DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.     

Temporal and spatial regulation of bone morphogenetic protein signaling in late lung development.

Bone morphogenetic proteins (BMPs) play important roles in early lung development. No study to date has addressed a role for BMP signaling in late lung development. We describe changes in the expression and localization of BMP receptors (Bmpr1a, Bmpr1b, and Bmpr2) and Smad (Smad1, Smad4, Smad5, and Smad8) intracellular signaling proteins during the saccular and alveolarization stages of late lung development. BMP signaling, assessed by Smad1/5 phosphorylation, nuclear translocation, and induction of id1, id2, and id3 gene expression, was evident throughout late lung development. Our data indicate that BMP signaling is active during late lung development, and points to roles for the BMP system in septal and vascular development, and in the homeostasis of the epithelial layer of large conducting airways in the mature lung.     

Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (Cftr(tmlUnc-/-)) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoid P. aeruginosa, the host, and antibacterial therapy.     

Co-Microencapsulation of Anthocyanins from Cornelian Cherry (Cornus mas L.) Fruits and Lactic Acid Bacteria into Antioxidant and Anti-Proliferative Derivative Powders

Driven by the modern lifestyle, the consumers are interested in healthier and balanced diets, including both probiotics and natural antioxidants. The beneficial health effects of probiotics are mainly due to their capacity of modulating the human intestinal microbiota, although achieving at least a 6 log of viable cells at the targeted site is still challenging. Therefore, in this study, an attempt to improve the bioaccessibility of Lacticaseibacillus casei (L. casei) 431^® through a co-microencapsulation by complex coacervation and freeze-drying, using an extract from Cornelian cherry and two biopolymeric matrices, whey protein isolates and casein (WPI-CN) and inulin (WPI-I), was studied. The powders showed a comparable anthocyanin content of around 32.00 mg cyanidin-3-rutinoside (C3R)/g dry matter (DM) and a microbial load of about 10 Log CFU/g DM. A high stability of the lactic acid bacteria was assessed throughout 90 days of storage, whereas the anthocyanins’ degradation during storage followed a first order kinetic model, allowing the estimation of a half-time of 66.88 ± 1.67 days for WPI-CN and 83.60 ± 2.46 days for WPI-I. The in vitro digestion showed a high stability of anthocyanins in the simulated gastric juice, whereas the release in the simulated intestinal juice was favored in the variant with inulin (up to 38%). The use of casein permitted to obtain finer spherosomes, with smaller diameters, whereas a double encapsulation was obvious in both variants, thus explaining the high resistance in the gastric environment. The anti-proliferative effect against the human colon cancer cell line (HT-29) was also demonstrated. No cytotoxicity has been found for the concentrations between 1 and 25 μg/mL for the WPI-I variant, whereas a cell proliferation effect was observed at low concentrations of 1–5 μg/mL.     

Effects of Solvent Additive and Micro-Patterned Substrate on the Properties of Thin Films Based on P3HT:PC70BM Blends Deposited by MAPLE

Lately, there is a growing interest in organic photovoltaic (OPV) cells due to the organic materials’ properties and compatibility with various types of substrates. However, their efficiencies are low relative to the silicon ones; therefore, other ways (i.e., electrode micron/nanostructuring, synthesis of new organic materials, use of additives) to improve their performances are still being sought. In this context, we studied the behavior of the common organic bulk heterojunction (P3HT:PC70BM) deposited by matrix-assisted pulsed laser evaporation (MAPLE) with/without 0.3% of 1,8-diiodooctane (DIO) additive on flat and micro-patterned ITO substrates. The obtained results showed that in the MAPLE process, a small quantity of additive can modify the morphology of the organic films and decrease their roughness. Besides the use of the additive, the micro-patterning of the electrode leads to a greater increase in the absorption of the studied photovoltaic structures. The inferred values of the filling factors for the measured cells in ambient conditions range from 19% for the photovoltaic structures with no additive and without substrate patterning to 27% for the counterpart structures with patterning and a small quantity of additive.     

A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.