Potential Molecular Biomarkers Research Articles

IL7R, GZMA and CD8A serve as potential molecular biomarkers for sepsis based on bioinformatics analysis.

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. However, the relationship between biomarkers and sepsis remains unclear. This study aimed to find potential molecular biomarkers, which could do some help to patients with sepsis. The sepsis dataset GSE28750, GSE57065 was downloaded from the GEO database, and ten patients with or without sepsis from our hospital were admitted for RNA-seq and the differentially expressed genes (DEGs) were screened. The Metascape database was used for functional enrichment analysis and was used to found the differential gene list. Protein-protein interaction network was used and further analyzed by using Cytoscape and STRING. Logistic regression and Correlation analysis were used to find the potential molecular biomarkers. Taking the intersection of the three datasets yielded 287 differential genes. The enrichment results included Neutrophil degranulation, leukocyte activation, immune effectors process, positive regulation of immune response, regulation of leukocyte activation. The top 10 key genes of PPI connectivity were screened using cytoHubba plugin, which were KLRK1, KLRB1, IL7R, GZMA, CD27, PRF1, CD8A, CD2, IL2RB, and GZMB. All of the hub genes are higher expressed in health group of different databases. Logistic regression showed that IL7R, GZMA and CD8A proteins were analyzed and all of them were statistically significant. Correlation analysis showed that there was a statistically significant correlation between IL7R, GZMA and CD8A. KLRK1, KLRB1, IL7R, GZMA, CD27, PRF1, CD8A, CD2, IL2RB, GZMB are key genes in sepsis, which associated with the development of sepsis. However, IL7R, GZMA and CD8A may serve as the attractively potential molecular biomarkers for sepsis.

Induction chemotherapy plus chemoradiotherapy in esophageal cancer: long-term results and exploratory analyses of a randomized controlled trial.

Previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to definitive chemoradiotherapy (CRT) failed to significantly improve the response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report long-term results and exploratory analyses to further evaluate the therapeutic value of IC. Patients with previously untreated, unresectable, stage II-IVA ESCC were randomly assigned to receive IC followed by CRT or CRT alone. The relationship between tumor response to IC and long-term survival was analyzed. Baseline tumor biopsies were collected for RNA-Seq to identify patients who may benefit from IC. Eligible patients were randomized to either the IC + CRT group (n = 55) or the CRT group (n = 55). With a median follow-up of 74.9 months, the 5-year overall survival rate was 31.8% in the IC + CRT group and 29.1% in the CRT group (P =.675; HR, 0.91; 95% CI, 0.58-1.43). Similarly, no significant differences were identified in 5-year progression-free survival between groups (30.5% vs 25.5%, P =.508; HR, 0.86; 95% CI, 0.56-1.34). Patients who responded to IC had significantly better survival than nonresponders. A risk-score model incorporating 6 key genes to predict IC efficacy was also constructed. Compared with definitive CRT alone, the addition of IC before CRT still failed to demonstrate superior survival in patients with unselected ESCC, based on long-term follow-up. However, because IC responders were associated with more favorable survival, potential molecular biomarkers were identified for selection of benefit population from IC. NCT02403531.

