Inflammation-related microRNAs Research Articles

Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.

Inflammation-Related microRNAs-146a and -155 Are Upregulated in Mild Cognitive Impairment Subjects Among Older Age Population in Montenegro.

Pathological and clinical features of Alzheimer's disease (AD) are in temporal discrepancy and currently accepted clinical tests provide the diagnosis decades after the initial pathophysiological events. In order to enable a more timely detection of AD, research efforts are directed to identification of biomarkers of the early symptomatic stage. Neuroinflammatory signaling pathways and inflammation-related microRNAs (miRNAs) could possibly have a crucial role in AD, making them promising potential biomarkers. We examined the expression of circulatory miRNAs with a documented role in AD pathophysiology: miR-29a/b, miR-101, miR-125b, miR-146a, and miR-155 in the plasma of AD patients (AD, n = 12), people with mild cognitive impairment (MCI, n = 9), and normocognitive group (CTRL, n = 18). We hypothesized that these miRNA expression levels could correlate with the level of participants' cognitive decline. The study participants completed the standardized interview, neurological examination, neuropsychological assessment, and biochemical analyses. miRNA expression levels were assessed by RT-PCR. Neurological and laboratory findings could not account for MCI, but miR-146a and -155 were upregulated in the MCI group compared to the control. miR-146a, known to mediate early neuroinflammatory AD events, was also upregulated in the MCI compared to AD group. ROC curve analysis for miRNA-146a showed 77.8% sensitivity and 94.4% specificity and 66.7% sensitivity and 88.9% specificity for miR-155. Determination of circulatory inflamma-miRs-146a and -155 expression, together with neuropsychological screening, could become a non-invasive tool for detecting individuals with an increased risk for AD, but research on a larger cohort is warranted.

Tumor necrosis factor alpha delivers exogenous inflammation-related microRNAs to recipient cells with functional targeting capabilities

Tumor necrosis factor alpha (TNF-α) is a critical pro-inflammatory cytokine in a wide range of tumors and infectious diseases. This study showed for the first time that TNF-α could specifically bind to certain intracellular or circulating inflammation-related microRNAs both invitro and invivo. The binding sites of TNF-α to microRNAs are located at the N-terminal of TNF-α and the 3'-GGUU motif of microRNAs. TNF-α could deliver exogenous unmodified single-stranded microRNAs into recipient cells through the TNF-α receptors (TNFRs) and stabilize them from being degraded by RNase in cells. Exogenous miR-146a or let-7c delivered into HCT116 cells by TNF-α could escape from lysosomes and specifically downregulate their target genes and then affect cell proliferation and migration invitro, as well as tumorigenesis invivo. Based on the above findings, the concept of "non-conjugated ligand-mediated RNA delivery (ncLMRD)" was proposed, which may serve as a promising strategy for therapeutic microRNA delivery in the future.

Decoding the role of inflammation-related microRNAs in cancer cachexia: a study using HPV16-transgenic mice and in silico approaches

Cachexia is associated with poor prognosis in cancer patients, and inflammation is one of its main drive factors. MicroRNAs have recently emerged as important players in cancer cachexia and are involved in reciprocal regulation networks with pro-inflammatory signaling pathways. We hypothesize that inflammation-driven cancer cachexia is regulated by specific microRNAs. The aim of this study is to explore the expression and role of inflammation-related microRNAs in muscle wasting. HPV16-transgenic mice develop systemic inflammation and muscle wasting and are a model for cancer cachexia. We employed gastrocnemius muscle samples from these mice to study the expression of microRNAs. Bioinformatic tools were then used to explore their potential role in muscle wasting. Among the microRNAs studied, miR-223-3p (p = 0.004), let-7b-5p (p = 0.034), miR-21a-5p (p = 0.034), miR-150-5p (p = 0.027), and miR-155-5p (p = 0.011) were significantly upregulated in muscles from cachectic mice. In silico analysis showed that these microRNAs participate in several processes related to muscle wasting, including muscle structure development and regulation of the MAPK pathway. When analyzing protein-protein interactions (PPI)-networks, two major clusters and the top 10 hubs were obtained. From the top 10, Kras (p = 0.050) and Ccdn1 (p = 0.009) were downregulated in cachectic muscles, as well as Map2k3 (p = 0.007). These results show that miR-223-3p, let-7b-5p, miR-21a-5p, miR-150-5p, and miR-155-5p, play a role in muscle wasting in HPV16 transgenic mice, possible through regulating the MAPK cascades. Future experimental studies are required to validate our in silico analysis, and to explore the usefulness of these microRNAs and MAPK signaling as new potential biomarkers or therapy targets for cancer cachexia.

