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https://www.readbyqxmd.com/read/28109166/a-novel-dual-amylin-and-calcitonin-receptor-agonist-dacra-kbp-089-induces-weight-loss-through-a-reduction-in-fat-but-not-lean-mass-while-improving-food-preference
#1
Sofie Gydesen, Sara Toftegaard Hjuler, Zenia Freving, Kim Vietz Andreassen, Nina Sonne, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
BACKGROUND AND PURPOSE: Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges - hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated...
January 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28109159/activity-dependent-regulation-of-t-type-calcium-channels-by-submembrane-calcium-ions
#2
Magali Cazade, Isabelle Bidaud, Philippe Lory, Jean Chemin
Voltage-gated Ca(2+) channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca(2+) ion itself. This is well exemplified by the Ca(2+)-dependent inactivation of L-type Ca(2+) channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca(2+) channels, a long-held view is that they are not regulated by intracellular Ca(2+). Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca(2+) channels...
January 21, 2017: ELife
https://www.readbyqxmd.com/read/28109147/-co-culture-with-umbilical-cord-mesenchymal-stem-cells-promotes-the-synthesis-and-mechnism-of-milk-protein-in-bovine-mammary-epithelial-cells
#3
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109144/-interferon-regulatory-factor-5-irf5-regulates-the-differentiation-of-bone-marrow-derived-macrophages-in-mice
#4
Kang Sun, Jianguo Qu, Jixiang Chen, Shengchun Dang, Songbing He, Jin Zhang, Rong Xie, Yun Wang, Jianxin Zhang
Objective To investigate the expression differences of interferon regulatory factor 5 (IRF5) between M1 and M2 macrophages derived from mouse bone marrow and the effects of small interfering RNA targeting IRF5 gene (IRF5 siRNA) on macrophage differentiation. Methods With the treatment of IFN-γ and lipopolysaccharide (LPS), mouse bone marrow-derived macrophages were differentiated into M1 macrophages; while with the treatment of IL-4, mouse bone marrow-derived macrophages were differentiated into M2 macrophages...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109139/-imiquimod-combined-with-dendritic-cell-vaccine-decreases-treg-proportion-and-enhances-anti-tumor-responses-in-mice-bearing-melanoma
#5
Shurong Ren, Qiubo Wang, Yanli Zhang, Cuixiu Lu, Ping Li, Yumei Li
Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109136/therapeutic-potential-of-targeting-wnt-%C3%AE-catenin-pathway-in-treatment-of-colorectal-cancer-rational-and-progress
#6
Afsane Bahrami, Forouzan Amerizadeh, Soodabeh ShahidSales, Majid Khazaei, Majid Ghayour-Mobarhan, Hamid Reza Sadeghnia, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
Wnt/β-catenin pathway is one of the main/frequent dysregulated pathways in several tumor types, including colon cancer. Aberrant activation of this pathway is associated with cell proliferation, invasive behaviors and cell resistance, suggesting its potential value as a therapeutic target in treatment of CRC. Several agents have been developed for targeting of this pathway (e.g, natural agents: curcumin, 3,3-diindolylmethane, phytoestrogen; Synthetic/small Wnt inhibitors: Rofecoxib; PRI-724, CWP232291; and monoclonal antibody against frizzled receptors, Vanituctumab...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28109128/population-pharmacokinetics-and-pharmacodynamics-of-benralizumab-in-healthy-volunteers-and-patients-with-asthma
#7
B Wang, L Yan, Z Yao, L K Roskos
Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) 1 κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site...
January 21, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28109095/-establishment-of-a-sd-rat-model-of-vulvar-lichen-simplex-chronicus-and-detection-of-the-expression-of-protease-activated-receptor-2
#8
Huan Yang, Zhen-Hua Fu, Hua-Jun Tang, Cheng-Zhi Li
OBJECTIVE: To establish a SD rat model of vulvar lichen simplex chronicus (LSC) and investigate the expression of protease activated receptor 2 (PAR2) in the genital skin. METHODS: Seventy female SD rats were randomly divided into group A (blank control group, n=10), group B (with application of acetone solution 3 times per week for 10 weeks, n=10), group C (with chronic mechanical irritation 3 times per week for 10 weeks, n=10), and group D (with topical treatment with 0...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28109074/determination-of-four-nadolol-stereoisomers-in-capsules-by-high-performance-liquid-chromatography-and-circular-dichroism
#9
Grazielle Prado Alexandre, Márcio Nardelli Wandermuren, Adriano Peron, Vanessa Franco Tavares, Denis Alexandre Ramalho Padeiro, Kelly Alessandra Sakiara, María Segunda Aurora-Prado, Anil Kumar Singh, Erika Rosa Maria Kedor-Hackmann, Maria Inês Rocha Miritello Santoro
Nadolol is a blocking agent with activity in β-adrenergic receptors. The objective of this research was to develop andvalidate an HPLC and circular dichroism method for the quantification of four nadolol stereoisomers in capsules. The HPLC method was validated using a Chiralcel OD column (250 × 4,6 mm, 10 μm). The mobile phase consisted of hexane-ethanol-diethylamine-acetic acid(86 + 14 + 0.3 + 0.3, v/v/v/v), with a flow rate of 0.7 mL/min and temperature of 25 ± 1°C and UV detection carried out at 220 nm...