EPCO-36. INTEGRATIVE DEEP-LEARNING AND PHARMACOGENOMIC PROFILING OF MALIGNANT GLIOMAS USING PATIENT-DERIVED TUMOR CELLS

Abstract Malignant glioma stands as a formidable cancer with limited therapeutic options due to many factors including pronounced genetic heterogeneity, the blood-brain barrier, among others. Precision medicine, tailoring treatment based on a patient’s unique molecular profiles, is a fitting approach for addressing intra- and inter-tumor heterogeneity. Previously, we have shown the advantage of using patient-derived tumor cells (PDCs) to evaluate drug efficacy across various cancer types. Unlike cancer cell lines, which significantly differ from primary tumors, PDCs capture the molecular features of primary tumors, showing predictive clinical responses in a retrospective study. Building on these encouraging results, we have expanded PDC-based drug screening to specifically target malignant gliomas. We have established an initial cohort of over 500 malignant glioma PDCs (~ 370 patients) and screened more than 100 drugs. We have complemented our cohort with molecular profiles, including genomic and transcriptomic data to infer the potential pharmacogenomic associations of malignant gliomas. We constructed a multi-modal deep-learning model that seamlessly integrates molecular features and drug structure to predict the drug sensitivity. By employing an explainable machine learning method, we retrospectively analyzed the model to investigate the potential molecular biomarkers and their contribution to drug sensitivity. Collectively, our study demonstrates the efficacy of using patient-derived tumor cells (PDCs) combined with deep-learning models to predict drug sensitivity in malignant gliomas. This integrative approach can potentially refine personalized treatment strategies and improve clinical outcomes for glioma patients.

Erythrocytic α-Synuclein in Parkinson's Disease and Progressive Supranuclear Palsy-A Pilot Study.

Background/Objectives: The current research examines the accuracy of α-synuclein in RBCs as a diagnostic biomarker for PD and PSP, despite their distinct molecular etiologies. Methods: We used ELISA to measure total, oligomeric, and p129-α-synuclein levels in erythrocytes from 8 PSP patients, 19 PD patients, and 18 healthy controls (HCs). The classification performances of RBC α-synuclein levels were investigated by receiver operator characteristic (ROC) curve. We also evaluated a possible correlation between RBC α-synuclein level and the biological and clinical features of our cohorts. Results: RBC total α-synuclein was higher in PSP patients compared to both PD patients and HCs, achieving good classification performance (AUC: 0.853) in distinguishing PSP patients from PD patients, with a sensitivity of 100% and a specificity of 70.6%; moreover, the levels of this biomarker positively correlated with disease severity in PSP group. Regarding oligomeric α-synuclein and p129-α-synuclein, the latter was slightly increased in RBCs from PSP patients compared to HCs, but no correlations were detected. Conclusions: Although these findings need to be confirmed in larger studies, our pilot work suggests that RBC total α-synuclein may represent a potential molecular biomarker for the differential diagnosis and clinical staging of PSP.

Sperm acrosome-associated 1 (SPACA1) mRNA and protein molecules deficiency indicate low fertility and semen quality of Bali bulls (Bos sondaicus)

Molecular-based biomarkers are believed to be more accurate in determining bulls' fertility and sperm's various fertility characteristics. The sperm acrosome-associated 1 (SPACA1) molecule, located in the anterior acrosomal and equatorial segments of the sperm head, is thought to be related to the function of binding and fusion between sperm and oocyte. This study aims to analyze the association of SPACA1 mRNA and protein with the fertility rate and semen quality of Bali bulls (Bos sondaicus) and assess its potential as a potential molecular biomarker determining bull fertility and sperm quality. Frozen semen from 20 Bali bulls was used in the research, which was then divided into two groups: high (HF) and low fertility (LF). SPACA1 mRNA abundance was analyzed using qRT-PCR, and SPACA1 protein abundance was analyzed using EIA. The semen quality parameters analyzed were motility (CASA), plasma membrane integrity (HOS test), sperm head morphology abnormalities (William staining), sperm viability (SYBR 14-PI), sperm capacitation (CTC assay), and sperm acrosome integrity (FITC-PNA). The results showed that there was a significant difference (P < 0.05) between high fertility (HF) and low fertility (LF) bulls, both in the abundance of SPACA1 at the mRNA, protein, and semen quality levels. Overall, the correlation test results showed a close relationship (P < 0.01) between the abundance of SPACA1 mRNA and protein with field fertility and various semen quality parameters tested in the study. A low level of SPACA1 molecules indicates low fertility and semen quality in Bali bulls. The SPACA1 molecule has the potential to be developed through further research to become a biomarker for determining fertility and semen quality in bulls.

