Non-invasive Biomarkers For Early Diagnosis Research Articles

Intestinal metabolomics in premature infants with late-onset sepsis

We aimed to investigate the characteristics of intestinal metabolomics and non-invasive biomarkers for early diagnosis of late-onset sepsis (LOS) by analyzing gut metabolites in preterm infants with LOS. We collected stool samples from septic and healthy preterm infants for analysis by liquid chromatography–mass spectrometry. 123 different metabolites were identified and 13 pathways were mainly involved. Glycine, serine, and threonine metabolism; glyoxylate and dicarboxylic acid metabolism; glutathione metabolism; primary bile acid biosynthesis; steroid synthesis; pentose and glucuronic acid interconversion may be involved in the pathogenesis of LOS in preterm infants. The significant changes of N-Methyldopamine, cellulose, glycine, gamma-Glutamyltryptophan, N-Ribosylnicotinamide and 1alpha, 25-dihydroxycholecalciferol showed specific diagnostic values and as non-invasive biomarkers for LOS.

A new methodology to reveal potential nucleic acid modifications associated with the risk of endometrial cancer through dispersive solid-phase extraction coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV.

Nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. Previous studies have shown that the early development of endometrial cancer (EC) is often accompanied by changes in methylation levels of related genes, and the expression of related proteins that regulate reactive oxygen species (ROS) shows significant differences in EC cells and tissues. However, it has not been reported whether nucleic acid modifications related to methylation or ROS can serve as biomarkers for EC. Accurate quantification of these nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine are complicated. In this study, a novel dispersive solid-phase extraction (DSPE) method based on chitosan-carbon nanotube-Al2O3 (CS-CNT-Al2O3) has been established for the analysis of 5-hydroxymethyluracil (5mU), 5-methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-formyl-2'-deoxycytidine (5-fdC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in EC patient urine samples coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV. Firstly, the synthesis of the CS-CNT-Al2O3 nanocomposite was conducted by a sono-coprecipitation method and was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and Fourier transform infrared (FTIR). Under the optimal extraction conditions of DSPE, we successfully quantified 5mU, 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in urine samples from 37 EC patients and 39 healthy controls. The results showed that there were significant differences in the levels of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in EC patients compared to the healthy control group. The receiver operator characteristic (ROC) curve analysis was carried out to evaluate the potential of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG to distinguish EC patients from healthy volunteers. The area under the curve (AUC) for 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG was 0.7412, 0.667, 0.8438, and 0.7981, respectively. It indicated that 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG had certain potential in distinguishing between EC patients and healthy volunteers and they could act as potential non-invasive biomarkers for early diagnosis of EC. Moreover, the present study would stimulate investigations of the effects of nucleic acid modifications on the initiation and progression of EC.

Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.

Non-invasive biomarkers for early diagnosis of pancreatic cancer risk: metabolite genomewide association study based on the KCPS-II cohort

BackgroundPancreatic cancer is a lethal disease with a high mortality rate. The difficulty of early diagnosis is one of its primary causes. Therefore, we aimed to discover non-invasive biomarkers that facilitate the early diagnosis of pancreatic cancer risk.MethodsThe study subjects were randomly selected from the Korean Cancer Prevention Study-II and matched by age, sex, and blood collection point [pancreatic cancer incidence (n = 128) vs. control (n = 256)]. The baseline serum samples were analyzed by non-targeted metabolomics, and XGBoost was used to select significant metabolites related to pancreatic cancer incidence. Genomewide association study for the selected metabolites discovered valuable single nucleotide polymorphisms (SNPs). Moderation and mediation analysis were conducted to explore the variables related to pancreatic cancer risk.ResultsEleven discriminant metabolites were selected by applying a cut-off of 4.0 in XGBoost. Five SNP presented significance in metabolite-GWAS (p ≤ 5 × 10–6) and logistic regression analysis. Among them, the pair metabolite of rs2370981, rs55870181, and rs72805402 displayed a different network pattern with clinical/biochemical indicators on comparison with allelic carrier and non-carrier. In addition, we demonstrated the indirect effect of rs59519100 on pancreatic cancer risk mediated by γ-glutamyl tyrosine, which affects the smoking status. The predictive ability for pancreatic cancer on the model using five SNPs and four pair metabolites with the conventional risk factors was the highest (AUC: 0.738 [0.661–0.815]).ConclusionsSignatures involving metabolites and SNPs discovered in the present research may be closely associated with the pathogenesis of pancreatic cancer and for use as predictive biomarkers allowing early pancreatic cancer diagnosis and therapy.

