RNA Status Research Articles

Increased unedited Alu RNA patterns found in cortex extracellular vesicles in Alzheimer's disease resemble hippocampus vasculature Alu RNA editing patterns but not cortex Alu RNA editing patterns.

Endogenous Alu RNAs form double-stranded RNAs recognized by double-stranded RNA sensors and activate IRF and NF-kB transcriptional paths and innate immunity. Deamination of adenosines to inosines by the ADAR family of enzymes, a process termed A-to-I editing, disrupts double-stranded RNA structure and prevents innate immune activation. Innate immune activation is observed in Alzheimer's disease, the most common form of dementia. We have previously reported loss of A-to-I editing in hippocampus vasculature, but no change in cortex or cortex vasculature, associated with Alzheimer's disease. Here, we investigated the status of Alu RNA A-to-I editing in cortex extracellular vesicles in Alzheimer's disease. We used existing RNA-seq data sets and the SPRINT software package to determine levels of Alu RNA A-to-I editing in cortex extracellular vesicles in Alzheimer's disease and control groups and compared these editing profiles to those found in both total cortex and hippocampus vasculature. We find substantial loss of Alu A-to-I editing in cortex extracellular vesicles in Alzheimer's disease. By measuring editing patterns on a gene-by-gene basis, we determined that editing patterns in cortex extracellular vesicles resemble editing patterns in hippocampus vasculature rather than total cortex. We conclude that hippocampus vasculature unedited Alu RNAs are packaged in extracellular vesicles, travel to the cortex, deliver their cargo and stimulate innate immunity and alter other basic biological processes contributing to Alzheimer's disease progression.

METTL14-mediated m6A modification enhances USP22-ERα axis to drive breast cancer malignancy

The abundance and activity of estrogen receptor alpha (ERα) are tightly regulated by ubiquitin-specific peptidase 22 (USP22) during the progression of breast cancer (BCa). However, the post-transcriptional modifications on the USP22-ERα axis remain elusive. N6-methyladenosine (m6A) is critical to modulate RNA status in eukaryotic cells. Here, we find that METTL14 positively regulates the mRNA expression of USP22 and ERα. Mechanistically, METTL14 potently binds to the USP22 and ERα mRNA, and thereby enhancing their stability through m6A modification. YTHDC1 and YTHDF1 function as readers for m6A-modified USP22 and ERα, respectively. Additionally, METTL14 promotes the growth and migration of ERα+ BCa via the USP22-ERα-Cyclin D1 axis. Enforced expression of USP22/ERα significantly reverses the METTL14 depletion-induced growth and migration inhibition in BCa. Moreover, our analysis of clinical samples shows that the expression of METTL14, USP22, and ERα is upregulated and correlated in BCa tissues. Overall, our findings reveal the key role of the METTL14-USP22-ERα axis in BCa progression, which further provides a druggable target to treat BCa.

Transcriptome-Wide Analysis of the 5' Cap Status of RNA Using 5' Monophosphate-Dependent Exonuclease Digestion and RNA Sequencing.

Eukaryotic mRNAs carry an N7-methylguanosine (m7G) cap structure at their 5' extremity, which protects them from the degradation by 5'-3' exoribonucleases and plays a pivotal role in mRNA metabolism, promoting splicing, nuclear export, and translation. Decapping, the enzymatic process that removes this structure, is a key event during cytoplasmic mRNA 5'-3' decay, leading to the degradation of the transcript body by Xrn1. In this chapter, we describe a procedure to assess the cap status of RNA at the transcriptome level. It is based on a treatment of total RNA extracts with a 5' monophosphate-dependent exonuclease, which like Xrn1 specifically degrades decapped RNAs harboring 5' monophosphate extremities, but not RNAs with intact m7G cap. The digested RNAs are then analyzed by RNA sequencing.

