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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/29789685/s100a4-protects-mice-from-high-fat-diet-induced-obesity-and-inflammation
#1
Shasha Hou, Ying Jiao, Qi Yuan, Junfeng Zhai, Tian Tian, Kaiji Sun, Zhinan Chen, Zhenlong Wu, Jinhua Zhang
As a member from S100 calcium-binding protein family, S100A4 is ubiquitous and elevated in tumor progression and metastasis, but its role in regulating obesity has not been well characterized. In this study, we showed that S100A4 was mainly expressed by stromal cells in adipose tissue and the S100A4 level in adipose tissue was decreased after high-fat diet (HFD). S100A4 deficient mice exhibited aggravated symptoms of obesity and suppressed insulin signaling after 12 weeks of HFD. Aggravated obesity in S100A4 deficient mice were found to be positively correlated with higher inflammatory status of the liver...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29789684/dipeptidyl-peptidase-iv-dpp-4-inhibition-alleviates-pulmonary-arterial-remodeling-in-experimental-pulmonary-hypertension
#2
Jian Xu, Jingjing Wang, Mengyu He, Honghao Han, Weiping Xie, Hong Wang, Hui Kong
Dipeptidyl peptidase IV (DPP-4) is well known for its role in glucose homeostasis, and DPP-4 inhibitor (DPP-4i) exhibits multiple actions in cardiovascular diseases. However, the effect of DPP-4i on pulmonary hypertension (PH) remains unclear. Therefore, this study aims to investigate the effect of DPP-4i on pulmonary arterial remodeling in rats with PH and the potential underlying mechanisms. Our results show that DPP-4 was expressed in epithelial cells, endothelial cells, smooth muscle cells, and inflammatory cells in lung...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29789683/bmp-2-restoration-aids-in-recovery-from-liver-fibrosis-by-attenuating-tgf-%C3%AE-1-signaling
#3
Yueh-Hua Chung, Ying-Hsien Huang, Tien-Huei Chu, Chun-Lin Chen, Pey-Ru Lin, Shih-Chung Huang, Deng-Chyang Wu, Chao-Cheng Huang, Tsung-Hui Hu, Ying-Hsien Kao, Ming-Hong Tai
Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29785051/hyaluronan-negatively-regulates-vascular-calcification-involving-bmp2-signaling
#4
Yonglun Kong, Qingchun Liang, Yanting Chen, Pingzhen Yang, Xiaoyu Liu, Yining Li, Siyuan Feng, Ji Wu, Wantao Liu, Jingyi Tang, Huimin Yu, Jing-Song Ou, Lihe Lu, Jianyun Yan
Vascular calcification is a highly regulated biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Hyaluronan (HA), a major structural component of the extracellular matrix in cartilage, has been shown to inhibit osteoblast differentiation. However, whether HA affects osteogenic differentiation and calcification of VSMCs remains unclear. In the present study, we used in vitro and ex vivo models of vascular calcification to investigate the role of HA in vascular calcification...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29785050/the-tumor-suppressor-dlc1-inhibits-cancer-progression-and-oncogenic-autophagy-in-hepatocellular-carcinoma
#5
Hui-Ta Wu, Cheng-Rong Xie, Jie Lv, He-Qiang Qi, Fei Wang, Sheng Zhang, Qin-Liang Fang, Fu-Qiang Wang, Yu-Yan Lu, Zhen-Yu Yin
Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29785049/involvement-of-inhibitor-kappa-b-kinase-2-ikk2-in-the-regulation-of-vascular-tone
#6
Youngin Kwon, Soo-Kyoung Choi, Seonhee Byeon, Young-Ho Lee
Inhibitor kappa B kinase 2 (IKK2) plays an essential role in the activation of nuclear factor kappa B (NF-kB). Recently, it has been suggested that IKK2 acts as a myosin light chain kinase (MLCK) and contributes to vasoconstriction in mouse aorta. However, the underlying mechanisms are still unknown. Therefore, we investigated whether IKK2 acts as a MLCK or regulates the activity of myosin light chain phosphatase (MLCP). Pressure myograph was used to measure vascular tone in rat mesenteric arteries. Immunofluorescence staining was performed to identify phosphorylation levels of MLC (ser19), MYPT1 (thr853 and thr696) and CPI-17 (thr38)...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29769698/mutation-screening-using-formalin-fixed-paraffin-embedded-tissues-a-stratified-approach-according-to-dna-quality
#7
Francesco Cucco, Alexandra Clipson, Hannah Kennedy, Joe Sneath Thompson, Ming Wang, Sharon Barrans, Moniek van Hoppe, Eguzkine Ochoa Ruiz, Josh Caddy, Debbie Hamid, Thomas Cummin, Cathy Burton, Andrew J Davies, Peter Johnson, Ming-Qing Du
DNA samples from formalin-fixed paraffin-embedded tissues are highly degraded with variable quality, and this imposes a big challenge for targeted sequencing due to false positives, largely caused by PCR errors and cytosine deamination. To eliminate false positives, a common practice is to validate the detected variants by Sanger sequencing or perform targeted sequencing in duplicate. Technically, PCR errors could be removed by molecular barcoding of template DNA prior to amplification as in the HaloPlexHS design...
