Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases

Sharaf-Eldin, Wessam E.; Kishk, Nirmeen A.; Gad, Yehia Z.; Hassan, Heba; Ali, Mohamed A.; Zaki, Maha S.; Mohamed, Mohamed R.; Essawi, Mona

doi:10.1016/j.jns.2017.11.014

Cited by 42 publications

(26 citation statements)

References 45 publications

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“…PI3K/AKT pathway plays an important biological role in cell apoptosis, survival, proliferation, cytoskeleton change and other biological processes [32]. It has been proved that the PI3K/AKT signalling pathway participates in the regulation of the pathological process of cerebral ischemia injury [33][34][35]. In addition, several studies have reported that Nrf2 is a downstream regulator of PI3K/AKT pathway [18,36].…”

Section: Discussionmentioning

confidence: 99%

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

Wang

Li²,

Zhang³

2019

Artificial Cells, Nanomedicine, and Biotechnology

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This study aimed to investigate the potential effect of Scutellaria barbata D. Don (SBD) on oxygen glucose deprivation/reperfusion (OGD/R)-injured PC12 cells. PC12 cells were pretreated with various concentrations of 0.1-0.8 mg/ml SBD for indicated times (12-48 h) and then subjected to OGD/R injury. Cell viability, apoptosis and proliferation were detected using MTT assay, flow cytometry, Ki67 staining and western blot. Oxidative damage was assessed by detecting MDA content, SOD activity and GSH levels. The mitochondrial membrane potential (Dwm) was measured by Rh123 staining. Western blot was performed to assess the expression levels of Nrf2 and PI3K/AKT pathway-related proteins. We found that SBD pretreatment promoted cell viability and proliferation but inhibited apoptosis of OGD/R-injured PC12 cells in dosage-and time-dependent manner. Meanwhile, SBD attenuated oxidative damage and restored mitochondria dysfunction, as evidenced by the reduced MDA content, the increased SOD and GSH levels, and the increased Dwm. Furthermore, SBD induced the expression of Nrf2 in a PI3K/AKT-dependent signalling. Knockdown of Nrf2 blocked the protective effects of SBD on PC12 cells. In conclusion, this study demonstrates that SBD pretreatment protects PC12 cells against OGD/R-induced injury. The potential mechanism may be through up-regulating the expression of Nrf2 in a PI3K/AKT-dependent pathway. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

Wang

Li²,

Zhang³

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…However, five articles were excluded by reading their complete articles due to article types, seven studies lacked available data to construct a 2×2 table, and four articles lacked a comparison between SLE patients and healthy controls. Finally, 17 studies [17][18][19][20][21][31][32][33][34][35][36][37][38][39][40][41][42] were included in the meta-analysis. The process of study selection was illustrated in Fig 1. Except the study of Zununi Vahed et al [42] is a cross-sectional trial, all others are prospective trials.…”

Section: Search Resultsmentioning

confidence: 99%

“…Additionally, the ideal time for specimen acquisition was before treatment. Unfortunately, only two of the studies [17,31] involved in our meta-analysis indicated that blood samples were collected before treatment, while six studies [20,33,37,39,40,42] did not clarify when the specimens were obtained, five studies [18,19,21,36,41] stated that samples were collected during the period of treatments, and four articles [32,34,35,38] indicated that the time for specimen collection was after the patients had stopped treatments for a period of time. Thus, these differences in patient and blood collection time could cause inevitable bias to our results.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

et al. 2019

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BackgroundIn recent years, many studies focused on the association between the microRNAs (miR-NAs) and the risk of systemic lupus erythematosus (SLE), especially miRNA-21 (miR-21). We aimed to investigate the role of circulating miRNAs, especially the miR-21, as a biomarker in detecting SLE. MethodsWe searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through Mar 3th, 2019. We performed this metaanalysis in a fixed/random-effect model using Meta-disc 1.4 and STATA 15.1. ResultsA total of 17 relevant studies were eligible to analyze pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.71 (95% confidence interval [CI], 0.69 to 0.72); pooled specificity, 0.81 (95%CI, 0.79 to 0.83); and area under the summary receiver operating characteristic curves value (SROC), 0.8797. The miR-21 detection was: pooled sensitivity, 0.68 (95%CI, 0.62 to 0.74); pooled specificity, 0.77 (95%CI, 0.69 to 0.84); and SROC, 0.8281. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that detection in plasma group had the largest AUC of SROC in all the subgroups: pooled sensitivity, 0.8 (95%CI, 0.78 to 0.82); pooled specificity, 0.83 (95%CI, 0.8 to 0.86); and SROC, 0.9068. ConclusionsOur meta-analysis demonstrated that circulating miRNAs might be potential novel biomarkers for detecting SLE, especially miR-21. Moreover, plasma is recommended as the clinical specimen for diagnostic detection.

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“…MiR-326 was shown to promote Th-17 differentiation and to be positively correlated with IL-17 production in MS patients (Du et al, 2009). Recently, the expression of various miRNAs has been shown to be significantly altered in the peripheral blood leukocytes, the cerebrospinal fluid and the brain tissue of MS, including miR-145, miR-223, and miR-219 (Bruinsma et al, 2017;Sharaf-Eldin et al, 2017;Sondergaard, Hesse, Krakauer, Sorensen, & Sellebjerg, 2013). However, the function of miRNAs expressed both in the brain tissue of MS/EAE mice and in activated astrocytes induced by IL-17 remains unknown.…”

mentioning

confidence: 99%

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

Liu

Feng

Yang

et al. 2018

Glia

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Th17 cells and interleukin‐17 (IL‐17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL‐17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the role and the regulatory mechanism of IL‐17‐activated astrocytes in inflammation and in the EAE process still remain largely unknown. Here, we elucidated that miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3 (SOCS3). Overexpression of miR‐409‐3p or miR‐1896 significantly reduced SOCS3 expression and increased phosphorylation of STAT3 as well as induced the inflammatory cytokines production (IL‐1β, IL‐6, IP‐10, MCP‐1, and KC), CD4+T cells migration and demyelination, in turn aggravating EAE development. Importantly, the effects of co‐overexpression of miR‐409‐3p and miR‐1896 in vitro or in vivo are strongly co‐operative. In contrast, simultaneously silenced miR‐409‐3p and miR‐1896 co‐operatively ameliorates inflammation and demyelination in the central nervous system of EAE mice. Collectively, our findings highlight that miR‐409‐3p and miR‐1896 co‐ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte‐directed chemotaxis of CD4+T cells, leading to aggravate pathogenesis in EAE mice. Co‐inhibition of miR‐409‐3p and miR‐1896 may be a therapeutic target for treating MS and neuroinflammation.

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Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases

Cited by 42 publications

References 45 publications

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

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