Retinal Changes in Parkinson's Disease: A Non-invasive Biomarker for Early Diagnosis.

Parkinson's disease (PD) is caused due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) which leads to the depletion of dopamine in the body. The lack of dopamine is mainly due to aggregation of misfolded α-synuclein which causes motor impairment in PD. Dopamine is also required for normal retinal function and the light-dark vision cycle. Misfolded α-synuclein present in inner retinal layers causes vision-associated problems in PD patients. Hence, individuals with PD also experience structural and functional changes in the retina. Mutation in LRRK2, PARK2, PARK7, PINK1, or SNCA genes and mitochondria dysfunction also play a role in the pathophysiology of PD. In this review, we discussed the different etiologies which lead to PD and future prospects of employing non-invasive techniques and retinal changes to diagnose the onset of PD earlier.

Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells.

Cysteine dioxygenase 1 (CDO1) is frequently methylated, and its expression is decreased in many human cancers including breast cancer (BC). However, the functional and mechanistic aspects of CDO1 inactivation in BC are poorly understood, and the diagnostic significance of serum CDO1 methylation remains unclear. We performed bioinformatics analysis of publicly available databases and employed MassARRAY EpiTYPER methylation sequencing technology to identify differentially methylated sites in the CDO1 promoter of BC tissues compared to normal adjacent tissues (NATs). Subsequently, we developed a MethyLight assay using specific primers and probes for these CpG sites to detect the percentage of methylated reference (PMR) of the CDO1 promoter. Furthermore, both LentiCRISPR/dCas9-Tet1CD-based CDO1-targeted demethylation system and CDO1 overexpression strategy were utilized to detect the function and underlying mechanism of CDO1 in BC. Finally, the early diagnostic value of CDO1 as a methylation biomarker in BC serum was evaluated. CDO1 promoter was hypermethylated in BC tissues, which was related to poor prognosis (p<.05). The CRISPR/dCas9-based targeted demethylation system significantly reduced the PMR of CDO1 promotor and increased CDO1 expression in BC cells. Consequently, this leads to suppression of cell proliferation, migration and invasion. Additionally, we found that CDO1 exerted a tumour suppressor effect by inhibiting the cell cycle, promoting cell apoptosis and ferroptosis. Furthermore, we employed the MethyLight to detect CDO1 PMR in BC serum, and we discovered that serum CDO1 methylation was an effective non-invasive biomarker for early diagnosis of BC. CDO1 is hypermethylated and acts as a tumour suppressor gene in BC. Epigenetic editing of abnormal CDO1 methylation could have a crucial role in the clinical treatment and prognosis of BC. Additionally, serum CDO1 methylation holds promise as a valuable biomarker for the early diagnosis and management of BC.

Immobilization-free dual-aptamer-based photoelectrochemical platform for ultrasensitive exosome assay

Exosomes, involved in cancer-specific biological processes, are promising noninvasive biomarkers for early diagnosis of cancer. Herein, an immobilization-free dual-aptamer-based photoelectrochemical (PEC) biosensor was proposed for the enrichment and quantification of cancer exosome based on photoactive bismuch oxyiodide/gold/cadmium sulfide (BiOI/Au/CdS) composites, nucleic acid-based recognition and signal amplification. In this biosensor, the recognition of exosome by two aptamers would trigger the deoxyribonucleotidyl transferase (TdT) enzyme-aided polymerization, leading to the enrichment of alkaline phosphatase (ALP) on Fe3O4 surface. After magnetic separation, ALP could catalyze the generation of ascorbic acid (AA) as electron donor and initiate the following redox cycle reaction for further signal amplification. Furthermore, all the above processes were performed in solution, the recognition and signal amplification efficiency would be superior than the heterogeneous strategy owing to the avoidance of steric hindrance effect. As a result, the proposed PEC biosensor was capable of enriching and detecting of cancer exosomes with high sensitivity and selectivity. The linear range of the biosensor was from 1.0 × 102 particles·μL−1 to 1.0 × 106 particles·μL−1 and the detection limit was estimated to be 21 particles·μL−1. Therefore, the proposed PEC biosensor holds great promise in quantifying tumor exosome for nondestructive early clinical cancer diagnosis and various other bioassay applications.

