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Background. COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic and mortality of people around the world. Some circular RNAs (circRNAs), one of the new types of noncoding RNAs (ncRNAs), act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, to regulate gene expression. In the present study, we aimed to evaluate the expression and roles of hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 in COVID-19 infection. Materials and Methods. After extraction of total RNA from peripheral blood mononuclear cells (PBMC) of 50 patients with symptomatic COVID-19, 50 patients with nonsymptomatic COVID-19, and 50 normal controls, cDNA synthesis was performed. Online in silico tools were applied to evaluate the interaction between the genes in the hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis, and its role in COVID-19-related pathways. Quantification of the expression of these genes and confirmation of their interaction was done using the quantitative real-time PCR (qRT-PCR) technique. Results. The expression levels of hsa_circ_0000479, RIG-I, and IL-6 were increased in COVID-19 patients compared to healthy controls, while hsa-miR-149-5p expression was decreased. Moreover, there was a significant negative correlation between hsa-miR-149-5p and hsa_circ_0000479, RIG-I, IL-6 expressions, and also a positive expression correlation between hsa_circ_0000479 and IL-6, RIG-I. Then, bioinformatics tools revealed the role of hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis in PI3K-AKT and STAT3 signaling pathways. Conclusion. Upregulation of hsa_circ_0000479, RIG-I, and IL-6, and downregulation of hsa-miR-149-5p, along with correlation studies, indicate that hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis could play a role in regulating the immune response against SARS-CoV-2. However, more studies are needed in this area.
There is a heterogeneous group of rare illnesses that fall into the vasculitis category and are characterized mostly by blood vessel inflammation. Ischemia and disrupted blood flow will cause harm to the organs whose blood arteries become inflamed. Kawasaki disease (KD) is the most prevalent kind of vasculitis in children aged 5 years or younger. Because KD's cardiovascular problems might persist into adulthood, it is no longer thought of as a self‐limiting disease. KD is a systemic vasculitis with unknown initiating factors. Numerous factors, such as genetic predisposition and infectious pathogens, are implicated in the etiology of KD. As endothelial cell damage and inflammation can lead to coronary endothelial dysfunction in KD, some studies hypothesized the crucial role of pyroptosis in the pathogenesis of KD. Additionally, pyroptosis‐related proteins like caspase‐1, apoptosis‐associated speck‐like protein containing a CARD (ASC), proinflammatory cytokines like IL‐1 and IL‐18, lactic dehydrogenase, and Gasdermin D (GSDMD) have been found to be overexpressed in KD patients when compared to healthy controls. These occurrences may point to an involvement of inflammasomes and pyroptotic cell death in the etiology of KD and suggest potential treatment targets. Based on these shreds of evidence, in this review, we aim to focus on one of the well‐defined inflammasomes, NLRP3, and its role in the pathophysiology of KD.
Background Breast cancer (BC) is one of the leading causes of death among women around the world. Circular RNAs (circRNAs) are a newly discovered group of non‐coding RNAs that their roles are being investigated in BC and other cancer types. In this study, we evaluated the association of hsa_circ_0005986 and hsa_circ_000839 in tumor and adjacent normal tissues of BC patients with their clinicopathological characteristics. Materials and methods Total RNA was extracted from tumors and adjacent non‐tumor tissues by the Trizol isolation reagent, and cDNA was synthesized using First Strand cDNA Synthesis Kit (Thermo Scientific). The expression level of hsa_circ_0005986 and hsa_circ_000839 was quantified using RT‐qPCR. Online in silico tools were used for identifying potentially important competing endogenous RNA (ceRNA) networks of these two circRNAs. Results The expression level of hsa_circ_0005986 and hsa_circ_000839 was lower in the tumor as compared to adjacent tissues. The expression level of hsa_circ_0005986 in the patients who had used hair dye in the last 5 years was significantly lower. Moreover, a statistically significant negative correlation between body mass index (BMI) and hsa_circ_000839 expression was observed. In silico analysis of the ceRNA network of these circRNAs revealed mRNAs and miRNAs with crucial roles in BC. Conclusion Downregulation of hsa_circ_000839 and hsa_circ_0005986 in BC tumors suggests a tumor‐suppressive role for these circRNAs in BC, meriting the need for more experimentations to delineate the exact mechanism of their involvement in BC pathogenesis.
