A5027397009- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Blood disorders and treatments
- Biological Stains and Phytochemicals
- Bioactive Natural Diterpenoids Research
- Chemotherapy-induced organ toxicity mitigation
- Retinoids in leukemia and cellular processes
- Phytochemical compounds biological activities
- Natural Antidiabetic Agents Studies
- 14-3-3 protein interactions
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Curcumin's Biomedical Applications
- Trace Elements in Health
- Bioactive Compounds and Antitumor Agents
- Microbial Natural Products and Biosynthesis
- Bioactive natural compounds
- Plant Genetic and Mutation Studies
- Cellular transport and secretion
- Wnt/β-catenin signaling in development and cancer
- Phytochemical Studies and Bioactivities
- Boron Compounds in Chemistry
- Cancer-related gene regulation
University of Geneva
2021-2025
University Hospital Cologne
2024
University of Cologne
2024
Weatherford College
2024
Far Eastern Federal University
2023
Lomonosov Moscow State University
2023
Universitas Gadjah Mada
2013-2020
Nara Institute of Science and Technology
2018
Curcumin has been reported to exhibit anti-tumorigenic activity; however, since its precise actions remain unclear, effects are considered be deceptive. In the present study, we confirmed of curcumin on CML-derived leukemic cells in a xenograft model and vitro culture system. pull-down mass analyses revealed series enzymes (carbonyl reductase, glutathione-S-transferase, glyoxalase, etc.) that function reactive oxygen species (ROS) metabolic pathway as curcumin-binding targets, expression...
De novo point mutations in GNAO1, gene encoding the major neuronal G protein Gαo, have recently emerged patients with pediatric encephalopathy having motor, developmental, and epileptic dysfunctions. Half of clinical cases affect codons Gly203, Arg209, or Glu246; we show that these accelerate GTP uptake inactivate hydrolysis through displacement Gln205 critical for hydrolysis, resulting constitutive binding by Gαo. However, mutants fail to adopt activated conformation display aberrant...
Abstract Background Defects in GNAO1 , the gene encoding major neuronal G‐protein Gαo, are related to neurodevelopmental disorders, epilepsy, and movement disorders. Nevertheless, there is a poor understanding of how molecular mechanisms explain different phenotypes. Objectives We aimed analyze clinical phenotype characterization ‐related Methods Patients were recruited collaboration with Spanish Association. For patient phenotyping, direct evaluation, analysis homemade‐videos, an online...
Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on highly metastatic breast cell line, 4T1 cells, as an anti-metastatic and anti-proliferative agent. Methods: Cell viability was using MTT assay; while cycle profile, apoptosis incidence, ROS intracellular level were determined by flow cytometry. senescence observed under senescence-associated-β-galactosidase (SA-β-gal) staining...
Context and significanceMutations in the gene GNAO1 lead to severe sometimes fatal pediatric encephalopathies that are poorly responsive current treatments. The pathogenic mutations produce aberrant variants of a major neuronal signaling protein Gαo. Salts zinc partially correct abnormal functioning mutant Here, dozens Gαo shown fall into distinct groups their responsiveness zinc, providing ground for patient stratification. Zinc supplementation is safe mouse disease models, leading...
Abstract Background Patients carrying pathogenic variants in GNAO1 present a phenotypic spectrum ranging from severe early‐onset epileptic encephalopathy and developmental delay to mild adolescent/adult‐onset dystonia. Genotype–phenotype correlation molecular mechanisms underlying the disease remain understudied. Methods We analyzed clinical course of child novel mutation c.38T>C;p.Leu13Pro, structural, biochemical, cellular properties corresponding mutant Gαo— ‐encoded protein—alongside...
Purpose: The current study aims to evaluate the in vitro cytotoxic and cell migration effects of synthetic curcumin its analogues on HER2 nuclear factor kappa B (NFκB) pathways, as well vivo inhibitory effect cancer growth metastatic breast cancer. Methods: Cell viability, protein expression, localization were determined using MTT assay, western blotting, immunofluorescence, respectively. Meanwhile, scratch wound healing assay gelatin zymography conducted investigate metastasis effect....
Gαo is the major G protein in neurons, where it transduces signals from numerous protein-coupled receptors (GPCRs) such as D2 dopamine, μ-opioid, M2 muscarinic, or α2-adrenergic receptors. In 2013, first mutations GNAO1, gene encoding Gαo, were described pediatric patients with encephalopathies (Nakamura et al., 2013), suffering movement disorders, epileptic seizures, and developmental delay. As of today, over 200 have been identified GNAO1 mutation carriers (https://gnao1.org/) mainly...
