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https://www.readbyqxmd.com/read/28324846/novel-alk5-inhibitor-tp0427736-reduces-tgf-%C3%AE-%C3%A3-induced-growth-inhibition-in-human-outer-root-sheath-cells-and-elongates-anagen-phase-in-mouse-hair-follicles
#1
Takumi Naruse, Mari Aoki, Natsuko Fujimoto, Seiji Arase, Hajimu Oura, Yasuji Ueda, Akiko Ikeda
BACKGROUND: Androgenic alopecia (AGA) occurs as a result of the contraction of the anagen phase because of the action of androgens on hair follicles. TGF-β production from dermal papillae is enhanced by androgens, and growth inhibition of hair-follicle cells is induced by TGF-β, and the hair cycle progresses from the anagen phase to the catagen phase. We investigated both the in vitro and in vivo potency of the newly identified ALK5 inhibitor TP0427736 {6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole}...
January 25, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28324804/high-density-lipoprotein-immunomodulates-the-functional-activities-of-macrophage-and-cytokines-produced-during-ex-vivo-macrophage-cd4-t-cell-crosstalk-at-the-recent-onset-human-type-1-diabetes
#2
Ibtissem Benghalem, Warda Meziane, Zeyneb Hadjidj, Lamia Ysmail-Dahlouk, Ahmed Belamri, Kheira Mouhadjer, Mourad Aribi
BACKGROUND: Both CD4(+) T cells and macrophages are mainly involved in the autoimmune-mediated β-cells destruction in type 1 diabetes (T1D). The aim of this study was to examine the effect of HDL on functional activities of macrophage and its ability to regulate the production of cytokines in autologous mixed macrophage/CD4(+) T cells at the recent-onset human type 1 diabetes. METHODS: Cell samples were isolated from volunteers with recent-onset T1D or healthy controls...
March 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28324784/an-in%C3%A2-vivo-active-1-2-5-oxadiazole-pt-ii-complex-a-promising-anticancer-agent-endowed-with-stat3-inhibitory-properties
#3
Federica Porta, Giorgio Facchetti, Nicola Ferri, Arianna Gelain, Fiorella Meneghetti, Stefania Villa, Daniela Barlocco, Daniela Masciocchi, Akira Asai, Nao Miyoshi, Silvia Marchianò, Byoung-Mog Kwon, Yena Jin, Valentina Gandin, Cristina Marzano, Isabella Rimoldi
New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3·HCl showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 μM) and a selective ability to interact with STAT3 (IC50 = 8.2 μM) versus STAT1 (IC50 > 30 μM). Its corresponding platinum complex Pt-3 exhibited an increased cytotoxicity (IC50 = 18.4 μM) and a stronger interaction with STAT3 (IC50 = 1.4 μM), leading to inhibition of its signaling pathway...
March 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28324760/trpv1-agonism-inhibits-endothelial-cell-inflammation-via-activation-of-enos-no-pathway
#4
Youping Wang, Lin Cui, Hui Xu, Suxiao Liu, Feiyun Zhu, Fengna Yan, Si Shen, Mingjun Zhu
BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca(2+)-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28324642/cinnamon-reduces-inflammatory-response-in-intestinal-fibroblasts-in-vitro-and-in-colitis-in-vivo-leading-to-decreased-fibrosis
#5
Yvonne Hagenlocher, Sabrina Satzinger, Mehtap Civelek, Katharina Feilhauer, Jörg Köninger, Stephan C Bischoff, Axel Lorentz
Intestinal fibrosis, a complication of inflammatory bowel disease, is currently being addressed by surgery alone, with no adequate alternative therapy available for patients. We propose that anti-inflammatory plant substances like cinnamon extract (CE) or its main compound cinnamaldeyde (CA) could aid in therapy. We recently found CE reducing inflammation in murine colitis. Here, we analysed effects of CE on fibrosis in IL-10(-/-) colitis METHODS AND RESULTS: IL-10(-/-) and wild type (wt) mice were orally treated with/without vehicle or CE...
