Correlation of Vitamin D3 with the Expression of RORγt and Foxp3 mRNAs in the Peripheral Blood of Myasthenia Gravis Patients

2020 ◽  
pp. 1-7
Author(s):  
Pan Huang ◽  
Xiao-ying He ◽  
Min Xu

<b><i>Objectives:</i></b> to investigate the expression levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> in the peripheral blood from patients with myasthenia gravis (MG) and to correlate levels with retinoid-related orphan receptor γt (RORγt) and forkhead or winged-helix transcription factor 3 (Foxp3) mRNA expression. <b><i>Methods:</i></b> Sixty-seven patients with MG were enrolled in the experimental group, and 50 normal subjects were selected as the control group. The expression levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> and RORγt and Foxp3 mRNAs were measured in the serum of the 2 patient groups and the relationship between factors were correlated with the severity score of MG. The relationship between the levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> and the relative expressions of RORγt and Foxp3 mRNAs was determined. <b><i>Results:</i></b> There were no differences between groups regarding patient’s baseline data. 1,25(OH)<sub>2</sub>D<sub>3</sub> and RORγt and Foxp3 mRNAs are differentially expressed in the MG group and the control group (<i>p</i> &#x3c; 0.05). QMG score is negatively correlated with the expression level of peripheral blood 1,25(OH)<sub>2</sub>D<sub>3</sub> and Foxp3 mRNA (<i>r</i> = −0.797, −0.543; <i>p</i> &#x3c; 0.01) and positively correlated with the relative expression level of RORγt mRNA (<i>r</i> = 0.539; <i>p</i> &#x3c; 0.01). 1,25(OH)<sub>2</sub>D<sub>3</sub> expression level was negatively correlated with the relative expression of RORγt mRNA (<i>r</i> = −0.559; <i>p</i> &#x3c; 0.01) and positively correlated with the relative expression of Foxp3 mRNA (<i>r</i> = 0.390; <i>p</i> &#x3c; 0.01). <b><i>Conclusions:</i></b> The levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> were shown to be lower in patients with MG compared to normal controls. The observed low levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> may lead to changes in the expression of RORγt and Foxp3 mRNAs involved in MG.

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Youyou Wang ◽  
Huijun Ren ◽  
Zhaohu Pan ◽  
Ben Liu ◽  
Fan Lin

Objective. To investigate the expression of miR-338-3p in nasopharyngeal carcinoma (NPC) and its relationship with STAT3 mRNA expression as well as their relationship with clinical pathological parameters and prognosis of patients. Methods. From September 2016 to September 2018, 71 patients with NPC were selected as the NPC group, and 71 samples of NPC tissues were collected during the operation. A total of 23 patients who underwent biopsy due to chronic nasopharyngitis were selected as the control group and 23 nasopharyngeal mucosal tissues were collected. The expressions of miR-338-3p and STAT3 mRNA in nasopharyngeal tissue of two groups were detected by real-time quantitative PCR, and the relationship between the two was analyzed. To collect clinical data of NPC patients and analyze the relationship between the expressions of miR-338-3p and STAT3 in NPC tissues and clinical pathological parameters of the patients, we followed up the patients with nasopharyngeal carcinoma for three years to observe the relationship between miR-338-3p, STAT3, and the prognosis of the patients. Results. The relative expression levels of miR-338-3p in nasopharyngeal tissues of the NPC group and the control group were 0.39 ± 0.05 and 1.01 ± 0.09, respectively ( P  < 0.05). The relative expression levels of STAT3 mRNA in nasopharyngeal tissues of the NPC group and the control group were 3.82 ± 0.21 and 1.04 ± 0.11, respectively ( P  > 0.05). miR-338-3p was negatively correlated with the relative expression of STAT3 mRNA in nasopharyngeal carcinoma (r = 0.038, P  > 0.05). The expression of miR-338-3p was related to the age of the patient, clinical TNM stage, T stage, and distant metastasis (all P  < 0.05). STAT3 expression was correlated with clinical TNM stage, T stage, and distant metastasis in our patient ( P  < 0.05). The expressions of miR-338-3p and STAT3 in nasopharyngeal carcinoma tissues from different gender, histological type, N stage, M stage, and degree of differentiation showed no statistical differences ( P  > 0.05). The survival rate of the group with low miR-338-3p expression was significantly lower than that of the group with high miR-338-3p expression ( P  > 0.05). The survival rate of patients with the high STAT3 expression group was significantly lower than that of patients with the low STAT3 expression group ( P  > 0.05). Conclusion. There is a negative correlation between the low expression of miR-338-3p and the high expression of STAT3 in NPC, which are all related to the TNM stage, T stage, and prognosis of the patient.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Man Tian ◽  
Ying Zhou ◽  
Haoyuan Jia ◽  
Xuming Zhu ◽  
Yubao Cui

