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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/28324844/serotonin-transporter-and-receptor-ligands-with-antidepressant-activity-as-neuroprotective-and-proapoptotic-agents
#2
REVIEW
Zdzislaw Chilmonczyk, Andrzej J Bojarski, Andrzej Pilc, Ingebrigt Sylte
Serotonin exhibits multiple non-neural functions involved in essential hypertension, early embryogenesis, follicle maturation and behaviour. The growth stimulatory effects of the neurotransmitter have been described for a variety of cell types. 5-HT was found to induce migration of the human prostate cancer cell lines - PC-3 and Du145 - and several 5-HT1A antagonists and serotonin reuptake inhibitors were reported to inhibit the growth of different tumour cell lines in vitro. Recent studies suggest that neurogenesis is involved in the action of antidepressants and an involvement of antidepressants in adult hippocampal neurogenesis has been demonstrated...
January 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#3
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324683/thermal-stress-impacts-reproductive-development-and-grain-yield-in-rice
#4
REVIEW
Muhammad Shakeel Arshad, Muhammad Farooq, Folkard Asch, Jagadish S V Krishna, P V Vara Prasad, Kadambot H M Siddique
Rice is highly sensitive to temperature stress (cold and heat), particularly during the reproductive and grain-filling stages. In this review, we discuss the effects of low- and high-temperature sensitivity in rice at various reproductive stages (from meiosis to grain development) and propose strategies for improving the tolerance of rice to terminal thermal stress. Cold stress impacts reproductive development through (i) delayed heading, due to its effect on anther respiration, which increases sucrose accumulation, protein denaturation and asparagine levels, and decreases proline accumulation, (ii) pollen sterility owing to tapetal hypertrophy and related nutrient imbalances, (iii) reduced activity of cell wall bound invertase in the tapetum of rice anthers, (iv) impaired fertilization due to inhibited anther dehiscence, stigma receptivity and ability of the pollen tube to germinate through the style towards the ovary, and (v) floret sterility, which increases grain abortion, restricts grain size, and thus reduces grain yield...
March 16, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28324658/mitochondrial-respiration-links-tor-complex-2-signaling-to-calcium-regulation-and-autophagy
#5
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
The Target of Rapamycin (TOR) kinase is a conserved regulator of cell growth and functions within 2 different protein complexes, TORC1 and TORC2, where TORC2 positively controls macroautophagy/autophagy during amino acid starvation. Under these conditions, TORC2 signaling inhibits the activity of the calcium-regulated phosphatase calcineurin and promotes the general amino acid control (GAAC) response and autophagy. Here we demonstrate that TORC2 regulates calcineurin by controlling the respiratory activity of mitochondria...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28324485/maintenance-of-human-embryonic-stem-cells-by-sphingosine-1-phosphate-and-platelet-derived-growth-factor
#6
Raymond C B Wong, Martin F Pera, Alice Pébay
Human embryonic stem cells (hESCs) have historically been cultivated on feeder layers of primary mouse embryonic fibroblasts (MEF) in a medium supplemented with fetal calf serum (FCS). However, serum contains a wide variety of biologically active compounds that might adversely affect hESC growth and differentiation. Thus, cultivation of stem cells in FCS complicates experimental approaches to define the intracellular mechanisms required for hESC maintenance. This chapter describes the serum-free maintenance of hESCs in culture by addition of sphingosine-1-phosphate (S1P) and platelet-derived growth factor (PDGF)...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324206/indeterminate-domain-protein-binding-sequences-in-the-5-untranslated-region-and-promoter-of-the-scarecrow-gene-play-crucial-and-distinct-roles-in-regulating-scarecrow-expression-in-roots-and-leaves
#7
Atsushi Kobayashi, Satoshi Miura, Akiko Kozaki
SCARECROW (SCR) and SHORT-ROOT (SHR), which belong to the GRAS transcription factor family, are key regulators of root and leaf growth and development. Despite the importance of SCR expression for proper plant development, the mechanism of SCR regulation has not been clarified. A previous study showed that an INDETERMINATE DOMAIN transcription factor, JACKDAW (JKD), is essential for the expression of SCR in combination with SCR and SHR. In this study, we characterized possible binding sequences of INDETERMINATE DOMAIN PROTEIN in the 1...
March 21, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28324173/effect-of-oaz1-overexpression-on-goose-ovarian-granulosa-cells
#8
Bo Kang, Dongmei Jiang, Hui He, Rong Ma, Ziyu Chen, Zhixin Yi
Ornithine decarboxylase antizyme 1 (OAZ1) regulates both polyamine biosynthesis and transport and acts as a tumor suppressor because of its functions in the regulation of cell proliferation, apoptosis and growth. However, the roles of OAZ1 in the regulation of polyamine metabolism, cell proliferation, apoptosis and hormone receptor expression in granulosa cells (GCs) from geese have not been determined. To define the roles of OAZ1 in primary GCs, we constructed and transfected an Oaz1 overexpression vector with a thymidine deletion into primary GCs...
