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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/30626892/central-cholinergic-neuronal-degeneration-promotes-the-development-of-postoperative-cognitive-dysfunction
#1
Huan Xu, Lingke Chen, Xiao Zhang, Xuliang Jiang, Weitian Tian, Weifeng Yu, Xiangrui Wang, Jie Tian, Diansan Su
Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality. However, its mechanism remains poorly understood. We hypothesized that central cholinergic neuronal degeneration facilitates the development of POCD. The impact of anesthesia/surgery (appendectomy) on learning and memory and the levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and choline transporter (CHT) in adult and aged mice were measured...
January 9, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30626891/traf6-neddylation-drives-inflammatory-arthritis-by-increasing-nf-%C3%AE%C2%BAb-activation
#2
Kewei Liu, Kaizhe Chen, Qian Zhang, Lianfang Zhang, Yufei Yan, Changjun Guo, Jin Qi, Kai Yang, Fei Wang, Ping Huang, Lei Guo, Lianfu Deng, Changwei Li
Neddylation is a process similar to ubiquitination, and is critical in various inflammatory diseases; however, its importance in the pathogenesis of inflammatory arthritis is not well understood. Here, we investigated the role of neddylation in collagen-induced arthritis (CIA) and its clinical relevance. We showed that neddylation-related genes, including NEDD8 and CULLIN-1, were significantly upregulated in inflamed arthritic synovia. Functionally, neddylation activation was crucial for synovitis of CIA, as the inhibition of neddylation by MLN4924 significantly suppressed synovial cell proliferation and inflammatory responses...
January 9, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30573872/spectrum-of-tau-pathologies-in-huntington-s-disease
#3
Swikrity Upadhyay Baskota, Oscar L Lopez, J Timothy Greenamyre, Julia Kofler
Huntington's disease (HD) is an autosomal dominant disorder caused by a trinucleotide expansion in the huntingtin gene. Recently, a new role for tau has been implicated in the pathogenesis of HD, whereas others have argued that postmortem tau pathology findings are attributable to concurrent Alzheimer's disease pathology. The frequency of other well-defined common age-related tau pathologies in HD has not been examined in detail. In this single center, retrospective analysis, we screened seven cases of Huntington's disease (5 females, 2 males, age at death: 47-73 years) for neuronal and glial tau pathology using phospho-tau immunohistochemistry...
December 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30573871/luminex-based-quantification-of-alzheimer-s-disease-neuropathologic-change-in-formalin-fixed-post-mortem-human-brain-tissue
#4
C Dirk Keene, Angela M Wilson, Mitchell D Kilgore, Lauren T Bruner, Nadia O Postupna, Martin Darvas
The vast majority of archived research and clinical pathological specimens are stored in the form of formalin fixed, paraffin-embedded (FFPE) tissues, but, unlike fresh frozen tissue samples, highly quantitative measures in FFPE tissues are limited to immunohistochemical and immunofluorescence thresholding image analysis studies, cell counting, and ordinal ranking systems. This poses a significant obstacle for clinical investigations that aim to correlate diagnostic markers of neurodegenerative diseases like Alzheimer's disease (AD) with parameters like age, gender, drug exposures, genotype, disease stage, co-morbidities, or environmental factors...
December 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30573870/rapid-diagnosis-of-idh1-mutated-gliomas-by-2-hg-detection-with-gas-chromatography-mass-spectrometry
#5
Hao Xu, Yu-Kun Xia, Chun-Jie Li, Jin-Ye Zhang, Ying Liu, Wei Yi, Zhi-Yong Qin, Liang Chen, Zhi-Feng Shi, Kai Quan, Zi-Xiao Yang, Kun-Liang Guan, Yue Xiong, Ho-Keung Ng, Dan Ye, Wei Hua, Ying Mao
The metabolic genes encoding isocitrate dehydrogenase (IDH1, 2) are frequently mutated in gliomas. Mutation of IDH defines a distinct subtype of glioma and predicts therapeutic response. IDH mutation has a remarkable neomorphic activity of converting α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. PCR-sequencing (n = 220), immunohistochemistry staining (IHC, n = 220), and gas chromatography mass spectrometry (GC-MS, n = 87) were applied to identify IDH mutation in gliomas, and the sensitivity and specificity of these strategies were compared...
