Biomarkers For Early Diagnosis Research Articles

Identification of Novel Biomarkers for Post-Kasai Portoenterostomy in Biliary Atresia through Shotgun Proteomics Analysis

Introduction: Biliary Atresia (BA) causes neonatal cholestasis jaundice. The primary therapeutic treatment for BA is the Kasai portoenterostomy. Current diagnostic approaches for BA are imprecise and time-consuming, making early diagnosis crucial for successful treatment outcomes. Objective: This study aims to analyze proteins from Peripheral Blood Mononuclear Cells (PBMCs) obtained from children with BA compared with healthy children Methods and Study Design: We employed a large-scale, total shotgun quantitative serum proteomics approach to analyze the protein from PBMC samples from a discovery cohort. This approach allowed for the simultaneous identification and quantification of multiple proteins, enabling the detection of disease-specific protein expression patterns. The study is proteomic-based study. Results: We identified 24 proteins, by Liquid Chromatography-Mass Spectrometry (LC-MS) analysis that exhibited high discriminatory power for five subjects with BA post-Kasai operation compared to ten healthy controls. ATP2A3, LIN28B, SLC25A3, ITGB3, COX5A, and HLA-B identified proteins of upregulation were predicted to associate with BA post-Kasai operation. Discussion: Our findings highlight the utility of proteomic techniques in BA research. The identified proteomic markers offer promise for improving BA diagnostic accuracy and timeliness, leading to enhanced treatment outcomes for affected children. Conclusion: Proteomic analysis revealed a set of potential biomarkers for early and accurate diagnosis of biliary atresia. These biomarkers hold significant clinical value and have the potential to transform the management of biliary atresia by facilitating timely intervention and improving patient outcomes.

Abstract B020: DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members

Abstract Introduction: Pancreatic cancer (PC) is a devastating disease, its etiology is not fully understood, and there is a paucity of non-invasive biomarkers for early diagnosis. While DNA methylation (DNAm) holds promise, associations between DNAm and PC risk are poorly understood, especially regarding temporal changes in associations. Therefore, we aimed to evaluate potential associations between DNAm in pre-diagnostic serum on 9 genes (BNIP3, CDKN1C, CLDN4, LCN2, p16, RASSF1, SFN, SPARC, and TFPI-2) and 2 repetitive elements (Alu and LINE-1) and PC risk in a US Department of Defense cohort. Methods : The study population included 82 PC cases, diagnosed 1991 - 2007, and 229 controls individually- matched on age (within 5 years), sex, race, and serum draw time period. Cases had up to 3 pre- diagnostic serum samples. Controls had 1 serum sample collected 0-10 years before their selection date (date of case diagnosis). DNA was extracted from serum and the percentage of cytosines at a given CpG site that were methylated was quantified via Pyrosequencing. For serum samples within a time window (<2, 2-<5, and 5-10 years pre-diagnosis), we computed odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of each CpG site with PC risk (66 sites in total across all genes and repetitive elements) with conditional logistic regression models. DNAm was evaluated as both a binary variable and a continuous variable. Results : In samples collected 5-10 years before diagnosis, those with no DNAm (0% DNAm) had increased odds of PC compared to those with DNAm (>0% DNAm) in the promoter region of BNIP3 (Chr10:131982293 OR, 95% CI: 5.63, 1.16 – 27.28) and those with lower DNAm (<median) had increased odds of PC compared to those with higher DNAm (≥median) in the promoter regions of CDKN1C (Chr11:2886398 OR, 95% CI: 4.07, 1.16 – 14.31; Chr11:2886388 OR, 95% CI: 3.51, 1.24 – 9.96) and RASSF1 (Chr3:50340841 OR, 95% CI: 3.98, 1.15 – 17.45). Similarly, in samples collected 2 - <5 years before diagnosis, lower DNAm (<median) was associated with increased odds of PC compared to those with higher DNAm (≥median) in the promoter region of TFPI-2 (Chr7:93890717 OR, 95% CI: 3.82, 1.20 – 12.15). In models with DNAm as a continuous measure and in samples collected <2 years before diagnosis, a 1% increase in DNAm in the promoter region of SFN was associated with increased odds of PC (Chr1:26863188 OR, 95% CI: 1.23, 1.01 – 1.51). There was no evidence of associations between DNAm on Alu, CLDN4, LCN2, LINE-1, p16, or SPARC and PC risk. Conclusions : Our findings of increased risk of PC associated with lower DNAm on BNIP3, CDKN1C and TFPI-2 and higher DNAm on SFN genes suggest there may be molecular patterns occurring prior to PC diagnosis that could be considered further for developing non-invasive biomarkers for early diagnosis of this aggressive carcinoma. The opinions and assertions expressed herein do not reflect the official policy or position of the Uniformed Services University, the Department of Defense, or the National Cancer Institute. Citation Format: Jordan McAdam, Ruth M Pfeiffer, Alexander P Keil, Ann Meyer, Anwar E Ahmed, Dechang Chen, Jennifer Rusiecki. DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B020.

