78 results on '"Han, Liu"'
Search Results
2. Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma.
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Juan Hu, Cong Xie, Shangcheng Xu, Qinli Pu, Han Liu, Liping Yang, Wei Wang, Longchun Mao, Zhiqiang Li, and Weixian Chen
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Medicine ,Science - Abstract
The mechanism of hepatocellular carcinoma (HCC) development induced by liver fibrosis is obscure. The objective of this study is to establish miRNAs from exosomes associated with liver fibrosis, and to identify potential biomarkers for the prediction of personalized clinical management effectiveness in HCC. Our research focused on miRNAs from exosomes and mRNA from liver fibrosis, which we found in the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) evaluated miRNAs from exosomes associated with liver fibrosis, and Wilcoxon analysis assessed differentially expressed mRNAs (DEGs) across liver fibrosis/normal tissues. Following that, DEGs were assessed through gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, based on the screened targeted genes, including SAMD12 and CADM2, we further elucidated their correlation in HCC patients from the BEST database. The Kaplan-Meier Plotter platform was applied to evaluate the prognostic values of miRNA in HCC. In vitro and vivo experiments validated our findings. Six miRNAs associated with liver fibrosis were evaluated in our investigation. In-depth research presented exosome-derived miR-106a-5p, SAMD12 and CADM2 could exert valuable predictive implications for HCC treatment and illness assessment. Serum miR-106a-5p derived from liver fibrosis was decreased compared with healthy individuals. SAMD12 and CADM2 were diminished in liver cancer cell lines, and their knockdown of them exacerbated the proliferation capacities of liver cells in vitro. Exosome-derived miRNA of liver fibrosis modulated tumorigenesis by targeting SAMD12 and CADM2 in HCC.
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- 2023
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3. Application of local fully Convolutional Neural Network combined with YOLO v5 algorithm in small target detection of remote sensing image
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Wentong Wu, Han Liu, Lingling Li, Yilin Long, Xiaodong Wang, Zhuohua Wang, Jinglun Li, and Yi Chang
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Medicine ,Science - Abstract
This exploration primarily aims to jointly apply the local FCN (fully convolution neural network) and YOLO-v5 (You Only Look Once-v5) to the detection of small targets in remote sensing images. Firstly, the application effects of R-CNN (Region-Convolutional Neural Network), FRCN (Fast Region-Convolutional Neural Network), and R-FCN (Region-Based-Fully Convolutional Network) in image feature extraction are analyzed after introducing the relevant region proposal network. Secondly, YOLO-v5 algorithm is established on the basis of YOLO algorithm. Besides, the multi-scale anchor mechanism of Faster R-CNN is utilized to improve the detection ability of YOLO-v5 algorithm for small targets in the image in the process of image detection, and realize the high adaptability of YOLO-v5 algorithm to different sizes of images. Finally, the proposed detection method YOLO-v5 algorithm + R-FCN is compared with other algorithms in NWPU VHR-10 data set and Vaihingen data set. The experimental results show that the YOLO-v5 + R-FCN detection method has the optimal detection ability among many algorithms, especially for small targets in remote sensing images such as tennis courts, vehicles, and storage tanks. Moreover, the YOLO-v5 + R-FCN detection method can achieve high recall rates for different types of small targets. Furthermore, due to the deeper network architecture, the YOL v5 + R-FCN detection method has a stronger ability to extract the characteristics of image targets in the detection of remote sensing images. Meanwhile, it can achieve more accurate feature recognition and detection performance for the densely arranged target images in remote sensing images. This research can provide reference for the application of remote sensing technology in China, and promote the application of satellites for target detection tasks in related fields.
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- 2021
4. NADPH oxidase 1 is highly expressed in human large and small bowel cancers.
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Jiamo Lu, Guojian Jiang, Yongzhong Wu, Smitha Antony, Jennifer L Meitzler, Agnes Juhasz, Han Liu, Krishnendu Roy, Hala Makhlouf, Rodrigo Chuaqui, Donna Butcher, Mariam M Konaté, and James H Doroshow
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Medicine ,Science - Abstract
To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer.
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- 2020
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5. Real-world efficacy of biological agents in moderate-to-severe plaque psoriasis: An analysis of 75 patients in Taiwan.
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Yu-Chen Chen, Yi-Ting Huang, Chao-Chun Yang, Edward Chia-Cheng Lai, Cheng-Han Liu, Chao-Kai Hsu, Tak-Wah Wong, Sheau-Chiou Chao, Hamm-Ming Sheu, and Chaw-Ning Lee
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Medicine ,Science - Abstract
BackgroundReal-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations.ObjectivesOur aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan.MethodsWe retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan.ResultsA total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers.ConclusionsThis real world data showed differential efficacy and safety of the four biological agents.
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- 2020
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6. Prognostic nomogram predicts overall survival in pulmonary large cell neuroendocrine carcinoma.
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Yanqi He, Han Liu, Shuai Wang, and Yu Chen
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Medicine ,Science - Abstract
BACKGROUND:Large cell neuroendocrine carcinoma (LCNEC) is a rare and typically aggressive malignancy with poor prognosis. This study developed a nomogram model to predict the overall survival (OS) of patients with LCNEC. METHODS:LCNEC patients were identified from the Surveillance, Epidemiology, and End Results database between 2004-2014. Univariate and multivariate Cox regression models were used to determine demographic and clinicopathological features associated with OS. A nomogram model was generated to predict OS and its performance was assessed by Harrell's concordance index (C-index), calibration plots, and subgroup analysis by risk scores. RESULTS:Of 3048 eligible patients with LCNEC, 2138 were randomly grouped into the training set and 910 into the validation set. Age at diagnosis, gender, tumor stage, N stage, tumor size, and surgery of primary site were independent prognostic factors of OS. C-index values of the nomogram were 0.75 (95% CI, 0.74-0.76) and 0.76 (95% CI, 0.74-0.77) in the training and validation sets, respectively. In both cohorts, the calibration plots showed good concordance between the predicted and observed OS at 3 and 5 years. Kaplan-Meier curves revealed significant differences in OS in patients stratified by nomogram-based risk score, and patients with a higher-than-median risk score had poorer OS. CONCLUSION:This is the first nomogram developed and validated in a large population-based cohort for predicting OS in patients with LCNEC, and it shows favorable discrimination and calibration abilities. Use of this proposed nomogram has the potential to improve prediction of survival risk, and lead to individualized clinical decisions for LCNEC.
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- 2019
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7. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis.
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Jingyue Xu, Han Liu, Ok Hee Chai, Yu Lan, and Rulang Jiang
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Medicine ,Science - Abstract
Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not well understood, however. In this study, by using the recently developed CRISPR genome editing technology, we genetically labeled the endogenous Osr1 protein and show that Osr1 interacts with Wt1 in the developing kidney. Whereas mice heterozygous for either an Osr1 or Wt1 null allele have normal kidneys at birth, most mice heterozygous for both Osr1 and Wt1 exhibit defects in metanephric kidney development, including unilateral or bilateral kidney agenesis or hypoplasia. The developmental defects in the Osr1+/-Wt1+/- mouse embryos were detected as early as E10.5, during specification of the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells. Moreover, expression of Gdnf, the major nephrogenic signal for inducing ureteric bud outgrowth, was significantly reduced in the metanephric mesenchyme in Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- littermates. By E11.5, as the ureteric buds invade the metanephric mesenchyme and initiate branching morphogenesis, kidney morphogenesis was significantly impaired in the Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- embryos. These results indicate that Osr1 and Wt1 act synergistically to regulate nephron endowment by controlling metanephric mesenchyme specification during early nephrogenesis.
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- 2016
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8. Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106.
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Tao Luo, Han Liu, and Jin Kyung Kim
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Medicine ,Science - Abstract
A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β.
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- 2016
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9. Cutoff Point of HbA1c for Diagnosis of Diabetes Mellitus in Chinese Individuals.
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Bing Wang, Ming-Chuan Liu, Xin-Yu Li, Xu-Han Liu, Qiu-Xia Feng, Lu Lu, Zhu Zhu, Ying-Shu Liu, Wei Zhao, and Zheng-Nan Gao
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Medicine ,Science - Abstract
The purpose of the present study was to find the optimal threshold of glycated hemoglobin (HbA1c) for diagnosis of diabetes mellitus in Chinese individuals.A total of 8 391 subjects (including 2 133 men and 6 258 women) aged 40-90 years with gradable retinal photographs were recruited. The relationship between HbA1c and diabetic retinopathy (DR) was examined. Receiver operating characteristic (ROC) curves were used to find the optimal threshold of HbA1c in screening DR and diagnosing diabetes.HbA1c values in patients with DR were significantly higher than in those with no DR. The ROC curve for HbA1c had an area under the curve of 0.881 (95%CI 0.857-0.905; P = 0.000). HbA1c at a cutoff of 6.5% had a high sensitivity (80.6%) and specificity (86.9%) for detecting DR.HbA1c can be used to diagnose diabetes in a Chinese population, and the optimal HbA1c cutoff point for diagnosis is 6.5%.
