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https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#1
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28720696/persistent-organic-pollutants-impair-insulin-secretory-function-of-pancreatic-beta-cells-human-and-in-vitro-evidence
#2
Yu-Mi Lee, Chae-Myeong Ha, Se-A Kim, Themis Thoudam, Young-Ran Yoon, Dae-Jung Kim, Hyeon-Chang Kim, Hyo-Bang Moon, Sungmi Park, In-Kyu Lee, Duk-Hee Lee
Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor of type 2 diabetes (T2D). We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 nondiabetic adults. Mathematical-model-based insulin secretion indices were estimated using a 2-hour 7-sample oral glucose tolerance test. Insulin secretion by INS1E beta-cells was measured after 48-hour treatment with 3 OCPs or a PCB mixture...
July 18, 2017: Diabetes
https://www.readbyqxmd.com/read/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#3
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28711495/evidence-for-constitutive-bone-morphogenetic-protein-2-secretion-by-m1-macrophages-constitutive-auto-paracrine-osteogenic-signaling-by-bmp-2-in-m1-macrophages
#4
Prabhatchandra R Dube, Lutz Birnbaumer, Guillermo Vazquez
Mechanisms mediating vascular calcification recapitulate osteogenic processes encompassing bone formation and imply participation of bone related proteins such as bone morphogenetic protein-2 (BMP-2). Macrophages are amongst the cells that contribute to vascular ossification by releasing cytokines that induce an osteogenic program in vascular smooth muscle cells, and also by becoming themselves osteoclast-like cells. In inflammatory vascular disease, the macrophage population in the vascular wall is diverse, with the M1 or inflammatory, and the M2 or anti-inflammatory macrophage types being dominant...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710139/hepatic-but-not-extra-hepatic-insulin-clearance-is-lower-in-african-american-than-in-european-american-women
#5
Francesca Piccinini, David C Polidori, Barbara A Gower, Richard N Bergman
African Americans (AA) tend to have higher plasma insulin concentrations than European Americans (EA); the increased insulin concentrations have been attributed to increased secretion and/or decreased insulin clearance by liver or other tissues. This work aims to characterize the contributions of hepatic versus extra-hepatic insulin degradation related to ethnic differences between AA versus EA. Using a recently-developed mathematical model employing insulin and C-peptide measurements from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT), we estimated hepatic vs...
July 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28708056/metarhizium-robertsii-produces-indole-3-acetic-acid-which-promotes-root-growth-in-arabidopsis-and-enhances-virulence-to-insects
#6
Xinggang Liao, Brian Lovett, Weiguo Fang, Raymond J St Leger
The plant root colonizing insect-pathogenic fungus Metarhizium robertsii has been shown to boost plant growth, but little is known about the responsible mechanisms. Here we show that M. robertsii promotes lateral root growth and root hair development of Arabidopsis seedlings in part through an auxin [indole-3-acetic acid (IAA)]-dependent mechanism. M. robertsii, or its auxin-containing culture filtrate promoted root proliferation, activated IAA-regulated gene expression and rescued the root hair defect of the IAA-deficient rhd6 Arabidopsis mutant...
July 15, 2017: Microbiology
https://www.readbyqxmd.com/read/28703796/p75-ntr-antagonists-attenuate-photoreceptor-cell-loss-in-murine-models-of-retinitis-pigmentosa
#7
María Platón-Corchado, Pablo F Barcelona, Sean Jmaeff, Miguel Marchena, Alberto M Hernández-Pinto, Catalina Hernández-Sánchez, H Uri Saragovi, Enrique J de la Rosa
ProNGF signaling through p75(NTR) has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at a rate dependent on the genetic mutation. There are more than 300 mutations causing RP, and this is a challenge to therapy. Our study was designed to explore a common mechanism for p75(NTR) in the progression of RP, and assess its potential value as a therapeutic target. The proNGF/p75(NTR) system is present in the dystrophic retina of the rd10 RP mouse model...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28701885/panax-ginseng-total-protein-promotes-proliferation-and-secretion-of%C3%A2-collagen-in-nih-3t3-cells-by-activating-extracellular-signal-related-kinase-pathway
#8
Xuenan Chen, Manying Wang, Xiaohao Xu, Jianzeng Liu, Bing Mei, Pingping Fu, Daqing Zhao, Liwei Sun
BACKGROUND: Recently, protein from ginseng was studied and used for the treatment of several kinds of diseases. However, the effect of ginseng total protein (GTP) on proliferation and wound healing in fibroblast cells remains unclear. METHODS: In this study, cell viability was analyzed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell cycle distribution was analyzed by flow cytometer. The levels of transforming growth factor β1, vascular endothelial growth factor, and collagens were analyzed by enzyme-linked immunosorbent assay and immunofluorescence staining...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28701725/prospective-study-on-association-of-prostatic-calcifications-with-clinical-symptoms-and-results-of-treatment-in-men-with-type-iii-prostatitis
#9
Xiang Fei, Wei Jin, Shengyu Hua, Yan Song
The purpose is to investigate the clinical significance of prostatic calculi in patients with chronic prostatitis and to discuss the possible treatment.The data from 277 young males with CP/CPPS were analyzed prospectively. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostatic Symptoms Score (IPSS). Sexual function was assessed by the International Index of Erectile Function (IIEF-5) questionnaire. After four weeks of therapy, the NIH-CPSI, IPSS, and IIEF-5 tests were repeated...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701510/immunomodulatory-molecule-irak-m-balances-macrophage-polarization-and-determines-macrophage-responses-during-renal-fibrosis
#10
Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, Georg Lorenz, Roman Günthner, Simone Romoli, Regina Gröbmayr, Heni-Eka Susanti, Jan Potempa, Joanna Koziel, Maciej Lech
Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD)...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701371/population-based-assessment-of-a-biomarker-based-screening-pathway-to-aid-diagnosis-of-monogenic-diabetes-in-young-onset-patients
#11
Beverley M Shields, Maggie Shepherd, Michelle Hudson, Timothy J McDonald, Kevin Colclough, Jaime Peters, Bridget Knight, Chris Hyde, Sian Ellard, Ewan R Pearson, Andrew T Hattersley
OBJECTIVE: Monogenic diabetes, a young-onset form of diabetes, is often misdiagnosed as type 1 diabetes, resulting in unnecessary treatment with insulin. A screening approach for monogenic diabetes is needed to accurately select suitable patients for expensive diagnostic genetic testing. We used C-peptide and islet autoantibodies, highly sensitive and specific biomarkers for discriminating type 1 from non-type 1 diabetes, in a biomarker screening pathway for monogenic diabetes. RESEARCH DESIGN AND METHODS: We studied patients diagnosed aged 30 years or younger, currently younger than 50 years, in two U...
July 12, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#12
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28692660/n-3-oxododecanoyl-l-homoserine-lactone-interactions-in-the-breast-tumor-microenvironment-implications-for-breast-cancer-viability-and-proliferation-in-vitro
#13
Brittany N Balhouse, Logan Patterson, Eva M Schmelz, Daniel J Slade, Scott S Verbridge
It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of breast cancer, yet the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose progressive phenotypes and therapy resistance, however the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression...
2017: PloS One
https://www.readbyqxmd.com/read/28692063/inflammation-dependent-cerebrospinal-fluid-hypersecretion-by-the-choroid-plexus-epithelium-in-posthemorrhagic-hydrocephalus
#14
Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard, Kristopher T Kahle
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept...
July 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28691114/structure-and-dynamics-of-type-iii-secretion-effector-protein-exou-as-determined-by-sdsl-epr-spectroscopy-in-conjunction-with-de-novo-protein-folding
#15
Axel W Fischer, David M Anderson, Maxx H Tessmer, Dara W Frank, Jimmy B Feix, Jens Meiler
ExoU is a 74 kDa cytotoxin that undergoes substantial conformational changes as part of its function, that is, it has multiple thermodynamically stable conformations that interchange depending on its environment. Such flexible proteins pose unique challenges to structural biology: (1) not only is it often difficult to determine structures by X-ray crystallography for all biologically relevant conformations because of the flat energy landscape (2) but also experimental conditions can easily perturb the biologically relevant conformation...
