Islets of Langerhans Are Protected from Inflammatory Cell Recruitment during Reperfusion of Rat Pancreas Grafts

Background: Ischemia/reperfusion (I/R) injury plays a pivotal role in the development of graft pancreatitis, with ischemia time representing one of its crucial factors. However, it is unclear, whether exocrine and endocrine tissue experience similar inflammatory responses during pancreas transplantation (PTx). This study evaluated inflammatory susceptibilities of islets of Langerhans (ILH) and exocrine tissue after different preservation periods during early reperfusion. Methods: PTx was performed in rats following 2 h (2h-I) or 18 h (18h-I) preservation. Leukocyte-endothelial cell interactions (LEI) were analyzed in venules of acinar tissue and ILH in vivo over 2 h reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. Results: In exocrine venules leukocyte rolling predominated in the 2h-I group. In the 18h-I group, additionally, high numbers of adherent leukocytes were found. Histology revealed significant edema formation and leukocyte extravasation in the 18h-I group. Notably, LEI in postcapillary venules of ILH were significantly lower. Leukocyte rolling was only moderately enhanced and few leukocytes were found adherent. Histology revealed minor leukocyte extravasation. Conclusion: Ischemia time contributes decisively to the extent of the I/R-injury in PTx. However, ILH have a significantly lower susceptibility towards I/R, even when inflammatory reactions in adjacent exocrine tissue are evident. Copyright (C) 2010 S. Karger AG, Base

Innate and Adaptive Immunity in Inflammatory Bowel Diseases

While barrier function and the effects of the intestinal microbiome have only recently moved into the focus of inflammatory bowel disease research, the role of the innate and the adaptive immune system in these gastrointestinal disorders has extensively been studied. Although still not completely understood, the increasing knowledge about the immune system's contribution to the pathophysiology of inflammatory bowel diseases has led to new diagnostic and therapeutic approaches. This review gives a compact overview on this important topic

Topological solitons in highly anisotropic two dimensional ferromagnets

e study the solitons, stabilized by spin precession in a classical two--dimensional lattice model of Heisenberg ferromagnets with non-small easy--axis anisotropy. The properties of such solitons are treated both analytically using the continuous model including higher then second powers of magnetization gradients, and numerically for a discrete set of the spins on a square lattice. The dependence of the soliton energy $E$ on the number of spin deviations (bound magnons) $N$ is calculated. We have shown that the topological solitons are stable if the number $N$ exceeds some critical value $N_{\rm{cr}}$. For $N < N_{\rm{cr}}$ and the intermediate values of anisotropy constant $K_{\mathrm{eff}} <0.35J$ ($J$ is an exchange constant), the soliton properties are similar to those for continuous model; for example, soliton energy is increasing and the precession frequency $\omega (N)$ is decreasing monotonously with $N$ growth. For high enough anisotropy $K_{\mathrm{eff}} > 0.6 J$ we found some fundamentally new soliton features absent for continuous models incorporating even the higher powers of magnetization gradients. For high anisotropy, the dependence of soliton energy E(N) on the number of bound magnons become non-monotonic, with the minima at some "magic" numbers of bound magnons. Soliton frequency $\omega (N)$ have quite irregular behavior with step-like jumps and negative values of $\omega$ for some regions of $N$. Near these regions, stable static soliton states, stabilized by the lattice effects, exist.Comment: 17 page

Soliton-Magnon Scattering in Two-Dimensional Isotropic Ferromagnets

It is studied the scattering of magnons by the 2d topological Belavin-Polyakov soliton in isotropic ferromagnet. Analytical solutions of the scattering problem are constructed: (i) exactly for any magnon wave vectors for the partial wave with the azimuthal number m=1 (translational mode), and (ii) in the long- and short-wave limits for the rest modes. The magnon mode frequencies are found for the finite size magnets. An effective equation of the soliton motion is constructed. The magnon density of states, connected with the soliton-magnon interaction, is found in a long-wave approximation.Comment: 4 pages, REVTe

Topological phase separation in 2D quantum lattice Bose-Hubbard system away from half-filling

