bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via PI3K/Akt pathway
Authors: Wang Xiaoyi , Jiang Huijiao , Guo Lijiao , Wang Sibo , Cheng Wenzhe , Wan Longfei , Zhang Zhongzhou , Xing Lihang , Zhou Qing , Yang Xiongfeng , Han Huanhuan , Chen Xueling , Wu Xiangwei 
Published: March 2020

Abstract
Background: Cell-based therapeutics bring great hope in areas of unmet medical needs. Mesenchymal stem cells (MSCs) has been suggested to facilitate neovascularization mainly by paracrine action, and endothelial progenitor cells (EPCs) can differentiate into mature endothelial cells. Studies have demonstrated that a combination cell therapy that includes MSCs and EPCs has a favorable effect on ischemic limbs. However, the mechanism of combination cell therapy remains unclear. Herein, we investigate whether stromal cell-derived factor (SDF)-1 secreted by MSCs contributes to. Furthermore, we examined whether SDF-1 affects EPC migration via Phosphoinositide 3-Kinases (PI3K)/protein kinase B (termed as Akt) signaling pathway.Methods: First, intramuscular MSC injections were supplemented with intravenous EPC injections in the mouse model of hind limb ischemia. The incorporation of Qdot® 525 labeled-EPC into the vasculature and capillary density was evaluated by CD31 immunohistochemistry and immunofluorescence, respectively. Then, the concentration of SDF-1 secreted by MSCs was detected via quantitative immunoassay. Flow cytometry was performed to quantify CXC chemokine receptor (CXCR) 4-positive EPCs. The effect of MSCs on EPC migration was measured by a transwell system and a tube-like structure formation on Matrigel. The SDF-1 antagonist AMD3100 and the PI3K inhibitor wortmannin were separately used to determine the participation of CXCR4 and PI3K into EPC migration. Finally, western blot assay was performed to detect the effect of SDF-1 secreted by MSCs on Akt phosphorylation in EPCs.Results: The combination delivery of MSCs and EPCs via a “dual-administration” approach enhanced the incorporation of EPCs into the vasculature and increased the capillary density in mouse ischemic hind limb. The SDF-1 concentration secreted by MSCs was 2.61 ng/ml after 48 h. CXCR4-positive EPCs increased after incubation with MSC-conditioned medium (CM). MSCs contributed to EPC migration and tube-like structure formation, both of which were suppressed by AMD3100 and wortmannin. Phospho-Akt induced by MSC-CM was attenuated when EPCs were pretreated with AMD3100 and wortmannin.Conclusions: The paracrine action of MSCs contributes to EPC migration. Furthermore, SDF-1 secreted by MSCs induces EPC migration. The mechanism of this migration is related to the activation of the Akt pathway
Adipose Stem Cells from Type 2 Diabetic Mice Exhibit Therapeutic Potential in Wound Healing
Authors: Sun Yongfa , Song Lili , Zhang Yong , Wang Hongjun , Dong Xiao 
Published: March 2020

Abstract
BACKGROUND: Diabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose-derived MSCs (ASCs) from type 2 diabetes donors are suitable for skin damage repair remains largely unknown. METHODS: In this study, we compared the phenotype and functionality of ASCs harvested from high fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D. RESULTS: T2D ASCs expressed similar cellular markers as control ASCs, but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration. CONCLUSIONS: From these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.
Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy through inhibiting NF-κB translocation
Authors: Han Min , Chen Xiao-Cui , Sun Ming-Hui , Gai Min-Tao , Yang Yi-Ning , Gao Xiao-Ming , Ma Xiang , Ma Yi-Tong , Chen Bang-Dang 
Published: March 2020

