A5089718146- Retinoids in leukemia and cellular processes
- Circadian rhythm and melatonin
- Computational Drug Discovery Methods
- Antioxidant Activity and Oxidative Stress
- Drug Transport and Resistance Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- Nanoparticle-Based Drug Delivery
- Cancer Cells and Metastasis
- Biotechnology and Related Fields
- Cancer Research and Treatments
- Estrogen and related hormone effects
- Pregnancy and Medication Impact
- Cancer Mechanisms and Therapy
- Psoriasis: Treatment and Pathogenesis
- Cytokine Signaling Pathways and Interactions
- Tuberculosis Research and Epidemiology
- Pancreatic function and diabetes
- Enzyme function and inhibition
- Genetics, Aging, and Longevity in Model Organisms
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Coenzyme Q10 studies and effects
- Natural Antidiabetic Agents Studies
- Seaweed-derived Bioactive Compounds
King Saud bin Abdulaziz University for Health Sciences
2016-2025
National Guard Health Affairs
2016-2025
King Abdullah International Medical Research Center
2016-2025
King Abdulaziz Medical City
2016-2023
GlaxoSmithKline (United Kingdom)
2005-2014
Molecular Discovery (United Kingdom)
2013
Imperial College London
2009
GlaxoSmithKline (India)
2009
New Frontier
2009
University of Michigan–Ann Arbor
1998-2002
We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene from P19 embryonal carcinoma cells that encodes basic helix–loop–helix (bHLH) protein shows highest sequence similarities to Drosophila Hairy and Enhancer split mouse Hes proteins. Stra13 does not bind known consensus motifs (E-box N-box) for bHLH proteins, but can repress activated transcription (through an α-helix rich domain) in part by interaction with general factors basal machinery. During embryogenesis,...
IL-17-producing CD4(+)Th17 cells, CD8(+)Tc17 and γδ T cells play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for differentiation Th17 expression IL-17. In this article, we describe a novel, potent, selective inverse agonist (TMP778), its inactive diastereomer (TMP776). This chemistry, first time to our knowledge, provides unique powerful set tools probe RORγt-dependent functions. TMP778, but not TMP776, blocked human Tc17 cell also acutely modulated IL-17A...
Pregnancy alters bile acid homeostasis and can unmask cholestatic disease in genetically predisposed but otherwise asymptomatic individuals. In this report, we show that normal pregnant mice have raised hepatic levels the presence of procholestatic gene expression. The nuclear receptor farnesoid X (FXR) regulates transcription majority these genes, both ablation activation Fxr prevent accumulation acids during pregnancy. These observations suggest function may be perturbed gestation....
Circadian rhythms govern a wide variety of physiological and metabolic functions in many organisms, from prokaryotes to humans. We previously reported that silent information regulator 1 (SIRT1), NAD + -dependent deacetylase, contributes circadian control. In addition, SIRT1 activity is regulated cyclic manner virtue the oscillation coenzyme . Here we used specific activator compounds both vitro vivo. tested show activation alters CLOCK:BMAL1-driven transcription different systems....
REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization a series agonists based GSK4112 (1) potency, selectivity, bioavailability. Potent 4, 10, 16, 23 are detailed their ability to suppress BMAL IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.
Marine algae are found to be excellent in their nutritional and potential therapeutic properties. This study explores the antidiabetic anticancer of fractionated polyphenolic extract Caulerpa racemosa, green macroalgae. Crude (CPE) C. racemosa its fractions (n-hexane, ethyl acetate, chloroform, distilled water) were tested for total phenol flavonoid contents antioxidant potential. The acetate fraction was subjected gas chromatography/mass spectrometry (GC/MS). vitro activity assessed by...
1,25-Dihydroxyvitamin D3 (D3) exerts its effects by binding to and activating nuclear vitamin receptors (VDRs) that regulate transcription of target genes. We have investigated regulation VDR levels in human skin vivo cultured keratinocytes. Quantitative ligand-binding analysis revealed expressed approximately 220 VDRs per cell, which bound with high affinity[ (dissociation constant (Kd) = 0.22 nm]. In extracts, exclusively DNA containing response elements as heterodimers retinoid X...
Rodents undergo gestational hepatomegaly to meet the increased metabolic demands on maternal liver during pregnancy. This is an important physiological process, but mechanisms and signals driving pregnancy-induced growth are not known. Here, we show that pregnancy precedes body weight gain, proportional fetal number, a result of hepatocyte hypertrophy associated with cell-cycle progression, polyploidy, altered expression regulators p53, Cyclin-D1, p27. Because circulating reproductive...