The environmental impact on aging: Insights from buccal mucosa and molecular biomarkers

Buccal epithelial cells serve as a primary barrier against the inhalation and ingestion of harmful substances, working alongside immune system cells such as natural killer cells to protect the body from health-damaging factors. These epithelial cells can also be used as an alternative tissue source for monitoring the genotoxic effects of external factors such as chemical exposure. This assessment can be performed using molecular biomarkers of aging, which reflect biological age and indicate cellular aging acceleration due to internal and external damage factors, such as environmental hazards. In contrast to chronological age, which merely reflects the passage of time, biological age accounts for individual variation in aging processes. Molecular biomarkers are crucial for distinguishing between normal and pathological processes in the body and for identifying the effects of external factors such as chemical exposures. The identification of specific biomarkers enhances the ability to detect and monitor adverse biological responses and accelerated aging. This review aims to highlight the routes through which environmental hazards enter the body, the application of buccal epithelial cells in assessing genetic modifications, and the introduction of potential molecular biomarkers. However, further research is necessary to elucidate the roles of these biomarkers in determining aging rates and individual variability. Understanding their implications may also help identify new therapeutic targets for preventing premature aging, treating age-related diseases, and developing potential treatments.

Ozone-Induced Lung Injury are Mediated Via PPAR-Mediated Ferroptosis in Mice.

In recent years, the concentration of PM2.5 in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1ppm, with 4h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics.

This study explores the prognostic impact of FLT3-ITD, NPM1, and WT1 mutations both independently and in combination in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) patients as they exhibit varying clinical outcomes. 150 CN-AML patients were selected to assess the prevalence and prognostic significance of WT1 mutations in combination with FLT3-ITD and NPM1 status using polymerase chain reaction (PCR) followed by Sanger sequencing. WT1 exon 7 mutations were present in 12.6% of patients. Elderly individuals, with a mean age of 49.4 years, were more prone to NPM1 mutations, though the association was not statistically significant (p=0.094). Significant associations were observed between lactate dehydrogenase (LDH) and hemoglobin (Hb) levels with FLT3-ITD and NPM1 mutations (p=0.003 and p=0.04, respectively). The M4 subtype exhibited the highest prevalence of WT1 mutations (p=0.0036). Patients with NPM1 mutations had a higher overall survival rate compared to NPM1 wild-type cases (p=0.057). There was no significant correlation between overall survival and WT1 and FLT3-ITD mutations. Regarding relapse-free survival, NPM1 mutation cases exhibited a higher survival probability compared to NPM1 wild-type cases. Similarly, WT1 mutated cases had a higher survival probability compared to WT1 wild-type cases, although these differences were not statistically significant. The combined mutation statuses of NPM1/FLT3-ITD with WT1 did not yield significant outcomes. The study suggests that larger cohort studies may reveal more relevant associations, given the relatively small cohort in this study. This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.

Unveiling molecular clues: Exploring IFNγ, IL-10, and MMP7 blood levels in gastric carcinoma patients

Objective: Gastric carcinoma is a leading cause of morbidity and mortality worldwide. Early detection can help reduce mortality rates. Biomarkers are being investigated globally for their potential in disease screening, monitoring, and follow-up in various cancers. However, currently, there is insufficient data on the role of biomarkers in gastric carcinoma. Material and Methods: This single center case control study was conducted from June 2018 to March 2021 from South India. Blood samples were collected from 85 patients diagnosed with gastric carcinoma and 85 apparently healthy individuals serving as the control group. The samples were collected in a fasting state. The serum levels of biomarkers interferon gamma (IFNγ), interleukin 10 (IL-10), and matrix metalloproteinase 7 (MMP7) were measured using enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Additionally, the levels of biomarkers were compared within the gastric cancer group based on disease location, stage, and histotype. Results: The serum levels of IFNγ and IL-10 were found to be significantly elevated in gastric carcinoma patients compared to the healthy control group. Both biomarkers exhibited high sensitivity and specificity in detecting carcinoma of the stomach. However, there was no significant difference in the serum level of MMP7 between gastric cancer patients and control group. Conclusion: IFNγ and IL-10 show promise as potential molecular biomarkers for the detection of gastric carcinoma. Further, well designed studies, involving larger and more diverse populations matched for stage and histological types, are necessary to establish the screening and monitoring utility of these biomarkers in gastric carcinoma.