Differential expression of circRNAs related to lipopolysaccharide-induced inflammation in bovine mammary epithelial cells

Circular RNAs (circRNAs) are widely involved in inflammatory responses, but their specific regulatory roles in cow mastitis remain controversial. In this study, RNA-seq was used to generate a circRNA expression profile, which identified 71 differentially expressed circRNAs (DEcircRNAs) in lipopolysaccharide (LPS)-stimulated MAC-T bovine mammary epithelial cells (bMECs) at different stages of inflammation. Functional analyses revealed that these DEcircRNAs may be involved in cellular proliferation, apoptosis, migration, and the inflammatory responses through regulation of numerous related signaling pathways. In addition, these data suggest that 2 novel circRNAs, named novel_circ_0004830 and novel_circ_0003097, may act as the key competing endogenous RNAs (ceRNAs) in the regulation of bovine mastitis through binding to inflammation-related microRNAs (miRNAs). These results provide a new angle for the study of the molecular regulatory mechanisms in dairy cow mastitis.

Analysis of inflammation-related microRNA expression in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a complex genetic disease characterized by axial skeletal inflammation. Available scientific evidence suggests that a relationship may exist between miRNA expression levels and the pathogenesis of AS. This study investigated the clinical diagnostic value of miR-146a, miR-15a, miR-20a, miR-125a-3p, miR-125a-5p, miR-125b-5p, miR-148a, miR-149a, miR-499, and miR-155a in AS. A total of 44 AS patients and 56 healthy controls (HCs) were included in the study. MiRNA expression levels were detected using fluorescence quantitative PCR (qPCR). Results showed that the expression levels of miR-146a, miR-125a-3p, miR-125a-5p, miR-125b-5p, and miR-155a decreased, whereas miR-499a expression increased significantly in AS patients compared to that in the controls. Logistic regression analysis with receiver operating characteristic (ROC) curves showed that combined miR-146a/miR-125a-5p/miR-125b-5p/miR-499a/miR-155a (area under curve [AUC] = 0.824, 95% confidence interval [CI] = 0.727-0.921) had high sensitivity and specificity for AS diagnosis. C-reactive protein (CRP) levels were positively correlated with the expression of miR-125a-5p (rs = 0.438, p = 0.005) and miR-155a (rs = 0.414, p = 0.006), which indicates that miR-125a-5p and miR-155a can perhaps aggravate AS-induced inflammation. Our findings suggest the association of miR-125a-5p and miR-155a with disease activity in AS patients. Furthermore, miR-146a, miR-125a-5p, miR-125b-5p, miR-499a, and miR-155a could have potential diagnostic value in AS.

High Added Dietary Sugar Intake and Circulating Inflammation‐Related MircoRNAs

The increased cardiovascular risk associated with high daily intake of dietary sugar (defined as >10% daily energy intake) is thought to be the result of chronic, low-grade inflammation. Although the mechanisms underlying the high dietary sugar-related increase in inflammatory burden are unclear, alterations in the expression of circulating inflammation-related microRNAs (miRs) may play a pivotal role. MiRs are short (18-22 nt), single stranded, noncoding RNAs that have been implicated in a number of physiological and pathological processes. Indeed, miRs are integral in the regulation of inflammation, vascular health, and, in-turn, cardiovascular disease risk, burden and severity. The aim of this study was to determine the influence of high daily sugar intake, independent of cardiovascular risk factors, on circulating levels of miR-34a, miR-92a, miR-125a, miR-126, miR-145, miR-146a, and miR-150. We hypothesized that there would be adverse differential expression of these inflammation-related miRs in adults who habitually consume high added dietary sugar. If so, this may explain, in part, the inflammatory effects of dietary sugar intake. As part of an ongoing study, 20 sedentary, middle-aged adults were studied: 12 with normal added dietary sugar intake (8M/4F; age: 55±2 yr; % sugar intake: 7.0±0.4% daily energy intake) and 8 with high added dietary sugar intake (3M/5F; 55±2 yr; 12.4±0.9% daily energy intake). All subjects were non-smokers, normotensive, and free of overt cardiometabolic diseases. Four-day diet records were used to assess daily sugar intake, and classifications were based on the 2015 Dietary Guidelines for Americans. Circulating miRs from a venous blood sample were determined using standard RT-PCR techniques with miR primers of interest. miR expression was normalized to exogenous C. elegansmiR-39 and reported as relative expression (AU). All blood samples were collected after a 10 h overnight fast (drinking water only). Circulating expression of miR-34a (3.08±0.23 vs. 1.91±0.08 AU) and miR-145 (1.1±0.1 vs. 0.6±0.1 AU) were significantly higher (~60% and ~80%, respectively); whereas miR-92a (5.92±0.60 vs. 8.55±0.52 AU), miR-125a (1.3±0.2 vs. 2.1±0.2 AU) and miR-146a (1.75±0.1 vs. 2.32±0.2 AU) were significantly lower (~30%, ~40% and ~20%, respectively) in the high added sugar compared with the normal added sugar group. There were no significant differences in circulating miR-126 (2.08±0.18 vs. 1.69±0.20 AU) or miR-150 (7.6±0.3 vs. 6.5±0.6 AU) between the normal and high added dietary sugar groups. These data indicate that high added dietary sugar intake adversely influences the expression of several inflammation-related miRs, supporting a proinflammatory state. Dysregulation of inflammation related miRs may contribute mechanistically to the heightened inflammatory state and increased CVD risk associated with a high dietary sugar intake.

