scholarly journals Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Guozhong Chen ◽  
Lin Li ◽  
Hongmiao Tao
Keyword(s):  
Ischemic Stroke ◽  
Heart Diseases ◽  
Bioinformatic Analysis ◽  
Diagnostic Value ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Regulation Network ◽  
Transcription Factor Regulation ◽  
Therapeutic Compounds

Background: Stroke is one of the most common deadly diseases with an estimated 780,000 new cases globally, of which ischemic stroke accounts for over 80% of all cases. Ferroptosis is a new form of programmed cell death that plays a vital role in many diseases, including ischemic stroke and heart diseases. The role of the ferroptosis-related gene in the diagnosis, prognosis, or therapy of ischemic stroke was not fully clarified.Methods: Ferroptosis-related differentially expressed genes (DEGs) in ischemic stroke were identified by bioinformatic analysis of the GSE16561 and GSE22255 datasets. Subsequently, receiver operator characteristic (ROC) monofactor analysis was performed to evaluate the diagnostic value of ferroptosis-related biomarkers in ischemic stroke.Results: A total of 10 ferroptosis-related DEGs were identified in ischemic stroke vs. normal control. GO and KEGG analysis revealed that these 10 ferroptosis-related DEGs were mainly enriched in response to oxidative stress, HIF-1 signaling pathway, ferroptosis, lipid, and atherosclerosis. Moreover, the random forest model suggested three ferroptosis-related biomarkers, namely, PTGS2, MAP1LC3B, and TLR4, for ischemic stroke. Interestingly, the expression of PTGS2, MAP1LC3B, and TLR4 was upregulated in ischemic stroke. ROC monofactor analysis demonstrated a good performance of MAP1LC3B, PTGS2, and TLR4 in the diagnosis of ischemic stroke. The expression and diagnostic value of MAP1LC3B, PTGS2, and TLR4 in ischemic stroke were also verified using GSE22255. We also revealed the transcription factor regulation network and co-expressed protein network of ferroptosis-related biomarkers. Several potential therapeutic compounds corresponding to MAP1LC3B, PTGS2, and TLR4 were also identified for ischemic stroke, including Zinc12503187 (Conivaptan), Zinc3932831 (Avodart), Zinc64033452 (Lumacaftor), Zinc11679756 (Eltrombopag), Zinc100378061 (Naldemedine), and Zinc3978005 (Dihydroergotamine).Conclusion: Our results suggested MAP1LC3B, PTGS2, and TLR4 as potential diagnostic biomarkers for ischemic stroke, providing more evidence about the vital role of ferroptosis in ischemic stroke.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals The Emerging Picture of the Roles of CircRNA-CDR1as in Cancer

2020 ◽  
Vol 8 ◽  
Author(s):  
Chaohua Jiang ◽  
Xiaohong Zeng ◽  
Renfeng Shan ◽  
Wu Wen ◽  
Jianfeng Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Antisense Rna ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Cerebellar Degeneration ◽  
Circular Rnas ◽  
Related Protein ◽  
Future Prospects ◽  
Biological Features

Circular RNAs (circRNAs) are covalently closed circular structures without 5′ caps and 3′ tails, which are mainly formed from precursor mRNAs (pre-mRNAs) via back-splicing of exons. With the development of RNA sequencing and bioinformatic analysis, circRNAs were recently rediscovered and found to be widely expressed in the tree of life. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as) is recognized as one of the most well-identified circRNAs. It contains over 70 miR-7 binding sites and can regulate gene activity by sponging miR-7. Increasing numbers of studies have recently demonstrated that CDR1as is abnormally expressed in many types of tumors, such as colorectal cancer, cholangiocarcinoma and osteosarcoma, and plays a vital role in the development of cancer. However, there are few reviews focusing on CDR1as and cancer. Hence, it is important to review and discuss the role of CDR1as in cancer. Here, we first review the main biological features of CDR1as. We then focus on the expression and roles of CDR1as in cancer. Finally, we summarize what is known on the role of CDR1as in cancer and discuss future prospects in this area of research.