BUB1 as a novel marker for predicting the immunotherapy efficacy and prognosis of breast cancer.

Budding uninhibited by benzimidazole 1 (BUB1) is a highly conserved serine/threonine kinase, showing prominent importance for proper function during mitosis. However, little is known about BUB1 mRNA expression in breast cancer (BRCA) and its correlation with prognosis and immune infiltration. Hence, we aimed to unveil its potential as groundbreaking biomarkers for immunotherapy efficacy and the prognosis of BRCA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) is a potent tool for identifying significant clusters of genes and pathways in the resulting dataset. In this study, gene set enrichment analysis of BUB1 was conducted using DAVID. The clinical characteristics of patients with or without altered BUB1 mRNA expression were compared using cBioPortal. Tumor Immune Estimation Resource (TIMER) is a known as database for comprehensive analysis of tumor-infiltrating immune cells in various cancers. In the present study, the relationship between BUB1 expression and the abundance of immune infiltrates was explored using TIMER in BRCA. Immunohistochemistry staining was performed to analyze the protein expression of BUB1 in tumor tissue specimens. We used PrognoScan and Kaplan-Meier Plotter to evaluate the prognosis of patients with different BUB1 expression levels. The expression of BUB1 in various tumor tissues was higher than that in adjacent normal tissues. BUB1 was mainly localized to the nucleoplasm and additionally localized to the cytosol. Functional enrichment analyses revealed that the cell cycle was the most significant pathway. Abnormal BUB1 mRNA expression was more frequently detected in invasive ductal carcinoma with higher histological grades and BRCAs with estrogen receptor (ER)-negative, human epidermal growth receptor 2 (HER2)-negative, and basal-like phenotypes. The BUB1 expression was correlated positively with tumor purity, B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, while BUB1 had no significant correlation with macrophages. The results of immunohistochemical staining from clinical samples further confirmed that BUB1 was overexpressed in BRCA compared to benign tumor (fibroadenoma of breast) (P<0.01). BRCA patients with lower BUB1 expression had a better prognosis than those with higher BUB1 expression in overall survival (OS) curves, distant metastasis-free survival (DMFS) curves, and relapse-free survival (RFS) curves (P<0.05). Our results suggest that BUB1 is a potential molecular biomarker for evaluating the prognosis and predicting the effectiveness of immunotherapy for BRCA.

Construction of CeRNA Regulatory Network Based on WGCNA to Reveal Potential Prognostic Biomarkers for AML Cancer

