- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Drug Transport and Resistance Mechanisms
- Neuropeptides and Animal Physiology
- Pharmacogenetics and Drug Metabolism
- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Pancreatic function and diabetes
- Pharmacological Effects and Toxicity Studies
- Tryptophan and brain disorders
- Medical Imaging and Pathology Studies
- Radiopharmaceutical Chemistry and Applications
- Fluoride Effects and Removal
- MicroRNA in disease regulation
- Bone and Dental Protein Studies
- Lung Cancer Treatments and Mutations
- Congenital heart defects research
- Child Development and Digital Technology
- Peptidase Inhibition and Analysis
- Inflammatory mediators and NSAID effects
- Microbial Metabolism and Applications
- Liver physiology and pathology
- Traditional Chinese Medicine Analysis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Phosphodiesterase function and regulation
Boston University
2017-2025
Northwest A&F University
2024
Zunyi Medical University
2023
Bristol-Myers Squibb (United States)
2008-2021
Kanazawa University Hospital
2018
Bay State College
2017
Lanzhou University
2007-2012
Cornell University
2007
Memorial Sloan Kettering Cancer Center
2007
Caspase activation, the executing event of apoptosis, is under deliberate regulation. IAP proteins inhibit caspase activity, whereas Smac/Diablo antagonizes IAP. XIAP, a ubiquitous IAP, can both caspase-9, initiator mitochondrial apoptotic pathway, and downstream effector caspases, caspase-3 caspase-7. Smac neutralizes XIAP inhibition caspase-9 by competing for binding BIR3 domain with how liberates caspases from not clear. It generally believed that generates steric hindrance prevents...
17α-Ethinylestradiol (EE2), a component of oral contraceptives, is known to undergo considerable first-pass 3-<i>O</i>-sulfation in the intestine and liver. Once formed, 3-<i>O</i>-sulfate conjugate (EE2-Sul) detected circulation at appreciable levels (versus parent EE2) present bile. Therefore, hepatic uptake EE2-Sul was assessed with suspensions cryopreserved human primary hepatocytes. In this instance, there evidence for active (temperature-dependent) uptake, which described by...
Abstract UBE3A is a common genetic factor in ASD etiology, and transgenic mice overexpressing exhibit typical autistic-like behaviors. Because AMPA receptors (AMPARs) mediate most of the excitatory synaptic transmission brain, dysregulation considered one primary cellular mechanisms pathology, we investigate here involvement AMPARs UBE3A-dependent ASD. We show that expression AMPAR GluA1 subunit decreased UBE3A-overexpressing mice, AMPAR-mediated neuronal activity reduced. mRNA trapped...
Kidney-derived Madin Darby canine kidney (MDCK) cells form lumina at their apices, and target luminal proteins to an intracellular vacuolar apical compartment (VAC) when prevented from polarizing. Hepatocytes, by contrast, organize surfaces (the bile canaliculi; BC) between lateral membranes, and, nonpolarized, they display that is distinct the VACs of MDCK cells. Overexpression serine/threonine kinase Par1b/EMK1/MARK2 induces BC-like a hepatic-type in cells, suggesting role for Par1b...
The balance of gut microbiota affects uric acid synthesis and excretion, influencing the development hyperuricemia. This study aimed to investigate effects mechanisms probiotics on hyperuricemia adenine- potassium oxonate-induced colonic damage. After two months gavage at 10
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Co‐administration of gemfibrozil significantly increases the exposure repaglinide. CYP3A4 and CYP2C8 are important in metabolism OATP1B1 polymorphism is an independent predictor repaglinide pharmacokinetics. Gemfibrozil its O‐glucuronide inhibitors. STUDY ADDS Acyl glucuronidation a major metabolic pathway vitro . glucuronide inhibit UGT1A1 enzyme responsible for AIM To further explore mechanism underlying interaction between gemfibrozil, alone or...
In the wake of financial crisis International Monetary Fund (IMF) began to publicly express support for what have traditionally been referred as 'capital controls'. This paper empirically examines extent which change in IMF discourse on these matters has resulted significant changes actual policy advice. By creating and analyzing a database Article IV reports, we examine whether had an independent impact capital controls. We find that IMF's level controls increased result vulnerabilities...
17alpha-Ethinylestradiol (EE2), a synthetic and potent estrogen receptor agonist, is extensively metabolized in both intestine liver largely excreted bile urine as the 3-O-sulfate (EE2-Sul) 3-O-glucuronide. In present study, EE2-Sul was evaluated substrate of various transporters known to be expressed kidney. Uptake studies were performed with human epithelial cells [human embryonic kidney (HEK)-293] that contained individually organic cation transporter 2 (OCT2), anion (OAT) forms 3 4,...