May 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29769697/establishment-of-a-nasopharyngeal-carcinoma-cell-line-capable-of-undergoing-lytic-epstein-barr-virus-reactivation
#8
Yim Ling Yip, Weitao Lin, Wen Deng, Lin Jia, Kwok Wai Lo, Pierre Busson, Benjamin Vérillaud, Xuefeng Liu, Chi Man Tsang, Maria Li Lung, Sai Wah Tsao
Epstein-Barr virus (EBV) infects more than 90% of the adult human population. Undifferentiated nasopharyngeal carcinoma (NPC) is common in Southeast Asia, with a particularly high incidence among southern Chinese. The EBV genome can be detected in practically all cancer cells in undifferentiated NPC. The role of EBV in pathogenesis of undifferentiated NPC remains elusive. NPC cell lines are known to be difficult to establish in culture. The EBV+ve NPC cell lines, even if established in culture, rapidly lost their EBV episomes upon prolonged propagation...
May 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29765110/mast-cells-contribute-to-enterovirus-71-infection-induced-pulmonary-edema-in-neonatal-mice
#9
Yuefei Jin, Chao Zhang, Hui Wang, Guangyuan Zhou, Xiangpeng Wang, Rongguang Zhang, Shuaiyin Chen, Jingchao Ren, Lu Chen, Dejian Dang, Peng Zhang, Yuanlin Xi, Weidong Wu, Weiguo Zhang, Guangcai Duan
Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs...
May 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29765109/microvascular-fractal-dimension-predicts-prognosis-and-response-to-chemotherapy-in-glioblastoma-an-automatic-image-analysis-study
#10
Cong Chen, Zhi-Cheng He, Yu Shi, Wenchao Zhou, Xia Zhang, Hua-Liang Xiao, Hai-Bo Wu, Xiao-Hong Yao, Wan-Chun Luo, You-Hong Cui, Shideng Bao, Hsiang-Fu Kung, Xiu-Wu Bian, Yi-Fang Ping
The microvascular profile has been included in the WHO glioma grading criteria. Nevertheless, microvessels in gliomas of the same WHO grade, e.g., WHO IV glioblastoma (GBM), exhibit heterogeneous and polymorphic morphology, whose possible clinical significance remains to be determined. In this study, we employed a fractal geometry-derived parameter, microvascular fractal dimension (mvFD), to quantify microvessel complexity and developed a home-made macro in Image J software to automatically determine mvFD from the microvessel-stained immunohistochemical images of GBM...
May 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29748615/specific-targeting-of-point-mutations-in-egfr-l858r-positive-lung-cancer-by-crispr-cas9
#11
Alvin Ho-Kwan Cheung, Chit Chow, Jinglin Zhang, Yuhang Zhou, Tingting Huang, Kayla Ching-Kei Ng, Terry Cho-Tsun Or, Yoyo Yao Yao, Yujuan Dong, Jackie Mei-Wah Fung, Lei Xiong, Aden Ka-Yin Chan, Wai-Ming Raymond Lung, Wei Kang, Ka-Fai To
Cancer cells are defined genetically by the mutations they harbor, commonly single nucleotide substitutions. Therapeutic approaches which specifically target cancer cells by recognizing these defining genetic aberrations are expected to exhibit minimal side-effects. However, current protein-based targeted therapy is greatly limited by the range of genes that can be targeted, as well as by acquired resistance. We hypothesized that a therapeutic oligonucleotide-based strategy may address this need of specific cancer targeting...