Background: Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic pathogenesis. The identification of potential molecular biomarkers could improve the AML diagnosis and targeted therapy. Recently, competing endogenous RNAs (ceRNAs) became an active area in cancer research to determine molecular mechanisms underlying tumor development. Objectives: The aim of the present study was to investigate the key molecular biomarkers that are closely related to AML through bioinformatics analysis. Methods: In this research, the RNA-seq data of 151 AML patients and 151 corresponding health samples were retrieved from The Cancer Genome Atlas (TCGA) database and GTEx Portal (genotype-tissue expression), respectively. After that we screened the differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs by “limma” package in R to construct the co-expression network ceRNA (miRNA-lncRNA-mRNA) with weighted gene co-expression network analysis (WGCNA) package in R and Cytoscape (version 3.7.2) software, respectively. Then the relevant modules were identified and functional enrichment analysis was used to uncover the modules that are biologically related to AML cancer. Results: Based on our bioinformatics studies, we constructed a significant module which contain 333 genes. Among them, five up-regulated miRNAs with the highest GS (gene significant), include hsa-miR-374B, hsa-miR-553, hsa-miR-3679, hsa-miR-548L, hsa-miR-597 and five down-regulated miRNAs with the lowest GS including hsa-miR-3934, hsa-miR-4746, hsa-miR-466, hsa-miR-6722, hsa-miR-4490. For protein-coding genes (PCGs), the top-five up-regulated PCGs with the highest GS were AMIGO3, H2AC17, SPACA5, GPR21, and OR13C3. The top-five down-regulated PCGs with the lowest GS were XBP1, TOMM6, TREX1, TNFRSF6B, and BOLA2. Among the lncRNAs, the five up-regulated lncRNAs with the highest level of GS were GREP1, ZBTB20-AS2, LINC01596, LINC00345, and RMRP. The five down-regulated lncRNAs with the lowest GS were LINC01609, LINC01707, LINC02270, LINC02309, and LINC02243. These lncRNAs can serve as potential biomarkers to distinguish between AML and normal samples. Conclusions: Finally, considering the role of ceRNA network in various biological processes, examining the role of ceRNAs in AML may provide a deeper insight into molecular mechanisms underlying the pathogenesis of cancer. This understanding may propose potential biomarkers for diagnosis and therapeutic interventions.

Identification of Autophagy-Related Genes in Patients with Acute Spinal Cord Injury and Analysis of Potential Therapeutic Targets.

Autophagy has been implicated in the pathogenesis and progression of spinal cord injury (SCI); however, its specific mechanisms remain unclear. This study is aimed at identifying potential molecular biomarkers related to autophagy in SCI through bioinformatics analysis and exploring potential therapeutic targets. The mRNA expression profile dataset GSE151371 was obtained from the GEO database, and R software was used to screen for differentially expressed autophagy-related genes (DE-ARGs) in SCI. A total of 39 DE-ARGs were detected in this study. Enrichment analysis, protein-protein interaction (PPI) network, TF-mRNA-miRNA regulatory network analysis, and the DSigDB database were used to investigate the regulatory mechanisms between DE-ARGs and identify potential drugs for SCI. Enrichment analysis revealed associations with autophagy, apoptosis, and cell death. PPI analysis identified the highest-scoring module and selected 10 hub genes to construct the TF-mRNA-miRNA network, revealing regulatory mechanisms. Analysis of the DSigDB database indicated that 1,9-Pyrazoloanthrone may be a potential therapeutic drug. Machine learning algorithms identified 3 key genes as candidate biomarkers. Additionally, immune cell infiltration results revealed significant correlations between PINK1, NLRC4, VAMP3, and immune cell accumulation. Molecular docking simulations revealed that imatinib can exert relatively strong regulatory effects on the three key proteins. Finally, in vivo experimental data revealed that the overall biological process of autophagy was disrupted. In summary, this study successfully identified 39 DE-ARGs and discovered several promising biomarkers, significantly contributing to our understanding of the underlying mechanisms of autophagy in SCI. These findings offer valuable insights for the development of novel therapeutic strategies.

Differential expression of long non-coding RNAs in colon cancer: Insights from transcriptomic analysis

BackgroundColon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. MethodsOur research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. ResultsThe data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. ConclusionTaken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.

Association of Obstructive Sleep Apnea with Nonalcoholic Fatty Liver Disease: Evidence, Mechanism, and Treatment.

Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.

Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population.