To observe the combination effect of doxorubicin and Citrus hystrix (kaffir lime's) peel ethanolic extract (ChEE) on blood serum alanine aminotransferase (ALT) aspartate (AST) activity cardio-hepato-histopathology female Sprague Dawley rats.Doxorubicin ChEE (5 rats per group) were administered in five groups 3 each for 11 d. Group I: (dox) 4.67 mg/kg body weight; II: dox+ChEE 500 III: 1 000 IV: V: untreated (control).ChEE repaired cardiohistopathology profile induced cardiotoxicity...
<title>Abstract</title> Rare diseases typically evade the application of standard drug discovery and development pipeline due to their understudied molecular etiology small market size. Here, we report a rare disease-directed workflow that rapidly studies features disorder, establishes high-throughput screening (HTS) platform, conducts an HTS thousands approved drugs identify validate repositioning candidates. Applied pediatric neurological disorder caused by <italic>de novo</italic>...
Rare diseases typically evade the application of standard drug discovery and development pipelines due to their understudied molecular etiology small market size. Herein, we report a rare disease-directed workflow that rapidly studies features disorder, establishes high-throughput screening (HTS) platform, conducts an HTS thousands approved drugs identify validate repositioning candidates. This study examines pediatric neurological disorder caused by de novo mutations in YWHAG, gene encoding...
ABSTRACT GNAO1 ‐associated disorders have a large spectrum of neurological symptoms, from early‐onset developmental and epileptic encephalopathies (DEE) to late‐onset movement disorders. First reported in 2013 now identified around 400 cases worldwide, this disease is caused by dominant, mostly de novo missense mutations , the gene encoding major neuronal G protein Gαo. Being immediate transducer number protein‐coupled receptors, Gαo plays crucial functions brain development physiology....
Cell cycle regulation and the NF-κB pathway in cancer cells are important mediating resistance to 5-Fluorouracil (5-FU). Pentagamavunon-1 (PGV-1), a curcumin analog, is known exhibit stronger growth inhibitory effects than itself several cells. In this study, we evaluated potency of PGV-1 combination with 5-FU WiDr colon MTT assays, did not only both curcumin, but also enhanced cytotoxicity 5-FU. Flow cytometry demonstrated that single treatments resulted different on cell profiles. induced...
Cinnamon (Cinnamomum spp.), an ancient spice, has been explored as a potential for medicinal purposes. Despite numerous studies about its potency in overcoming of diseases, the anti-cancer would be challenge. This current article provides review and chemoprevention cinnamon major constituents: cinnamaldehyde, cinnamic acid, 2-hydroxycinnamaldehyde, 2-methoxycinnamaldehyde, eugenol. Comprehensively, constituents exhibit cancer prevention activities through various mechanisms: (1)...
Cisplatin is drug of choice toward cervical cancer despite having many side effects, thus researches are conducted in order to find the effective and synergistic co-chemoterapeutic agent combined with cisplatin. In this study, we observed potential cinnamon essential oil (CEO) isolated from Cinnamomum burmannii as cisplatin on HeLa cells covering cytotoxic effect, cell cycle modulation induction apoptosis. Cytotoxic effect was determined by using MTT assay; while apoptosis profile were flow...
De novo mutations in GNAO1, the gene encoding major neuronal G protein Gαo, cause a spectrum of pediatric encephalopathies with seizures, motor dysfunction, and developmental delay. Of >80 distinct missense pathogenic variants, many appear to uniformly destabilize guanine nucleotide handling mutant protein, speeding up GTP uptake deactivating hydrolysis. Zinc supplementation emerges as promising treatment option for this disease, Zn2+ ions reactivate hydrolysis on Gαo restore cellular...
Abstract De novo mutations in GNAO1 – the gene encoding major neuronal G-protein Gαo cause pediatric encephalopathies largely refractory to available therapies. Zn 2+ emerged restore GTP hydrolysis and cellular interactions of pathogenic Gαo; dietary supplementation improves lifespan motoric function a Drosophila disease model. Here we show that 16 different missense cluster three distinct groups their responsiveness , provide safety study mouse We further describe treatment 3 years-old...
Cinnamon (Cinnamomum burmannii) shows anticancer activity in several types of cancer cells. The aim this study is to observe the cytotoxic cinnamon essential oil (CEO) solely and its combination with doxorubicin, also ability induce apoptosis on T47D breast CEO was prepared through distillation dry bark. Cytotoxic assay performed by using MTT determination done double staining ethidium bromide acridine orange. result showed that exhibited effect cells IC50 values 75 µg/ml. Moreover,...
Abstract GNAO1 encephalopathy is a rare pediatric disease characterized by motor dysfunction, developmental delay, and epileptic seizures 1-3 . De novo point mutations in the gene encoding Gαo, major neuronal G protein, lie at core of this dominant genetic malady 4 Half clinical case fall on codons Gly203, Arg209, or Glu246 near GTP binding/hydrolysis pocket Gαo We here show that these pathologic strongly speed up uptake inactivate hydrolysis resulting constitutive binding protein. Molecular...