This study assessed the changes and clinical significance of microRNA-1 (miR-1) and inflammatory factors in the peripheral blood of children with acute-stage asthma. 100 children with acute-stage asthma (study group) and 100 healthy children (control group) were enrolled. For all enrolled children, the peripheral blood levels of miR-1, interleukin-4 (IL-4), IL-5, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) were measured. The relative expression levels of miR-1 and IFN-γ in the peripheral blood of children in the study group were significantly lower than those in the control group, whereas expression levels of IL-4, IL-5, IL-8, and TNF-α were significantly higher. Moreover, these levels changed to a greater extent in patients with severe disease (P < 0.05). Further analyses showed that the miR-1 expression level positively correlated with IFN-γ and negatively correlated with IL-4, IL-5, IL-8, and TNF-α expression levels (P < 0.05). ROC curve analysis to identify diagnostic specificity and sensitivity showed that, for diagnosing exacerbation in asthma, the area under the curve (AUC) for miR-1 was the highest (AUC = 0.900, P < 0.05) of all tested markers; this held true for diagnosing severe asthma as well (AUC = 0.977, P < 0.05). Compared to healthy children, children with acute-stage asthma had a low miR-1 expression level and a Th1/Th2 imbalance in their peripheral blood. The changes were closely related, became more exaggerated with an increase in disease severity, and could be used as auxiliary variables for diagnosing asthma exacerbation and evaluating disease severity.


2020 ◽  
Author(s):  
Arash Adamnejad Ghafour ◽  
Demet Akdeniz Odemis ◽  
Seref Bugra Tuncer ◽  
Busra Kurt ◽  
Mukaddes Avsar Sarali ◽  
...  

Abstract The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America(USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous)monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Arash Adamnejad Ghafour ◽  
Demet Akdeniz Odemis ◽  
Seref Bugra Tuncer ◽  
Busra Kurt ◽  
Mukaddes Avsar Saral ◽  
...  

AbstractThe most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.


2021 ◽  
Author(s):  
Feifei Huo ◽  
Xueyang Zou ◽  
Yi Zhang ◽  
Rongchao Zhang ◽  
Xiaoya Wang ◽  
...  

Abstract Background: Recent trans-ethnic genome-wide association study (GWAS) showed that autoimmune regulator (Aire) played a pivotal role in Rheumatoid Arthritis (RA). Our preliminary research showed that Aire can affect T follicular helper (Tfh) cells differentiation by regulating the expression of inducible costimulator molecule ligand (ICOSL) on DCs. The abnormal levels of Tfh cells are related to the pathogenesis of RA, which can promote autoantibody production by helping autoreactive B cells activation.Therefore, the abnormal expression of the Aire in RA patients may lead to increased expression of ICOSL, promoting the differentiation of Tfh cells and the secretion of autoantibodies, consequently resulting in RA. However, to date, changes in the Aire, Tfh cell, and ICOSL levels in the peripheral blood of RA patients have not been reported. This study assessed the expression level of Aire and ICOSL and the number of Tfh cells in the peripheral blood of patients with RA and then explored the relationship between these three factors and RA severity. We are attempting to further explore the pathogenesis of RA to develop targeted treatments.Methods: Fifteen RA patients were enrolled, basic clinical information of the patients was collected, blood samples were collected to examine the Aire expression, ICOSL expression and CD4+CXCR5+PD1+ (Tfh cell) numbers in circulation before treatment. The relationship between these three factors and RA severity was explored.Results: This study showed that compared with the control group, the levels of circulating Aire in RA group significantly reduced, while the ICOSL expression levels and Tfh cell numbers in the peripheral blood of RA group were increased. Additionally, the Aire expression levels were negatively correlated with the ICOSL expression levels and Tfh cell numbers, and the ICOSL expression levels were positively correlated with Tfh cell numbers. Moreover, the Aire and ICOSL expression levels and Tfh cell numbers were correlated with anti-cyclic citrullinated peptide antibodies (ACPA) levels and disease activity score in 28 joints (DAS28). Conclusions: These results suggested the abnormal Aire gene expression in RA patients may affect Tfh differentiation by regulating the expression of ICOSL, leading to the autoantibodies production and promote the onset of RA.