Gestational diabetes mellitus (GDM) is an intolerance of carbohydrate of any degree, which appears for the first time or is diagnosed during pregnancy. The objective of this study is to assess the differences in circular RNA (circRNA) in a Polish pregnant population with and without GDM. A total of 62 pregnant women, 34 with GDM and 28 controls, were enrolled in the study. Total RNAs were extracted from plasma and reverse transcription to complementary DNA (cDNA) was performed. A panel covering 271 amplicons, targeting both linear and circular as well as negative control gene transcripts, was used. Next-generation sequencing was used to evaluate the circRNA quantity. Data analysis was performed using the Coverage Analysis plugin in the Torrent Suite Software (Torrent Suite 5.12.3). A two-step normalization was performed by dividing each transcript read count by the total number of reads generated for the sample, followed by dividing the quantity of each transcript by β-actin gene expression. Both circular and linear forms of RNAs were independently evaluated. A total of 57 transcripts were dysregulated between pregnant women with GDM and controls. Most of the targets (n = 25) were downregulated (cut-off ratio below 0.5), and one target showed a trend toward strong upregulation (ratio 1.45). A total of 39 targets were positively correlated with fasting plasma glucose (FPG), but none of the tested targets were correlated with insulin, CRP or HOMA-IR levels. Among the pregnant women with gestational diabetes, the relative quantity of hsa_circ_0002268 (PHACTR1) was approximately 120% higher than among healthy pregnant women: 0.046 [0.022-0.096] vs. 0.021 [0.007-0.047], respectively, (p = 0.0029). Elevated levels of hsa_circ_0002268 (PHACTR1) might be specific to the Polish population of pregnant women with GDM, making it useful as a potential molecular biomarker in the management of GDM in Poland.

Molecular Biomarkers of Canine Reproductive Functions.

The aim of the current study is to review potential molecular biomarker substances selected so far as useful for assessing the quality of dog semen. Proteins, lipids, carbohydrates, and ions can serve as molecular biomarkers of reproductive functions (BRFs) for evaluating male reproductive health and identifying potential risk factors for infertility or reproductive disorders. Evaluation of BRF levels in semen samples or reproductive tissues may provide insights into the underlying causes of infertility, such as impaired sperm function, abnormal sperm-egg interaction, or dysfunction of the male reproductive tract. Molecular biomarker proteins may be divided into two groups: proteins that are well-studied, such as A-kinase anchoring proteins (AKAPs), albumins (ALBs), alkaline phosphatase (ALPL), clusterin (CLU), canine prostate-specific esterase (CPSE), cysteine-rich secretory protein 2 (CRISP2), lactotransferrin (LTF), metalloproteinases (MMPs), and osteopontin (OPN) and proteins that are not well-studied. Non-protein markers include lipid-based substances (fatty acids, phosphatidylcholine), carbohydrates (glycosaminoglycans), and ions (zinc, calcium). Assessing the levels of BRFs in semen samples may provide valuable information for breeding management and reproductive assessments in dogs. This review systematizes current knowledge that could serve as a starting point for developing practical tests with the use of biomarkers of canine reproductive functions and their predictive value for assisted reproductive technique outcomes and semen preservation.

Investigating SNHG3 and BCYRN1 lncRnas expression in the peripheral blood cells of multiple sclerosis patients

ABSTRACT Background MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. Methods A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. Results Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02). Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). Discussion Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.

Unveiling the relationship between the UGT2B gene family and neoadjuvant treatment response in patients with HER2-positive breast cancer.

