A5008276506- Pregnancy and preeclampsia studies
- Adenosine and Purinergic Signaling
- Virus-based gene therapy research
- Erythrocyte Function and Pathophysiology
- Birth, Development, and Health
- Biochemical and Molecular Research
- RNA modifications and cancer
- Hemoglobinopathies and Related Disorders
- Reproductive System and Pregnancy
- Neonatal Health and Biochemistry
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Heme Oxygenase-1 and Carbon Monoxide
- Sphingolipid Metabolism and Signaling
- Cancer-related gene regulation
- Blood properties and coagulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Sexual function and dysfunction studies
- Cytomegalovirus and herpesvirus research
- Cancer, Hypoxia, and Metabolism
- Animal Genetics and Reproduction
- Sexuality, Behavior, and Technology
- Signaling Pathways in Disease
- Epigenetics and DNA Methylation
Chongqing Medical University
2025
Children's Hospital of Chongqing Medical University
2025
The University of Texas Health Science Center at Houston
2013-2022
The University of Texas MD Anderson Cancer Center
2019-2022
Xiangya Hospital Central South University
2011-2017
Central South University
2011-2017
The University of Tokyo
2014-2017
Second Military Medical University
2017
Texas A&M University
2017
University of Turku
2016
Abstract Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that S1P levels rapidly increase 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing 16 days concurrently elevated sphingonisne kinase (Sphk1) activity haemoglobin (Hb) oxygen (O 2 ) release capacity. Mouse genetic...
Adenosine deaminase (ADA) is a purine catabolic enzyme that manages levels of the biologically active purines adenosine and 2'-deoxyadenosine in tissues cells. ADA-deficient mice die at 3 wk age from severe respiratory distress. This phenotype progressive linked to perturbations pulmonary metabolism. The inflammatory changes found lungs included an accumulation activated alveolar macrophages eosinophils. These were accompanied by pronounced enlargement spaces increases mucus production...
Chronic kidney disease (CKD) is a prevalent life-threatening frequently associated with hypertension, progression to renal fibrosis, and eventual failure. Although the pathogenesis of CKD remains largely unknown, an increased inflammatory response known be has long been speculated contribute development. However, causative factors, exact role cascade in CKD, underlying mechanisms for its remain unidentified. Here we report that interleukin 6 (IL-6) expression levels were significantly...
Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity mortality. Recent evidence indicates endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 have not been identified. We tested the hypothesis angiotensin II type 1 (AT(1)) receptor activating autoantibodies, which occur women with...
The methotrexate-resistant AT-3000 line of S-180 cells has at least 150-fold more immunologically cross-reactive folate reductase than sensitive cells. Highly specific immunologic and protein purification procedures were used to show that the increased enzyme levels in this are due a corresponding increase rate synthesis. This observation indicates relative turnover is not significantly different two lines. Folate was purified homogeneity from both Comparison various physical, kinetic,...
Preeclampsia (PE), a syndrome affecting 5% of pregnancies, characterized by hypertension and proteinuria, is leading cause maternal fetal morbidity mortality. The condition often accompanied the presence circulating autoantibody, angiotensin II type I receptor agonistic autoantibody (AT 1 -AA). However, prevalence AT -AA in PE remains unknown, correlation titers with severity disease undetermined. We used sensitive high-throughput luciferase bioassay to detect levels serum 30 normal, 37...
Maternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular growth factor and placental factor. Angiotensin II (Ang II) potent vasoconstrictor that increases concomitant sFlt-1 during pregnancy. Therefore, we speculated Ang may promote the expression Here report infusion significantly levels pregnant mice, thereby demonstrating regulator secretion vivo. Furthermore, stimulated production dose-...
Alternative polyadenylation (APA) is emerging as a major post-transcriptional mechanism for gene regulation, and dysregulation of APA contributes to several human diseases. However, the functional consequences in cancer are not fully understood. Particularly, there no large-scale analysis cell lines.We characterized global profiles 6398 patient samples across 17 types from The Cancer Genome Atlas 739 lines Cell Line Encyclopedia. We built linear regression model explore correlation between...
Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent dysfunction. It common among males sickle cell disease (SCD), SCD transgenic mice are an accepted model disorder. Current strategies to manage priapism suffer from a poor fundamental understanding molecular mechanisms underlying Here we report that lacking adenosine deaminase (ADA), enzyme necessary for breakdown adenosine, displayed...
Background: High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust hypoxia may lead pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation high reveal novel therapeutics counteract detrimental consequences hypoxia. Methods: Using high-throughput, unbiased metabolomic profiling, we report that metabolic pathway responsible for production erythrocyte 2,3-bisphosphoglycerate...
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates multicellular functions through interactions with its receptors on cell surfaces. S1P enriched and stored in erythrocytes; however, it not clear whether alterations are involved the prevalent debilitating hemolytic disorder sickle disease (SCD). Here, using metabolomic screening, we found highly elevated blood of mice humans SCD. In murine models SCD, demonstrated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling...
Adenosine deaminase (ADA) deficiency in humans leads to a combined immunodeficiency. The mechanisms involved the lymphoid specificity of disease are not fully understood due inaccessibility human tissues for detailed analysis and absence an adequate animal model disease. We report use two-stage genetic engineering strategy generate ADA-deficient mice that retain many features associated with ADA humans, including Severe T B cell lymphopenia was accompanied by pronounced accumulation...
We have generated mice with a null mutation at the Ada locus, which encodes purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4). ADA-deficient fetuses exhibited hepatocellular impairment and died perinatally. Their lymphoid tissues were not largely affected. Accumulation of ADA substrates was detectable in conceptuses as early 12.5 days postcoitum, dramatically increasing during late utero development, is likely cause liver damage fetal death. The results presented here demonstrate...
p53-binding protein-1 (53BP1) is phosphorylated in response to DNA damage and rapidly relocalizes presumptive sites of along with Mre11 the histone 2A variant, γ-H2AX. 53BP1 associates BRCA1 tumor suppressor, knock-down experiments small interfering RNA have revealed a role for protein checkpoint damage. By generating mice defective m53BP1(m53BP1tr/tr), we created an animal model further explore its biochemical genetic roles vivo. We find that m53BP1tr/tr animals are growth-retarded show...
Methotrexate-resistant cells, which contain a 500-fold amplification of dihydrofolate reductase (DHFR) genes, were used as model system for studying the regulation DHFR gene expression during growth stimulation. We have shown that threefold increase in mRNA levels following stimulation results from corresponding production (i.e., delivery to cytoplasm) and is not result change half-life. previously showed accompanied by an relative rate transcription gene. This suggested changes are due...
Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT1) receptors are also highly associated with preeclampsia.We tested hypothesis AT1 receptor-agonistic (AT1-AAs) could activate receptors, leading to an...
The goal of the research reported here is to identify evolutionarily conserved amino acid residues associated with enzymatic deamination adenosine. To do this, we isolated molecular clones Escherichia coli adenosine deaminase gene by functional complementation deficient bacteria and deduced sequence enzyme from nucleotide gene. Nucleotide analysis revealed presence a 996-nucleotide open reading frame encoding protein 332 acids having weight 36,345. E. has approximately 33% identity those...
The mouse dihydrofolate reductase gene (dhfr) is a housekeeping expressed under the control of promoter region embedded in CpG island--a rich unmethylated dinucleotides. A divergent transcription unit exists immediately upstream dhfr which coamplified with some but not all methotrexate-resistant cell lines. We show that for this pair consists two bidirectional promoters, major and minor promoter, are situated within 660-base-pair ATG translation initiation codon. controls over 90%...
Abstract Pulmonary fibrosis is a common feature of numerous lung disorders, including interstitial diseases, asthma, and chronic obstructive pulmonary disease. Despite the prevalence fibrosis, molecular mechanisms governing inflammatory fibroproliferative aspects disorder are not clear. Adenosine purine-signaling nucleoside that generated in excess during cellular stress damage. This signaling molecule has been implicated regulation features disease; however, impact adenosine on well...