A study of the role of androgen receptor and androgen receptor variant 7 in TNBC patients and the effect of their targeting by Enzalutamide and EPI-001 in MDA-MB-231

The lack of targeted therapy for triple-negative breast cancer (TNBC) is among the mainsprings of its poor prognosis. This study aimed to elucidate the role of the androgen receptor (AR) and its splice variant 7 (ARv7) in TNBC patients. Further, the molecular impact of their blockers, Enzalutamide and EPI-001, on the TNBC cell line MDA-MB-231 was investigated. Thereby, immunohistochemical expression of AR/ARv7 was assessed for TNBC Egyptian patients. Moreover, bioinformatics analysis of AR/ARv7 RNA status was carried out on TNBC patients from The Cancer Genome Atlas Breast Carcinoma project (TCGA-BRCA). Data from both groups was correlated with patients’ clinicopathological features. Besides, scratch wound healing assay and ELISA were employed to assess the effect of AR/ARv7 blockers on several metastasis markers in MDA-MB-231 cell line. In the Egyptian-TNBC patients, AR expression was associated with worse 7-year DFS (40.6 ± 18.6 %). In addition, ARv7 showed cytoplasmic and nuclear patterns, and both cytoplasmic and nuclear ARv7+ patients demonstrated a worse 7-year DFS (22.7 ± 17.7 % and 20 ± 17.9 %) and overall survival (63.6 ± 14.5 % and 40 ± 21.8 %). Importantly, 80 % of the nuclear ARv7+ patients developed distant metastasis. The data of the TCGA-TNBC patients showed a tendency for poor outcomes in the high ARv7-expressing patients. Molecularly, in MDA-MB-231, both inhibitors modulated metastasis and epithelial to mesenchymal transition (EMT) markers ROCK1, ROCK2, c-Myc, E-cadherin and N-cadherin, with EPI-001 downregulating NF-ĸB level as well. We concluded that ARv7 indicated poor prognosis in the studied cohorts and that blocking of AR/ARv7 abated metastasis and key regulators of EMT in MDA-MB-231, at least in part by targeting ROCK/NF-ĸB/c-Myc axis.

EIF2Bβ confers resistance to Turnip mosaic virus by recruiting ALKBH9B to modify viral RNA methylation.

Eukaryotic translation initiation factors (eIFs) are the primary targets for overcoming RNA virus resistance in plants. In a previous study, we mapped a BjeIF2Bβ from Brassica juncea representing a new class of plant virus resistance genes associated with resistance to Turnip mosaic virus (TuMV). However, the mechanism underlying eIF2Bβ-mediated virus resistance remains unclear. In this study, we discovered that the natural variation of BjeIF2Bβ in the allopolyploid B. juncea was inherited from one of its ancestors, B. rapa. By editing of eIF2Bβ, we were able to confer resistance to TuMV in B. juncea and in its sister species of B. napus. Additionally, we identified an N6-methyladenosine (m6A) demethylation factor, BjALKBH9B, for interaction with BjeIF2Bβ, where BjALKBH9B co-localized with both BjeIF2Bβ and TuMV. Furthermore, BjeIF2Bβ recruits BjALKBH9B to modify the m6A status of TuMV viral coat protein RNA, which lacks the ALKB homologue in its genomic RNA, thereby affecting viral infection. Our findings have applications for improving virus resistance in the Brassicaceae family through natural variation or genome editing of the eIF2Bβ. Moreover, we uncovered a non-canonical translational control of viral mRNA in the host plant.

Relationship between HBV RNA level and pregnancy outcomes among hepatitis B carriers.