e12651 Background: Achieving a pathological complete response (pCR) following neoadjuvant treatment (NAT) in HER2-positive tumors significantly enhances patient survival, resulting in a remarkable 92% reduction in mortality risk. However, it is crucial to identify biomarkers capable of predicting the NAT response, moving towards more personalized medicine. This approach would enable the identification of patients likely to respond to specific therapies, thereby facilitating the implementation of targeted treatment strategies. Our study aims to identify potential molecular biomarkers predictive of NAT response through a comprehensive analysis of differential gene expression in tissue samples from patients with HER2-positive, hormone receptor (HR)-negative breast cancer. Methods: Total RNA was extracted from FFPE tissue samples from two independent cohorts of women diagnosed with localized or locally advanced HER2-positive, HR-negative breast cancer. These patients underwent NAT in several hospitals in Andalusia, Spain. Standard chemotherapy, including taxanes and/or anthracyclines, and targeted anti-HER2 treatment such as trastuzumab and pertuzumab were administered. The patients were stratified into responders (R), achieving pCR, and non-responders (nR). In a discovery cohort (n=20), RNA hybridization using Clariom D microarray was conducted to discern differentially expressed transcripts between R and nR. Subsequently, gene expression patterns, and related pathways involved in NAT response, were analyzed using Transcriptome Analysis Console (TAC). The selected transcripts then underwent validation through quantitative PCR (qPCR) in an independent cohort (n=40). The area under the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the genes as predictive biomarkers. Results: Microarray analysis of the discovery cohort, revealed 954 differentially expressed transcripts between R and nR, following criteria of fold change greater than 1.5 or less than -1.5 and a p-value below 0.05. Among these, 643 were upregulated, while 311 were downregulated in nR compared to R. Bioinformatic analysis and a comprehensive literature review guided the selection of genes UGT2B10, UGT2B11, UGT2B15, UGT2B17, and UGT2B28 for further investigation. Subsequent qPCR analysis in the validation cohort, demonstrated the overexpression of these genes in non-responders, with statistical significance achieved only for UGT2B15. Conclusions: The UGT2B family genes encode enzymes involved in glucuronidation and metabolic pathways associated with drug detoxification and elimination. Our findings suggest that variations in the UGT2B15 expression may impact the metabolism rate of specific drugs, underscoring the necessity for additional research in this area.

Feasibility of Using a Type I IFN-Based Non-Animal Approach to Predict Vaccine Efficacy and Safety Profiles.

Animal-based tests are used for the control of vaccine quality. However, because highly purified and safe vaccines are now available, alternative approaches that can replace or reduce animal use for the assessment of vaccine outcomes must be established. In vitro tests for vaccine quality control exist and have already been implemented. However, these tests are specifically designed for some next-generation vaccines, and this makes them not readily available for testing other vaccines. Therefore, universal non-animal tests are still needed. Specific signatures of the innate immune response could represent a promising approach to predict the outcome of vaccines by non-animal methods. Type I interferons (IFNs) have multiple immunomodulatory activities, which are exerted through effectors called interferon stimulated genes (ISGs), and are one of the most important immune signatures that might provide potential candidate molecular biomarkers for this purpose. This paper will mainly examine if this idea might be feasible by analyzing all relevant published studies that have provided type I IFN-related biomarkers for evaluating the safety and efficacy profiles of vaccines using an advanced transcriptomic approach as an alternative to the animal methods. Results revealed that such an approach could potentially provide biomarkers predictive of vaccine outcomes after addressing some limitations.

Integrated transcriptomic and metabolomic approaches reveal molecular response and potential biomarkers of the deep-sea mussel Gigantidas platifrons to copper exposure

Metal pollution caused by deep-sea mining activities has potential detrimental effects on deep-sea ecosystems. However, our knowledge of how deep-sea organisms respond to this pollution is limited, given the challenges of remoteness and technology. To address this, we conducted a toxicity experiment by using deep-sea mussel Gigantidas platifrons as model animals and exposing them to different copper (Cu) concentrations (50 and 500 μg/L) for 7 days. Transcriptomics and LC-MS-based metabolomics methods were employed to characterize the profiles of transcription and metabolism in deep-sea mussels exposed to Cu. Transcriptomic results suggested that Cu toxicity significantly affected the immune response, apoptosis, and signaling processes in G. platifrons. Metabolomic results demonstrated that Cu exposure disrupted its carbohydrate metabolism, anaerobic metabolism and amino acid metabolism. By integrating both sets of results, transcriptomic and metabolomic, we find that Cu exposure significantly disrupts the metabolic pathway of protein digestion and absorption in G. platifrons. Furthermore, several key genes (e.g., heat shock protein 70 and baculoviral IAP repeat-containing protein 2/3) and metabolites (e.g., alanine and succinate) were identified as potential molecular biomarkers for deep-sea mussel’s responses to Cu toxicity. This study contributes novel insight for assessing the potential effects of deep-sea mining activities on deep-sea organisms.