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Immune responses reflect a complex interplay of cellular and extracellular components which define the microenvironment of a tissue. Therefore, factors that locally influence the microenvironment and re‐establish tolerance might be beneficial to mitigate immune‐mediated reactions, including the rejection of a transplant. In this study, we demonstrate that pre‐incubation of donor tissue with the immune modulator soluble CD83 (sCD83) significantly improves graft survival using a high‐risk corneal transplantation model. The induction of tolerogenic mechanisms in graft recipients was achieved by a significant upregulation of Tgfb, Foxp3, Il27, and Il10in the transplant and an increase of regulatory dendritic cells (DCs), macrophages (Mφ), and T cells (Tregs) in eye‐draining lymph nodes. The presence of sCD83 during in vitro DC and Mφ generation directed these cells toward a tolerogenic phenotype leading to reduced proliferation‐stimulating activity in MLRs. Mechanistically, sCD83 induced a tolerogenic Mφ and DC phenotype, which favors Treg induction and significantly increased transplant survival after adoptive cell transfer. Conclusively, pre‐incubation of corneal grafts with sCD83 significantly prolongs graft survival by modulating recipient Mφ and DCs toward tolerance and thereby establishing a tolerogenic microenvironment. This functional strategy of donor graft pre‐treatment paves the way for new therapeutic options in the field of transplantation. Antigen‐presenting cells improve long‐term corneal graft survival when donor tissue is pre‐incubated with immune modulatory sCD83.

Immune responses reflect a complex interplay of cellular and extracellular components which define the microenvironment of a tissue. Therefore, factors that locally influence the microenvironment and re-establish tolerance might be beneficial to mitigate immune-mediated reactions, including the rejection of a transplant. In this study, we demonstrate that pre-incubation of donor tissue with the immune modulator soluble CD83 (sCD83) significantly improves graft survival using a high-risk corneal transplantation model. The induction of tolerogenic mechanisms in graft recipients was achieved by a significant upregulation of Tgfb, Foxp3, Il27, and Il10in the transplant and an increase of regulatory dendritic cells (DCs), macrophages (Mφ), and T cells (Tregs) in eye-draining lymph nodes. The presence of sCD83 during in vitro DC and Mφ generation directed these cells toward a tolerogenic phenotype leading to reduced proliferation-stimulating activity in MLRs. Mechanistically, sCD83 induced a tolerogenic Mφ and DC phenotype, which favors Treg induction and significantly increased transplant survival after adoptive cell transfer. Conclusively, pre-incubation of corneal grafts with sCD83 significantly prolongs graft survival by modulating recipient Mφ and DCs toward tolerance and thereby establishing a tolerogenic microenvironment. This functional strategy of donor graft pre-treatment paves the way for new therapeutic options in the field of transplantation.

The most frequent complication of deep venous thrombosis (DVT) is post-thrombotic syndrome (PTS). We recently showed inhibition of varicose vein development by atorvastatin and rosuvastatin. The aim of this study was to test the influence of lipid-lowering therapy with statins on PTS development.

Nonclassical crystallization typically yields materials with pronounced roughness and porosity as it is driven by nanoparticle self-organization. Here, we demonstrate that bio-inspired nonclassical mineralization viamagnesium-doped polymer-induced liquid precursors (PILP) can yield ultra-smooth and space-filling CaCO3films featuring an unprecedented low roughness of 0.285 nm.

AbstractCancer is one of the biggest challenges facing the medical research in our time. The goals are to improve not only the therapeutic outcome, even in the cases of advanced and metastatic cancer, but also the methods of treatment, which often have considerable adverse effects. In addition, the current developments, such as demographic change, population growth, and increasing healthcare costs, have to be taken into consideration. In all likelihood, nanotechnology and, in particular, the use of magnetic nanoparticles consisting of the elements nickel, cobalt, and iron can make a significant contribution. The greatest potential can be ascribed to the drug delivery systems: magnetic nanoparticles are functionalized by binding them to various substances, including chemotherapeutic agents, radionuclides, nucleic acids, and antibodies. They can then be guided and accumulated using a magnetic field. Hyperthermia can be induced with an alternating magnetic field, providing another therapeutic option. Magnetic nanoparticles may be useful in overcoming cancer drug resistance. They also contribute to realizing a combination of diagnostic investigation and therapy in the field of “theranostics”. The multifaceted and promising results of research in the recent years offer the prospect of a real advance in cancer therapy in the near future.

AbstractThe use of nanoparticles in tumor imaging, molecular imaging, and drug delivery has significantly expanded in the last few years. The relatively new field of “theranostics” combines their capacity for drug delivery with their potential as contrast agents. Depending on the imaging modality used, several types of nanoparticles are available, such as gold for optical imaging or superparamagnetic iron oxide for magnetic resonance imaging. This review will give a short overview of the different types of nanoparticles as well as their development and potential application in recent years. Furthermore, it describes the research on classic imaging modalities as well as on new techniques to image nanoparticles in vivoand focuses on magnetic-based imaging modalities.

Background: Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol‐induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.

Plasma cells secreting affinity-matured antibodies develop in germinal centers (GCs), where B cells migrate persistently and directionally over defined periods of time. How modes of GC B cell migration influence plasma cell development remained unclear. Through genetic deletion of the F-actin bundling protein Swiprosin-1/EF-hand domain family member 2 (EFhd2) and by two-photon microscopy, we show that EFhd2 restrains B cell speed in GCs and hapten-specific plasma cell output. Modeling the GC reaction reveals that increasing GC B cell speed promotes plasma cell generation. Lack of EFhd2 also reduces contacts of GC B cells with follicular dendritic cells in vivo. Computational modeling uncovers that both GC output and antibody affinity depend quantitatively on contacts of GC B cells with follicular dendritic cells when B cells migrate more persistently. Collectively, our data explain how GC B cells integrate speed and persistence of cell migration with B cell receptor affinity.