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The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCsin vitroandin vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCsin vitroafter irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a- and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC-mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC-mediated tissue regeneration post-radiation.Significance StatementRadiotherapy combined with surgery for the settlement of skeletal tumors usually leads to large bone defects and hampers wound healing. Skeletal stem cells (SSCs) have been defined as tissue-specific stem cells in skeletons and are highlighted in bone development and regeneration. Ferulic acid is a phytochemical with a wide range of therapeutic effects, including alleviation of radiation-induced oxidative stress and promotion of tissue regeneration. In the current study, promising data based on anin vitrocell model and anin vivoanimal model demonstrates that ferulic acid alleviates radiation-induced impairment of SSCs and promotes SSC-mediated bone regeneration post-radiation.

Mian Zeng, Qingui Chen, Wenjie Liang, Wanmei He, Haichong Zheng, Chunrong Huang Department of Medical Intensive Care Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Background: Impaired renal function is often neglected in COPD patients. Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients.Methods: COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016. Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1. Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min–1 1.73 m–2) and having concealed CRF (normal serum creatinine while eGFR

The Editor, We read with great interest the article by Dr Eljack and colleagues [1] in the June 2010 issue of the British Journal of Radiology. In their article, they described the radiological changes of this rare kidney tumor [1]. Until now, radiological characteristics of solitary renal parapelvic neurofibroma have been considered non-specific, and difficult to differentiate from malignant tumors [1-5]. In some cases, radical surgical operations have been performed on these patients because of radiological similarities between solitary renal parapelvic neurofibroma and malignant tumors [1,3,5]. Therefore, pre-operative identification of the benign nature of the tumour is important for the choice of surgical operation. Here, we suggest possible methods of identification of the nature of the tumour. The theory of Folkman's tumour angiogenesis factor provided a theoretical basis for (CT and MRI) perfusion imaging [6]. Perfusion experiments were executed on a large number of patients with nodules of the lung and breast, which demonstrated that time-signal intensity curves obtained by perfusion parameters were reliable for the diagnosis of benign and malignant lesions [7-9]. In a prior study, benign lesions of the breast demonstrated a curve of increasing enhancement or plateau of signal intensity, which was different from the type of washout of signal intensity obtained by malignant lesions [8]. In another study, by analysis of histology, vascular density and vascular permeability in benign and malignant lesions of the breast, they concluded that vascular permeability was the main factor in determining the curve pattern [9]. Furthermore, malignant nodules had high vascular permeability, but benign had low vascular permeability, both of which were related to the expression of the degree of vascular endothelial growth factor [9]. Renal parapelvic neurofibroma is a benign lesion confirmed by pathological histology [1]. Therefore, we believe that there may be a curve of increasing enhancement or plateau of signal intensity based on low vascular permeability. Further more, we suggest that perfusion imaging may be of help in differentiating renal parapelvic neurofibroma from malignant lesions of the kidney. Yours etc.