Somatic ablation of IKKβ in liver and leukocytes is not tolerated in obese mice but hepatic IKKβ deletion improves fatty liver and insulin sensitivity.

The kinase IKKβ controls pro-inflammatory gene expression, and its activity in the liver and leukocytes was shown to drive metabolic inflammation and insulin resistance in obesity. However, it was also proposed that liver IKKβ signaling protects obese mice from insulin resistance and endoplasmic reticulum (ER) stress by increasing XBP1s protein stability. Furthermore, mice lacking IKKβ in leukocytes display increased lethality to lipopolysaccharides.

JNK1 ablation improves pancreatic β-cell mass and function in db/db diabetic mice without affecting insulin sensitivity and adipose tissue inflammation.

The cJun N-terminal Kinases (JNK) emerged as a major link between obesity and insulin resistance, but their role in the loss of pancreatic β-cell mass and function driving the progression from insulin resistance to type-2 diabetes and in the complications of diabetes was not investigated to the same extent. Furthermore, it was shown that pan-JNK inhibition exacerbates kidney damage in the db/db model of obesity-driven diabetes. Here we investigate the role of JNK1 in the db/db model of obesity-driven type-2 diabetes.

Effect of acetylsalicylic acid on inflamed adipose tissue. Insulin resistance and hepatic steatosis in a mouse model of diet-induced obesity.

Aims: Obesity represents a global health problem. Excessive caloric intake promotes the release of inflammatory mediators by hypertrophic adipocytes and obesity-induced inflammation is now recognized as a risk factor for the development of several diseases, such as cardiovascular diseases, insulin resistance, type-II diabetes, liver steatosis and cancer. Since obesity causes inflammation, we tested the ability of acetylsalicylic acid (ASA), a potent anti-inflammatory drug, in counteracting this inflammatory process and in mitigating obesity-associated health complications.

Experimental Paradigm for the Assessment of the Non-pharmacological Mechanism of Action in Medical Device Classification: The Example of Glycerine as Laxative.

The evolution of medical devices has led to the introduction of medical devices that include "substances" and which, due to their presentation and sites of application may resemble medicinal products. The difference between substance-based medical devices and medicinal products lies in the proper definition of the principal mechanism of action. The major problem at the moment is the lack of a proper procedure for the demonstration of a mechanism that is "not pharmacological, immunological or metabolic.

T cell costimulation blockade blunts pressure overload-induced heart failure.

Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients.

Three months of Western diet induces small intestinal mucosa alteration in TLR KO mice.

Several studies support the role of Western-style diet (WD) in inflammatory bowel disease (IBD). Toll-like receptors/NOD-like receptors (TLRs/NLRs) are important to maintain a healthy epithelium as well as inducing inflammation. Given that dietary factors influence IBD development, that epithelial dysfunction is thought to be involved in initiating intestinal inflammation and that TLR-NLR are involved in maintenance of the functionality of intestinal epithelium as well as in regulating inflammation, we decided to examine the role of TLR signals in the triggering events that lead to alteration of the small intestinal epithelium associated to consumption of WD.

Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model.

In recent years, tumor Adoptive Cell Therapy (ACT), using administration of ex vivo-enhanced T cells from the cancer patient, has become a promising therapeutic strategy. However, efficient homing of the anti-tumoral T cells to the tumor or metastatic site still remains a substantial hurdle. Yet the tumor site itself attracts both tumor-promoting and anti-tumoral immune cell populations through the secretion of chemokines.

Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis.

Calcitonin Gene-Related Peptide (CGRP) inhibits microglia inflammatory activation in vitro. We here analyzed the involvement of CGRP and Receptor Component Protein (RCP) in experimental autoimmune encephalomyelitis (EAE). Alpha-CGRP deficiency increased EAE scores which followed the scale alpha-CGRP null>heterozygote>wild type.

Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis.

Background: Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis.

Methods: Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1.