Potential Non-invasive Biomarkers Research Articles

Machine learning-based detection of immune-mediated diseases from genome-wide cell-free DNA sequencing datasets

The early detection of tissue and organ damage associated with autoimmune diseases (AID) has been identified as key to improve long-term survival, but non-invasive biomarkers are lacking. Elevated cell-free DNA (cfDNA) levels have been observed in AID and inflammatory bowel disease (IBD), prompting interest to use cfDNA as a potential non-invasive diagnostic and prognostic biomarker. Despite these known disease-related changes in concentration, it remains impossible to identify AID and IBD patients through cfDNA analysis alone. By using unsupervised clustering on large sets of shallow whole-genome sequencing (sWGS) cfDNA data, we uncover AID- and IBD-specific genome-wide patterns in plasma cfDNA in both the obstetric and general AID and IBD populations. We demonstrate that pregnant women with AID and IBD have higher odds of receiving inconclusive non-invasive prenatal screening (NIPS) results. Supervised learning of the genome-wide patterns allows AID prediction with 50% sensitivity at 95% specificity. Importantly, the method has the potential to identify pregnant women with AID during routine NIPS. Since AID pregnancies have an increased risk of severe complications, early recognition or detection of new-onset AID can redirect pregnancy management and limit potential adverse events. This method opens up new avenues for screening, diagnosis and monitoring of AID and IBD.

Association between lncRNAs in plasma exosomes and diabetic retinopathy.

BackgroundLong noncoding RNA (lncRNA) in plasma exosomes is a potential non-invasive diagnostic biomarker for diabetic retinopathy (DR). However, the changes in plasma exosomal lncRNAs and diagnostic relevance in patients with DR patients remain unclear.MethodsA case–control study with type 2 diabetes mellitus (T2DM) and patients with comorbid DR were enrolled, and their clinical information and blood samples were collected. Plasma exosomes were extracted, and the relative expression levels of representative differentially expressed exosomal lncRNAs were determined. A logistic regression model was used to analyze the relationships of DR with relative lncRNA expression and DR-related factors, and receiver operating characteristic (ROC) curve analysis was used to evaluate the value of exosomal lncRNAs for DR diagnosis.ResultsSixty-two patients with T2DM and sixty-two patients with DR were matched by age, sex, and disease duration. The fasting blood glucose concentration, glycosylated hemoglobin level (HbA1c), and relative expression of the plasma exosomal lncRNA DLX6-AS1 were significantly higher in the DR group than in the T2DM group, whereas the 2-h C-peptide concentration and relative expression of the lncRNAs PRINS and FAM190A-3 were lower in the DR group. After adjusting for relevant confounders, the fasting blood glucose concentration, HbA1c level, 2-h C-peptide concentration, and relative expression of lncRNA DLX6-AS1, PRINS, and FAM190A-3 were found to be associated with DR. Both DLX6-AS1 [area under the curve (AUC): 0.658 (0.562–0.754)], PRINS [AUC: 0.798 (0.722–0.873)], and FAM190A-3 [AUC: 0.603 (0.503-0.702)] expression had predictive value for DR diagnosis. The combination of DLX6-AS1 and PRINS yielded an AUC of 0.813 (0.740–0.886). In males, the combination of DLX6-AS1 and PRINS yielded an AUC of 0.860 (0.780–0.940).ConclusionThe fasting blood glucose concentration, HbA1c level, and exosomal DLX6-AS1 expression were identified as risk factors for DR, whereas the 2-h C-peptide concentration and exosomal PRINS and FAM190A-3 were identified as protective against DR. The combination of exosomal DLX6-AS1 and PRINS had good diagnostic value for DR in the general population and males. More attention should be paid to the role of exosomal PRINS expression as a predictive and diagnostic DR biomarker in females.

Relationship between Coronary Arterial Geometry and the Presence and Extend of Atherosclerotic Plaque Burden: A Review Discussing Methodology and Findings in the Era of Cardiac Computed Tomography Angiography.

Coronary artery disease (CAD) represents a modern pandemic associated with significant morbidity and mortality. The multi-faceted pathogenesis of this entity has long been investigated, highlighting the contribution of systemic factors such as hyperlipidemia and hypertension. Nevertheless, recent research has drawn attention to the importance of geometrical features of coronary vasculature on the complexity and vulnerability of coronary atherosclerosis. Various parameters have been investigated so far, including vessel-length, coronary artery volume index, cross-sectional area, curvature, and tortuosity, using primarily invasive coronary angiography (ICA) and recently non-invasive cardiac computed tomography angiography (CCTA). It is clear that there is correlation between geometrical parameters and both the haemodynamic alterations augmenting the atherosclerosis-prone environment and the extent of plaque burden. The purpose of this review is to discuss the currently available literature regarding this issue and propose a potential non-invasive imaging biomarker, the geometric risk score, which could be of importance to allow the early detection of individuals at increased risk of developing CAD.

