34 results on '"Ching Yan Chu"'
Search Results
2. Receptor Tyrosine Kinase Inhibitor Sunitinib as Novel Immunotherapy to Inhibit Myeloid-Derived Suppressor Cells for Treatment of Endometriosis
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Ying He, Sze Wan Hung, Bo Liang, Ruizhe Zhang, Yating Gao, Ching Yan Chu, Tao Zhang, Hui Xu, Jacqueline Pui Wah Chung, and Chi Chiu Wang
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endometriosis ,myeloid-derived suppressor cells ,Sunitinib ,immunosuppression ,gene expressions ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Endometriosis is a common, benign, and hormone-dependent gynaecological disorder that displays altered immunoinflammatory profiles. Myeloid-derived suppressor cells (MDSCs) suppressed immunosurveillance in endometriosis in human and mouse model. Receptor tyrosine kinase inhibitor Sunitinib can induce MDSC apoptosis and suppress the progression of cancer. However, the effects of Sunitinib on MDSCs in endometriosis and the underlying mechanism are not clear. In this study, we employed an animal study of the endometriosis model in mice for treatment of Sunitinib. After syngeneic endometrium transplantation and treatment, endometriotic lesion volume, weight, and histology were compared. Peritoneal fluid, peripheral blood, and bone marrow MDSC subsets and their molecular signaling were monitored by flow cytometry. Peritoneal cytokines were assayed by ELISA. The gene expression profiles of isolated CD11b+Ly6G+Ly6Clo cells were studied by RNA sequencing. We found that Sunitinib significantly decreased the endometriotic lesion size and weight after 1 and 3 weeks, and decreased p-STAT3 activation in MDSCs after 1 week of treatment. In the first week, Sunitinib specifically increased the G-MDSC population in peritoneal fluid but the isolated CD11b+Ly6G+Ly6Clo MDSCs after Sunitinib treatment were presented as mature polynuclear MDSCs, while the control group had immature mononuclear MDSCs. Importantly, we found Sunitinib differentially suppressed gene expressions of immunosuppressive function and differentiation in peritoneal G-MDSCs. Apelin signaling pathway associated genes and inflammation related genes were upregulated, and amino acid metabolism regulator genes were downregulated in bone marrow G-MDSCs. For endometriotic lesions, the PPARG gene governing glucose metabolism and fatty acid storage, which is important for the development of endometriosis was upregulated. In conclusion, Sunitinib inhibited endometriotic lesions, by promoting peritoneal fluid MDSCs maturation and inhibiting the immunosuppressive function. These findings suggest that Sunitinib changed the immune microenvironment and inhibited the development of endometriosis, which has potential therapeutic effects as novel immunotherapy to promote MDSCs maturation, differentiation, and metabolism for the treatment of endometriosis.
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- 2021
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3. Long noncoding RNA SAM promotes myoblast proliferation through stabilizing Sugt1 and facilitating kinetochore assembly
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Leina Lu, Liang Zhou, Yuying Li, Hao Sun, Huating Wang, Xiaona Chen, Fengyuan Chen, Jie Yuan, Suyang Zhang, Yu Zhao, and Ching Yan Chu
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0301 basic medicine ,Myoblast proliferation ,Cell division ,Satellite Cells, Skeletal Muscle ,Chromosomal Proteins, Non-Histone ,Science ,Kinetochore assembly ,General Physics and Astronomy ,Cell Cycle Proteins ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,Myoblasts ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Muscle stem cells ,Myocyte ,Regeneration ,Animals ,lcsh:Science ,Kinetochores ,Mitosis ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Regulation of gene expression ,Mice, Knockout ,Multidisciplinary ,Chemistry ,Protein Stability ,RNA ,General Chemistry ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Long non-coding RNAs ,Mice, Inbred mdx ,lcsh:Q ,RNA, Long Noncoding ,Microtubule-Associated Proteins - Abstract
The functional study of lncRNAs in skeletal muscle satellite cells (SCs) remains at the infancy stage. Here we identify SAM (Sugt1 asssociated muscle) lncRNA that is enriched in the proliferating myoblasts. Global deletion of SAM has no overt effect on mice but impairs adult muscle regeneration following acute damage; it also exacerbates the chronic injury-induced dystrophic phenotype in mdx mice. Consistently, inducible deletion of SAM in SCs leads to deficiency in muscle regeneration. Further examination reveals that SAM loss results in a cell-autonomous defect in the proliferative expansion of myoblasts. Mechanistically, we find SAM interacts and stabilizes Sugt1, a co-chaperon protein key to kinetochore assembly during cell division. Loss of SAM or Sugt1 both disrupts kinetochore assembly in mitotic cells due to the mislocalization of two components: Dsn1 and Hec1. Altogether, our findings identify SAM as a regulator of SC proliferation through facilitating Sugt1 mediated kinetochore assembly during cell division., Long noncoding RNA SAM (Sugt1 associated muscle) is upregulated in the proliferating myoblast cells. Here the authors investigate SAM knockout mice and suggest that SAM binds and stabilizes Sugt1, a co-chaperone protein that regulates kinetochore assembly.