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- 2016
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10. Cardioprotective Effect of Licochalcone D against Myocardial Ischemia/Reperfusion Injury in Langendorff-Perfused Rat Hearts.
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Xuan Yuan, Hai-tao Niu, Peng-long Wang, Jie Lu, Hong Zhao, Shi-han Liu, Qiu-sheng Zheng, and Chang-gui Li
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Medicine ,Science - Abstract
Flavonoids are important components of 'functional foods', with beneficial effects on cardiovascular function. The present study was designed to investigate whether licochalcone D (LD) could be a cardioprotective agent in ischemia/reperfusion (I/R) injury and to shed light on its possible mechanism. Compared with the I/R group, LD treatment enhanced myocardial function (increased LVDP, dp/dtmax, dp/dtmin, HR and CR) and suppressed cardiac injury (decreased LDH, CK and myocardial infarct size). Moreover, LD treatment reversed the I/R-induced cleavage of caspase-3 and PARP, resulting in a significant decrease in proinflammatory factors and an increase in antioxidant capacity in I/R myocardial tissue. The mechanisms underlying the antiapoptosis, antiinflammation and antioxidant effects were related to the activation of the AKT pathway and to the blockage of the NF-κB/p65 and p38 MAPK pathways in the I/R-injured heart. Additionally, LD treatment markedly activated endothelial nitric oxide synthase (eNOS) and reduced nitric oxide (NO) production. The findings indicated that LD had real cardioprotective potential and provided support for the use of LD in myocardial I/R injury.
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- 2015
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11. Branched-chain amino acids and arginine improve performance in two consecutive days of simulated handball games in male and female athletes: a randomized trial.
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Chen-Kang Chang, Kun-Ming Chang Chien, Jung-Hsien Chang, Mei-Hsuan Huang, Ya-Chuan Liang, and Tsung-Han Liu
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Medicine ,Science - Abstract
The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days.Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34 ± 0.60%, PB trial: -0.21 ± 0.69%; second half: AA trial: -1.68 ± 0.58%, PB trial: 0.49 ± 0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2 ± 0.3) than the PB trial (15.1 ± 0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.
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- 2015
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12. Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development.
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Heather L Evans-Marin, Anthony T Cao, Suxia Yao, Feidi Chen, Chong He, Han Liu, Wei Wu, Maria G Gonzalez, Sara M Dann, and Yingzi Cong
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Medicine ,Science - Abstract
T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD). As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9-/- mice demonstrate a high level of Foxp3+ Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.
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- 2015
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13. Mitochondrial p38β and manganese superoxide dismutase interaction mediated by estrogen in cardiomyocytes.
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Han Liu, Mounica Yanamandala, Tiffany C Lee, and Jin Kyung Kim
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Medicine ,Science - Abstract
While etiology behind the observed acceleration of ischemic heart disease in postmenopausal women is poorly understood, collective scientific data suggest cardioprotective effects of the endogenous female sex hormone, estrogen. We have previously shown that 17β-estradiol (E2) protects cardiomyocytes exposed to hypoxia-reoxygenation (H/R) by inhibiting p38α - p53 signaling in apoptosis and activating pro-survival p38β mitogen activated protein kinase (p38β MAPK), leading to suppression of reactive oxygen species (ROS) post H/R. However, little is known about the mechanism behind the antioxidant actions of E2-dependent p38β. The aim of this study is to determine whether the cytoprotection by estrogen involves regulation of manganese superoxide dismutase (MnSOD), a major mitochondrial ROS scavenging enzyme, via cardiac p38β.We identified mitochondrial p38β by immunocytochemistry and by immunoblotting in mitochondria isolated from neonatal cardiomyocytes of Sprague-Dawley rats. E2 facilitated the mitochondrial localization of the active form of the kinase, phosphorylated p38β (p-p38β). E2 also reduced the H/R-induced mitochondrial membrane potential decline, augmented the MnSOD activity and suppressed anion superoxide generation, while the dismutase protein expression remained unaltered. Co-immunoprecipitation studies showed physical association between MnSOD and p38β. p38β phosphorylated MnSOD in an E2-dependent manner in in-vitro kinase assays.This work demonstrates for the first time a mitochondrial pool of active p38β and E2-mediated phosphorylation of MnSOD by the kinase. The results shed light on the mechanism behind the cytoprotective actions of E2 in cardiomyocytes under oxidative stress.
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- 2014
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14. A small peptide with potential ability to promote wound healing.
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Jing Tang, Han Liu, Chen Gao, Lixian Mu, Shilong Yang, Mingqiang Rong, Zhiye Zhang, Jie Liu, Qiang Ding, and Ren Lai
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Medicine ,Science - Abstract
Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β) are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2]) containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1) the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2) the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3) tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6) in murine macrophages and activating mitogen-activated protein kinases (MAPK) signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β), tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.
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- 2014
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15. Application of local fully Convolutional Neural Network combined with YOLO v5 algorithm in small target detection of remote sensing image
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Yi Chang, Jinglun Li, Yilin Long, Zhuohua Wang, Wentong Wu, Han Liu, Xiaodong Wang, and Lingling Li
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Satellite Imagery ,Computer science ,Computer Vision ,Social Sciences ,Transportation ,Convolutional neural network ,Pattern Recognition, Automated ,Remote Sensing ,Machine Learning ,Geoinformatics ,Psychology ,Network architecture ,Remote Sensing Imagery ,Multidisciplinary ,Geography ,Artificial neural network ,Applied Mathematics ,Simulation and Modeling ,Process (computing) ,Transportation Infrastructure ,Sports Science ,Physical Sciences ,Engineering and Technology ,Medicine ,Algorithm ,Algorithms ,Research Article ,Sports ,Computer and Information Sciences ,Neural Networks ,Airports ,Imaging Techniques ,Science ,Feature extraction ,Research and Analysis Methods ,Civil Engineering ,Image (mathematics) ,Machine Learning Algorithms ,Artificial Intelligence ,Remote sensing ,Behavior ,Feature recognition ,Biology and Life Sciences ,Target Detection ,Data set ,Earth Sciences ,Recreation ,Neural Networks, Computer ,Mathematics ,Neuroscience - Abstract
This exploration primarily aims to jointly apply the local FCN (fully convolution neural network) and YOLO-v5 (You Only Look Once-v5) to the detection of small targets in remote sensing images. Firstly, the application effects of R-CNN (Region-Convolutional Neural Network), FRCN (Fast Region-Convolutional Neural Network), and R-FCN (Region-Based-Fully Convolutional Network) in image feature extraction are analyzed after introducing the relevant region proposal network. Secondly, YOLO-v5 algorithm is established on the basis of YOLO algorithm. Besides, the multi-scale anchor mechanism of Faster R-CNN is utilized to improve the detection ability of YOLO-v5 algorithm for small targets in the image in the process of image detection, and realize the high adaptability of YOLO-v5 algorithm to different sizes of images. Finally, the proposed detection method YOLO-v5 algorithm + R-FCN is compared with other algorithms in NWPU VHR-10 data set and Vaihingen data set. The experimental results show that the YOLO-v5 + R-FCN detection method has the optimal detection ability among many algorithms, especially for small targets in remote sensing images such as tennis courts, vehicles, and storage tanks. Moreover, the YOLO-v5 + R-FCN detection method can achieve high recall rates for different types of small targets. Furthermore, due to the deeper network architecture, the YOL v5 + R-FCN detection method has a stronger ability to extract the characteristics of image targets in the detection of remote sensing images. Meanwhile, it can achieve more accurate feature recognition and detection performance for the densely arranged target images in remote sensing images. This research can provide reference for the application of remote sensing technology in China, and promote the application of satellites for target detection tasks in related fields.
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- 2021
16. Real-world efficacy of biological agents in moderate-to-severe plaque psoriasis: An analysis of 75 patients in Taiwan
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Hamm Ming Sheu, Sheau Chiou Chao, Chao Kai Hsu, Cheng Han Liu, Chao Chun Yang, Yi Ting Huang, Chaw Ning Lee, Tak Wah Wong, Yu Chen Chen, and Edward C. Lai
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Male ,Economics ,Cancer Treatment ,Social Sciences ,Cardiovascular Medicine ,Severity of Illness Index ,Etanercept ,Geographical Locations ,Biological Factors ,Medical Conditions ,Medicine and Health Sciences ,Medicine ,skin and connective tissue diseases ,Multidisciplinary ,Pharmaceutics ,Middle Aged ,humanities ,Cardiovascular Therapy ,Treatment Outcome ,Oncology ,Research Design ,Cardiovascular Diseases ,Female ,Ustekinumab ,medicine.drug ,Research Article ,musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Asia ,Adolescent ,Clinical Research Design ,Science ,Immunology ,Taiwan ,Cardiology ,Research and Analysis Methods ,Antibodies, Monoclonal, Humanized ,Autoimmune Diseases ,Young Adult ,Health Economics ,Drug Therapy ,Psoriasis Area and Severity Index ,Psoriasis ,Internal medicine ,Adalimumab ,Humans ,Adverse effect ,Aged ,Retrospective Studies ,business.industry ,Biology and Life Sciences ,medicine.disease ,Health Care ,People and Places ,Secukinumab ,Clinical Immunology ,Adverse Events ,Clinical Medicine ,business ,Body mass index ,Health Insurance - Abstract
Background Real-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations. Objectives Our aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan. Methods We retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan. Results A total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers. Conclusions This real world data showed differential efficacy and safety of the four biological agents.