This study aims to investigate the relationship between hepatitis B virus (HBV) RNA level and pregnancy outcomes among hepatitis B carriers. This study collected pregnant women who attended the Affiliated Hospital of Guizhou Medical University (Guizhou, China) from June 2020 to June 2023. The levels of HBV DNA, HBV RNA, and HBeAg status in HBV carriers were detected. Pregnancy outcomes including intrahepatic cholestasis of pregnancy (ICP), gestational hypertension (GH), pre-eclampsia, gestational diabetes mellitus (GDM), preterm prelabour rupture of membranes (PPROM), mode of delivery, preterm birth, low birth weight (LBW) and macrosomia. A total of 562 pregnant women were collected, 203 (36.12%) were infected with HBV. Compared with HBsAg negative, HBsAg positive pregnant women had a higher risk of ICP. There were no significant differences in the rates of GDM, GH, pre-eclampsia, PPROM, preterm birth, LBW, macrosomia, and mode of delivery among women in the two groups. Multivariate logistic regression analysis showed that maternal HBV RNA level (OR = 3.814, 95% CI: 2.036~7.142, P< 0.001) was an independent risk factor for ICP in HBsAg-positive pregnant women. The receiver operating characteristics (ROC) curve revealed that the areas under the curve of HBV RNA for prediction of ICP was 0.8652(95% confidence interval 0.7636-0.9669, P< 0.001). The HBV RNA level has a significant negative impact on pregnancy outcomes. It may serve as an indicator to guide the prevention of ICP and improve maternal health.

Non-coding RNAs Function in Periodontal Ligament Stem Cells.

Non-coding RNA has many types which has rich functions and plays an important role in the study of basic molecular mechanisms. Many non-coding RNA have important implications for pluripotent stem cells and embryonic stem cells. It has been found to affect the self-renewal and osteogenesis of many types of stem cells. They have also been found to regulate stem cell proliferation and induct bone differentiation. Periodontal ligament stem cells are essential for the regeneration of periodontal tissue. In recent years, in the field of stomatology, studies have found that many non-coding RNA also have significant regulatory effects on the proliferation and differentiation of periodontal stem cells and may become potential therapeutic targets for many common periodontal diseases such as periodontitis, bone/tooth/soft tissue loss and orthodontic treatment. Therefore, we summarized the current research status of non-coding RNA in the field of molecular mechanism of periodontal ligament stem cells and prospected its future progress.

Grafting based DNA methylation alteration of snoRNAs in upland cotton (Gossypium L.)

The effects of grafting in response to various biotic and abiotic stressors have been studied, however, the methylation status of small nucleolar RNA (snoRNA) genes in heterograft and homograft cotton needs investigation. This study was undertaken to determine grafting effects on DNA methylation of snoRNA genes in Upland cotton. Rootstocks used were Pima 3–79 (Gossypium barbadense acc. Pima 3–79) and Texas Marker-1 (G. hirsutum acc. TM-1), representing two different species with different fiber properties, adaptations, and morphologies. The methylation ratio and differently methylated cytosines (DMCs) of 10935 snoRNA genes in mature seeds of heterograft and homograft cotton samples were studied using the whole genome bisulfite sequencing method. Seedling vigor and seed weight were studied to investigate phenotype alterations that might be associated with altered methylation levels among grafts. Statistically significant DMC differences among gene elements of snoRNA genes and between homograft and heterograft cotton samples were identified in the absence of DNA sequence alterations. DNA methylation alterations of snoRNA genes associated with seedling vigor and 100 seed weight. The majority of snoRNA genes showed higher numbers of mCG + mCHG-DMCs with increased methylation levels in heterograft, while there were higher numbers of mCG + mCHG-DMCs with decreased methylation levels in homograft. Since snoRNAs regulate essential genes for plant growth and development and plant adaptation to different habitats or extreme environments, their altered methylation levels should be related with plant physiology.

Evaluation of a fully automated high-throughput serology assay for detection of Hepatitis D virus antibodies

