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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/30237457/poldip2-knockdown-inhibits-vascular-smooth-muscle-proliferation-and-neointima-formation-by-regulating-the-expression-of-pcna-and-p21
#1
Srinivasa Raju Datla, Lula L Hilenski, Bonnie Seidel-Rogol, Anna E Dikalova, Mark Harousseau, Lili Punkova, Giji Joseph, W Robert Taylor, Bernard Lassègue, Kathy K Griendling
Polymerase delta-interacting protein 2 (Poldip2) is a multi-functional protein with numerous roles in the vasculature, including the regulation of cell apoptosis and migration, as well as extracellular matrix deposition; however, its role in VSMC proliferation and neointimal formation is unknown. In this study, we investigated the role of Poldip2 in intraluminal wire-injury induced neointima formation and proliferation of vascular smooth muscle cells in vitro and in vivo. Poldip2 expression was observed in the intima and media of human atherosclerotic arteries, where it colocalized with proliferating cell nuclear antigen (PCNA)...
September 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206314/western-type-diet-differentially-modulates-osteoblast-osteoclast-and-lipoblast-differentiation-and-activation-in-a-background-of-apoe-deficiency
#2
Nicholaos I Papachristou, Harry C Blair, Eleni S Kalyvioti, Spyros A Syggelos, Eleni A Karavia, Vassilios Kontogeorgakos, Dragana Nikitovic, George N Tzanakakis, Kyriakos E Kypreos, Dionysios J Papachristou
During the past few years, considerable evidence has uncovered a strong relationship between fat and bone metabolism. Consequently, alterations in plasma lipid metabolic pathways strongly affect bone mass and quality. We recently showed that the deficiency of apolipoprotein A-1 (APOA1), a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, results in reduced bone mass in C57BL/6 mice. It is documented that apolipoprotein E (APOE), a lipoprotein know for its atheroprotective functions and de novo biogenesis of HDL-C, is associated with the accumulation of fat in the liver and other organs and regulates bone mass in mice...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206313/application-of-ex-vivo-spheroid-model-system-for-the-analysis-of-senescence-and-senolytic-phenotypes-in-uterine-leiomyoma
#3
Jia Xie, Xiuhua Xu, Ping Yin, Yinuo Li, Haiyang Guo, Stacy Kujawa, Debabrata Chakravarti, Serdar Bulun, J Julie Kim, Jian-Jun Wei
Cellular senecence is an important biologic endpoint. Naturally occuring (aging) senescence is common in uterine leiomyoma (ULM). AKT is one of major pathways in promoting ULM growth and survival. Inactivation of AKT by MK2206 in ULM resulted in stress-induced senescence in vitro. Study of the senescent phenotypes and molecular changes in ULM may greatly facilitate the understanding of the tumor biology and potential clinical therapy for this common disease associated with high morbidity. To study senescence in a model system that closely resembles primary ULM in vivo, we applied an ex vivo model of three-dimensional (3D) spheroid culture system which maintained the molecular and cellular characteristics of primary ULM and matched myometrium as seen in vivo...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206312/the-stat3-inhibitor-s3i-201-suppresses-fibrogenesis-and-angiogenesis-in-liver-fibrosis
#4
Zhuo Wang, Jia'an Li, Wen'ang Xiao, Jiafu Long, Hongmin Zhang
Liver fibrosis is a common pathological response to chronic hepatic injury. STAT3 is actively involved in the fibrogenesis and angiogenesis seen in liver fibrosis. S3I-201 (NSC 74859) is a chemical inhibitor of STAT3 activity, which blocks the dimerization of STAT3, STAT3-DNA binding and transcription activity. This study evaluated the effects of S3I-201 against liver fibrosis. S3I-201 inhibited the proliferation, migration, and actin filament formation in primary human hepatic stellate cells (HSCs), as well as the expression of α-SMA, collagen I and TIMP1 in both primary HSC and in a CCl4 -induced fibrosis mouse model...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206311/trends-in-the-characteristics-of-human-functional-genomic-data-on-the-gene-expression-omnibus-2001-2017
#5
Daniel D Liu, Lanjing Zhang
The gene expression omnibus (GEO) is the world's largest public repository of functional genomic data. Despite its broad use in secondary genomic analyses, the temporal trends in the characteristics of genomic data on GEO, including experimental procedures, geographic origin, funder(s), and related disease, have not been examined. We identified 75,376 Series deposited to the GEO during 2001-2017 and built a database of all human genomic data (39,076 Series, 51.8% of all Series). Using the associated publications, we obtained funding information and identified the related disease area...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206310/vitamin-d-protects-human-melanocytes-against-oxidative-damage-by-activation-of-wnt-%C3%AE-catenin-signaling