Ferroptosis in Renal Cancer Therapy: A Narrative Review of Drug Candidates.

Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer.

A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Study on serum miR-182 as a marker for diagnosis and prognosis of cervical cancer.

Cervical cancer (CC) is a common female malignancy, with a global incidence rate second only to breast cancer. To propose a new idea for early treatment and auxiliary diagnosis of CC by exploring the diagnostic and prognostic implications of serum miR-182 in CC. We enrolled 70 CC patients, 35 cervical intraepithelial neoplasia (CIN) patients and 35 healthy controls (HCs), who visited The First Affiliated Hospital of Hainan Medical College Hospital between January 2015 and April 2016. miR-182 expression was quantified by real-time quantitative PCR and compared among the three groups. The correlation of serum miR-182 expression with patients' clinical features was evaluated. The receiver operating characteristic curve (ROC) and the Kaplan-Meier method were used to evaluate the early diagnostic value and prognostic value of serum miR-182. Cox regression analysis was performed to determine serum miR-182 expression and its important role in predicting CC patients' prognosis. Serum miR-182 expression was determined to be 0.345 ± 0.094, 0.369 ± 0.076, and 0.586 ± 0.157 in CC patients, CIN patients, and HCs, respectively (P< 0.001). Serum miR-182 expression had an obvious association with lymph node metastasis and pathological differentiation (P< 0.05). The area under the ROC curve (AUC) of serum miR-182 was 0.709 (95% CI: 0.622-0.795), the critical value was 0.456, the sensitivity was 81.4%, and the specificity was 52.9%. CC patients were grouped as either the low- (miR-182 < 0.3) or high-level group (miR-182 ⩾ 0.03) based on serum miR-182 levels, and a Cox regression model of OS was established. Serum miR-182 expression was identified as a factor independently influencing CC patients' OS (P= 0.028); the death risk of the high-level group was 3.246 times that of the low-level group. Serum miR-182 expression is not only a biomarker for early diagnosis of CC, but also one of the independent factors influencing the survival and prognosis of CC patients.

Antibodies as key mediators of protection against Mycobacterium tuberculosis.

Tuberculosis (TB) is caused by infection with the bacterial pathogen Mycobacterium tuberculosis (M.tb) in the respiratory tract. There was an estimated 10.6 million people newly diagnosed with TB, and there were approximately 1.3 million deaths caused by TB in 2022. Although the global prevalence of TB has remained high for decades and is an annual leading cause of death attributed to infectious diseases, only one vaccine, Bacillus Calmette-Guérin (BCG), has been approved so far to prevent/attenuate TB disease. Correlates of protection or immunological mechanisms that are needed to control M.tb remain unknown. The protective role of antibodies after BCG vaccination has also remained largely unclear; however, recent studies have provided evidence for their involvement in protection against disease, as biomarkers for the state of infection, and as potential predictors of outcomes. Interestingly, the antibodies generated post-vaccination with BCG are linked to the activation of innate immune cascades, providing further evidence that antibody effector functions are critical for protection against respiratory pathogens such as M.tb. In this review, we aim to provide current knowledge of antibody application in TB diagnosis, prevention, and treatment. Particularly, this review will focus on 1) The role of antibodies in preventing M.tb infections through preventing Mtb adherence to epithelium, antibody-mediated phagocytosis, and antibody-mediated cellular cytotoxicity; 2) The M.tb-directed antibody response generated after vaccination and how humoral profiles with different glycosylation patterns of these antibodies are linked with protection against the disease state; and 3) How antibody-mediated immunity against M.tb can be further explored as early diagnosis biomarkers and different detection methods to combat the global M.tb burden. Broadening the paradigm of differentiated antibody profiling and antibody-based detection during TB disease progression offers new directions for diagnosis, treatment, and preventative strategies. This approach involves linking the aforementioned humoral responses with the disease state, progression, and clearance.