March 21, 2017: Amino Acids
https://www.readbyqxmd.com/read/28324125/exercise-and-cancer-from-healthy-to-therapeutic
#9
REVIEW
Manja Idorn, Per Thor Straten
Exercise improves functional capacity and patient-reported outcomes across a range of cancer diagnoses. The mechanisms behind this protection have been largely unknown, but exercise-mediated changes in body composition, sex hormone levels, systemic inflammation, and immune cell function have been suggested to play a role. We recently demonstrated that voluntary exercise leads to an influx of immune cells in tumors, and a more than 60% reduction in tumor incidence and growth across several mouse models. Given the common mechanisms of immune cell mobilization in mouse and man during exercise, we hypothesize that this link between exercise and the immune system can be exploited in cancer therapy in particular in combination with immunotherapy...
March 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28324115/regenerative-responses-and-axon-pathfinding-of-retinal-ganglion-cells-in-chronically-injured-mice
#10
Benjamin J Yungher, Márcio Ribeiro, Kevin K Park
Purpose: Enhanced regeneration of retinal ganglion cell (RGC) axons can be achieved by modification of numerous neuronal-intrinsic factors. However, axon growth initiation and the pathfinding behavior of these axons after traumatic injury remain poorly understood outside of acute injury paradigms, despite the clinical relevance of more chronic settings. We therefore examined RGC axon regeneration following therapeutic delivery that is postponed until 2 months after optic nerve crush injury...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324111/arap1-deficiency-causes-photoreceptor-degeneration-in-mice
#11
Ala Moshiri, Devin Humpal, Brian C Leonard, Denise M Imai, Addy Tham, Lynette Bower, Dave Clary, Thomas M Glaser, K C Kent Lloyd, Christopher J Murphy
Purpose: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Methods: Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324051/androgen-stimulates-growth-of-mouse-preantral-follicles-in-vitro-interaction-with-follicle-stimulating-hormone-and-with-growth-factors-of-the-tgf%C3%AE-superfamily
#12
Mhairi Laird, Kacie Thomson, Mark Fenwick, Jocelyn Mora, Stephen Franks, Kate Hardy
Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aims of investigating interaction with FSH, the steroidogenic pathway and with growth factors of the TGFβ superfamily that are known to have a role in early follicle development...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324045/ring-finger-protein-6-mediates-androgen-induced-granulosa-cell-proliferation-and-follicle-growth-via-modulation-of-androgen-receptor-signaling
#13
Jung Jin Lim, Chae Young Han, Dong Ryul Lee, Benjamin K Tsang
The destiny of the ovarian follicle (growth or atresia) is tightly regulated by actions and interactions of endocrine, paracrine and autocrine factors. Although androgens are known to be important in the regulation of folliculogenesis, whether they facilitate or suppress follicular growth has been controversial and the mechanisms involved are not fully understood. Moreover, the role and regulation of its receptor (AR) in mediating androgen signaling during follicular development is not clear. Here, we report that the active androgen dihydrotestosterone (DHT) up-regulates the expression of AR and its E3 ligase Ring Finger Protein 6 (RNF6), increasing site-specific AR polyubiquitination and AR transcriptional activity for sKit-L expression in preantral follicle growth...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-beta-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#14
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/28324020/paracrine-pathways-in-uterine-leiomyoma-stem-cells-involve-insulin-like-growth-factor-2-and-insulin-receptor-a
#15
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/28324019/no-mediated-regulation-of-glut-by-t3-and-fsh-in-rat-granulosa-cells
#16
Ye Tian, Yu Ding, Juan Liu, Dai Heng, Kaili Xu, Wenbo Liu, Cheng Zhang
Thyroid hormones (THs) are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. Here, we present evidence that T3 and FSH co-treatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake...
March 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324013/acute-parathyroid-hormone-injection-increases-c-terminal-but-not-intact-fibroblast-growth-factor-23-levels
#17
V M Knab, B Corbin, O Andrukhova, J M Hum, P Ni, S Rabadi, A Maeda, K E White, R G Erben, H Jüppner, M Christov
The acute effects of PTH on FGF23 in vivo are not well understood. After a single s.c. PTH(1-34) injection (50nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 mRNA and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by 3-5-fold within two hours following PTH injection, which returned to baseline by 4 hours...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#18
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323982/versican-proteolysis-by-adamts-proteases-and-its-influence-on-sex-steroid-receptor-expression-in-uterine-leiomyoma
#19
Ndeye-Aicha Gueye, Timothy J Mead, Christopher D Koch, Charles V Biscotti, Tommaso Falcone, Suneel S Apte
Context: Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. Objective: To investigate ADAMTS protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. Design: We used qRT-PCR, western blotting, immunohistochemistry and RNA in situ hybridization for analysis of myometrium, leiomyoma, and immortalized myometrium and leiomyoma cells...
February 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323945/coordinated-regulation-among-progesterone-prostaglandins-and-egf-like-factors-in-human-ovulatory-follicles
#20
Yohan Choi, Kalin Wilson, Patrick R Hannon, Katherine L Rosewell, Mats Brännström, James W Akin, Thomas E Curry, Misung Jo
CONTEXT: In animal models, the LH surge increases progesterone (P4)/its receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. OBJECTIVES: To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. DESIGN AND PARTICIPANTS: Timed periovulatory follicles were obtained from cycling women...
March 9, 2017: Journal of Clinical Endocrinology and Metabolism
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