The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroquine (CQ), an old antimalarial drug, and Hydroxychloroquine (HCQ) in the treatment of COVID-19 infection. HCQ is derived from CQ by adding a hydroxyl group into it and is a less toxic derivative of CQ for the treatment of COVID-19 infection because it is more soluble. This article summarizes pharmacokinetic properties and toxicity considerations for CQ and HCQ, drug interactions, and their potential efficacy against COVID-19. The authors also look at the biochemistry changes and clinical uses of CQ and HCQ, and supportive treatments following toxicity occurs. It was believed that CQ and HCQ may provide few benefits to COVID-19 patients. A number of factors should be considered to keep the drug safe, such as dose, in vivo animal toxicological findings, and gathering of metabolites in plasma and/or tissues. The main conclusion of this review is that CQ and HCQ with considered to their ADMET properties has major shortcomings and fully irresponsible.
Background SARS‐CoV‐2 is one of the most contagious viruses in the Coronaviridae (CoV) family, which has become a pandemic. The aim of this study is to understand more about the role of hsa_circ_0004812 in the SARS‐CoV‐2 related cytokine storm and its associated molecular mechanisms. Materials and Methods cDNA synthesis was performed after total RNA was extracted from the peripheral blood mononuclear cells (PBMC) of 46 patients with symptomatic COVID‐19, 46 patients with asymptomatic COVID‐19, and 46 healthy controls. The expression levels of hsa_circ_0004812, hsa‐miR‐1287‐5p, IL6R, and RIG‐I were determined using qRT‐PCR, and the potential interaction between these molecules was confirmed by bioinformatics tools and correlation analysis. Results hsa_circ_0004812, IL6R, and RIG‐I are expressed higher in the severe symptom group compared with the negative control group. Also, the relative expression of these genes in the asymptomatic group is lower than in the severe symptom group. The expression level of hsa‐miR‐1287‐5p was positively correlated with symptoms in patients. The results of the bioinformatics analysis predicted the sponging effect of hsa_circ_0004812 as a competing endogenous RNA on hsa‐miR‐1287‐5p. Moreover, there was a significant positive correlation between hsa_circ_0004812, RIG‐I, and IL‐6R expressions, and also a negative expression correlation between hsa_circ_0004812 and hsa‐miR‐1287‐5p and between hsa‐miR‐1287‐5p, RIG‐I, and IL‐6R. Conclusion The results of this in‐vitro and in silico study show that hsa_circ_0004812/hsa‐miR‐1287‐5p/IL6R, RIG‐I can play an important role in the outcome of COVID‐19.
Background: Circular RNAs (circRNAs), covalently closed single-stranded non-coding RNAs (ncRNAs), play pivotal roles in development and progression of breast cancer (BC). Although the roles of hsa_circ_0013958 and hsa_circ_0003028 in some malignancies have been explored, their function and expression in breast tumors are still unknown. This study was aimed to bioinformatically and experimentally evaluates the expression and potential function of hsa_circ_0013958 and hsa_circ_0003028 in BC. Materials and Methods: The quantitative real-time PCR method was used to determine the expression of hsa_circ_0013958 and hsa_circ_0003028 in 50 tumor samples and matched adjacent non-cancerous tissues. Besides, we used bioinformatic approaches to identify potentially important competing endogenous RNA (ceRNA) networks that are regulated by these circRNAs using some databases and software tools. Results: The hsa_circ_0013958 was significantly down-regulated in breast tumors compared with adjacent normal tissues, while the hsa_circ_0003028 had an upregulated pattern. Interestingly, it is found the higher expression of hsa_circ_0013958 showed association with a lack of use of hair dye as well as age at menarche ≥14 years in subjects. On the other hand, hsa_circ_0003028 expression was meaningfully related to age at first full-term pregnancy, antiperspirants use, and regular menstruation. Next, we found that these two circRNAs can potentially regulate some circRNAs-mediated miRNA sponge regulatory networks. Conclusion: The current work indicated that the hsa_circ_0013958 and hsa_circ_0003028 had reverse expression patterns in breast tumors, and it seems that they play key roles in the physiopathology of this cancer through potential key regulatory ceRNA functions. However, further functional studies are needed to validate these bioinformatically observed roles. [GMJ.2021;10:e2064]
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