bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1
Authors: Huo Rujie , Tian Xinli , Chang Qin , Liu Dai , Wang Chen , Bai Jingcui , Wang Runjuan , Zheng Guoping , Tian Xinrui 
Published: June 2020

Abstract
Background and objective TGF-β1 is a key cytokine involved in airway inflammation and airway remodeling in asthma, owing to its anti-inflammatory and profibrotic effects. In our previous study, we found that the knockdown of cytosolic β-catenin mitigated the profibrogenic effect of TGF-β1 without affecting its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to CBP, attenuated airway inflammation by increasing the level of the anti-inflammatory cytokines IL-10, IL-35, and reducing the level of proinflammation cytokine IL-17. Suppressing β-catenin with ICG001 has an inhibitory effect on airway remodeling via reducing the level of TGF-β1 and the expression of MMP-7 and Snail, upregulating expression of E-cadherin, downregulating expressions of α-SMA and Fn. Inhibiting β-catenin with ICG001 suppressed TGF-β1-induced proliferation and activation of lung fibroblast (CCC-REPF-1) cells, and blocked TGF-β1-induced, blocked TGF-β1 induced EMT of alveolar type II epithelial (RLE-6TN) cells. Conclusions Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing proinflammatory and anti-inflammatory cytokine.
Clinical Outcomes After Coronary Artery Bypass Grafting in Patients with Dialysis-Dependent End-Stage Renal Disease and an Analysis of the Related Influencing Factors
Authors: Li Xihui , Zhang Siyu , Xiao Feng 
Published: June 2020

Abstract
Backgroud Perioperative and short/mid-term survival rates of dialysis-dependent patients with end-stage renal disease (ESRD), who undergo coronary artery bypass grafting (CABG), and the factors influencing mortality are not well evaluated In China. Method We retrospectively analyzed the perioperative and postoperative 1-, 3-, and 5-year survival rates of 53 dialysis-dependent ESRD patients who underwent CABG, and compared the factors related to perioperative mortality and all-cause mortality during the postoperative follow-up. Survival rates were expressed as Kaplan–Meier survival curves, and factors influencing the follow-up survival rates were analyzed using the log rank (Mantel–Cox) test. Result There were eight perioperative deaths, resulting in 15.1% mortality. Intraoperative intra-aortic balloon pump use (P=0.01), advanced age (P=0.0027), and high EuroSCORE II score (P=0.047) were associated with increased perioperative mortality. Forty-five discharged patients were followed from 2 months to 10 years (median, 4.2 years) postoperatively. There were 19 all-cause deaths, including 10 cardiac deaths (10/19, 52.6%). Comparisons between groups indicated that the presence of peripheral artery disease (PAD) increased mortality during follow-up (P=0.025); 1-, 3-, and 5-year survival rates were 93.3%, 79.5%, and 66.8%, respectively. The results of the long-rank analysis indicated that the presence of PAD was a risk factor for postoperative survival (log rank χ 2 =4.543; P=0.033). Conclusion Dialysis-dependent patients with ESRD had high perioperative mortality and unsatisfactory short- and medium-term survival after CABG. PAD was a risk factor affecting patients’ postoperative survival. Multidisciplinary teamwork is needed to enhance postoperative management and reduce complications, to improve postoperative survival in these patients.
Choline and Bile Acids Mixture Improved Growth Performance and Intestinal Immunity via Altering Gut Microbiota and Bacterial Metabolites in the Colon of Weaned Piglets.
Authors: Qiu Yueqin , Li Kebiao , Liu Shilong , Wang Li , Gao Kaiguo , Yang Xuefen , Jiang Zongyong 
Published: June 2020

