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https://www.readbyqxmd.com/read/28646487/immunotoxic-effects-of-thymus-in-mice-following-exposure-to-nanoparticulate-tio2
#1
Fashui Hong, Yaoming Zhou, Yingjun Zhou, Ling Wang
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg(-1) body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices...
June 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#2
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28645305/high-expression-of-collagen-triple-helix-repeat-containing-1-cthrc1-facilitates-progression-of-oesophageal-squamous-cell-carcinoma-through-mapk-mek-erk-fra-1-activation
#3
Chunni Wang, Zitong Li, Fei Shao, Xueying Yang, Xiaoli Feng, Susheng Shi, Yibo Gao, Jie He
BACKGROUND: Oesophageal cancer is one of the most common malignancies worldwide,and oesophageal squamous cell carcinoma (ESCC) is the predominant histological type both globally and in China. Collagen triple helix repeat containing 1 (CTHRC1) has been found to be upregulated in ESCC. However, its role in tumourigenesis and progression of ESCC remains unclear. METHODS: Using our previous ESCC mRNA profiling data, we screened upregulated genes to identify those required for proliferation...
June 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28645294/3-5-4-trihydroxy-6-7-3-trimethoxyflavone-protects-against-beta-amyloid-induced-neurotoxicity-through-antioxidative-activity-and-interference-with-cell-signaling
#4
Alona Telerman, Rivka Ofir, Yoel Kashman, Anat Elmann
BACKGROUND: Alzheimer's disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidative stress are major contributors to Alzheimer's disease, therefore, protecting neuronal cells against Aβ-induced toxicity and oxidative stress might form an effective approach for treatment of this disease. 3,5,4'-trihydroxy-6,7,3'-trimethoxyflavone (TTF) is a flavonoid we have purified from the plant Achillea fragrantissima; and the present study examined, for the first time, the effects of this compound on Aβ-toxicity to neuronal cells...
June 23, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28644965/3-4-dihydroxybenzalacetone-attenuates-lipopolysaccharide-induced-inflammation-in-acute-lung-injury-via-down-regulation-of-mmp-2-and-mmp-9-activities-through-suppressing-ros-mediated-mapk-and-pi3k-akt-signaling-pathways
#5
Wei Chao, Jeng-Shyan Deng, Shyh-Shyun Huang, Pei-Ying Li, Yu-Chia Liang, Guan-Jhong Huang
3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)-induced acute lung injuries in mice. Pretreatment with DBL significantly improved LPS-induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and the activities of matrix metalloproteinase (MMP)-2 and -9 in the bronchoalveolar lavage fluid...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28644955/turning-on-proteasomes
#6
Jan Henrik Krahn, Farnusch Kaschani, Markus Kaiser
While proteasome inhibitors are now well-established research tools and chemotherapeutics, proteasome activators are much less explored. In this issue of Cell Chemical Biology, in a study from the groups of Berkers and Ovaa (Leestemaker et al., 2017), a chemical screen was used to identify a p38 MAPK inhibitor as a proteasome activator. This compound furthermore enhanced clearance of protein aggregates, thereby implicating alternative chemotherapeutic options for treating neurodegenerative diseases.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28644741/ras-signaling-regulates-stem-cells-and-amelogenesis-in-the-mouse-incisor
#7
X Zheng, A F Goodwin, H Tian, A H Jheon, O D Klein
The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28644441/micrornas-143-and-145-induce-epithelial-to-mesenchymal-transition-and-modulate-the-expression-of-junction-proteins
#8
Lidia Avalle, Danny Incarnato, Aurora Savino, Marta Gai, Francesca Marino, Sara Pensa, Isaia Barbieri, Michael B Stadler, Paolo Provero, Salvatore Oliviero, Valeria Poli
Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma's metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644145/colorectal-carcinoma-with-osseous-metaplasia
#9
Xibo Liu, Jinghong Xu, Lirong Chen
Osseous metaplasia (OM) is rarely observed in colorectal cancer (incidence < 0.4% in rectal cancer), where it has a non-specific clinical presentation and unknown pathogenesis. Here, we report three cases of colorectal carcinoma with OM and propose a new hypothesis. All three patients (two males and one female) were Chinese and had different sites of colorectal carcinoma with OM: rectum, sigmoid colon, and appendix. The pathologic diagnoses were serrated adenocarcinoma; moderately to poorly differentiated adenocarcinoma with micropapillary carcinoma and cribriform comedo-type adenocarcinoma; and mucinous adenocarcinoma, respectively...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643937/proinflammatory-effects-and-mechanisms-of-calprotectin-on-human-gingival-fibroblasts
#10
H Gao, J Hou, H Meng, X Zhang, Y Zheng, L Peng
BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643916/a-review-of-craniofacial-and-dental-findings-of-the-rasopathies
#11
REVIEW
H Cao, N Alrejaye, O D Klein, A F Goodwin, S Oberoi
OBJECTIVES: The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML or LEOPARD syndrome), neurofibromatosis type 1 (NF1), Costello syndrome (CS), cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type 1-like syndrome (NFLS or Legius syndrome) and capillary malformation-arteriovenous malformation syndrome (CM-AVM)...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643892/calcitriol-exerts-an-anti-tumor-effect-in-osteosarcoma-by-inducing-the-endoplasmic-reticulum-er-stress-response
#12
Takatsune Shimizu, Walied A Kamel, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Akihiro Muto, Hideyuki Saya
Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of FDA-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS)...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#13
Nadjib Hammoudi, Dongtak Jeong, Rajvir Singh, Ahmed Farhat, Michel Komajda, Eric Mayoux, Roger Hajjar, Djamel Lebeche
PURPOSE: Cardiovascular (CV) diseases in type 2 diabetes (T2DM) represent an enormous burden with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as a new antidiabetic class that improves glucose control, as well as body weight and blood pressure with no increased risk of hypoglycemia. The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated...