BackgroundHDV antibody testing is recommended for universal screening and as the first line in an HDV double reflex testing strategy for effectively identifying patients with active infection for therapeutic treatments. ObjectiveThe aim of this study is to evaluate the performance of a newly developed ARCHITECT HDV Total Ig (ARCHITECT HDV Ig) prototype assay. Study designPerformance characteristics were determined for the ARCHITECT HDV Ig and a reference test, LIAISON XL Anti-HDV using a well-characterized specimen panel, comprising HDV RNA positive (n = 62) and negative (n = 70) samples, and healthy US blood donors. ResultsHealthy US blood donors (n=200) showed 99.5% (199/200, 95%CI=97.65–99.98) specificity with ARCHITECT HDV Ig and 98.5 % (197/200, 95 %CI = 96.10–99.64) with LIAISON Anti-HDV. Among known HDV RNA positive samples, ARCHITECT HDV Ig detected 59/62 demonstrating 95.2 % sensitivity while LIAISON Anti-HDV sensitivity was 90.3 % (56/62). Among 101 HBV positive samples, 70 were reactive in the ARCHITECT test, 59 of which tested positive for HDV RNA for a positive predictive value (PPV) for the presence of HDV RNA was 84.3 %. For LIAISON Anti-HDV, 79 specimens were reactive and 56 contained HDV RNA: PPV for HDV RNA was 70.9 %. Among 70 HDV RNA negative samples, 39 were HBV positive. ARCHITECT HDV Ig negative predictive value (NPV) was 71.8 % and LIAISON Anti-HDV NPV was 41 % for the HBV positive group, respectively. ConclusionWhen compared to the LIASON Anti-HDV test, the ARCHITECT HDV Ig assay demonstrated enhanced sensitivity and specificity and better NPV and PPV values for HDV RNA status. The ARCHITECT HDV Ig assay represents a promising tool for universal screening of all HBsAg-positive persons.

Clinicopathologic features and survival outcomes of CD30 expression in extranodal natural killer/T-cell lymphoma.

Previous studies have been inconsistent concerning the association between the prognostic value of CD30 expression and extranodal natural killer/T-cell lymphoma (ENKTL). CD30 expression in 82 patients with newly diagnosed ENKTL (mean age, 50 years; 73.2% male) was assessed by immunohistochemistry on paraffin-embedded sections. The level of CD30 expression was categorized into negative (0%, no staining) and positive groups. Sixty-seven cases exhibited positive CD30 expression, and the main between-group difference was the Chinese Southwest Oncology Group and Asia Lymphoma Study Group (CA) ENKTL stage and Eastern Cooperative Oncology Group (ECOG) performance status. The cutoff point for CD30 expression was 40% by restricted cubic splines analysis. The overall survival of patients with high expression (>40%) was statistically superior to negative (0%) and low-expression groups. A positive correlation was observed between CD30 and Epstein-Barr virus-encoded small RNA status (r = 0.305). Multivariable analysis suggested that positive CD30 expression (hazard ratio, 0.420 [95% CI, 0.193-0.914]; P = .029) and CA advanced stage (hazard ratio, 2.844 [95% CI, 1.371-5.896]; P = .005) were independent prognostic factors for ENKTL. Positive CD30 expression was a favorable prognostic factor for ENKTL, and CD30 expression could restratify the survival of patients in clinical subgroups.

Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.

Method for the Enrichment of N6-Methyladenosine-Modified Cellular and HIV-1 RNA.

N6-methyladenosine (m6A) modification of RNA is an important area in studying viral replication, cellular responses, and host immunity. HIV-1 RNA contains multiple m6A modifications that regulate viral replication and gene expression. HIV-1 infection of CD4+ T-cells or HIV-1 envelope protein treatment upregulates m6A levels of cellular RNA. Changes in the m6A modification of cellular transcripts in response to HIV-1 infection provide new insights into the mechanisms of posttranscriptional gene regulation in the host cell. To better investigate the functions of m6A modification in HIV-1 infection and innate immune responses, it is helpful to standardize basic protocols. Here, we describe a method for the selective enrichment of m6A-modified RNA from HIV-1-infected primary CD4+ T-cells based on immunoprecipitation. The enriched RNA with m6A modifications can be used in a variety of downstream applications to determine the methylation status of viral or cellular RNA at resolution from transcript level down to single nucleotide.