Abstract
Background: Choline or bile acids has many beneficial roles in physiological function. However, little was known about growth performance, intestinal mucosal function and microbiota-host interactions of weaned piglets in response to choline or bile acids supplementation. This study aimed to investigate the effect of choline and bile acids mixtures (ChB) supplementation on growth performance, intestinal mucosal barrier function, gut microbiota and bacterial metabolites of weaned piglets. One hundred and twenty-eight crossbred (Duroc × Landrace × Large White) weaned piglets (initial body weight: approximately 8 kg; 21 d of age) were randomly allocated to four different dietary treatments(a control diet (Control) and the other three groups were control diet supplemented with 800 mg/kg choline chloride (choline), 500 mg/kg bile acids (bile acids) or 800 mg/kg choline chloride plus 500 mg/kg bile acids (ChB), respectively) and for 28-d feeding trail. Results: ChB significantly increased average daily gain (ADG) and reduced feed/gain (F/G) ratio, associated with elevation of lipase activity and total bile acids level in ileal digesta compared with control diet. Additionally, ChB altered colonic microbiota by increasing the relative abundance of Lactobacillus and Faecalibacterium , and decreasing the relative abundances of unidentified-Clostridiales , Parabacteroides and Unidentified-Ruminococcaceae , when compared with control diet. Meanwhile, ChB increased the butyrate level and decreased the production of bile acid profiles in the colonic digesta. Besides, feeding ChB improved gut immunity, as reflected by increasing the abundance of IL-10 , FXR and mucin2 transcript, while downregulated expression of TLR4 , MyD88 , NF-κBp65 and TNF-α genes in the intestinal mucosa. Quantitative proteomics of jejunal mucosa further showed that ChB regulated the proteins that were related to inflammatory response. Furthermore, the changes in the ADG and genes expression were associated with alteration of gut microbiota composition and their metabolites. Conclusions: Collectively, our findings demonstrated that choline and bile acids mixture may improve the growth performance and intestinal immune response of weaned piglets through alteration of gut microbiota composition and bacterial metabolites, which promoted gut health.
Primary epithelioid angiosarcoma originating from the mandibular gingiva: a case report of an extremely rare oral lesion
Authors: Komatsu Yuko , Miyamoto Ikuya , Ohashi Yu , Katagiri Katsunori , Saito Daisuke , Obara Mizuki , Takeda Yasunori , Shiga Kiyoto , Yamada Hiroyuki 
Published: June 2020

Abstract
BackgroundAngiosarcoma occurs very rarely in the oral cavity, and the epithelioid type is even rarer. Here we report a rare case involving an elderly man with a primary epithelioid angiosarcoma that originated from the mandibular gingiva and resembled a dentigerous cyst on radiographs.Case presentationA 66-year-old Japanese man visited our hospital with a chief complaint of gingival swelling in right mandibular third molar region. A panoramic radiograph showed bone resorption around the crown of right mandibular third molar, which was impacted. Incisional biopsy confirmed a diagnosis of epithelioid angiosarcoma. The lesion exhibited aggressive proliferation after biopsy resulting in uncontrolled bleeding and difficulty in closing the mouth. Mandibular segmental resection including the tumor was performed without reconstruction. Because of the aggressive preoperative course of the tumor, the patient received adjuvant chemotherapy. There were no signs of recurrence during a 1-year follow-up period.ConclusionsA review of the literature yielded only three reported cases of epithelioid angiosarcoma in the jaw region, with the lesions occurring in the maxilla in all three cases. To our knowledge, this is the first case of primary epithelioid angiosarcoma in the mandible.
Puerarin Inhibits FUNDC1-mediated Mitochondrial Autophagy and CSE-induced Apoptosis of Human Bronchial Epithelial Cells by Activating the PI3K/AKT/MTOR Signaling Pathway
Authors: Wang Li , Jiang Weizhou , Wang Jing , Xie Yuanyuan , Wang Weisi 
Published: June 2020

Abstract
Background: Growing evidence suggests that the pathogenesis of chronic obstructive pulmonary disease (COPD) is related to mitochondrial autophagy mediated by FUN14 domain protein 1 (FUNDC1). Recent studies have shown that puerarin has protective effects against excessive oxidative damage in cells. We hypothesized that puerarin might be involved in the progression of COPD induced by cigarette smoke extract (CSE) by regulating FUNDC1-mediated mitochondrial autophagy.Material/Methods: Different concentrations of puerarin were used to intervene in CSE-treated human bronchial epithelial cells (HBECs). MTT assay and flow cytometry were used to detect cell activity and apoptosis. The mitochondrial membrane potential (MMP) level, reactive oxygen species (ROS) content and ATP content were detected by flow cytometry or kits; Western Blotting was used to detect mitochondrial autophagy-related proteins expression such as DRP1, FUNDC1, PINK1, Parkin. Next, protein phosphatase inhibitor (PH0321) was used to inhibit the phosphorylation of FUNDC1, the changes of MMP, ROS, ATP and mitochondrial autophagy related proteins were detected. Furthermore, mitochondrial autophagy inhibitors (Mdivi) were used to block autophagy, and then the changes of mitochondrial autophagy, cell activity and apoptosis were detected, respectively. Finally, the changes of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western Blotting.Results: Puerarin reversed cell activity decrease and apoptosis increase of CSE-induced HBECs, and down-regulated apoptosis-related proteins expression. Puerarin up-regulated MMP level and ATP content in CSE-induced HBECs, and down-regulated ROS content and mitochondrial autophagy-related proteins expression. PH0321 promotes mitochondrial autophagy by promoting the dephosphorylation of FUNDC1, puerarin inhibits the dephosphorylation of FUNDC1, up-regulated the MMP level and ATP content of CSE-induced HBECs, reduces ROS content and mitochondrial autophagy-related proteins expression. Compared with Mdivi group, the protein expression changes of PINK1 and Parkin in puerarin-treated group were not significantly different, and the cell activity decrease and apoptosis increase of CSE-induced HBECs were also significantly reversed by puerarin, which was not significantly different from Mdivi group. Puerarin significantly upregulated the protein expression of p-PI3K, p-AKT and p-mTOR, suggesting that puerarin may participate in the progression of COPD by activating the PI3K/AKT/mTOR signaling pathway.Conclusions: Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of HBECs by activating the PI3K/AKT/mTOR signaling pathway.
Serum Amyloid a in Stable COPD Patients is Associated With the Frequent Exacerbator Phenotype
Authors: Zhao Dongxing , Abbasi Asghar , Rossiter Harry B , Su Xiaofen , Liu Heng , Pi Yuhong , Sang Li , Zhong Weiyong , Yang Qifeng , Guo Xiongtian , Zhou Yanyan , Li Tianyang , Casaburi Richard , Zhang Nuofu 
Published: June 2020

