MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

Download Full-text

Analysis of Circulating microRNA Signatures and Preeclampsia Development

Cells ◽

10.3390/cells10051003 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1003

Author(s):

Margarita L. Martinez-Fierro ◽

Idalia Garza-Veloz

Keyword(s):

Pregnant Women ◽

Expression Profiling ◽

Gene Prediction ◽

Microrna Expression ◽

Differentially Expressed ◽

Control Group ◽

Case Group ◽

Circulating Microrna ◽

Activated T Cells ◽

Serum Microrna

microRNAs are important regulators of cell processes and have been proposed as potential preeclampsia biomarkers. We evaluated serum microRNA expression profiling to identify microRNAs involved in preeclampsia development. Serum microRNA expression profiling was evaluated at 12, 16, and 20 weeks of gestation (WG), and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan low-density array plates: a control group with 18 normotensive pregnant women and a case group with 16 patients who developed preeclampsia during the follow-up period. Fifty-three circulating microRNAs were differentially expressed between groups (p < 0.05). Compared with controls, hsa-miR-628-3p showed the highest relative quantity values (at 12 WG = 7.7 and at 20 WG = 3.45) and the hsa-miRs -151a-3p and -573 remained differentially expressed from 16 to 20 WG (p < 0.05). Signaling pathways including cancer-related, axon guidance, Neurotrophin, GnRH, VEGF, and B/T cell receptor, were most commonly altered. Further target gene prediction revealed that nuclear factor of activated T-cells 5 gene was included among the transcriptional targets of preeclampsia-modulated microRNAs. Specific microRNAs including hsa-miRs -628-3p, -151a-3p, and -573 were differentially expressed in serum of pregnant women before they developed preeclampsia compared with controls and their participation in the preeclampsia development should be considered.

Download Full-text

Predicting mortality in adults with suspected infection in a Rwandan hospital: an evaluation of the adapted MEWS, qSOFA and UVA scores

BMJ Open ◽

10.1136/bmjopen-2020-040361 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040361

Author(s):

Amanda Klinger ◽

Ariel Mueller ◽

Tori Sutherland ◽

Christophe Mpirimbanyi ◽

Elie Nziyomaze ◽

...

Keyword(s):

Decision Making ◽

Quality Improvement ◽

Clinical Decision Making ◽

Clinical Decision ◽

Tertiary Hospital ◽

Early Warning Score ◽

Receiver Operating Curve ◽

Predictive Capacity ◽

Suspected Infection ◽

Significant Difference

RationaleMortality prediction scores are increasingly being evaluated in low and middle income countries (LMICs) for research comparisons, quality improvement and clinical decision-making. The modified early warning score (MEWS), quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and Universal Vital Assessment (UVA) score use variables that are feasible to obtain, and have demonstrated potential to predict mortality in LMIC cohorts.ObjectiveTo determine the predictive capacity of adapted MEWS, qSOFA and UVA in a Rwandan hospital.Design, setting, participants and outcome measuresWe prospectively collected data on all adult patients admitted to a tertiary hospital in Rwanda with suspected infection over 7 months. We calculated an adapted MEWS, qSOFA and UVA score for each participant. The predictive capacity of each score was assessed including sensitivity, specificity, positive and negative predictive value, OR, area under the receiver operating curve (AUROC) and performance by underlying risk quartile.ResultsWe screened 19 178 patient days, and enrolled 647 unique patients. Median age was 35 years, and in-hospital mortality was 18.1%. The proportion of data missing for each variable ranged from 0% to 11.7%. The sensitivities and specificities of the scores were: adapted MEWS >4, 50.4% and 74.9%, respectively; qSOFA >2, 24.8% and 90.4%, respectively; and UVA >4, 28.2% and 91.1%, respectively. The scores as continuous variables demonstrated the following AUROCs: adapted MEWS 0.69 (95% CI 0.64 to 0.74), qSOFA 0.65 (95% CI 0.60 to 0.70), and UVA 0.71 (95% CI 0.66 to 0.76); there was no statistically significant difference between the discriminative capacities of the scores.ConclusionThree scores demonstrated a modest ability to predict mortality in a prospective study of inpatients with suspected infection at a Rwandan tertiary hospital. Careful consideration must be given to their adequacy before using them in research comparisons, quality improvement or clinical decision-making.

Download Full-text

Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

Download Full-text

Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽

10.1530/rep-14-0095 ◽

2014 ◽

Vol 148 (1) ◽

pp. 33-41 ◽

Cited By ~ 48

Author(s):

Fulu Dong ◽

Yuan Zhang ◽

Fei Xia ◽

Yi Yang ◽

Sidong Xiong ◽

...