#6
Luyan Tang, Wei Fang, Jinran Lin, Jian Li, Wenyu Wu, Jinhua Xu
Vitamin D analogs have been widely utilized for the treatment of vitiligo, but the molecular mechanism underlying their pharmacological effects (especially their antioxidant properties) has not yet been investigated. We evaluated the relationship between serum vitamin D level and oxidative damage severity in vitiligo patients, and investigated the molecular mechanism of vitamin D in protecting melanocytes against oxidative stress. Serum levels of 25-hydroxyvitamin D and malondialdehyde (MDA) were first measured in patients...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30206309/enediyne-activated-egfr-targeted-human-%C3%AE-defensin-1-has-therapeutic-efficacy-against-non-small-cell-lung-carcinoma
#7
Wen-Juan Liu, Kun-Li Zhu, Jian Xu, Jia-Lin Wang, Hui Zhu
Human β-defensins contain an oncolytic motif that binds to tumor cell membranes and mediate permeabilization, rapid induction of cytolysis, and apoptosis. Previous studies have indicated that a fragment of the mature human β-defensin-1 (HBD1) peptide (DF) has antitumor properties. While targeted drug treatments using fusion proteins have been shown to increase drug efficacy, this phenomenon has not been studied for this defensin. Thus, in this study, we designed and prepared a fusion protein containing this HBD1 fragment and an epidermal growth factor receptor (EGFR)-targeting oligopeptide (Ec) as well as lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, which consists of an apoprotein (LDP) and a highly active enediyne (AE)...
September 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30181553/ki67-reproducibility-using-digital-image-analysis-an-inter-platform-and-inter-operator-study
#8
Balazs Acs, Vasiliki Pelekanou, Yalai Bai, Sandra Martinez-Morilla, Maria Toki, Samuel C Y Leung, Torsten O Nielsen, David L Rimm
Ki67 expression has been a valuable prognostic variable in breast cancer, but has not seen broad adoption due to lack of standardization between institutions. Automation could represent a solution. Here we investigate the reproducibility of Ki67 measurement between three image analysis platforms with supervised classifiers performed by the same operator, by multiple operators, and finally we compare their accuracy in prognostic potential. Two breast cancer patient cohorts were used for this study. The standardization was done with the 30 cases of ER+ breast cancer that were used in phase 3 of International Ki67 in Breast Cancer Working Group initiatives where blocks were centrally cut and stained for Ki67...
September 4, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30181552/the-oncogenic-rna-binding-protein-srsf1-regulates-lig1-in-non-small-cell-lung-cancer
#9
Elena Martínez-Terroba, Teresa Ezponda, Cristina Bértolo, Cristina Sainz, Ana Remírez, Jackeline Agorreta, Irati Garmendia, Carmen Behrens, Ruben Pio, Ignacio I Wistuba, Luis M Montuenga, María J Pajares
In recent years, the relevance of RNA metabolism has been increasingly recognized in a variety of diseases. Modifications in the levels of RNA-binding proteins elicit changes in the expression of cancer-related genes. Here we evaluate whether SRSF1 regulates the expression of DNA repair genes, and whether this regulation has a relevant role in lung carcinogenesis. An in silico analysis was performed to evaluate the association between the expression of SRSF1 and DNA repair genes. In vitro functional analyses were conducted in SRSF1 or DNA ligase 1 (LIG1)-downregulated non-small cell lung cancer (NSCLC) cell lines...
September 4, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30177831/an-immunohistochemical-approach-to-detect-oncogenic-ctnnb1-mutations-in-primary-neoplastic-tissues
#10
Aytekin Akyol, Günes Güner, Havva Solak Özşeker, Aynur Işık, Özge Atcı, Sarp Uzun, Emine Atayar, Fatih Ozaltin, Gökhan Gedikoğlu, Cenk Sökmensüer, Eric R Fearon
The Wnt/β-catenin signaling pathway is dysregulated in different types of neoplasms including colorectal cancer (CRC). Aberrant activation of this signaling pathway is a key early event in the development of colorectal neoplasms, and is mainly caused by loss of function mutations in Adenomatous Polyposis Coli (APC), and less frequently by β-catenin stabilization mutations via missense or interstitial genomic deletions in CTNNB1. In this study, we have defined an immunohistochemical algorithm to dissect Wnt pathway alterations in formalin-fixed and paraffin-embedded neoplastic tissues...