Abstract The preparation of mesoporous iron oxides with controllable physiochemical properties for effective therapeutic drug delivery remains a formidable challenge. Herein, oxide magnetic microparticles (IO-MMMs) were prepared by modified reverse hard-templating approach using, the first time, acid-prepared spheres (APMS) as hard silica template. obtained mesostructures exhibited remarkably high surface area and large pore volumes ( S BET = 240 m 2 /g V 0.55 cm 3 /g), average sizes,...
Peroxisome proliferator-activated receptors (PPARs) are considered good drug targets for breast cancer because of their involvement in fatty acid metabolism that induces cell proliferation. In this study, we used the KAIMRC1 line. We showed PPARE-Luciferase reporter gets highly activated without adding any exogenous ligand when PPAR alpha is co-transfected, and antagonist GW6471 can inhibit activity. Using system, screened 240 compounds representing kinase inhibitors, epigenetic modulators,...
Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined potentials different fractions (hexane, chloroform, ethyl acetate, methanol) N. abor-tristis flower extract for first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy adult acute myeloid (AML) chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T MCF7 cell lines....
Biological samples usually require cumbersome preparation steps before SEM imaging. Here we propose a simple, fast and inexpensive method to prepare visualize biological cell culture in few easy steps. We have tested this with success on several adherent breast cancer non-adherent leukemia lines. This gives results comparable other well-established techniques, it can be convenient day-to-day sample for imaging.•An rapid specimens under SEM.•Cells are grown carbon tapes gold coated.•Air...
Breast cancer is one of the most common and a leading cause death in women. Up to date commonly used breast cell lines are originating from Caucasians or Afro-Americans but rarely cells being derived other ethnic groups. Here we describe for first time establishment naturally transformed line, KAIMRC1 an Arab woman age 62 suffering stage IIB (T2N1M0). Moreover, have characterized these biological molecular markers, induction MAPK pathways as well its response different commercially available...
The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB (GR) agonist assay (representing transrepression effects) over MMTV GR transactivation effects). Quinolones, indoles, C- N-linked quinolines some the that provide selectivity. For example, isoquinoline 49D1E2 has agonism pIC50 8.66 (89%) reduced (6%), quinoline 55D1E1 9.30...
We report the development of a chemotherapeutic nanoformulation made polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake cell death were evaluated in three types cells: two metastatic cancerous MCF-7 MDA-MB-231 cells nontumorigenic MCF-10A cells. While Fl-PMNPs not toxic even at highest concentrations used, Dox-loaded...
The membrane receptor for retinol-binding protein (RBP) has been solubilized from human placental brush-border membranes with octyl-beta-glucoside, Nonidet P-40 and CHAPS. A method, based on the preferential precipitation of 125I-RBP-receptor complex poly(ethylene glycol) 8000, was developed in order to measure RBP-binding activity detergent extracts. fairly stable (4 degrees C, 7 days) octyl-beta-glucoside P-40, but quickly lost detergent-solubilized form retained all properties...
Skeletal development throughout the embryonic and postnatal phases is a dynamic process, based on bone remodeling balance between activities of osteoclasts osteoblasts modulating skeletal homeostasis. The Notch signaling pathway regulator several developmental processes, plays crucial role in human skeleton by regulating proliferation differentiation cells. Delta Like-1 (DLL1) gene an important signaling. We propose that identified alteration DLL1 protein may affect downstream In this...
The axon initial segment (AIS), the site of action potential initiation in neurons, is a critical determinant neuronal excitability. Growing evidence indicates that appropriate recruitment AIS macrocomplex essential for synchronized firing. However, disruption structure linked to etiology multiple disorders, including autism spectrum disorder (ASD), condition characterized by deficits social communication, stereotyped behaviors, and very limited interests. To date, complete understanding...
Specific binding of 125I-labelled bovine odour-binding protein (OBP) to isolated membranes from nasal mucosa was demonstrated. The interaction reached equilibrium within 30 min at 37 degrees C and reversible. A Scatchard analysis the revealed a single population sites, with calculated dissociation constant maximum number sites being 2.25 +/- 0.5 microM 18.5 2 pmol/mg membrane respectively (n = 2). Receptor activity decreased on digestion by trypsin, proteinase K or endoglycosidase H, heat...
The intestinal-derived secondary bile acid (BA) lithocholic (LCA) is hepatotoxic and implicated in the pathogenesis of cholestatic diseases. LCA an endogenous ligand xenobiotic nuclear receptor pregnane X (PXR), but there currently no consensus on respective roles hepatic intestinal PXR mediating protection against vivo. Under conditions reported here, we show that mice lacking Pxr are resistant to LCA-mediated hepatotoxicity. This unexpected phenotype found association with enhanced urinary...