Increased levels of N6-methyladenosine in peripheral blood RNA: a perspective diagnostic biomarker and therapeutic target for non-small cell lung cancer

Due to lack of effective biomarkers for non-small cell lung cancer (NSCLC), many patients are diagnosed at an advanced stage, which leads to poor prognosis. Dysregulation of N6-methyladenosine (m6A) RNA contributes significantly to tumorigenesis and tumor progression. However, the diagnostic value of m6A RNA status in peripheral blood to screen NSCLC remains unclear. Peripheral blood samples from 152 NSCLC patients and 64 normal controls (NCs) were applied to assess the m6A RNA levels. Bioinformatics and qRT-PCR analysis were performed to identify the specific immune cells in peripheral blood cells and investigate the mechanism of the alteration of m6A RNA levels. Robust elevation of m6A RNA levels of peripheral blood cells was exhibited in the NSCLC group. Moreover, the m6A levels increased as NSCLC progressed, and reduced after treatment. The m6A levels contained area under the curve (AUC) was 0.912, which was remarkably greater than the AUCs for CEA (0.740), CA125 (0.743), SCC (0.654), and Cyfra21-1 (0.730). Furthermore, the combination of these traditional biomarkers with m6A levels elevated the AUC to 0.970. Further analysis established that the expression of m6A erasers FTO and ALKBH5 were both markedly reduced and negatively correlated with m6A levels in peripheral blood of NSCLC. Additionally, GEO database and flow cytometry analysis implied that FTO and ALKBH5 attributes to peripheral CD4+ Tcells proportion and activated the immune functions of Tcells. These findings unraveled that m6A RNA of peripheral blood immune cells was a prospective biomarker for the diagnosis of NSCLC.

Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women.

The Preeclampsia (PE) molecular mechanisms are not fully revealed and different biological processes are involved in the pathogenesis of PE. We aimed to evaluate adenosine and hypoxia-related signaling molecules in PE patients in the current study. Decidua tissue and peripheral blood samples were taken from 25 healthy pregnant and 25 PE women at delivery time. CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-α) were evaluated in mRNA and protein level using real-time PCR and western blotting techniques, respectively. Also, miR-30a, miR-206, and miR-18a expression were evaluated by real-time PCR. At last, secretion levels of IGF and TGF-β in the taken serum of blood samples were measured by ELISA. Our results revealed that Expression of CD39 is decreased in PE cases versus healthy controls at mRNA and protein levels (p = 0.0003 for both). CD73 and HIF-α showed an increased level of expression in PE patients at RNA and protein status (p = 0.0157 and p < 0.0001 for protein evaluation of CD73 and HIF-α, respectively). The miRNA-30a (p = 0.0037) and miR-206 (p = 0.0113) showed elevated expression in the decidua of the PE group. The concentration of secreted IGF-1 (p = 0.0002) and TGF-β (p = 0.0101) in serum samples of PE cases compared to the healthy group were decreased. In conclusion, our results showed that aberrant expression of molecules that are involved in ATP catabolism and the hypoxic conditions is observed in PE cases and involved in their hypertension and inflammation could be served as PE prognosis by more confirming in comprehensive future studies. miR-206 and miR-30a play a role by regulating CD39 and CD73 as molecules that are involved in ATP catabolism as well as regulating the production of IGF-1 in the process of hypertension, which is the main feature in patients with preeclampsia. On the other hand, decreased level of miR-18a lead to upregulation of HIF-1a, and the consequence condition of hypoxia increases hypertension and inflammation in these patients.

