Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures

AxFoundation/strax: v1.5.4

What's Changed Split compare_metadata into utils.compare_meta by @dachengx in https://github.com/AxFoundation/strax/pull/754 Change endtime - time >= 0 to endtime >= time by @JYangQi00 in https://github.com/AxFoundation/strax/pull/756 Mandatorily wrap _read_chunk in a check_chunk_n decorator by @dachengx in https://github.com/AxFoundation/strax/pull/758 New Contributors @JYangQi00 made their first contribution in https://github.com/AxFoundation/strax/pull/756 Full Changelog: https://github.com/AxFoundation/strax/compare/v1.5.3...v1.5.

Influence of the Long-Chain/Short-Chain Amphiphile Ratio on Lateral Diffusion of PEG-Lipid in Magnetically Aligned Lipid Bilayers as Measured via Pulsed-Field-Gradient NMR

Lateral diffusion measurements of polyethylene glycol(PEG)-lipid incorporated into magnetically aligned lipid bilayers, composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) plus 1 mol % (relative to DMPC) dimyristoyl phosphatidylethanolamine-n-[methoxy(polyethylene glycol)-2000] (DMPE-PEG 2000), were performed using stimulated-echo pulsed-field-gradient proton ((1)H) nuclear magnetic resonance spectroscopy. The DMPE-PEG 2000 (1 mol %, 35°C) lateral diffusion coefficient D varied directly with the mole fraction of DMPC, X(DMPC) = q/(1+q) where q = DMPC/DHPC molar ratio, decreasing progressively from D = 1.65 × 10(−11) m(2) s(−1) at q ≈ 4.7 to D = 0.65 × 10(−11) m(2) s(−1) at q ≈ 2.5. Possible sources of this dependence, including orientational disorder, obstruction, and PEG-lipid sequestration, were simulated using, respectively, a diffusion-in-a-cone model, percolation theory, and a two-phase PEG distribution model. Orientational disorder alone was not capable of reproducing the observations, but in combination with either obstruction or PEG-lipid two-phase distribution models did so satisfactorily. A combination of all three models yielded the most reasonable fit to the observed dependence of lateral diffusion on q. These same effects would be expected to influence lateral diffusion of any bilayer-associating species in such systems

Lateral Diffusion of PEG-Lipid in Magnetically Aligned Bicelles Measured Using Stimulated Echo Pulsed Field Gradient (1)H NMR

Lateral diffusion measurements of PEG-lipid incorporated into magnetically aligned bicelles are demonstrated using stimulated echo (STE) pulsed field gradient (PFG) proton ((1)H) nuclear magnetic resonance (NMR) spectroscopy. Bicelles were composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) (q = DMPC/DHPC molar ratio = 4.5) plus 1 mol % (relative to DMPC) dimyristoyl phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000] (DMPE-PEG 2000) at 25 wt % lipid. (1)H NMR STE spectra of perpendicular aligned bicelles contained only resonances assigned to residual HDO and to overlapping contributions from a DMPE-PEG 2000 ethoxy headgroup plus DHPC choline methyl protons. Decay of the latter's STE intensity in the STE PFG (1)H NMR experiment (g(z) = 244 G cm(−1)) yielded a DMPE-PEG 2000 (1 mol %, 35°C) lateral diffusion coefficient D = 1.35 × 10(−11) m(2) s(−1). Hence, below the “mushroom-to-brush” transition, DMPE-PEG 2000 lateral diffusion is dictated by its DMPE hydrophobic anchor. D was independent of the diffusion time, indicating unrestricted lateral diffusion over root mean-square diffusion distances of microns, supporting the “perforated lamellae” model of bicelle structure under these conditions. Overall, the results demonstrate the feasibility of lateral diffusion measurements in magnetically aligned bicelles using the STE PFG NMR technique

Changes in the hepatic mitochondrial and membrane proteome in mice fed a non-alcoholic steatohepatitis inducing diet.

Non-alcoholic steatohepatitis (NASH) accounts for a large proportion of cryptic cirrhosis in the Western societies. Nevertheless, we lack a deeper understanding of the underlying pathomolecular processes, particularly those preceding hepatic inflammation and fibrosis. In order to gain novel insights into early NASH-development from the first appearance of proteomic alterations to the onset of hepatic inflammation and fibrosis, we conducted a time-course analysis of proteomic changes in liver mitochondria and membrane-enriched fractions of female C57Bl/6N mice fed either a mere steatosis or NASH inducing diet. This data was complemented by quantitative measurements of hepatic glycerol-containing lipids, cholesterol and intermediates of the methionine cycle. Aside from energy metabolism and stress response proteins, enzymes of the urea cycle and methionine metabolism were found regulated. Alterations in the methionine cycle occur early in disease progression preceding molecular signs of inflammation. Proteins that hold particular promise in the early distinction between benign steatosis and NASH are methyl-transferase Mettl7b, the glycoprotein basigin and the microsomal glutathione-transferase