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retinoid investigation

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https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#1
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR) whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28298266/metabolic-effects-of-inflammation-on-vitamin-a-and-carotenoids-in-humans-and-animal-models
#2
REVIEW
Lewis P Rubin, A Catharine Ross, Charles B Stephensen, Torsten Bohn, Sherry A Tanumihardjo
The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28267642/fundamental-studies-of-adrenal-retinoid-x-receptor-protein-isoform-tissue-expression-subcellular-distribution-and-ligand-availability
#3
Behling Cheng, Fatema H Al-Shammari, Isra'a A Ghader, Fatima Sequeira, Jitendra Thakkar, Thazhumpal C Mathew
Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions...
March 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28264498/retinoic-acid-negatively-impacts-proliferation-and-mctc-specific-attributes-of-human-skin-derived-mast-cells-but-reinforces-allergic-stimulability
#4
Magda Babina, Metin Artuc, Sven Guhl, Torsten Zuberbier
The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28251414/molecular-dynamics-simulations-and-molecular-flooding-studies-of-the-retinoid-x-receptor-ligand-binding-domain
#5
Geoffrey M Gray, Ning Ma, Carl E Wagner, Arjan van der Vaart
Bexarotene is an FDA approved retinoid X-receptor (RXR) agonist for the treatment of cutaneous T-cell lymphoma, and its use in other cancers and Alzheimer's disease is being investigated. The drug causes serious side effects, which might be reduced by chemical modifications of the molecule. To rationalize known agonists and to help identify sites for potential substitutions we present molecular simulations in which the RXR ligand-binding domain was flooded with a large number of drug-like molecules, and molecular dynamics simulations of a series of bexarotene-like ligands bound to the RXR ligand-binding domain...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28249598/the-prognostic-utility-of-the-transcription-factor-srf-in-docetaxel-resistant-prostate-cancer-in-vitro-discovery-and-in-vivo-validation
#6
D J Lundon, A Boland, M Prencipe, G Hurley, A O'Neill, E Kay, S T Aherne, P Doolan, S F Madden, M Clynes, C Morrissey, J M Fitzpatrick, R W Watson
BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28230922/adipose-derived-aldehyde-dehydrogenase-expressing-cells-promote-dermal-regenerative-potential-with-collagen-glycosaminoglycan-scaffold
#7
Hajime Matsumine, Kazuyuki Numakura, Satoshi Tsunoda, Huan Wang, Rui Matsumine, Mihail Climov, Giorgio Giatsidis, Vikas P Sukhatme, Dennis P Orgill
Aldehyde dehydrogenase (ALDH) is an enzyme that plays an important role in retinoid metabolism and highly expressed in stem cells. This study isolated ALDH-expressing cells from subcutaneous adipose tissue and investigated their potential to enhance healing in a full-thickness skin wound in rats by co-implanting them with collagen-glycosaminoglycan (c-GAG) scaffolds. ALDH-positive cells were isolated by a fluorescence-activated cell sorting technique from Lewis rat's stromal-vascular-fraction (SVF) and transplanted with c-GAG scaffolds in a rat full-thickness skin wound model...
November 7, 2016: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#8
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28222789/is-ccnu-lomustine-valuable-for-treatment-of-cutaneous-epitheliotropic-lymphoma-in-dogs-a-critically-appraised-topic
#9
REVIEW
Aurore Laprais, Thierry Olivry
BACKGROUND: CCNU and other treatment protocols are commonly offered to owners for the treatment of dogs diagnosed with cutaneous (epitheliotropic) T-cell lymphoma (CTCL). Chemotherapy protocols provide variable benefits; they have different side-effects, and they typically require monitoring to detect drug toxicity at a non-negligible cost to the owner. At this time, even though CCNU is most often recommended to treat dogs with CTCL, there is no clear consensus on the benefit of this drug...
February 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28155143/autofluorescence-spectroscopy-for-monitoring-metabolism-in-animal-cells-and-tissues
#10
Anna C Croce, Giovanni Bottiroli
Excitation of biological substrates with light at a suitable wavelength can give rise to a light emission in the ultraviolet (UV)-visible, near-infrared (IR) spectral range, called autofluorescence (AF). This is a widespread phenomenon, ascribable to the general presence of biomolecules acting as endogenous fluorophores (EFs) in the organisms of the whole life kingdom. In cytochemistry and histochemistry, AF is often an unwanted signal enhancing the background and affecting in particular the detection of low signals or rare positive labeling spots of exogenous markers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28153738/myocilin-expression-is-regulated-by-retinoic-acid-in-the-trabecular-meshwork-derived-cellular-environment
#11
Cécile Prat, Corinne Belville, Aurélie Comptour, Geoffroy Marceau, Gael Clairefond, Frédéric Chiambaretta, Vincent Sapin, Loïc Blanchon
Glaucoma is the leading cause of irreversible blindness and is usually classified as angle closure and open angle glaucoma (OAG). Primary open angle glaucoma represents the most frequent clinical presentation leading to ganglion cell death and optic nerve degeneration as a main consequence of an intraocular pressure' (IOP) increase. The mechanisms of this IOP increase in such pathology remain unclear but one protein called Myocilin could be a part of the puzzle in the trabecular meshwork (TM). Previously described to be transcriptionally regulated by glucocorticoids, the comprehension of the trabecular regulation of Myocilin' expression has only weakly progressed since 15 years...
