Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage

The identification of an agent effective for the treatment of intestinal and bone marrow injury following radiation exposure remains a major issue in radiological medicine. In this study, we evaluated the therapeutic impact of single agent or combination treatments with 2-(3-aminopropylamino) ethylsulphanyl phosphonic acid (WR-2721) and peptidoglycan (PGN, a toll-like receptor 2 (TLR-2) agonist) on radiation-induced injury of the intestine and bone marrow in lethally irradiated male C57BL/6 mice. A dose of 3 mg of WR-2721 per mouse (167 mg/kg, intraperitoneally) was given 30 min before irradiation, and 30 μg of PGN per mouse (1.7 mg/kg) was injected intraperitoneally 24 h after 10 Gy irradiation. Bone marrow cluster of differentiation (CD)45⁺ and CD34⁺ markers of multiple haematopoietic lineages, number of granulocyte–erythroid–macrophage–megakaryocyte (GEMM) progenitor colonies, bone marrow histopathology, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) expression in the intestines, xylose absorption and intestinal histopathology were all assessed at various time-points after irradiation. Furthermore, nuclear factor kappa B (NF-κB) p65 protein in the ileum was stained by immunofluorescent labelling. PGN-treated irradiated mice showed an increase in CD45⁺CD34⁺ cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05). Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45⁺CD34⁺ cells 4 days after 10 Gy IR. Single agent PGN or WR-2721 treatment after 10 Gy IR clearly increased Lgr5-positive pit cells (P < 0.05) and xylose absorption (P < 0.05). However only PGN and WR-2721 combination treatment markedly increased villus height (P < 0.05), number of crypts (P < 0.05) and whole-body weights after 10 Gy whole-body irradiation (WBI). The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway. Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.     

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential

Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy, hemochromatosis arthropathy, and osteoarthritis (OA). Currently, increased evidence has shown that iron accumulation is closely associated with multiple pathological changes of these arthropathies. This review summarizes system-level and intracellular regulation of iron homeostasis, and emphasizes the role of iron in synovial alterations, cartilage degeneration, and subchondral bone of several arthropathies. Of note, we discuss the potential link between iron homeostasis and OA pathogenesis. Finally, we discuss the therapeutic potential of maintaining iron homeostasis in these arthropathies.     

T1ρ MRI of human musculoskeletal system

Magnetic resonance imaging (MRI) offers the direct visualization of the human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI techniques based on T₁‐ and T₂‐weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage, with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article we focus on cartilage biochemical composition, basic principles of T_1ρ MRI, implementation of T_1ρ pulse sequences, biochemical validation, and summarize the potential applications of the T_1ρ MRI technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we also review the potential advantages, challenges, and future prospects of T_1ρ MRI for widespread clinical translation. J. Magn. Reson. Imaging 2015;41:586–600. © 2014 Wiley Periodicals, Inc.     

受照脑胶质瘤细胞诱导神经干细胞旁效应

目的 探讨受照脑胶质瘤细胞U251是否可通过在未受照神经干细胞（NSCs）中产生旁效应从而影响神经干细胞的增殖、干性及分化等特性。方法 将细胞分为NSCs组、NSCs+U251组（与U251共培养的NSCs）和NSCs+受照U251组（与10 Gy X射线照射后的U251共培养的NSCs）。采用插入式小室共培养U251和NSCs。通过细胞计数、测量神经球直径等方法评估NSCs增殖、成球能力的变化;采用免疫荧光实验检测Nestin蛋白的表达评估NSCs干性维持能力的变化;检测Tuj1、GFAP蛋白的表达、测量分化后神经元细胞的树突数目、轴突长度以及胶质细胞突起终端数、突起长度等评估神经干细胞分化能力的变化情况。结果 NSCs+受照U251组的细胞数量明显低于NSCs+U251组（t=2.52,P<0.05）;NSCs+受照U251组的Nestin阳性率和成球能力明显低于NSCs+U251组（t=-3.50,P<0.05）;NSCs+受照U251组向神经元和胶质细胞（t=6.09,P<0.05）分化的比例和程度也明显低于NSCs+U251组。结论 受照胶质瘤细胞可通过电离辐射旁效应显著抑制未受照神经干细胞的增殖、干性和分化能力。     

Investigation of the PGNAA using the LaBr3 scintillation detector

The Joint Research Centre of the European Commission develops instrumentation for detection of hazardous materials. In relation to this a new experimental facility was constructed for research into methods applying the detection of characteristic gamma rays subsequent to neutron irradiation. This includes the detection of prompt gamma rays from neutron inelastic scattering and neutron capture. For this purpose the device employs LaBr₃ scintillation detectors. The paper investigates the applicability of the LaBr₃ scintillation detector to PGNAA.     

Evaluation of magnetic resonance imaging and radionuclide bone scan in early spondyloarthropathy

IntroductionSpondyloarthropathy (SpA) comprises a small percentage of low backache (LBA) and presents with inflammatory pain. Sacroiliitis in SpAs forms the basis of diagnosis, and may take 7–8 years to become visible in plain radiographs. In order to achieve significant modification of the course of the disease it is imperative to make an early diagnosis, identify risk factors for aggressive disease and initiate the therapy right at outset. Magnetic resonance imaging (MRI) is a promising modality to pick up inflammation and structural damage early in the course of the disease.ObjectiveTo assess the role of MRI and radionuclide bone scan in patients with early SpA of less than 2 years.MethodsPatients with inflammatory LBA, defined according to the Calin criteria and satisfying the European Spondyloarthropathy Study Group (ESSG) criteria for SpA of less than 2 years duration, were included. Controls had mechanical LBA. A detailed clinical assessment and assessment of disease activity and functional impairment was done with validated measures. Radiological assessment included conventional radiograph of the pelvis, radionuclide scan and MRI of sacroiliac joints (SI joints). The sensitivity, specificity and predictive value of each modality in contributing to the diagnosis of SpA were assessed.ResultsAssessment of 132 SI joints in 33 patients (Age 31 ± 6.14 years, M:F 24:9) and 33 controls (Age 31.8 ± 7.21 years, M:F 27:5) was done. The mean disease duration of cases was 10.7 (± 6.97) months. Conventional radiograph failed to pick up sacroiliitis in any of the cases. Positive bone scan was present in 27 patients (21 bilateral sacroiliitis, 6 unilateral sacroiliitis). Bone scan had a sensitivity of 81.8% and a specificity of 88%. MRI abnormality was present in 29 patients (50 joints, bilateral in 21 and unilateral in 8) and in none of the controls. This accounted for a sensitivity of 87.9% and a specificity of 100%. The MRI changes included bone marrow oedema (89%), synovial enhancement (55%), subchondral oedema (41%), erosions (51%) and sclerosis (28%). Both inflammatory and structural changes in MRI showed positive correlation with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = 0.034, 0.02) and erythrocyte sedimentation rate (ESR) (P = 0.02, 0.001).ConclusionsIn patients with early SpA of less than 2 years duration, conventional radiographs did not pick up sacroiliitis; however, both the radionuclide scan and MRI were useful.