Accurately identifying new therapeutic uses for drugs is crucial for advancing pharmaceutical research and development. Matrix factorization is often used in association prediction due to its simplicity and high interpretability. However, existing matrix factorization models do not enable real-time interaction between molecular feature matrices and similarity matrices, nor do they consider the geometric structure of the matrices.
View Article and Find Full Text PDFMixed gonadal dysgenesis is caused by a variety of chromosome abnormalities, most commonly Y chromosome mosaicism. An 8-year-old boy presented with short stature for possible treatment with recombinant growth hormone. He had a history of mixed gonadal dysgenesis (hypospadias, bilateral cryptorchidism, processus vaginalis, and dysplastic immature uterus) and a series of corrective surgeries.
View Article and Find Full Text PDFRecognizing drug-target interactions (DTI) stands as a pivotal element in the expansive field of drug discovery. Traditional biological wet experiments, although valuable, are time-consuming and costly as methods. Recently, computational methods grounded in network learning have demonstrated great advantages by effective topological feature extraction and attracted extensive research attention.
View Article and Find Full Text PDFZhongguo Dang Dai Er Ke Za Zhi
November 2023
Objectives: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD).
Methods: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022.
Results: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.
The accurate prediction of drug-target binding affinity (DTA) is an essential step in drug discovery and drug repositioning. Although deep learning methods have been widely adopted for DTA prediction, the complexity of extracting drug and target protein features hampers the accuracy of these predictions. In this study, we propose a novel model for DTA prediction named MSGNN-DTA, which leverages a fused multi-scale topological feature approach based on graph neural networks (GNNs).
View Article and Find Full Text PDFDuring acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR.
View Article and Find Full Text PDFMouse senile amyloidosis is a disorder in which apolipoprotein A-II (APOA2) deposits as amyloid fibrils (AApoAII) in many organs. We previously reported that AApoAII amyloidosis can be transmitted by feces, milk, saliva and muscle originating from mice with amyloid deposition. In this study, the ability of blood components to transmit amyloidosis was evaluated in our model system.
View Article and Find Full Text PDFUnlabelled: Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs.
View Article and Find Full Text PDFMouse senile amyloidosis is a disorder in which apolipoprotein A-II deposits extracellularly in many organs as amyloid fibrils (AApoAII). In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1-Apoa2(c) mice, to induce AApoAII amyloidosis.
View Article and Find Full Text PDFAim: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice.
Results: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio.