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https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#1
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28868184/multiple-endocrine-neoplasia-2b-differential-increase-in-enteric-nerve-subgroups-in-muscle-and-mucosa
#2
John M Hutson, Pam J Farmer, Cristal J Peck, Chung W Chow, Bridget R Southwell
Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit...
August 15, 2017: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/28859475/identification-of-slirp-as-a-g-quadruplex-binding-protein
#3
Preston Williams, Lin Li, Xiaoli Dong, Yinsheng Wang
The guanine quadruplex (G4) structure in DNA is a secondary structure motif that plays important roles in DNA replication, transcriptional regulation, and maintenance of genomic stability. Here, we employed a quantitative mass spectrometry-based approach to profile the interaction proteomes of three well-defined G4 structures derived from the human telomere and the promoters of cMYC and cKIT genes. We identified SLIRP as a novel G4-interacting protein. We also demonstrated that the protein could bind directly with G4 DNA with Kd values in the low nanomolar range and revealed that the robust binding of the protein toward G4 DNA requires its RRM domain...
September 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28782271/comparison-of-nitrergic-signaling-in-circular-and-longitudinal-smooth-muscle-of-murine-ileum
#4
B Voussen, K Beck, N Mauro, J Keppler, A Friebe
BACKGROUND: Gastrointestinal (GI) motility originates from coordinated movements of circular (CM) and longitudinal (LM) smooth muscle. How the two muscle layers react individually to nitrergic input and how they integrate nitrergic signaling is not thoroughly understood. METHODS: We used immunohistochemistry to unveil expression of NO-sensitive guanylyl cyclase (NO-GC) in the ileum. For functional analyses, we measured tone of ileal CM and spontaneous contractions in both ileal muscle layers from mice lacking NO-GC globally (GCKO) and specifically in smooth muscle cells (SMC-GCKO)...
August 7, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28774773/degradation-of-extracellular-dna-by-dnase1-significantly-reduces-testicular-damage-after-testicular-torsion-in-rats
#5
Michael Boettcher, Dennis Meier, Miguel Jiménez-Alcázar, Georg Eschenburg, Stefan Mietzsch, Deirdre Vincent, Michaela Klinke, Magdalena Trochimiuk, Birgit Appl, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
OBJECTIVE: To examine the effects of DNase1 treatment on testicular damage after TT aim of this study. It has been demonstrated that testicular torsion (TT) induces thrombus formation and that anticoagulation significantly reduces testicular damage after TT. It was hypothesized that these thrombi are dependent on neutrophil extracellular traps (NETs) and thus NETs disintegration would reduce testicular cell damage. METHODS: In 10 rats a sham operation was performed...
July 31, 2017: Urology
https://www.readbyqxmd.com/read/28736634/gastrointestinal-stromal-tumors-gists-point-mutations-matter-in-management-a-review
#6
REVIEW
Peter J Oppelt, Angela C Hirbe, Brian A Van Tine
The therapeutic implications of the genomic alterations seen within the drivers of gastrointestinal stromal tumors (GIST) are among the best understood in all of solid tumors. Sequencing of cKIT and PDGFRα should be considered standard practice for the treatment of GIST patients. In this article, we will review the common mutations and how they are utilized in clinical management. In addition, we will review the rare D842V PDGFRα mutation and the diverse molecular group that lacks a mutation in either cKIT or PDGFRα (wild-type GIST) which are best treated on clinical trial...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28669364/expression-of-markers-for-germ-cells-and-oocytes-in-cow-dermal-fibroblast-treated-with-5-azacytidine-and-cultured-in-differentiation-medium-containing-bmp2-bmp4-or-follicular-fluid
#7
José Jackson do Nascimento Costa, Glaucinete Borges de Souza, Joyla Maria Pires Bernardo, Regislane Pinto Ribeiro, José Renato de Souza Passos, Francisco Taiã Gomes Bezerra, Márcia Viviane Alves Saraiva, José Roberto Viana Silva
This study aims to investigate the effect 5-azacytidine (5-Aza) during induction of pluripotency in bovine fibroblasts and to evaluate the effects of BMP2, BMP4 or follicular fluid in the differentiation of reprogrammed fibroblasts in primordial germ cells and oocytes. It also analysis the mRNA levels for OCT4, NANOG, REX, SOX2, VASA, DAZL, cKIT, SCP3, ZPA and GDF9 after culturing 5-Aza treated fibroblasts in the different tested medium. Dermal fibroblasts were cultured and exposed to 0.5, 1.0 or 2.0 μM of 5-Aza for 18 h, 36 h or 72 h...