- Published
- 2020
17. HIV-1 Tat protein increases microglial outward K(+) current and resultant neurotoxic activity.
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Jianuo Liu, Peng Xu, Cory Collins, Han Liu, Jingdong Zhang, James P Keblesh, and Huangui Xiong
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Medicine ,Science - Abstract
Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-α, IL-1β, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K(+) current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K(+) channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K(+) channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders.
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- 2013
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18. A school-based study with Rome III criteria on the prevalence of functional gastrointestinal disorders in Chinese college and university students.
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Yan-Yan Dong, Fei-Xue Chen, Yan-Bo Yu, Chao Du, Qing-Qing Qi, Han Liu, and Yan-Qing Li
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Medicine ,Science - Abstract
BACKGROUND: Functional gastrointestinal disorders, including functional dyspepsia, irritable bowel syndrome and functional constipation are very common worldwide. OBJECTIVE: This research aims to estimate the prevalence and associated factors involved in functional gastrointestinal disorders in Chinese college and university students using the Rome III criteria. METHODS: A total of 5000 students from Shandong University in China were asked in January-May 2012 to complete questionnaires, including the Rome III questionnaire, hospital anxiety and depression scale, and negative life events scale. RESULTS: Based on the 4638 students who completed the questionnaire, the prevalence of functional dyspepsia, irritable bowel syndrome and functional constipation in college and university students of North China worked out to be 9.25%, 8.34% and 5.45% respectively. They were more frequent in female students. The factors of anxiety (OR 1.07; 95% CI 0.99 to 1.16, P=0.002
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- 2013
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19. Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis.
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Yu Han Liu, Vijesh Vaghjiani, Jing Yang Tee, Kelly To, Peng Cui, Ding Yuan Oh, Ursula Manuelpillai, Ban-Hock Toh, and James Chan
- Subjects
Medicine ,Science - Abstract
Human amniotic epithelial cells (hAEC) have stem cell-like features and immunomodulatory properties. Here we show that hAEC significantly suppressed splenocyte proliferation in vitro and potently attenuated a mouse model of multiple sclerosis (MS). Central nervous system (CNS) CD3(+) T cell and F4/80(+) monocyte/macrophage infiltration and demyelination were significantly reduced with hAEC treatment. Besides the known secretion of prostaglandin E2 (PGE2), we report the novel finding that hAEC utilize transforming growth factor-β (TGF-β) for immunosuppression. Neutralization of TGF-β or PGE2 in splenocyte proliferation assays significantly reduced hAEC-induced suppression. Splenocytes from hAEC-treated mice showed a Th2 cytokine shift with significantly elevated IL-5 production. While transferred CFSE-labeled hAEC could be detected in the lung, none were identified in the CNS or in lymphoid organs. This is the first report documenting the therapeutic effect of hAEC in a MS-like model and suggest that hAEC may have potential for use as therapy for MS.
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- 2012
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20. Immune sculpting of norepinephrine on MHC-I, B7-1, IDO and B7-H1 expression and regulation of proliferation and invasion in pancreatic carcinoma cells.
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Liancai Wang, Han Liu, Xiangli Chen, Min Zhang, Keping Xie, and Qingyong Ma
- Subjects
Medicine ,Science - Abstract
BACKGROUND: The sympathetic neurotransmitter Norepinephrine (NE) contributes to tumorigenesis and cancer progression. This study aims to investigate the role of NE in modulating the immune phenotype and allowing pancreatic carcinoma (PC) cells to escape the immune response. METHODS: Varied concentrations of NE and interferon-gamma (IFN-γ) were administrated to MIA PaCa-2 and BxPC-3 cell lines for 48 hours. Proliferation and invasion were then investigated using an MTT assay and a membrane invasion culture system respectively. MHC-I, B7-1, IDO and B7-H1 expression were measured using real-time quantitative RT-PCR, western blotting and immunocytochemistry. The synergistic and time-dependent effects of NE/IFN-γ were also investigated. Adrenergic antagonists were used to identify the relevant target receptor of NE. RESULTS: The results showed that NE had dose-dependent and time-dependent effects on cell biological processes as well as on the expression of MHC-I, B7-1, IDO and B7-H1. These effects occurred mainly via the β(2)-adrenergic receptor. Long-term NE treatment was able to antagonize some of the effects of IFN-γ (after 2 weeks of treatment), but NE and IFN-γ had significant synergistic stimulatory effects on IDO and B7-H1 expression. The residual effects on biological activities lasted for 2 weeks, while the immunophenotypic changes decreased at early time points after treatment. CONCLUSIONS: NE plays important roles in modulating PC cell biological activities and affecting MHC-I, B7-1, IDO and B7-H1 expression in vitro, mainly via the β2-adrenergic receptor (β2-AR) in a time- and dose-dependent fashion. Only at extended treatment durations could NE affect PC cell progression and immune evasion.
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- 2012
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21. Changes in culture expanded human amniotic epithelial cells: implications for potential therapeutic applications.
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Gita Pratama, Vijesh Vaghjiani, Jing Yang Tee, Yu Han Liu, James Chan, Charmaine Tan, Padma Murthi, Caroline Gargett, and Ursula Manuelpillai
- Subjects
Medicine ,Science - Abstract
Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell-like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal-stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymal-stromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, α- and β-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-β1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications.
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- 2011
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22. High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR.
- Author
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Liang Han, Qingyong Ma, Junhui Li, Han Liu, Wei Li, Guodong Ma, Qinhong Xu, Shuang Zhou, and Erxi Wu
- Subjects
Medicine ,Science - Abstract
Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.
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- 2011
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23. Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.
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Junhui Li, Qingyong Ma, Han Liu, Kun Guo, Feng Li, Wei Li, Liang Han, Fengfei Wang, and Erxi Wu
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. METHODOLOGY/PRINCIPAL FINDINGS: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000). CONCLUSIONS/SIGNIFICANCE: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.
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- 2011
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24. Regulation of ErbB2 receptor status by the proteasomal DUB POH1.
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Han Liu, Richard Buus, Michael J Clague, and Sylvie Urbé
- Subjects
Medicine ,Science - Abstract
Understanding the factors, which control ErbB2 and EGF receptor (EGFR) status in cells is likely to inform future therapeutic approaches directed at these potent oncogenes. ErbB2 is resistant to stimulus-induced degradation and high levels of over-expression can inhibit EGF receptor down-regulation. We now show that for HeLa cells expressing similar numbers of EGFR and ErbB2, EGFR down-regulation is efficient and insensitive to reduction of ErbB2 levels. Deubiquitinating enzymes (DUBs) may extend protein half-lives by rescuing ubiquitinated substrates from proteasomal degradation or from ubiquitin-dependent lysosomal sorting. Using a siRNA library directed at the full complement of human DUBs, we identified POH1 (also known as Rpn11 or PSMD14), a component of the proteasome lid, as a critical DUB controlling the apparent ErbB2 levels. Moreover, the effects on ErbB2 levels can be reproduced by administration of proteasomal inhibitors such as epoxomicin used at maximally tolerated doses. However, the extent of this apparent loss and specificity for ErbB2 versus EGFR could not be accounted for by changes in transcription or degradation rate. Further investigation revealed that cell surface ErbB2 levels are only mildly affected by POH1 knock-down and that the apparent loss can at least partially be explained by the accumulation of higher molecular weight ubiquitinated forms of ErbB2 that are detectable with an extracellular but not intracellular domain directed antibody. We propose that POH1 may deubiquitinate ErbB2 and that this activity is not necessarily coupled to proteasomal degradation.
