Expression Levels Of miRNA-155 Research Articles

Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis.

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.

Kaempferol Ameliorated Alcoholic Hepatitis through Improving Intestinal Barrier Function by Targeting miRNA-155 Signaling

Introduction: The aim of this study was to investigate the effect and mechanism of kaempferol on alcoholic steatohepatitis. Methods: C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. Kaempferol was given as the interventional drug to chronic alcohol-fed mice for 6 weeks to assess its effects. In vitro, intestinal epithelial Caco-2 cells were stimulated by alcohol, and miRNA-155 mimics were used to further study the effect of kaempferol to miRNA-155 signaling in intestinal epithelial cells. HE staining and oil red O staining were used to observe the liver and intestinal tissue damage in each group of mice, and ALT, AST, IL-1β, and TNF-α were detected by kits; lipopolysaccharide (LPS) expression was detected by ELISA kit, and the expression of IL-1β and TNF-α was assessed by qRT-PCR; Western blot was utilized to assess the excessive inflammatory response of liver and colon tissue and the related signaling pathway activation. Results: Kaempferol treatment significantly improved pathological changes such as steatosis and vacuolated lesions in liver tissue of the alcohol diet model group, and reduced serum ALT and AST enzyme activities and liver tissue interleukin-1β and tumor necrosis factor-α mRNA expression levels. Kaempferol significantly reduced the expression of miRNA-155 in the intestinal tissue of alcohol-fed mice, significantly increased their cytokine suppressor signaling 1 (SOCS1) protein expression, inhibited the activation of nuclear factor kappa-B and significantly increased the production of the intestinal tight junction proteins occludin and zonula occludens-1. More importantly, kaempferol significantly reduced serum LPS levels in alcoholic steatohepatitis mice. In vitro experiments showed that compared with the control group, kaempferol significantly inhibited the expression level of miRNA-155 in Caco-2 cells under ethanol exposure, decreased the activation of nuclear factor kappa-B, led to an increase in the expression of SOCS1 protein, and increased the production level of occludin protein in Caco-2 cells under the effect of alcohol. In contrast, overexpression of miRNA-155 significantly decreased occludin and SOCS1 protein production and increased nuclear factor kappa-B activation levels in Caco-2 cells, and the administration of kaempferol significantly inhibited this effect. Conclusion: Kaempferol improved the stability of gut barrier function to ameliorate hepatic injury induced by alcohol intake through enhancing occludin protein expression, by targeting miR-155 to inhibit the excessive inflammatory response in the intestine.

CD-36 variants and circulating miRNAs as prognostic biomarkers and potential therapeutic targets in breast cancer patients

The influence of the CD-36 variant on the susceptibility to breast cancer (BC) and correlations between miRNA-375 / CD-36 axes and breast cancer is still not fully determined. The current study aimed to determine the impact of CD-36 rs1761667 and rs1527483 presence of breast cancer and its prognosis, as well as the relationship between these variants and miRNA-375 and miRNA-155 expression levels as potential biomarkers for BC.Overall, 176 individuals were enrolled in this study, 48 patients with metastatic BC, 50 patients with non-metastatic BC, 43 patients with benign BC, and 35 healthy volunteers. Genotyping and serum expression profiles were assessed using qPCR, and CD-36 was measured by ELISA. The genotype AA of rs1761667 was associated with increased BC occurrence. Serum CD-36 was significantly increased in metastatic BC patients versus healthy controls. In addition, miRNA-155 and miRNA-375 were upregulated in BC.The current study demonstrates that miRNA-375 and CD-36 have the potential to be used as non-invasive prognostic biomarkers for BC.

Low expression levels of miRNA-155 and miRNA-499a are associated with obesity in Type 2 diabetes.

Background & aims: This study investigated a possible correlation between three circulating miRNAs, previously observed to be associated to diabetic polyneuropathy, and the obesity condition. Methods & results: The expression levels of miR-128a, miR-155 and miR499a were evaluated in 49 participants with Type 2 diabetes, divided into different groups based on the presence or absence of obesity and central obesity. The analyses revealed a significant decrease of miR-155 and miR-499a expression levels in obese subjects. In particular, the reduction appears to be even more significant in Type 2 diabetes subjects with central obesity. Conclusion: The results suggest that these miRNAs could be involved in obesity-driven pathogenetic mechanisms.