June 30, 2017: ACS Omega
https://www.readbyqxmd.com/read/28689096/discovery-of-phenylsulfonyl-acetic-acid-derivatives-with-improved-efficacy-and-safety-as-potent-free-fatty-acid-receptor-1-agonists-for-the-treatment-of-type-2-diabetes
#16
Zheng Li, Chunxia Liu, Xue Xu, Qianqian Qiu, Xin Su, Yuxuan Dai, Jianyong Yang, Huilan Li, Wei Shi, Chen Liao, Miaobo Pan, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) has emerged as an attractive anti-diabetic target that mediates glucose-stimulated insulin secretion. Several FFA1 agonists have been reported, but many of them possessed somewhat high lipophilicity and/or molecular weight. Herein, we describe the identification of sulfone-carboxylic acid moiety with the multiple advantages of reducing lipophilicity, cytotoxicity and β-oxidation associated with compound 2. Further structure-activity relationship study based on the previleged scaffolds led to the discovery of 2-{(4-[(2'-chloro-[1,1'-biphenyl]-3-yl)methoxy]phenyl)sulfonyl}acetic acid (compound 20), which showed a better balance than compound 2 in terms of physicochemical properties, cytotoxicity profiles and pharmacokinetic properties...
July 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28684684/impact-of-premature-senescence-on-radiosensitivity-measured-by-high-throughput-cell-based-assays
#17
Razmik Mirzayans, Bonnie Andrais, David Murray
In most p53 wild-type human cell types, radiosensitivity evaluated by the colony formation assay predominantly reflects stress-induced premature senescence (SIPS) and not cell death (Int. J. Mol. Sci. 2017, 18, 928). SIPS is a growth-arrested state in which the cells acquire flattened and enlarged morphology, remain viable, secrete growth-promoting factors, and can give rise to tumor-repopulating progeny. The impact of SIPS on radiosensitivity measured by short-term assays remains largely unknown. We report that in four p53 wild-type human solid tumor-derived cell lines (HCT116, SKNSH, MCF7 and A172): (i) the conventional short-term growth inhibition assay (3 days post-irradiation) generates radiosensitivity data comparable to that measured by the laborious and time-consuming colony formation assay; (ii) radiation dose-response curves obtained by multiwell plate colorimetric/fluorimetric assays are markedly skewed towards radioresistance, presumably reflecting the emergence of highly enlarged, growth-arrested and viable cells; and (iii) radiation exposure (e...
July 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28683738/anti-diabetic-activity-of-aerial-parts-of-sarcopoterium-spinosum
#18
Uriel Elyasiyan, Adi Nudel, Nir Skalka, Konstantin Rozenberg, Elyashiv Drori, Rachela Oppenheimer, Zohar Kerem, Tovit Rosenzweig
BACKGROUND: Sarcopoterium spinosum (S. spinosum) is used by Bedouin medicinal practitioners for the treatment of diabetes. While the anti-diabetic activity of S. spinosum root extract was validated in previous studies, the activity of aerial parts of the same plants has not been elucidated yet. The aim of this study was to clarify the glucose lowering properties of the aerial parts of the shrub. METHODS: Anti-diabetic properties were evaluated by measuring the activity of carbohydrate digesting enzymes, glucose uptake into 3 T3-L1 adipocytes, and insulin secretion...
July 6, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28680437/knots-untie-molecular-determinants-involved-in-knot-formation-induced-by-pseudomonas-savastanoi-in-woody-hosts
#19
REVIEW
Eloy Caballo-Ponce, Jesús Murillo, Marta Martínez-Gil, Alba Moreno-Pérez, Adrián Pintado, Cayo Ramos
The study of the molecular basis of tree diseases is lately receiving a renewed attention, especially with the emerging perception that pathogens require specific pathogenicity and virulence factors to successfully colonize woody hosts. Pathosystems involving woody plants are notoriously difficult to study, although the use of model bacterial strains together with genetically homogeneous micropropagated plant material is providing a significant impetus to our understanding of the molecular determinants leading to disease...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28679671/breast-regression-protein-39-chitinase-3-like-1-promotes-renal-fibrosis-after-kidney-injury-via-activation-of-myofibroblasts
#20
Tinika A Montgomery, Leyuan Xu, Sherene Mason, Amirtha Chinnadurai, Chun Geun Lee, Jack A Elias, Lloyd G Cantley
The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α2 (IL13Rα2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI...
July 5, 2017: Journal of the American Society of Nephrology: JASN
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