Transfer RNA-derived fragments as novel biomarkers of the onset and progression of gastric cancer.

Gastric cancer (GC) is a particularly malignant disease; thus, early diagnosis and treatment are especially important. Transfer RNA-derived small RNAs (tsRNAs) have been implicated in the onset and progression of various cancers. Therefore, the aim of this study was to explore the role of tRF-18-79MP9P04 (previously named tRF-5026a) in the onset and progression of GC. Expression levels of tRF-18-79MP9P04 were quantified in gastric mucosa specimens of healthy controls and plasma samples of patients with different stages of GC. The results showed that plasma levels of tRF-18-79MP9P04 were significantly decreased in the early and advanced stages of GC. The results of the nucleocytoplasmic separation assay found that tRF-18-79MP9P04 was localized in the nuclei of GC cells. High-throughput transcriptome sequencing identified genes regulated by tRF-18-79MP9P04 in GC cells, and the function of tRF-18-79MP9P04 was predicted by bioinformatics. Collectively, the findings of this study suggest that tRF-18-79MP9P04 would be useful as non-invasive biomarker for early diagnosis of GC and is related to cornification, the type I interferon signaling pathway, RNA polymerase II activities, and DNA binding.

Hypomethylation of Tumor necrosis factor-like cytokine 1A(TL1A) and its decoy receptor 3 expressive level increase has diagnostic value in HBV-associated cirrhosis

For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the clinical significance of TL1A, which is a susceptibility gene for hepatic fibrosis, and DR3 in the development of cirrhosis and fibrosis. We analyzed the expression of TL1A, DR3, and other inflammatory cytokines associated with liver fibrosis in serum and PBMCs in 200 patients.TL1A methylation level was lower in patients with HBV-associated LC than in the other groups. In addition, the mRNA level and serum of TL1A and DR3 expression levels were found to increase in the LC. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis. These results indicate that TL1A and DR3 may play an important role in the pathogenesis of LC and TL1A methylation levels may serve as a noninvasive biomarker for early diagnosis and progression of LC.

Diagnostic accuracy of circular RNA for diabetes Mellitus: a systematic review and diagnostic Meta-analysis

BackgroundThis study aimed to investigate the pooled diagnostic ability of circular RNA (circRNA) molecules for diabetes mellitus.MethodsWe searched PubMed, Scopus, and Web of Science for relevant studies. A total of 2070 participants, including 775 diabetic patients and 1295 healthy individuals, from five studies were included in this meta-analysis. True positive, true negative, false positive, and false negative data were extracted to calculate pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristics curve. The Deeks’ funnel plot was applied for publication bias assessment, Cochran’s Q test and I2 index were applied for inter-study heterogeneity assessment. Besides, a subgroup analysis was performed for determining the source of heterogeneity between studies. P value < 0.05 was considered significance. All analysis were done by STATA version 14.ResultsCircRNA presented a sensitivity of 76% (95% confidence interval [95%CI]: 66-84%), specificity of 77% (95%CI: 58-89%), positive LR of 3.25 (95%CI: 1.69–6.23), negative LR of 0.31 (95%CI: 0.21–0.46), DOR of 10.41 (95%CI: 4.26–25.41), and AUC of 0.82 (95%CI: 0.79–0.85) for diabetes mellitus detection. More specifically, hsa_circ_0054633 showed a sensitivity of 67% (95%CI: 53-81%) and a specificity of 82% (95%CI: 63-100%).ConclusionCircRNAs show highly accurate diagnostic capability for type 2 diabetes mellitus and gestational diabetes mellitus. High sensitivity of circRNAs introduces them as potential noninvasive biomarkers for early diagnosis of diabetes mellitus and their high specificity introduces them as potential therapeutic targets by regulation of their expression.

Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers.

Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The five-year survival rate of EC is less than 20%. Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular profile of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body fluids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC.

The Emerging Role of Circular RNA Homeodomain Interacting Protein Kinase 3 and Circular RNA 0046367 through Wnt/Beta-Catenin Pathway on the Pathogenesis of Nonalcoholic Steatohepatitis in Egyptian Patients.

