Long noncoding RNA expression analysis in Crimean Congo hemorrhagic fever patients.

Crimean Congo hemorrhagic fever (CCHF) is an acute viral infection that can cause death. The detection of host transcriptome is important for understanding differences in the pathogenesis of the disease. Long noncoding RNAs (lncRNAs) regulate gene expression in different biological processes. They have also emerged as key molecules for therapeutic targets. We investigated the lncRNA gene expression profiles by utilizing the microarray for the first time in CCHF. LncRNAs were determined by the comparisons between case-control, fatal case-control, and fatal case-nonfatal cases. Quantitative polymerase chain reaction was applied to validate the microarray results of some lncRNAs. In our study, 39 lncRNAs (5 downregulated and 34 upregulated) were found to be significantly regulated in the cases when compared to the controls (p < 0.05; FC ≥ 2). One hundred ten lncRNAs exhibited a statistically significant difference between fatal cases and controls. FER1L4, ECRP, and LOC100133669 are important lncRNAs in both case and fatal case groups compared with controls. These lncRNAs may be considered important therapeutic targets for the CCHF in further studies.

MicroRNA analysis from acute to convalescence in Crimean Congo hemorrhagic fever.

Crimean Congo hemorrhagic fever (CCHF) is one of the most important viral infections and is caused by Crimean Congo hemorrhagic fever orthonairovirus (CCHFV). Severity of CCHF can vary from a mild and nonspecific illness to a severe disease with fatal outcomes. MicroRNAs (miRNAs) have an increasing impact on the different pathways of viral infections. Within the transition process from acute phase to convalescence with 18 CCHF patients, we investigated the impacts on miRNA via microarray for the first time. We also compared miRNA gene expression in 16 severe and 15 mild cases. We identified Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways associated with significant miRNAs utilizing DIANA TOOLS mirPath v.3. In this study, miR-15b-5p and miR-29a-3p were significantly downregulated in statistical terms; miR-4741, miR-937-5p, miR-6068, miR-7110-5p, miR-6126, and miR-7107-5p were upregulated in acute cases in comparison with convalescent patients (p ≤ .05). In total, 28 miRNAs (8 downregulated, 20 upregulated) were differentially expressed in severe CCHF patients as compared with mild cases (p ≤ .05). Whereas miR-6732-3p, miR-4436b-5p, miR-483-3p, and miR-6807-5p had the highest downregulation, miR-532-5p, miR-142-5p, miR-29c-3p, and let-7f-5p had the highest upregulation in severe patients in comparison with mild cases. Consequently, we determined that CCHF-induced miRNAs are associated with antiviral and proinflammatory pathways in acute and severe cases. In comparison with convalescence, these miRNAs in acute period may be therapeutic targets.

Investigation of NEAT1, IFNG-AS1, and NRIR expression in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF), whose causative agent is CCHF orthonairovirus (CCHFV), demonstrates different symptoms in patients. Long noncoding RNAs (lncRNAs) take part in various pathological processes of viral diseases. They are prominent regulators of antiviral immune responses. To our knowledge, this study is the first study to investigate nuclear paraspeckle assembly transcript 1 (NEAT1), interferon (IFN) gamma antisense RNA 1 (IFNG-AS1), and negative regulator of IFN response (NRIR) expression in CCHF in the literature. We selected these lncRNAs because they are related to IFN signal or IFN-stimulated genes. We investigated NEAT1, IFNG-AS1, and NRIR gene expression in patients with CCHF. Total RNA was extracted from blood samples of 100 volunteers and NEAT1, IFNG-AS1, and NRIR expression were measured using a quantitative real-time polymerase chain reaction. NRIR expression was statistically significant in cases versus controls (p < .001), fatals versus controls (p < .001), and fatals versus nonfatals (p = .01). Furthermore, NRIR was found statistically significant at some clinical parameters including alanine aminotransferase (p = .03), international normalized ratio (p = .03), prothrombin time (p = .02), and active partial thromboplastin time (p = .01) in CCHF cases. NEAT1 and IFNG-AS1 expression were downregulated in the case and fatal groups which were compared with controls. Our results demonstrate that NRIR may be important in CCHF pathogenesis and the target of CCHF treatment.

Identification of potential microRNA markers related to Crimean-Congo hemorrhagic fever disease.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future.

