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#34522028   2021/09/14 To Up

The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme.

Deregulated polyamine biosynthesis is emerging as a common feature of neuroblastoma and drugs targeting this metabolic pathway such as DFMO are in clinical and preclinical development. The polyamine analog verlindamycin inhibits the polyamine biosynthesis pathway enzymes SMOX and PAOX, as well as the histone demethylase LSD1. Based on our previous research in acute myeloid leukemia (AML), we reasoned verlindamycin may also unblock neuroblastoma differentiation when combined with all-trans-retinoic acid (ATRA). Indeed, co-treatment with verlindamycin and ATRA strongly induced differentiation regardless of MYCN status, but in MYCN-expressing cells, protein levels were strongly diminished. This process was not transcriptionally regulated but was due to increased degradation of MYCN protein, at least in part via ubiquitin-independent, proteasome-dependent destruction. Here we report that verlindamycin effectively induces the expression of functional tumor suppressor-antizyme via ribosomal frameshifting. Consistent with previous results describing the function of antizyme, we found that verlindamycin treatment led to the selective targeting of ornithine decarboxylase (the rate-limiting enzyme for polyamine biosynthesis) as well as key oncoproteins, such as cyclin D and Aurora A kinase. Retinoid-based multimodal differentiation therapy is one of the few interventions that extends relapse-free survival in MYCN-associated high-risk neuroblastoma and these results point toward the potential use of verlindamycin in this regimen.
Zuzanna Urban-Wójciuk, Amy Graham, Karen Barker, Colin Kwok, Yordan Sbirkov, Louise Howell, James Campbell, Patrick M Woster, Evon Poon, Kevin Petrie, Louis Chesler

2977 related Products with: The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme.

1100 μg

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#34516292   2021/09/13 To Up

Synthetic Retinoids Beyond Cancer Therapy.

While the uses of retinoids for cancer treatment continue to evolve, this review focuses on other therapeutic areas in which retinoids [retinol (vitamin A), all- retinoic acid (RA), and synthetic retinoic acid receptor (RAR)α-, β-, and γ-selective agonists] are being used and on promising new research that suggests additional uses for retinoids for the treatment of disorders of the kidneys, skeletal muscles, heart, pancreas, liver, nervous system, skin, and other organs. The most mature area, in terms of US Food and Drug Administration-approved, RAR-selective agonists, is for treatment of various skin diseases. Synthetic retinoid agonists have major advantages over endogenous RAR agonists such as RA. Because they act through a specific RAR, side effects may be minimized, and synthetic retinoids often have better pharmaceutical properties than does RA. Based on our increasing knowledge of the multiple roles of retinoids in development, epigenetic regulation, and tissue repair, other exciting therapeutic areas are emerging. Expected final online publication date for the , Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Lorraine J Gudas

2081 related Products with: Synthetic Retinoids Beyond Cancer Therapy.



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#34514637   2021/09/13 To Up

Differences in acne therapy prescribing patterns between dermatologists and pediatricians: A population-based study.

Acne is a common skin condition that may be treated by both dermatologists and pediatricians. However, the treatments provided by dermatologists and pediatricians may differ. We aimed to describe acne therapy prescribing patterns of dermatologists and pediatricians.
Madison E Jones, Sarah P Pourali, Alison H Kohn, Yasmin Gutierrez, Jeffrey R Rajkumar, April W Armstrong

1932 related Products with: Differences in acne therapy prescribing patterns between dermatologists and pediatricians: A population-based study.

100 μg 1 G2 Pieces/Box100ul100ug1 Set100ug Lyophilized

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#34511970   2021/09/01 To Up

Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients.

This study aimed to understand the pathophysiology of host responses to infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) and Middle East respiratory syndrome coronavirus (MERS-CoV) and to identify proteins for patient stratification with different grades of illness severity.
Ayodele Alaiya, Abeer Alshukairi, Zakia Shinwari, Mariam Al-Fares, Jawaher Alotaibi, Waleed AlOmaim, Ibtihaj Alsharif, Razan Bakheet, Layla Alharbi, Rabab Allam, Ayed Asiri, Ziad Memish, Khaldoun Alromaih, Maha Al-Mozaini

1073 related Products with: Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients.

250 mg96T 5 G 1 G 2x5L500 MG250 mg 1 G 100 G

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#34509914   2021/09/07 To Up

Chemoproteomic profiling reveals cellular targets of nitro-fatty acids.