Non-alcoholic fatty liver disease is a major problem worldwide that needs non-invasive biomarkers for early diagnosis and treatment response assessment. We aimed to assess the correlation between circRNA-HIPK3 and miRNA-29a expression and its role as miRNA-29a sponge, as well as the correlation between circRNA-0046367 and miRNA-34a expression and its role as miRNA-34a sponge and their effect on regulation of the Wnt/β catenin pathway, which may provide a new target for treatment of non-alcoholic steatohepatitis. the research was performed on 110 participants: group (I): fifty-five healthy donors served as controls and group (II): fifty-five patients with fatty liver pattern on abdominal ultrasound. Lipid profile and liver functions were assessed. RT-PCR was performed to assess the RNAs: circRNA-HIPK3, circRNA-0046367, miRNA-29a, miRNA-34a and Wnt mRNA gene expression. ELISA was performed to determine β-catenin protein levels. miRNA-34a and circRNA-HIPK3 expression were significantly greater, while miRNA-29a and circRNA-0046367 expression were significantly less, in patients than in controls. Wnt/β-catenin regulated by miRNA-29a and miRNA-34a showed a significant decrease that leads to its abnormal effect on lipid metabolism. our results imply that miRNA-29a can be investigated as a target for circRNA-HIPK3, while miRNA-34a can be investigated as a target for circRNA-0046367, and that circRNA-HIPK3 and circRNA-0046367 may have emerging roles that can affect the pathogenesis of nonalcoholic steatohepatitis through the Wnt/β-catenin pathway and thus be used as therapeutic targets for the disease.

Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis.

Acute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment. Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway-T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene. A total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples. Our study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.

Photoelectrochemical biosensor based on FTO modified with BiVO4 film and gold nanoparticles for detection of miRNA-25 biomarker and single-base mismatch

MicroRNAs (miRNAs) are of great important as non-invasive biomarkers for early diagnosis of cancer. Based on this, a photoelectrochemical (PEC) biosensor was developed to measure the concentration of microRNA-25 (miR-25), as a lung cancer biomarker. To fabricate the PEC biosensor, a suitable amino modified probe was immobilized on the surface of a florin tin oxide (FTO) electrode modified with bismuth vanadate (BiVO4) film and gold nanoparticles (AuNPs). The fabrication steps of the PEC biosensor were monitored by electrochemical impedance spectroscopy (EIS) and PEC measurements. The results indicate that the combination of BiVO4 film and AuNPs enhances the separation of photogenerated electrons and increase the photocurrent signal. Upon hybridization of the probe immobilized on the biosensor with miR-25, the photocurrent is significantly decreased. This current decrease is attributed to the fact that the hybridization processes blocks the electrode surface by creating a steric hindrance and by decrease the diffusion of AA to the electrode surface, it reduces the AA oxidation and subsequently decreases the capture photogenerated holes. Therefore, the amount of photocurrent decrease is dependent on the miR-25 concentration, and this PEC biosensor can be used to measure miR-25. The developed PEC biosensor shows good sensitivity for the determination of miR-25 in the linear concentration range of 1.0 × 10−14 M to 1.0 × 10−6 M with a detection limit of 3.4 fM, under optimal conditions. Using this biosensor, miR-25 can be detected from a non-complementary and one base mismatch sequence. It is also possible to measure miR-25 in human serum samples with satisfactory results using the PEC biosensor.

Early Diagnosis of Coronary Artery Disease by Inflammatory Biomarkers of Atherosclerosis in Patients with Angina.

Early diagnosis of coronary artery disease (CAD) in patients with chest pain is a challenge. Currently diagnosis of CAD is confirmed by coronary angiography, which is invasive and not easily available in developing countries. Therefore, it is imperative to establish noninvasive biomarker for early diagnosis of CAD in patients with angina and determine the diagnostic accuracy of inflammatory biomarkers of atherosclerosis in comparison to angiography and correlate with severity of CAD in patients with angina. Diagnostic accuracy study was carried out in tertiary care hospitals, Rawalpindi, Pakistan. Total of 58 patients aged 55.24 ± 11.61 years, with chest pain and troponin-I -ve, having coronary artery stenosis ≥50% were included as cases of CAD and 55 subjects having stenosis <50% were included as controls. Nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were analyzed on immunoassay analyzers. The receiver operating characteristic curve analysis revealed significant (P < 0.05) high area under curve (95% confidence interval) with sensitivity and specificity of NF-κB 0.76 (0.65-0.85), 73% and 65%; TNF-α 0.72 (0.61-0.81), 71% and 69%; IL-6 0.62 (0.52-0.71), 64% and 53% and hs-CRP 0.62 (0.52-0.71), and 53% and 56% in CAD patients compared to controls. There was significant positive correlation between NF-κB (r = 0.44), TNF-α (r = 0.37), IL-6 (r = 0.23), and hs-CRP (r = 0.23) with severity of CAD by Gensini score. The inflammatory biomarkers, especially NF-κB and TNF-α, have highest diagnostic accuracy and indicate severity of atherosclerosis in patients with angina. These markers may be used as noninvasive biomarkers to exclude healthy individuals before undergoing angiography.

