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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/30413815/sex-associated-preventive-effects-of-low-dose-aspirin-on-obesity-and-non-alcoholic-fatty-liver-disease-in-mouse-offspring-with-over-nutrition-in-utero
#1
Yi Zhou, Hui Peng, Zhimin Liu, Ke K Zhang, Chelsea Jendrusch, Madeline Drake, Yi Hao, Linglin Xie
Aspirin has been found to diminish hypertriglyceridemia and hyperglycemia in both obese rodents and patients with type 2 diabetes mellitus. We aimed to test whether low-dose aspirin can prevent obesity and the progression of non-alcoholic fatty liver disease (NAFLD) in high-risk subjects. We used offspring mice with maternal over-nutrition as a high-risk model of obesity and NAFLD. The offspring were given postnatal HF-diet and diethylnitrosamine (DEN) to induce obesity and NAFLD, and were treated with or without a low dose of aspirin for 12 weeks (ASP or CTL groups)...
November 9, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30413814/sensory-nerve-supports-epithelial-stem-cell-function-in-healing-of-corneal-epithelium-in-mice-the-role-of-trigeminal-nerve-transient-receptor-potential-vanilloid-4
#2
Yuka Okada, Takayoshi Sumioka, Kana Ichikawa, Hiromi Sano, Atsushi Nambu, Kenta Kobayashi, Kunitoshi Uchida, Yoshiro Suzuki, Makoto Tominaga, Peter Sol Reinach, Syu-Ichi Hirai, James V Jester, Masayasu Miyajima, Kumi Shirai, Hiroki Iwanishi, Winston Whei-Yang Kao, Chia-Yang Liu, Shizuya Saika
In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue...
November 9, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30401959/nondestructive-multiplex-three-dimensional-mapping-of-immune-infiltrates-in-core-needle-biopsy
#3
Steve Seung-Young Lee, Vytautas P Bindokas, Mark W Lingen, Stephen J Kron
Enumeration of tumor-infiltrating lymphocytes (TILs) in H&E stained tissue sections has demonstrated limited value in predicting immune responses to cancer immunotherapy, likely reflecting the diversity of cell types and immune activation states among tumor infiltrates. Multiparametric flow cytometry enables robust phenotypic and functional analysis to distinguish suppression from activation, but tissue dissociation eliminates spatial context. Multiplex methods for immunohistochemistry (IHC) are emerging, but these interrogate only a single tissue section at a time...
November 6, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30401958/membrane-protein-cd9-is-repositioned-and-released-to-enhance-uterine-function
#4
Maki Iwai, Toshio Hamatani, Akihiro Nakamura, Natsuko Kawano, Seiya Kanai, Woojin Kang, Noriko Yoshii, Yasushi Odawara, Mitsutoshi Yamada, Yoshitaka Miyamoto, Takakazu Saito, Hidekazu Saito, Mami Miyado, Akihiro Umezawa, Kenji Miyado, Mamoru Tanaka
Tetraspanin CD9 is essential for sperm-egg fusion and also contributes to uterine repair through microexosome formation. Microexosomes share CD9 with exosomes and are released from eggs and uterine epithelial cells. However, the mechanism for the formation of microexosomes remains unknown. To address this issue, we examined membrane localization and extracellular release of CD9 proteins using uterine epithelial cells and secretions in mice and humans. In mice, CD9 localized predominantly on the basal region of the plasma membrane and relocated to the apical region upon embryo implantation...
November 6, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30401957/live-imaging-of-collagen-deposition-during-experimental-hepatic-schistosomiasis-and-recovery-a-view-on-a-dynamic-process
#5
Marina C G Harvie, Donald P McManus, Hong You, Vanessa A Rivera, Sujeevi K Nawaratna, Kelli P A MacDonald, Grant A Ramm, Geoffrey N Gobert
Hepatic fibrosis is the central cause of chronic clinical pathology resulting from infection by the blood flukes Schistosoma japonicum or S. mansoni. Much has been elucidated regarding the molecular, cellular and immunological responses that correspond to the formation of the granulomatous response to trapped schistosome eggs. A central feature of this Th2 response is the deposition of collagen around the periphery of the granuloma. To date, traditional histology and transcriptional methods have been used to quantify the deposition of collagen and to monitor the formation of the hepatic granuloma during experimental animal models of schistosomiasis...