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- 2009
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25. Prognostic nomogram predicts overall survival in pulmonary large cell neuroendocrine carcinoma
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Yu Chen, Shuai Wang, Han Liu, and Yanqi He
- Subjects
0301 basic medicine ,Oncology ,Male ,Lung Neoplasms ,Cancer Treatment ,Kaplan-Meier Estimate ,Lung and Intrathoracic Tumors ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Risk Factors ,Medicine and Health Sciences ,Aged, 80 and over ,Multidisciplinary ,Framingham Risk Score ,Statistics ,Age Factors ,Middle Aged ,Prognosis ,Surgical Oncology ,030220 oncology & carcinogenesis ,Cohort ,Physical Sciences ,Medicine ,Female ,Anatomy ,Risk assessment ,Research Article ,Clinical Oncology ,medicine.medical_specialty ,Histology ,Science ,Concordance ,Clinical Decision-Making ,Subgroup analysis ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Risk Assessment ,Decision Support Techniques ,03 medical and health sciences ,Diagnostic Medicine ,Internal medicine ,medicine ,Cancer Detection and Diagnosis ,Humans ,Statistical Methods ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Cancers and Neoplasms ,Biology and Life Sciences ,Nomogram ,Large cell neuroendocrine carcinoma of the lung ,medicine.disease ,Carcinoma, Neuroendocrine ,Nomograms ,030104 developmental biology ,ROC Curve ,Multivariate Analysis ,Carcinoma, Large Cell ,Clinical Medicine ,Secondary Lung Tumors ,business ,Mathematics ,SEER Program - Abstract
Background Large cell neuroendocrine carcinoma (LCNEC) is a rare and typically aggressive malignancy with poor prognosis. This study developed a nomogram model to predict the overall survival (OS) of patients with LCNEC. Methods LCNEC patients were identified from the Surveillance, Epidemiology, and End Results database between 2004-2014. Univariate and multivariate Cox regression models were used to determine demographic and clinicopathological features associated with OS. A nomogram model was generated to predict OS and its performance was assessed by Harrell's concordance index (C-index), calibration plots, and subgroup analysis by risk scores. Results Of 3048 eligible patients with LCNEC, 2138 were randomly grouped into the training set and 910 into the validation set. Age at diagnosis, gender, tumor stage, N stage, tumor size, and surgery of primary site were independent prognostic factors of OS. C-index values of the nomogram were 0.75 (95% CI, 0.74-0.76) and 0.76 (95% CI, 0.74-0.77) in the training and validation sets, respectively. In both cohorts, the calibration plots showed good concordance between the predicted and observed OS at 3 and 5 years. Kaplan-Meier curves revealed significant differences in OS in patients stratified by nomogram-based risk score, and patients with a higher-than-median risk score had poorer OS. Conclusion This is the first nomogram developed and validated in a large population-based cohort for predicting OS in patients with LCNEC, and it shows favorable discrimination and calibration abilities. Use of this proposed nomogram has the potential to improve prediction of survival risk, and lead to individualized clinical decisions for LCNEC.
- Published
- 2019
26. NADPH oxidase 1 is highly expressed in human large and small bowel cancers
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Mariam M. Konaté, Krishnendu Roy, Hala R. Makhlouf, Jiamo Lu, Jennifer L. Meitzler, Han Liu, Yongzhong Wu, Donna Butcher, Smitha Antony, Guojian Jiang, Rodrigo F. Chuaqui, James H. Doroshow, and Agnes Juhasz
- Subjects
0301 basic medicine ,Colorectal cancer ,Biochemistry ,0302 clinical medicine ,Superoxides ,Adenocarcinomas ,Intestine, Small ,Medicine and Health Sciences ,Small interfering RNAs ,Staining ,Multidisciplinary ,Tissue microarray ,biology ,Cell Staining ,Oxides ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Nucleic acids ,Chemistry ,Oncology ,030220 oncology & carcinogenesis ,NOX1 ,Colonic Neoplasms ,Physical Sciences ,cardiovascular system ,NADPH Oxidase 1 ,Immunohistochemistry ,Adenocarcinoma ,Medicine ,Antibody ,Anatomy ,HT29 Cells ,Research Article ,medicine.drug_class ,Colon ,Science ,Monoclonal antibody ,Research and Analysis Methods ,Models, Biological ,Carcinomas ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,medicine ,Genetics ,Humans ,Molecular Biology Techniques ,Non-coding RNA ,Molecular Biology ,Immunohistochemistry Techniques ,Colorectal Cancer ,Chemical Compounds ,Cancers and Neoplasms ,Biology and Life Sciences ,medicine.disease ,Gene regulation ,Gastrointestinal Tract ,Histochemistry and Cytochemistry Techniques ,030104 developmental biology ,Specimen Preparation and Treatment ,Cancer cell ,biology.protein ,Cancer research ,Immunologic Techniques ,RNA ,Gene expression ,Caco-2 Cells ,Digestive System ,Cloning - Abstract
To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer.
- Published
- 2019
27. Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development
- Author
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Yingzi Cong, Feidi Chen, Heather L. Evans-Marin, Sara M. Dann, Suxia Yao, Han Liu, Anthony T. Cao, Wei Wu, Maria G. Gonzalez, and Chong He
- Subjects
Regulatory T cell ,T cell ,lcsh:Medicine ,Mice, Transgenic ,Biology ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,Mice ,Receptors, CCR ,0302 clinical medicine ,medicine ,Cytotoxic T cell ,Animals ,IL-2 receptor ,Antigen-presenting cell ,lcsh:Science ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,ZAP70 ,lcsh:R ,FOXP3 ,Natural killer T cell ,Colitis ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Immunology ,lcsh:Q ,030215 immunology ,Research Article - Abstract
T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD). As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9-/- mice demonstrate a high level of Foxp3+ Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.
- Published
- 2015
28. Dexmedetomidine Acts via the JAK2/STAT3 Pathway to Attenuate Isoflurane-Induced Neurocognitive Deficits in Senile Mice
- Author
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Si, Yanna, primary, Zhang, Yuan, additional, Han, Liu, additional, Chen, Lihai, additional, Xu, Yajie, additional, Sun, Fan, additional, Ji, Muhuo, additional, Yang, Jianjun, additional, and Bao, Hongguang, additional
- Published
- 2016
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29. Branched-chain amino acids and arginine improve performance in two consecutive days of simulated handball games in male and female athletes: a randomized trial
- Author
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Jung-Hsien Chang, Chen-Kang Chang, Tsung-Han Liu, Ya-Chuan Liang, Mei-Hsuan Huang, and Kun-Ming Chang Chien
- Subjects
Male ,medicine.medical_specialty ,Arginine ,Taiwan ,lcsh:Medicine ,Athletic Performance ,Placebo ,Running ,law.invention ,Animal science ,Randomized controlled trial ,law ,Humans ,Medicine ,Exertion ,lcsh:Science ,Analysis of Variance ,Multidisciplinary ,biology ,Muscle fatigue ,Athletes ,business.industry ,lcsh:R ,biology.organism_classification ,Sprint ,Dietary Supplements ,Muscle Fatigue ,Exercise Test ,Physical therapy ,Female ,lcsh:Q ,Analysis of variance ,business ,human activities ,Amino Acids, Branched-Chain ,Research Article - Abstract
The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days.Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34 ± 0.60%, PB trial: -0.21 ± 0.69%; second half: AA trial: -1.68 ± 0.58%, PB trial: 0.49 ± 0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2 ± 0.3) than the PB trial (15.1 ± 0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.
- Published
- 2015
30. Cardioprotective Effect of Licochalcone D against Myocardial Ischemia/Reperfusion Injury in Langendorff-Perfused Rat Hearts
- Author
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Haitao Niu, Xuan Yuan, Penglong Wang, Qiusheng Zheng, Jie Lu, Hong Zhao, Shi-han Liu, and Changgui Li
- Subjects
Male ,Cardiotonic Agents ,Nitric Oxide Synthase Type III ,Ischemia ,Nitric Oxide Synthase Type II ,lcsh:Medicine ,Apoptosis ,Myocardial Reperfusion Injury ,In Vitro Techniques ,Pharmacology ,medicine.disease_cause ,p38 Mitogen-Activated Protein Kinases ,Nitric oxide ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Chalcones ,Enos ,Malondialdehyde ,medicine ,Animals ,Cardioprotective Agent ,Phosphorylation ,lcsh:Science ,PI3K/AKT/mTOR pathway ,Inflammation ,Multidisciplinary ,biology ,Superoxide Dismutase ,Myocardium ,lcsh:R ,medicine.disease ,biology.organism_classification ,Glutathione ,Perfusion ,Oxidative Stress ,chemistry ,Heart Function Tests ,Immunology ,lcsh:Q ,Proto-Oncogene Proteins c-akt ,Reperfusion injury ,Oxidative stress ,Research Article - Abstract
Flavonoids are important components of ‘functional foods’, with beneficial effects on cardiovascular function. The present study was designed to investigate whether licochalcone D (LD) could be a cardioprotective agent in ischemia/reperfusion (I/R) injury and to shed light on its possible mechanism. Compared with the I/R group, LD treatment enhanced myocardial function (increased LVDP, dp/dt max, dp/dt min, HR and CR) and suppressed cardiac injury (decreased LDH, CK and myocardial infarct size). Moreover, LD treatment reversed the I/R-induced cleavage of caspase-3 and PARP, resulting in a significant decrease in proinflammatory factors and an increase in antioxidant capacity in I/R myocardial tissue. The mechanisms underlying the antiapoptosis, antiinflammation and antioxidant effects were related to the activation of the AKT pathway and to the blockage of the NF-κB/p65 and p38 MAPK pathways in the I/R-injured heart. Additionally, LD treatment markedly activated endothelial nitric oxide synthase (eNOS) and reduced nitric oxide (NO) production. The findings indicated that LD had real cardioprotective potential and provided support for the use of LD in myocardial I/R injury.