Abstract
Background: Inflammation and oxidative stress play a predominant role in the initiation and progression of ischemia/reperfusion (I/R) injury, of which nuclear factor kappa B (NF-κB) is considered to be a crucial mediator. Inactivation of NF-κB could benefit cardiomyocytes through inhibiting apoptosis. IκBα, an inhibitor of NF-κB, is hypothesized to protects cardiomyocytes from H2O2-induced apoptosis and autophagy through inhibiting the NF-κB pathway.Methods: We designed an AAV9-delivered mutated IκBαS32A, S36A and investigated its effect on neonatal rat ventricular cardiomyocytes (NRVMs) in response to hydrogen peroxide (H2O2). NRVMs were divided into Normal (blank), Control (H2O2), GFP +H2O2, IκBα+H2O2, and Pyrrolidine dithiocarbamate (PDTC)+H2O2 groups. NF-κB p65 nuclear translocation was evaluated by immunofluorescence and western blot. Cell viability was assessed by a cell counting kit-8 kit. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD, and the mitochondrial membrane potential (△Ψm) was detected by JC-1. Western bolt was used to detect apoptosis and autophagy related proteins.Results: Consequently, H2O2-treated NRVMs showed reductions in cell viability but increased IκBα degradation and NF-κB p65 nuclear translocation in a time-dependent manner. Furthermore, LDH and MDA content, LC3-Ⅱ/LC3-Ⅰ ratio, Bax and Beclin-1 expressions, and apoptotic cells were upregulated in NRVMs exposed to H2O2, whereas △Ψm and Bcl-2 expression were downregulated. Additionally, IκBα transduction or PDTC pretreatment both attenuated the nuclear translocation of the p65 subunit and reversed the H2O2-stimulated effects in NRVMs.Conclusion: These findings suggest that IκBα could ameliorate H2O2-induced apoptosis and autophagy through targeted inhibition of NF-κB activation, which may guide strategies to prevent cardiac I/R jury.
Temporal and Spatial Trends of Ischemic Heart Disease Burden in Chinese and Subgroup Populations from 1990 to 2016
Authors: Wang Chenran , Wang Chunping , Liu Mi , Chen Zhe , Liu Shiwei 
Published: March 2020

Abstract
Background Ischemic heart disease (IHD) is a leading cause of premature death which poses public health challenges worldwide. Previous studies have focused on the overall population in China. However variations in temporal and spatial pattern across subgroups remain unknown. This study was to analyze how the IHD burden among Chinese and subgroup populations changes in response to temporal and spatial trends from 1990-2016.Methods Based on data from the updated estimates in the 2016 Global Burden of Disease (GBD) study, we used years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) to describe the IHD burden. The percentage and annual average percentage changes were applied to illustrate temporal and spatial variations of the IHD burden stratified by age-sex and province from 1990-2016, 1990-2005, and 2005-2016.Results YLD rates, YLL rates, and DALY rates for IHD underwent a notable increase among all age groups and increased by 119.4%, 83.3%, and 84.5% nationally from 1990-2016. In YLD rates, an evident rise was seen in females (124.4%) compared to males (114.0%) while males experienced a more substantial increase than that in females in YLL rates (99.3% vs. 60.5%) and DALY rates (99.7% vs. 63.2%) from 1990 to 2016. Compared with 1990-2005, annual average changes in overall population in YLL (3.5% vs. 1.8%) and DALY rates (3.5% vs. 1.9%) showed a tardier increase whereas higher annual average growth of YLD rates (3.5% vs. 4.0%) was observed from 2005-2016. Geographically, all provinces saw declines in YLLs/YLDs ratios from 2005-2016 with seventeen provinces showing an upward trend between 1990 and 2005. Most of the provinces in China witnessed a remarkable upsurge in the age-standardized DALY rate from 1990-2016 whereas the economically advantaged region Macao (52.2%) saw the most marked reduction.Conclusions China has made significant achievements in preventing premature death from IHD along with the increased risk of disability. Substantial disparities in the temporal and spatial trends of IHD burden emphasize concerns for elderly men and those in economically disadvantaged regions with resource constraints. By having identified these disparities, targeted IHD prevention and control will help to bridge these gaps in IHD burden.
Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib
Authors: Bornemann Lea , Schuster Marc , Schmitz Saskia , Sobczak Charlyn , Bessen Clara , Merz Simon F. , Jöckel Karl-Heinz , Haverkamp Thomas , Gunzer Matthias , Göthert Joachim R. 
Published: March 2020

Abstract
Background The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML). Methods A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient’s neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2. Results Despite cytoreductive therapy with hydroxyurea, the patient’s WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils display strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within one week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted. Conclusion These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.
Identification of Protein Changes in The Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach
Authors: Masood Afshan , Benabdelkamel Hicham , Jammah Anwar A , Ekhzaimy Aishah A , Alfadda Assim A 
Published: March 2020