June 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#8
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28639308/discovery-of-wt-ret-and-v804m-ret-inhibitors-from-hit-to-lead
#9
Luca Mologni, Martina Dalla Via, Adriana Chilin, Manlio Palumbo, Giovanni Marzaro
Oncogenic activation of RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma, and non-small-cell lung cancer. Currently approved RET inhibitors were not originally designed to be RET inhibitors, and their potency against RET kinase has not been optimized. Hence, novel compounds able to inhibit both wild-type RET ((wt) RET) and its mutants (e.g., (V804M) RET) are needed. Herein we present the development and the preliminary evaluation of a new sub-micromolar (wt) RET/(V804M) RET inhibitor, N-(2-fluoro-5-trifluoromethylphenyl)-N'-{4'-[(2''-benzamido)pyridin-4''-ylamino]phenyl}urea (69), endowed with a 4-anilinopyridine structure, starting from our previously identified 4-anilinopyrimidine hit compound...
June 22, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28638859/a-review-of-the-aetiopathogenesis-and-clinical-and-histopathological-features-of-oral-mucosal-melanoma
#10
REVIEW
Liviu Feller, Razia A G Khammissa, Johan Lemmer
Oral mucosal melanoma is an uncommon, usually heavily melanin-pigmented, but occasionally amelanotic aggressive tumour with a poor prognosis. Despite radical surgery, radiotherapy, or chemotherapy, local recurrence and distant metastasis are frequent. Microscopical examination is essential for diagnosis, and routine histological staining must be supplemented by immunohistochemical studies. The aetiology is unknown, the pathogenesis is poorly understood, and the 5-year survival rate rarely exceeds 30%. In most cases, oral mucosal melanoma arises from epithelial melanocytes in the basal layer of the epithelium and less frequently from immature melanocytes arrested in the lamina propria...
2017: TheScientificWorldJournal
https://www.readbyqxmd.com/read/28593990/loss-of-asxl2-leads-to-myeloid-malignancies-in-mice
#11
Jianping Li, Fuhong He, Peng Zhang, Shi Chen, Hui Shi, Yanling Sun, Ying Guo, Hui Yang, Na Man, Sarah Greenblatt, Zhaomin Li, Zhengyu Guo, Yuan Zhou, Lan Wang, Lluis Morey, Sion Williams, Xi Chen, Qun-Tian Wang, Stephen D Nimer, Peng Yu, Qian-Fei Wang, Mingjiang Xu, Feng-Chun Yang
ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2(-/-) mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2(-/-) and Asxl2(+/-) BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28586009/fli-1-overexpression-in-erythroleukemic-cells-promotes-erythroid-de-differentiation-while-spi-1-pu-1-exerts-the-opposite-effect
#12
Laura M Vecchiarelli-Federico, Tangjingjun Liu, Yao Yao, Yuanyuan Gao, Yanmei Li, You-Jun Li, Yaacov Ben-David
The ETS transcription factors play a critical role during hematopoiesis. In F-MuLV-induced erythroleukemia, Fli‑1 insertional activation producing high expression of this transcription factor required to promote proliferation. How deregulated Fli‑1 expression alters the balance between erythroid differentiation and proliferation is unknown. To address this issue, we exogenously overexpressed Fli‑1 in an erythroleukemic cell harboring activation of spi‑1/PU.1, another ETS gene involved in erythroleukemogenesis...
June 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28570944/oral-feeding-with-polyunsaturated-fatty-acids-fosters-hematopoiesis-and-thrombopoiesis-in-healthy-and-bone-marrow-transplanted-mice
#13
Kedar Limbkar, Ankita Dhenge, Dipesh D Jadhav, Hirekodathakallu V Thulasiram, Vaijayanti Kale, Lalita Limaye
Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set...
May 17, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28541695/discovery-of-potent-selective-stem-cell-factor-receptor-platelet-derived-growth-factor-receptor-alpha-c-kit-pdgfr%C3%AE-dual-inhibitor-for-the-treatment-of-imatinib-resistant-gastrointestinal-stromal-tumors-gists
#14
Yanli Lu, Fei Mao, Xiaokang Li, Xinyu Zheng, Manjiong Wang, Qing Xu, Jin Zhu, Jian Li
Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFRα) kinases play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFRα dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRα. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PDGFRα-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines...
