Serum microRNA-122 predicts survival in patients with liver cirrhosis

Background: Liver cirrhosis is associated with high morbidity and mortality. MicroRNAs (miRs) circulating in the blood are an emerging new class of biomarkers. In particular, the serum level of the liver-specific miR-122 might be a clinically useful new parameter in patients with acute or chronic liver disease. Aim: Here we investigated if the serum level of miR-122 might be a prognostic parameter in patients with liver cirrhosis. Methods: 107 patients with liver cirrhosis in the test cohort and 143 patients in the validation cohort were prospectively enrolled into the present study. RNA was extracted from the sera obtained at the time of study enrollment and the level of miR-122 was assessed. Serum miR-122 levels were assessed by quantitative reverse-transcription PCR (RT-PCR) and were compared to overall survival time and to different complications of liver cirrhosis. Results: Serum miR-122 levels were reduced in patients with hepatic decompensation in comparison to patients with compensated liver disease. Patients with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome had significantly lower miR-122 levels than patients without these complications. Multivariate Cox regression analysis revealed that the miR-122 serum levels were associated with survival independently from the MELD score, sex and age. Conclusions: Serum miR-122 is a new independent marker for prediction of survival of patients with liver cirrhosis

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have faile

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed

Development of abiotic stress tolerance via bZIP-type transcription factor LIP19 in common wheat

BackgroundAutotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.MethodsPatients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.Results270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, PConclusionSerum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients

NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network

Mouse B cells lacking NFATc1 exhibit defective proliferation, survival, isotype class switching, cytokine production, and T cell help

Risk factors for acute unplanned tracheostomy during panendoscopy in HNSCC patients.

BackgroundDespite of careful pre-operative risk evaluation some patients require an acute unplanned tracheostomy during panendoscopy.MethodsRisk factors of patients requiring an unplanned tracheostomy during panendoscopy (n = 32) were compared to a control group with panendoscopy without tracheostomy (n = 180).Results2131 panendoscopies for Head and Neck squamous cell carcinoma were performed at our Department between 2000 and 2014. Unplanned tracheostomies were necessary in 1.6% of all panendoscopies. Patients with laryngeal cancer (p = 0.001) or abnormal activated partial thromboplastin time (aPTT) (p = 0.03) had a statistically significant higher risk of unplanned tracheostomy. Regression analysis showed that patients with advanced laryngeal cancer had an almost 6 times higher risk for tracheostomy than patients with early stage oropharyngeal cancer.ConclusionsWe identified abnormal aPTT and laryngeal carcinoma as significant predictors for unplanned tracheostomy during panendoscopy. The results of our study could improve preoperative risk evaluation in HNSCC patients

Regional grey matter volume reduction in adolescents engaging in non-suicidal self-injury

There is a high prevalence of non-suicidal self-injury (NSSI) amongst adolescents worldwide and therefore an urgency to investigate the underlying mechanisms that may facilitate such behaviours. This study aimed to investigate neurobiological alterations, specifically in regional brain volumes of the frontolimbic system, in adolescents engaging in NSSI in comparison to healthy controls. Regional grey matter volumes were compared between 29 adolescent female patients who presented with incidents of NSSI on >= 5 days within the last 12 months (DSM-5 criteria for NSSI) and 21 healthy age, gender and education matched controls who had never received any psychiatric diagnosis/treatment, or engaged in NSSI. Significant group effects in regional brain volumes were observed in insula, and a suggested change in the anterior cingulate cortex (ACC), while controlling for total segmented volume. Additionally, ACC volume showed a significant association with past suicide attempts, where estimated marginal means showed even smaller ACC volume in adolescents engaging in NSSI with a history of suicide attempt in comparison to those with no history of suicide attempt, including healthy controls. This study provides the first evidence of volumetric changes in adolescents engaging in NSSI and a potential neurobiological link between NSSI and suicide attempt