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

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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Identification and analysis of circulating long non-coding RNAs with high significance in diabetic cardiomyopathy

Scientific Reports ◽

10.1038/s41598-021-82345-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tarun Pant ◽

Anuradha Dhanasekaran ◽

Ming Zhao ◽

Edward B. Thorp ◽

Joseph M. Forbess ◽

...

Keyword(s):

Cardiac Function ◽

Diabetic Cardiomyopathy ◽

Bioinformatic Analysis ◽

Mitogen Activated Protein Kinase ◽

Diagnostic Biomarker ◽

Diagnostic Biomarkers ◽

Mitogen Activated Protein ◽

Non Coding Rnas ◽

Α Chain ◽

Factor Α

AbstractDiabetic cardiomyopathy (DCM) lacks diagnostic biomarkers. Circulating long non-coding RNAs (lncRNAs) can serve as valuable diagnostic biomarkers in cardiovascular disease. To seek potential lncRNAs as a diagnostic biomarker for DCM, we investigated the genome-wide expression profiling of circulating lncRNAs and mRNAs in type 2 diabetic db/db mice with and without DCM and performed bioinformatic analyses of the deregulated lncRNA-mRNA co-expression network. Db/db mice had obesity and hyperglycemia with normal cardiac function at 6 weeks of age (diabetes without DCM) but with an impaired cardiac function at 20 weeks of age (DCM) on an isolated Langendorff apparatus. Compared with the age-matched controls, 152 circulating lncRNAs, 127 mRNAs and 3355 lncRNAs, 2580 mRNAs were deregulated in db/db mice without and with DCM, respectively. The lncRNA-mRNA co-expression network analysis showed that five deregulated lncRNAs, XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135, have the maximum connections with differentially expressed mRNAs. Bioinformatic analysis revealed that these five lncRNAs were highly associated with the development and motion of myofilaments, regulation of inflammatory and immune responses, and apoptosis. This finding was validated by the ultrastructural examination of myocardial samples from the db/db mice with DCM using electron microscopy and changes in the expression of myocardial tumor necrosis factor-α and phosphorylated p38 mitogen-activated protein kinase in db/db mice with DCM. These results indicate that XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135 are crucial circulating lncRNAs in the pathogenesis of DCM. These five circulating lncRNAs may have high potential as a diagnostic biomarker for DCM.

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Correction to: Genome Analysis and Genomic Comparison of the Novel Species Arthrobacter ipis Reveal Its Potential Protective Role in Its Bark Beetle Host

Microbial Ecology ◽

10.1007/s00248-021-01811-x ◽

2021 ◽

Author(s):

L. I. González-Dominici ◽

Z. Saati-Santamaría ◽

P. García-Fraile

Keyword(s):

Bark Beetle ◽

Genome Analysis ◽

Novel Species ◽

Protective Role ◽

The Novel ◽

Genomic Comparison

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MiR-320a as a Diagnostic Biomarker for Alzheimer’s Disease and Its Protective Role against Amyloid-β Induced Neurotoxicity

Advances in Clinical Medicine ◽

10.12677/acm.2021.112094 ◽

2021 ◽

Vol 11 (02) ◽

pp. 646-654

Author(s):

群张

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Protective Role ◽

Diagnostic Biomarker

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Bufei Qingyu Granules Inhibit the Development of Systemic Sclerosis via Notch-1/Jagged-2 Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6709278 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16

Author(s):

Minhui Su ◽

Fang Tian ◽

Bingchen Ouyang ◽

Xiaoyu Wu ◽

Feng Guo ◽

...

Keyword(s):

Systemic Sclerosis ◽

Notch Signaling ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Smooth Muscle Actin ◽

Notch Signaling Pathway ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Notch 1 ◽

Bioinformatics Analyses

Systemic sclerosis (SSc) is a rare chronic autoimmune disorder, mainly characterized by skin sclerosis. In this study, Bufei Qingyu Granules (BQG), a Chinese herbal formula, was used to treat SSc. To better understand the effects and molecular mechanisms of BQG, we successfully established a Bleomycin- (BLM-) induced SSc mouse model, and the mice were treated by BQG. Meanwhile, transcriptomic and bioinformatics analyses were conducted on those samples. As a result, we visually showed that BQG ameliorated the overall health of mice, including body weight, spleen, and thymus index. Thus, it also significantly alleviated inflammation presented by Chemokine (C-X-C motif) ligand 2 (Cxcl2), vasculopathy characterized by α-smooth muscle actin (α-SMA), and fibrotic changes elaborated by not only pathological images, but also the hydroxyproline (HYP) content. After testing by transcriptomic analysis, Cxcl2, Synaptosomal-associated protein 25 (Snap25), and Eukaryotic translation initiation factor 3, and subunit J2 (Eif3j2) which were differentially expressed genes, were verified, so that the data were credible. We further found that BQG could regulate Notch signaling pathway by significantly decreasing both mRNA and protein expression levels of Notch-1 and Jagged-2. Hence, this study demonstrated that BQG could ameliorate the sclerotic skin in mice model involved in inflammation, vascular changes, and fibrosis effects, which was partly mediated by Notch signaling pathway.