Exosomal Non-Coding RNAs: New Insights into the Biology of Hepatocellular Carcinoma.

Exosomes, extracellular vesicles with a diameter of 40 to 160 nm, are among the smallest extracellular vesicles released by cells. They deliver different cargoes, including proteins, DNAs, and RNAs, and facilitate communication between cells to coordinate a variety of physiological and pathological functions. Hepatocellular carcinoma (HCC) is the sixth common malignant tumor and the fourth leading cause of cancer-related death worldwide. Its molecular mechanism remains largely unknown, and there is a lack of reliable and noninvasive biomarkers for early diagnosis and prognosis prediction. Mounting evidence has shown that exosomes carry a variety of ncRNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which play critical roles in the occurrence and progression of HCC. In this review, we summarize the recent findings of exosomal miRNAs, lncRNAs, and circRNAs in HCC from their impact on the development of HCC to their potential applications in the diagnosis and treatment of HCC.

Possible relation between expression of circulating microRNA and plasma cytokine levels in cases of pulmonary tuberculosis.

Tuberculosis (TB) is a life-threatening infection and early diagnosis is critical for treatment and prevention of transmission. There is evidence of correlation between miRNA expression and cytokine regulation during TB infection. The aim of this study was to determine the relationship between expression levels of miRNAs in plasma and cytokine levels as a potential biomarker for genetic predisposition and/or early diagnosis of TB infection. The expression levels of 86 miRNAs were examined in plasma samples of 44 TB patients and 44 healthy controls by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation, South San Francisco, CA, USA) system. The levels of plasma TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, and IL-12/P40 were examined with ELISA. We identified dysregulation of 18 miRNAs which included upregulation of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-100-5p, miR-106b-5p, miR-128-3p, miR-133a-3p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-205-5p, miR-210-3p, and miR-296-5p, and downregulation of miR-15b-5p, miR-16-5p, and miR-25-3p in plasma samples of patients with pulmonary TB (p < 0.05). A significant correlation between the expression levels of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-15b-5p, miR-100-5p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-210-3p and cytokine levels of TNF-α, IFN-γ, IL-1β, IL-8 and IL-10 was identified (p < 0.05). We demonstrated that altered expression levels of plasma miRNAs consistent with immunological response have the potential to serve as non-invasive biomarkers for early diagnosis of pulmonary TB. Additional investigations with larger sample sizes will be required to confirm our findings and to determine if miRNAs can be possible targets for TB management strategies.

Artificial intelligence in ophthalmology: an insight into neurodegenerative disease.

The aging world population accounts for the increasing prevalence of neurodegenerative diseases such as Alzheimer's and Parkinson's which carry a significant health and economic burden. There is therefore a need for sensitive and specific noninvasive biomarkers for early diagnosis and monitoring. Advances in retinal and optic nerve multimodal imaging as well as the development of artificial intelligence deep learning systems (AI-DLS) have heralded a number of promising advances of which ophthalmologists are at the forefront. The association among retinal vascular, nerve fiber layer, and macular findings in neurodegenerative disease is well established. In order to optimize the use of these ophthalmic parameters as biomarkers, validated AI-DLS are required to ensure clinical efficacy and reliability. Varied image acquisition methods and protocols as well as variability in neurogenerative disease diagnosis compromise the robustness of ground truths that are paramount to developing high-quality training datasets. In order to produce effective AI-DLS for the diagnosis and monitoring of neurodegenerative disease, multicenter international collaboration is required to prospectively produce large inclusive datasets, acquired through standardized methods and protocols. With a uniform approach, the efficacy of resultant clinical applications will be maximized.

Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer

BackgroundMajority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC.MethodsWe performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies.ResultsWe identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation.ConclusionsWe identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.