Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer.

Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC.

Airway epithelial development and function: A key player in asthma pathogenesis?

Though asthma is a common and relatively easy to diagnose disease, attempts at primary or secondary prevention, and cure, have been disappointing. The widespread use of inhaled steroids has dramatically improved asthma control but has offered nothing in terms of altering long-term outcomes or reversing airway remodeling and impairment in lung function. The inability to cure asthma is unsurprising given our limited understanding of the factors that contribute to disease initiation and persistence.

Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease.

The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, nontypeable Haemophilus influenzae (NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multifunctional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host-pathogen cross-talk, impair macrophage and neutrophil function.

Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy.

HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included.

Effects of combined administration of doxorubicin and chloroquine on lung pathology in mice with solid Ehrlich ascites carcinoma.

Combined use of a chemotherapeutic agent and an autophagy inhibitor is a novel cancer treatment strategy. We investigated the effects of chloroquine (CQ) on lung pathology caused by both solid Ehrlich ascites carcinoma (EAC) and doxorubicin (DXR). A control group and eight experimental groups of adult female mice were inoculated subcutaneously with 2.

Outcome of refractory to conventional and/or biologic treatment adult Still's disease following canakinumab treatment: Countrywide data in 50 patients.

Objective: To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use.

Methods: In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatment with corticosteroids (n = 11), conventional and synthetic (n = 34) and/or biologic disease modifying anti-rheumatic drugs (n = 30), we assessed the efficacy of canakinumab 150-300 mg administered every 4 (n = 47) or 8 weeks (n = 3) as combination therapy or monotherapy (n = 7) during a median follow-up of 27 (3-84) months.

Results: Α complete response was initially observed in 78% of patients within 3 months (median), irrespective of age at disease onset.

Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg-negative chronic hepatitis B.

Reliable predictors of outcomes after treatment discontinuation in HBeAg-negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon-inducible protein-10 (IP10) and hepatitis B core-related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg-negative CHB patients who discontinued long-term antiviral therapy. All HBsAg-positive (n = 57) patients of the prospective DARING-B study were included and followed monthly for 3 months, every 2/3 months until month-12 and every 3/6 months thereafter.

Factors Associated With Progression and Outcomes of Early Stage Primary Biliary Cholangitis.

Background & Aims: Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival.

Methods: We obtained data from 1615 patients (mean age, 55.

DARING-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B.

Background: The remission rates after stopping antivirals in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) vary among studies, while reliable predictors of relapse have not been identified. This prospective study assessed rates and predictors of relapse and retreatment in 57 non-cirrhotic hepatitis B surface antigen (HBsAg)-positive patients with HBeAg-negative CHB who discontinued effective ≥4-year entecavir or tenofovir disoproxil fumarate (TDF) therapy.

Methods: A total of 57 patients discontinued therapy after median virological remission of 5.

Chloroquine Used in Combination with Chemotherapy Synergistically Suppresses Growth and Angiogenesis and .

Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy.

Materials And Methods: The cytotoxic effect of doxorubicin (0.1-1 μM), chloroquine (0.

Prioritization for interferon-free regimens and potential drug interactions of current direct-acting anti-hepatitis C agents in routine clinical practice.

Background: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs).

Methods: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure.

COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis.

Background & Aims: Recently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, we assessed whether serum COMP levels can be used as a non-invasive fibrosis marker in patients with chronic viral hepatitis (CVH) and compared this marker with standard methods for disease stage assessment [histology, transient elastography (TE), APRI, FIB-4].

Methods: Sera from 116 CVH patients, 66 HBV [24 female; median age 53(22-76)] and 50 HCV [21 female; median age 48.

Anti-angiogenic effect of a Palladium(II)-Saccharinate Complex of Terpyridine in vitro and in vivo.

Anti-angiogenic activity of palladium (Pd)(II)-based complexes is unknown despite their quite powerful anticancer activity. This study was therefore carried out to evaluate both in vivo anti-angiogenic effect and in vitro cytotoxic activity of a Pd(II)-based complex. ([Pd(sac)(terpy)](sac)·4HO(sac=saccharinate and terpy=2,2':6',2″-terpyridine)) on HUVEC cells.

