scholarly journals Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

2021 ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Fariba Dehghanian ◽  
Sheyda Khalilian ◽  
Majid Kheirollahi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Area Under The Curve ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Sporadic Group ◽  
Axonal Dysfunction

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction in myelin-less areas. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Results Our results showed that the expression level of IL7R was decreased in MS patients versus healthy controls. Also IL7R expression was significantly down-regulated in the sporadic group as compared to other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls was also seen. Our results represented an increased expression level of RNF213 in the familial patients as compared to the control group. Diagnostic evaluation was performed by ROC curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and EDSS with our gene expression levels were also assessed. Conclusions Overall, decreased expression level of IL7R and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. The RNF213 should be evaluated further for its potential as a candidate biomarker of inflammatory activity in MS in a larger cohort.

scholarly journals Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Sheyda Khalilian ◽  
Fariba Dehghanian ◽  
Majid Kheirollahi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Area Under The Curve ◽  
Group Versus ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Axonal Dysfunction

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

scholarly journals Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10377
Author(s):  
Mohammadreza Ardalan ◽  
Seyyedeh Mina Hejazian ◽  
Hassan Fazlazar Sharabiyani ◽  
Farahnoosh Farnood ◽  
Amirhossein Ghafari Aghdam ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Glycogen Synthase ◽  
Expression Level ◽  
Glycogen Synthase Kinase ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Gsk 3Β

Background Glycogen synthase kinase-3 (GSK-3β) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3β in kidney cells has a harmful role in podocyte injury. Methods In this article, the expression levels of GSK-3β and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria. Results Levels of GSK-3β mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3β expression level in NS (P = 0.001), MGN (P = 0.002), and FSGS (P = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS (P = 0.020), MGN (P = 0.040), and FSGS (P = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3β in discriminating patients from healthy controls (AUC: 0.72, P = 0.002) with high sensitivity and specificity. Conclusions Dysregulated levels of GSK-3β and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.

Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

2018 ◽  
Vol 94 (1111) ◽  
pp. 278-283 ◽  
Author(s):  
Xue-Feng Xie ◽  
Xiao-Hui Huang ◽  
Ai-Zong Shen ◽  
Jun Li ◽  
Ye-Huan Sun
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Sample Type ◽  
Healthy Controls ◽  
Eligibility Criteria ◽  
Effect Model ◽  
Healthy Control

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.

scholarly journals Nrf2 Dysregulation in Major Depressive and Bipolar Disorders

2021 ◽  
Vol 10 ◽  
pp. e2074
Author(s):  
Maryam Ghanbarirad ◽  
Mehrdad Hashemi ◽  
Seyed Mehdi Saberi ◽  
Ahmad Majd
Keyword(s):  
Mental Disorders ◽  
Defense Mechanisms ◽  
Bipolar Disorders ◽  
Expression Level ◽  
Control Group ◽  
Roc Curve Analysis ◽  
Major Depressive ◽  
Control Subjects ◽  
Healthy Control ◽  
Nrf2 Expression

Background: Major depressive disorder (MDD) and bipolar disorder (BPD) are two of the most important mental disorders that greatly impact different aspects of life. These conditions imply heavy health and economic burden and are heterogeneous in nature. Inflammation is reported as the etiology of mental disorders. Nrf2 transcription factor plays a key role in the defense mechanisms against inflammation and oxidative stress. So, this study aimed to evaluate the expression level of Nrf2 in MDD and BPD patients and compared it with healthy control subjects. Materials and Methods: In this study, real-time PCR was conducted to evaluate the expression level of Nrf2 in 100 MDD and 100 BPD patients compared to 100 healthy control subjects. Statistical analysis conducted on GraphPad Prism 8 and SPSS21 included ANOVA, Tukey’s test, receiver operating characteristic (ROC), and odds ratio. Results: Results suggest a significant downregulation of Nrf2 in these conditions compared to the control group. ROC curve analysis demonstrates Nrf2 as a biomarker of these psychiatric disorders. Conclusion: The elevated levels of reactive oxygen species and downregulation of detoxifying enzymes were observed in MDD and BPD, which can be associated with the downregulation of Nrf2. Concerning its role in inflammatory response pathways, alternation of Nrf2 expression can be associated with the pathology of these conditions.

scholarly journals Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Zongxin Ling ◽  
Yiwen Cheng ◽  
Xiumei Yan ◽  
Li Shao ◽  
Xia Liu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Intestinal Microbiota ◽  
Area Under The Curve ◽  
Fecal Microbiota ◽  
Host Immunity ◽  
Chinese Patients ◽  
Healthy Controls ◽  
Cytokines And Chemokines ◽  
Functional Bacteria ◽  
Functional Profiles

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.

scholarly journals Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Rui Chang ◽  
Ying Zhu ◽  
Jing Xu ◽  
Lin Chen ◽  
Guannan Su ◽  
...  
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Multivariate Statistical ◽  
Flight Mass Spectrometry ◽  
Laboratory Biomarkers ◽  
Vkh Disease

The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.