Abstract
Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotypein stable COPD patients i.e. those with two or more exacerbations in the previous year.Methods:88 stable, severe, COPD patients (4 females)were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO);inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.Results:Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%)had greater serum concentration(median (25th-75th quartile)) of serum amyloid A (SAA; 134(84-178) vs. 71(38-116) ng/ml; P=0.024), surfactant protein D (SP-D;15.6(9.0-19.3)vs. 8.5(3.6-14.9) ng/ml; P=0.049) and interleukin-4 (IL-4; 0.12(0.08-1.44)vs. 0.03(0.01-0.10) pg/ml;P=0.001). SAA,SP-D and IL-4were not significantly correlated with FEV1 %predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012).The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (³124.1ng/ml) than the lowest SAA quartile (£44.1ng/ml) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators with an optimal SAA cut-offof 131.7 ng/ml.Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA maybe a usefulserum biomarker to inform progression or management in COPD.
Estrogen-Related Receptor-α Promotes Pancreatic Cancer Progression by Enhancing the Transcription of PAI1 and Activating the MEK/ERK Signaling Pathway
Authors: Liu Shi-lei , Wu Xiang-song , Li Feng-nan , Yao Wen-yan , Wu Zi-you , Dong Ping , Wang Xue-feng , Gong Wei 
Published: June 2020

Abstract
Background: Estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, was reported to be highly associated with the progression and tumorigenesis of several human malignancies. However, the biological role and underlying molecular mechanisms of ERRα in pancreatic cancer (PC) remain unknown.Methods: The expression of ERRα in PC tissues was determined by qRT-PCR and immunohistochemistry. A series of in vitro and in vivo assays were performed to investigate the function of ERRα and Plasminogen activator inhibitor 1 (PAI1) in tumorigenesis in PC cells. The relationship between ERRα and PAI1 was identified by RNA sequencing, Chromatin immunoprecipitation and dual-luciferase reporter assays. The effects of ERRα on the MEK/ERK signaling pathway were determined by western blotting and rescue assays using ERK inhibitor GDC-0994.Results: ERRα was significantly overexpressed in PC tissues and cell lines. Its high expression was correlated with tumor size, distant metastasis, TNM stage, tumor differentiation and poor prognosis of PC. Subsequent functional assays showed that ERRα promoted PC cell proliferation, tumor growth, as well as migration and invasion via activating the epithelial-mesenchymal transition. In addition, knockdown of ERRα induced apoptosis and G0/G1 cell cycle arrest in PC cells. PAI1 was identified by RNA sequencing, knockdown of which could suppress the cell proliferation, migration and invasion that promoted by ERRα overexpression. Further mechanistic investigation using chromatin immunoprecipitation and dual-luciferase reporter assays revealed that ERRα could bind to the PAI1 promoter region and transcriptionally enhance PAI1 expression. Moreover, our data indicated that ERRα played its oncogenic role in PC via activating the MEK/ERK pathway.Conclusions: Our study demonstrates that ERRα promotes PC progression by enhancing the transcription of PAI1 and activation of the MEK/ERK pathway, pointing to ERRα as a novel diagnostic and therapeutic target for PC.
A New Scoring System Combining A Four-Section Honeycomb Lung Percentage on HRCT and Other Comprehensive Multiparameter for Evaluating Pulmonary Fibrosis Severity
Authors: Yin Chengsheng , Zhang Yuan , Su Yiliang , Zhang Feng , Shi Jingyun , Chen Yanan , Weng Dong , Chen Tao , Zhao Mengmeng , Zhou Ying , Jiang Xing , Zhang Aihong , Li Huiping 
Published: June 2020