MiR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

BackgroundChildhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients.ResultsThe expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model.ConclusionsmiR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

Urinary exosomal long non-coding RNAs as noninvasive biomarkers for diagnosis of bladder cancer by RNA sequencing

IntroductionCystoscopy is the standard methodology for diagnosis of bladder cancer (BC), but it is invasive and relatively expensive. Previous studies have found that urinary exosomal long non-coding RNAs (lncRNAs) may act as potential noninvasive biomarkers for diagnosis. Here we identified urinary exosomal lncRNAs that are differentially expressed between BC and controls, and established a panel for diagnosis of BC.MethodsWe performed RNA sequencing in urinary exosomes of 7 controls and 7 patients, subsequently the differentially expressed lncRNAs were detected in training cohort (50 controls and 50 patients) and validation cohort (43 controls and 43 patients). The diagnostic power of lncRNAs for BC was calculated by the area under curve (AUC). The panel for diagnosis of BC was calculated by logistic regression.ResultsThe results of RNA sequencing in urinary exosomes showed that 240 upregulated lncRNAs and 275 downregulated lncRNAs were differentially expressed. The levels of MKLN1-AS, TALAM1, TTN-AS1 and UCA1 in BC patients were higher than that in controls in the training and validation cohort by real-time PCR. Using logistic regression, with the combination of these four lncRNAs and NMP22, we identified a panel of five parameters capable of classifying BC patients versus controls on the basis of the training cohort (AUC=0.850). Moreover, the performance of the panel exhibited better performance than either single parameter in the validation cohort.ConclusionCollectively, this study confirmed the diagnostic value of lncRNAs for BC by high-throughout urinary exosomal RNA sequencing.

Impact of microbiota-immunity axis in pancreatic cancer management.

The microbiota impact on human diseases is well-known, and a growing body of literature is providing evidence about the complex interplay between microbiota-immune system-human physiology/pathology, including cancers. Together with the defined risk factors (e.g., smoke habits, diet, diabetes, and obesity), the oral, gut, biliary, and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system. Unfortunately, a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured. Given the poor pancreatic cancer prognosis, complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential non-invasive biomarkers, new therapeutic targets, and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.

Efficacy prediction of acupuncture in treatment of moderate-to-severe allergic rhinitis based on miRNA expression profile

To investigate the differential characteristics of plasma mircoRNA (miRNA) expression profile in the patients of moderate-to-severe allergic rhinitis treated with acupuncture so as to provide an index for screening the potential biomarkers of acupuncture efficacy. Of 33 patients of moderate-to-severe allergic rhinitis underwent acupuncture, the superior efficacy patients (superior efficacy group, 3 cases) and the inferior efficacy patients (inferior efficacy group, 3 cases) were selected. Using human miRNA microarray technology, the differences in plasma miRNA expression before and after treatment were analyzed in the patients of two groups. Besides, 10 cases of superior efficacy and 10 cases of inferior one were selected respectively among the patients of moderate-to-severe allergic rhinitis treated with same acupuncture regimen; and the real-time PCR was used to validate miRNAs of differential expression determined by microarray technology. The bioinformatics analysis was performed for miRNAs of significant differences in expression so as to predict the potential functional target genes, and then, the predicted target genes were annotated in reference with the databases of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). Before treatment, there were 51 miRNAs of differential expression between two groups, of which, the expression levels of 26 miRNAs were up-regulated and those of 25 miRNAs were down-regulated. Compared with before treatment, 33 miRNAs presented differential expression in the superior efficacy group after treatment. The results of real-time PCR showed that the expression levels of hsa-miR-126-3p, hsa-miR-15a-5p, hsa-miR-494-3p and hsa-miR-574-5p were consistent with the results of microarray analysis in tendency. GO/KEGG analysis indicated that miRNAs with significant differences of expression between two groups were involved in regulating various biological processes, molecular functions and signaling pathways. Plasma miRNA-mediated biological processes may be associated with the efficacy response of acupuncture in treatment of moderate-to-severe allergic rhinitis. Plasma miRNAs of differential expression may be the potential non-invasive biomarkers to predict the effectiveness of acupuncture on moderate-to-severe allergic rhinitis.

