Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines.

Objective: MicroRNAs (miRNA/miR) are stably present in body fluids and are increasingly explored as disease biomarkers. Here, we investigated influence of impaired wound healing on the plasma miRNA signature and their functional importance in patients with type 2 diabetes mellitus.

Approach And Results: miRNA array profiling identified 41 miRNAs significantly deregulated in diabetic controls when compared with patients with diabetes mellitus-associated peripheral arterial disease and chronic wounds.

Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators.

Objective: In HCV infected individuals graft infection occurs shortly after orthotopic liver transplantation (OLT). We aimed to describe the composition of the inflammatory response at this time, how it affects the HCV replication cycle and identify novel proviral and antiviral factors.

Design: We used a Luminex assay to quantify 50 inflammatory mediators in sera before and shortly after OLT.

Angiogenic and growth factors in gastric cancer.

Background: Antiangiogenic treatment is at the horizon in the palliative treatment of gastric cancer (GC), but data on proangiogenic biomarkers are still limited. The aim of this study was to analyze five proteins with a function in tumor angiogenesis: vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), follistatin, leptin, and platelet endothelial cell adhesion molecule 1 (CD31) in peripheral blood and corresponding tumor tissue.

Material And Methods: From 2008-2010, tumor tissue (n = 76) and corresponding preoperative serum (n = 69) of patients with localized GC were collected; 45 had perioperative chemotherapy.

Pretransplant metabolic distress predicts relapse of acute myeloid leukemia after allogeneic stem cell transplantation.

Background: The impact of nutritional status on outcome of allogeneic stem cell transplantation (alloSCT) is controversial. This study investigates the influence of pretransplant weight loss and serologic indicators of nutritional homeostasis on relapse and death of acute myeloid leukemia (AML) after alloSCT.

Methods: Pretransplant weight loss along with serum levels of total serum protein (TSP), albumin, C-reactive protein, and leptin were collected retrospectively in a training cohort (n = 149) and correlated with clinical outcome.

Data-derived modeling characterizes plasticity of MAPK signaling in melanoma.

The majority of melanomas have been shown to harbor somatic mutations in the RAS-RAF-MEK-MAPK and PI3K-AKT pathways, which play a major role in regulation of proliferation and survival. The prevalence of these mutations makes these kinase signal transduction pathways an attractive target for cancer therapy. However, tumors have generally shown adaptive resistance to treatment.

Experimental colitis is exacerbated by concomitant infection with Mycobacterium avium ssp. paratuberculosis.

Background: Crohn's disease (CD) is a chronic inflammatory disorder of the human gastrointestinal tract. Although genetic, immunological, environmental, and bacterial factors have been implicated, the pathogenesis is incompletely understood. The histopathological appearance of CD strikingly resembles Johne's disease, a ruminant inflammatory bowel disease, caused by Mycobacterium avium ssp.

Anti-HDV IgM as a marker of disease activity in hepatitis delta.

Background: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.

BRaf and MEK inhibitors differentially regulate cell fate and microenvironment in human hepatocellular carcinoma.

Purpose: Small molecule inhibitors of the mitogen-activated protein kinase (MAPK) pathway, such as sorafenib, represent novel treatment options for advanced hepatocellular carcinoma. The aim of our study was to identify downstream targets as biomarker candidates that are directly linked to the oncogenic MAPK pathway in hepatocellular carcinoma and correlate with inhibition of this pathway by multikinase inhibitors.

Experimental Design: Hepatocellular carcinoma cell lines and fresh tumor and tumor-free liver tissues from patients with hepatocellular carcinoma were incubated with different BRaf or MEK inhibitors and analyzed for kinase phosphorylation, proliferation, induction of apoptosis, and chemokine secretion.

Ablation of proximal tubular suppressor of cytokine signaling 3 enhances tubular cell cycling and modifies macrophage phenotype during acute kidney injury.

Suppressor of cytokine signaling 3 (SOCS-3) is an important intracellular negative regulator of several signaling pathways. We found that SOCS-3 is highly expressed in renal proximal tubules during acute kidney injury. To test the impact of this, conditional proximal tubular knockout mice (SOCS-3(sglt2Δ/sglt2Δ)) were created.

The Peripheral NK Cell Repertoire after Kidney Transplantation is Modulated by Different Immunosuppressive Drugs.

In the context of kidney transplantation, little is known about the involvement of natural killer (NK) cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.

[Differences in the response to sepsis between C57BL/6 and BALB/c mice].

Objective: To compare the responses to sepsis between C57BL/6 and BALB/c mice.

Methods: Thirty C57BL/6 mice and 30 BALB/c mice were randomized into sham-operated group and sepsis group (n=15). Sepsis model was established by cecal ligation puncture (CLP) in the mice, and 6 h after the operation, 5 mice from each group were selected randomly for cytokine detection including IL-1beta, IL-2, IL-4, IL-5, IL-10, GM-CSF, IFN-gamma and TNF-alpha by Bio-plex.

[Effect of FK506 on cytokine secretion in whole blood].

Objective: To investigate the effect of FK506 on cytokine secretions in whole blood from healthy individuals.

Methods: Blood samples collected from healthy volunteers were co-cultured with different concentrations of FK506 and stimulated with PMA and IONO. The concentrations of 8 cytokines including IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF were detected by Bio-Plex suspension system.

The "Miracle" fetus: an excellent model for apoptotic cell-induced immune tolerance?

For several decades, people have wondered why pregnant mothers do not reject fetuses bearing allogeneic paternal antigens. Several hypotheses have been proposed, including a physical barrier between fetus and mother, immaturity of fetal antigens and temporary dormancy of the maternal immune system. Based on the "cell death immune recognition model," the author proposes a hypothesis that pregnancy tolerance is an active immune response of the maternal immune system, which is induced by apoptotic cells bearing paternal antigens.

[Necrotic cells induce and promote inflammatory responses in vitro].

Objective: To investigate the effect of necrotic cells on the secretion of inflammatory cytokines.

Methods: RAW264.7 macrophages and necrotic mouse thymocytes induced by heating were incubated for 18 h at a ratio of 5:1 in the absence or presence of lipopolysaccharide (LPS, 100 ng/ml).

Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood.

It is critical to determine the status of the immune system in transplant recipients, but there are currently no clinical methods available to do so. To address this, we have developed an innovative method to evaluate the effects of immunosuppressants that involves measuring phytohemagglutinin (PHA)-stimulated cytokine secretions in vitro in response to treatments with dexamethasone (DEX), FK506 or mycophenolic acid (MPA). The results revealed that DEX nonspecifically and dose-dependently inhibited the production of 12 cytokines (IL-2, IFN-gamma, TNF-alpha, IL-8, IL-1beta, IL-17, IL-4, IL-5, IL-6, IL-10, IL-13, and G-CSF).

Cell death recognition model for the immune system.

It is essential for the immune system to recognize markers or understand rules required for discriminating antigens that should be actively responded to from those be tolerated. Although the classic self-nonself theory over the past five decades has been challenged by "danger" model and "infectious nonself" model, etc., no theories could fit for all.