The effect of trehalose administration on the serum expression levels of microRNAs associated with lipid metabolism and autophagy process in patients with myocardial infarction - the post-hoc analysis of the TREAT-IR trial.

IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels of miRNAs associated with lipids metabolism and autophagy process in MI patients to assess the potential protective effects of TRE in these patients.Material and methodsThis post hoc investigation was performed on serum samples obtained from a pilot randomized, double blind, placebo-controlled clinical trial that recruited 14 men (aged 18-80) who had MI and systemic inflammation. The patients were randomized in a 2:1 ratio to either TRE (15 g/week, intravenous (IV) ad-ministration) (N=10) or placebo groups (equal volume of saline 0.9 %) (N=4) for a period of 12 weeks. To measure the relative serum expression levels of miRNA-155, miRNA-221, and miRNA-33, the SYBR Green qPCR method was used.ResultsmiRNA-155 showed significantly higher serum expression levels in the TRE group (2.772±0.73; P=0.009) when compared to the placebo group. Also, significant reductions in miRNA-155 (0.171±0.03; P=0.016), miRNA-221 (0.116±0.07; P=0.013), and miRNA-33a (0.076±0.07; P=0.025) were observed in the placebo group at the end of the study. Nevertheless, the reduction (normalized to the baseline) of the serum expres-sion levels of miRNA-221 (FC:0.87±0.20 vs FC:0.18±0.08; P=0.009) and miRNA-33a (FC:0.73±0.22 vs FC:0.13±0.08; P=0.025) were significantly less in TRE group than in the placebo group.ConclusionsIV TRE administration did not reduce the expression of miRNA-221 and miRNA33a as much as placebo. Keeping a steady state of the serum expression levels of these miRNAs associated with lipoproteins metabolism and autophagy in the TRE group might have protective effects in patients with MI.

CRISPR/Cas13a-triggered Cas12a biosensing method for ultrasensitive and specific miRNA detection

Constructing an ultrasensitive CRISPR/Cas-based biosensing strategy is highly significant for the detection of trace targets. Here we presented a dual-amplified biosensing method based on CRISPR/Cas13a-triggered Cas12a, namely, Cas13a-12a amplification. As proof-of-principle, the developed strategy was used for miRNA-155 detection. The target bound to the Cas13a-crRNA complex and activated the cleavage activity of Cas13a for cleaving uracil ribonucleotides (rU) in the bulge structure of blocker strand (BS), resulting in the release of primer strand (PS) from the BS modified on magnetic beads. Then, the released PS activated the cleavage activity of Cas12a to cleave single-strand DNA reporter probes, producing a significantly increased fluorescent signal. The detection limit of the Cas13a-12a amplification using synthetic miRNA-155 was as low as 0.35 fM, which was much lower than that of the only Cas13a-based assay. The applied performance of this amplification strategy was verified by accurately quantifying miRNA-155 expression levels in different cancer patients. Therefore, the developed strategy offers a supersensitive and highly specific miRNAs sensing platform for clinical application.

MicroRNA - biomarker of aggressiveness of choroidal melanoma

Almost 50 % of microRNAs (a family of small noncoding RNAs) are associated with the regions of the genome responsible for the development of tumors. These microRNAs play the role of oncogenes or tumor suppressor genes. In 2008, there were reports of the possibility of using microRNA as a predictive biomarker of the metastatic risk of uveal melanoma. Initially, microRNAs were investigated in melanoma samples; later, the possibility of using blood plasma for these purposes was shown.Purpose: to study the character of expression of miRNA- 146a, miRNA-155, miRNA-223, miRNA-126, miRNA-27b in the blood plasma of patients with choroidal melanoma (CM) and determine their significance in predicting possible hematogenous metastases. Material and methods. The study included 84 patients with CM aged 35–86 (ave 63.4 ± 1.2 yrs). The thickness of the CM varied in the range of 0.77–17.19 mm (ave 7.21 ± 0.43 mm). The control group consisted of 28 volunteers aged 45-78 (62.90 ± 1.42 yrs). MicroRNA expression levels were determined by quantitative PCR.Results. An increase in the expression level of miRNA-155, miRNA-146a, miRNA-126, miRNA-223, and miRNA-27b in blood plasma in all 84 patients with CM was revealed.Conclusion. The study of miRNA levels (miRNA-146, miRNA-155, miRNA-223, miRNA-126 and miRNA-27b) in the blood plasma of patients with CM can be used both to confirm the diagnosis of CM in difficult diagnostic cases and to determine the aggressiveness of the course tumor and prediction of metastasis.