March 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28324208/the-%C3%AE-subunit-of-%C3%AE-conglycinin-and-various-glycinin-subunits-of-soy-are-not-required-to-modulate-hepatic-lipid-metabolism-in-rats
#6
Cynthia Chatterjee, Jiajie Liu, Carla Wood, Christine Gagnon, Elroy R Cober, Judith A Frégeau-Reid, Stephen Gleddie, Chao-Wu Xiao
PURPOSE: This study examined the effect of soy proteins with depletion of different subunits of the two major storage proteins, β-conglycinin and glycinin, on hepatic lipids and proteins involved in lipid metabolism in rats, since the bioactive component of soy responsible for lipid-lowering is unclear. METHODS: Weanling Sprague Dawley rats were fed diets containing either 20% casein protein in the absence (casein) or presence (casein + ISF) of isoflavones or 20% alcohol-washed soy protein isolate (SPI) or 20% soy protein concentrates derived from a conventional (Haro) or 2 soybean lines lacking the α' subunit of β-conglycinin and the A1-3 (1TF) or A1-5 (1a) subunits of glycinin...
March 21, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28324067/gestational-protein-restriction-impairs-glucose-disposal-in-the-gastrocnemius-muscles-of-female-rats
#7
C S Blesson, V Chinnathambi, S Kumar, C Yallampalli
Gestational low protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP exposed female offspring. Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months and gastrocnemius muscles were treated with insulin ex vivo for 30 min...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324061/progesterone-protects-against-bpa-induced-arrhythmias-in-female-rat-cardiac-myocytes-via-rapid-signaling
#8
Jianyong Ma, Kui Hong, Hong-Sheng Wang
Bisphenol A (BPA) is an estrogenic endocrine disrupting chemical (EDC) that has a range of potential adverse health effects. Previously we showed that acute exposure to BPA promoted arrhythmias in female rat hearts through estrogen receptor rapid signaling. Progesterone (P4) and estrogen have antagonistic or complementary actions in a number of tissues and systems. In the current study, we examined the influence, and possible protective effect, of P4 on the rapid cardiac actions of BPA in female rat cardiac myocytes...
January 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#9
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-beta-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#10
J A Maybin, L Boswell, V J Young, W C Duncan, Hod Critchley
Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The TGFβ superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesised that TGFβ1 is important for endometrial repair and women with HMB have aberrant TGFβ1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women and menstrual blood loss objectively measured (HMB >80ml/cycle, normal menstrual bleeding, NMB <80ml)...
January 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324027/follistatin-targets-distinct-pathways-to-promote-brown-adipocyte-characteristics-in-brown-and-white-adipose-tissues
#11
Rajan Singh, Melissa Braga, Srinivasa T Reddy, Se-Jin Lee, Meher Parveen, Victor Grijalva, Laurent Vergnes, Shehla Pervin
We previously demonstrated that Fst expression is highest in brown adipose tissue (BAT) and skeletal muscle, but is also present at substantial levels in epididymal (Epi) and subcutaneous (SC) white adipose tissues (WAT). Fst promotes mouse brown preadipocyte differentiation and promotes browning during differentiation of mouse embryonic fibroblasts (MEFs). Fst-transgenic (Fst-Tg) mouse show significant increase in circulating Fst levels and increased brown adipose mass. BAT of Fst-Tg mice had increased expression of brown adipose-associated markers including uncoupling protein 1 (UCP1), PRDM16, PGC-1α and Glut4...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324020/paracrine-pathways-in-uterine-leiomyoma-stem-cells-involve-insulin-like-growth-factor-2-and-insulin-receptor-a
#12
Molly B Moravek, Ping Yin, John S Coon V, Masanori Ono, Stacy A Druschitz, Saurabh S Malpani, Matthew T Dyson, Alfred W Rademaker, Jared C Robins, Jian-Jun Wei, J Julie Kim, Serdar E Bulun
Context: Uterine leiomyoma (fibroids) are the most common benign tumor in women. Recently, three populations of leiomyoma cells were discovered based on CD34 and CD49b expression, but the molecular differences between these populations remain unknown. Objective: Define differential gene expression and signaling pathways in leiomyoma cell populations. Design: Cells from human leiomyoma were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323924/guanabenz-sensitizes-pancreatic-%C3%AE-cells-to-lipotoxic-endoplasmic-reticulum-stress-and-apoptosis
#13
Baroj Abdulkarim, Miriam Hernangomez, Mariana Igoillo Esteve, Daniel A Cunha, Lorella Marselli, Piero Marchetti, Laurence Ladriere, Miriam Cnop
Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323904/pyrrolidine-dithiocarbamate-administered-during-ex-vivo-lung-perfusion-promotes-rehabilitation-of-injured-donor-rat-lungs-obtained-after-prolonged-warm-ischemia
#14
Cyril Francioli, Xingyu Wang, Roumen Parapanov, Etienne Abdelnour, Jérôme Lugrin, Fabrizio Gronchi, Jean Perentes, Philippe Eckert, Hans-Beat Ris, Lise Piquilloud, Thorsten Krueger, Lucas Liaudet
Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2...