Role of Calcium Homeostasis in Ischemic Stroke: A Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Abhilash Ludhiadch ◽  
Rashmi Sharma ◽  
Aishwarya Muriki ◽  
Anjana Munshi
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Death ◽  
Complex Disease ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Vital Role ◽  
Calcium Accumulation ◽  
Cell Death Pathway

: Stroke is the second most common cause of death worldwide. It occurs due to the insufficient supply of oxygen-rich blood to the brain. It is a complex disease with multiple associated risk factors including smoking, alcoholism, age, sex, ethnicity, etc. Calcium ions are known to play a vital role in cell death pathways, which is a ubiquitous intracellular messenger during and immediately after an ischemic period. Disruption in normal calcium hemostasis is known to be a major initiator and activator of the ischemic cell death pathway. Under Ischemic stroke conditions, glutamate is released from the neurons and glia which further activates the N-methyl-D-aspartate (NMDA) receptor and triggers the rapid translocation of Ca2+ from extracellular to intracellular spaces in cerebral tissues and vice versa. Various studies indicated that Ca2+ could have harmful effects on neurons under acute ischemic conditions. Mitochondrial dysfunction also contributes to delayed neuronal death, and it was established decades ago that massive calcium accumulation triggers mitochondrial damage. Elevated Ca2+ levels cause mitochondria to swell and release their contents. As a result oxidative stress and mitochondrial calcium accumulation activate mitochondrial permeability transition and lead to depolarization-coupled production of reactive oxygen species. This association between calcium levels and mitochondrial death suggests that elevated calcium levels might have a role in the neurological outcome in ischemic stroke. Previous studies have also reported that elevated Ca2+ levels play a role in the determination of infarct size, outcome, and recurrence of ischemic stroke. The current review has been compiled to understand the multidimensional role of altered Ca2+ levels in the initiation and alteration of neuronal death after ischemic attack. The underlying mechanisms understood to date have also been discussed.

scholarly journals Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Juan Liu ◽  
Kun-shan Zhang ◽  
Bin Hu ◽  
Si-guang Li ◽  
Qing Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Expression Profiles ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Rna Regulation ◽  
Systematic Analysis ◽  
Short Interspersed Elements ◽  
Regulation Network ◽  
Cerebral Artery Occlusion

Although extensive studies have identified large number of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE) mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD) which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA) hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

scholarly journals Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoping Xie ◽  
Jiangbi Li ◽  
Feng Gu ◽  
Ke Zhang ◽  
Zilong Su ◽  
...  
Keyword(s):  
Systematic Review ◽  
Large Scale ◽  
Biological Effects ◽  
Bone Destruction ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide

Background: Osteomyelitis is an inflammatory process characterized by progressive bone destruction. Moreover, chronic bacterial osteomyelitis is regarded as a difficult-to-treat clinical entity due to its long-standing course and frequent infection recurrence. However, the role of genetic factors in the occurrence and development of bacterial osteomyelitis is poorly understood.Methods: We performed a systematic review to assess the frequency of individual alleles and genotypes of single-nucleotide polymorphisms (SNPs) among patients with bacterial osteomyelitis and healthy people to identify whether the SNPs are associated with the risk of developing bacterial osteomyelitis. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes analyses were performed to identify the potential biological effects of these genes on the pathogenesis of bacterial osteomyelitis.Result: Fourteen eligible studies containing 25 genes were analyzed. In this review, we discovered that the SNPs in IL1B, IL6, IL4, IL10, IL12B, IL1A, IFNG, TNF, PTGS2, CTSG, vitamin D receptor (VDR), MMP1, PLAT, and BAX increased the risk of bacterial osteomyelitis, whereas those in IL1RN and TLR2 could protect against osteomyelitis. The bioinformatic analysis indicated that these osteomyelitis-related genes were mainly enriched in inflammatory reaction pathways, suggesting that inflammation plays a vital role in the development of bacterial osteomyelitis. Furthermore, functional notation for 25 SNPs in 17 significant genes was performed using the RegulomeDB and NCBI databases. Four SNPs (rs1143627, rs16944, rs2430561, and rs2070874) had smaller scores from regulome analysis, implying significant biological function.Conclusion: We systematically summarized several SNPs linked to bacterial osteomyelitis and discovered that these gene polymorphisms could be a genetic factor for bacterial osteomyelitis. Moreover, further large-scale cohort studies are needed to enhance our comprehensive understanding of the development of osteomyelitis to provide earlier individualized preventions and interventions for patients with osteomyelitis in clinical practice.