Comparison of brain microstructure alterations on diffusion kurtosis imaging among Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals.

ObjectiveOur study aimed to explore the differences in brain microstructure in patients with Alzheimer’s disease (AD) and with mild cognitive impairment (MCI) and in individuals with normal cognition using diffusion kurtosis imaging (DKI) to identify a potential non-invasive biomarker of AD.Materials and methodsA total of 61 subjects were included in our study, including 20 subjects diagnosed with AD, 21 patients diagnosed with amnestic MCI, and 20 cognitively normal individuals. We acquired magnetic resonance imaging (MRI) scans, and DKI images were processed. Twelve regions of interest were drawn, and various parameters were measured and analyzed using SPSS version 11.0 software.ResultsComparative analysis showed that differences in brain regions in terms of mean diffusion (MD) and mean kurtosis (MK) between groups were the most marked. Precuneus MD, temporal MK, precuneus MK, and hippocampal MK were significantly correlated with neuropsychological test scores. Hippocampal MK showed the strongest correlation with the medial temporal lobe atrophy score (r = −0.510), and precuneus MD had the strongest correlation with the Koedam score (r = 0.463). The receiver operating curve analysis revealed that hippocampal MK exhibited better diagnostic efficacy than precuneus MD for comparisons between any group pair.ConclusionDKI is capable of detecting differences in brain microstructure between patients with AD, patients with MCI, and cognitively normal individuals. Moreover, it compensates for the deficiencies of conventional MRI in detecting pathological changes in microstructure before the appearance of macroscopic atrophy. Hippocampus MK was the most sensitive single parameter map for differentiating patients with AD, patients with MCI, and cognitively normal individuals.

Aberrant Expression of Serum MicroRNA-153 and -199a in Generalized Epilepsy and its Correlation with Drug Resistance.

Epilepsy is one of the common neurological disorders affecting approximately 50 million people worldwide. Despite the recent introduction of new antiepileptic drugs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early recognition of patients with drug-resistant epilepsy may help direct these patients to appropriate nonpharmacological treatment. The possible use of serum microRNAs (miRNAs) as noninvasive biomarkers has been explored in various brain diseases, including epilepsy. In this study, we are aiming at analyzing the expression levels of circulating miRNA-153 and miRNA-199a in patients with generalized epilepsy and their correlation with drug resistance. Our study comprised 40 patients with generalized epilepsy and 20 healthy controls. 22 patients were drug-resistant and 18 patients were drug-responsive. The expression levels of miRNA-153 and -199a in serum were analyzed using quantitative real-time polymerase chain reaction. Data analysis was done by IBM SPSS Statistics 20.0. The expression of miRNA-153 and -199a in serum was significantly downregulated in patients with generalized epilepsy compared with that of the healthy control (P < .001). Combined expression level of serum miRNA-153 and -199a had a sensitivity of 85% and a specificity of 90% in the diagnosis of generalized epilepsy. Furthermore, the expression levels of miRNA-153 and -199a were significantly decreased in drug-resistant patients compared to the drug-responsive group, and the combination of both markers gave the best results in differentiating between the two groups. We suggest that serum miRNAs-153 and -199a expression levels could be potential noninvasive biomarkers supporting the diagnosis of generalized epilepsy. Moreover, they could be used for the early detection of refractory generalized epilepsy.

Integrative analysis of circulating microRNAs and the placental transcriptome in recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a major type of pathological pregnancy that still lacks reliable early diagnosis and effective treatment. The placenta is critical to fetal development and pregnancy success because it participates in critical processes such as early embryo implantation, vascular remodeling, and immunological tolerance. RPL is associated with abnormalities in the biological behavior of placental villous trophoblasts, resulting in aberrant placental function. MicroRNAs (miRNAs) are increasingly being recognized as essential regulators of placental development, as well as potential biomarkers. In this study, plasma miRNAs and placental messenger RNAs (mRNAs) from RPL patients and normal pregnant (NP) controls were sequenced and analyzed. Compared to those in NP controls, 108 circulating miRNAs and 1199 placental mRNAs were differentially expressed in RPL samples. A total of 140 overlapping genes (overlapping between plasma miRNA target genes and actual placental disorder genes) were identified, and functional enrichment analysis showed that these genes were mainly related to cell proliferation, angiogenesis, and cell migration. The regulatory network among miRNAs, overlapping genes, and downstream biological processes was analyzed by protein–protein interactions and Cytoscape. Moreover, enriched mRNAs, which were predictive targets of the differentially expressed plasma miRNAs miR-766-5p, miR-1285-3p, and miR-520a-3p, were accordingly altered in the placenta. These results suggest that circulating miRNAs may be involved in the pathogenesis of RPL and are potential noninvasive biomarkers for RPL.