- Published
- 2015
31. A School-Based Study with Rome III Criteria on the Prevalence of Functional Gastrointestinal Disorders in Chinese College and University Students
- Author
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Fei-Xue Chen, Yan-Qing Li, Chao Du, Han Liu, Qingqing Qi, Yan-Yan Dong, and Yanbo Yu
- Subjects
Male ,Abdominal pain ,Constipation ,Gastrointestinal Diseases ,lcsh:Medicine ,Comorbidity ,Anxiety ,Irritable Bowel Syndrome ,Adolescent Psychiatry ,Risk Factors ,Surveys and Questionnaires ,Prevalence ,lcsh:Science ,Irritable bowel syndrome ,Depression (differential diagnoses) ,Stomach and Duodenum ,Psychiatry ,Multidisciplinary ,Depression ,Gastrointestinal Motility Disorders ,digestive, oral, and skin physiology ,Mental Health ,Gastritis ,Medicine ,Small Intestine ,Female ,medicine.symptom ,Research Article ,medicine.medical_specialty ,China ,Universities ,Clinical Research Design ,Colon ,Gastroenterology and Hepatology ,Risk Assessment ,Young Adult ,Asian People ,medicine ,Humans ,Dyspepsia ,Students ,Survey Research ,business.industry ,Mood Disorders ,lcsh:R ,medicine.disease ,digestive system diseases ,Logistic Models ,Defecation ,Functional constipation ,lcsh:Q ,business - Abstract
BACKGROUND: Functional gastrointestinal disorders, including functional dyspepsia, irritable bowel syndrome and functional constipation are very common worldwide. OBJECTIVE: This research aims to estimate the prevalence and associated factors involved in functional gastrointestinal disorders in Chinese college and university students using the Rome III criteria. METHODS: A total of 5000 students from Shandong University in China were asked in January-May 2012 to complete questionnaires, including the Rome III questionnaire, hospital anxiety and depression scale, and negative life events scale. RESULTS: Based on the 4638 students who completed the questionnaire, the prevalence of functional dyspepsia, irritable bowel syndrome and functional constipation in college and university students of North China worked out to be 9.25%, 8.34% and 5.45% respectively. They were more frequent in female students. The factors of anxiety (OR 1.07; 95% CI 0.99 to 1.16, P=0.002
- Published
- 2013
32. Immune sculpting of norepinephrine on MHC-I, B7-1, IDO and B7-H1 expression and regulation of proliferation and invasion in pancreatic carcinoma cells
- Author
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Han Liu, Qingyong Ma, Xiangli Chen, Liancai Wang, Keping Xie, and Min Zhang
- Subjects
Time Factors ,animal diseases ,Tumor Physiology ,lcsh:Medicine ,medicine.disease_cause ,Biochemistry ,B7-H1 Antigen ,Metastasis ,Norepinephrine ,Cell Movement ,Molecular Cell Biology ,Basic Cancer Research ,Interferon gamma ,Receptor ,lcsh:Science ,Receptors, Interferon ,Regulation of gene expression ,Multidisciplinary ,biology ,Neurochemistry ,Neurotransmitters ,Receptors, Adrenergic ,Gene Expression Regulation, Neoplastic ,Surgical Oncology ,Oncology ,B7-1 Antigen ,Medicine ,Neurochemicals ,Cell Division ,medicine.drug ,Research Article ,Tumor Immunology ,Immunology ,chemical and pharmacologic phenomena ,Norepinephrine (medication) ,Interferon-gamma ,Immune system ,Cell Line, Tumor ,MHC class I ,medicine ,Humans ,Indoleamine-Pyrrole 2,3,-Dioxygenase ,Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Histocompatibility Antigens Class I ,lcsh:R ,Cancer ,biochemical phenomena, metabolism, and nutrition ,Immunologic Subspecialties ,medicine.disease ,Pancreatic Neoplasms ,Cancer research ,biology.protein ,bacteria ,Surgery ,lcsh:Q ,Carcinogenesis - Abstract
BACKGROUND: The sympathetic neurotransmitter Norepinephrine (NE) contributes to tumorigenesis and cancer progression. This study aims to investigate the role of NE in modulating the immune phenotype and allowing pancreatic carcinoma (PC) cells to escape the immune response. METHODS: Varied concentrations of NE and interferon-gamma (IFN-γ) were administrated to MIA PaCa-2 and BxPC-3 cell lines for 48 hours. Proliferation and invasion were then investigated using an MTT assay and a membrane invasion culture system respectively. MHC-I, B7-1, IDO and B7-H1 expression were measured using real-time quantitative RT-PCR, western blotting and immunocytochemistry. The synergistic and time-dependent effects of NE/IFN-γ were also investigated. Adrenergic antagonists were used to identify the relevant target receptor of NE. RESULTS: The results showed that NE had dose-dependent and time-dependent effects on cell biological processes as well as on the expression of MHC-I, B7-1, IDO and B7-H1. These effects occurred mainly via the β(2)-adrenergic receptor. Long-term NE treatment was able to antagonize some of the effects of IFN-γ (after 2 weeks of treatment), but NE and IFN-γ had significant synergistic stimulatory effects on IDO and B7-H1 expression. The residual effects on biological activities lasted for 2 weeks, while the immunophenotypic changes decreased at early time points after treatment. CONCLUSIONS: NE plays important roles in modulating PC cell biological activities and affecting MHC-I, B7-1, IDO and B7-H1 expression in vitro, mainly via the β2-adrenergic receptor (β2-AR) in a time- and dose-dependent fashion. Only at extended treatment durations could NE affect PC cell progression and immune evasion.
- Published
- 2012
33. Relationship between Neural Alteration and Perineural Invasion in Pancreatic Cancer Patients with Hyperglycemia
- Author
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Han Liu, Feng Li, Liang Han, Erxi Wu, Junhui Li, Qingyong Ma, Fengfei Wang, Wei Li, and Kun Guo
- Subjects
Blood Glucose ,Male ,endocrine system diseases ,Tumor Physiology ,Neoplasms, Nerve Tissue ,Perineural invasion ,lcsh:Medicine ,Gastroenterology ,Biochemistry ,Nerve Growth Factor ,Gastrointestinal Cancers ,Basic Cancer Research ,Tumor Microenvironment ,Histochemistry ,lcsh:Science ,Multidisciplinary ,Cancer Risk Factors ,Peripheral Nervous System Diseases ,Neurochemistry ,Middle Aged ,Immunohistochemistry ,medicine.anatomical_structure ,Oncology ,Cytochemistry ,Medicine ,Female ,Neurochemicals ,Pancreas ,Immunohistochemical Analysis ,Research Article ,Carcinoma, Pancreatic Ductal ,Paraneoplastic Syndromes, Nervous System ,medicine.medical_specialty ,Histology ,Immunology ,Blood sugar ,Gastroenterology and Hepatology ,Pancreatic Cancer ,Population Metrics ,Internal medicine ,Pancreatic cancer ,Diabetes mellitus ,Death Rate ,Gastrointestinal Tumors ,Gastrointestinal Surgery ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Peripheral Nerves ,Biology ,Population Biology ,business.industry ,lcsh:R ,Case-control study ,Cancers and Neoplasms ,medicine.disease ,Pancreatic Neoplasms ,Endocrinology ,Case-Control Studies ,Hyperglycemia ,Immunologic Techniques ,lcsh:Q ,Clinical Immunology ,Surgery ,business - Abstract
BACKGROUND: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. METHODOLOGY/PRINCIPAL FINDINGS: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000). CONCLUSIONS/SIGNIFICANCE: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.