A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position carboxylic acid, key pharmacophore GPR40. Addition 4-cis-CF3 to improves human binding Ki and agonist efficacy. After further optimization, discovery minor enantiomeric impurity with activity led finding that enantiomers (R,R)-68 (S,S)-68 have differential effects on radioligand used assay, potentiating displacing...
Two classes of structurally different tachykinin neurokinin3 (NK3) antagonists were used to evaluate species difference in antagonist binding between human and rat NK3 receptors. In competition experiments with [125I-MePhe7]NKB as radioligand, PD 154740, 157672, SR 48968, 142801 displayed lower Ki values for the receptor (40 +/- 4, 12 1,350 50, 0.40 0.05 nM, respectively) than (2450 130, 288 25, > 10,000, 11.0 0.5 respectively). Data from vitro functional assay showed similar preference...
To assess targeting of an epothilone folate conjugate (BMS-753493) to the receptor (FR)-overexpressed tumor in mice bearing both FR+ and FR- tumors, a series experiments were conducted by quantitative whole-body autoradiography (QWBA) LC-MS/MS following i.v. administration BMS-753493 or its active moiety, BMS-748285 (98M109) (M109) tumors. QWBA showed [3H]BMS-753493-derived radioactivity was extensively distributed various tissues. The FR over-expressing 98M109 tumors consistently higher...
Autism spectrum disorder (ASD) is a neurodevelopmental with high genetic heterogeneity, affecting one in 44 children the United States. Recent genomic sequencing studies from autistic human individuals indicate that PARK2, gene has long been considered pathogenesis of Parkinson's disease, involved ASD. Here, we report Prkn knockout (KO) mice demonstrate autistic-like behaviors including impaired social interaction, elevated repetitive behaviors, and deficits communication. In addition, KO...
Duplication and haploinsufficiency of the USP7 gene are implicated in autism spectrum disorders (ASD), but role for neurodevelopment contribution to ASD pathogenesis remain unknown. We find that primary neurons, overexpression increases dendritic branch number total length, whereas knockdown leads opposite alterations. Besides, deubiquitinates X-linked inhibitor apoptosis protein (XIAP). The USP7-induced increase XIAP suppresses caspase 3 activity, leading a reduction tubulin cleavage...
Abstract Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method treat the hepatic metastasis of pancreatic cancer than intravenous (iv) administration because higher tumor exposure lower systemic exposure. To clarify uptake mechanism nucleoside anticancer drugs, including gemcitabine (GEM), in cancer, we investigated uptakes radiolabeled uridine (a general substrate transporters) GEM cell lines MIA‐PaCa2 As‐PC1. Uridine was inhibited by non‐labeled...
Dental fluorosis is a common chemical disease. It currently unclear how occurs at the molecular level. We used miRNA-seq to look differences between miRNAs in cell line of ameloblasts LS8 that had been treated with 3.2 mmol/L NaF. also performed gene ontology (GO) and Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses. miR-1a-3p levels were significantly lower mouse cells NaF, miR-1a-3p-targeted genes enriched MAPK pathway. divided into four groups: control, NaF+miR-1a-3p...
Overexpression of the Ube3a gene and resulting increase in protein are linked to autism spectrum disorder (ASD). However, cellular molecular processes underlying Ube3a-dependent ASD remain unclear. Using both male female mice, we find that neurons somatosensory cortex 2× Tg mouse model display reduced dendritic spine density increased immature filopodia density. Importantly, dosage astrocytes alone is sufficient confer alterations as protrusions, observed primary hippocampal neuron cultures....
Despite a recent expansion in the recognition of potential utility coproporphyrin (CP) as an endogenous biomarker organic anion-transporting polypeptide (OATP) 1B activity, there have been few detailed studies CP's pharmacokinetic behavior and overall poor understanding its fate from tissues excretion. Here, we describe pharmacokinetics octadeuterium-labeled I (CPI-d8) cynomolgus monkeys following oral intravenous administration. CPI-d8 has half-life bioavailability 7.6 hours 3.2%,...
Abstract Tritium‐labeled [1,2‐ 3 H]ethylamine hydrochloride was prepared through a multiple‐step sequence in high radioactive specificity. The labeled amine isolated purity following cartridge filtration and used subsequently the synthesis of [ N ‐ethyl‐1,2‐ H]apadenoson, an adenosine A 2a receptor agonist. overall yield for this transformation 56% radiochemical final product greater than 99%. Copyright © 2008 John Wiley & Sons, Ltd.