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- 2020
4. Meconium-stained liquor during labor is associated with raised neonatal cord blood 8-iso-prostaglandin F2-alpha concentration
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Bao Yi Liu, Chi Chiu Wang, Chi Pui Pang, Tze Kin Lau, Ching Yan Chu, Tse Ngong Leung, and Rogers, Michael Scott
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Meconium aspiration syndrome -- Complications and side effects ,Umbilical arteries -- Research ,Labor, Complicated -- Research ,Health - Abstract
The study compares the umbilical arterial 8-iso-prostaglandin F2-alpha, concentrations between pregnancies that were complicated by moderate or thick meconium stained liquor and those with clear liquor. Moderate of thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy.
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- 2005
5. Adverse reproductive effects of maternal low-dose melamine exposure during pregnancy in rats
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Ching Yan Chu, Ling Ying Tang, Kwok-Pui Fung, Alisa Sau Wun Shum, Chi Chiu Wang, and Lu Li
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0301 basic medicine ,medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Physiology ,Management, Monitoring, Policy and Law ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,Medicine ,Adverse effect ,Fetus ,Pregnancy ,business.industry ,Embryo culture ,General Medicine ,medicine.disease ,030104 developmental biology ,Endocrinology ,chemistry ,Gestation ,medicine.symptom ,business ,Melamine ,Weight gain ,Toxicant - Abstract
Melamine is a heterocyclic, aromatic amine and nitrogen-enriched environmental toxicant, found in not only adulterated foodstuffs but also industrial household tableware and paints. Previous studies demonstrated adverse effects of high-dose melamine on human infants and pregnant animals, but effects of low-dose melamine on pregnancy have not been reported. In this study, reproductive effects of low-dose melamine were investigated in pregnant rats. Melamine in the range of 12.5-50 mg/kg was administered to pregnant rats at different gestational stages. Maternal weight gain was not significantly affected, and other maternal morbidity was not observed. Low-dose melamine exposure during pregnancy increased fetal size but reduced somite number in gastrulation (GD8.5-GD10.5) and organogenesis (GD10.5-GD16.5) periods, and increased incidence of stillbirth in whole gestational period (GD0.5 to delivery). Embryotoxicity of melamine was further confirmed by whole embryo culture in vitro that melamine retarded embryonic growth, impaired development of brain and heart, and induced open neural tube and atrioventricular defects with increased apoptosis. In conclusion, adverse reproductive effects of low-dose melamine during pregnancy were identified in the developing rat embryos and the perinatal effects of melamine were gestational and developmental stage dependent. Detailed hazard and risk assessment of melamine in reproduction system are warrant. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 131-138, 2017.
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- 2015
6. Effects of low-dose melamine exposure during pregnancy on maternal and fetal kidneys in rats
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Ching Yan Chu, Chi Chiu Wang, and Kwok-Pui Fung
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0301 basic medicine ,Health, Toxicology and Mutagenesis ,Organogenesis ,Physiology ,Embryonic Development ,Management, Monitoring, Policy and Law ,Toxicology ,Kidney ,Nephrotoxicity ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Fetus ,Pregnancy ,medicine ,Animals ,Maternal-Fetal Exchange ,business.industry ,Triazines ,Gastrulation ,General Medicine ,Hyperplasia ,medicine.disease ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,In utero ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Gestation ,Female ,Melamine ,business - Abstract
Despite the previous reports on melamine contamination in high concentrations some years ago, there were not many studies on low-level exposure in daily life, particularly in pregnancy. We investigated the effect of low-dose melamine on the kidneys of the pregnant rats and their developing embryos/fetuses during various gestational stages namely implantation, gastrulation, organogenesis, maturation and whole pregnancy. Our results showed that the repeated low level of melamine (12.5, 25, and 50 mg/kg bw/d) during pregnancy did not cause obstruction of renal tubules although more precipitating crystals were found in the early gestational periods. Simple hyperplasia in the maternal tubules and pelvic epithelium were more prominent after exposed to melamine during the whole gestational period. Neonatal kidneys significantly suffered more from congestion in glomeruli and interstitium, dilated tubules and interstitial edema after melamine administration to the mother in the late and the whole gestational periods. A trend of advance of glomerular development in fetuses was also observed. We conclude that in utero exposure of low-level melamine could post a risk on the kidneys of the pregnant mother as well as the developing fetuses, which may further increase the possibility of other health problems later in life.