November 6, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30401956/znf326-promotes-proliferation-of-non-small-cell-lung-cancer-cells-by-regulating-ercc1-expression
#6
Jingjing Wu, Xiupeng Zhang, Qiang Han, Xu Han, Xuezhu Rong, Minghao Wang, Xiaoying Zheng, Enhua Wang
The roles and downstream target genes of the transcription factor ZNF326 in malignant tumors are unclear. Out of 146 lung cancer tissue samples, we found that high expression of ZNF326 in 82 samples was closely related to low differentiation and a high pTNM stage of non-small cell lung cancer (NSCLC) cells. In vitro and in vivo analyses showed that ZNF326 significantly promoted cell cycle progression, colony formation, and proliferation as well as the growth of NSCLC transplanted tumors. Chromatin immunoprecipitation sequencing, dual-luciferase assay, and electrophoretic mobility shift assay confirmed that the C2H2 structure of ZNF326 binds to the -833 to -875 bp region of the ERCC1 promoter to initiate transcriptional activity...
November 6, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30390010/p17-from-hiv-induces-brain-endothelial-cell-angiogenesis-through-egfr-1-mediated-cell-signalling-activation
#7
Donghui Liu, Yasmin Zeinolabediny, Francesca Caccuri, Glenn Ferris, Wen-Hui Fang, Ria Weston, Jerzy Krupinski, Laura Colombo, Mario Salmona, Ruben Corpas, Sara Sarroca, Coral Sanfeliu, Arnaldo Caruso, Baoqiang Guo, Xianwei Zeng, Mark Slevin
HIV-associated neurocognitive disorder in HIV patients substantially reduces their quality of life. We previously showed that the HIV matrix protein, p17 could stimulate lymph-angiogenesis in vitro potentially contributing to lymphoma tumour growth and in addition is associated with vascular activation in neuro-degenerating brain tissue; here, therefore, we have investigated the detailed molecular mechanisms of this action. We performed in vitro cell culture, angiogenesis experiments, phospho-protein microarrays and Western blotting to identify cellular signalling induced by p17 within human brain endothelial cells (HbMEC), and inhibitor studies to block p17-induced vascular growth...
November 2, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30382235/correction-high-mobility-group-box-1-induces-endoplasmic-reticulum-stress-and-activates-hepatic-stellate-cells
#8
Qin He, Yu Fu, Xiangming Ding, Dongxiao Li, Zi Wang, Dean Tian, Wei Yan
Following publication of the original article, the authors noticed some errors in Figs. 1-3. The correct figures can be found in the correction.
October 31, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30353131/t-cell-trafficking-plays-an-essential-role-in-tumor-immunity
#9
Daniel J Aires, Masaru Yoshida, Stephen K Richardson, Mei Bai, Luzheng Liu, Roberto Moreno, Alexander J F Lazar, Jo A Wick, Benjamin E Rich, George Murphy, Richard S Blumberg, Robert C Fuhlbrigge, Thomas S Kupper
Distinct populations of effector memory T cells use different homing receptors to traffic to the skin and gut. Whether tissue-selective T cells are needed for early rejection of a neoplasm growing in these tissues remains an open question. We chose to study an allogeneic tumor model because growth of such a fully mismatched tumor would signify a profound immune deficit. We implanted allogeneic tumor cells in the skin or gut of mice deficient in either α(1,3) fucosyltransferases IV and VII, enzymes critical for generating E-selectin ligands on skin-homing T cells, or β7 integrin, a component of the α4β7 integrin ligand for the mucosal adressin MAdCAM...