HULC and 7SL RNA expression levels in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean-Congo hemorrhagic fever virus. Long non-coding RNAs (lncRNAs) are generally classified as transcripts longer than 200 nucleotides (nt). The various lncRNAs expressed in infected cells are responsible for regulating the expression of viral and host genes. This is the first study to investigate hepatocellular carcinoma upregulated long non-coding RNA (HULC) and 7SL RNA expression levels in patients with CCHF. Blood samples were taken from 100 individuals (60 patients and 40 controls), and total RNA isolation was performed. Quantitative polymerase chain reaction (qPCR) was performed using the SYBR Green method to determine HULC and 7SL RNA expression levels in the study population. Compared the patient and control groups, HULC was upregulated statistically significantly (P = 0.04) and 7SL RNA was downregulated (P = 0.93) in patients. Also, there was a statistically significant difference between fatal cases and surviving patients for HULC and 7SL RNA (P < 0.01 and P = 0.03, respectively). In addition, HULC expression was increased statistically significantly in fatal cases compared with surviving patients in terms of clinical parameters such as aspartate aminotransferase (P < 0.01), alanine aminotransferase (P < 0.01), international normalized ratio (P = 0.05), prothrombin time (P = 0.01), active partial thromboplastin time (P < 0.01), and lactate dehydrogenase (P < 0.01). These findings highlighted that HULC and 7SL RNA could be important mediators for studying the pathogenesis of CCHF and significant therapeutic targets of the disease.

Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) is a pandemic that is still affecting people and has caused many deaths. Toll-like receptors (TLRs) have an important role in the binding of disease agents to the host cell, disease susceptibility and severity, and host disease resistance. In this study, we investigated the frequencies of TLR7 (C.4-151 A/G), TLR9 (T-1486C and G2848A), and TLR10 (720A/C and 992T/A) single nucleotide polymorphisms in 150 cases with COVID-19 and 171 control samples. We also examined whether TLR7, TLR9, and TLR10 were related to COVID-19 severity. Furthermore, we analyzed the association between COVID-19 and some clinical parameters. Polymerase chain reaction based on restriction fragment length polymorphisms performed for the TLR7, TLR9, and TLR10 single nucleotide polymorphisms. TLR7 C.4-151 A/G G allele and GG genotype; TLR9 T-1486C C allele and TC, CC genotypes; and TLR10 720A/C C allele; TLR10 992T/A A allele and AA genotype frequencies were statistically significant in cases with COVID-19 compared with controls (P < 0.05*). In addition, there was a statistically significant difference in the distribution of TLR7, TLR9, and TLR10 allele and genotype frequencies between the severity groups (P < 0.05*). Our findings suggest that TLR7, TLR9, and TLR10 polymorphisms may be crucial for the clinical course and susceptibility to infection.

Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis.

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organization (WHO) data. Atherosclerosis is considered as a chronic inflammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were compared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA)  which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual. METHODS: lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Differentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically significant genes between CAP and IMA tissue. RESULTS AND CONCLUSIONS: In our study, 345 DEGs were found to be statistically significant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identified genes that correlated with statistically significant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.

Effects of MPO-463G/A and -129G/A polymorphisms on coronary artery disease risk and patient survival in a Turkish population.

Myeloperoxidase (MPO) is an oxidative hemoprotein compound expressed in polymorphonuclear leukocytes that contributes to inflammatory responses. Coronary artery disease (CAD), as the most prevalent form of heart disease, is considered to originate from an interaction between genetic and environmental factors. In the present study, the potential associations between MPO-463G/A and -129G/A polymorphisms with CAD were investigated in a Turkish population using a polymerase chain reaction-based restriction fragment length polymorphism (RFLP) assay technique. To the best of our knowledge, the study was the first to examine the association of MPO-463G/A and -129G/A with patient survival rate in a Turkish population. The study population consisted of 201 patients with CAD and 201 healthy controls. The results indicated that there was a significant association of the GA genotype of MPO-463G/A with the case population (P=0.048). Meanwhile, in the patients with CAD, the frequency distributions of the MPO-129A allele (P=0.006) and GA genotype (P=0.001) were significantly increased compared with the G allele and GG genotype, respectively, in CAD patients. Additionally, compared with the GG genotype, the frequency distribution of MPO-129A was significantly increased in the patient group regarding smoking status (P=0.001) and the presence of hypercholesterolemia (P=0.028). However, survival analysis did not detect an effect of either polymorphism on the survival rate of the CAD patients (P>0.05). Therefore, the MPO-129GA genotype may be a significant risk factor for the development of CAD.