Keyword(s):

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Normal Pregnancy ◽

Recurrent Spontaneous Abortion ◽

Future Research ◽

Rna Molecules ◽

Non Coding Rna ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

Download Full-text

Cryptocurrency bubble risk and the FOMC announcements during COVID-19 black swan event

Journal of Investment Compliance ◽

10.1108/joic-12-2020-0048 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Anis Jarboui ◽

Emna Mnif

Keyword(s):

Federal Reserve ◽

Abnormal Returns ◽

Relevant Information ◽

Future Research ◽

Open Market ◽

Predictive Capacity ◽

Federal Open Market Committee ◽

Content Type ◽

Cumulative Abnormal Returns ◽

Practical Implications

Purpose After the COVID-19 outbreak, the Federal Reserve has undertaken several monetary policies to alleviate the pandemic consequences on the markets. This paper aims to evaluate the effects of the Federal Reserve monetary policy on the cryptocurrency dynamics during the COVID19 pandemic. Design/methodology/approach We examine the response and feedback effects via an event study methodology. For this purpose, abnormal returns (AR) and cumulative abnormal returns (CARs) around the first FOMC (Federal Open Market Committee) announcement related to the COVID-19 pandemic for the top five cryptocurrencies are explored. We, further investigate the effect of the eight FOMC statement announcements during the COVID19 pandemic on these cryptocurrencies (Bitcoin, Ethereum, Tether, Litecoin, and Ripple). In the above-mentioned crypto-currency markets, we investigate the presence of bubbles by using the PSY test. We then examine the concordance of the dates of these bubbles with the dates of the FOMC announcements. Findings The empirical results show that the first FOMC event has a negative significant effect after 4 days of the announcement date for all studied cryptocurrencies except Tether. The results also indicate that cumulative abnormal returns are significant during the event windows of (−3,8), (−3,9), and (−3,10). Besides, we find that Bitcoin, Ethereum and, Litecoin lived short bubbles lasting for a few days. However, Ripple and Tether markets present no bubbles and no explosive periods. Research limitations/implications This paper presents trained proof that FOMC announcements have a positive effect on volatility's predictive capacity. This work therefore promotes the study of the data quality of volatility in future research as well. Practical implications The justified effect of the FOMC announcements on cryptocurrency as a speculative asset has practical implications for investors in building their trading strategies in anticipation of the next FOMC announcement. Therefore, this study implies that the FOMC announcements contain very relevant information for investors in the cryptocurrency market. This research may not only encourage a better understanding of the evolution of the expectations of policymakers, but also facilitate a better understanding of how these expectations are developed. Originality/value The COVID-19 pandemic has disturbed the stability of financial markets, inciting the Fed to take some monetary regulations. To the best of our knowledge, this study is the first one that analyses the response of five major cryptocurrencies to FOMC announcements during COVID 19 pandemic and associates these dates with bubble occurrences.

Download Full-text

The Serum MicroRNA Expression Modified the Genic Toxicity Caused by Aflatoxin B1

Aflatoxin-Control, Analysis, Detection and Health Risks ◽

10.5772/intechopen.68419 ◽

2017 ◽

Cited By ~ 2

Author(s):

Xiao-Ying Huang ◽

Chun-Ying Luo ◽

Xue-Ming Wu ◽

Jin-Guang Yao ◽

Chao Wang ◽

...

Keyword(s):

Aflatoxin B1 ◽

Microrna Expression ◽

Serum Microrna

Download Full-text

MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect

Molecular and Cellular Biochemistry ◽

10.1007/s11010-017-3146-2 ◽

2017 ◽

Vol 439 (1-2) ◽

pp. 171-187 ◽

Cited By ~ 1

Author(s):

Hui Chai ◽

Zhaoyuan Yan ◽

Ke Huang ◽

Yuanqing Jiang ◽

Lin Zhang

Keyword(s):

Ventricular Septal Defect ◽

Signaling Pathways ◽

Target Genes ◽

Septal Defect ◽

Microrna Expression

Download Full-text

Assessing COVID-19-related anxiety and functional impairment amongst nurses in Malawi

African Journal of Primary Health Care & Family Medicine ◽

10.4102/phcfm.v13i1.2823 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Genesis Chorwe-Sungani

Keyword(s):