scholarly journals Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 793
Author(s):  
Eric Gustavo Ramírez-Salazar ◽  
Luis Vicente Gayosso-Gómez ◽  
Renata Baez-Saldaña ◽  
Ramcés Falfán-Valencia ◽  
Rogelio Pérez-Padilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cigarette Smoking ◽  
Smoking Status ◽  
Diagnostic Value ◽  
Circulating Microrna ◽  
Diagnostic Biomarkers ◽  
Expression Levels ◽  
Lung Cancer Patients ◽  
Never Smokers

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.

scholarly journals The Role of miRNAs 340-5p, 92a-3p, and 381-3p in Patients with Endometriosis: A Plasma and Mesenchymal Stem-Like Cell Study

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Afshin Bahramy ◽  
Narges Zafari ◽  
Pantea Izadi ◽  
Fatemeh Soleymani ◽  
Saeideh Kavousi ◽  
...  
Keyword(s):  
Zinc Finger Protein ◽  
In Silico Analysis ◽  
Bioinformatic Analysis ◽  
Diagnostic Methods ◽  
Diagnostic Biomarkers ◽  
Women's Lives ◽  
Noninvasive Biomarker ◽  
Gynecological Disease ◽  
The Relationship

Background. Endometriosis is the most prevalent gynecological disease with elusive etiology. The mysterious entity and the lack of noninvasive diagnostic methods affect women’s lives negatively. This study is aimed at finding the relationship between miR-340-5p, 92a-3p, and miR-381-3p and the pathogenesis of endometriosis in endometrial mesenchymal stem-like cells (eMSCs) of endometriosis and assessing their potential as a noninvasive biomarker in plasma. Methods. Peripheral blood and eMSC specimens were collected from suspected women of endometriosis before laparoscopy. Total RNA was isolated from plasma and cultured eMSCs to synthesize complementary DNA. The expression of miR-340-5p, miR-92a-3p, and miR-381-3p was analyzed by RT-qPCR. To understand these miRNAs’ role, we also did a bioinformatic analysis. Results. There was a downregulation of miR-340-5p, miR-92a-3p, and miR-381-3p in plasma, and the upregulation of miR-340-5p and the downregulation of miR-92a-3p and miR-381-3p in eMSCs of women with endometriosis. There was a positive concordance between the expression of miR-92a-3p and miR-381-3p in plasma and eMSCs. Our study also showed three genes, Solute Carrier Family 6 Member 8 (SLC6A8), Zinc Finger Protein 264 (ZNF264), and mouse double minute 2 (MDM2), as common targets of these miRNAs. Conclusions. This study has been one of the first attempts to examine the expression of miR-340-5p, miR-92a-3p, and miR-381-3p in both plasma and eMSCs and revealed their possible role in endometriosis based on in silico analysis. Biomarkers pave the way to develop a new therapeutic approach to the management or treatment of endometriosis patients. Our result as a first report shows that combined levels of miRNAs 340-5p and 381-3p may have the potential to be utilized as diagnostic biomarkers for endometriosis.