A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients

BackgroundThe COVID-19 pandemic has become the world’s main life-threatening challenge in the third decade of the twenty-first century. Numerous studies have been conducted on SARS-CoV2 virus structure and pathogenesis to find reliable treatments and vaccines. The present study aimed to evaluate the immune-phenotype and IFN-I signaling pathways of COVID-19 patients with mild and severe conditions.Material and methodsA total of 100 COVID-19 patients (50 with mild and 50 with severe conditions) were enrolled in this study. The frequency of CD4 + T, CD8 + T, Th17, Treg, and B lymphocytes beside NK cells was evaluated using flow cytometry. IFN-I downstream signaling molecules, including JAK-1, TYK-2, STAT-1, and STAT-2, and Interferon regulatory factors (IRF) 3 and 7 expressions at RNA and protein status were investigated using real-time PCR and western blotting techniques, respectively. Immune levels of cytokines (e.g., IL-1β, IL-6, IL-17, TNF-α, IL-2R, IL-10, IFN-α, and IFN-β) and the existence of anti-IFN-α autoantibodies were evaluated via enzyme-linked immunosorbent assay (ELISA).ResultsImmune-phenotyping results showed a significant decrease in the absolute count of NK cells, CD4 + T, CD8 + T, and B lymphocytes in COVID-19 patients. The frequency of Th17 and Treg cells showed a remarkable increase and decrease, respectively. All signaling molecules of the IFN-I downstream pathway and IRFs (i.e., JAK-1, TYK-2, STAT-1, STAT-2, IRF-3, and IRF-7) showed very reduced expression levels in COVID-19 patients with the severe condition compared to healthy individuals at both RNA and protein levels. Of 50 patients with severe conditions, 14 had anti-IFN-α autoantibodies in sera. Meanwhile, this result was 2 and 0 for patients with mild symptoms and healthy controls, respectively.ConclusionOur results indicate a positive association of the existence of anti-IFN-α autoantibodies and immune cells dysregulation with the severity of illness in COVID-19 patients. However, comprehensive studies are necessary to find out more about this context.5mo_nwLJpK7s-uZity9h4-Video abstract

Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis.

BACKGROUNDOccult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects.AIMTo highlight the global prevalence of OCI.METHODSWe performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran's Q-test and the I2 test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses.RESULTSThe electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I2 = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa.CONCLUSIONIn conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.

Association of Keap1 (rs11085735) polymorphism and lncRNA MEG3 hypermethylation status with the risk of preeclampsia

BackgroundPreeclampsia (PE) is one of the complications of pregnancy. The pathogenesis of PE has not been completely understood. The aims of the present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA (lncRNA) MEG3 in the risk of PE.MethodsIn a case–control study, 150 pregnant women, including 75 PE patients and 75 healthy pregnant women recruited from Western Iran with Kurdish ethnic background, were studied for Keap1 variants using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). The methylation status of lncRNA MEG3 was investigated using methylation-specific PCR (MSP) among 50 preeclamptic patients and 50 controls.ResultsThe frequency of Keap1 A allele was significantly lower (5.3%) in preeclamptic patients compared to controls (12.7%, p = 0.024). The frequencies of hemimethylated (UM) and full methylated (MM) lncRNA MEG3 were 94 and 6% (p = 0.04), respectively, in all patients, 86.4, and 13.6% (p = 0.04), respectively, in patients with severe preeclampsia and 98 and 0% in controls. The frequency of full methylated lncRNA MEG3 was 14.3% in early-onset preeclampsia and 2.8% in late-onset preeclampsia (p = 0.12). Patients with PE had significantly higher levels of liver biomarkers (including ALT, AST, ALP, and total bilirubin) and lower PLT counts compared to healthy pregnant women.ConclusionThe present study suggests the presence of hypermethylation status of lncRNA MEG3 in preeclampsia that might contribute to the pathogenesis and development of preeclampsia. Also, Keap1 rs11085735 polymorphism might be involved in the risk of preeclampsia.

Effects of environmental low-dose irradiation on functional-metabolic organ responses in a natural mouse population (Apodemus agrarius Pallas, 1771) within the East Urals Radioactive Trace (EURT) area, Russia