Transient Increases in Neural Oscillations and Motor Deficits in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD's pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between the motor symptoms of PD and transient changes in brain oscillations before and after motor tasks in different brain regions remain unclear. This study aimed to investigate neural oscillations in both healthy and PD model mice using local field potential (LFP) recordings from multiple brain regions during rest and locomotion. The histological evaluation confirmed the significant dopaminergic neuron loss in the injection side in 6-OHDA lesioned mice. Behavioral tests showed motor deficits in these mice, including impaired coordination and increased forelimb asymmetry. The LFP analysis revealed increased delta, theta, alpha, beta, and gamma band activity in 6-OHDA lesioned mice during movement, with significant increases in multiple brain regions, including the primary motor cortex (M1), caudate-putamen (CPu), subthalamic nucleus (STN), substantia nigra pars compacta (SNc), and pedunculopontine nucleus (PPN). Taken together, these results show that the motor symptoms of PD are accompanied by significant transient increases in brain oscillations, especially in the gamma band. This study provides potential biomarkers for early diagnosis and therapeutic evaluation by elucidating the relationship between specific neural oscillations and motor deficits in PD.

Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: A Multiplatform Population-Based Study

Background & AimsSteatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD. MethodsWe examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from four population-based cohort studies (Rotterdam study, ALSPAC, IRASFS, and SOL). Metabolites were assessed in the Nightingale platform (n=225 metabolites) by NMR spectroscopy and in the Metabolon platform (n=991 metabolites) by UHPLC-mass spectrometry. Serum levels of liver enzymes (ALT, AST, and GGT) were measured and SLD was diagnosed by ultrasound or CT-scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate (-FDR) < 0.05 was considered as significant threshold. ResultsSeveral metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (HDL, IDL, and small-LDL), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism. ConclusionsOur study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.

CDKN1A promotes Cis-induced AKI by inducing cytoplasmic ROS production and ferroptosis

Background and objectiveThis study focuses on investigating the role of CDKN1A in cisplatin-induced AKI (acute kidney injury, AKI) and its potential as a biomarker for early diagnosis and therapeutic intervention by integrating bioinformatics analysis, machine learning, and experimental validation. MethodsWe analyzed the GSE85957 dataset to find genes that changed between control and cisplatin-treated rats. Using bioinformatics and machine learning, we found 13 important genes related to ferroptosis and the P53 pathway. The key gene, CDKN1A, was identified using various algorithms. We then tested how reducing CDKN1A in human kidney cells affected cell health, ROS, and iron levels. We also checked how CDKN1A changes the levels of proteins linked to ferroptosis using Q-PCR and Western Blot. ResultsCDKN1A was found to negatively regulate the G1/S phase transition and was associated with ferroptosis in p53 signaling. Experiments in human renal tubular epithelial cells (HK-2) and rat NRK-52E cells showed that CDKN1A knockdown mitigated cisplatin-induced cell injury by reducing oxidative stress and ferroptosis. ConclusionOur integrated approach identified CDKN1A as a biomarker for cisplatin-induced AKI. Its regulation could be key in AKI pathogenesis, offering new therapeutic insights and aiding in early diagnosis and intervention.