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- 2017
7. Determination of exogenous epigallocatechin gallate peracetate in mouse plasma using liquid chromatography with quadrupole time-of-flight mass spectrometry
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Ching Yan Chu, Tak Hang Chan, Chi Pui Pang, Gene Chi Wai Man, Chi Chiu Wang, Kai On Chu, and Kwok Ping Chan
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chemistry.chemical_compound ,Chromatography ,chemistry ,Pharmacokinetics ,Linear range ,Coefficient of variation ,Extraction (chemistry) ,Filtration and Separation ,Ether ,Ion suppression in liquid chromatography–mass spectrometry ,Epigallocatechin gallate ,Mass spectrometry ,Analytical Chemistry - Abstract
A robust method for the quantitation of epigallocatechin gallate peracetate in plasma for pharmacokinetic studies is lacking. We have developed a validated method to quantify this compound using liquid chromatography with quadrupole time-of-flight mass spectrometry with isopropanol and tert-butyl methyl ether (3:10) extraction and thin-layer chromatography purification. The epigallocatechin gallate peracetate-1-(13) C8 isotope was used as an internal standard. The linear range (r(2) > 0.9950) was from 0.05 to 100.00 μg/mL. The lower limit of quantification of the method was 0.05 μg/mL. Reproducibility, coefficient of variation, was between 0.7 and 12.6% (n = 6), accuracy between 83.7 and 104.6% (n = 5), and recovery ranged from 82.4 to 109.0% (n = 4). Ion suppression was approximately 40%. No mass spectral peaks were found to interfere between the standard and internal standard or the blank plasma extracts. Epigallocatechin gallate peracetate in plasma was stably stored at -80°C over three months even after three freeze-thaw cycles. Extracts were stable in the sampler at 4°C for over 48 h. Plasma levels were maintained at 1.36 μg/mL for 360 min after intraorbital intravenous injection at 50 mg/kg in mice. This method can be used to reliably measure epigallocatechin gallate peracetate in plasma for pharmacokinetic studies.
- Published
- 2014
8. Serotonin Receptor 6 Mediates Defective Brain Development in Monoamine Oxidase A-deficient Mouse Embryos
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Christoph Ufer, Gene Chi Wai Man, Chi Chiu Wang, Hartmut Kühn, Aslihan Ugun-Klusek, Astrid Borchert, E. Ellen Billett, and Ching Yan Chu
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Serotonin ,Cell signaling ,Monoamine oxidase ,Biology ,Biochemistry ,Mice ,Gene Knockdown Techniques ,Animals ,Monoamine Oxidase ,Molecular Biology ,Gene knockdown ,Caspase 3 ,Brain ,Gene Expression Regulation, Developmental ,Cell Biology ,Molecular biology ,Caspase 9 ,Cell biology ,Monoamine neurotransmitter ,Receptors, Serotonin ,biology.protein ,Signal transduction ,Monoamine oxidase A ,Signal Transduction ,Developmental Biology - Abstract
Monoamine oxidases A and B (MAO-A and MAO-B) are enzymes of the outer mitochondrial membrane that metabolize biogenic amines. In the adult central nervous system, MAOs have important functions for neurotransmitter homeostasis. Expression of MAO isoforms has been detected in the developing embryo. However, suppression of MAO-B does not induce developmental alterations. In contrast, targeted inhibition and knockdown of MAO-A expression (E7.5-E10.5) caused structural abnormalities in the brain. Here we explored the molecular mechanisms underlying defective brain development induced by MAO-A knockdown during in vitro embryogenesis. The developmental alterations were paralleled by diminished apoptotic activity in the affected neuronal structures. Moreover, dysfunctional MAO-A expression led to elevated levels of embryonic serotonin (5-hydroxytryptamine (5-HT)), and we found that knockdown of serotonin receptor-6 (5-Htr6) expression or pharmacologic inhibition of 5-Htr6 activity rescued the MAO-A knockdown phenotype and restored apoptotic activity in the developing brain. Our data suggest that excessive 5-Htr6 activation reduces activation of caspase-3 and -9 of the intrinsic apoptotic pathway and enhances expression of antiapoptotic proteins Bcl-2 and Bcl-XL. Moreover, we found that elevated 5-HT levels in MAO-A knockdown embryos coincided with an enhanced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and a reduction of proliferating cell numbers. In summary, our findings suggest that excessive 5-HT in MAO-A-deficient mouse embryos triggers cellular signaling cascades via 5-Htr6, which suppresses developmental apoptosis in the brain and thus induces developmental retardations.