May 10, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29748614/nanovesicle-mediated-delivery-of-anticancer-agents-effectively-induced-cell-death-and-regressed-intrahepatic-tumors-in-athymic-mice
#12
Joseph George, Irene K Yan, Tushar Patel
Hepatocellular carcinoma is highly resistant to chemotherapy. Here we evaluated the use and efficacy of milk-derived nanovesicles (MNV) as an approach to improve delivery of anticancer agents into HCC cells and intrahepatic tumors. We developed a protocol for isolation of MNVs from skim milk using ultracentrifugation, and characterized using nanoparticle tracking analysis (NTA) and electron microscopy. MNVs were loaded with doxorubicin (dox-MNV) or miR221 antisense oligonucleotides (anti-miR221-MNV), and further evaluated using spectrophotometry, NTA, and zeta potential measurements...
May 10, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29743728/spatially-correlated-phenotyping-reveals-k5-positive-luminal-progenitor-cells-and-p63-k5-14-positive-stem-cell-like-cells-in-human-breast-epithelium
#13
Werner Boecker, Laura van Horn, Göran Stenman, Christine Stürken, Udo Schumacher, Thomas Loening, Lukas Liesenfeld, Eberhard Korsching, Doreen Gläser, Katharina Tiemann, Igor Buchwalow
Understanding the mechanisms regulating human mammary epithelium requires knowledge of the cellular constituents of this tissue. Different and partially contradictory definitions and concepts describing the cellular hierarchy of mammary epithelium have been proposed, including our studies of keratins K5 and/or K14 as markers of progenitor cells. Furthermore, we and others have suggested that the p53 homolog p63 is a marker of human breast epithelial stem cells. In this investigation, we expand our previous studies by testing whether immunohistochemical staining with monospecific anti-keratin antibodies in combination with an antibody against the stem cell marker p63 might help refine the different morphologic phenotypes in normal breast epithelium...
May 9, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29588491/identification-of-inhibitors-regulating-cell-proliferation-and-fus-ddit3-expression-in-myxoid-liposarcoma-using-combined-dna-mrna-and-protein-analyses
#14
David Svec, Soheila Dolatabadi, Christer Thomsen, Nicole Cordes, Mark Shannon, Paul Fitzpatrick, Göran Landberg, Pierre Åman, Anders Ståhlberg
FUS-DDIT3 belongs to the FET (FUS, EWSR1, and TAF15) family of fusion oncogenes, which collectively are considered to be key players in tumor development. Even though over 90% of all myxoid liposarcomas (MLS) have a FUS-DDIT3 gene fusion, there is limited understanding of the signaling pathways that regulate its expression. In order to study cell proliferation and FUS-DDIT3 regulation at mRNA and protein levels, we first developed a direct cell lysis approach that allows DNA, mRNA, and protein to be analyzed in the same sample using quantitative PCR, reverse transcription quantitative qPCR and proximity ligation assay, respectively...
March 27, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29581580/reduced-expression-of-the-h19-long-non-coding-rna-inhibits-pancreatic-cancer-metastasis
#15
Hisashi Yoshimura, Yoko Matsuda, Masami Yamamoto, Masaki Michishita, Kimimasa Takahashi, Norihiko Sasaki, Naoshi Ishikawa, Junko Aida, Kaiyo Takubo, Tomio Arai, Toshiyuki Ishiwata
H19 is an oncofetal RNA expressed in the developing embryo as well as in bladder, breast, gastric, pancreatic, hepatocellular, and prostate cancers. Recent studies have shown that H19 enhances cancer invasion and metastasis; however, its roles in cancer remain controversial. In the current study, H19 exhibited the second largest increase (82.4-fold) and represented the only non-protein coding gene among 11 genes identified that were elevated over 10-fold in lung-metastasis-derived pancreatic cancer cells compared with their parental cells using a mouse metastatic model...