October 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30353130/characterization-of-immune-cell-subtypes-in-three-commonly-used-mouse-strains-reveals-gender-and-strain-specific-variations
#10
Jonathan A Hensel, Vinayak Khattar, Reading Ashton, Selvarangan Ponnazhagan
The lack of consensus on bone marrow (BM) and splenic immune cell profiles in preclinical mouse strains complicates comparative analysis across different studies. Although studies have documented relative distribution of immune cells from peripheral blood in mice, similar studies for BM and spleen from naïve mice are lacking. In an effort to establish strain- and gender-specific benchmarks for distribution of various immune cell subtypes in these organs, we performed immunophenotypic analysis of BM cells and splenocytes from both genders of three commonly used murine strains (C57BL/6NCr, 129/SvHsd, and BALB/cAnNCr)...
October 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30353129/bmp9-induced-osteoblastic-differentiation-requires-functional-notch-signaling-in-mesenchymal-stem-cells
#11
Jing Cui, Wenwen Zhang, Enyi Huang, Jia Wang, Junyi Liao, Ruidong Li, Xinyi Yu, Chen Zhao, Zongyue Zeng, Yi Shu, Ruyi Zhang, Shujuan Yan, Jiayan Lei, Chao Yang, Ke Wu, Ying Wu, Shifeng Huang, Xiaojuan Ji, Alexander Li, Cheng Gong, Chengfu Yuan, Linghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Liping An, Bo Zhang, Zhengyu Dai, Yi Shen, Wenping Luo, Xi Wang, Ailong Huang, Hue H Luu, Russell R Reid, Jennifer Moriatis Wolf, Gopal Thinakaran, Michael J Lee, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into multiple lineages including osteoblastic lineage. Osteogenic differentiation of MSCs is a cascade that recapitulates most, if not all, of the molecular events occurring during embryonic skeletal development, which is regulated by numerous signaling pathways including bone morphogenetic proteins (BMPs). Through a comprehensive analysis of the osteogenic activity, we previously demonstrated that BMP9 is the most potent BMP for inducing bone formation from MSCs both in vitro and in vivo...
October 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30353128/overexpression-of-hif-1%C3%AE-contributes-to-melphalan-resistance-in-multiple-myeloma-cells-by-activation-of-erk1-2-akt-and-nf-%C3%AE%C2%BAb
#12
Masanobu Tsubaki, Tomoya Takeda, Yoshika Tomonari, Yu-Ichi Koumoto, Motohiro Imano, Takao Satou, Shozo Nishida
Multiple myeloma (MM) commonly displays multidrug resistance and is associated with poor prognosis. Therefore, it is important to identify the mechanisms by which MM cells develop multidrug resistance. Our previous study showed that multidrug resistance is correlated with overexpression of multidrug resistance protein 1 (MDR1) and Survivin, and downregulation of Bim expression in melphalan-resistant RPMI8226/L-PAM cells; however, the underlying mechanism of multidrug resistance remains unclear. In the present study, we investigated the mechanism of multidrug resistance in melphalan-resistant cells...
October 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30337693/correction-mir-9-5p-mir-124-3p-and-mir-132-3p-regulate-bcl2l11-in-tuberous-sclerosis-complex-angiomyolipoma
#13
Yi Cai, Wenda Wang, Hao Guo, Hanzhong Li, Yu Xiao, Yushi Zhang
Following the publication of this article, the authors noticed an error was in Figure 5C. In the miR-124-3p mimics, the same image was used accidentally for the miR-132-3p mimics. This does not affect the results and conclusions of the article.
October 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30315255/effect-of-sept6-on-the-biological-behavior-of-hepatic-stellate-cells-and-liver-fibrosis-in-rats-and-its-mechanism
#14
Yuhui Fan, Zhipeng Du, Christian J Steib, Qiang Ding, Panpan Lu, Dean Tian, Mei Liu
Hepatic stellate cells (HSCs) are key effectors during the development of liver fibrosis. Septin 6 (SEPT6) is a highly evolutionarily conserved GTP-binding protein that regulates various cell biological behaviors. The expression and function of SEPT6 in HSCs remain unknown. Here we demonstrate that SEPT6 expression is significantly elevated following the activation of primary rat HSCs, the human hepatic stellate cell line LX-2 and the rat hepatic stellate cell line HSC-T6, as well as in both human and rat fibrotic liver tissue...