January 21, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28109061/urocortin-suppresses-endometrial-cancer-cell-migration-via-crfr2-and-its-system-components-are-differentially-modulated-by-estrogen
#10
Gemma L Owens, Kevin M Lawrence, Tom R Jackson, Emma J Crosbie, Berna S Sayan, Henry C Kitchener, Paul A Townsend
Urocortin (UCN1) peptide shares structural and functional homology with corticotropin-releasing factor (CRF). UCN1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of UCN1 on the proliferation and migration of Ishikawa and HEC1A cells. We also determined the expression levels of UCN1 and its receptors produced by estrogen receptor agonists, and the effect of UCN1 on estrogen receptor expression, using quantitative polymerase chain reaction...
January 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28109053/frogs-model-man-in-vivo-thyroid-hormone-signaling-during-development
#11
REVIEW
Laurent M Sachs, Daniel R Buchholz
Thyroid hormone (TH) signaling comprises TH transport across cell membranes, metabolism by deiodinases, and molecular mechanisms of gene regulation. Proper TH signaling is essential for normal perinatal development, most notably for neurogenesis and fetal growth. Knowledge of perinatal TH endocrinology needs improvement to provide better treatments for premature infants and endocrine diseases during gestation and to counteract effects of endocrine disrupting chemicals. Studies in amphibians have provided major insights to understand in-vivo mechanisms of TH signaling...
January 21, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28109042/expression-and-characterization-of-a-codon-optimized-blood-coagulation-factor-viii
#12
S A Shestopal, J-J Hao, E Karnaukhova, Y Liang, M V Ovanesov, M Lin, J H Kurasawa, T K Lee, J H McVey, A G Sarafanov
BACKGROUND: Production of recombinant factor VIII (FVIII) is challenging due to its low expression. It was previously shown that codon-optimization of a B domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well-recognized that synonymous mutations may affect the protein structure and function. OBJECTIVES: To compare biochemical properties of a BDD-FVIII expressed from codon-optimized (CO) and the wild-type (WT) cDNAs. METHODS: Each variant of the BDD-FVIII was expressed in several independent CHO cell lines, generated using a lentiviral platform...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109039/nkx2-5-regulates-endothelin-converting-enzyme-1-during-pharyngeal-arch-patterning
#13
Jennifer M Iklé, Andre L P Tavares, Marisol King, Hailei Ding, Sophie Colombo, Beth A Firulli, Anthony B Fiulli, Kimara L Targoff, Deborah Yelon, David E Clouthier
In gnathostomes, dorsoventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediates this process is Endothelin-1 (EDN1). Loss of EDN1 binding to the Endothelin-A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate-limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme-1 (ECE1)...
January 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#14
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108989/tigit-signaling-pathway-negatively-regulates-cd4-t-cell-responses-in-systemic-lupus-erythematosus
#15
Lie Mao, Hongyan Hou, Shiji Wu, Yu Zhou, Juan Wang, Jing Yu, Xiaohui Wu, Yanfang Lu, Liyan Mao, Munyemana Jean Bosco, Feng Wang, Ziyong Sun
B lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T cell-dependent, and CD4(+) T cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4(+) T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4(+) T cells. Here, we addressed the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4(+) T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108967/specific-sites-of-metastases-in-invasive-lobular-carcinoma-a-retrospective-cohort-study-of-metastatic-breast-cancer
#16
Masayuki Inoue, Hiroshi Nakagomi, Haruka Nakada, Kazushige Furuya, Kou Ikegame, Hideki Watanabe, Masao Omata, Toshio Oyama
BACKGROUND: Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. METHODS: We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC...
January 20, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28108950/t-cell-receptor-engineered-t-cells-for-cancer-treatment-current-status-and-future-directions
#17
REVIEW
Yu Ping, Chaojun Liu, Yi Zhang
T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1)...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108849/toll-like-receptor-4-affects-the-cerebral-biochemical-changes-induced-by-mptp-treatment
#18
Carmela Conte, Luca Roscini, Roccaldo Sardella, Giuseppina Mariucci, Stefania Scorzoni, Tommaso Beccari, Laura Corte
The etiology and pathogenesis of Parkinson's disease (PD) are still unclear. However, multiple lines of evidence suggest a critical role of the toll like receptor 4 (TLR4) in inflammatory response and neuronal death. Neuroinflammation may be associated with the misfolding and aggregation of proteins accompanied by a change in their secondary structure. Recent findings also suggest that biochemical perturbations in cerebral lipid content could contribute to the pathogenesis of central nervous system (CNS) disorders, including PD...
January 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#19
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28108820/prevention-of-chemotherapy-induced-nausea-the-role-of-neurokinin-1-nk1-receptor-antagonists
#20
Snežana M Bošnjak, Richard J Gralla, Lee Schwartzberg
Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK1RAs when combined with 5-HT3RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC)...
January 20, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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