| 1 | HBB-deficient Macaca fascicularis monkey presents with human β-thalassemia显示文摘Dear Editor,β-Thalassemia is a common severe genetic disease caused by mutations in HBB and affects approximately 1.5% of the global population (Origa, 2017). In southern China, the carrier rate of β-thalassemia is as high as 6.43%, creating a high socio-economic burden (Xiong et al., 2010). In adult humans, there are three types of hemoglobin: HbA1 (~97%), HbA2 (~2%) and HbF (~1%). HbA1 (α2β2) is composed of two a-globin and two β-globi n sub units en coded by HBA and HBB, respectively;HbF (α2β2)is made up of two α-globin subunits and two β-globin sub units en coded by HBG. Mutations in the coding region or regulatory region of HBB are involved in β-thalassemia pathogenesis. Except for some rare dominant mutations, most HBB mutations are recessive (Origa, 2017). Depending on the mutation type, the β-globin level will either be reduced or completely depleted, resulting in α-globin accumulation and precipitation. These α-globin precipitates lead to red blood cell death, resulting in anemia and tissue damage, and even death in thalassemia major patients. Blood transfusions can help slow disease progression but lead to iron overload, ultimately resulting in iron toxicity. Bone marrow transfer is the only cure in the clinic and is available only to a small percentage of patients with human leukocyte antigervmatched donors. Recently, gene therapy and gene editing therapy have shown great promise in curing β-thalassemia (Glaser et al., 2015;Thompson et al., 2018). However, no appropriate animal models are available for evaluating the safety and efficacy of such advanced therapeutic strategies in vivo.β-thalassemia mice are the sole animal model available for research. However, substantial differences have been reported between the types and expressi on patter ns of human and mouse globins (McColl and Vadolas, 2016). Moreover, mice contain no fetal globin gene equivalent, and homozygous mutations of HBB in mouse for early models of β-thalassemia major or Cooley anemia are all embryonic lethal (Huo et al., 2009). Recently, significant phenotype and physiology differences have been reported between SIRT6- null mice and the non-human primate model (Zhang et al., 2018). Thus, an appropriate non-human primate model is needed for human β-thalassemia studies and treatments. | Yan Huang Chenhui Ding Puping Liang Duanduan Li Yu Tang Wei Meng Hongwei Sun Hongyu Lu Yu Chen Xueying Chen Qunshan Huang Jianpei Fang Canquan Zhou Shihua Yang Junjiu Huang | 2019 | Protein & Cell2019，10，7： | 4 |
| 5 | Effects of tissue heterogeneity on trabecular micromechanics examined by microCT-based finite element analysis and digital volume correlation显示文摘Trabecular bone is natural material with heterogeneous tissue properties.The effect of tissue heterogeneity on the micromechanical behavior of trabecular bone is commonly evaluated by microCT-based finite element(microFE)analysis.Results from prior work remain inconclusive and lack of experimental validation.To address these issues,we combined microFE analysis with mechanical testing and microCT-based digital volume correlation(DVC),as a validation for the microFE approach.Porcine trabecular specimens were tested in compression as sequential microCT scans were taken.DVC was performed to extract“realistic”boundary conditions that were applied to microFE models,and to measure microstructural deformation and strain of the trabecular specimens.Heterogeneous and homogeneous microFE models of each trabecular specimen were created and compared with the experimentally measured microstructural displacement and strains.Results showed strong correlations between DVC-measured and microFE-predicted trabecular displacement and strain fields(R^(2)>0.9,p<0.05),regardless of heterogeneous or homogeneous material assignments.The heterogeneous and homogeneous models predicted similar magnitudes for maximum or minimum principal strains(R^(2)=1,p<0.05).However,incorporation of tissue heterogeneity decreased more than 16.5%in the overall stress level of the trabecular tissues.Regardless,very strong correlations were found between the heterogeneous and homogeneous model-predicted principal strains or stresses.These results together suggest that tissue heterogeneity may have little effect on microFE modeling of typical elastic displacement and strains in the trabecular bone,suggesting that homogeneous material models might be sufficient to predict general trabecular micromechanics. | Jizhi Fu Haoye Meng Changhao Zhang Youjun Liu Duanduan Chen Aiyuan Wang Russell P.Main Haisheng Yang | 2021 | Medicine in Novel Technology and Devices2021，，3： | 0 |
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