Signs of Anxiety and Salivary Copeptin Levels in Dogs Diagnosed with Separation-Related Problems in a Short Separation Test

Simple SummaryUp to 56% of the general dog population show signs of separation-related problems, a group of problems characterized by highly variable phenotypes on which research, to date, has mostly provided contradictory findings. In the present study, we analyzed the behavior and salivary concentrations of copeptin, a biologically stable biomarker of stress, in dogs with separation distress and in dogs with no problems. The animals were tested before, during and after three-minute separation from the owner, in a new environment. Dogs in the two groups differed significantly in their activity levels and stress-relief activities during the three observation phases. In addition, a different tendency in the two groups was found in salivary copeptin concentration behavior.The need for faster diagnosis and more accurate treatment decisions in separation-related problems (SRPs) in dogs is urgent, and a more precise behavioral phenotyping and the development of biomarkers may be of great value. Vasopressin could be a potential non-invasive biomarker of anxiety in dogs with SRPs, but reliable measurement of its concentration is challenging. Here, we compared the behavior and salivary concentrations of copeptin, an arginine vasopressin surrogate, in dogs with SRPs (Case group, n = 13) and with no problems (Control group, n = 15) as they were introduced to a novel environment and subjected to a short episode of separation and reunion with the owner. Dogs in the Case group had greater odds of showing locomotory or oral behaviors during the pre- and post-separation than Controls, while the odds were significantly lower during separation. They also had greater odds of being persistent in seeking attention and proximity from the stranger during reunion. Overall, dogs with SRPs were more likely to express an anxiety-like state during the entire test than Controls, with separation from the owner, and even its anticipation, possibly accounting for this group difference. Although salivary copeptin concentrations did not differ between the two groups, a different trend was detected in Cases and Controls that is worth exploring in further validation studies involving a larger sample.

Circulating ciRS-7 as a potential non-invasive biomarker for epithelial ovarian cancer: An investigative study.

BackgroundOvarian cancer (OC) is the most common malignant neoplasm of the female reproductive system in developed countries. Early detection, diagnosis and prognosis are particularly important to OC. The potential of circulating circular RNAs (circRNAs) as non-invasive biomarkers of various tumors has been especially described in recent years. The aim of this study was to explore the diagnostic and prognostic value of circulating cirRS-7 in patients with epithelial ovarian cancer (EOC).MethodsPre- and postoperative plasma samples from 111 EOC patients (47 cases with FIGO stage IA-IIB and 64 cases with FIGO stage IIB-IV) and healthy female volunteers was collected. Circulating ciRS-7 and hsa-miR-7-5p was analyzed using reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of circulating cirRS-7 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan–Meier analysis.ResultsThe preoperative expression levels of circulating ciRS-7 were increased in plasma of EOC FIGO stage I-IV patients than in the healthy controls (p < 0.001). However, the expression levels of ciRS-7 in the postoperative period were significantly lower in EOC FIGO stage IIA-IIA patients than healthy controls and EOC FIGO stage IIB-IV patients (p < 0.05, p < 0.001). The AUC of ciRS-7 for diagnosing EOC FIGO stage I-IV patients in pre-and postoperative periods was 0.90, 0.92, 0.84, 0.88, 0.58 and 0.86, respectively. Higher circulating ciRS-7 expression is associated with lymph node invasion, FIGO stage, distant metastasis, and worse overall survival (OS) of patients. Moreover, multivariate Cox analysis showed that higher circulating ciRS-7 was an independent predictor of OS in EOC FIGO stage IIB-IV patients. In addition, in plasma of EOC patients, ciRS-7 negatively correlated with has-miR-7-5p in pre-and postoperative periods (p < 0.001).ConclusionsCirculating ciRS-7 levels in plasma can be considered a potential candidate biomarker for diagnosing EOC patients. Dysregulation of ciRS-7 may participate in the molecular mechanism of EOC through hsa-miR-7-5p sponging.