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- 2014
9. Toxicity of Melamine: The Public Health Concern
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Ching Yan Chu and Chi Chiu Wang
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Cancer Research ,medicine.medical_specialty ,Food Safety ,Triazines ,business.industry ,Health, Toxicology and Mutagenesis ,Public health ,Food Contamination ,Food safety ,Toxicology ,chemistry.chemical_compound ,chemistry ,Environmental health ,Toxicity ,medicine ,Animals ,Humans ,Public Health ,business ,Melamine ,Adverse effect ,Target organ - Abstract
Melamine contamination in food has resulted in sickness and deaths of human infants, pets, and farm animals in the past decade. The majority of the victims suffered from acute kidney injury, nephrolithiasis, and urolithiasis. Since then, animal studies have revealed the possible target organs of the melamine toxicity and the extent of the adverse effects of the contaminant. State-of-the-art analytical methods have been developed to achieve the "zero tolerance" aim for such economically motivated adulteration. These studies provide in-depth understanding of the melamine toxicity and promising analytical methods, which can help us safeguard our dairy food source.
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- 2013
10. Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice
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Ching Yan Chu, Yi Xin He, Gene Chi Wai Man, Chi Chiu Wang, Kai On Chu, Gang Li, Tat San Lau, Tao Zhang, Hui Xu, Joseph Kwong, Tak Hang Chan, Jimmy Tin Yan Cheng, and Ling Qin
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Cancer Research ,medicine.medical_specialty ,Physiology ,Angiogenesis ,Clinical Biochemistry ,Endometriosis ,Biological Availability ,Angiogenesis Inhibitors ,Apoptosis ,Pharmacology ,Endometrium ,complex mixtures ,Catechin ,Neovascularization ,Lesion ,Mice ,Ovarian Follicle ,In vivo ,Internal medicine ,medicine ,Animals ,Prodrugs ,heterocyclic compounds ,Neovascularization, Pathologic ,Tea ,business.industry ,food and beverages ,Prodrug ,medicine.disease ,Bioavailability ,medicine.anatomical_structure ,Endocrinology ,Female ,sense organs ,medicine.symptom ,business ,Oxidation-Reduction - Abstract
Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.
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- 2012
11. Distribution of melamine in rat foetuses and neonates
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Chi Chiu Wang, C. M. Lau, Kit-Man Chu, Ching Yan Chu, X. Z. Liu, Kwok-Pui Fung, Chris K C Wong, Judy Yuet-Wa Chan, T. L. Ting, Tai Fai Fok, and Chung Shun Ho
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medicine.medical_specialty ,Amniotic fluid ,Placenta ,Biology ,Breast milk ,Toxicology ,Rats, Sprague-Dawley ,Andrology ,chemistry.chemical_compound ,Fetus ,Pregnancy ,Internal medicine ,medicine ,Animals ,Tissue Distribution ,reproductive and urinary physiology ,Kidney ,Triazines ,General Medicine ,medicine.disease ,Rats ,Milk ,medicine.anatomical_structure ,Endocrinology ,Animals, Newborn ,chemistry ,In utero ,embryonic structures ,Female ,Melamine - Abstract
Pharmacokinetics of melamine has not been studied in pregnancies despite of the many reports on the effect on renal damage in adult and neonates. In this study, Sprague-Dawley rats have been used as a model to study the single-dose effect of melamine administration in late pregnancy and in neonates within 24h. Melamine concentrations in maternal serum, breast milk, whole foetus, amniotic fluid, neonatal serum and neonatal kidney was measured by liquid chromatography coupled with mass spectrometry. Melamine was detected in all the samples, including foetal rats and amniotic fluid in utero. Melamine was able to pass through placenta and reach the foetus, and to accumulate in lactating mammary gland and neonatal kidney. Moreover, melamine was eliminated through the placenta of the foetus and the kidneys of the neonates, and later excreted into the amniotic fluid. The study characterised for the first time the distribution of melamine in foetuses and neonates, providing reference for toxicological study of melamine during pregnancy.
