Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Background:Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancerrelated deaths and its morbidity and mortality are increasing. PDAC patients have a very poor prognosis because of aggressive features of PDAC cells, shortage of reliable diagnostic biomarkers and deficiency of effective therapeutics.Objective:The article aims to discuss the recent progress in the discovery of novel molecular targets and their related mechanisms in the invasion and metastasis of PDAC cells.Methods:Literatures based on Pubmed database were searched and those related to the molecular targets involved in the invasion and metastasis of PDAC were reviewed.Results:The most promising discovery of molecular targets and phenomena include epithelialmesenchymal transition (EMT), cancer stem cells (CSCs), metastasis-related genes, hypoxiainducible factors (HIFs), non-coding RNAs (ncRNAs) and L1 cell adhesion molecule (L1CAM), which contribute to the vital biological behaviors of PDAC cells and tumor microenvironments.Conclusion:This review summarizes recent advances in novel molecular targets that regulate the invasion and metastasis of PDAC cells, and how they are targeted for developing diagnostic and therapeutic tools for combating PDAC. Further understanding the regulatory mechanisms of these molecular targets may help to discover biomarkers used for early diagnosis, predicting the prognosis and monitoring treatment response, and also to develop novel effective therapeutics.

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Expression Profile Analysis of Differentially Expressed Circular RNAs in Steroid-Induced Osteonecrosis of the Femoral Head

Disease Markers ◽

10.1155/2019/8759642 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Zhongxin Zhu ◽

Wenxi Du ◽

Huan Yu ◽

Hongting Jin ◽

Peijian Tong

Keyword(s):

Femoral Head ◽

Bioinformatics Analysis ◽

Profile Analysis ◽

Circular Rnas ◽

Healthy Individuals ◽

Bioinformatics Analyses ◽

Diagnostic Biomarkers ◽

Qrt Pcr ◽

Expression Profile Analysis

Background. A growing number of studies have suggested that circular RNAs (circRNAs) serve as potential diagnostic biomarkers in many diseases. However, the role of circRNAs in steroid-induced osteonecrosis of the femoral head (SONFH) has not been reported. Methods. Secondary sequencing was performed to profile circRNA expression in peripheral blood samples from three SONFH patients and three healthy individuals. We confirmed our preliminary findings by qRT-PCR. Bioinformatics analysis was conducted to predict their functions. Results. The result showed 345 dysregulated circRNAs. qRT-PCR of eight selected circRNAs preliminarily confirmed the results, which were consistent with RNA sequencing. Bioinformatics analyses were performed to predict the functions of circRNAs to target the genes of miRNAs and the networks of circRNA-miRNA-mRNA interactions. Conclusions. This study provides a new and fundamental circRNA profile of SONFH and a theoretical basis for further studies on the functions of circRNAs in SONFH.

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MiR-27a as a diagnostic biomarker and potential therapeutic target in systemic sclerosis

10.21203/rs.3.rs-770195/v1 ◽

2021 ◽

Author(s):

Paria Bayati ◽

Mahsa Kalantari ◽

Mohammad-Ali Assarehzadegan ◽

Hadi Poormoghim ◽

Nazanin Mojtabavi

Keyword(s):

Systemic Sclerosis ◽

Rna Isolation ◽

Protective Role ◽

The Novel ◽

Diagnostic Biomarker ◽

Contributing Factors ◽

Skin Tightening ◽

Bioinformatics Analyses ◽

Diagnostic Biomarkers ◽

Patient Groups

Abstract Background Systemic sclerosis (SSc) or scleroderma is a multiorgan rheumatoid disease characterized by skin tightening or organ dysfunction due to fibrosis, vascular damage, and autoimmunity. No specific cause has been discovered for this illness, and hence no effective treatment exists for it. On the other hand, due to the lack of diagnostic biomarkers capable of effectively and specifically differentiating the patients, early diagnosis has not been possible. Due to their potent regulatory roles in molecular pathways, microRNAs are among the novel candidates for the diagnosis and treatment of diseases like SSc. MiR-27a is a microRNA known for its role in the pathogenesis of fibrosis and cancer, both of which employ similar signaling pathways; hence we hypothesized that Mir-27a could be dysregulated in the blood of individuals affected by SSc and it might be useful in the diagnosis or treatment of this disease. Methods Blood was collected from 60 SSc patients (30 limited and 30 diffused) diagnosed by rheumatologist according to ACR/AULAR criteria; following RNA isolation and cDNA synthesis; real-time qPCR was performed on the samples using Taq-Man probes and data were analyzed by the ΔΔCT method. Also, potential targets of miR-27a were evaluated using bioinformatics. Results It was revealed that miR-27a was significantly down-regulated in SSc patients in comparison to the healthy individuals, but there was no difference in miR-27 expression between limited and diffused SSc patients. Besides, miR-27a was found to target several contributing factors to SSc. Conclusion It seems that miR-27a has a protective role in SSc, and its downregulation could result in the disease's onset. Based on bioinformatics analyses, it is speculated that miR-27a likely targets factors contributing to the pathogenesis of SSc, which are elevated upon the downregulation of miR-27a; hence, miR-27a mimics could be considered as potential therapeutic agents for the treatment of SSc in future studies. Since no difference was observed between limited and diffused patient groups, it is unlikely that this microRNA has a role in disease progression. According to ROC analysis of qPCR data, miR-27a could be employed as a valuable diagnostic biomarker for SSc.

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Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

Clinical Science ◽

10.1042/cs20191213 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2243-2262

Author(s):

Danlin Liu ◽

Gavin Richardson ◽

Fehmi M. Benli ◽

Catherine Park ◽

João V. de Souza ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Molecular Targets ◽

Therapeutic Interventions ◽

Low Grade ◽

Cardiovascular Research ◽

Inflammatory Processes ◽

Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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