- Published
- 2011
34. A Small Peptide with Potential Ability to Promote Wound Healing
- Author
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Han Liu, Shilong Yang, Jing Tang, Chen Gao, Lixian Mu, Zhiye Zhang, Mingqiang Rong, Ren Lai, Jie Liu, and Qiang Ding
- Subjects
Male ,Proteomics ,MAPK/ERK pathway ,lcsh:Medicine ,Smad Proteins ,Biochemistry ,Epithelium ,Mice ,Cell Movement ,Drug Discovery ,Medicine and Health Sciences ,lcsh:Science ,Myofibroblasts ,Skin ,Multidisciplinary ,integumentary system ,biology ,Kinase ,Immunochemistry ,Granulation tissue ,Cell Differentiation ,Cell migration ,Animal Models ,Cell biology ,medicine.anatomical_structure ,Physical Sciences ,Cytokines ,Signal transduction ,Research Article ,Biotechnology ,Drug Research and Development ,MAP Kinase Signaling System ,Molecular Sequence Data ,Immunology ,Materials Science ,Mouse Models ,Research and Analysis Methods ,Cell Line ,Transforming Growth Factor beta1 ,Biomaterials ,Model Organisms ,medicine ,Animals ,Humans ,Synthetic Peptide ,Amino Acid Sequence ,Interleukin 6 ,Cell Proliferation ,Pharmacology ,Wound Healing ,business.industry ,Macrophages ,lcsh:R ,Biology and Life Sciences ,Transforming growth factor beta ,Fibroblasts ,Small Molecules ,biology.protein ,lcsh:Q ,Peptides ,Wound healing ,business - Abstract
Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β) are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2]) containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1) the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2) the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3) tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6) in murine macrophages and activating mitogen-activated protein kinases (MAPK) signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β), tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.
- Published
- 2014
35. HIV-1 Tat Protein Increases Microglial Outward K+ Current and Resultant Neurotoxic Activity
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Jingdong Zhang, Han Liu, James Keblesh, Jianuo Liu, Peng Xu, Huangui Xiong, and Cory Collins
- Subjects
Small interfering RNA ,Anatomy and Physiology ,Neuroimmunology ,lcsh:Medicine ,Toxicology ,Ion Channels ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,Immunodeficiency Viruses ,Immune Physiology ,Molecular Cell Biology ,Neurobiology of Disease and Regeneration ,lcsh:Science ,Mitogen-Activated Protein Kinase 1 ,Neurons ,0303 health sciences ,Kv1.3 Potassium Channel ,Mitogen-Activated Protein Kinase 3 ,Multidisciplinary ,Microglia ,Up-Regulation ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Biochemistry ,Gene Knockdown Techniques ,Medicine ,Infectious diseases ,tat Gene Products, Human Immunodeficiency Virus ,HIV clinical manifestations ,Cellular Types ,Research Article ,medicine.drug ,Neurotoxicology ,MAP Kinase Signaling System ,Immune Cells ,Neurotoxins ,Immunology ,Viral diseases ,Biology ,Microbiology ,Nitric oxide ,03 medical and health sciences ,Downregulation and upregulation ,Virology ,Potassium Channel Blockers ,medicine ,Animals ,Channel blocker ,030304 developmental biology ,lcsh:R ,Margatoxin ,HIV ,Potassium channel blocker ,Immunologic Subspecialties ,Electrophysiological Phenomena ,Rats ,nervous system ,chemistry ,Apoptosis ,Cellular Neuroscience ,HIV-1 ,Potassium ,Clinical Immunology ,lcsh:Q ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-α, IL-1β, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K(+) current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K(+) channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K(+) channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders.
- Published
- 2013
36. High Glucose Promotes Pancreatic Cancer Cell Proliferation via the Induction of EGF Expression and Transactivation of EGFR
- Author
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Wei Li, Guodong Ma, Shuang Zhou, Qinhong Xu, Liang Han, Erxi Wu, Han Liu, Junhui Li, and Qingyong Ma
- Subjects
Tumor Physiology ,lcsh:Medicine ,Transactivation ,Endocrinology ,0302 clinical medicine ,Epidermal growth factor ,Basic Cancer Research ,lcsh:Science ,Receptor ,0303 health sciences ,Multidisciplinary ,Cancer Risk Factors ,3. Good health ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Research Article ,Transcriptional Activation ,medicine.medical_specialty ,Biology ,Predisposing Conditions and Syndromes ,Pancreatic Cancer ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,Pancreatic cancer ,Internal medicine ,Gastrointestinal Tumors ,Diabetes Mellitus ,medicine ,Humans ,Secretion ,Cell Proliferation ,030304 developmental biology ,Diabetic Endocrinology ,Epidermal Growth Factor ,Cell growth ,lcsh:R ,Cancers and Neoplasms ,Diabetes Mellitus Type 2 ,medicine.disease ,Pancreatic Neoplasms ,Glucose ,Cell culture ,Hyperglycemia ,Cancer research ,lcsh:Q - Abstract
Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.
- Published
- 2011
37. Changes in Culture Expanded Human Amniotic Epithelial Cells: Implications for Potential Therapeutic Applications
- Author
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James Chan, Jing Yang Tee, Yu Han Liu, Charmaine Tan, Gita Pratama, Padma Murthi, Caroline E. Gargett, Vijesh Vaghjiani, and Ursula Manuelpillai
- Subjects
Anatomy and Physiology ,Cellular differentiation ,0302 clinical medicine ,Immune Physiology ,Molecular Cell Biology ,Immune Response ,Cells, Cultured ,0303 health sciences ,Multidisciplinary ,biology ,Stem Cells ,Cell Differentiation ,Flow Cytometry ,Immunohistochemistry ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Amniotic epithelial cells ,cardiovascular system ,Cytokines ,Medicine ,Cellular Types ,Research Article ,Science ,T cell ,Immunology ,Antibodies ,Immunophenotyping ,Immunomodulation ,03 medical and health sciences ,Microscopy, Electron, Transmission ,Antigens, CD ,medicine ,Humans ,Amnion ,Biology ,030304 developmental biology ,CD40 ,Mesenchymal stem cell ,CD44 ,Epithelial Cells ,Molecular Development ,Alkaline Phosphatase ,Culture Media ,Transplantation ,Immune System ,Karyotyping ,Cancer research ,biology.protein ,Clinical Immunology ,CD80 ,Developmental Biology - Abstract
Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell-like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal-stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymal-stromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, α- and β-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-β1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications.
- Published
- 2011
38. Regulation of ErbB2 Receptor Status by the Proteasomal DUB POH1
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Richard Buus, Michael J. Clague, Han Liu, and Sylvie Urbé
- Subjects
Proteasome Endopeptidase Complex ,Receptor Status ,Receptor, ErbB-2 ,Cell Biology/Cell Growth and Division ,lcsh:Medicine ,Down-Regulation ,Biology ,Catalysis ,Cell Biology/Cell Signaling ,Deubiquitinating enzyme ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Epoxomicin ,Cell Biology/Membranes and Sorting ,Ubiquitin ,Downregulation and upregulation ,Humans ,RNA, Small Interfering ,lcsh:Science ,skin and connective tissue diseases ,Receptor ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,PSMD14 ,lcsh:R ,Flow Cytometry ,Molecular biology ,Cell biology ,chemistry ,Proteasome ,030220 oncology & carcinogenesis ,Trans-Activators ,biology.protein ,lcsh:Q ,HeLa Cells ,Research Article - Abstract
Understanding the factors, which control ErbB2 and EGF receptor (EGFR) status in cells is likely to inform future therapeutic approaches directed at these potent oncogenes. ErbB2 is resistant to stimulus-induced degradation and high levels of over-expression can inhibit EGF receptor down-regulation. We now show that for HeLa cells expressing similar numbers of EGFR and ErbB2, EGFR down-regulation is efficient and insensitive to reduction of ErbB2 levels. Deubiquitinating enzymes (DUBs) may extend protein half-lives by rescuing ubiquitinated substrates from proteasomal degradation or from ubiquitin-dependent lysosomal sorting. Using a siRNA library directed at the full complement of human DUBs, we identified POH1 (also known as Rpn11 or PSMD14), a component of the proteasome lid, as a critical DUB controlling the apparent ErbB2 levels. Moreover, the effects on ErbB2 levels can be reproduced by administration of proteasomal inhibitors such as epoxomicin used at maximally tolerated doses. However, the extent of this apparent loss and specificity for ErbB2 versus EGFR could not be accounted for by changes in transcription or degradation rate. Further investigation revealed that cell surface ErbB2 levels are only mildly affected by POH1 knock-down and that the apparent loss can at least partially be explained by the accumulation of higher molecular weight ubiquitinated forms of ErbB2 that are detectable with an extracellular but not intracellular domain directed antibody. We propose that POH1 may deubiquitinate ErbB2 and that this activity is not necessarily coupled to proteasomal degradation.
- Published
- 2009
39. Changes in Culture Expanded Human Amniotic Epithelial Cells: Implications for Potential Therapeutic Applications.
- Author
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Pratama, Gita, Vaghjiani, Vijesh, Jing Yang Tee, Yu Han Liu, James Chan, Charmaine Tan, Murthi, Padma, Gargett, Caroline, and Manuelpillai, Ursula
- Subjects
EPITHELIAL cells ,IMMUNOSUPPRESSIVE agents ,FIBROSIS ,MEDICAL research ,MEDICAL sciences - Abstract
Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell-like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal-stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymalstromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, α- and β-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-β1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
40. Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization.