Thrombospondin 2 is a tumor stemness protein marker based on the cluster analysis combined with immune infiltration in gastric cancer

Platelet reactive protein 2 (PRP2) is closely related to the characteristics of tumor stem cells. Its role in cancer development and metastasis has received increasing attention, especially its interaction with the immune microenvironment. The study used cluster analysis to extract expression data of multiple cancer types from public databases, and combined with immune infiltration analysis, to evaluate the expression level of PRP2 and its correlation with different immune cell infiltration. Bioinformatics tools were used to analyze the correlation between PRP2 and tumor stem cell markers. The results show that PRP2 is significantly upregulated in a variety of cancers and is closely related to tumor stem cell characteristics. Immunoinfiltration analysis showed that the high expression of PRP2 was associated with a significant increase in immunosuppression-related cell infiltration. Through cluster analysis, we identified the expression pattern of PRP2 in different cancer types, indicating that it may be used as a biomarker for early diagnosis and prognosis assessment, and its expression is closely related to the immune microenvironment, indicating its important role in cancer biology and potential application value in the tumor immune microenvironment.

Identification of susceptibility modules and characteristic genes to osteoarthritis by WGCNA.

The susceptibility modules and characteristic genes of patients with osteoarthritis (OA) were determined by weighted gene co-expression network analysis (WGCNA), and the role of immune cells in OA related microenvironment was analyzed. GSE98918 and GSE117999 data sets are from GEO database. R language was used to conduct difference analysis for the new data set after merging. The formation of gene co-expression network, screening of susceptibility modules and screening of core genes are all through WGCNA. GO and KEGG enrichment analyses were used for Hub genes. The characteristic genes of the disease were obtained by Lasso regression screening. SSGSEA was used to estimate immune cell abundance in sample and a series of correlation analyses were performed. WGCNA was used to form 6 gene co-expression modules. The yellow-green module is identified as the susceptible module of OA. 202 genes were identified as core genes. Finally, RHOT2, FNBP4 and NARF were identified as the characteristic genes of OA. The results showed that the characteristic genes of OA were positively correlated with plasmacytoid dendritic cells, NKT cells and immature dendritic cells, but negatively correlated with active B cells. MDSC were the most abundant immune cells in cartilage. This study identified the Hippo signaling pathway, mTOR signaling pathway, and three characteristic genes (RHOT2, FNBP4, NARF) as being associated with osteoarthritis (OA). These three genes are downregulated in the cartilage of OA patients and may serve as biomarkers for early diagnosis and targeted therapy. Proper regulation of immune cells may aid in the treatment of OA. Future research should focus on developing tools to detect these genes and exploring their therapeutic applications.

An intelligent fluorescence sensing platform based on entropy-driven toehold-mediated strand displacement cycle reaction for point-of-care testing of miRNA

BackgroundMicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications. ResultsIn this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 μM∼10 μ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment. SignificanceIn summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences.

417P EV derived miR-21 as a promising biomarker for early diagnosis and tumor activity in discrete BC subtypes: The Exobreast project

417P EV derived miR-21 as a promising biomarker for early diagnosis and tumor activity in discrete BC subtypes: The Exobreast project

Shared and unique transcriptomic signature genes and pathways among biopsy, peripheral blood mononuclear cells and bronchoalveolar lavage samples in IPF patients revealed using comparative meta-transcriptome analysis.

Idiopathic pulmonary fibrosis (IPF) affects the tissue surrounding the alveoli and occurs when the lung tissue becomes thick and stiff for unknown reasons. Clinical findings are fairly well settled, but the molecular mechanisms of IPF are still poorly known. To further our understanding, we collected publicly available transcriptome dataset from IPF cohorts, grouped them according to sampling method [bronchoalveolar lavage (BAL), biopsy, blood], and performed comparative meta-transcriptome study to (I) unravel key pathways (II), set out differences in discovered genes, pathways, and functional annotation with respect to the sampling method, and (III) find biomarkers for early diagnosis. The resulting lists are also compared with DisGeNet reported genes, earlier work, and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Several pathways are shared among BAL and biopsy samples while blood samples point to alternative pathways, indicating the noise in information obtained from these samples. Common to all sampling methods, interleukin-10 pathway and extracellular signaling pathways are pointed as further targets.

Clinical characteristics and prognosis of early diagnosed Wilson's disease: A large cohort study.

Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure. A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes. Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01). Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome.