Comparative meta-analysis on the various vascularized bone flaps used for the treatment of scaphoid nonunion.

We did a meta-analysis of the literature in order to clarify which of the vascularized bone flaps (VBF) used for scaphoid non-union treatment has the best outcome with regard to various parameters. We analyzed 54 articles that present nine different types of VBF. The analysis concerned demographical patient information, radiographic parameters, fracture classification, including the presence or non-presence of avascular necrosis of the scaphoid proximal pole (PP AVN), parameters that have to do with the surgery itself and the postoperative protocol, the healing of the nonunion and functional scores.

The Forgotten Asclepieion of Peparithos and the Islander Worshippers of the Snake God.

The ancient Asclepieion of the island of Peparithos, modern Skopelos, had been build in an ideal position, one kilometer from the ancient city of Peparithos. The angry north Aegean Sea brought in the surface its north wall at the beginning of the 60s decade. The monument was identified as an Asclepieion from one partially saved ceramic inscription "ASCL…" (Greek: ΑΣΚΛ…).

Review article: autoimmune hepatitis -- current management and challenges.

Background: Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression.

Aim: To review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH.

Methods: Published studies on AIH extracted mainly from PubMed during the last 15 years.

The shaping of invasive glioma phenotype by the ubiquitin-proteasome system.

Protein degradation is an indispensable process for cells which is often deregulated in various diseases, including malignant conditions. Depending on the specific cell type and functions of expressed proteins, this aberration may have different effects on the determination of malignant phenotypes. A discrete, inherent feature of malignant glioma is its profound invasive and migratory potential, regulated by the expression of signaling and effector proteins, many of which are also subjected to post-translational regulation by the ubiquitin-proteasome system (UPS).

Adipokines as mediators of endothelial function and atherosclerosis.

For many decades, adipose tissue was considered as an inactive body compartment that was only used as an energy store. During the recent years, an increasing amount of data has revealed that adipose tissue is a major endocrine and paracrine organ producing numerous enzymes, hormones and growth factors which are collectively termed as adipokines. Several experimental and clinical studies showed that adipokines modulate insulin sensitivity and have an influence on glucose/fat metabolism and obesity.

Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can progress to cirrhosis, liver failure, and hepatocellular carcinoma. In the last two decades, the prevalence of NAFLD has been growing in most developed countries, mainly as a consequence of its close association with obesity and diabetes mellitus. The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression have not been completely understood.

Metabolic acidosis during treatment of mushroom poisoning: a diagnostic pitfall.

Metabolic acidosis is a frequently encountered acid-base disturbance in hospitalized patients that occasionally develops in the course of treatment with medications used in everyday clinical practice, including propylene glycol-containing drugs (lorazepam, diazepam, etomidate, pentobarbital). Disruption of enterohepatic circulation with activated charcoal is a common practice for several intoxications, including mushroom poisoning. Herein, we present a patient who was hospitalized due to mushroom intoxication and developed severe metabolic acidosis as a treatment side effect rather than from the mushroom poisoning.

Anti-α actinin antibodies as new predictors of response to treatment in autoimmune hepatitis type 1.

Background: We reported that combined presence of autoantibodies (Abs) against filamentous-actin (AFA) and α-actinin are specific for autoimmune hepatitis type 1 (AIH-1) diagnosis.

Aim: To explore our data and assess whether anti-α-actinin and AFA Abs could be used as indicators of response to treatment and predictors of AIH-1 flares in a large cohort of AIH-1 patients.

Methods: Seven hundred and sixty-four serial serum samples of 86 consecutive AIH-1 patients, 509 pathological and 110 normal controls were tested for the presence of anti-α-actinin and AFA Abs by an in-house IgG-specific ELISA and a standardised commercially available ELISA respectively.

Effect of simulated gastro-duodenal digestion on the allergenic reactivity of beta-lactoglobulin.

Background: Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children.