mi R-122 negatively correlates with liver fibrosis as detected by histology and FibroScan

AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections(types B, C), 19 with autoimmune liver diseases(autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology(alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNAisolation, expression levels of mi R-21, mi R-122, mi R-214, mi R-221, mi R-222, and mi R-224 were determined using Taq Man Micro RNA Assays applying mi R-140 as the reference. Selection of mi RNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of mi RNAs was correlated with fibrosis stage and liver stiffness(LS) value measured by transient elastography, as well as with serum alanine aminotransferase(ALT) level.RESULTS: The expression of individual mi RNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of mi R-122 in stage F4 was statistically significant(P < 0.04). When analyzing mi RNA expression in relation to fibrosis, levels of mi R-122 and mi R-221 showed negative correlations with fibrosis stage, and mi R-122 was found to correlate negatively and mi R-224 positively with LS values(all P < 0.05). ALT levels displayed a positive correlation with mi R-21(P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between mi R-122 and fibrosis stage and LS values(P < 0.05), and in the samples of chronic viral hepatitis, between mi R-221 and fibrosis stage(P < 0.01), whereas mi R-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases(P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values(P < 0.01) when etiology of fibrosis was not taken into account.CONCLUSION: Reduced expression of mi R-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.

ECG stress test induced atrial ischemia in a patient with old inferior myocardial infarction due to a distal coronary artery lesion

A 78-year-old man with a history of mitral valve prolapse underwent echocardiography during his cardiological check-up examination in 2011 in a symptom-free stage. Echocardiography revealed akinesis of the inferior septum and inferobasal free wall as a novel finding suggesting a distal right coronary artery （RCA） lesion （Figure 1）. The systolic left ventricular function was normal. Earlier echocardiographies did not show wall motion abnormalities.

Elevated miR-33a and miR-224 in steatotic chronic hepatitis Cliver biopsies

AIM: To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues.

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn&#x02019;s disease (CD) and the effect of transforming growth factor-&#x003b2; (TGF-&#x003b2;) on these miRs in duodenal epithelial and fibroblast cells.METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-&#x003b2; (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 &#x000b1; 0.50 vs CD intact: 0.62 &#x000b1; 0.26, P &#x02264; 0.01) and to the control group (CD inflamed: 3.21 &#x000b1; 0.50 vs C: 1.00 &#x000b1; 0.33, P &#x02264; 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 &#x000b1; 1.02 vs Control: 1.00 &#x000b1; 0.40, P &#x02264; 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-&#x003b2; treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-&#x003b2;: 0.7 &#x000b1; 0.083 vs Control: 1 &#x000b1; 0.09, P &#x02264; 0.05) and also the expression of miR-146a (TGF-&#x003b2;: 0.67 &#x000b1; 0.04 vs Control: 1 &#x000b1; 0.15, P &#x02264; 0.01) and miR-155 (TGF-&#x003b2;: 0.72 &#x000b1; 0.09 vs Control: 1 &#x000b1; 0.06, P &#x02264; 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-&#x003b2; treatment did not influence the expression of miR-122.CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-&#x003b2; plays an important role in the regulation of the expression of these miRs.

Involvement of heat shock proteins in gluten-sensitive enteropathy

Gluten-sensitive enteropathy,also known as coeliac disease(CD),is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients.As it is triggered by dietary gluten and related prolamins present in wheat,rye and barley,the accepted treatment for CD is a strict gluten-free diet.However,a complete exclusion of gluten-containing cereals from the diet is often difficult,and new therapeutic strategies are urgently needed.A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins(HSPs),which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors.HSPs are expressed in several tissues,including the gastrointestinal tract,and their levels are significantly increased under stress circumstances.HSPs exert immunomodulatory effects,and also play a crucial role in the maintenance of epithelial cell structure and function,as they are responsible for adequate protein folding,influence the degradation of proteins and cell repair processes after damage,and modulate cell signalling,cell proliferation and apoptosis.The present review discusses the involvement of HSPs in the pathophysiology of CD.Furthermore,HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective,immunomodulatory,and anti-apoptotic effects in the intestinal mucosal barrier.

Inflammation and oxidative stress caused might lead to left ventricular diastolic and hypertension by nitric oxide synthase uncoupling systolic dysfunction in patients with

Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.