The Role of Epigenetics in Disease Development

Epigenetics, the study of heritable changes in gene expression without alterations to the DNA sequence, plays a critical role in the development of various diseases. These epigenetic mechanisms, which include DNA methylation, histone modifications, and non-coding RNA-mediated gene silencing, regulate essential cellular processes such as differentiation, development, and tissue-specific gene expression. Environmental factors and lifestyle choices influence these epigenetic changes, often leading to disease by modifying transcriptional profiles. This paper discusses the role of epigenetics in the onset and progression of diseases like cancer and cardiovascular disorders, highlighting the potential of epigenetic biomarkers for early diagnosis and the promise of epigenetic therapies. Understanding the intricate relationship between epigenetics and disease mechanisms can open new avenues for personalized treatment strategies. Keywords: Epigenetics, DNA methylation, histone modification, disease development, cancer, cardiovascular diseases

Bioinformatics analysis of neutrophil-associated hub genes and ceRNA network construction in septic cardiomyopathy.

Septic cardiomyopathy (SCM) is a critical sepsis complication characterized by reversible cardiac depression during early septic shock. Neutrophils, integral to innate immunity, can mediate organ damage when abnormal, but their specific role in sepsis-induced myocardial damage remains elusive. Our study focuses on elucidating the role of Neutrophil-Related Genes (NRGs) in SCM, finding early diagnosis and treatment biomarkers. We identified shared differentially expressed genes (DEGs) from datasets GSE79962 and GSE44363 and pinpointed hub DEGs using the cytoHubba plugin in Cytoscape software. The Neutrophil-Related Hub Gene (NRHG) MRC1 was identified via intersecting hub DEGs with NRGs from WGCNA. We validated MRC1's abnormal expression in SCM using our data and external datasets. Furthermore, a neutrophil-related ceRNA network (AC145207.5/ miR-23a-3p/MRC1) was constructed and validated. Our findings reveal MRC1 as a potential NRHG in SCM pathogenesis, offering insights into neutrophil-mediated mechanisms in SCM and providing a novel molecular target for early diagnosis and intervention in SCM.

Advances in new biomarkers for early diagnosis of pancreatic cancer

Advances in new biomarkers for early diagnosis of pancreatic cancer

Exosomal miRNAs as Potential Biomarkers for Preeclampsia: miR-1283 Has the Highest Expression, while miR-152-3p Has the Lowest Expression

BACKGROUND: Preeclampsia management is necessary, as it is one of the leading causes of death during pregnancy. Exosomal microRNAs (miRNAs) can serve as biomarkers for early detection, diagnosis, and prognosis of preeclampsia. NanoStrings is an effective method for identifying exosomal miRNA due to their high sensitivity and ability to work with small amounts of miRNA; however, the analysis using this method for determining preeclampsia biomarker is still limited. Therefore, this study was conducted to utilize the NanoStrings method in identifying preeclampsia biomarkers related to its underlying pathophysiology.METHODS: This study involved 12 pregnant women at 20–40 weeks of gestation, including 6 preeclampsia women and 6 normotension women. The miRNAs from plasma exosomes were processed using NanoStrings method with NanoString nCounter SPRINT Profiler. Enrichment analysis of The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were performed to examine the pathophysiological pathways of preeclampsia, using the DIANA–miRPath v3.0.RESULTS: Forty-eight miRNAs were downregulated and 7 were upregulated (miR-1283, miR-613, miR-520a-3p, miR-3185, miR-556-3p, miR-1973, and miR-598-3p) in women with preeclampsia. The highest expression was observed in miR-1283 (log fold-change: 3.69) and the most lowest expression was in miR-152-3p (log fold-change: 1.41). Enrichment analysis showed that the most upregulated miRNAs pathways was estrogen signaling pathway, and the most downregulated was Hippo signaling pathways.CONCLUSION: miR-1283 has the highest expression, while and miR-152-3p has the lowest expression in preeclampsia women. These miRNAs are shown to be linked to specific pathways, shedding light on the pathophysiology of preeclampsia, and may serve as promising biomarkers.KEYWORDS: exosomes, biomarker, miRNAs, pathophysiology, preeclampsia, pregnancy