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis

Purpose: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. Materials and Methods: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. Results: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells’ (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. Conclusions: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

Seminal plasma extracellular vesicles tRF-Val-AAC-010 can serve as a predictive factor of successful microdissection testicular sperm extraction in patients with non-obstructive azoospermia

BackgroundThere is a lack of biomarkers for distinguishing non-obstructive azoospermia (NOA) patients with successful sperm retrieval (Sp+) from those with failed sperm retrieval (Sp-). This study aimed to determine the potential of extracellular vesicles tRNA-derived small RNA (tsRNA) as a novel non-invasive biomarker for successful sperm retrieval by microdissection testicular sperm extraction (mTESE).MethodsThe study included 18 patients with NOA with successful sperm retrieval (Sp+) and 23 patients with NOA with failed sperm retrieval (Sp-), 15 obstructive azoospermia (OA) patients, 5 idiopathic oligospermia (IO) patients, and 12 healthy people. Seminal plasma extracellular vesicles tsRNA levels were used in a two-stage case-control study (screened by tsRNA sequencing on Illumina NextSeq instrument and validated by qRT-PCR). The bioinformatic analysis was performed to determine the role of tsRNA in the pathogenesis of non-obstructive azoospermia.ResultsTwo tsRNAs (tRF-Val-AAC-010: AUC = 0.96, specificity = 80%, sensitivity = 95%; tRF-Pro-AGG-003: AUC = 0.96, specificity = 87%, sensitivity = 95%) were found to have high predictive accuracy for distinguishing the origin of azoospermia. In addition, the extracellular vesicles tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P < 0.0001) in predicting the presence of sperm in non-obstructive azoospermia undergoing mTESE. Finally, bioinformatic analysis revealed that tRF-Val-AAC-010 were involved in spermatogenesis.ConclusionsThis study identified that the extracellular vesicles tRF-Val-AAC-010 and tRF-Pro-AGG-003 are biomarkers for the diagnosis of non-obstructive azoospermia, and that tRF-Val-AAC-010 as a potential non-invasive biomarker for predicting the presence of sperm in non-obstructive azoospermia testicular tissue.

Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing.

Objective:NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells. However, the developmental progression, transcriptomic landscape, and functional subtypes of liver NK cells are not well defined. Hepatocellular carcinoma (HCC) accounts for approximately 80% of primary liver cancer worldwide, yet the biological characteristics of NK cells in the HCC environment are unclear. Therefore, we aimed to determine these cells’ roles in tumorigenesis and prognosis.Methods:We compared the single-cell RNA sequencing profiles of NK cells purified from blood (n = 1), healthy liver tissues (n = 3), HCC tumor tissues (n = 4), and peritumor liver tissues (n = 1) to identify NK cell subsets. Furthermore, we performed bioinformatics analysis by using The Cancer Genome Atlas (TCGA) data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC.Results:Transcriptomic analysis revealed 5 NK cell subsets (L1-NK-CD56bright, L2-NK-CD56dim, L3-NK-HLA, L4-LrNK-FCGR3A, and L5-LrNK-XCL1) in the healthy liver tissues. However, the transitional L3 subset and the CXCR6+CD16+ L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues. Furthermore, 4 common prognosis-associated genes (RHOB, TALDO1, HLA-DPA1, and TKT) were significantly overexpressed in the paired tumor tissue and blood.Conclusions:Our study revealed 5 specific subsets of NK cells in healthy human liver tissues. However, only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues. The cytotoxic NK cell subsets were absent in HCC tissues. Furthermore, we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.

MiR-10 and Its Negative Correlation with Serum IL-35 Concentration and Positive Correlation with STAT5a Expression in Patients with Rheumatoid Arthritis.

Circulating free-cell miRNAs are increasingly important as potential non-invasive biomarkers due to the easy accessibility of clinical materials. Moreover, their epigenetic role may provide insight into the mechanisms of pathogenesis. Nevertheless, these aspects are mostly studied in the area of oncological diseases. Therefore, this research aimed to find the potential association of selected miRNAs in serum with the expression of Th17/Treg transcription factors and clinical features in RA patients. Accordingly, experiments was conducted on rheumatoid arthritis (RA), osteoarthritis (OA) and healthy subjects (HC). Analysis of miRNAs level in serum was performed using LNA miRNA PCR assays. mir-10 was detected only in RA patients. Furthermore, its expression was correlated with IL-35 serum concentration and the mRNA level of STAT5a in whole blood in RA. Additionally, a tendency of the raised level of miR-10 was noted in RA patients with high activity disease. miR-326 was significantly upregulated in RA patients with rheumatoid factor presence. In HC the correlation between miR-26 and IL-21 serum levels and expression of SMAD3 have been found. In OA patients, correlations between miR-126 and HIF1 expression and between miR-146 and RORc have been noted. The differential association of transcription factor expression with serum miRNA levels may be important in the diagnosis and progression of RA and OA.