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study.

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

МикроРНК и эндокринная офтальмопатия, участие в глюкокортикоидном ответе

The accumulated clinical experience proves the existence of glucocorticoid-resistant forms of endocrine ophthalmopathy. It is assumed that epigenetic factors (miRNA) affect the pathogenesis of the disease and are involved in the formation of the glucocorticoid response. Purpose. To study the role of miRNA-146a and miRNA-155 in patients with clinical forms of endocrine ophthalmopathy and to assess their effect on the glucocorticoid response. Material and method: The study included 20 patients (40 orbits) with image intensifier tubes, treated with glucocorticoids (GC) with a negative result, mean age – 52.65 ± 12.6 years. The control group - 28 volunteers without autoimmune and tumor diseases, age 62.9 ± 7.54 years. The expression level of miRNA-155 and miRNA-146a was determined by real-time PCR. Results: The obtained data indicate an increase in the expression level of miRNA-146a and miRNA-155 in patients with clinical forms of endocrine ophthalmopathy at the stage of fibrosis (p <0.01). Conclusion: The obtained results of the functional activity of miRNA-146a and miRNA-155 confirm their participation in the pathogenesis of the development of edematous exophthalmos and endocrine myopathy by activating the fibroplastic process. Key words: endocrine ophthalmopathy, GC therapy, microRNA.

Metformin and omega-3 fish oil elicit anti-inflammatory effects via modulation of some dysregulated micro RNAs expression and signaling pathways in experimental induced arthritis

ObjectiveRheumatoid arthritis is a progressive inflammatory disease with multiple dysfunctional intracellular signaling pathways that necessitate new approaches for its management. Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate. MethodsFourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with metformin (200 mg/kg/day) and/or omega-3 (300 mg/kg/day) or intraperitoneally with methotrexate (2 mg/kg/week) for 4 weeks. Results and conclusionAll drug treatments amended the arthrogram score and hind paw swelling as well as decreased serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. On the molecular level, all therapies activated phospho-5′adenosine monophosphate-activated protein kinase (p-AMPK) and protein phosphatase 2A (PP2A), while they inhibited phospho-mammalian target of rapamycin (p-mTOR), phospho-signal transducers and activators of transcription (p-STAT3), nuclear factor (NF)-κB p65 subunit, phosho38 mitogen-activated protein kinase (p38 MAPK) and phospho- c-Jun N-terminal kinase (p-JNK). In addition, they decreased the elevated expression level of miRNA-155, 146a and increased the expression level of miRNA-34 and they decreased the expression level of retinoic acid receptor related orphan receptor γT (RORγT) and increased that of fork head box P3 (FOXP3), correcting Th17/Treg cells balance. On most of the aforementioned parameters, the effect of the combination therapy was comparable to that of methotrexate, emphasizing that this combination possesses better additive anti-inflammatory effect than either drug when used alone. In addition, the combination was capable of normalizing the serum transaminases levels as compared to untreated group offering hepatoprotective effect and suggesting the possibility of its use as a replacement therapeutic strategy for MTX in rheumatoid arthritis.

Micro-RNA 155 in non-Hodgkin lymphoma

Background Micro-RNAs (miRNAs) are a class of small RNAs of 17–25 nucleotides in length. miRNA-155 has a great role in lymphomagenesis through several mechanisms. Recent years have shown clearly a growth in knowledge of the etiology and pathogenesis of non-Hodgkin lymphomas (NHLs). Aim This work aimed to study the expression of miRNA-155 in patients with NHL and its correlation with clinical and pathological criteria of these patients; so that we could achieve a new biomarker in the prediction of progression of the disease. Settings and study design This is a cross-sectional study with a nested control group. Cases and controls were recruited from the Clinical Pathology Department at South Egypt Cancer Institute. Patients and methods This study was conducted on 32 patients with NHL. Peripheral blood and bone marrow samples were analyzed using 7500 Fast real-time PCR (Applied Biosystems). Statistical analysis used Results were performed using IBM SPSS Statistics, version 20 (SPSS Inc.). Results There was a significant correlation between expression levels of miRNA-155 in patients with NHL and their clinical stages or international prognostic indices. Conclusion It has been found that expression levels of miRNA-155 in patients’ samples were higher in cases of advanced clinical stage or higher international prognostic index. In addition, this study showed the correlation between miRNA-155 and behavior of B-NHL subtypes, total leukocytic count, and hemoglobin levels of patients. These findings revealed the great role of miRNA-155 in lymphomagenesis and also its usage as a new predictive biomarker in patients with NHL.