2019 ◽  
Vol 17 ◽  
pp. 205873921984406
Author(s):  
Tao Zheng ◽  
Qingyun Zhou ◽  
Zhe Chen ◽  
Qinning Wang

The study aimed to study the correlation between expression levels of interleukin-37 (IL-37), granulocyte macrophage colony-stimulating factor (GM-CSF), and C-reactive protein (CRP) in peripheral blood and the status of atherosclerosis (AS) and plaque stability and to confirm the clinical significance of these inflammatory factors in the pathogenesis of AS. A total of 64 AS patients (case group) were selected and divided into unstable plaque group (group A, 28 cases) and stable plaque group (group B, 36 cases) according to the color ultrasonography results of arterial vessels. At the same time, 30 healthy subjects were classified into the control group. General information of the enrolled subjects was collected, including levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), CRP, and homocysteine (Hcy). The expression levels of IL-37 and GM-CSF in the serum of peripheral blood samples collected from these subjects were measured by enzyme-linked immunosorbent assay (ELISA). There was no significant difference between the case group and the control group in the levels of TC, TG, HDL, and LDL ( P > 0.05). However, the expression level of Hcy in the case group was significantly higher than that in the control group ( P < 0.05). Compared with the control group, the expression levels of IL-37, GM-CSF, and CRP in the case group were significantly increased ( P < 0.05). In addition, compared with group B, the expression level of GM-CSF in group A was significantly increased ( P < 0.05), while no significant difference was detected between group A and group B in the expression levels of IL-37 and CRP ( P > 0.05). In conclusion, inflammatory factors IL-37, GM-CSF, CRP, and Hcy were all involved in the pathogenesis of AS, and the increased levels of GM-CSF were closely related to the progress of unstable plaques. These results may aid the early diagnosis/treatment of AS.


2019 ◽  
Vol 17 ◽  
pp. 205873921882022
Author(s):  
Ge Zhang ◽  
Wei Huang ◽  
Ying Wang

The study aimed to detect the expression level of interleukin-37 (IL-37) in patients with rheumatoid arthritis (RA) and explore its clinical significance. A total of 40 peripheral blood samples from active and stable RA patients were collected (40 patients with RA), and peripheral blood from 40 healthy volunteers was used as the control group. Peripheral blood serum and peripheral blood mononuclear cells (PBMCs) were isolated. The expression of IL-37 mRNA in PBMCs was detected by real-time fluorescence quantitative PCR. Serum levels of IL-37, rheumatoid factor (RF), and anticyclic citrullinated peptide antibody (CCP) were measured by enzyme-linked immunosorbent assay (ELISA). The results were then calculated and analyzed. The results showed that expression of IL-37 mRNA in the PBMCs of patients with RA was significantly higher than that in the control group ( P < 0.05). Expression of IL-37 mRNA in the PBMCs of the active period group was significantly higher than that in the stable period group ( P < 0.05). IL-37 levels in patients with RA were significantly higher than those of the control group ( P < 0.05). IL-37 levels in the active period group were also significantly higher than those of the stable period group ( P < 0.05). The comparative analysis of RF and anti-CCP antibody levels showed that IL-37 was positively correlated with RF and anti-CCP levels in patients with RA. In conclusion, the expression level of IL-37 in peripheral blood of RA patients was significantly higher than that of normal control group, and it was correlated with RF and CCP antibody levels, indicating that IL-37 plays an important role in the development of RA.


2014 ◽  
Vol 34 (5) ◽  
pp. 497-505 ◽  
Author(s):  
F Guo ◽  
YB Sun ◽  
L Su ◽  
S Li ◽  
ZF Liu ◽  
...  

Paraquat (PQ) is one of the most widely used herbicides in the world and can cause pulmonary fibrosis in the cases with intoxication. Losartan, an angiotensin II type 1 receptor antagonist, has beneficial effects on the treatment of fibrosis. The aim of this study was to examine the effect of losartan on pulmonary fibrosis in PQ-intoxicated rats. Adult male Sprague Dawley rats ( n = 32, 180–220 g) were randomly assigned to four groups: (i) control group; (ii) PQ group; (iii) PQ + losartan 7d group; and (iv) PQ + losartan 14d group. Losartan treatment (intragastrically (i.g.), 10 mg/kg) was performed for 7 and 14 days after a single i.g. dose of 40 mg/kg PQ. All rats were killed on the 16th day, and hematoxylin–eosin and Masson’s trichrome staining were used to examine lung injury and fibrosis. The levels of hydroxyproline and transforming growth factor β1 (TGF-β1), matrix metallopeptidase 9 (Mmp9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) messenger RNA (mRNA) expression and relative expression levels of collagen type I and III were also detected. PQ caused a significant increase in hydroxyproline content, mRNA expression of TGF-β1, Mmp9, and TIMP-1, and relative expression levels of collagen type I and III (  p < 0.05), while losartan significantly decreased the amount of hydroxyproline and downregulated TGF-β1, Mmp9, and TIMP-1 mRNA and collagen type I and III expressions (  p < 0.05). Histological examination of PQ-treated rats showed lung injury and widespread inflammatory cell infiltration in the alveolar space and pulmonary fibrosis, while losartan could markedly reduce such damage and prevent pulmonary fibrosis. The results of this study indicated that losartan could reduce lung damage and prevent pulmonary fibrosis induced by PQ.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2429-2429
Author(s):  
Olivier Pierre-Louis ◽  
Joris Andrieux ◽  
Christophe Desterke ◽  
Eric Lippert ◽  
Vincent Praloran ◽  
...  