Abstract
Background: How to accurately assess IPF severity and predict prognosis remains a problem. This study aimed to develop a new method, which can be easily used to assess pulmonary fibrosis severity.Method:1. Development of a HRCT combined pulmonary function & physiological parameter (CTPF) assessment method: The method included two parts. 1) CT-based fibrosis staging: Four representative lung CT sections were selected and evenly divided into 100 small areas. The percentage of honeycomb lesion area in the four sections was determined fibrosis stage,2) PF-based severity grade: FVC%pred,DLco%pred,SpO2% age and gender were used to assess PF severity grade. 2. Validation of the new method: The method was used to assess 192 patients with IPF. Two radiologists used the CT-based fibrosis staging method to determine the fibrosis stage. Pulmonologist determined the PF severity grade. 3. Statistical analyses: By Intra-group correlation coefficient and Spearman correlation coefficient to estimate the consistency between the CT scores from the two radiologists and the correlation between CT scores and lung function parameters. Using the competitive risk Fine–Gray model to analyze the relationship between CT-based stage/PF-based grade and prognosis. CT-based stage, PF-based grade, and GAP stage were used as predictor models to predicted the death risk. Results: 1. The intra-group correlation coefficient of the CT scores of the two radiologists was 0.95, P<0.05. 2. The CT scores negatively correlated with pulmonary function. 3. The CTPF comprehensive model, showed higher predictive accuracy.Conclusion: Combined CT-based staging and PF-based grading methods CTPF can be adopted easily in clinical practice, and can assess IPF severity and predict death risk more accurately.
Polyhexamethylene Guanidine-induced Lung Injuries and Tumorigenesis in a Rat Model: Radiologic Evaluation With Pathologic Correlation and RNA Sequencing
Authors: Kim Cherry , Jeong Sang Hoon , Kim Jaeyoung , Lee Ki Yeol , Cha Jaehyung , Lee Chang Hyun , Park Eun-Kee , Lee Ju-Han 
Published: June 2020

Abstract
Background: Polyhexamethylene guanidine phosphate (PHMG) is was used as humidifier disinfectants. We aimed to evaluate PHMG-induced lung injuries and their chronological changesin a rat model using chest CT with pathologic correlation, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT.Methods: A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4 weeks after instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing.Results: At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time.The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected.Conclusions: PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according toPHMG exposure under the guidance of CT.
Feasibility of intraoperative radiotherapy with X-rays for the treatment of superior sulcus tumours
Authors: PAN YI , Yang Xuening , Chen Zhiyong , Liang Yu , Hou Qingyi , Liao Riqiang , Dong Song , Xie Songxi , Zhong Wenzhao , Wu Yi-Long 
Published: June 2020

Abstract
Background

Preoperative concurrent chemoradiotherapy (CCRT) followed by surgery has become the standard treatment for potentially resectable superior sulcus (SS) tumours. To date, intraoperative radiotherapy (IORT) for SS tumour treatment is primarily performed via brachytherapy; it achieves high local control, but has no influence on overall survival. Therefore, a novel therapy is required to increase the local control of SS tumours. The purpose of this study was to evaluate the feasibility and safety of IORT with low-energy X-rays for treating SS tumours.

Methods

Patients diagnosed with stage IIB-IIIA SS tumours with chest wall invasion and scheduled to undergo surgery were eligible for this prospective pilot study. Every patient was discussed at a lung cancer multidisciplinary team meeting. Patients with potentially resectable tumour were scheduled for neoadjuvant chemoradiotherapy followed by surgery, while those with resectable tumour were scheduled to receive surgery alone. Neoadjuvant chemotherapy consisted of two cycles of platinum-based doublet chemotherapy. Concurrent radiotherapy of 50 Gy in 25 fractions over 5 weeks was performed via intensity-modulated radiation therapy. IORT was administered to the tumour bed with close margin. The primary endpoint was acute toxicity and secondary endpoints were late spinal cord and brachial plexus toxicity.

Results

Between August 22, 2014 and November 30, 2017, we enrolled nine patients (seven males and two females). Anaemia was the most common acute complication, with grade 3 anaemia occurring in three patients who received preoperative CCRT. Other side effects included pneumonia (1 patient), prolonged air leakage (1), and grade 1 brachial plexus injury (1). The average follow-up period was 29.4 (range; 13.3-50.4) months. All patients are alive. Distant metastasis was observed in two patients, one with contralateral lung metastasis and another with pericardial metastasis.

Conclusions

IORT with low-energy X-rays is a technically feasible and relatively safe treatment modality for patients with superior pulmonary sulcus tumours.