Eine kurze Geschichte der Metaphysik

A very short history of metaphysics

TAK-242 reverses the visceral hypersensitivity phenotype in DIO mice.

<p>Administration of the selective TLR4 antagonist TAK-242 (i.v. 10mg/kg) significantly reduces visceral pain responses in DIO (A) but not in lean mice (B). Moreover, the antagonist normalizes the decreased pain threshold in DIO mice (C) without affecting the pain threshold in lean mice (D). * p<0.05; ** p<0.01; independent sample t-test or repeated measures 2-way analysis of variance followed by Bonferroni’s post-hoc test; baseline response to CRD was not different between individual groups/conditions; data represent mean ± standard error of the mean (SEM).</p

Diet-induced obesity.

<p>Long-term exposure to high-fat diet increases body-weight (A), percentage of adipose body mass (B) and a relative decrease in percentage of lean body mass (C) in diet-induced obese (DIO) mice compared to lean controls fed on a low-fat diet. *** p<0.001; independent sample t-test; data represent mean ± standard error of the mean (SEM).</p

Increased cytokine levels following LPS spleen stimulation in DIO mice.

<p>Cytokine levels of IL6 and TNFα in spleen cell culture supernatant following stimulation with lipopolysaccharide (LPS; 1 μg/ml, 37°C, 24 h) were measured in mice fed on a low- or high-fat diet over 16 weeks. Exposure to HFD (DIO mice) increased significantly spleen levels of IL6 <b>(A)</b> and TNFα <b>(B)</b> after the stimulation with LPS, compared to mice fed on a LFD (lean mice). * p<0.05; ** p<0.01 vs. lean mice; 2-way analysis of variance followed by Bonferroni’s post-hoc test; data represent mean ± standard error of the mean (SEM).</p

Morphology of CD.siRNA complexes assessed by transmission electron microscopy.

<p>(a) Cationic CD alone with no siRNA (magnification: x 60,000) (b) Cationic CD: PEGylated CD Molar ratio 1∶0 (i.e. no PEG) (magnification: x 250,000) and (c) Cationic CD: PEGylated CD Molar ratio 1∶1 (magnification: x 60,000). (Negative staining with 2% uranyl acetate).</p

Serotonin 2C receptor gene structure.

<p>A) The human full-length 5-HT_2C gene, located on the X chromosome and processed from mRNA encoded from exon 3 to exon 6 after splicing out intronic sequence is depicted (not including 3′- or 5′- untranslated regions and not according to scale). B) The 5-HT_2C gene is translated into a seven-transmembrane G-protein coupled receptor. The editing cassette is located in the second intracellular loop. C) The nucleotide sequence of the 5-HT_2C editing cassette is depicted including the five nucleotide positions prone to adenosine to inosine editing.</p

Monoamine analysis in brain regions.

<p>Decreased serotonin turnover is observed in hippocampus and hypothalamus of <i>ob/ob</i> mice compared to control. Unpaired, two-tailed T-test; statistical significance is notated as *** p<0.001, ** p<0.01 compared to lean control; n = 8 for hypothalamus, n = 10 for hippocampus.</p

Chemical structures and properties of CDs and complexes.

<p>(a, b) Chemical structures and schematic representations of Cationic CD (a) and PEGylated CD (n = 10–12) (b). (c) Gel electrophoresis showing siRNA binding within co-formulated CD.siRNA complexes. (d) Size (Z-Ave (nm), black bars) and charge (zeta potential (mV), grey square boxes) of co-formulated CD.siRNA complexes. Data are presented as the Mean ± S.D (n = 3).</p

Milk protein hydrolysates activate 5-HT2C serotonin receptors: influence of the starting substrate and isolation of bioactive fractions

Milk protein hydrolysates generated with different starting substrates, including sodium caseinate (NaCN), acid casein (Acid CN), skim milk powder (SMP) and glycomacropeptide (GMP) were demonstrated to behave as serotonin 2C (5-HT2C) receptor agonists. The 5-HT2C receptor activating potential of NaCN hydrolysates correlated with an increased protein hydrolysis, most likely due to enhanced release of bioactive peptides over the time course of hydrolysis. In its unhydrolysed form, GMP was the only starting substrate showing 5-HT2C serotonin receptor agonist activity. The 5-HT2C serotonin receptor agonist activity of its corresponding hydrolysate (GMPH-240 min) was significantly higher (P < 0.05). Fractionation of the 240 min NaCNH using ultrafiltration (UF), solid-phase extraction (SPE), semipreparative reverse-phase high performance liquid chromatography (RP-HPLC) and isoelectric focusing (IEF) was carried out. Characterisation of the fractions obtained shows that the bioactive peptides had a relatively low molecular mass (<1 kDa), were hydrophobic in nature and had a pI between 8.6 and 13.2. These different physicochemical characteristics together with the stability of NaCNH-240 min to simulated intestinal digestion, allow prediction of a favourable outcome regarding the bioavailability of the bioactive peptides therein. These results reinforce the potential of milk-derived bioactive peptides to be developed into functional foods targeted at 5-HT2C receptor modulation

Body weight and food intake in mouse model of obesity.

<p>A) Repeated measures ANOVA showed significant increase in body weight in <i>ob/ob</i> mice; F(1;14) = 66.421;p<0.001. B) Food intake was significantly higher in <i>ob/ob</i> mice compared to lean control as analysed using repeated measures ANOVA; F(1;2) = 52.333;p<0.001; n = 8 per genotype.</p