December 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30568176/lysyl-oxidase-enzymes-mediate-tgf-%C3%AE-1-induced-fibrotic-phenotypes-in-human-skin-like-tissues
#6
Mengqi Huang, Zhiyi Liu, Lauren Baugh, Jason DeFuria, Anna Maione, Avi Smith, Olga Kashpur, Lauren D Black Iii, Irene Georgakoudi, Michael L Whitfield, Jonathan Garlick
Cutaneous fibrosis is a common complication seen in mixed connective tissue diseases. It often occurs as a result of TGF-β-induced deposition of excessive amounts of collagen in the skin. Lysyl oxidases (LOXs), a family of extracellular matrix (ECM)-modifying enzymes responsible for collagen cross-linking, are known to be increased in dermal fibroblasts from patients with fibrotic diseases, denoting a possible role of LOXs in fibrosis. To directly study this, we have developed two bioengineered, in vitro skin-like models: human skin equivalents (hSEs), and self-assembled stromal tissues (SASs) that contain either normal or systemic sclerosis (SSc; scleroderma) patient-derived fibroblasts...
December 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30552364/mir-608-and-mir-4513-significantly-contribute-to-the-prognosis-of-lung-adenocarcinoma-treated-with-egfr-tkis
#7
Nasha Zhang, Yankang Li, Yan Zheng, Li Zhang, Yuan Pan, Jinming Yu, Ming Yang
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptors (EGFR) significantly prolong the survival of lung adenocarcinoma patients with sensitizing EGFR mutations. Unfortunately, 10-30% patients do not show objective responses to EGFR-TKIs, and undergo rapid disease progression during the EGFR-TKIs therapy. Single nucleotide polymorphisms (SNPs) in mature microRNA (miRNA) sequences may influence target site interactions and modulate downstream pathways, such as the EGFR pathway. For this reason, we hypothesized that miRNA SNPs may impact the prognosis of lung adenocarcinoma patients after EGFR-TKI treatment...
December 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30542068/cytoplasmic-expression-of-epithelial-cell-transforming-sequence-2-in-lung-adenocarcinoma-and-its-implications-for-malignant-progression
#8
Zeinab Kosibaty, Yoshihiko Murata, Yuko Minami, Tomoko Dai, Junko Kano, Ryota Matsuoka, Noriyuki Nakano, Masayuki Noguchi
Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is predominantly localized in the nucleus of non-transformed cells and functions to regulate cytokinesis. ECT2 is also localized in the cytoplasm of cancer cells. Aberrant cytoplasmic expression of ECT2 is thought to drive tumor growth and invasion. In this study, we investigated the cytoplasmic expression of ECT2 and its prognostic and biological significance in lung adenocarcinoma. Western blotting of cellular fractions from the nucleus and cytoplasm was performed to determine the subcellular localization of ECT2 in lung adenocarcinoma cell lines...
December 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30542067/microrna-amplification-and-detection-technologies-opportunities-and-challenges-for-point-of-care-diagnostics
#9
REVIEW
Vivek Priy Dave, Tien Anh Ngo, Anna-Karin Pernestig, Diana Tilevik, Krishna Kant, Trieu Nguyen, Anders Wolff, Dang Duong Bang
The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC...
December 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30487596/the-role-of-ca-2-in-acid-sensing-ion-channel-1a-mediated-chondrocyte-pyroptosis-in-rat-adjuvant-arthritis
#10
Xiaoshan Wu, Guiling Ren, Renpeng Zhou, Jinfang Ge, Fei-Hu Chen
Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1β/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis. The decrease in the pH of joint fluid is a main pathogenic feature of RA and leads to excessive apoptosis in chondrocytes...