- Author
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Guo, Haiyang, Shu, Jinghao, Hu, Guangbing, Liu, Bingyang, Li, Jie, Sun, Jinhong, Wang, Xiaobo, Liu, Han, Xiong, Shiyu, Tang, Yong, Yin, Yaolin, and Wang, Xianfei
- Subjects
SQUAMOUS cell carcinoma ,MACROPHAGES ,CALCIUM-binding proteins ,DOWNREGULATION ,GENE expression - Abstract
Reticulocalbin 1 (RCN1) is a calcium-binding protein involved in the regulation of calcium homeostasis in the endoplasmic reticulum. The aim of this study was to explore the clinical value and biological role of RCN1 in esophageal squamous cell carcinoma (ESCC). In addition, we investigated the effect of RCN1 on the polarization of tumor-associated macrophages (TAMs). The GSE53625 dataset from the Gene Expression Omnibus database was used to analyze the expression of RCN1 mRNA and its relationship with clinical value and immune cell infiltration. Immunohistochemistry was used to validate the expression of RCN1 and its correlation with clinicopathological characteristics. Subsequently, transwell and cell scratch assays were conducted to evaluate the migration and invasion abilities of ESCC cells. The expression levels of epithelial–mesenchymal transition (EMT)-related proteins were evaluated by western blot, while apoptosis was detected by flow cytometry and western blot. Additionally, qRT‒PCR was utilized to evaluate the role of RCN1 in macrophage polarization. RCN1 was significantly upregulated in ESCC tissues and was closely associated with lymphatic metastasis and a poor prognosis, and was an independent prognostic factor for ESCC in patients. Knockdown of RCN1 significantly inhibited the migration, invasion, and EMT of ESCC cells, and promoted cell apoptosis. In addition, RCN1 downregulation inhibited M2 polarization. RCN1 is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 inhibits ESCC progression and M2 polarization. RCN1 can serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Research on the synergetic development of producer services and manufacturing in northwest China's inland central cities—A case study of Lanzhou.
- Author
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Gong, Weimin, Zhang, Zhibin, Zhang, Ming, Wang, Jian, and Men, Dan
- Subjects
INNER cities ,FLEXIBLE manufacturing systems ,REGIONAL development ,ECONOMIC development ,RESEARCH & development ,SUBURBS - Abstract
Under the post Ford flexible production organization system, the existence of specialized division of labor has made the forward and backward connections between the producer services as an intermediate input and the manufacturing increasingly close. With the proposal of the "Belt and Road" and the deepening of "The development of the western region in China", the northwest region plays an increasingly important role in China's regional development strategy, and the economic transformation, especially the transformation and upgrading of the manufacturing, and it is crucial to its completion of the strategic mission entrusted by the state. Taking Lanzhou City as a case area, based on the measurement of the cooperative development level of producer services and manufacturing, this paper explores the internal law of the synergetic development of producer services and manufacturing in the northwest inland central city. The study found: The overall synergy development level of producer services and manufacturing in Lanzhou has been significantly improved in the dynamic evolution process, and two industries are in the transition stage from the primary coordinated development to the intermediate coordinated development at present. The spatial layout of producer services and manufacturing in Lanzhou City has certain spatial proximity, and the overall presents a "center-periphery" spatial pattern with the main urban area as the main component. From the perspective of the synergistic development of producer services and manufacturing in Lanzhou, the two industries have initially formed an interactive relationship of two-way promotion at present, but there is a significant asymmetry in the two-way promoting effect of the two industries. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
42. Mental health status of pregnant women during COVID-19 in healthcare centers of Iran: A cross-sectional study.
- Author
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Sayahi, Masoumeh, Nikbina, Maryam, Jahangirimehr, Azam, and Barati, Barat
- Subjects
COVID-19 pandemic ,MATERNAL health ,MENTAL health ,WOMEN'S mental health ,MENTAL illness - Abstract
Background and objective: The COVID-19 pandemic impacted every single aspect of life. In addition to being a public health emergency, the COVID-19 outbreak impacted the mental health of individuals, especially pregnant women. This study aimed to examine the mental health status of pregnant women and also the effect of sociodemographic factors on their mental health status during COVID-19 in healthcare centers of Iran. Methods: This cross-sectional, analytical-descriptive study was conducted among pregnant women referring to healthcare centers in Shoushtar, Iran, in 2021. Multistage cluster sampling was used to select participants. Data were collected using the General Health Questionnaire-28 (GHQ-28). Data were analyzed using SPSS software version 22. The Pearson correlation coefficient was used to examine the association between quantitative variables. A generalized linear model (GLM) was applied to estimate the effect of independent variables on the dependent variable (mental health). Results: A total of 197 participants with a mean ± SD age of 27.85 ± 6.37 years took part in this study. The total mean score of mental health was estimated at 17.47±8.20. The highest mean ± SD score was, respectively, related to social dysfunction (6.63 ± 2.86), anxiety and insomnia (5.28 ± 3.53), and somatic symptoms (4.17 ± 3.27). Mental health disorder was significantly correlated with participants' age (R =.223, P =.00), number of pregnancy (gravida) (R =.272, P =.00), number of births (para) (R = 0.272, P =.00), and number of abortions (R =.172, P =.015). About 80% of pregnant women did not reveal impaired mental health conditions or psychological distress, while 19.3% showed scores that indicate probable mental health conditions. Conclusion: Social dysfunction was the most common mental health problem among pregnant women. It is necessary to pay more attention to the mental health status of pregnant women during a pandemic. Interventions such as practical strategies to promote social support and improve pregnant women's mental health during pregnancy are highly important. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
43. Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma.
- Author
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Hu, Juan, Xie, Cong, Xu, Shangcheng, Pu, Qinli, Liu, Han, Yang, Liping, Wang, Wei, Mao, Longchun, Li, Zhiqiang, and Chen, Weixian
- Subjects
LIVER cells ,HEPATIC fibrosis ,HEPATOCELLULAR carcinoma ,EXOSOMES ,GENE expression ,GENE regulatory networks - Abstract
The mechanism of hepatocellular carcinoma (HCC) development induced by liver fibrosis is obscure. The objective of this study is to establish miRNAs from exosomes associated with liver fibrosis, and to identify potential biomarkers for the prediction of personalized clinical management effectiveness in HCC. Our research focused on miRNAs from exosomes and mRNA from liver fibrosis, which we found in the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) evaluated miRNAs from exosomes associated with liver fibrosis, and Wilcoxon analysis assessed differentially expressed mRNAs (DEGs) across liver fibrosis/normal tissues. Following that, DEGs were assessed through gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, based on the screened targeted genes, including SAMD12 and CADM2, we further elucidated their correlation in HCC patients from the BEST database. The Kaplan-Meier Plotter platform was applied to evaluate the prognostic values of miRNA in HCC. In vitro and vivo experiments validated our findings. Six miRNAs associated with liver fibrosis were evaluated in our investigation. In-depth research presented exosome-derived miR-106a-5p, SAMD12 and CADM2 could exert valuable predictive implications for HCC treatment and illness assessment. Serum miR-106a-5p derived from liver fibrosis was decreased compared with healthy individuals. SAMD12 and CADM2 were diminished in liver cancer cell lines, and their knockdown of them exacerbated the proliferation capacities of liver cells in vitro. Exosome-derived miRNA of liver fibrosis modulated tumorigenesis by targeting SAMD12 and CADM2 in HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Offline events and online hate.
- Author
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Lupu, Yonatan, Sear, Richard, Velásquez, Nicolas, Leahy, Rhys, Restrepo, Nicholas Johnson, Goldberg, Beth, and Johnson, Neil F.
- Subjects
INTERNET content moderation ,SOCIAL media ,HATE speech ,RESEARCH questions ,USER-generated content - Abstract
Online hate speech is a critical and worsening problem, with extremists using social media platforms to radicalize recruits and coordinate offline violent events. While much progress has been made in analyzing online hate speech, no study to date has classified multiple types of hate speech across both mainstream and fringe platforms. We conduct a supervised machine learning analysis of 7 types of online hate speech on 6 interconnected online platforms. We find that offline trigger events, such as protests and elections, are often followed by increases in types of online hate speech that bear seemingly little connection to the underlying event. This occurs on both mainstream and fringe platforms, despite moderation efforts, raising new research questions about the relationship between offline events and online speech, as well as implications for online content moderation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