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28495881/dynamic-expression-and-regulatory-mechanism-of-tgf-%C3%AE-signaling-in-chicken-embryonic-stem-cells-differentiating-into-spermatogonial-stem-cells
#15
Qisheng Zuo, Kai Jin, Yani Zhang, Jiuzhou Song, Bichun Li
This study investigated the dynamic expression and regulatory mechanism of TGF-β signaling involved in embryonic stem cells (ESCs) differentiation into male germ cells. Candidate genes involved in TGF-β signaling pathway were screened from RNA-seq, which were further validated by quantitative real time PCR(qRT-PCR). Bone morphogenetic protein 4 (BMP4) was used to induce differentiation of ESCs in vitro Inhibition of TGF-β signaling pathway was reflected by western blot of SMAD 2 and SMAD 5 expression. Differentiating efficiency of germ cells was evaluated by immunofluorescence and fluorescence activated cell sorting(FACS)...
May 11, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28490570/mouse-runx1c-regulates-premegakaryocytic-erythroid-output-and-maintains-survival-of-megakaryocyte-progenitors
#16
Julia E Draper, Patrycja Sroczynska, Hui Sun Leong, Muhammad Z H Fadlullah, Crispin Miller, Valerie Kouskoff, Georges Lacaud
RUNX1 is crucial for the regulation of megakaryocyte specification, maturation, and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B, respectively, which differ solely in their N-terminal amino acid sequences. RUNX1C is the most abundantly expressed isoform in adult hematopoiesis, present in all RUNX1-expressing populations, including the cKit(+) hematopoietic stem and progenitor cells. RUNX1B expression is more restricted, being highly expressed in the megakaryocyte lineage but downregulated during erythropoiesis...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28461508/conditional-knockin-of-dnmt3a-r878h-initiates-acute-myeloid-leukemia-with-mtor-pathway-involvement
#17
Yu-Jun Dai, Yue-Ying Wang, Jin-Yan Huang, Li Xia, Xiao-Dong Shi, Jie Xu, Jing Lu, Xian-Bin Su, Ying Yang, Wei-Na Zhang, Pan-Pan Wang, Song-Fang Wu, Ting Huang, Jian-Qing Mi, Ze-Guang Han, Zhu Chen, Sai-Juan Chen
DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin(-)Sca1(+)cKit(+) cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28419818/local-group-2-innate-lymphoid-cells-promote-corneal-regeneration-after-epithelial-abrasion
#18
Jun Liu, Chengju Xiao, Hanqing Wang, Yunxia Xue, Dong Dong, Cuipei Lin, Fang Song, Ting Fu, Zhaorui Wang, Jiansu Chen, Hongwei Pan, Yangqiu Li, Dongqing Cai, Zhijie Li
Corneal injuries and infections are the leading cause of blindness worldwide. Thus, understanding the mechanisms that control healing of the damaged cornea is critical for the development of new therapies to promptly restore vision. Innate lymphoid cells (ILCs) are a recently identified heterogeneous cell population that has been reported to orchestrate immunity and promote tissue repair in the lungs and skin after injury. However, whether ILCs can modulate the repair process in the cornea remains poorly understood...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28402059/molecular-markers-of-putative-spermatogonial-stem-cells-in-the-domestic-cat
#19
S J Bedford-Guaus, S Kim, L Mulero, J M Vaquero, C Morera, R Adan-Milanès, A Veiga, Á Raya
Spermatogonial stem cells (SSCs) are an important tool for fertility preservation and species conservation. The ability to expand SSCs by in vitro culture is a crucial premise for their use in assisted reproduction. Because SSCs represent a small proportion of the germ cells in the adult testis, culture success is aided by pre-enrichment through sorting techniques based on cell surface-specific markers. Given the importance of the domestic cat as a model for conservation of endangered wild felids, herein we sought to examine culture conditions as well as molecular markers for cat SSCs...
April 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28394335/progenitor-t-cell-differentiation-from-hematopoietic-stem-cells-using-delta-like-4-and-vcam-1
#20
Shreya Shukla, Matthew A Langley, Jastaranpreet Singh, John M Edgar, Mahmood Mohtashami, Juan Carlos Zúñiga-Pflücker, Peter W Zandstra
The molecular and cellular signals that guide T-cell development from hematopoietic stem and progenitor cells (HSPCs) remain poorly understood. The thymic microenvironment integrates multiple niche molecules to potentiate T-cell development in vivo. Recapitulating these signals in vitro in a stromal cell-free system has been challenging and limits T-cell generation technologies. Here, we describe a fully defined engineered in vitro niche capable of guiding T-lineage development from HSPCs. Synergistic interactions between Notch ligand Delta-like 4 and vascular cell adhesion molecule 1 (VCAM-1) were leveraged to enhance Notch signaling and progenitor T-cell differentiation rates...
May 2017: Nature Methods
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