September 3, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30171204/endogenous-and-exogenous-galectin-3-promote-the-adhesion-of-tumor-cells-with-low-expression-of-muc1-to-huvecs-through-upregulation-of-n-cadherin-and-cd44
#11
Zhanqi Cao, Zhaojun Hao, Ming Xin, Lugang Yu, Lei Wang, Ying Zhang, Xinke Zhang, Xiuli Guo
Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration...
August 31, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30143751/ursodeoxycholate-inhibits-mast-cell-activation-and-reverses-biliary-injury-and-fibrosis-in-mdr2-mice-and-human-primary-sclerosing-cholangitis
#12
Fanyin Meng, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Hannah Jones, Taronish Madeka, Allen Karstens, Kevin Chappell, Gianfranco Alpini, Amelia Sybenga, Pietro Invernizzi, Francesca Bernuzzi, Sharon DeMorrow, Heather Francis
Ursodeoxycholic acid (UDCA) is used to treat biliary disorders; and, bile acids alter mast cell (MC) histamine release. MCs infiltrate Mdr2-/- mice liver (model of primary sclerosing cholangitis (PSC)). MC-derived histamine increases inflammation, hepatic stellate cell (HSC) activation and fibrosis. The objective was to determine the effects of UDCA treatment on MC infiltration, biliary damage, inflammation and fibrosis in Mdr2-/- mice and human PSC. Wild-type and Mdr2-/- mice were fed bile acid control diet or UDCA (0...
August 24, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089858/iso-alpha-acids-from-hops-humulus-lupulus-inhibit-hepatic-steatosis-inflammation-and-fibrosis
#13
Abdo Mahli, Andreas Koch, Kim Fresse, Tobias Schiergens, Wolfgang Erwin Thasler, Christina Schönberger, Ina Bergheim, Anja Bosserhoff, Claus Hellerbrand
Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. Iso-alpha acids (IAAs), hop-derived bitter compounds in beer, have been shown to beneficially affect different components of the metabolic syndrome such as insulin resistance and dyslipidemia. However, IAAs have not yet been studied in the context of chronic liver disease. Here we analyzed the effect of IAA on the pathogenesis of NAFLD. Once, we applied IAA to mice in combination with a NAFLD-inducing Western-type diet (WTD), and observed that IAA significantly inhibited WTD-induced body weight gain, glucose intolerance, and hepatic steatosis...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089857/the-direct-binding-of-collagen-xvii-and-collagen-iv-is-disrupted-by-pemphigoid-autoantibodies
#14
Mayumi Kamaguchi, Hiroaki Iwata, Wataru Nishie, Ellen Toyonaga, Hideyuki Ujiie, Ken Natsuga, Yoshimasa Kitagawa, Hiroshi Shimizu
The basement membrane zone (BMZ) is framed by hemidesmosomes and extracellular matrix (ECM) including collagen IV (COL4). Hemidesmosomes are multiprotein complexes that include collagen XVII (COL17). BMZ proteins can be targeted in autoimmune subepidermal blistering diseases, e.g., pemphigoid targeting COL17. The blistering mechanisms in pemphigoid have not been fully elucidated, especially in mucous membrane pemphigoid (MMP), which mainly affects the mucosa. In this study, we showed that oral lesions in pemphigoid may be attributed to the inhibition of protein-protein interactions by autoantibodies...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089856/the-effect-of-mesenchymal-stem-cells-secretome-on-lung-cancer-progression-is-contingent-on-their-origin-primary-or-metastatic-niche
#15
Oshrat Attar-Schneider, Liat Drucker, Maya Gottfried
The fatality of non-small-cell lung cancer (NSCLC) and the role of the cancer microenvironment in its resistance to therapy are long recognized. Accumulating data allocate a significant role for mesenchymal stem cells (MSCs) in the malignant environment. Previously, we have demonstrated that MSCs from NSCLC metastatic bone marrow (BM) niche deleteriously affected NSCLC cells. Here, we have decided to examine the effect of MSCs from the primary niche of the lung (healthy or adjacent to tumor) on NSCLC phenotype...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089855/wild-type-p53-modulated-autophagy-and-autophagic-fibroblast-apoptosis-inhibit-hypertrophic-scar-formation
#16
Jihong Shi, Houan Xiao, Jun Li, Julei Zhang, Yan Li, Jian Zhang, Xujie Wang, Xiaozhi Bai, Ke Tao, Dahai Hu, Hao Guan