Inflammation-related microRNAs are involved in stressful life events exposure and in trauma-focused psychotherapy in treatment-resistant depressed patients

ABSTRACT Background: About 30% of major depressive disorder (MDD) patients are classified as resistant to treatment (treatment-resistant depression, TRD). Among the factors associated with unfavourable treatment outcomes, stressful life events play a relevant role, and trauma-focused psychotherapy has been successfully proposed for the treatment of patients with a history of such events. Stressful experiences are related to enhanced inflammation and, recently, microRNAs (miRNAs) have emerged as potential mediators of the association between these experiences and psychiatric disorders. To date, no study has explored the effects of stressful life events on miRNAs in MDD patients. Objective: The objective of the present study was to assess possible miRNA blood expression alterations in TRD patients induced by the exposure to stressful life events and to investigate the effects of trauma-focused psychotherapy on the expression profiles of the same miRNAs, as well as their possible predictivity in relation to therapy outcome. Method: The basal levels (T0) of seven candidate miRNAs (miR-15a/miR-29a/miR-125b/miR-126/miR-146a/miR-195/let-7f) were measured in the whole blood of 41 TRD patients. A subgroup of patients (n = 21) underwent trauma-focused psychotherapy; for all of them, miRNA levels were also longitudinally assessed (T4: after 4 weeks of treatment; T8: end of treatment; T12: follow-up visit), contextually to clinical evaluations. Results: miR-146a levels negatively correlated with recent stressful life event scores (p = .001), whereas the levels of miR-15a, miR-29a, miR-126, miR-195, and let-7f changed during the psychotherapy (best p = 1.98*10−9). miR-29a was also identified as a response predictor, with lower baseline levels predicting non-response (p = .019) or worse improvement in mood symptoms (p = .032). Conclusions: The study results could contribute to clarify the underlying molecular mechanisms and to identify novel biomarkers of stressful experiences and response to targeted treatments.

Alleviation of DSS-induced colitis via Lactobacillus acidophilus treatment in mice.

Gut microbiota play a major role in host physiology and immunity. Inflammatory bowel diseases (IBDs), the important immune-related diseases, can occur through immune system malfunction originating due to dysregulation of the gut microbiota. The aim of this study was to investigate the capabilities and mechanisms of Lactobacillus acidophilus (L. acidophilus) KBL402 and KBL409 treatment in the alleviation of colitis using the in vivo dextran sodium sulfate (DSS)-induced colitis mice model. Various colitis symptoms of mice, including disease activity index score [4.55 ± 0.99 (P < 0.001) and 5.12 ± 0.94 (P < 0.001), respectively], colon length [6.18 ± 0.43 mm (P < 0.001) and 6.62 ± 0.47 mm (P < 0.001), respectively], and colon histological score [(5.33 ± 1.03 (P < 0.001) and 4.00 ± 0.89 (P < 0.01), respectively)], were significantly restored with L. acidophilusKBL402 or KBL409 administration (1×109colony-forming units) for 8 days. Moreover, inflammatory cytokines, chemokines, and myeloperoxidase were downregulated in mice with L. acidophilus treatment. Upregulation of anti-inflammatory cytokine IL-10 or regulatory T cells were discovered with L. acidophilus KBL402 (12.90 ± 7.87 pg mL-1) (P < 0.05) or L. acidophilus KBL409 treatment (10.63 ± 2.70%) (P < 0.05), respectively. Expressions of inflammation-related micro-RNAs (miRs) were also significantly altered in mice with L. acidophilus. Finally, L. acidophilus treatment could restore the diversity of the gut microbiota. Mice with L. acidophilus KBL402 treatment showed a high relative abundance of the genus Akkermansia (0.022 ± 0.017) and Prevotella (0.010 ± 0.006) (P < 0.01). Butyrate and propionate, the major short-chain fatty acids, in the ceca of DSS + KBL402-treated mice were significantly higher than in that of the mice with DSS-induced colitis (0.03 ± 0.02 ng mg-1 and 0.03 ± 0.01 ng mg-1, respectively) (P < 0.05). Our study suggests that L. acidophilus KBL402 and KBL409 could be useful for the prevention or treatment of IBDs in various ways including the modulation of immune responses and miR expression, restoration of the gut microbiota, and production of metabolites.