The Role of Serum Procalcitonin Level as an Early Marker of Ascitic Fluid Infection in Post Hepatitic Cirrhotic Patients

2020 ◽  
Vol 19 ◽  
Author(s):  
Mohamed Zakaria Abu Rahma ◽  
Zainab Gaber Mahran ◽  
Engy Adel Shafik ◽  
Dina Ahmed Mohareb ◽  
Nessren M. Abd El-Rady ◽  
...  
Keyword(s):  
Prospective Study ◽  
Ascitic Fluid ◽  
Fluorescence Analysis ◽  
Diagnostic Value ◽  
Emergency Setting ◽  
Diagnostic Biomarkers ◽  
Bacterial Peritonitis ◽  
Cirrhotic Patients ◽  
Fluid Culture

Background & Aims: The early diagnosis of spontaneous bacterial peritonitis (SBP) has been considered important in overall patient’s survival. Ascitic fluid culture examination performance, in the emergency setting, is time consuming and not always available, so there is a need for easy to apply, rapid and reliable markers to predict diagnosis in patients with ascites. This present prospective study aimed to determine the early diagnostic value of serum procalcitonin (PCT) levels in decompensated cirrhotic patients (DCPs) with SBP. Methods: 47 HCV cirrhotic patients with ascites were enrolled for this prospective study. The severity of cirrhosis was classified based on the Child–Pugh criteria. All patients were subjected to paracentesis and ascitic fluid (AF) culture. Serum PCT levels were measured using enzyme-linked fluorescence analysis (ELFA). Results: The diagnostic value of serum PCT levels and WBC/PLT ratios for detecting infections were serum PCT levels (3.63 ± 3.47 ng/mL) in DCPs with infections which was significantly higher than in DCPs without infections (0.505 ± 0.230 ng/mL); p < 0.05. The cut-off value for serum PCT levels was 0.7 ng/mL for the diagnosis of infections in DCPs, for which the sensitivity and specificity were 93.1% and 73.2%, respectively. The AUC was 0.91 (95% CI: 0.83–0.99). Conclusions: Serum procalcitonin seems to provide satisfactory diagnostic biomarkers in SBP.

scholarly journals 2D:4D Ratio differs in ischemic stroke: A single center experience

2018 ◽  
Vol 9 (1) ◽  
pp. 142-146 ◽  
Author(s):  
Ke Yang ◽  
XianHui Ding ◽  
ZhiMing Zhou ◽  
XiaoLei Shi
Keyword(s):  
Ischemic Stroke ◽  
Sex Hormones ◽  
Ring Finger ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Stroke Severity ◽  
Single Center Experience ◽  
Predicting Performance ◽  
Role Of It

Abstract Background The index to ring finger length (2D:4D) ratio is a proxy biomarker for prenatal exposure of sex hormones. Sex hormones are associated with the pathogenesis of ischemic stroke. The purpose of the study was to demonstrate the association between 2D:4D and ischemic stroke. Methodology This study retrospectively reviewed the data of 100 patients with first ever ischemic stroke between September, 2016 and June, 2017. The lengths of index finger and ring finger of both hands were measured using electronic calipers and calculated for 2D:4D ratios. Receive operating characteristic (ROC) mode was used to detect predicting performance of 2D:4D ratios for ischemic stroke. Results 2D:4D ratios in ischemic stroke patients were higher than controls in both hands (P < 0.05), except right 2D:4D ratio in females. The ROC analyses showed that the area under the curve (AUC) were 0.635 (95%CI: 0.527-0.743) for left 2D:4D ratio, and 0.647 for right (95%CI: 0.539-0.755) (P < 0.05). The AUC of left and right 2D:4D ratio in male were 0.667 (95%CI: 0.514-0.820) and 0.670 (95%CI: 0.519-0.822) (P < 0.05). In female, no significance were found in ROC analysis. And there were no correlation between 2D:4D value and stroke severity (P > 0.05). Conclusions The current study indicated that the diagnostic value of 2D:4D ratio was limited in ischemic stroke. Further research is required to explore the role of it in screening ischemic stroke.

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