Hypertrophic scarring is a serious fibrotic skin disease, and the abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies its pathogenesis. Our previous studies have demonstrated that the dysregulation of autophagy in HSFs is associated with fibrosis. However, knowledge regarding the regulation of HS fibrosis by p53-modulated autophagy is limited. Here, we investigated the effect of p53-modulated autophagy on HS fibrosis. The overexpression of wtp53 (Adp53) promoted autophagic capacity and inhibited collagen and α-SMA expression in HSFs...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089854/genome-wide-dna-methylation-encodes-cardiac-transcriptional-reprogramming-in-human-ischemic-heart-failure
#17
Mark E Pepin, Chae-Myeong Ha, David K Crossman, Silvio H Litovsky, Sooryanarayana Varambally, Joseph P Barchue, Salpy V Pamboukian, Nikolaos A Diakos, Stavros G Drakos, Steven M Pogwizd, Adam R Wende
Ischemic cardiomyopathy (ICM) is the clinical endpoint of coronary heart disease and a leading cause of heart failure. Despite growing demands to develop personalized approaches to treat ICM, progress is limited by inadequate knowledge of its pathogenesis. Since epigenetics has been implicated in the development of other chronic diseases, the current study was designed to determine whether transcriptional and/or epigenetic changes are sufficient to distinguish ICM from other etiologies of heart failure. Specifically, we hypothesize that genome-wide DNA methylation encodes transcriptional reprogramming in ICM...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089853/remifentanil-upregulates-hepatic-il-18-binding-protein-il-18bp-expression-through-transcriptional-control
#18
Xiaohua Liu, Hao Yang, Yan Liu, Yingfu Jiao, Liqun Yang, Xiangrui Wang, Weifeng Yu, Diansan Su, Jie Tian
Interleukin (IL)-18 plays an important role in liver ischemia/reperfusion (I/R) injury. We have previously demonstrated that remifentanil protects against liver I/R injury by upregulating the hepatic expression of IL-18-binding protein (IL-18BP), a natural IL-18 inhibitor. The current study was performed to further clarify the effects of remifentanil on IL-18BP expression in the liver as well as investigate the underlying mechanisms. In Sprague-Dawley (SD) rats, we demonstrated that remifentanil significantly increased the expression of IL-18BP in normal rat liver tissue over a 24-h time period with maximal expression at 24 h after treatment...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089852/phf20l1-antagonizes-sox2-proteolysis-triggered-by-the-mll1-wdr5-complexes
#19
Qianqian Wang, Min Yu, Yue Ma, Xiaoming Zhang, Hui Zhang, Shuiming Li, Rongfeng Lan, Fei Lu
Transcriptional factor SOX2 regulates stem cell pluripotency, cell differentiation and tumorigenesis. As a key factor, the expression of SOX2 is tightly regulated at transcriptional and post-translational levels. However, the underlying mechanism of SOX2 protein stability remains to be elucidated. Here we show that the histone-lysine N-methyltransferase MLL1/WDR5 complexes physically interact with SOX2 and evoke SOX2 proteolysis, possibly through methylation on a potential site lysine 42 (K42). Small interfering RNA (siRNA)-mediated gene silencing of the components of the MLL1/WDR5 complexes WDR5, MLL1, RBBP5, and ASH2L lead to the accumulation of SOX2, while forced expression of WDR5 promotes SOX2 ubiquitination and proteolysis...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30089851/interferon-%C3%AE-mediates-the-protective-effects-of-soluble-receptor-for-advanced-glycation-end-product-in-myocardial-ischemia-reperfusion
#20
Mengqiu Dang, Xiangjun Zeng, Buxing Chen, Hongxia Wang, Huihua Li, Fenghe Du, Caixia Guo
The ubiquitin-proteasome system (UPS) is essential for protein degradation and plays critical roles in myocardial ischemia/reperfusion (MI/R) injuries. Previous studies have demonstrated that the soluble receptor for advanced glycation end-product (sRAGE) inhibited MI/R-induced apoptosis by upregulating proteasome subunits. However, the mechanism remains unknown. An MI/R model was established by left anterior descending (LAD) coronary artery ligation in mice. Recombinant sRAGE protein or saline was injected intramyocardially with or without neutralizing interferon-γ (IFN-γ) antibody injected intraperitoneally before ligation...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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