Predictive Value of The Combined Detection of Platelets, D-Dimer, and Procalcitonin On Severe Heat Stroke

2021 ◽  
Author(s):  
wang lei ◽  
jiang dai shan ◽  
zhang Yi ◽  
jia han yu ◽  
shen jun hua
Keyword(s):  
Body Temperature ◽  
Characteristic Curve ◽  
Heat Stroke ◽  
Area Under The Curve ◽  
General Information ◽  
The Body ◽  
Control Group ◽  
Clinical Test ◽  
Roc Curve Analysis ◽  
Combined Detection

Abstract BackgroundTo explore the clinical characteristics of patients with severe heat stroke, we explored the early sensitive indicators of heat stroke (HS) patients, with a view to early intervention for HS patients. MethodsFrom July 30, 2015 to October 5, 2020, 70 inpatients with severe heat stroke admitted to the Second Affiliated Hospital of Nantong University, Jiangsu Province were selected as the research objects. The general information and clinical test indicators of the patients were recorded, and all patients were assessed for acute physiology (APACH Ⅱ) upon admission. According to the severity of heatstroke, they were divided into three groups: control group (heat cramps and heat exhaustion), EHS, and CHS to compare the differences in indicators of each group. Further draw the receiver operating characteristic curve (ROC).Results1. According to the severity of heat stroke, 28 cases were divided into the control group, 24 cases in the EHS group, and 18 cases in the CHS group. The body temperature of the EHS group and the CHS group was significantly higher than that of the control group (both P<0.05), but there was no statistical difference in the body temperature of the EHS group and the CHS group; the DD, PCT, and APACH of the EHS group were significantly higher than those of the control group and the CHS group (both P＜0.05); PLT, CRP, Na, GLU of EHS group were lower than those of control group and CHS group (all P＜0.05), and the decrease of PLT was more significant; CHS group HbA1C was significantly higher than that of control group and EHS group (all P <0.05). 2. ROC curve analysis the areas under the curves of DD, PCT, and PLT are 0.670, 0.705, 0.791, respectively, the sensitivity is 40.48%, 100%, 73.81%, and the specificity is 96.43%, 32.14%, 78.57%, respectively. Using the combined analysis of the three series tests, the area under the curve was 0.838, the sensitivity was 71.43%, and the specificity was 85.71%. ConclusionsEHS patients have higher DD, PCT, APACH, but PLT, CRP, Na, and blood sugar are lower. At the same time, the significant decrease of PLT and the increase of PCT and DD may be early sensitive indicators of HS. The combined detection of the three can be used as a reference basis for early diagnosis of HS and critical illness.

scholarly journals Inflammation-related plasma and CSF biomarkers for multiple sclerosis

2020 ◽  
Vol 117 (23) ◽  
pp. 12952-12960 ◽  
Author(s):  
Jesse Huang ◽  
Mohsen Khademi ◽  
Lars Fugger ◽  
Örjan Lindhe ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Area Under The Curve ◽  
Csf Biomarkers ◽  
Healthy Controls ◽  
Protein Biomarkers ◽  
Neurofilament Light Chain ◽  
Diagnostic Efficacy ◽  
Neurofilament Light

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

scholarly journals Changes in Amino Acid and Acylcarnitine Plasma Profiles for Distinguishing Patients with Multiple Sclerosis from Healthy Controls

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Marat F. Kasakin ◽  
Artem D. Rogachev ◽  
Elena V. Predtechenskaya ◽  
Vladimir J. Zaigraev ◽  
Vladimir V. Koval ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acid ◽  
Discriminant Analysis ◽  
Clinical Decision ◽  
Partial Least Square ◽  
Least Square ◽  
Control Group ◽  
Healthy Controls ◽  
Linear Discriminant ◽  
Tandem Mass Spectrometric

McDonald criteria and magnetic resonance imaging (MRI) are used for the diagnosis of multiple sclerosis (MS); nevertheless, it takes a considerable amount of time to make a clinical decision. Amino acid and fatty acid metabolic pathways are disturbed in MS, and this information could be useful for diagnosis. The aim of our study was to find changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls. We have applied a targeted metabolomics approach based on tandem mass-spectrometric analysis of amino acids and acylcarnitines in dried plasma spots followed by multivariate statistical analysis for discovery of differences between MS (n=16) and control (n=12) groups. It was found that partial least square discriminant analysis yielded better group classification as compared to principal component linear discriminant analysis and the random forest algorithm. All the three models detected noticeable changes in the amino acid and acylcarnitine profiles in the MS group relative to the control group. Our results hold promise for further development of the clinical decision support system.

scholarly journals A logistic regression analysis of risk factors in ME/CFS pathogenesis

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Eliana M. Lacerda ◽  
Keith Geraghty ◽  
Caroline C. Kingdon ◽  
Luigi Palla ◽  
Luis Nacul
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Regression Analysis ◽  
Risk Factor ◽  
Family History ◽  
Disease Onset ◽  
Healthy Controls ◽  
Lower Income ◽  
Wide Range ◽  
History Of

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. Methods This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). Results A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). Conclusions Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.

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