- Published
- 2010
12. Effects of different inspired oxygen fractions on lipid peroxidation during general anaesthesia for elective Caesarean section
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Chi Chiu Wang, Kim S. Khaw, Ching Yan Chu, Floria F. Ng, Wing Hung Tam, W.D. Ngan Kee, Michael S. Rogers, and Lester A. H. Critchley
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Adult ,Minimum alveolar concentration ,Isoprostane ,Partial Pressure ,Isoprostanes ,Sevoflurane ,Lipid peroxidation ,Young Adult ,chemistry.chemical_compound ,Pregnancy ,medicine ,Anesthesia, Obstetrical ,Humans ,Maternal-Fetal Exchange ,Oxygen toxicity ,Hyperoxia ,Intraoperative Care ,Cesarean Section ,business.industry ,Infant, Newborn ,Oxygen Inhalation Therapy ,Pregnancy Outcome ,Venous blood ,Fetal Blood ,medicine.disease ,Oxygen ,Anesthesiology and Pain Medicine ,chemistry ,Anesthesia ,Arterial blood ,Female ,Lipid Peroxidation ,medicine.symptom ,Anesthesia, Inhalation ,business ,medicine.drug - Abstract
During general anaesthesia (GA) for Caesarean section (CS), fetal oxygenation is increased by administering an inspired oxygen fraction (Fi(o(2))) of 1.0. However, it is unclear whether such high Fi(o(2)) will increase oxygen free radical activity.We randomized 39 ASA I-II parturients undergoing elective CS under GA to receive 30% (Gp 30), 50% (Gp 50), or 100% (Gp 100) oxygen with nitrous oxide and sevoflurane adjusted to provide equivalent minimum alveolar concentration. Baseline maternal arterial blood before preoxygenation and maternal arterial, umbilical arterial and venous blood at delivery were sampled for assays of the by-product of lipid peroxidation, isoprostane, and for measurement of blood gases and oxygen content.Maternal and umbilical isoprostane concentrations were similar among the three groups at delivery, despite significantly increased maternal and fetal oxygenation in Gp 100. However, paired comparisons of maternal delivery vs baseline concentration of isoprostane showed an increase at delivery for all groups [Gp 30: mean 342 (sd 210) vs 154 (65) pg ml(-1), P=0.016; Gp 50: 284 (129) vs 156 (79) pg ml(-1), P=0.009; Gp 100: 332 (126) vs 158 (68) pg ml(-1), P0.001]. The magnitude of increase was similar in all three groups and independent of the Fi(o(2)) or duration after induction.GA for CS is associated with a marked increase in free radical activity in the mother and baby. The mechanism is unclear but it is independent of the inspired oxygen in the anaesthetic mixture. Therefore, when 100% oxygen is administered with sevoflurane for GA, fetal oxygenation can be increased, without inducing an increase in lipid peroxidation.
- Published
- 2010
13. Oxidative stress in midpregnancy as a predictor of gestational hypertension and pre-eclampsia
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K O Chu, Ching Yan Chu, Wing Hung Tam, Chi Chiu Wang, C. Y. Li, and Michael S. Rogers
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Adult ,Blood Glucose ,Gestational hypertension ,medicine.medical_specialty ,Urine ,Dinoprost ,Preeclampsia ,Pre-Eclampsia ,Pregnancy ,Prenatal Diagnosis ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Glucose tolerance test ,Eclampsia ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,Hypertension, Pregnancy-Induced ,Glucose Tolerance Test ,medicine.disease ,Oxidative Stress ,Endocrinology ,Pregnancy Trimester, Second ,Gestation ,Female ,business - Abstract
Objectives To explore the relationship between the levels of maternal oxidative stress and glycaemia during pregnancy and to compare the predictive values of 8-epimer of prostaglandin F2alpha (8-isoPGF2α) and mean arterial pressure (MAP) in midpregnancy for the development of hypertensive complications in later pregnancy. Design Prospective observational study as an ancillary study to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study. Setting Obstetric clinics and wards of a university teaching hospital in Hong Kong. Population Selected women with singleton pregnancies attending the antenatal clinic. Methods Pregnant women who met HAPO inclusion criteria were recruited for the study. Glucose tolerance was assessed by a 75-g 2-hour oral glucose tolerance test (OGTT) at 24–32 weeks of gestation. Fasting plasma samples for 8-isoPGF2α estimation and urine samples for 8-isoPGF2α and 2,3-dinor 8-isoPGF2α assays were collected and blood pressures measured during the OGTT visit. Random plasma and urine samples were also obtained at 34–37 weeks. Glucose results were unblinded to the attending obstetrician if limits preset under the HAPO protocol were met. Main outcome measures Maternal plasma 8-isoPGF2α and urinary 8-isoPGF2α and 2,3-dinor 8-isoPGF2α both at the time of OGTT (24–32 weeks) and at 34–37 weeks of gestation. Incidence of pre-eclampsia and gestational hypertension. Results Of the 408 women who attended for OGTT at 24–32 weeks, two met the glucose criteria for unblinding and 25 had missing 8-isoPGF2α values and thus were excluded from analysis. Of the 381 women, 338 (88.7%) attended for random plasma samples at 34–37 weeks. Significant correlations were observed between maternal fasting plasma isoprostane and both fasting (r= 0.20; P < 0.001) and 2-hour (r= 0.39; P < 0.001) plasma glucose levels at the time of OGTT. Gestational