January 30, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28123100/hepatic-detoxification-of-bisphenol-a-is-retinoid-dependent
#12
Igor O Shmarakov, Vira L Borschovetska, William S Blaner
Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl) propane) is a widely used industrial chemical. The extensive distribution of BPA in the environment poses risks to humans however the molecular mechanisms underlying BPA toxicity as well as its effective detoxification and elimination are not well understood. We have investigated specifically for BPA the notion raised in the literature that the optimal sensing, detoxification and elimination of xenobiotics requires retinoid (natural derivatives and synthetic analogs of vitamin A) actions...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28119491/reactive-oxygen-species-mediated-synergism-of-fenretinide-and-romidepsin-in-preclinical-models-of-t-cell-lymphoid-malignancies
#13
Monish R Makena, Balakrishna Koneru, Thinh H Nguyen, Min H Kang, C Patrick Reynolds
T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitor romidepsin and the synthetic cytotoxic retinoid fenretinide both have achieved durable clinical responses in T-cell lymphomas as single agents. We investigated the potential for using these two agents in combination in TCLMs. We demonstrated cytotoxic synergy between romidepsin and fenretinide in fifteen TCLM cell lines at clinically-achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells)...
January 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28114934/effect-of-a-retinoid-x-receptor-partial-agonist-on-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#14
Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Naohiro Oda, Daisuke Morichika, Etsuko Murakami, Hikari Nakayama, Koichi Waseda, Mikio Kataoka, Hiroki Kakuta, Mitsune Tanimoto, Arihiko Kanehiro
BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners-e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined...
January 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28105175/analysis-of-transcription-profile-to-reveal-altered-signaling-pathways-following-the-overexpression-of-human-desumoylating-isopeptidase-2-in-pancreatic-cancer-cells
#15
Yu-Yin Fu, Yu-Huan Kang, Cong-Cong Shen, Rui-Xue Wang, Lin Yu, Xin-Yue Li, Dan-Dan Cui, Jin-Liang Yang, Yu-Qin Yao, Lan-Tu Gou
Human desumoylating isopeptidase 2 (DESI-2) is a member of the DESI family and contains a conserved PPPDE1 domain. Previous studies have demonstrated that DESI-2 overexpression may induce cell apoptosis. In the present study, differentially expressed genes were analyzed using a transcription microarray in DESI-2 overexpressing PANC-1 pancreatic cancer cells. A total of 45,033 genes were examined by microarray, which identified 1,766 upregulated and 1,643 downregulated genes. A series of altered signaling pathways were analyzed, in which certain essential signaling factors, including retinoid X receptor (RXR), BH3 interacting-domain death agonist, Ras homolog gene family member A (RhoA) and Rho-associated protein kinase, were further investigated at the protein level...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28102440/thyroid-hormones-retinol-and-clinical-parameters-in-relation-to-mercury-and-organohalogen-contaminants-in-great-blue-heron-ardea-herodias-nestlings-from-the-st-lawrence-river-qu%C3%A3-bec-canada
#16
Louise Champoux, Monique Boily, Guy Fitzgerald
The exposure and effects of persistent environmental contaminants were investigated in great blue heron (Ardea herodias) nestlings sampled in 2001, 2002, 2006, and 2007 in freshwater and estuarine heronries along the St. Lawrence River, Québec (Canada). Biomarkers (retinoids, thyroid hormones, and clinical parameters) and contaminants (organochlorine contaminants, polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), and mercury (Hg)) were analyzed in blood, and Hg was analyzed in feathers (generally 9 nestlings per colony and 4 colonies per year)...
February 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28088372/nanoformulation-of-dual-bexarotene-tailed-phospholipid-conjugate-with-high-drug-loading
#17
Ruiyu He, Yawei Du, Longbing Ling, Muhammad Ismail, Yongpeng Hou, Chen Yao, Xinsong Li
Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method...
March 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#18
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28054069/challenge-and-perspective-the-relevance-of-ultraviolet-uv-radiation-and-the-vitamin-d-endocrine-system-vdes-for-psoriasis-and-other-inflammatory-skin-diseases
#19
Jörg Reichrath, Roman Saternus, Thomas Vogt
During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
January 5, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28041994/a-dominant-mutation-in-rpe65-d477g-delays-dark-adaptation-and-disturbs-the-visual-cycle-in-the-mutant-knock-in-mice
#20
Younghwa Shin, Gennadiy Moiseyev, Dibyendu Chakraborty, Jian-Xing Ma
RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP...
December 30, 2016: American Journal of Pathology
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