Nitro-fatty acids are a class of endogenous electrophilic lipid mediators with anti-inflammatory and cytoprotective effects in a wide range of inflammatory and fibrotic disease models. While these beneficial biological effects of nitro-fatty acids are mainly attributed to their ability to form covalent adducts with proteins, only a small number of proteins are known to be nitro-alkylated and the scope of protein nitro-alkylation remains undetermined. Here we describe the synthesis and application of a clickable nitro-fatty acid probe for the detection and first global identification of mammalian proteins that are susceptible to nitro-alkylation. 184 high confidence nitro-alkylated proteins were identified in THP1 macrophages, majority of which are novel targets of nitro-fatty acids, including extended synaptotagmin 2 (ESYT2), signal transducer and activator of transcription 3 (STAT3), toll-like receptor 2 (TLR2), retinoid X receptor alpha (RXRα) and glucocorticoid receptor (NR3C1). In particular, we showed that 9-nitro-oleate covalently modified and inhibited dexamethasone binding to NR3C1. Bioinformatic analyses revealed that nitro-alkylated proteins are highly enriched in endoplasmic reticulum and transmembrane proteins, and are overrepresented in lipid metabolism and transport pathways. This study significantly expands the scope of protein substrates targeted by nitro-fatty acids in living cells and provides a useful resource towards understanding the pleiotropic biological roles of nitro-fatty acids as signaling molecules or as multi-target therapeutic agents.
Ming-Yu Fang, Kuan-Hsun Huang, Wei-Ju Tu, Yi-Ting Chen, Pei-Yun Pan, Wan-Chi Hsiao, Yi-Yu Ke, Lun K Tsou, Mingzi M Zhang

1050 related Products with: Chemoproteomic profiling reveals cellular targets of nitro-fatty acids.

1,000 tests 1 G100 5 G5 mg 1 G2.5 mg 1 G100 assays5 x 50 ug

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#34508587   2021/09/11 To Up

The vitamin a transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling.

The retinal pigment epithelium of the vertebrate eyes acquires vitamin A from circulating retinol binding protein for chromophore biosynthesis. The chromophore covalently links with an opsin protein in the adjacent photoreceptors of the retina to form the bipartite visual pigment complexes. We here analyzed visual pigment biosynthesis in mice deficient for the retinol binding protein receptor STRA6. We observed that chromophore content was decreased throughout the life cycle of these animals, indicating that lipoprotein-dependent delivery pathways for the vitamin cannot substitute for STRA6. Changes in the expression of photoreceptor marker genes, including a down-regulation of the genes encoding rod and cone opsins, paralleled the decrease in ocular retinoid concentration in STRA6-deficient mice. Despite this adaptation, cone photoreceptors displayed absent or mislocalized opsins at all ages examined. Rod photoreceptors entrapped the available chromophore but exhibited significant amounts of chromophore-free opsins in the dark-adapted stage. Treatment of mice with pharmacological doses of vitamin A ameliorated the rod phenotype but did not restore visual pigment synthesis in cone photoreceptors of STRA6-deficient mice. The imbalance between chromophore and opsin concentrations of rod and cone photoreceptors was associated with an unfavorable retinal physiology, including diminished electrical responses of photoreceptors to light, and retinal degeneration during aging. Together, our study demonstrates that STRA6 is critical to adjust the stoichiometry of chromophore and opsins in rod cone photoreceptors and to prevent pathologies associated with ocular vitamin A deprivation.
Srinivasagan Ramkumar, Vipul M Parmar, Ivy Samuels, Nathan A Berger, Beata Jastrzebska, Johannes von Lintig

2154 related Products with: The vitamin a transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling.

11 mg100 μg2.5 mg

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#34502180   2021/08/27 To Up

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium.