We suppose that the doping of the 2D hard-core boson system away from half-filling may result in the formation of multi-center topological inhomogeneity (defect) such as charge order (CO) bubble domain(s) with Bose superfluid (BS) and extra bosons both localized in domain wall(s), or a {\it topological} CO+BS {\it phase separation}, rather than an uniform mixed CO+BS supersolid phase. Starting from the classical model we predict the properties of the respective quantum system. The long-wavelength behavior of the system is believed to remind that of granular superconductors, CDW materials, Wigner crystals, and multi-skyrmion system akin in a quantum Hall ferromagnetic state of a 2D electron gas. To elucidate the role played by quantum effects and that of the lattice discreteness we have addressed the simplest nanoscopic counterpart of the bubble domain in a checkerboard CO phase of 2D hc-BH square lattice. It is shown that the relative magnitude and symmetry of multi-component order parameter are mainly determined by the sign of the $nn$ and $nnn$ transfer integrals. In general, the topologically inhomogeneous phase of the hc-BH system away from the half-filling can exhibit the signatures both of $s,d$, and $p$ symmetry of the off-diagonal order.Comment: 12 pages, 6 figure

Internal Modes and Magnon Scattering on Topological Solitons in 2d Easy-Axis Ferromagnets

We study the magnon modes in the presence of a topological soliton in a 2d Heisenberg easy-axis ferromagnet. The problem of magnon scattering on the soliton with arbitrary relation between the soliton radius R and the "magnetic length" Delta_0 is investigated for partial modes with different values of the azimuthal quantum numbers m. Truly local modes are shown to be present for all values of m, when the soliton radius is enough large. The eigenfrequencies of such internal modes are calculated analytically on limiting case of a large soliton radius and numerically for arbitrary soliton radius. It is demonstrated that the model of an isotropic magnet, which admits an exact analytical investigation, is not adequate even for the limit of small radius solitons, R<<Delta_0: there exists a local mode with nonzero frequency. We use the data about local modes to derive the effective equation of soliton motion; this equation has the usual Newtonian form in contrast to the case of the easy-plane ferromagnet. The effective mass of the soliton is found.Comment: 33 pages (REVTeX), 12 figures (EPS

TGFβ and the Tumor Microenvironment in Colorectal Cancer

Growing evidence supports an important role of the tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC). Resident cells such as fibroblasts or immune cells infiltrating into the TME maintain continuous crosstalk with cancer cells and thereby regulate CRC progression. One of the most important molecules involved is the immunoregulatory cytokine transforming growth factor-β (TGFβ). TGFβ is released by various cells in the TME, including macrophages and fibroblasts, and it modulates cancer cell growth, differentiation, and cell death. Mutations in components of the TGF pathway, including TGFβ receptor type 2 or SMAD4, are among the most frequently detected mutations in CRC and have been associated with the clinical course of disease. Within this review, we will discuss our current understanding about the role of TGFβ in the pathogenesis of CRC. This includes novel data on the molecular mechanisms of TGFβ signaling in TME, as well as possible strategies for CRC therapy targeting the TGFβ pathway, including potential combinations with immune checkpoint inhibitors

Molecular Endoscopy for the Diagnosis and Therapeutic Monitoring of Colorectal Cancer

Colorectal cancer (CRC) is one of the leading causes of cancer related death in the western world. Its successful treatment requires early detection and removal of precursor lesions as well as individualized treatment of advanced disease. During recent years, molecular imaging techniques have shown promising results to improve current clinical practice. For instance, molecular endoscopy resulted in higher detection rates of precursors in comparison to conventional endoscopy in preclinical and clinical studies. Molecular confocal endomicroscopy allowed a further classification of suspect lesions as well as the prediction and monitoring of the therapeutic response. In this review, we summarize recent achievements for molecular imaging of CRC in preclinical studies, initial clinical trials and the remaining challenges for future translation into clinical practice

Lack of Intestinal Epithelial Atg7 Affects Paneth Cell Granule Formation but Does Not Compromise Immune Homeostasis in the Gut

Genetic polymorphisms of autophagy-related genes have been associated with an increased risk to develop inflammatory bowel disease (IBD). Autophagy is an elementary process participating in several cellular events such as cellular clearance and nonapoptotic programmed cell death. Furthermore, autophagy may be involved in intestinal immune homeostasis due to its participation in the digestion of intracellular pathogens and in antigen presentation. In the present study, the role of autophagy in the intestinal epithelial layer was investigated. The intestinal epithelium is essential to maintain gut homeostasis, and defects within this barrier have been associated with the pathogenesis of IBD. Therefore, mice with intestinal epithelial deletion of Atg7 were generated and investigated in different mouse models. Knockout mice showed reduced size of granules and decreased levels of lysozyme in Paneth cells. However, this was dispensable for gut immune homeostasis and had no effect on susceptibility in mouse models of experimentally induced colitis