2017: PloS One
https://www.readbyqxmd.com/read/28323896/biological-phosphorylation-of-an-unnatural-base-pair-ubp-using-a-drosophila-melanogaster-deoxynucleoside-kinase-dmdnk-mutant
#15
Fei Chen, Yuan Zhang, Ashley B Daugherty, Zunyi Yang, Ryan Shaw, Mengxing Dong, Stefan Lutz, Steven A Benner
One research goal for unnatural base pair (UBP) is to replicate, transcribe and translate them in vivo. Accordingly, the corresponding unnatural nucleoside triphosphates must be available at sufficient concentrations within the cell. To achieve this goal, the unnatural nucleoside analogues must be phosphorylated to the corresponding nucleoside triphosphates by a cascade of three kinases. The first step is the monophosphorylation of unnatural deoxynucleoside catalyzed by deoxynucleoside kinases (dNK), which is generally considered the rate limiting step because of the high specificity of dNKs...
2017: PloS One
https://www.readbyqxmd.com/read/28323861/overexpression-of-c-jun-contributes-to-sorafenib-resistance-in-human-hepatoma-cell-lines
#16
Yuki Haga, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Reina Sasaki, Koji Takahashi, Shuang Wu, Osamu Yokosuka
BACKGROUND: Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC). Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown. METHODS: The expression of molecules involved in the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28323847/role-of-the-mapks-tgf-%C3%AE-1-traf6-signaling-pathway-in-postoperative-atrial-fibrillation
#17
Daoliang Zhang, Xiaoqing Chen, Qian Wang, Shaohui Wu, Yue Zheng, Xu Liu
OBJECTIVES: To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis. METHODS: A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28323844/nuclear-localization-of-amyloid-%C3%AE-precursor-protein-binding-protein-fe65-is-dependent-on-regulated-intramembrane-proteolysis
#18
Niina A Koistinen, Anna K Edlund, Preeti K Menon, Elena V Ivanova, Smaranda Bacanu, Kerstin Iverfeldt
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65...
2017: PloS One
https://www.readbyqxmd.com/read/28323486/enterolactone-induces-g1-phase-cell-cycle-arrest-in-nonsmall-cell-lung-cancer-cells-by-downregulating-cyclins-and-cyclin-dependent-kinases
#19
Shireen Chikara, Kaitlin Lindsey, Harsharan Dhillon, Sujan Mamidi, Jeffrey Kittilson, Melpo Christofidou-Solomidou, Katie M Reindl
Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28320107/pre-conditioning-with-tanshinone-iia-attenuates-the-ischemia-reperfusion-injury-caused-by-liver-grafts-via-regulation-of-hmgb1-in-rat-kupffer-cells
#20
Xuanfei Li, Yakun Wu, Wenfeng Zhang, Jianping Gong, Yao Cheng
OBJECTIVE: We have evaluated the protective mechanism of tanshinone IIA in ischemia/reperfusion injury (IRI) induced by liver grafts, revealing novel supplementary immunotherapy for liver transplantation. METHODS: The tanshinone IIA preconditioning group (TP group) was pretreated with tanshinone IIA via intraperitoneal injection for 1 week before receiving orthotopic liver transplantation with hepatic arterial ischemia for 30min. The sham-operation group (SO group), control graft group (CG group) and IRI group were pretreated with an equivalent volume of normal saline...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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