Predictive Inflammation-related microRNAs for Cardiovascular Events Following Early-Onset Coronary Artery Disease

Early-onset coronary artery disease (EOCAD) increases the risk of major cardiac adverse events (MACE) at the level of safety/effectiveness-related events. Since adverse events affect the quality of life of young patients with EOCAD, MACE prediction is of great importance for improving medical decision-making. We sought to determine whether the most important inflammation-related microRNAs in atherogenesis could predict MACE among patients with EOCAD. This nested case-control study recruited 143 young patients (males ≤45 and females ≤55years old), selected from a cohort of patients with premature coronary atherosclerosis at a median follow-up period of 64.1months. Total RNAs were extracted from their peripheral blood mononuclear cells. The expression levels of 18 miRNAs, which are involved in inflammation and atherogenesis, were analyzed via quantitative reverse transcription PCR. A scoring model based on the upregulation of miR-146a_1 and miR-342_1, along with a history of myocardial infarction and the chronic usage of antithrombotic drugs, was able to predict MI/death at the level of safety-related events (higher vs lower risk scores: sHR: 4.61, 95% CI: 1.57-13.57, and p=0.005). Another prediction model based on the downregulation of miR-145_1, age, and a history of unstable angina was also able to predict revascularization at the level of effectiveness-related events (higher vs lower risk scores: sHR: 2.90, 95% CI: 1.49-5.66, and p=0.002). Our results highlighted the role of miRNAs in adverse cardiac events and suggest that miR-146a_1, miR-342_1, and miR-145_1 may be useful biomarkers in predictive and preventive cardiology.

Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-\u03baB pathway

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway.

Expression Profiles of Inflammation-related MicroRNAs in Mycoplasma bovis Infected Milk of Holstein-Friesian and Doğu Anadolu Kırmızısı Cows

Mycoplasma bovis is an important pathogen associated with several clinical diseases in cattle, such as mastitis, arthritis, and pneumonia. TableIn this study, we aimed to identify miRNA candidate biomarkers associated with inflammation in Mycoplasma bovis -infected milk samples and normal milk samples of Holstein-Friesian (HF) and Doğu Anadolu Kırmızısı (DAK) cows in Turkey. The expression levels of miRNAs in milk from mastitis-infected cows and uninfected cows were analyzed using a qRT-PCR. The results revealed that miR-21, miR-146a, miR-155, miR-222, miR-383, miR-200a, miR-205, miR-122, and miR-182 were upregulated in mastitis milk. Among the miRNA candidate biomarkers, miR-21 and miR-222 were significantly upregulated only in mastitis milk samples from HF cows, and miR-146a and miR-383 were significantly upregulated only in mastitis milk samples from DAK cows. These results shed light on miRNA candidate biomarkers in milk from HF and DAK cows with subclinical mastitis. The upregulated miRNAs detected in the present study could be used as biomarkers in the diagnosis of subclinical mastitis caused by Mycoplasma bovis.