hypertension/pre-eclampsia occurred in 17 (4.2%) women, and at the time of OGTT, they had significantly higher fasting plasma 8-isoPGF2α (P < 0.001), urine 8-isoPGF2α (P < 0.005) and urine 2,3-dinor 8-isoPGF2α to creatinine ratios (P < 0.001), as well as higher MAP (P < 0.001) than women who remained normotensive. At 34–37 weeks, only random plasma 8-isoPGF2α was significantly higher (P < 0.001) among the women with gestational hypertension/pre-eclampsia. Conclusions Plasma markers of oxidative stress were positively correlated with plasma glucose at the time of OGTT (24–32 weeks). Women who subsequently developed gestational hypertension/pre-eclampsia had significantly higher plasma and urine markers of oxidative stress at the time of OGTT but only higher plasma markers at 34–37 weeks. Plasma 8-isoPGF2α appears to be a very good predictor of subsequent gestational hypertension/pre-eclampsia when measured at the time of OGTT, but its ability to discriminate deteriorates as pregnancy advances.
- Published
- 2006
14. Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats
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Kwong Wai Choy, Chi Pui Pang, Kai On Chu, Chi Chiu Wang, Kwok Ping Chan, Ching Yan Chu, and Michael S. Rogers
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medicine.medical_specialty ,Placenta ,Cmax ,Pharmaceutical Science ,Green tea extract ,Catechin ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Fetus ,Pharmacokinetics ,Pregnancy ,Internal medicine ,Blood plasma ,medicine ,Animals ,Tissue Distribution ,Maternal-Fetal Exchange ,reproductive and urinary physiology ,Tea ,Chemistry ,Rats ,medicine.anatomical_structure ,Endocrinology ,In utero ,embryonic structures ,Female - Abstract
We carried out a pharmacokinetic study to determine the levels and profiles of catechins in pregnant rats and their fetuses after ingestion of green tea extract (GTE). We measured total catechin levels after enzyme digestions. Dams, at 15.5 days of gestation, were fed with GTE and catechins were measured in the maternal plasma, placenta, and fetus 0, 0.5, 1, 2, 3, 5, 8, 10, 12, 16, and 20 h after maternal GTE intake. The pharmacokinetic changes were analyzed by non compartmental models. We found that maternal plasma concentrations of catechins were about 10 times higher than in placenta and 50-100 times higher than in the fetus. AUC and Cmax levels of (-)-epicatechin (EC) were the highest in plasma while the levels of (-)-epigallocatechin gallate (EGCG) were the highest in the placenta and the fetus. The exposure level of catechin derivatives was higher than the gallate derivatives in maternal plasma after normalization but reversed in the placenta and fetus. The absorption of epi-isomers in plasma was found to be more favorable than their non epi-isomer counterparts. EGCG had the highest level of exposure (AUC) and the highest Cmax in the fetus, implying it may have potential for in utero antioxidant protection.
- Published
- 2006
15. Meconium-stained liquor during labor is associated with raised neonatal cord blood 8-iso-prostaglandin F2α concentration
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Bao Yi, Liu, Chi Chiu, Wang, Tze Kin, Lau, Ching Yan, Chu, M, Phil, Chi Pui, Pang, Michael Scott, Rogers, and Tse Ngong, Leung
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Adult ,Meconium ,Fetal heart ,Dinoprost ,Umbilical cord ,Fetal Distress ,Andrology ,fluids and secretions ,Pregnancy ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,reproductive and urinary physiology ,8 iso prostaglandin f2α ,business.industry ,food and beverages ,Obstetrics and Gynecology ,Amniotic Fluid ,Fetal Blood ,equipment and supplies ,medicine.disease ,Oxidative Stress ,medicine.anatomical_structure ,Case-Control Studies ,Anesthesia ,Cord blood ,embryonic structures ,Arterial blood ,Female ,business ,Biomarkers - Abstract
Objective The purpose of this study was to compare the umbilical arterial 8-iso-prostaglandin F 2α, concentrations between pregnancies that were complicated by moderate or thick meconium-stained liquor and those with clear liquor. Study design Umbilical cord arterial blood samples were collected from 247 singleton pregnancies with either moderate or thick meconium-stained liquor at any stage of labor or clear liquor at all stages of labor for the determination of the total 8-iso-prostaglandins F 2α concentration. Results The median total 8-iso-prostaglandins F 2α concentration of the meconium-stained liquor group was significantly higher than that of the control group (719.2 vs 115.8 pg/mL). Among the meconium-stained liquor group, those who had a change from "clear liquor" at early labor to "moderate/ thick meconium-stained liquor" at late first stage or at delivery (late meconium-stained liquor group) had higher 8-iso-prostaglandins F 2α concentration, compared with those who had moderate/ thick meconium-stained liquor since early labor (early meconium-stained liquor group; 959.8 vs 499.9 pg/mL). With the use of multiple regression analysis, meconium-stained liquor, duration of second stage of labor, and abnormal fetal heart tracings were independent determinants of cord blood 8-iso-prostaglandins F 2α concentration. Conclusion Moderate or thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy.