March 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29581579/restoration-of-e-cadherin-by-ppbica-protects-against-cisplatin-induced-acute-kidney-injury-by-attenuating-inflammation-and-programmed-cell-death
#16
Li Gao, Ming-Ming Liu, Hong-Mei Zang, Qiu-Ying Ma, Qin Yang, Ling Jiang, Gui-Ling Ren, Hai-Di Li, Wei-Feng Wu, Jia-Nan Wang, Biao Wei, Xue-Qi Liu, Cheng Jiang, Cheng Huang, Jun Li, Xiao-Ming Meng
E-cadherin is a major component of tubular adherent proteins that maintain intercellular contacts and cell polarity in epithelial tissue. It is involved in pathological processes of renal cell carcinoma and fibrotic diseases via epithelial-mesenchymal transition. Although studies have shown E-cadherin is significantly downregulated in acute kidney injury (AKI), its function in AKI is unknown. Here, we evaluated cell damage and inflammation in cisplatin-stimulated tubular epithelial cell lines after disrupting E-cadherin and restoring it with PPBICA, a small molecule identified by high-throughput screening...
March 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29581578/heparin-binding-epidermal-growth-factor-contributes-to-copd-disease-severity-by-modulating-airway-fibrosis-and-pulmonary-epithelial-mesenchymal-transition
#17
Tianwen Lai, Yanyu Li, Min Chen, Guihai Pan, Xiaoxia Wen, Zongjiong Mai, Yalian Yuan, Yingying Lv, Quanchao Lv, Ruilian Cen, Huajuan Yi, Mengling Wen, Dongming Li, Bin Wu, Dong Wu, Chao Cao
Although airway fibrosis and epithelial-mesenchymal transition (EMT) contribute to airway remodeling in chronic obstructive pulmonary disease (COPD), the mechanisms underlying their development have not been fully elucidated. In the present study, we aimed to assess heparin-binding epidermal growth factor (HB-EGF) expression in the airways of patients with COPD and to elucidate the possible role of HB-EGF in the pathology of COPD. Sputum and lung tissue HB-EGF expression was evaluated in control subjects and patients with COPD...
March 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29572498/a-single-high-fat-meal-provokes-pathological-erythrocyte-remodeling-and-increases-myeloperoxidase-levels-implications-for-acute-coronary-syndrome
#18
Tyler W Benson, Neal L Weintraub, Ha Won Kim, Nichole Seigler, Sanjiv Kumar, Jonathan Pye, Tetsuo Horimatsu, Rod Pellenberg, David W Stepp, Rudolf Lucas, Vladimir Y Bogdanov, Sheldon E Litwin, Julia E Brittain, Ryan A Harris
High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial infarction in patients with atherosclerosis, but the mechanisms are poorly understood. Erythrocytes (red blood cells, RBCs) intimately interact with inflammatory cells and blood vessels and play a complex role in regulating vascular function. Chronic high-fat feeding in mice induces pathological RBC remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction. However, whether acute HFM can induce RBC remodeling in humans is unknown...
March 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29545598/ubiquitin-specific-protease-11-serves-as-a-marker-of-poor-prognosis-and-promotes-metastasis-in-hepatocellular-carcinoma
#19
Sheng Zhang, Chengrong Xie, Honghe Li, Kang Zhang, Jie Li, Xiaomin Wang, Zhenyu Yin
Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo. A large body of evidence supports a link between UPS11 and tumorigenesis. However, the clinical significance and biological function of USP11 in hepatocellular carcinoma (HCC) remains unclear. Here, USP11 expression was assessed by immunohistochemistry in a pilot series of 71 HCC clinical samples, and the association between USP11 expression and clinicopathological features and overall survival time was analyzed...
March 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29540862/proteomic-signature-of-circulating-extracellular-vesicles-in-dilated-cardiomyopathy
#20
Santiago Roura, Ana Gámez-Valero, Josep Lupón, Carolina Gálvez-Montón, Francesc E Borràs, Antoni Bayes-Genis
Dilated cardiomyopathy (DCM) remains a major cause of heart failure and carries a poor prognosis despite important advances in recent years. Better disease characterization using novel molecular techniques is needed to refine its progression. This study explored the proteomic signature of plasma-derived extracellular vesicles (EVs) obtained from DCM patients and healthy controls using size-exclusion chromatography (SEC). EV-enriched fractions were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS)...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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