Role of microRNA-21 and microRNA-155 as biomarkers for bronchial asthma.

MicroRNA (miRNA)-21 and miRNA-155 are important regulators of gene expression of different immunological molecules. This study aimed to investigate the role of miRNA-21 and miRNA-155 as biomarkers in asthma by comparing their serum expression levels in asthmatic patients to those in healthy controls and correlating their levels with serum IL-4. The expression levels of miRNA-21 and miRNA-155 were evaluated by quantitative RT-PCR. Serum levels of IL-4 were determined using ELISA. Asthmatic patients showed significantly higher serum miRNA-21 and miRNA-155 expression levels compared to controls. A statistically significant positive correlation between the expression levels of miRNA-21 and IL-4 serum levels in asthmatic patients was detected. Nonetheless, no correlation was detected between miRNA-155 expression and each of IL-4 and miRNA-21. A receiver operating characteristic curve analysis showed that at a cut-off value of 1.37, the sensitivity of miRNA-21 as an asthma biomarker was 100% and the specificity was 95%. At a cut-off value of 1.96, the sensitivity of miRNA-155 as an asthma biomarker was 100% and the specificity was 100%. It can be concluded that miRNA-21 and miRNA-155 are potential non-invasive biomarkers in the diagnosis of eosinophilic asthma and its response to therapy.

The Impact of miRNA-155 Expression on Treatment Outcome in Adult Acute Myeloid Leukemia Patients

Background: Acute myeloid leukemia is a heterogeneous hematologic malignancy associated with gene mutations, chromosomal rearrangements, deregulation of gene expression and epigenetic modifications. The treatment outcome of AML is highly variable signifying the heterogeneous nature of the disease. Aim of the Study: To evaluate miRNA-155 expression level as a prognostic marker for adult patients with acute myeloid leukemia. Patients and Methods: 101 subjects were included in this study. They were classified into 2 groups, patient group (61 adult patients with newly diagnosed acute myeloid leukemia) and control group (40 apparently healthy adult subjects). miRNA-155 expression was assessed using real time PCR using QIAGEN, miScript, Quanti Tect and Rotor-isc (QIAGEN Group) PAXgene (pre Analytix Gmbh). Samples were either peripheral blood or bone marrow aspiration sample. Results: Roc curve detected 2.85 as best fit value of miRNA-155 for discriminating patients from healthy controls with sensitivity 92.3%, specificity 88.5%, AUC 0.98 and CI (0.96 - 0.99) (p th percentile value of the patient group was taken as prognostic cut off value with a value The expression level of miRNA-155 was significantly higher in AML patients than in controls (p = 0.002). Patients with high miRNA expression had a significantly higher white blood cells count (p = 0.002), bone marrow blasts (p = 0.006) and peripheral blood blasts (p = 0.006) compared to patients with low miRNA-155 expression. Patients with poor cytogentics had a significantly higher level of miRNA-155 expression compared to patients with favorable cytogentics (p = 0.007). The complete remission rate was significantly higher in patients with low miRNA-155 expression compared to those with high expression (86.4% and 23.5%, consequently, p = 0.004). The disease free survival was significantly shorter in patients with high miRNA-155 expression compared to those with low expression (median 12 months, 95% CI (7.4 - 15.5) and median notreached, consquenly, p = 0.001). The overall survival was significantly higher (p = 0.002) in patients with low miRNA-155 expression (median overall survival was not reached) compared to patients with high miRNA-155 expression (median overall survival 14.5 months, 95% CI; 10.2 - 17.6). Conclusion: The expression level of miR-155 was significantly higher in AML patients than in control groups and high miRNA-155 expression level was significantly associated with poor cytogenetics, poor response to therapy and shorter disease free and overall survival conferring a poor outcome.

The role of plasma miRNAs in the diagnosis of pulmonary nodules.

