RESUMEN
BACKGROUND: The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro. METHODS: DNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients. RESULTS: We detected 21 IGF1R defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of IGF1R. Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation. CONCLUSION: We report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS.
Asunto(s)
Anomalías Múltiples/genética , Desarrollo Fetal/genética , Retardo del Crecimiento Fetal/genética , Trastornos del Crecimiento/genética , Receptor IGF Tipo 1/genética , Anomalías Múltiples/epidemiología , Anomalías Múltiples/fisiopatología , Adolescente , Niño , Enanismo/genética , Enanismo/fisiopatología , Femenino , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/fisiopatología , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/fisiopatología , Heterocigoto , Homocigoto , Humanos , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Factor I del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Microcefalia/genética , Microcefalia/fisiopatología , Mutación Missense/genética , Linaje , Polimorfismo de Nucleótido Simple/genética , Receptores de Somatomedina/genéticaRESUMEN
Parkinson's disease (PD) is characterized by progressive locomotive defects and loss of dopaminergic neurons. Polyscias fruticosa leaves are used by Vietnamese as herbal medicines to support the treatment of some diseases related to neurodegeneration such as Parkinson's and Alzheimer's diseases. However, recent scientific data have not provided sufficient evidence for the use of P. fruticosa leaves to treat PD or decelerate PD progression. In the present study, the capacity of P. fruticosa leaf extract for PD treatment on the dietary supplementation was investigated using dUCH-knockdown Drosophila model. The results indicated that P. fruticosa leaf extract decelerated dopaminergic neuron degeneration induced by dUCH knockdown in not only the larval stage but also the adult stage, which might result in the amelioration in locomotor ability of dUCH-knockdown larvae and flies. Furthermore, antioxidant activities and some key phytochemicals such as saponins, polyphenols, and flavonoids that might contribute to the effects of the P. fruticosa leaf extract were identified.
Asunto(s)
Araliaceae , Enfermedad de Parkinson , Animales , Neuronas Dopaminérgicas , Drosophila , Drosophila melanogaster , Enfermedad de Parkinson/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Free fatty acids (FFAs) were obtained from hydrolyzed virgin coconut oil (VCO) by Candida rugosa lipase (CRL). Four factors' influence on hydrolysis degree (HD) was examined. The best hydrolysis conditions in order to get the highest HD value were determined at VCO to buffer ratio 1 : 5 (w/w), CRL concentration 1.5% (w/w oil), pH 7, and temperature 40°C. After 16 hours' reaction, the HD value achieved 79.64%. FFAs and residual hydrolyzed virgin coconut oil (HVCO) were isolated from the hydrolysis products. They were tested for their antibacterial activity against Gram-negative and Gram-positive bacteria, which can be found in contaminated food and cause food poisoning. FFAs showed their inhibition against Bacillus subtilis (ATCC 11774), Escherichia coli (ATCC 25922), Salmonella enteritidis (ATCC 13076), and Staphylococcus aureus (ATCC 25923) at minimum inhibitory concentration (MIC) of 50%, 60%, 20%, and 40%, respectively. However, VCO and HVCO did not show their antibacterial activity against these tested bacteria.