αconcentrations. The relative abundance of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 was higher (P≤0.001) in both young and old mares with endometritis. We noticed that eca-miR-155, eca-miR-223, eca-miR-200a, and eca-miR-205 revealed higher (0.001≤P≤0.01) expression level in old than young mares with endometritis. Conclusions: To the best of our knowledge, this is the first study revealed that serum miRNA and serum inflammatory mediators (IL-6, PGE2, and PGF2α) could be used as non-invasive gold standard biomarkers, and therefore might be served as an important additional diagnostic tool for endometritis in Arabian mares.

2021 ◽  
Vol 8 (6) ◽  
pp. 98
Author(s):  
Sally Ibrahim ◽  
Mohamed Hedia ◽  
Mohamed O. Taqi ◽  
Mohamed K. Derbala ◽  
Karima Gh. M. Mahmoud ◽  
...  

So far the intimate link between serum microRNA (miRNA) and uterine inflammation in mares is unknown. We aimed (I) to investigate expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 (II) and to measure concentrations of interleukin 6 (IL-6), and prostaglandins (PGF2α and PGE2) in serum of mares with healthy and abnormal uterine status (endometritis). This study was conducted on 80 Arabian mares: young (4–7 years), and old (8–14 years). Mares were divided into 48 sub-fertile (endometritis) and 32 fertile (control) at stud farms. Serum was collected for measuring IL-6, PGF2α, and PGE2, as well as miRNA isolation and qRT-PCR. Concentrations of IL-6, PGE2, and PGF2α were higher in mares with endometritis compared to control. Age of mares had a remarkable effect on IL-6, PGE2, and PGF2α concentrations. Relative abundance of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 was higher in both young and old mares with endometritis. We noticed that eca-miR-155, eca-miR-223, eca-miR-200a, and eca-miR-205 revealed higher expression level in old than young mares with endometritis. This is the first study that has revealed the changes in cell free miRNA and serum inflammatory mediators during endometritis, and these findings could be used for a better understanding the pathophysiology mechanisms of endometritis in equine.


2020 ◽  
Vol 47 (12) ◽  
pp. 1760-1767
Author(s):  
Sarah M. Wade ◽  
Trudy McGarry ◽  
Siobhan C. Wade ◽  
Ursula Fearon ◽  
Douglas J. Veale

ObjectiveMicroRNA (miRNA) are small endogenous regulatory RNA molecules that have emerged as potential therapeutic targets and biomarkers in autoimmunity. Here, we investigated serum miRNA levels in patients with psoriatic arthritis (PsA) and further assessed a serum miRNA signature in therapeutic responder versus nonresponder PsA patients.MethodsSerum samples were collected from healthy controls (HC; n = 20) and PsA patients (n = 31), and clinical demographics were obtained. To examine circulatory miRNA in serum from HC and PsA patients, a focused immunology miRNA panel was analyzed utilizing a miRNA Fireplex assay (FirePlex Bioworks Inc.). MiRNA expression was further assessed in responders versus nonresponders according to the European League Against Rheumatism response criteria.ResultsSix miRNA (miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, miR-26a-5p, and miR-21-5p) were significantly higher in PsA compared to HC (all P < 0.05), with high specificity and sensitivity determined by receiver-operating characteristic curve analysis. Analysis of responder versus nonresponders demonstrated higher baseline levels of miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, and miR-26a-5p were associated with therapeutic response.ConclusionThis study identified a 6-serum microRNA signature that could be attractive candidates as noninvasive markers for PsA and may help to elucidate the disease pathogenesis.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5791-5791 ◽  
Author(s):  
Issa F. Khouri ◽  
Simone Anfossi ◽  
Rima M Saliba ◽  
Lisa S. St. John ◽  
Jeffrey J. Molldrem ◽  
...  