In this study, we aimed to assess the clinical utility of detection of plasma microRNAs (miRNAs) in the diagnosis of pulmonary nodules. Fifty-seven patients with pulmonary nodules who had undergone surgery were enrolled in our study from July 2016 to July 2017 at Sun Yat-sen University Cancer Center. We measured the expression levels of 12 miRNAs (miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210) in plasma samples of 57 patients, including 15 benign pulmonary nodules patients and 42 malignant pulmonary nodules patients. The levels of these miRNAs were detected by Real-time quantitative polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of plasma miRNAs for non-small cell lung cancer (NSCLC). The expression levels of plasma miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210 are not associated with gender, age, pTNM stage, differentiation grade. The levels of miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210 in NSCLC patients are significantly higher than those in benign pulmonary nodules patients (P<0.05). However, there are no significant differences for the expression levels of miRNA-155 and miRNA-126. For diagnosing NSCLC, the sensitivity and specificity was 66.7% and 80.0% for miRNA-17, 54.8% and 86.7% for miRNA-146a, 64.3% and 86.7% for miRNA-200b, 83.3% and 73.3% for miRNA-182, 54.8% and 80.0% for miRNA-221, 73.8% and 80.0% for miRNA-205, 78.6% and 73.3% for miRNA-7, 78.6% and 60.0% for miRNA-21, 78.6% and 73.3% for miRNA-145, 76.2% and 73.3% for miRNA-210. Plasma miRNAs (miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210) have relatively high sensitivity and specificity for the diagnosis of NSCLC. These plasma miRNAs may be the potential biomarkers for early diagnosis of lung cancer.

Evaluation of microRNA-155 as a diagnostic serum-based biomarker in patients with breast cancer

Background Breast cancer (BC) is the most common cancer among Egyptian women, and its early detection is accompanied with decreased mortality rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression and affect cancer development. The expression level of miRNA-155 is up-regulated in BC and correlates with its invasive properties, offering a great potential as a noninvasive biomarker for BC screening. Objective The aim of this study is to evaluate the role of miRNA-155 as an early diagnostic serum-based biomarker of BC. Patients and methods This study was conducted on 30 patients newly diagnosed with BC and associated 20 healthy women as a control group. Serum level of miRNA-155 was measured for all studied cases using real-time quantitative PCR technique. Results MiRNA-155 expression was up-regulated in serum of patients with BC compared with control group (P Conclusion The results validate miRNA-155 as a promising diagnostic and even a prognostic marker in cases of BC.

Evaluation of the miRNA-146a and miRNA-155 Expression Levels in Patients with Oral Lichen Planus.

Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2-ΔΔct method. The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than those of healthy controls. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.

Role of 3-Acetyl-11-Keto-Beta-Boswellic Acid in Counteracting LPS-Induced Neuroinflammation via Modulation of miRNA-155.

Neuroinflammation is one of the most important mechanisms underlying neurodegeneration. Lipopolysaccharide (LPS) is a potent inflammogen which causes cognitive dysfunction. Boswellia serrata is known since many years as a powerful anti-inflammatory herbal drug. Its beneficial effect mainly arises from inhibition of 5-lipoxygenase (5-LO) enzyme. 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent 5-LO inhibitor extracted from the oleo-gum-resin of Boswellia serrata. The aim of the present work is to study the molecular mechanisms underlying the anti-inflammatory and neuroprotective effects of AKBA and dexamethasone (DEX) in LPS-induced neuroinflammatory model. A single intraperitoneal (i.p.) dose of LPS (0.8mg/kg) was injected to induce cognitive dysfunction. The LPS-treated mice were administered for 7days with either AKBA or DEX at intraperitoneal doses of 5 and 1mg/kg, respectively. Cognitive, locomotor functions, and anxiety level were first examined. The level of the phosphorylated inhibitory protein for NF-κB, IκB-α (P-IκB-α), was measured, and the expression levels of the inflammatory microRNA-155 (miR-155) and its target gene, suppressor of cytokine signaling-1 (SOCS-1), were determined in the brain. Moreover, the level of carbonyl proteins as a measure of oxidative stress and several cytokines as well as markers for apoptosis and amyloidogenesis was detected. Results showed that AKBA and DEX reversed the behavioral dysfunction induced by LPS. AKBA decreased P-IκB-α, miRNA-155 expression level, and carbonyl protein content. It restored normal cytokine level and increased SOCS-1 expression level. It also showed anti-apoptotic and anti-amyloidogenic effects in LPS-injected mice. These findings suggest AKBA as a therapeutic drug for alleviating the symptoms of neuroinflammatory disorders.

