@article{WeissenbergerWeissenbergerWagenbrenneretal.2020, author = {Weissenberger, Manuel and Weissenberger, Manuela H. and Wagenbrenner, Mike and Heinz, Tizian and Reboredo, Jenny and Holzapfel, Boris M. and Rudert, Maximilian and Groll, J{\"u}rgen and Evans, Christopher H. and Steinert, Andre F.}, title = {Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0237479}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230494}, year = {2020}, abstract = {Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.}, language = {en} } @article{RommelMildeEberleetal.2020, author = {Rommel, Marcel G. E. and Milde, Christian and Eberle, Regina and Schulze, Harald and Modlich, Ute}, title = {Endothelial-platelet interactions in influenza-induced pneumonia: A potential therapeutic target}, series = {Anatomia, Histologia, Embryologia}, volume = {49}, journal = {Anatomia, Histologia, Embryologia}, number = {5}, doi = {10.1111/ahe.12521}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213610}, pages = {606 -- 619}, year = {2020}, abstract = {Every year, influenza viruses spread around the world, infecting the respiratory systems of countless humans and animals, causing illness and even death. Severe influenza infection is associated with pulmonary epithelial damage and endothelial dysfunction leading to acute lung injury (ALI). There is evidence that an aggressive cytokine storm and cell damage in lung capillaries as well as endothelial/platelet interactions contribute to vascular leakage, pro-thrombotic milieu and infiltration of immune effector cells. To date, treatments for ALI caused by influenza are limited to antiviral drugs, active ventilation or further symptomatic treatments. In this review, we summarize the mechanisms of influenza-mediated pathogenesis, permissive animal models and histopathological changes of lung tissue in both mice and men and compare it with histological and electron microscopic data from our own group. We highlight the molecular and cellular interactions between pulmonary endothelium and platelets in homeostasis and influenza-induced pathogenesis. Finally, we discuss novel therapeutic targets on platelets/endothelial interaction to reduce or resolve ALI.}, language = {en} } @article{RiedererterMeulen2020, author = {Riederer, Peter and ter Meulen, Volker}, title = {Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, number = {9}, issn = {0300-9564}, doi = {10.1007/s00702-020-02230-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314637}, pages = {1217-1228}, year = {2020}, abstract = {While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.}, language = {en} } @article{KesslerFeldheimSchmittetal.2020, author = {Kessler, Almuth F. and Feldheim, Jonas and Schmitt, Dominik and Feldheim, Julia J. and Monoranu, Camelia M. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten}, title = {Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients}, series = {Biomedicines}, volume = {8}, journal = {Biomedicines}, number = {7}, doi = {10.3390/biomedicines8070192}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236105}, year = {2020}, abstract = {Inhibition of the protein kinase MPS1, a mitotic spindle-checkpoint regulator, reinforces the effects of multiple therapies against glioblastoma multiforme (GBM) in experimental settings. We analyzed MPS1 mRNA-expression in gliomas WHO grade II, III and in clinical subgroups of GBM. Data were obtained by qPCR analysis of tumor and healthy brain specimens and correlated with the patients' clinical data. MPS1 was overexpressed in all gliomas on an mRNA level (ANOVA, p < 0.01) and correlated with tumor aggressiveness. We explain previously published conflicting results on survival: high MPS1 was associated with poorer long term survival when all gliomas were analyzed combined in one group (Cox regression: t < 24 months, p = 0.009, Hazard ratio: 8.0, 95\% CI: 1.7-38.4), with poorer survival solely in low-grade gliomas (LogRank: p = 0.02, Cox regression: p = 0.06, Hazard-Ratio: 8.0, 95\% CI: 0.9-66.7), but not in GBM (LogRank: p > 0.05). This might be due to their lower tumor volume at the therapy start. GBM patients with high MPS1 mRNA-expression developed clinical symptoms at an earlier stage. This, however, did not benefit their overall survival, most likely due to the more aggressive tumor growth. Since MPS1 mRNA-expression in gliomas was enhanced with increasing tumor aggressiveness, patients with the worst outcome might benefit best from a treatment directed against MPS1.}, language = {en} } @article{AltieriDiDatoModicaetal.2020, author = {Altieri, Barbara and Di Dato, Carla and Modica, Roberta and Bottiglieri, Filomena and Di Sarno, Antonella and Pittaway, James F.H. and Martini, Chiara and Faggiano, Antongiulio and Colao, Annamaria}, title = {Bone metabolism and vitamin D implication in gastroenteropancreatic neuroendocrine tumors}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {4}, issn = {2072-6643}, doi = {10.3390/nu12041021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203823}, year = {2020}, abstract = {Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.}, language = {en} }