Evaluation of expression CXCL8 chemokine and its relationship with oocyte maturation and embryo quality in the intracytoplasmic sperm injection method.

The present study aimed to evaluate the expression of the chemokine CXCL8 in both mRNA and protein levels in the serum, follicular fluid (FF), and cumulus cells (CCs) and its relationship with oocyte maturation and embryo quality in women undergoing intracytoplasmic sperm injection (ICSI). A total of 87 women who underwent an ICSI cycle were evaluated in two groups, including the case group (female factor infertility) and the control group (fertile). In the serum, FF, and CCs, the protein and mRNA expression of CXCL8 were measured using immunosorbent assay and Real-Time PCR, respectively. The quality and quantity of the oocytes and embryos were assessed, and the relationship of protein and mRNA CXCL8 was evaluated with oocyte maturation and embryo quality. The level of protein and mRNA of CXCL8 was significantly higher in the serum, FF, and CCs in the case group than in the control group. In the case group, the expression of mRNA and protein of CXCL8 had a significant increase in FF and CCs compared to serum; also, there was a CXCL8 protein significant increase in FF compared to CCs. The count of oocytes obtained, MII oocytes and the percentage of oocyte maturity significantly decreased in the case group. The expression of CXCL8 was inversely related to oocyte maturation, but no relationship was observed with embryo quality. The elevated concentrations of CXCL8 in the serum and FF seem to be a predictor as a potential non-invasive biomarker for the oocyte maturation outcome in women with different causes of female factor infertility.

FRI202 - Multiplexed digital spatial protein profiling reveals potential non-invasive biomarkers to predict advanced fibrosis

FRI202 - Multiplexed digital spatial protein profiling reveals potential non-invasive biomarkers to predict advanced fibrosis

Vascular endothelial growth factor (VEGF): A Noninvasive Biomarker for the Prediction of Invasive Placentation

Background: Abnormally invasive placentation (AIP) is a life-threatening obstetric condition which is responsible for massive obstetric hemorrhage that is a leading cause of pregnancy related death. The optimal management of this complication requires a valid antenatal diagnostic tool other than Doppler ultrasound (US). Of these, a handful of laboratory markers have been so far used for the antenatal detection of invasive placentation. Objective: This study sought to establish whether low maternal serum VEGF is related to AIP. Materials and Methods: Over a period of 0ne year, a case control study was conducted in the department of Obstetrics and Gynecology at AL-Yarmouk Teaching Hospital, including 90 pregnant ladies with gestational age 28 week and beyond, of whom 43 cases were diagnosed with placenta accrete using Doppler ultrasound and 47 healthy pregnant ladies with normal placentation. The serum vascular endothelial growth factor was measured by Enzyme-linked immunosorbent assays in all participants, and each individual was followed up regarding intraoperative and postoperative outcomes. Results: a significantly lower serum vascular endothelial growth factor level was found in women having placenta accrete when compared with control group with (P LESS THAN 0.001). At a level of 95.85 pg/ml, serum vascular endothelial growth factor was 90% sensitive, 64% specific in the identification of cases with placenta accrete spectrum. Conclusion: Vascular endothelial growth factor levels may be a potential noninvasive biomarker to aid in the antepartum diagnosis of invasive placentation.

The Role of Non-Coding RNAs in the Pathogenesis of Parkinson’s Disease: Recent Advancement

Parkinson’s disease (PD) is a prevalent neurodegenerative aging disorder that manifests as motor and non-motor symptoms, and its etiopathogenesis is influenced by non-coding RNAs (ncRNAs). Signal pathway and gene sequence studies have proposed that alteration of ncRNAs is relevant to the occurrence and development of PD. Furthermore, many studies on brain tissues and body fluids from patients with PD indicate that variations in ncRNAs and their target genes could trigger or exacerbate neurodegenerative pathogenesis and serve as potential non-invasive biomarkers of PD. Numerous ncRNAs have been considered regulators of apoptosis, α-syn misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation in PD etiology, and evidence is mounting for the determination of the role of competing endogenous RNA (ceRNA) mechanisms in disease development. In this review, we discuss the current knowledge regarding the regulation and function of ncRNAs as well as ceRNA networks in PD pathogenesis, focusing on microRNAs, long ncRNAs, and circular RNAs to increase the understanding of the disease and propose potential target identification and treatment in the early stages of PD.