45. EEG-based vibrotactile evoked brain-computer interfaces system: A systematic review.
- Author
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Huang, Xiuyu, Liang, Shuang, Li, Zengguang, Lai, Cynthia Yuen Yi, and Choi, Kup-Sze
- Subjects
BRAIN-computer interfaces ,SOMATOSENSORY evoked potentials ,MOTOR imagery (Cognition) ,SIGNAL processing ,ELECTROENCEPHALOGRAPHY - Abstract
Recently, a novel electroencephalogram-based brain-computer interface (EVE-BCI) using the vibrotactile stimulus shows great potential for an alternative to other typical motor imagery and visual-based ones. (i) Objective: in this review, crucial aspects of EVE-BCI are extracted from the literature to summarize its key factors, investigate the synthetic evidence of feasibility, and generate recommendations for further studies. (ii) Method: five major databases were searched for relevant publications. Multiple key concepts of EVE-BCI, including data collection, stimulation paradigm, vibrotactile control, EEG signal processing, and reported performance, were derived from each eligible article. We then analyzed these concepts to reach our objective. (iii) Results: (a) seventy-nine studies are eligible for inclusion; (b) EEG data are mostly collected among healthy people with an embodiment of EEG cap in EVE-BCI development; (c) P300 and Steady-State Somatosensory Evoked Potential are the two most popular paradigms; (d) only locations of vibration are heavily explored by previous researchers, while other vibrating factors draw little interest. (e) temporal features of EEG signal are usually extracted and used as the input to linear predictive models for EVE-BCI setup; (f) subject-dependent and offline evaluations remain popular assessments of EVE-BCI performance; (g) accuracies of EVE-BCI are significantly higher than chance levels among different populations. (iv) Significance: we summarize trends and gaps in the current EVE-BCI by identifying influential factors. A comprehensive overview of EVE-BCI can be quickly gained by reading this review. We also provide recommendations for the EVE-BCI design and formulate a checklist for a clear presentation of the research work. They are useful references for researchers to develop a more sophisticated and practical EVE-BCI in future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Application of local fully Convolutional Neural Network combined with YOLO v5 algorithm in small target detection of remote sensing image.
- Author
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Wu, Wentong, Liu, Han, Li, Lingling, Long, Yilin, Wang, Xiaodong, Wang, Zhuohua, Li, Jinglun, and Chang, Yi
- Subjects
CONVOLUTIONAL neural networks ,REMOTE sensing ,ALGORITHMS ,OPTICAL remote sensing ,STORAGE tanks ,TENNIS courts - Abstract
This exploration primarily aims to jointly apply the local FCN (fully convolution neural network) and YOLO-v5 (You Only Look Once-v5) to the detection of small targets in remote sensing images. Firstly, the application effects of R-CNN (Region-Convolutional Neural Network), FRCN (Fast Region-Convolutional Neural Network), and R-FCN (Region-Based-Fully Convolutional Network) in image feature extraction are analyzed after introducing the relevant region proposal network. Secondly, YOLO-v5 algorithm is established on the basis of YOLO algorithm. Besides, the multi-scale anchor mechanism of Faster R-CNN is utilized to improve the detection ability of YOLO-v5 algorithm for small targets in the image in the process of image detection, and realize the high adaptability of YOLO-v5 algorithm to different sizes of images. Finally, the proposed detection method YOLO-v5 algorithm + R-FCN is compared with other algorithms in NWPU VHR-10 data set and Vaihingen data set. The experimental results show that the YOLO-v5 + R-FCN detection method has the optimal detection ability among many algorithms, especially for small targets in remote sensing images such as tennis courts, vehicles, and storage tanks. Moreover, the YOLO-v5 + R-FCN detection method can achieve high recall rates for different types of small targets. Furthermore, due to the deeper network architecture, the YOL v5 + R-FCN detection method has a stronger ability to extract the characteristics of image targets in the detection of remote sensing images. Meanwhile, it can achieve more accurate feature recognition and detection performance for the densely arranged target images in remote sensing images. This research can provide reference for the application of remote sensing technology in China, and promote the application of satellites for target detection tasks in related fields. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. Real-world efficacy of biological agents in moderate-to-severe plaque psoriasis: An analysis of 75 patients in Taiwan.
- Author
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Chen, Yu-Chen, Huang, Yi-Ting, Yang, Chao-Chun, Lai, Edward Chia-Cheng, Liu, Cheng-Han, Hsu, Chao-Kai, Wong, Tak-Wah, Chao, Sheau-Chiou, Sheu, Hamm-Ming, and Lee, Chaw-Ning
- Subjects
ADALIMUMAB ,PSORIASIS ,ASIANS ,ETANERCEPT ,CARDIOVASCULAR diseases - Abstract
Background: Real-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations. Objectives: Our aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan. Methods: We retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan. Results: A total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers. Conclusions: This real world data showed differential efficacy and safety of the four biological agents. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
48. NADPH oxidase 1 is highly expressed in human large and small bowel cancers.
- Author
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Lu, Jiamo, Jiang, Guojian, Wu, Yongzhong, Antony, Smitha, Meitzler, Jennifer L., Juhasz, Agnes, Liu, Han, Roy, Krishnendu, Makhlouf, Hala, Chuaqui, Rodrigo, Butcher, Donna, Konaté, Mariam M., and Doroshow, James H.
- Subjects
ADENOMATOUS polyps ,SMALL intestine cancer ,NADPH oxidase ,LARGE intestine ,MONOCLONAL antibodies ,WESTERN immunoblotting ,COLON cancer - Abstract
To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
49. Prognostic nomogram predicts overall survival in pulmonary large cell neuroendocrine carcinoma.
- Author
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He, Yanqi, Liu, Han, Wang, Shuai, and Chen, Yu
- Subjects
NEUROENDOCRINE cells ,NOMOGRAPHY (Mathematics) ,CARCINOMA ,RISK assessment ,RECEIVER operating characteristic curves - Abstract
Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare and typically aggressive malignancy with poor prognosis. This study developed a nomogram model to predict the overall survival (OS) of patients with LCNEC. Methods: LCNEC patients were identified from the Surveillance, Epidemiology, and End Results database between 2004–2014. Univariate and multivariate Cox regression models were used to determine demographic and clinicopathological features associated with OS. A nomogram model was generated to predict OS and its performance was assessed by Harrell’s concordance index (C-index), calibration plots, and subgroup analysis by risk scores. Results: Of 3048 eligible patients with LCNEC, 2138 were randomly grouped into the training set and 910 into the validation set. Age at diagnosis, gender, tumor stage, N stage, tumor size, and surgery of primary site were independent prognostic factors of OS. C-index values of the nomogram were 0.75 (95% CI, 0.74–0.76) and 0.76 (95% CI, 0.74–0.77) in the training and validation sets, respectively. In both cohorts, the calibration plots showed good concordance between the predicted and observed OS at 3 and 5 years. Kaplan-Meier curves revealed significant differences in OS in patients stratified by nomogram-based risk score, and patients with a higher-than-median risk score had poorer OS. Conclusion: This is the first nomogram developed and validated in a large population-based cohort for predicting OS in patients with LCNEC, and it shows favorable discrimination and calibration abilities. Use of this proposed nomogram has the potential to improve prediction of survival risk, and lead to individualized clinical decisions for LCNEC. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
50. Impact of universal drug susceptibility testing and effective management of multidrug-resistant tuberculosis in Taiwan.
- Author
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Lee, Pin-Hui, Chan, Pei-Chun, Peng, Yen-Ting, Chu, Po-Wei, Wu, Mei-Hua, Jou, Ruwen, Yu, Ming-Chih, Lin, Chou-Jui, Huang, Yi-Wen, Chien, Shun-Tien, Lee, Jen-Jyh, and Chiang, Chen-Yuan
- Subjects
MULTIDRUG-resistant tuberculosis ,BACTERIAL diseases ,TUBERCULOSIS ,TREATMENT effectiveness ,COMMUNICABLE diseases - Abstract
Background: The treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients in the 1990s in Taiwan was not satisfactory. To strengthen programmatic management of drug-resistant tuberculosis (PMDT), Taiwan MDR-TB Consortium (TMTC) was established in 2007. We assess the performance and epidemiologic impact of TMTC. Methodology/Principle findings: We analyzed the trends of proportion of TB cases with drug susceptibility testing, enrollment of MDR-TB patients into TMTC and outcomes of treatment of all MDR-TB patients in Taiwan from 2007–2016. We computed the trends of both incidence and prevalence of MDR-TB from 2007–2016. We assessed the trends of MDR-TB among both new and recurrent TB cases. The proportion of TB cases with drug susceptibility testing results increased from 24.2% in 2007 to 97.9% in 2016. Of the 1,452 MDR-TB patients who were eligible for TMTC care, 1,197 (82.4%) were enrolled in TMTC, in whom 82.9% had treatment success. MDR-TB incidence was 9.0 cases per million in 2007, which declined to 4.6 cases per million in 2016 (p<0.0001). MDR-TB prevalence decreased from 19.4 cases per million in 2007 to 8.4 cases per million in 2016 (p<0.0001). The proportion of MDR-TB among new TB cases decreased from 1.4% in 2010 to 1.0% in 2016 (p = 0.039); and that among recurrent TB cases from 9.0% in 2010 to 1.8% in 2016 (p<0.0001). Conclusions: We concluded that effective PMDT have had a significant impact on the epidemic of drug-resistant TB in Taiwan. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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