RepoMed (Medizinische Hochschule Hannover)
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Generating low immunogenic pig pancreatic islet cell clusters for xenotransplantation.
No full textXenotransplantation of pancreatic islets offers a promising alternative to overcome the shortage of allogeneic donors. Despite significant advances, either immune rejection or oxygen supply in immune protected encapsulated islets remains major bottlenecks for clinical application. To decrease xenogeneic immune responses, we generated tissue engineered swine leucocyte antigen (SLA)-silenced islet cell clusters (ICC). Single-cell suspensions from pancreatic islets were generated by enzymatic digestion of porcine ICCs. Cells were silenced for SLA class I and class II by lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin or class II transactivator, respectively. SLA-silenced ICCs-derived cells were then used to form new ICCs in stirred bioreactors in the presence of collagen VI. SLA class I silencing was designed to reach a level of up to 89% and class II by up to 81% on ICCs-derived cells. Xenogeneic T cell immune responses, NK cell and antibody-mediated cellular-dependent immune responses were significantly decreased in SLA-silenced cells. In stirred bioreactors, tissue engineered islets showed the typical 3D structure and insulin production. These data show the feasibility to generate low immunogenic porcine ICCs after single-cell engineering and post-transduction islet reassembling that might serve as an alternative to allogeneic pancreatic islet cell transplantation
In vitro effects of Streptococcus oralis biofilm on peri-Implant soft tissue cells
No full textHuman gingival epithelial cells (HGEps) and fibroblasts (HGFs) are the main cell types in peri-implant soft tissue. HGEps are constantly exposed to bacteria, but HGFs are protected by connective tissue as long as the mucosa-implant seal is intact. Streptococcus oralis is one of the commensal bacteria, is highly abundant at healthy implant sites, and might modulate soft tissue cells-as has been described for other streptococci. We have therefore investigated the effects of the S. oralis biofilm on HGEps and HGFs. HGEps or HGFs were grown separately on titanium disks and responded to challenge with S. oralis biofilm. HGFs were severely damaged after 4 h, exhibiting transcriptional inflammatory and stress responses. In contrast, challenge with S. oralis only induced a mild transcriptional inflammatory response in HGEps, without cellular damage. HGFs were more susceptible to the S. oralis biofilm than HGEps. The pro-inflammatory interleukin 6 (IL-6) was attenuated in HGFs, as was interleukin 8 (CXCL8) in HGEps. This indicates that S. oralis can actively protect tissue. In conclusion, commensal biofilms can promote homeostatic tissue protection, but only if the implant-mucosa interface is intact and HGFs are not directly exposed
Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane
No full textRheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive mediators, whose regulation has been the focus of our previous studies. Since the expression of these proteins commonly depends on AP-1, the expression of the AP-1-forming subunits cJun, JunB, JunD, and cFos was assessed in synovial membrane (SM) samples of RA, osteoarthritis (OA), joint trauma (JT), and normal controls (NC) using ELISA and qRT-PCR. With respect to an observed discrepancy between mRNA and protein levels, the expression of the mRNA stability-modifying factors AU-rich element RNA-binding protein (AUF)-1, tristetraprolin (TTP), and human antigen R (HuR) was measured. JunB and JunD protein expression was significantly higher in RA-SM compared to OA and/or NC. By contrast, jun/fos mRNA expression was significantly (cjun) or numerically decreased (junB, junD, cfos) in RA and OA compared to JT and/or NC. Remarkably, TTP and HuR were also affected by discrepancies between their mRNA and protein levels, since they were significantly decreased at the mRNA level in RA versus NC, but significantly or numerically increased at the protein level when compared to JT and NC. Discrepancies between the mRNA and protein expression for Jun/Fos and TTP/HuR suggest broad alterations of post-transcriptional processes in the RA-SM. In this context, increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos and ttp/hur mRNA, whereas abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein with potential consequences for the composition of the resulting AP-1 complexes and the expression of AP-1-dependent genes in R
Das zytotoxische und genotoxische Potential der Typ-1-Fotoinitiatoren BAPO und TPO bei humanen oralen Keratinozyten und V79-Fibroblasten
No full textRehabilitation Service Assessment and Workforce Capacity Building in Albania: A Civil Society Approach
Get PDFFür ein gutes Leben: ein Brief zur gemeindepsychiatrischen Entwicklung in Deutschland und in Frankfurt am Main
Get PDFSocioeconomic inequalities in type 2 diabetes in employed individuals, nonworking spouses and pensioners.
No full textType 2 diabetes (T2D) is a rising global epidemic with lower socioeconomic groups being more affected. Considering specific population subgroups to examine prevalence and socioeconomic inequalities in T2D is rare. Moreover, using one indicator to depict socioeconomic inequalities in health is a common practice despite evidence on differences in what different socioeconomic indicators ought to measure. This study has two aims: 1. Examine the prevalence of T2D in employed individuals, nonworking spouses and pensioners. 2. Examine socioeconomic inequalities in T2D in the three population subgroups and determine the explanatory power of income, education and occupation in employed individuals and nonworking spouses. This study is based on claims data from a statutory health insurance provider in Lower Saxony, Germany. T2D prevalence in the period between 2013 and 2017 was examined in employed individuals, nonworking spouses and pensioners. Multivariate logistic regression analysis was applied to examine socioeconomic inequalities in T2D in the three population subgroups. Explanatory power of the three socioeconomic indicators was determined by deviance analysis. Results showed that T2D prevalence was four times higher in male nonworking spouses (24.2%) and 2.6 times higher in female nonworking spouses (12.7%) compared to employed men (6.4%) and women (4.7%) respectively, while it accounted for 40% of men and 36% of women in pensioners. T2D inequalities emerged for all three socioeconomic indicators and were observed in the three subgroups. School education had the highest explanatory power in employed men and women and male nonworking spouses. Nonworking spouses are an important target group in T2D prevention interventions. The three socioeconomic indicators have independent effects and differ in their explanatory power where low school education appears to be a major risk factor. It can be discussed that health literacy and the associated health behavior play a role in mediating the association between school education and T2D
Interplay of Heme with Macrophages in Homeostasis and Inflammation.
No full textMacrophages are an integral part of the mononuclear phagocyte system that is critical for maintaining immune homeostasis. They play a key role for initiation and modulation of immunological responses in inflammation and infection. Moreover, macrophages exhibit a wide spectrum of tissue-specific phenotypes in steady-state and pathophysiological conditions. Recent clinical and experimental evidence indicates that the ubiquitous compound heme is a crucial regulator of these cells, e.g., in the differentiation of monocytes to tissue-resident macrophages and/ or in activation by inflammatory stimuli. Notably, heme, an iron containing tetrapyrrole, is essential as a prosthetic group of hemoproteins (e.g., hemoglobin and cytochromes), whereas non-protein bound free or labile heme can be harmful via pro-oxidant, pro-inflammatory, and cytotoxic effects. In this review, it will be discussed how the complex interplay of heme with macrophages regulates homeostasis and inflammation via modulating macrophage inflammatory characteristics and/ or hematopoiesis. A particular focus will be the distinct roles of intra- and extracellular labile heme and the regulation of its availability by heme-binding proteins. Finally, it will be addressed how heme modulates macrophage functions via specific transcriptional factors, in particular the nuclear repressor BTB and CNC homologue (BACH)1 and Spi-C