October 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30310180/multiplexed-high-throughput-measurements-of-cell-contraction-and-endothelial-barrier-function
#15
Ramin Rokhzan, Chandra C Ghosh, Niccole Schaible, Jacob Notbohm, Haruka Yoshie, Allen J Ehrlicher, Sarah J Higgins, Ruyuan Zhang, Hermann Haller, Corey C Hardin, Sascha David, Samir M Parikh, Ramaswamy Krishnan
Vascular leakage, protein exudation, and edema formation are events commonly triggered by inflammation and facilitated by gaps that form between adjacent endothelial cells (ECs) of the vasculature. In such paracellular gap formation, the role of EC contraction is widely implicated, and even therapeutically targeted. However, related measurement approaches remain slow, tedious, and complex to perform. Here, we have developed a multiplexed, high-throughput screen to simultaneously quantify paracellular gaps, EC contractile forces, and to visualize F-actin stress fibers, and VE-cadherin...
October 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30305721/correction-advances-in-development-of-new-tools-for-the-study-of-phosphohistidine
#16
Mehul V Makwana, Richmond Muimo, Richard Fw Jackson
Since the publication of the paper the authors have noted some errors in the text (please read the full correction for more information). These errors have now been corrected in both the HTML and PDF versions of the paper.
October 10, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30291325/the-cofilin-phosphatase-slingshot-homolog-1-restrains-angiotensin-ii-induced-vascular-hypertrophy-and-fibrosis-in-vivo
#17
Holly C Williams, Jing Ma, Daiana Weiss, Bernard Lassègue, Roy L Sutliff, Alejandra San Martín
The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin. The reorganization of the actin cytoskeleton has been implicated in chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel wall components. Therefore, using a novel Ssh1-/- mouse model, we investigated the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and vascular remodeling. We found that loss of SSH1 did not produce overt phenotypic changes and that baseline blood pressures as well as heart rates were comparable between Ssh1+/+ and Ssh1-/- mice...
October 5, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30291324/first-trimester-placental-endothelial-cells-from-pregnancies-with-abnormal-uterine-artery-doppler-are-more-sensitive-to-apoptotic-stimuli
#18
Nicoletta Charolidi, Amanda J Host, Sandra Ashton, Zoe Tryfonos, Karin Leslie, Baskaran Thilaganathan, Judith E Cartwright, Guy S Whitley
Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE...
October 5, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30291323/mitochondrial-pyruvate-carrier-1-functions-as-a-tumor-suppressor-and-predicts-the-prognosis-of-human-renal-cell-carcinoma
#19
Xiao-Peng Tang, Qian Chen, Yi Li, Yan Wang, Hong-Bo Zou, Wen-Juan Fu, Qin Niu, Qian-Guang Pan, Pei Jiang, Xiao-Song Xu, Ke-Qin Zhang, Hong Liu, Xiu-Wu Bian, Xiong-Fei Wu
Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue...
October 5, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30258096/activation-of-brown-adipose-tissue-enhances-the-efficacy-of-caloric-restriction-for-treatment-of-nonalcoholic-steatohepatitis
#20
Laurence Poekes, Justine Gillard, Geoffrey C Farrell, Yves Horsmans, Isabelle A Leclercq
Nonalcoholic steatohepatitis (NASH) is the form of nonalcoholic fatty liver disease that can evolve into cirrhosis. Lifestyle modifications achieving 10% weight loss reverse NASH, but there are no effective approved drug treatments. We previously identified defective adaptive thermogenesis as a factor contributing to metabolic syndrome and hepatic steatosis. We have now tested whether increasing nonshivering thermogenesis can improve preexisting NASH in mice. In high-fat diet-fed foz/foz mice with established NASH, treatment with β3AR agonist restored brown adipose tissue (BAT) function, decreased body weight, improved glucose tolerance, and reduced hepatic lipid content compared to untreated counterparts, but had no impact on liver inflammation or on nonalcoholic fatty liver disease activity score (NAS)...
September 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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