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Sexual Dimorphism in Colon Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.607909 ◽

2020 ◽

Vol 10 ◽

Author(s):

Maria Abancens ◽

Viviana Bustos ◽

Harry Harvey ◽

Jean McBryan ◽

Brian J. Harvey

Keyword(s):

Sexual Dimorphism ◽

Older Women ◽

Epithelial Mesenchymal Transition ◽

Protective Role ◽

Survival Outcome ◽

The Novel ◽

Sex Steroid Hormone ◽

Mesenchymal Transition ◽

Vegf Signaling ◽

Kv Channels

A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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miR-217 Is a Useful Diagnostic Biomarker and Regulates Human Podocyte Cells Apoptosis via Targeting TNFSF11 in Membranous Nephropathy

BioMed Research International ◽

10.1155/2017/2168767 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jing Li ◽

Bin Liu ◽

Hen Xue ◽

Qiao Qiao Zhou ◽

Ling Peng

Keyword(s):

Membranous Nephropathy ◽

Target Gene ◽

In Vitro Experiments ◽

Diagnostic Biomarker ◽

Diagnostic Biomarkers ◽

Cutoff Value ◽

Pathological Mechanism ◽

Opposite Change ◽

And Control

Background. MicroRNAs have recently been verified as useful diagnostic biomarkers in various diseases. In this study, we investigated whether miR-217 is a useful diagnostic biomarker and the possible pathological mechanism of miR-217 in this disease. Methods. Patients with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and diabetic nephropathy (DN) and control patients were enrolled in this study. The miR-217 inhibitor and mimics were transfected into human podocyte cells to investigate the pathological mechanism of miR-217 in this disease. Relevant indicators were detected and tested. Results. Compared with control patients, miR-217 was significantly downregulated and TNFSF11 was significantly upregulated in MN. Then, miR-217 had obvious separation between patients with MN and control patients, with an AUC of 0.941, a cutoff value of <750.0 copies/ul, and sensitivity and specificity of 88.9% and 75.9%. In addition, the TNFSF11 was confirmed to be the target gene of miR-217. Finally, in in vitro experiments, the upregulation of miR-217 could decrease the expression of TNFSF11 and not induce human podocyte cells apoptosis; however, the downregulation of miR-217 could bring about an opposite change. Conclusions. miR-217 is a useful diagnostic biomarker and is involved in human podocyte cells apoptosis via targeting TNFSF11 in membranous nephropathy.

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Prosthetic rehabilitation for a patient with systemic sclerosis and sjögren's syndrome: a clinical report and review

Dental Update ◽

10.12968/denu.2019.46.5.450 ◽

2019 ◽

Vol 46 (5) ◽

pp. 450-461

Author(s):

Funmi Oluwajana ◽

Lucy Ferguson ◽

Phillip Wragg

Keyword(s):

Systemic Sclerosis ◽

Mouth Opening ◽

Signs And Symptoms ◽

Clinical Report ◽

The Novel ◽

Prosthetic Rehabilitation ◽

Limited Mouth Opening ◽

Dental Management ◽

Management Plans ◽

The Impact

Systemic sclerosis, although a rare disease, has numerous direct and indirect effects on the oral cavity. This article aims to inform clinicians of the signs and symptoms they may see in patients with the disease and the impact it can have on dental management. The main effect, microstomia, is not just limited to systemic sclerosis, thus the clinical and laboratory techniques described may be helpful when managing other patients with limited mouth opening. CPD/Clinical Relevance: Clinicians should be able to recognize how systemic sclerosis will have an impact on their patient's oral health and implement management plans to prevent deterioration of their dentition. The novel techniques used will provide dentists and dental technicians with alternative techniques that can be employed in a variety of cases when considering prosthetic rehabilitation.

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

Gene Reports ◽

10.1016/j.genrep.2020.100956 ◽

2020 ◽

Vol 21 ◽

pp. 100956

Author(s):

Basavaraj Vastrad ◽

Chanabasayya Vastrad ◽

Anandkumar Tengli

Keyword(s):

Molecular Targets ◽

Bioinformatics Analyses ◽

Diagnostic Biomarkers

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Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

Journal of Clinical Medicine ◽

10.3390/jcm9041130 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1130

Author(s):

Peter Jirak ◽

Rudin Pistulli ◽

Michael Lichtenauer ◽

Bernhard Wernly ◽

Vera Paar ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Biomarkers ◽

Control Group ◽

The Novel ◽

Significant Elevation ◽

Serum Samples ◽

Diagnostic Challenge ◽

Diagnostic Biomarkers ◽

Diagnostic Potential ◽

Cardiovascular Biomarkers

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM. Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA. Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls (p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group (p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients (p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group (p < 0.0001) and HFpEF patients (p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713–0.870) and GDF-15 (0.787, 95% CI 0.696–0.878) as paramount diagnostic biomarkers for HFpEF patients. Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.

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