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1.
Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction
osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal
stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced
bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing
in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the
appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications)
and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. 相似文献
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Ting Zhang Bai‐Ge Miao Bo Wang Yan‐Qiong Peng Clive T. Darwell 《Ecological Entomology》2019,44(6):844-848
1. Species interactions in tightly bound ecological mutualisms often feature highly specialised species' roles in which competitive exclusion may preclude multi‐species coexistence. Among the 800 fig (Ficus) species, it was originally considered that each was pollinated by their own wasp (Agaonidae). However, recent investigations show that this ‘one‐to‐one’ rule often breaks down, as fig species regularly host multiple agaonids but in ways suggesting that competitive processes still mediate biodiversity outcomes. 2. A phenological survey was conducted of the fig–fig wasp pair, Ficus microcarpa and its associated pollinating wasp, alongside its sister species, the cheating wasp, in Xishuangbanna, China. 3. Reproductive output underwent extreme seasonal variation. Seed and pollinator production fell markedly during cooler, drier months, although high levels of fig production continued. However, this resource was predominantly utilised by the cheater species, which offers no pollination services. Pollinators and cheaters rarely co‐occur, suggesting that temporal coexistence is constrained by competition for access to figs. 4. The overall findings indicate periodic rearrangements of mutualism dynamics, probably resulting from a strongly seasonal environment. Sympatric co‐occurrence may result from a window of opportunity for a functionally divergent agaonid, potentially due to constraints on the main pollinator in adapting to variable year‐round conditions that prevent competitive exclusion. 相似文献
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Xiao‐Juan Yu Xiao‐Ren Peng Tong‐Huan Li 《Journal of cellular and molecular medicine》2014,18(12):2530-2535
Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta‐analysis were performed. The PubMed and CNKI database was searched for case‐control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild‐type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04–1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05–1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta‐analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians. 相似文献
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Edward Harrison 《BMJ (Clinical research ed.)》1916,1(2888):645-647
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Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress 总被引:3,自引:0,他引:3
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Peng Wang Ronghua Luo Min Zhang Yaqing Wang Tianzhang Song Tingting Tao Zhongyu Li Lin Jin Hongyi Zheng Wenwen Chen Mengqian Zhao Yongtang Zheng Jianhua Qin 《Cell death & disease》2020,11(12)
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection 相似文献