Leukocyte cell recruitment into the vascular subendothelium constitutes an early event in the atherogenic process. As the effect of the constitutive androstane receptor (CAR) on leukocyte recruitment and endothelial dysfunction is poorly understood, this study investigated whether the role of CAR activation can affect this response and the underlying mechanisms involved. Under physiological flow conditions, TNFα-induced endothelial adhesion of human leukocyte cells was concentration-dependently inhibited by preincubation of human umbilical arterial endothelial cells with the selective human CAR ligand CITCO. CAR agonism also prevented TNFα induced VCAM-1 expression, as well as MCP-1/CCL-2 and RANTES/CCL-5 release in endothelial cells. Suppression of CAR expression with a small interfering RNA abrogated the inhibitory effects of CITCO on these responses. Furthermore, CITCO increased interaction of CAR with Retinoid X Receptor (RXR) and reduced TNFα-induced p38-MAPK/NF-κB activation. In vivo, using intravital microscopy in the mouse cremasteric microcirculation treatment with the selective mouse CAR ligand TCPOBOP inhibited TNFα-induced leukocyte rolling flux, adhesion, and emigration and decreased VCAM-1 in endothelium. These results reveal that CAR agonists can inhibit the initial inflammatory response that precedes the atherogenic process by targeting different steps in the leukocyte recruitment cascade. Therefore, CAR agonists may constitute a new therapeutic tool in controlling cardiovascular disease-associated inflammatory processes.
Mireia López-Riera, Rebeca Ortega, Luisa Hueso, María Carmen Montesinos, Mari Carmen Gomez-Cabrera, María Jesús Sanz, José T Real, Laura Piqueras

2919 related Products with: Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium.

96T100 96T100 100.00 ug100 μg

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#34502048   2021/08/24 To Up

The Role of Histone Deacetylase 3 Complex in Nuclear Hormone Receptor Action.

Nuclear hormone receptors (NRs) regulate transcription of the target genes in a ligand-dependent manner in either a positive or negative direction, depending on the case. Deacetylation of histone tails is associated with transcriptional repression. A nuclear receptor corepressor (N-CoR) and a silencing mediator for retinoid and thyroid hormone receptors (SMRT) are the main corepressors responsible for gene suppression mediated by NRs. Among numerous histone deacetylases (HDACs), HDAC3 is the core component of the N-CoR/SMRT complex, and plays a central role in NR-dependent repression. Here, the roles of HDAC3 in ligand-independent repression, gene repression by orphan NRs, NRs antagonist action, ligand-induced repression, and the activation of a transcriptional coactivator are reviewed. In addition, some perspectives regarding the non-canonical mechanisms of HDAC3 action are discussed.
Sumiyasu Ishii

1651 related Products with: The Role of Histone Deacetylase 3 Complex in Nuclear Hormone Receptor Action.

100 UG2 Pieces/Box100ug100 μg100ug96 wells (1 kit) 5 G10mg50 ul1 mg100ug Lyophilized

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#34501349   2021/08/30 To Up

Pili Torti: A Feature of Numerous Congenital and Acquired Conditions.

Pili torti is a rare condition characterized by the presence of the hair shaft, which is flattened at irregular intervals and twisted 180° along its long axis. It is a form of hair shaft disorder with increased fragility. The condition is classified into inherited and acquired. Inherited forms may be either isolated or associated with numerous genetic diseases or syndromes (e.g., Menkes disease, Björnstad syndrome, Netherton syndrome, and Bazex-Dupré-Christol syndrome). Moreover, pili torti may be a feature of various ectodermal dysplasias (such as Rapp-Hodgkin syndrome and Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome). Acquired pili torti was described in numerous forms of alopecia (e.g., lichen planopilaris, discoid lupus erythematosus, dissecting cellulitis, folliculitis decalvans, alopecia areata) as well as neoplastic and systemic diseases (such as cutaneous T-cell lymphoma, scalp metastasis of breast cancer, anorexia nervosa, malnutrition, cataracts, and chronic graft-vs.-host disease). The condition may also be induced by several drugs (epidermal growth factor receptor inhibitors, oral retinoids, sodium valproate, and carbamide perhydrate). The diagnosis of pili torti is based on trichoscopic or microscopic examination. As pili torti is a marker of numerous congenital and acquired disorders, in every case, the search for the signs of underlying conditions is recommended.
Aleksandra Hoffmann, Anna Waśkiel-Burnat, Jakub Żółkiewicz, Leszek Blicharz, Adriana Rakowska, Mohamad Goldust, Małgorzata Olszewska, Lidia Rudnicka

2652 related Products with: Pili Torti: A Feature of Numerous Congenital and Acquired Conditions.

100μg50 ug 10 mg1 ml1 mg1000 tests100ul200ul25 mg100ug10 mg

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