November 28, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30487595/the-subcellular-location-of-cyclin-b1-and-cdc25-associated-with-the-formation-of-polyploid-giant-cancer-cells-and-their-clinicopathological-significance
#11
Fei Fei, Jie Qu, Kai Liu, Chunyuan Li, Xinlu Wang, Yuwei Li, Shiwu Zhang
Polyploid giant cancer cells (PGCCs) are key contributors to cancer heterogeneity, and the formation of PGCCs is associated with changes in the expression of cell-cycle-related proteins. This study investigated the intracellular localization and expression level of multiple cell-cycle-related proteins in PGCCs derived from BT-549 and HEY cells. In addition, the formation of PGCCs and the clinicopathological significance of cell-cycle-related proteins in human breast and ovarian cancer were examined. The expression levels of cell-cycle-related proteins, including cyclin B1, CDC25B, CDC25C, and other cell cycle phosphoproteins, including Chk2, and Aurora-A kinase, were determined using immunostaining and western blotting both in vitro and in vivo...
November 28, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30470772/abrogation-of-transforming-growth-factor-%C3%AE-induced-tissue-fibrosis-in-mice-with-a-global-genetic-deletion-of-nox4
#12
Peter J Wermuth, Fabian A Mendoza, Sergio A Jimenez
Excessive connective tissue deposition in skin and various internal organs is characteristic of systemic sclerosis (SSc). The profibrotic growth factor TGF-β plays a crucial role in SSc pathogenesis. The expression of NADPH oxidase 4 (NOX4), a critical mediator of oxidative stress, is potently stimulated by TGF-β. Here, we evaluated the effect of NOX4 on the development of TGF-β-induced tissue fibrosis. C57BL6/J control mice and Nox4 knockout mice were implanted subcutaneously with osmotic pumps containing either saline or 2...
November 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30451982/heparin-binding-epidermal-growth-factor-hb-egf-drives-emt-in-patients-with-copd-implications-for-disease-pathogenesis-and-novel-therapies
#13
REVIEW
Mathew Suji Eapen, Pawan Sharma, Isobel E Thompson, Wenying Lu, Stephen Myers, Philip M Hansbro, Sukhwinder Singh Sohal
Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation...
November 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30446717/mef2b-is-a-member-of-the-bcl6-gene-transcriptional-complex-and-induces-its-expression-in-diffuse-large-b-cell-lymphoma-of-the-germinal-center-b-cell-like-type
#14
Siraj M El Jamal, Zakaria Grada, Mohamed H El Dinali, He Zhou, Sofie-Yasmin Hassan, Ali G Saad, Bradley Gibson, Xinchun Zhou, Hend A Abulsayen, Helmi S Khadra, Jessica Friedman, Hosam Shalaby, Abida Kadi, Mosaad Megahed, Myesa Emberesh, Julie Teruya-Feldstein, Adolfo Firpo-Betancourt, Youssef Haikel, Mostafa Fraig, Mohamed Hassan
Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK...
November 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30429507/klf2-regulates-osteoblast-differentiation-by-targeting-of-runx2
#15
Zhenyang Hou, Zhen Wang, Yunxia Tao, Jiaxiang Bai, Binqing Yu, Jining Shen, Houyi Sun, Long Xiao, Yaozeng Xu, Jun Zhou, Zhirong Wang, Dechun Geng
Osteoblast differentiation plays a critical role in bone formation and maintaining balance in bone remodeling. Runt-related transcription factor 2 (Runx2) is a central transcription factor regulating osteoblast differentiation and promoting bone mineralization. Until now, the molecular regulatory basis and especially the gene regulatory network of osteogenic differentiation have been unclear. Krüppel-like factor 2 (KLF2) is a zinc finger structure and DNA-binding transcription factor. The current study aimed to investigate the physiological function of KLF2 in osteoblast differentiation...
November 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30420690/o-glcnacylation-of-gli-transcription-factors-in-hyperglycemic-conditions-augments-hedgehog-activity
#16
Shamik Das, Sarah K Bailey, Brandon J Metge, Ann Hanna, Dominique C Hinshaw, Mateus Mota, Andres Forero-Torres, John C Chatham, Rajeev S Samant, Lalita A Shevde
Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis. Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway. In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation...
November 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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
#17
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
#18
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
#19
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
#20
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
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