Abstract Background: Noncoding RNAs play an important role in the pathogenesis of CLL. Recent publications suggested that higher miR-155 plasma levels (above 56th percentile) were associated with a significantly lower survival rate (P= 0.0122) in CLL patients treated with conventional treatments (Ferrajoli et al. Blood 2013;122:1891). Other studies revealed that expression of miR-29b or miR-181b significantly inhibits T cell leukemia/lymphoma 1(Tcl1) oncogene (Pekarsky et al. Cancer Res 2006;66:11590) whereas high Tcl1 expression correlates with aggressive CLL phenotype showing unmutated immunoglobulin variable region genes and ZAP70 positivity. The impact of these miR expressions in CLL patients undertaking allogeneic stem cell transplantation (alloSCT) is unknown. Methods and Patients: We identified 41 patients with relapsed/refractory CLL who had received a non-myeloablative alloSCT at our center and in whom pre-transplant serum samples collected before initiating the patients’ allogeneic conditioning were available. We measured the serum expression of miR-155 as well as miR-15a/16-1 cluster, miR-29b and miR-181b. Total RNA was isolated from 100 µL of serum using the Total RNA Purification Kit. Serum miRNA levels were measured by qRT-PCR (TaqMan MicroRNA assays). The relative serum levels of miR-155, miR -15, miR-29b, miR-181b, and miR-16-1 were calculated using the equation 2−ΔCt, where ΔCt = mean CtmiRNA – mean Ctcel-miR-39, and Ct = threshold cycle. Twenty fmol of synthetic C. elegans miRNA (cel-miR-39) was spiked into each serum samples to normalize the experimental qRT-PCR data (cel-miR-39 Ct mean ± SD = 17.777± 0.628). Forty one patients were initially evaluated. Thirteen of these 41 patients were later excluded as they received alemtuzumab for graft-versus-host disease (GVHD) prophylaxis. Therefore, our analysis was limited to 28 patients who received their alloSCT between 2000-2010. Median age (range) was 59 (45-70) years. Median number of prior therapies was 3 (range, 2-8). Eleven (39%) had a beta-2 microglobulin level of >3 mg/L. Ten of 12 (83%) patients with data that could be evaluated had unmutated immunoglobulin variable-region heavy-chain gene, and 4/19 (21%) had 17p13.1 deletion. 46% of patients had refractory disease at transplantation. The proportion of patients who received a matched related and a matched unrelated donor was 68% and 32%, respectively. All patients received non-myeloablative conditioning with fludarabine, cyclophosphamide, and rituximab as previously published (Khouri et al. Cancer 2011;117:4679). GVHD prophylaxis consisted of tacrolimus and methotrexate. Results: Median (range) follow-up months was 68 (43-141). OS from the time of alloSCT was studied according to the relative expressions of miR under investigation (low, below median; high, above median). The 5-year OS rates of patients with low and high mir-155 were 63% and 50%, respectively (HR=1.6, P=0.4; Figure). No statistically significant differences were found in the other miRs studied. The 5-year OS was 57% for both the low and high miR-15a expression. The 5-year OS in low and high miR-29b and miR-181b were 52% and 61% (HR=0.8; P=0.7), and 60% and 53% (HR=1.1, P=0.9), respectively. The 5-year OS in low and high miR-16 were 43% and 71% (HR=0.4, P=0.2). Conclusions: Our preliminary results suggest that serum levels of miR-155, miR -15, miR-29b, miR-181b, and miR-16 are not a statistically significant prognostic biomarker for survival in relapsed/refractory CLL undertaking alloSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 58 (3) ◽  
pp. 610-618 ◽  
Author(s):  
Rui Liu ◽  
Xi Chen ◽  
Yiqi Du ◽  
Weiyan Yao ◽  
Lin Shen ◽  
...  

Abstract BACKGROUND Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA–based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA–based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS These data demonstrate that the 7 miRNA–based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.


2013 ◽  
Vol 7 ◽  
pp. BBI.S10501 ◽  
Author(s):  
Madhu Beta ◽  
Nalini Venkatesan ◽  
Madavan Vasudevan ◽  
Umashankar Vetrivel ◽  
Vikas Khetan ◽  
...  

Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient's serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≥ +2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≤ –2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1055
Author(s):  
Elena S. Vashukova ◽  
Polina Y. Kozyulina ◽  
Roman A. Illarionov ◽  
Natalya O. Yurkina ◽  
Olga V. Pachuliia ◽  
...  

