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The aim of this study was to investigate the effect of dihydrotestosterone (DHT), 17-β-estrogen (E2), genistein (GEN) and equol (EQ) on bone remodeling and bone morphology during healing of osteoporotic male rat tibiae.

180 Sprague-Dawley male rats were divided in 5 groups of 36 animals. After orchidectomy (ORX) and development of osteoporosis, trepanation of the tibia was performed. Until the time of trepanation all groups received soya free food (SF), then food change occurred and treatment started. At day 95, 102 and 151, samples were taken and histomorphometry was performed to analyze changes in bone structure under treatment. At day 33 and 70 all animals received calcein respective alizarin for polychrome bone labeling.

The cortical bone was particularly affected. Treatment with DHT and E2 led to a significant long-term expansion of the thickness of the diaphyseal cortical bone, while the phytoestrogens EQ and GEN only had a positive short-term effect in this area. Only E2 preserved the trabecular vertheless, effects via purely androgenic mechanisms can also be demonstrated. The role of a phytohormone therapy is only marginal and if only useful for a short-term supportive approach. The role of the periosteal to endosteal shift during male osteoporotic bone healing needs to be further examined.We describe a new approach to audio labeling of 3D objects such as appliances, 3D models and maps that enables a visually impaired person to audio label objects. Our approach to audio labeling is called CamIO, a smartphone app that issues audio labels when the user points to a hotspot (a location of interest on an object) with a handheld stylus viewed by the smartphone camera. The CamIO app allows a user to create a new hotspot location by pointing at the location with a second stylus and recording a personalized audio label for the hotspot. In contrast with other audio labeling approaches that require the object of interest to be constructed of special materials, 3D printed, or equipped with special sensors, CamIO works with virtually any rigid object and requires only a smartphone, a paper barcode pattern mounted to the object of interest, and two inexpensive styluses. Moreover, our approach allows a visually impaired user to create audio labels independently. We describe a co-design performed with six blind participants exploring how they label objects in their daily lives and a study with the participants demonstrating the feasibility of CamIO for providing accessible audio labeling.Apolipoprotein C2 (ApoC2) is a key activator of lipoprotein lipase for plasma triglyceride metabolism. ApoC2-deficient patients present with severe hypertriglyceridemia and recurrent acute pancreatitis, for whom the only effective treatment is the infusion of normal plasma containing ApoC2. However, since ApoC2 has a fast catabolic rate, a repeated infusion is required, which limits its clinical use. To explore a safe and efficient approach for ApoC2 deficiency, we herein established an adeno-associated virus expressing human ApoC2 (AAV-hApoC2) to evaluate the efficacy and safety of gene therapy in ApoC2-deficient hypertriglyceridemic hamsters. Administration of AAV-hApoC2 via jugular or orbital vein in adult and neonatal ApoC2-deficient hamsters, respectively, could prevent the neonatal death and effectively improve severe hypertriglyceridemia of ApoC2-deficient hamsters without side effects in a long-term manner. Our novel findings in the present study demonstrate that AAV-hApoC2-mediated gene therapy will be a promising therapeutic approach for clinical patients with severe hypertriglyceridemia caused by ApoC2 deficiency.Hematopoietic stem cell (HSC) gene therapy has the potential to cure many genetic, malignant, and infectious diseases. We have shown in a nonhuman primate gene therapy and transplantation model that the CD34+CD90+ cell fraction was exclusively responsible for multilineage engraftment and hematopoietic reconstitution. https://www.selleckchem.com/products/dt-2216.html In this study, we show the translational potential of this HSC-enriched CD34 subset for lentivirus-mediated gene therapy. Alternative HSC enrichment strategies include the purification of CD133+ cells or CD38low/- subsets of CD34+ cells from human blood products. We directly compared these strategies to the isolation of CD90+ cells using a good manufacturing practice (GMP) grade flow-sorting protocol with clinical applicability. We show that CD90+ cell selection results in about 30-fold fewer target cells in comparison to CD133+ or CD38low/- CD34+ hematopoietic stem and progenitor cell (HSPC) subsets without compromising the engraftment potential in vivo. Single-cell RNA sequencing confirmed nearly complete depletion of lineage-committed progenitor cells in CD90+ fractions compared to alternative selections. Importantly, lentiviral transduction efficiency in purified CD90+ cells resulted in up to 3-fold higher levels of engrafted gene-modified blood cells. These studies should have important implications for the manufacturing of patient-specific HSC gene therapy and gene-engineered cell products.Arginase is a complex and unique enzyme that plays diverse roles in health and disease. By metabolizing arginine, it can shape the outcome of innate and adaptive immune responses. The immunomodulatory capabilities of arginase could potentially be applied for local immunosuppression or induction of immune tolerance. With the use of an enhanced DNA delivery approach, we designed and studied a DNA-encoded secretable arginase enzyme as a tool for immune modulation and evaluated its immunomodulatory function in vivo. Strong immunosuppression of cluster of differentiation 4 (CD4) and CD8 T cells, as well as macrophages and dendritic cells, was observed in vitro in the presence of an arginase-rich supernatant. To further evaluate the efficacy of DNA-encoded arginase on in vivo immunosuppression against an antigen, a cancer antigen vaccine model was used in the presence or absence of DNA-encoded arginase. Significant in vivo immunosuppression was observed in the presence of DNA-encoded arginase. The efficacy of this DNA-encoded arginase delivery was examined in a local, imiquimod-induced, psoriasis-like, skin-inflammation model. Pretreatment of animals with the synthetic DNA-encoded arginase led to significant decreases in skin acanthosis, proinflammatory cytokines, and costimulatory molecules in extracted macrophages and dendritic cells. These results draw attention to the potential of direct in vivo-delivered arginase to function as an immunomodulatory agent for treatment of local inflammation or autoimmune diseases.