Maternal supplementation with fish oil modulates inflammation-related MicroRNAs and genes in suckling lambs

Dietary n-3 long-chain fatty acids (n-3 LCFA) have been shown to modify lipid metabolism and immune function. The objective of this study was to evaluate the effect of periparturient fish oil (FO) supplementation on the inflammation and metabolic health of ewes and their lambs at a molecular level. Prepartum ewes were fed control diet (CON, n = 12) or CON supplemented with 2% DM of calcium soap of FO (n = 12) from 28 days before until 21 days after parturition. The ewes were evaluated for plasma metabolites and milk composition. The experiment was followed by analyzing the relative transcript abundance of circulating microRNAs (miRNAs) in plasma and targeted miRNA/mRNA expression in peripheral blood mononuclear cells (PBMCs) in both ewes and lambs. FO treatment decreased prepartum feed intake (1812 ± 35 vs 1674 ± 33 g/day, P < 0.01), whereas the influence on plasma metabolites was negligible. Dietary FO supplementation decreased milk fat percentage (8.82 ± 0.49 vs 7.03 ± 0.45, P = 0.02) and reduced milk n-6/n-3 (P < 0.05). Also, it altered the expression of plasma-circulating miRNAs in both ewe and lamb (P < 0.05). Furthermore, maternal nutrition of FO downregulated the relative expression of miR-33a and miR-146b and transcript abundance of genes IL-1β (0.41-fold) and NF-κB (0.25-fold) in lambs' PBMC. In conclusion, results showed that FO supplementation starting antepartum affects milk composition and circulating miRNA in dams and the inflammatory markers in lambs delivered by the supplemented ewes. These may provide a strategy to maintain immune balance during gestation and develop the immune system in lambs.

Inflammation-Related MicroRNAs Are Associated with Plaque Stability Calculated by IVUS in Coronary Heart Disease Patients.

Objectives This study aimed to investigate the association between inflammation-related microRNAs (miR-21, 146a, 155) and the plaque stability in coronary artery disease patients. Methods The expression of miR-21, 146a, and 155 was measured by real-time PCR in 310 consecutive patients. The level of hs-CRP, IL-6, and IL-8 was measured by ELISA. The plaque stability of coronary stenotic lesions was evaluated with intravascular ultrasound (IVUS). Results (1) The levels of hs-CRP, IL-6, and IL-8 were significantly increased in the UAP and AMI groups compared with the CPS group (P < 0.01). (2) The expression of miR-21 and miR-146a in peripheral blood mononuclear cells (PBMCs) and plasma was significantly higher in CAD patients compared with non-CAD patients, whereas the miR-155 expression in PBMCs and plasma was significantly lower in patients with CAD. (3) The miR-21 expression in PBMCs was higher in UAP and AMI groups compared with CPS group. The miR-146a expression in PBMCs was higher in SAP, UAP, and AMI groups than in CPS group. Although the level of miR-155 in PBMCs was lower in SAP, UAP, and AMI groups than in CPS group. The expression patterns of miR-21, miR-146a, and miR-155 in plasma were consistent with those of PBMCs. (4) The expressions of miR-21 and miR-146a in PBMCs and plasma were significantly higher in the vulnerable plaque group than those in stable plaque group. While miR-155 in PBMCs and plasma was significantly lower in vulnerable plaque group compared with stable plaque group. (5) The levels of miR-21 and miR-146a in PBMCs and plasma were significantly higher in soft plaque group than in fibrous plaque group and calcified plaque group. However, miR-155 in PBMCs and plasma was significantly lower in soft plaque group. Conclusions The expression of miR-21 and miR-146a are associated with the plaque stability in coronary stenotic lesions, whereas miR-155 expression is inversely associated with the plaque stability.

The role of inflammation and its related microRNAs in breast cancer: A narrative review.

Breast cancer is recognized as the most common type of cancer among women with a high rate of mortality all over the world. Over the past years, growing attention has been regarded to realize more about the mechanisms underlying the disease process. It is revealed that the progression of breast cancer may be strongly linked to chronic inflammation owing to the role of inflammatory factors in genetic instability and subsequent cancer predisposition. Although the association between breast cancer and inflammatory pathways has been well-defined now, only recent evidence pointed towards the inflammation-related microRNAs (miRNAs) as potential biomarkers and therapeutic targets involved in the crosstalk of multiple pathways during breast cancer development. Moreover, the practical interactions between these miRNAs and inflammatory factors are also a little characterized. In this review, we intended to describe the effects of predominant inflammatory pathways such as cytokines, phosphoinositide 3-kinase/protein kinase B, and nuclear factor kappa B in association with tumor promoting and tumor suppressing miRNAs on breast cancer progression. Providing new studies in the field of combining biomarkers for early diagnosis, prognosis, and monitoring breast cancer are very important. Notably, understanding the underlying mechanisms of miRNAs as a possible link between inflammation and tumorigenesis may offer a novel insight for combating this epidemic.

Inflammation-related microRNA expression level in the bovine milk is affected by mastitis

MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis.