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities.


2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii21-ii21
Author(s):  
Shumpei Onishi ◽  
Fumiyuki Yamasaki ◽  
Motoki Takano ◽  
Ushio Yonezawa ◽  
Kazuhiko Sugiyama ◽  
...  

Abstract Objective: Glioblastoma (GBM) and Primary Central Nervous System Lymphoma (PCNSL) are common intracranial malignant tumors. They sometimes present similar radiological findings and diagnoses could be difficult without surgical biopsy. For improving the current management, development of non-invasive biomarkers are desired. In this study, we explored the differently expressed circulating small noncoding RNA (sncRNA) in serum for specific diagnostic tool of GBM and PCNSL. Material & Methods: Serum samples were obtained from three groups: 1) GBM patients (N=26), 2) PCNSL patients (N=14) 3) healthy control (N=114). The total small RNAs were extracted from serum. The whole expression profiles of serum sncRNAs were measured using Next-Generation Sequencing System. We analyzed serum levels of sncRNAs (15–55 nt) in each serum samples. The difference of sncRNAs expression profile among three groups were compared. Data analysis was performed by logistic regression analysis followed by leave-one-out cross-validation (LOOCV). The accuracy of diagnostic models of sncRNAs combination were evaluated by receiver operating characteristic (ROC) analysis. Results: We created the combination models using three sncRNA in each models based on the logistic regression analysis. The model 1 (based on sncRNA-X1, X2 and X3) enabled to differentiate GBM patients form healthy control with a sensitivity of 92.3% and a specificity of 99.2% (AUC: 0.993). The model 2 (based on sncRNA-Y1, Y2 and Y3) enabled to differentiate PCNSL patients form healthy control with a sensitivity of 100% and a specificity of 93.9% (AUC: 0.984). The model 3 (based on sncRNA-Z1, Z2 and Z3) enabled to differentiate GBM patients form PCNSL patients with a sensitivity of 92.3% and a specificity of 78.6% (AUC: 0.920). Conclusion: We found three diagnostic models of serum sncRNAs as non-invasive biomarkers potentially useful for detection of GBM and PCNSL from healthy control, and for differentiation GBM from PCNSL.


Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Tibor Szarvas ◽  
Michèle J. Hoffmann ◽  
Csilla Olah ◽  
Eszter Szekely ◽  
Andras Kiss ◽  
...  

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1345
Author(s):  
Mahathir Humaidi ◽  
Wei Ping Tien ◽  
Grace Yap ◽  
Choon Rong Chua ◽  
Lee Ching Ng

Dengue diagnosis is largely dependent on clinical symptoms and routinely confirmed with laboratory detection of dengue virus in patient serum samples collected via phlebotomy. This presents a challenge to patients not amenable to venipuncture. Non-invasive methods of dengue diagnosis have the potential to enhance the current dengue detection algorithm. In this study, samples from dengue infected patients were collected between January 2012 until September 2012 and September 2013 until December 2013 in two different setups. Panel A samples (blood, urine, and saliva) were collected daily when the 39 patients were hospitalised and during their follow-up visits while Panel B samples (saliva) were collected from 23 patients during the acute stage of dengue. Using DENV PCR on Panel A, from day 2 to day 4 post fever onset, serum showed the best overall positivity followed by saliva and urine (100%/82.1%/67.9%). From day 5 until day 10 post fever onset, serum and urine had similar positivity (67.4%/61.2%), followed by saliva (51.3%). Beyond day 10 post fever onset, DENV was undetectable in sera, but urine and saliva showed 56.8% and 28.6% positivity, respectively. DENV in urine was detectable up until 32 days post fever. Panel B results showed overall sensitivity of 32.4%/36% (RNA/NS1) for DENV detection in saliva. Our results suggest that the urine-based detection method is useful especially for late dengue detection, where DENV is undetected in sera but still detectable in urine. This provides a potential tool for the physician to pick up new cases in an area where there is ongoing dengue transmission and subsequently prompt for intensified vector control activities.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.


Sign in / Sign up

Export Citation Format

Share Document