Mental Health ◽

Functional Impairment ◽

Area Under The Curve ◽

Reliability And Validity ◽

Psychosocial Interventions ◽

Well Being ◽

Receiver Operating Curve ◽

Future Research ◽

Online Data ◽

Cross Sectional

Background: Psychological well-being of nurses is crucial for them to effectively discharge their duties. However, coronavirus disease 2019 (COVID-19)-related anxiety can interfere with nurses’ performance and reduce their self-efficacy.Aim: The primary aim of this study was to assess COVID-19-related anxiety and functional impairment amongst nurses in Malawi. The secondary aim of the study was to determine reliability and validity of the Coronavirus Anxiety Scale.Setting: The study was conducted in Malawi.Methods: This was a cross-sectional study that collected quantitative data from 102 nurses in Malawi online. Data were analysed using descriptive statistics and receiver operating curve analysis.Results: This study found that 25.5% (26) of respondents had COVID-19-related anxiety and 48% (49) functional impairment. There were significant differences in the numbers of respondents who had functional impairment in relation to workplace (Χ2 = 8.7, p = 0.03), with many of those working in hospitals (58.6%, n = 34) having highest levels (mean = 20.6 ± 10.4). The Coronavirus Anxiety Scale proved to be an effective instrument (Sensitivity = 73.1%; Specificity = 60.5%; area under the curve = 0.73) for assessing COVID-19-related anxiety amongst nurses.Conclusion: It is necessary to screen nurses for COVID-19-related anxiety and functional impairment and provide them effective psychosocial interventions. Policymakers should place more emphasis on allocation of financial resources to mental health services and staff support programmes targeting nurses during pandemics. There is a need to conduct future research on mental health interventions that might be used to assist nurses with COVID-19-related anxiety and functional impairment.

Download Full-text

Integration and Visualization of Regulatory Elements and Variations of the EPAS1 Gene in Human

Genes ◽

10.3390/genes12111793 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1793

Author(s):

Aleša Kristan ◽

Nataša Debeljak ◽

Tanja Kunej

Keyword(s):

Target Genes ◽

Regulatory Elements ◽

Future Research ◽

Protein Abundance ◽

Interacting Proteins ◽

Pas Domain ◽

Expression Stability ◽

Post Translational Modifications ◽

Oxygen Homeostasis ◽

Cancer Types

Endothelial PAS domain-containing protein 1 (EPAS1), also HIF2α, is an alpha subunit of hypoxia-inducible transcription factor (HIF), which mediates cellular and systemic response to hypoxia. EPAS1 has an important role in the transcription of many hypoxia-responsive genes, however, it has been less researched than HIF1α. The aim of this study was to integrate an increasing number of data on EPAS1 into a map of diverse OMICs elements. Publications, databases, and bioinformatics tools were examined, including Ensembl, MethPrimer, STRING, miRTarBase, COSMIC, and LOVD. The EPAS1 expression, stability, and activity are tightly regulated on several OMICs levels to maintain complex oxygen homeostasis. In the integrative EPAS1 map we included: 31 promoter-binding proteins, 13 interacting miRNAs and one lncRNA, and 16 post-translational modifications regulating EPAS1 protein abundance. EPAS1 has been associated with various cancer types and other diseases. The development of neuroendocrine tumors and erythrocytosis was shown to be associated with 11 somatic and 20 germline variants. The integrative map also includes 12 EPAS1 target genes and 27 interacting proteins. The study introduced the first integrative map of diverse genomics, transcriptomics, proteomics, regulomics, and interactomics data associated with EPAS1, to enable a better understanding of EPAS1 activity and regulation and support future research.

Download Full-text

Identification of key genes and associated pathways in neuroendocrine tumors through bioinformatics analysis and predictions of small drug molecules

10.1101/2020.12.23.424165 ◽

2020 ◽

Author(s):

Praveenkumar Devarbhavi ◽

Basavaraj Vastrad ◽

Anandkumar Tengli ◽

Chanabasayya Vastrad ◽

Iranna Kotturshetti

Keyword(s):

Drug Target ◽

Target Gene ◽

Molecular Mechanisms ◽

Target Genes ◽

Regulatory Elements ◽

Future Research ◽

High Morbidity ◽

Hub Genes ◽

Go Enrichment ◽

Significant Difference

AbstractNeuroendocrine tumor (NET) is one of malignant cancer and is identified with high morbidity and mortality rates around the world. With indigent clinical outcomes, potential biomarkers for diagnosis, prognosis and drug target are crucial to explore. The aim of this study is to examine the gene expression module of NET and to identify potential diagnostic and prognostic biomarkers as well as to find out new drug target. The differentially expressed genes (DEGs) identified from GSE65286 dataset was used for pathway enrichment analyses and gene ontology (GO) enrichment analyses and protein - protein interaction (PPI) analysis and module analysis. Moreover, miRNAs and transcription factors (TFs) that regulated the up and down regulated genes were predicted. Furthermore, validation of hub genes was performed. Finally, molecular docking studies were performed. DEGs were identified, including 453 down regulated and 459 up regulated genes. Pathway and GO enrichment analysis revealed that DEGs were enriched in sucrose degradation, creatine biosynthesis, anion transport and modulation of chemical synaptic transmission. Important hub genes and target genes were identified through PPI network, modules, target gene - miRNA network and target gene - TF network. Finally, survival analyses, receiver operating characteristic (ROC) curve and RT-PCR validated the significant difference of ATP1A1, LGALS3, LDHA, SYK, VDR, OBSL1, KRT40, WWOX, NINL and PPP2R2B between metastatic NET and normal controls. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying NET and provide candidate targets for future research.

Download Full-text