MicroRNA-155 in patients with Chronic Stable Angina

Background: Atherosclerotic cardiovascular disease is a chronic inflammatory disease and one of the major causes of death worldwide. MicroRNAs are associated with many physiological and pathological situations as inflammation and cardiovascular disease. The communication between microRNAs, inflammation, and atherosclerosis, drive attention to the possibility that inflammation-related microRNAs, miRNA-155, could have a role in atherosclerosis progression. Objectives: We aimed to determine the levels of circulating miRNA-155 in chronic stable angina patients and to study the impact of microRNA-155 on coronary artery disease severity and extent. Methods: MicroRNA was extracted and assessed from plasma of 50 subjects (20 normal controls and 30 patients with chronic stable angina) using quantitative reverse-transcription PCR (RT-PCR). Levels were compared in the two groups and correlated with Gensini score in the group with chronic stable angina (CSA). Results : Plasma levels of microRNA 155 were significantly lower in CSA patients (0.59±0.48, 1.94±0.76, in patients and control group respectively (P<0.001). The expression of miR-155 correlated negatively with Gensini scores (P<0.001), total cholesterol (P <0.001), LDL-c (P= 0.002) and triglycerides (P= 0.03). There was a significant difference in miRNA-155 levels among the quartiles of the CSA group (P < 0.001) denoting negative correlation between microRNA 155 and coronary artery disease extent. ROC curve showed that microRNA-155 sensitivity and specificity for the prediction of severity of atherosclerosis were 86.67% and 80% respectively. Conclusion: Plasma miRNA-155 is significantly lower in CSA angina patients and levels significantly decreases with the progression of atherosclerosis. DOI: 10.21276/AABS.2017.1383

Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) expression

Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.

Involvement of inflammation and its related microRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed type of cancer. The tumor inflammatory microenvironment regulates almost every step towards liver tumorigenesis and subsequent progression, and regulation of the inflammation-related signaling pathways, cytokines, chemokines and non-coding RNAs influences the proliferation, migration and metastasis of liver tumor cells. Inflammation fine-tunes the cancer microenvironment to favor epithelial-mesenchymal transition, in which cancer stem cells maintain tumorigenic potential. Emerging evidence points to inflammation-related microRNAs as crucial molecules to integrate the complex cellular and molecular crosstalk during HCC progression. Thus understanding the mechanisms by which inflammation regulates microRNAs might provide novel and admissible strategies for preventing, diagnosing and treating HCC. In this review, we will update three hypotheses of hepatocarcinogenesis and elaborate the most predominant inflammation signaling pathways, i.e. IL-6/STAT3 and NF-κB. We also try to summarize the crucial tumor-promoting and tumor-suppressing microRNAs and detail how they regulate HCC initiation and progression and collaborate with other critical modulators in this review.

Dipeptidyl Vinyl Sulfone as a Novel Chemical Tool to Inhibit HMGB1/NLRP3-Inflammasome and Inflamma-miRs in Aβ-Mediated Microglial Inflammation.

Rapid microglial activation and associated inflammatory pathways contribute to immune-defense and tissue repair in the central nervous system (CNS). However, persistent activation of these cells will ultimately result in vast production of pro-inflammatory mediators and other neurotoxic factors, which may induce neuronal damage and contribute to chronic neurodegenerative diseases, as Alzheimer's disease (AD). Therefore, small molecules with immunomodulatory effects on microglia may be considered as potential tools to counteract their proinflammatory phenotype and neuroimmune dysregulation in such disorders. Indeed, reducing amyloid-β (Aβ)-induced microglia activation is believed to be effective in treating AD. In this study, we investigated whether dipeptidyl vinyl sulfone (VS) was able to attenuate Aβ-mediated inflammatory response using a mouse microglial (N9) cell line and a solution containing a mixture of Aβ aggregates. We show that low levels of VS are able to prevent cell death while reducing microglia phagocytosis upon Aβ treatment. VS also suppressed Aβ-induced expression of inflammatory mediators in microglia, such as matrix metalloproteinase (MMP)-2 and MMP-9, as well as high-mobility group box protein-1 (HMGB1), nod-like receptor protein 3 (NLRP3)-inflammasome, and interleukin (IL)-1β. Interestingly, increased expression of the two critical inflammation-related microRNAs (miR)-155 and miR-146a in microglia upon Aβ treatment was also prevented by VS coincubation. Taken together, VS emerges as a potential new therapeutic strategy worthy of further investigation in improved cellular and animal models of AD.