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BACKGROUND This study used in vivo three-dimensional to two-dimensional image registration techniques to compare the glenohumeral kinematics of shoulders with massive rotator cuff tears that were successfully treated conservatively and those of normal shoulders. METHODS Ten patients (age, 67.4 ± 3.63 years) with massive rotator cuff tears on one side and without contralateral tears were enrolled. We performed computed tomography and fluoroscopy on both shoulder joints and created three-dimensional bone models of the humerus and scapula using image registration techniques. We measured the humeral superoinferior translation, angle of humeral external rotation, scapular upward rotation, scapular anteroposterior tilt, and scapular external rotation of the torn shoulders with good range of motion after effective conservative treatment and compared these measurements to those of the contralateral normal shoulders. FINDINGS There was a significant difference in the initial position of the humeral head relative to the glenoid in the tear group; it was 2.0 mm higher than that in the normal group (p less then .05). This difference disappeared in the range from 40° to full elevation. The scapular motion of the tear group was significantly more upwardly rotated than that of the normal group by 9.9° at rest (p less then .05) and by 11.6° at terminal elevation (p less then .05). No significant differences were detected for humeral head external rotation, scapular anteroposterior tilt, and scapular external rotation between the two groups. INTERPRETATION Kinematics of shoulders with massive cuff tears could not be recovered completely even though the patients had no significant symptoms after successful conservative treatment. This work is the first report when multiharmonic analysis (MHA) was applied for electron paramagnetic resonance imaging (EPRI) for in vivo applications. Phantom studies were performed for established methodology, and in vivo imaging was conduct as a proof-of-concept. Phantom studies showed at least six times improvement of the signal - to - noise (S/N) ratio. Application MHA for 3D EPR in vivo imaging provides images of spin probe distribution in mouse head. The EPRI, in combination with nitroxide and trityl spin probe, was performed to obtained 3D EPR in vivo images using MHA. For both used spin probes, MHA provided images with better S/N ratio, especially in the case of nitroxide, where projections obtained using conventional CW did not allow for reconstructing reliable data. Trityl radical exhibited high resolution and quality of obtained images after MHA. The MHA methodology allows the selection of a second modulation amplitude even 40 times higher than the natural EPR linewidth of the spin probe without line shape distortion, which highly improves the sensitivity of the acquired signal and allowing for imaging mice regardless of their size in a routine animal experiment. Retinal pigment epithelial (RPE) cell dysfunction and death play vital roles in age-related macular degeneration (AMD) pathogenesis. Previously we showed that oxidative cleavage of docosahexenoate (DHA) phospholipids generates an α,β-unsaturated aldehyde, 4-hydroxy-7-oxohept-4-enoic acid (HOHA) lactone, that forms ω-carboxyethylpyrrole (CEP) derivatives through adduction to proteins and ethanolamine phospholipids. CEP derivatives and autoantibodies accumulate in the retinas and blood plasma of individuals with AMD and are a biomarker of AMD. They promote the choroidal neovascularization of "wet AMD". Immunization of mice with CEP-modified mouse serum albumin induces "dry AMD"-like lesions in their retinas as well as interferon-gamma and interleukin-17 production by CEP-specific T cells that promote inflammatory M1 polarization of macrophages. The present study confirms that oxidative stress or inflammatory stimulus produces CEP in both the primary human ARPE-19 cell line and hRPE cells. Exposure of these cells to HOHA lactone fosters production of reactive oxygen species. Thus, HOHA lactone participates in a vicious cycle, promoting intracellular oxidative stress leading to oxidative cleavage of DHA to produce more HOHA lactone. We now show that HOHA lactone is cytotoxic, inducing apoptotic cell death through activation of the intrinsic pathway. This suggests that therapeutic interventions targeting HOHA lactone-induced apoptosis may prevent the loss of RPE cells during the early phase of AMD. We also discovered that ARPE-19 cells are more susceptible than hRPE cells to HOHA lactone cytotoxicity. This is consistent with the view that, compared to normal RPE cells, ARPE-19 cells exhibit a diseased RPE phenotype that also includes elevated expression of the mesenchymal indicator vimentin, elevated integrin a5 promotor strength and deficient secretion of the anti-VEGF molecule pigment-epithelium-derived factor fostering weaker tight junctions. Radiation therapy is a frequently used treatment for prostate cancer patients. Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of radiation-induced fibrosis (RIF). However, understanding the molecular pathway changes associated with these compounds remains limited for radioprotection. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment activated the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Therefore, we hypothesize that MnTE-2-PyP protects the prostate from RIF by activating the NRF2 signaling pathway. MRTX-1257 solubility dmso We identified that MnTE-2-PyP is a post-translational activator of NRF2 signaling in prostate fibroblast cells, which plays a major role in fibroblast activation and myofibroblast differentiation. The mechanism of NRF2 activation involves an iy MnTE-2-PyP is at least a partial mechanism of radioprotection in prostate fibroblast cells. In mass casualty events involving radiation exposure, there is a substantial unmet need for identifying and developing an orally bioavailable agent that can be used to protect the hematopoietic stem cell pool and regenerate hematopoiesis after radiation injury. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study investigates the radioprotective effects of DMSO on oral administration. Single dose of oral DMSO administrated before irradiation conferred 100% survival of C57BL6/J mice receiving otherwise lethal as well as super-lethal radiation dose, with wide radioprotective time frame (from 15min to 4h). Oral DMSO not only protected radiation-induced acute hematopoietic stem and progenitor cell (HSPC) injury, but also ameliorated long-term BM suppression following irradiation in mice. Mechanistically, DMSO directly protected HSPC survival after irradiation in vitro and in vivo, whereas no radioprotective effect was seen in MLL-AF9-induced leukemia cells.
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