Hypothesis The level of radiation-induced functional metabolic reactivity can differ among organs (spleen, liver and myocardium) and reproductive-sexual groups (breeding and non-breeding under-yearlings: females and males). Materials and methods We analyzed Apodemus agrarius individuals captured in the zone of the East Urals Radioactive Trace (EURT, Russia). In this area, concentrations are 90Sr and 137Cs at 10,000 and 1000 Bq/kg, respectively, in a layer of soil not deeper than 10 cm. Comparative analysis was based on six biochemical parameters including the glycolysis level, peroxidation of lipids, H2O2-oxidoreductase status and concentrations of protein, DNA and RNA in tissues. Results External and internal doses of 137Cs and 90Sr for A. agrarius varied by an order of magnitude, from 0.013 to 0.177 mGy/d. The level of radiation exposure was found to not differ among females but it differed between the two male reproductive groups (breeding < non-breeding under-yearlings). Sexually mature males received a significantly lower dose than females. An increase in the dose rate correlated with an increase in all biochemical indicators, thus indicating high level of tissue metabolic functions. The reproductive status of females did not affect their radiation-induced organ response rate, whereas the response to radiation of breeding males was more than 1.5-fold higher than that of non-breeding males and 2-fold higher than that of females. Conclusions We believe that the variation of the dose load is due to migration processes: breeding males are more likely to migrate than females and therefore have less contact with radionuclides. The higher the response to radiation of breeding males can be explained by a hormonal factor: testosterone causes radiosensitivity. The reactivity of the tissues examined (myocardium < liver < spleen) develops apparently in accordance with the degree of their ‘staticity’ in accordance with the law of radiosensitivity of Bergonié and Tribondeau.

An Integrative Analysis Framework for Identifying the Prognostic Markers from Multidimensional RNA Data of Clear Cell Renal Cell Carcinoma

The altered regulatory status of long noncoding RNA (lncRNA), miRNA, and mRNA and their interactions play critical roles in tumor proliferation, metastasis, and progression, which ultimately influence cancer prognosis. However, there are limited studies of comprehensive identification of prognostic biomarkers from combined data sets of the three RNA types in the highly metastatic clear cell renal cell carcinoma (ccRCC). The current study employed an integrative analysis framework of functional genomics approaches and machine learning methods to the lncRNA, miRNA, and mRNA data and identified 16 RNAs (3 lncRNAs, 6 miRNAs, and 7 mRNAs) of prognostic value, with 9 of them novel. A 16 RNA-based score was established for prognosis prediction of ccRCC with significance (P < 0.0001). The area under the curve for the score model was 0.868 to 0.870 in the training cohort and 0.714 to 0.778 in the validation cohort. Construction of the lncRNA-miRNA-mRNA interaction network showed that the downstream mRNAs and upstream lncRNAs in the network initiated from the miRNA or lncRNA markers exhibit significant enrichment in functional classifications associated with cancer metastasis, proliferation, progression, or prognosis. The functional analysis provided clear support for the role of the RNA biomarkers in predicting cancer prognosis. This study provides promising biomarkers for predicting prognosis of ccRCC using multidimensional RNA data, and these findings are expected to facilitate potential clinical applications of the biomarkers.

Clinical and immunological characteristics of coronavirus disease 2019 patients with redetectable viral RNA post-discharge during the quarantine period

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. The global pandemic poses a serious challenge to the medical community. Detection of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) is crucial for the diagnosis of COVID-19. IgG is particularly important for antiviral response assessment. Our study divided 51 patients into "persistence" and "non-persistence" groups according to the status of positive RNA, and the clinical and immunological characteristics of two groups of patients with redetectable viral RNA post-discharge during their quarantine period were studied, including the clinical signs, symptoms, hospitalization time and laboratory blood routine tests, biochemical indexes, and IgM/IgG antibodies titers detecting. Overall, the median age was 57.0 (21–90) years, and the median time was 9 days from discharge to redetectable viral RNA. The median titers of IgM and IgG antibodies were 23.19 AU/mL and 170.36 AU/mL (<i>P</i>&gt;0.05), respectively. The median ratio of IgG/IgM was 6.63 and the median ratio of IgG/IgM was 8.02 and 4.03 for persistence and non-persistence groups, respectively (<i>P</i>=0.079). The median length of hospital stays for patients that had reached the composite endpoint was 16.5 and 9 days in the persistence and non-persistence groups. In conclusion, there was a significant difference in hospitalization time between the two groups of patients, but there was no statistical difference in the IgM/IgG titer detection, which required more data to verify.