Abstract
Background The thyroid gland and thyroid hormones control a multitude of homeostatic functions including the functions kidney related to fluid and electrolyte balance and formation of urine. In the present study we aimed to define changes in the urinary proteome characterizing alterations in thyroid hormone status.Methods An untargeted proteomic approach with network analysis was used to study 9 age-matched subjects with newly diagnosed overt hypothyroidism. Urine was collected from subjects pre and post L-thyroxine treatment. Proteome analysis was performed using two-dimensional difference in gel electrophoresis coupled with mass spectrometry.Results 42 proteins were found to have significant differential abundance (≥1.5-fold change, ANOVA, p ≤ 0.05). 28 proteins were upregulated and 14 proteins were downregulated in the hypothyroid compared to the euthyroid state. The differentially abundant proteins investigated by Ingenuity Pathway Analysis showed involvement of signaling pathways related to MAPK Kinase, VEGF, Pi3 Kinase/Akt, Pkc, and nvolvement of pathway related to amino acid metabolism, molecular transport, small molecule biochemistry.Conclusions The differentially abundant proteins identified revealed their involvement in regulating TH and Tg metabolism. The alterations in levels of identified proteins in indicate a compensatory increase in the regulation of Tg to increase circulating TH levels in the hypothyroid state.
Da Vinci robot-assisted resection to treat abdominal ectopic thyroid: A case report and literature review
Authors: Zhao Zhanwei , Huang Yun , Zhang Xiliang , Zhao Huibin , Zhang Chaojun 
Published: March 2020

Abstract
Background : Although ectopic thyroid can be found in thoracic locations, the discovery of abdominal ectopic thyroid is often an accidental event. Moreover, abdominal ectopic thyroid is easily misdiagnosed due to the rarity of these cases and the difficulties in the preoperative diagnosis process. Thus, we aimed to assess the prevalence and features of abdominal ectopic thyroid and to highlight the current knowledge about the clinical characteristics and management of this condition by analyzing a case report of abdominal ectopic thyroid and reviewing the literature. Case presentation : A 70-year-old woman with a 3-year history of gradually increasing abdominal distension in the right lower quadrant of the abdomen was admitted to the hospital. Contrast-enhanced computed tomography (CT) of the abdomen revealed a retroperitoneal mass. The patient underwent Da Vinci robotic surgery, and the retroperitoneal mass was completely resected. Subsequently, the pathologic diagnosis of the mass was ET. The patient had no discomfort or symptoms when she was discharged from the hospital and at the postoperative 1, 3, 6, 9 and 12 month follow-up. The summary of literature review suggested that abdominal ectopic thyroid is still rare although there are some reports. Nonetheless, the cause of abdominal ectopic thyroid is unclear, and abdominal ectopic thyroid has the following characteristics: more common in women than in men, asymptomatic in the majority of the cases, difficult to diagnose, and found by excluding metastasis. Most ectopic thyroid is treated with surgery, and minimally invasive techniques have been increasingly performed. Conclusion : This is the first report on Da Vinci robotic resection for large rare retroperitoneal ET, and this case highlights that ET should be considered when patients present with similar imaging findings in the abdomen.
Pancreatic cystadenoma coexistent with incidental neuroendocrine tumor: a case report and literature review
Authors: Wu Jingjin , Zhang Li , Yu Zhiyong 
Published: March 2020

Abstract
Background Pancreatic cystadenoma coexistent with neuroendocrine tumor is a rare disease which is reported sporadically. Case Presentation We herein present one such interesting case in a 67-year old man. There was only one mass detected preoperatively by different examinations. Endoscopic ultrasound-guided biopsy indicated a pancreatic neuroendocrine tumor. Therefore, a distal pancreatectomy was performed and the final histopathology revealed two separate masses in the pancreas, one was serious cystadenoma and the other neuroendocrine tumor. Conclusions SCA coexistent with PNET is rarely found during clinical practice. The component of PNET may not be confirmed until the operation. Based on the recorded cases, the malignant potential, clinical characteristics, treatment, and prognosis are remaining further researches.
The benefits evaluation of abdominal deep inspiration breath hold based on knowledge-based radiotherapy treatment planning for left-sided breast cancer
Authors: Xu Jiaqi , Wang Jiazhou , Zhao Feng , Hu Weigang , Bu Luyi , Yao Guorong , Lu Zhongjie , Yan Senxiang 
Published: March 2020