June 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28642873/serum-amyloid-a-induces-a-vascular-smooth-muscle-cell-phenotype-switch-through-the-p38-mapk-signaling-pathway
#14
Xincai Zhang, Jinqin Chen, Shixun Wang
Atherosclerosis is an important pathological condition which is accompanied by a vascular smooth muscle cell (VSMC) phenotype switch toward a synthetic phenotype. As an acute-phase protein, Serum Amyloid A (SAA) is thought to have a close relationship to atherosclerosis development. However, no study has investigated the direct effect of SAA on the VSMC phenotype switch, as well as the underlying mechanisms. The purpose of our study was to explore the effect of SAA on the VSMC phenotype switch and the potential mechanisms involved...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642802/perk-dependent-defective-tcr-mediated-activation-of-cd4-t-cells-in-end-stage-renal-disease-patients
#15
Ling Huang, Nicolle H R Litjens, Nynke M Kannegieter, Mariska Klepper, Carla C Baan, Michiel G H Betjes
BACKGROUND: Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extracellular signals into an intracellular response. T cell receptor (TCR)-induced phosphorylation of ERK (pERK) may show an age-associated decline, which can be reversed by inhibiting dual specific phosphatase (DUSP) 6, a cytoplasmic phosphatase with substrate specificity to dephosphorylate pERK...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#16
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642614/ultrasound-mediated-piezoelectric-differentiation-of-neuron-like-pc12-cells-on-pvdf-membranes
#17
Marcus Hoop, Xiang-Zhong Chen, Aldo Ferrari, Fajer Mushtaq, Gagik Ghazaryan, Theo Tervoort, Dimos Poulikakos, Bradley Nelson, Salvador Pané
Electrical and/or electromechanical stimulation has been shown to play a significant role in regenerating various functionalities in soft tissues, such as tendons, muscles, and nerves. In this work, we investigate the piezoelectric polymer polyvinylidene fluoride (PVDF) as a potential substrate for wireless neuronal differentiation. Piezoelectric PVDF enables generation of electrical charges on its surface upon acoustic stimulation, inducing neuritogenesis of PC12 cells. We demonstrate that the effect of pure piezoelectric stimulation on neurite generation in PC12 cells is comparable to the ones induced by neuronal growth factor (NGF)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642475/a-novel-bzip-protein-gsb1-is-required-for-oxidative-stress-response-mating-and-virulence-in-the-human-pathogen-cryptococcus-neoformans
#18
Seon Ah Cheon, Eun Jung Thak, Yong-Sun Bahn, Hyun Ah Kang
The human pathogen Cryptococcus neoformans, which causes life-threatening meningoencephalitis in immunocompromised individuals, normally faces diverse stresses in the human host. Here, we report that a novel, basic, leucine-zipper (bZIP) protein, designated Gsb1 (general stress-related bZIP protein 1), is required for its normal growth and diverse stress responses. C. neoformans gsb1Δ mutants grew slowly even under non-stressed conditions and showed increased sensitivity to high or low temperatures. The hypersensitivity of gsb1Δ to oxidative and nitrosative stresses was reversed by addition of a ROS scavenger...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642281/utility-of-genomic-analysis-in-circulating-tumor-dna-from-patients-with-carcinoma-of-unknown-primary
#19
Shumei Kato, Nithya Krishnamurthy, Kimberly C Banks, Pradip De, Kirstin Williams, Casey Williams, Brian Leyland-Jones, Scott M Lippman, Richard B Lanman, Razelle Kurzrock
Carcinoma of unknown primary (CUP) is a rare and difficult-to-treat malignancy, the management of which might be improved by the identification of actionable driver mutations. We interrogated interrogated 54-70 genes in 442 patients with CUP using targeted clinical-grade, next-generation sequencing (NGS) of circulating tumor DNA (ctDNA). Overall, 80% of patients exhibited ctDNA alterations; 66%, ≥ 1 characterized alteration(s) excluding variants of unknown significance. TP53-associated genes were most commonly altered (37...
June 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#20
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
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