MiRNA-146a, miRNA-155 and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis

Osteoarthritis (OA) is the most common joint disease characterized by joint pain and a progressive loss of articular cartilage. OA known as a non-inflammatory disease. Despite this the recent studies are shown synovitis and low inflammation to have a role in OA pathophysiology. The aim of this study to determine the roles of a potential therapeutic targets miRNA-146a, miRNA-155 and JNK expression levels in OA patients. Peripheral mononuclear blood cells (PBMCs) were extracted from OA patients and healthy subjects. The expression levels of miRNA-146a, miRNA-155 and JNK were quantified using by real-time PCR assay. According to study results a statistically significant increase was observed only in miRNA-155 expression level (p=0,039). However, miRNA-146a and miRNA-155 expressions increased in the progressive stages (grade 3 and grade 4) in OA patients. Our data suggests that correlation of miRNAs regulating and signal pathways can play an important role in OA pathogenesis and disease progression.

Prognostic Value of miRNA-155 Expression in B-Cell Non-Hodgkin Lymphoma.

Objective:MicroRNA-155 (miRNA-155) resides within the B-cell integration cluster gene on chromosome 21. It can act either as an oncogene or as a tumor-suppressor gene, depending on the cell background in which miRNA-155 is performing its specific target gene controlling function. Therefore, the aim of this study was to investigate miRNA-155 expression in patients with B-cell non-Hodgkin lymphoma (NHL) and its relation to disease prognosis in diffuse large B-cell lymphoma (DLBCL) patients.Materials and Methods:Reverse transcription-polymerase chain reaction assay was performed to evaluate the expression levels of miRNA-155 in 84 patients with newly diagnosed B-cell NHL and 15 normal controls.Results:Compared with normal controls, miRNA-155 expression was significantly upregulated in patients. Moreover, higher levels of miRNA-155 were associated with the presence of B symptoms, involvement of extranodal sites, and high Eastern Cooperative Oncology Group (ECOG) score. Higher levels of miRNA-155 in DLBCL were associated with non-germinal B-cell-like type, the presence of B symptoms, involvement of extranodal sites, and higher International Prognostic Index (IPI) and ECOG scores. Only the high IPI score and high miRNA-155 expression indicated a higher risk of lower event-free survival using multivariate Cox regression analysis. Our data demonstrated that the expression of miRNA-155 was upregulated in newly diagnosed B-cell NHL patients. miRNA-155 is expressed at a lower level in GCB-subtype DLBCL. Low IPI score and miRNA-155 expression were predictors of longer event-free survival.Conclusion:Despite contradicting literature reports, the current findings suggest the potential value of miRNA-155 as a biomarker of prognosis and monitoring in B-cell NHL, and especially that of the DLBCL type.

Tumor burden and cisplatin treatment alters the expression levels of microRNA-146a and -155 in spleen and cancer cells in an experimental mouse model of Ehrlich ascite carcinoma

Background: MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit translation and stability of messengerRNAs (mRNAs) and as such control expression of genes involved in different cellular processes. Several miRNAs have beenlinked to cancer and immune cells but whether there is a correlation between their expressions in both cells is still indistinct. Aim: In this study, we aimed to analyze miRNAs in tumor and immune cells in tumor bearing mice treated with or withoutchemotherapy. Methods: CD1 mice were inoculated with intraperitoneal (i.p.) injection of 106 viable cells from Ehrlich ascetic carcinoma (EAC)cell line to form ascities. Mice were then i.p. treated with PBS ascontrol or with cispaltin (10 or 40 μg/mouse). Semiquantificationof miRNAs 146a and 155 in spleen and tumor cells was done after 1 or 2 weeks of treatments using RT-PCR. Results: The transcription level of miRNA-146a decreased in EAC and spleen cells, while miRNA-155 expression level increased.In EAC-bearing mice treated with CIS for 1 week, miRNA-155 expression level considerably increased in spleen and tumor cellsas compared to tumor-non-bearing and untreated tumor-bearing mice. In contrast, the miRNA-146a transcription level decreasedin both spleen and tumor cells as compared to its expression level in naive and untreated EAC- bearing mice. Two weeks postCIS treatment of EAC-bearing mice, spleen cells still show low expression levels of miRNA-146a, while theexpression levels ofmiRNA-155 increased in both spleen and tumor cells. Taken together, these results suggest that miRNA expression is significantlyaltered by tumor progression and by chemotherapy.