Abstract MMM is a myeloproliferative disorder characterized by extramedullary hematopoiesis and reactive myelofibrosis. Recently, HMGA2 dysregulation has been demonstrated in 2 MMM patients showing 12q15 rearrangement and confirmed in 25 consecutive MMM patients without cytogenetic abnormalities (Andrieux, 2004). HMGA2 proteins belong to the high mobility group A (HMGA) family of architectural transcription factors regulating the expression of several genes. As MMM is a clonal disorder of CD34+ hematopoietic progenitors, we analyzed HMGA2 expression in peripheral blood sub-populations of 5 MMM patients and 7 healthy donors to determine in which sub-population HMGA2 was dysregulated. RNA was extracted from peripheral blood mononuclear cells (PBMC) and CD15+ granulocytic cells (PBCD15+) separated through Ficoll centrifugation or from immunomagnetically selected circulating CD34+ cells (PBCD34+). Real-time quantitative PCR (RQ-PCR) using Taqman technology was performed on cDNA. As different isoforms were described in malignancies, we used two primer sets : the first one allowing the amplification of all HMGA2 isoforms (exon 1 to 3) (HMGA2 1–3), the second one allowing the amplification of the full length HMGA2 isoform (exon 1 to 5)(HMGA2 1–5). In healthy donors and in MMM, PBMC HMGA2 expression levels were heterogeneous, depending of the cellular sub-population purity. HMGA2 1–3 or HMGA2 1–5 were both expressed in MMM and normal PBCD34+ cells, but with a higher expression level for HMGA2 1–3 as compared to HMGA2 1–5. Furthermore, both HMGA2 1–3 and HMGA2 1–5 expression levels were significantly increased in PBCD34+ MMM patients (p&lt;10−6) compared to healthy donors. In MMM, HMGA2 expression level was significantly increased (p&lt;10−5) in PBCD15+ as compared to PBCD34+. Moreover, PBCD15+ HMGA2 1–3 expression level was significantly higher in MMM patients compared to PBCD15+ from healthy donors (p&lt;10−7). A persistence of HMGA2 1–5 expression was only observed in MMM PBCD15+ but was undetectable neither in normal PB neutrophils (purity&gt;98%) nor in PB neutrophils from other myeloproliferative disorders (Polycythemia Vera and Essential Thrombocythemia). To determine if HMGA2 level was modified during hematopoietic differentiation, we quantified HMGA2 1–3 and 1–5 isoform expression on purified healthy donor PB CD34+ and MMM CD34+ before and after culture with specific lineage growth factors (12 day-culture). Primary results showed that both HMGA2 isoform expression levels were higher during granulocytic differentiation. Our results demonstrate that HMGA2 1–5 isoform is discriminately overexpressed in MMM PBCD15+. The persistence of this HMGA2 full length expression in MMM myeloid lineage could be considered as a marker of the disease.


2019 ◽  
Vol 9 (12) ◽  
pp. 1670-1675
Author(s):  
Pan Huang ◽  
Xiao-Ying He ◽  
Min Xu

The study is to investigate the expression of miRNA-146a in PBMC of myasthenia Gravis (MG), and to explore the molecular regulatory network of miRNA-146a in the pathogenesis of MG by bioinformatics. 108 patients with MG were selected as the experimental group (MG group), and 50 healthy subjects were selected as the control group. The relative expression of miRNA-146a in PBMC was detected by RT-PCR. The cross-target gene of miRNA-146a was predicted by TargetScan and CoMeTa database. miRNA-146a target gene GO enrichment and KEGG Pathway enrichment analysis was performed using the DAVID database. Our results shows that the expression level of miRNA-146a in peripheral blood of MG patients was significantly higher than that of the control group, the difference was statistically significant (P < 0 05), and the nucleotide sequence was highly conserved. The potential target genes of miRNA-146a include 88 kinds; GO analysis showed that miRNA-146a target gene function is mainly enriched in cell proliferation regulation, neuronal differentiation, etc. KEGG Pathway analysis shows that miRNA-146a is mainly enriched in Toll-like receptor signaling pathway, neurotransmitter regulatory signaling pathways, EB signaling pathways and other signaling pathways. In conclusion, the expression of miRNA-146a in PBMC of MG patients is up-regulated and participates in the pathogenesis of MG by acting on multiple signaling pathways.


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