Abstract
Purpose Study the impact of abdominal deep inspiration breath hold (DIBH) technique on knowledge-based radiotherapy treatment planning for left-sided breast cancer to guide the application of DIBH radiotherapy technology. Methods and Materials Two kernel density estimation (KDE) models were developed based on 40 left-sided breast cancer patients with two CT acquisitions of free breathing (FB-CT) and DIBH (DIBH-CT). Each KDE model was used to predict DVHs based on DIBH-CT and FB-CT for another 10 new patients similar to our training datasets. The predicted DVHs were taken as a substitute to dose constraints and objective functions in the Eclipse treatment planning system, with the same requirements for the planning target volume (PTV). The mean doses to the heart, the left anterior descending coronary artery (LADCA) and the ipsilateral lung were evaluated and compared using the T-test among clinical plans, KDE predictions, and KDE plans.Results Our study demonstrated that the KDE model can generate deliverable simulations equivalent to clinically applicable plans. The T-test was applied to test the consistency hypothesis on another 10 left-sided breast cancer patients. In cases of the same breathing status, there was no statistically significant difference between the predicted and the clinical plans for all clinically relevant dose volume histogram (DVH) indices (p>0.05), and all predicted DVHs can be transferred into deliverable plans. For DIBH-CT images, significant differences were observed in Dmean between FB model predictions and the clinical plans (p<0.05). DIBH model prediction cannot be optimized to a deliverable plan based on FB-CT, with a counsel of perfection. Conclusion This study demonstrated that the KDE prediction results were well fitted for the same breathing condition but degrade with different breathing conditions. The benefits of DIBH can be evaluated quickly and effectively by the specific knowledge-based treatment planning for left-sided breast cancer radiotherapy. This study will help to further realize the goal of automatic treatment planning.
Blocking of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells
Authors: Lee Young-shin , Heo Woong , Choi Ho-Jung , Cho Hae-Ryung , Nam Ji Ho , Ki Yong Gan , Kang Chi Dug , Bae Jaeho 
Published: March 2020

Abstract
Background Since ionizing radiation has showed the dramatic effect to kill the cancer cells by direct DNA damage as well as triggering anti-cancer immune responses through release of various tumor antigens and induction of NK activating molecules, it has been used for long time to treat many cancer patients including patients with melanoma. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system. One of the suggested ways is induction of a ligand for programmed death-1 (PD-L1) after radiotherapy in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity in T cells. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1/2 in malignant melanoma cells and the receptor, PD-1, in NK-92 cells. Results Surface PD-L1/2 levels on melanoma cells were increased by ionizing radiation in a dose-dependent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1/2 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1/2+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene to inhibit PD-1/PD-L1 axis, they reversed the activity of the suppressed NK cells. Conclusions Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.
Altered Gut Microbiota Associated with Hemorrhage in Chronic Radiation Proctitis
Authors: Liu Liangzhe , Chen Bingcheng , Chen Chaoyun , Ding Chen , Xiao Nana , Liang Jinjun 
Published: March 2020

Abstract
Background: Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient’s quality of life. Here, we aimed to characterize the gut microbiota of CRP patients and reveal the association of dysbiosis and hematochezia. A comparative metagenomic study of CRP with and without hematochezia was conducted by 16S rRNA gene sequencing. Results: Different patterns of dysbiosis were observed in CRP patients with and without hematochezia. The abundance of Bacteroides was higher in CRP patients without hematochezia. The Verrucomicrobia phylum was enriched while the compositions of the Enterobacteriales family and the Porphyromonadaceae genus were relatively lower in the microbiota of CRP patients with hematochezia. PICRUSt analysis suggested that the expression of Fe-S protein, Glutathione peroxidase and Glutaredoxin-related protein were increased, indicating an exacerbated inflammation state in hematochezia patients. Conclusions: This study provides new insight to the altered composition and function of gut microbiota in patients with hematochezia, implying the link of CRP symptom and bacterial ecosystem on rectal epithelial layer.
SIR model for novel coronavirus-infected transmission process and its application
Authors: Tang Tao , Cao Lei , Lan Chunyu , Cao Li 
Published: March 2020

Abstract
Background: To establish a novel coronavirus-infection transmission process model in Wuhan, and to provide a decision support for epidemic prediction and prevention. Methods: SIR model for novel coronavirus-infection transmission process was built based on the data of the infected persons, discharged patients and discharged patients during the period of isolation and control in Wuhan. Least squares estimation method was used to estimate the key parameters of the model. Results: The changing trend of the predicted value of SIR model was basically consistent with the actual value, and fitting effect was well. Based on the prediction results of model, future development trend of the epidemic showed that the inflection point of the epidemic was the 38th day, namely at the end of February, the peak number of infected persons was about 22000 (excluding clinical diagnosis cases); Different infection intensity and removal intensity had an impact on the development of the epidemic. Conclusion: The SIR model for novel coronavirus-infection transmission process in Wuhan has high veracity. Through the prediction and application of the model, it can provide guidance and advice for the actual epidemic prevention and control, and take effective measures to control the epidemic situation in time.