- Published
- 2005
16. Determination of exogenous epigallocatechin gallate peracetate in mouse plasma using liquid chromatography with quadrupole time-of-flight mass spectrometry
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Kai On, Chu, Gene Chi Wai, Man, Kwok Ping, Chan, Ching Yan, Chu, Tak Hang, Chan, Chi Pui, Pang, and Chi Chiu, Wang
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Mice ,Mice, Inbred ICR ,Plasma ,Animals ,Female ,Chromatography, Thin Layer ,Peracetic Acid ,Catechin ,Chromatography, High Pressure Liquid ,Mass Spectrometry - Abstract
A robust method for the quantitation of epigallocatechin gallate peracetate in plasma for pharmacokinetic studies is lacking. We have developed a validated method to quantify this compound using liquid chromatography with quadrupole time-of-flight mass spectrometry with isopropanol and tert-butyl methyl ether (3:10) extraction and thin-layer chromatography purification. The epigallocatechin gallate peracetate-1-(13) C8 isotope was used as an internal standard. The linear range (r(2)0.9950) was from 0.05 to 100.00 μg/mL. The lower limit of quantification of the method was 0.05 μg/mL. Reproducibility, coefficient of variation, was between 0.7 and 12.6% (n = 6), accuracy between 83.7 and 104.6% (n = 5), and recovery ranged from 82.4 to 109.0% (n = 4). Ion suppression was approximately 40%. No mass spectral peaks were found to interfere between the standard and internal standard or the blank plasma extracts. Epigallocatechin gallate peracetate in plasma was stably stored at -80°C over three months even after three freeze-thaw cycles. Extracts were stable in the sampler at 4°C for over 48 h. Plasma levels were maintained at 1.36 μg/mL for 360 min after intraorbital intravenous injection at 50 mg/kg in mice. This method can be used to reliably measure epigallocatechin gallate peracetate in plasma for pharmacokinetic studies.
- Published
- 2014
17. Human normal tear proteome
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Chi Chiu Wang, Chi Pui Pang, Chiu Fai Pong, Chuen Wai Poon, and Ching Yan Chu
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Cellular and Molecular Neuroscience ,Ophthalmology ,Proteome ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Tears ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Computational biology ,Biology ,Eye Proteins ,Sensory Systems - Published
- 2008
18. Trolox-Equivalent Antioxidant Capacity Assay Versus Oxygen Radical Absorbance Capacity Assay in Plasma
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Kim S. Khaw, Ching Yan Chu, Chi Pui Pang, Kai On Chu, Michael S. Rogers, Kwong Wai Choy, and Chi Chiu Wang
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Chromatography ,Antioxidant ,ABTS ,Oxygen radical absorbance capacity ,medicine.medical_treatment ,Radical ,Biochemistry (medical) ,Clinical Biochemistry ,Trolox equivalent antioxidant capacity ,Ferric reducing ability of plasma ,Antioxidants ,chemistry.chemical_compound ,Metmyoglobin ,chemistry ,Biochemistry ,medicine ,Humans ,Benzothiazoles ,Trolox ,Chromans ,Sulfonic Acids ,Reactive Oxygen Species - Abstract
Because of difficulty in measuring each antioxidant component separately and interactions among antioxidants, methods have been developed to assess the total antioxidant capacity of serum or plasma. The 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity (TEAC) assay (1), the oxygen radical absorbance capacity (ORAC) assay (2), and the ferric reducing ability of plasma (FRAP) assay (3) are commonly used and have been extensively evaluated. Although comparable mean results have been obtained with the TEAC and ORAC assays (4)(5), no correlation has been found between ORAC and TEAC values or between FRAP and TEAC values (6). This lack of correlation between TEAC and other assays is likely attributable to underestimation of overall antioxidant capacity. Underestimation may be related to the effects of dilution (7) and to premature measurement of inhibition percentage at a fixed time of 3 min (6). In fact, both the ORAC and TEAC assays are inhibition methods: a sample is added to a free- radical-generating system, and the inhibition of the free radical action is measured. This inhibition is related to the antioxidant capacity of the sample. In addition, both assay methods measure antioxidants in serum or plasma proteins, including albumin (6). In this study we investigated the performance of the TEAC assay, modified the procedure, and then reevaluated the TEAC for comparison with the ORAC assay. The TEAC assay, commercialized by Randox Laboratories Ltd., is based on the suppression of the absorbance of radical cations of 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) (ABTS) by antioxidants in the test sample when ABTS incubates with a peroxidase (metmyoglobin) and H2O2 (1). If the inhibition time is fixed at 3 min, as stated in the manufacturer’s instructions, the added antioxidants quench ABTS radicals in a nonlinear dose–response fashion (6). To optimize the incubation period for the complete inhibition of ABTS radical …
- Published
- 2004
19. Melamine in prenatal and postnatal organs in rats
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Kai On Chu, Ching Yan Chu, Chi Chiu Wang, Sung Shing Kwok, Chung Shun Ho, Ho Ming Chan, and Kwok-Pui Fung
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medicine.medical_specialty ,Food Safety ,Population ,Physiology ,Toxicology ,Kidney ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Fetus ,Pregnancy ,Internal medicine ,medicine ,Animals ,Tissue Distribution ,education ,Maternal-Fetal Exchange ,education.field_of_study ,business.industry ,Triazines ,Kidney metabolism ,medicine.disease ,Rats ,Resins, Synthetic ,Endocrinology ,chemistry ,Animals, Newborn ,In utero ,Gestation ,Female ,Melamine ,business ,Breast feeding - Abstract
Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding. In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats. Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages. Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood. Distribution of melamine in all postnatal organs was higher than that in prenatal organs. Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs. It may relate to the high vulnerability to the toxicity of melamine in this population.
- Published
- 2012
20. Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis*
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Wai Ting Lui, E. Ellen Billett, Ching Yan Chu, Aslihan Ugun-Klusek, Hartmut Kühn, Christoph Ufer, Chi Chiu Wang, Ling Yin Tang, and Astrid Borchert
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Clorgyline ,Monoamine Oxidase Inhibitors ,Monoamine oxidase ,Apoptosis ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Mice ,Gene silencing ,Animals ,Cyclin D1 ,RNA, Small Interfering ,Molecular Biology ,Monoamine Oxidase ,Cell Proliferation ,Gene knockdown ,biology ,Caspase 3 ,Embryogenesis ,Brain ,Gene Expression Regulation, Developmental ,Embryo ,Cell Biology ,Embryo, Mammalian ,Caspase 9 ,Cell biology ,Monoamine neurotransmitter ,Gene Knockdown Techniques ,biology.protein ,Monoamine oxidase A ,Developmental Biology - Abstract
Monoamine oxidases (MAO-A, MAO-B) metabolize biogenic amines and have been implicated in neuronal apoptosis. Although apoptosis is an important process in embryo development, the role of MAO isoenzymes has not been investigated in detail. We found that expression of MAO-A and MAO-B can be detected early on during embryo development. Expression levels remained constant until around midgestation but then dropped to almost undetectable levels toward birth. Similar expression kinetics were observed in the brain. Isoform-specific expression silencing of MAO-A mediated by siRNA during in vitro embryogenesis induced developmental defects, as indicated by a reduction of the crown rump length and impaired cerebral development. These alterations were paralleled by elevated serotonin levels. Similar abnormalities were observed when embryos were cultured in the presence of the MAO-A inhibitor clorgyline or when the transcriptional inhibitor of MAO-A expression R1 was overexpressed. In contrast, no such alterations were detected when expression of MAO-B was knocked down. To explore the underlying mechanisms for the developmental abnormalities in MAO-A knockdown embryos, we quantified the degree of developmental apoptosis in the developing brain. MAO-A knockdown reduced the number of apoptotic cells in the neuroepithelium, which coincided with impaired activation of caspases 3 and 9. Moreover, we observed reduced cyclin D1 levels as an indicator of impaired cell proliferation in MAO-A knockdown embryos. This data highlights MAO-A as a vital regulator of embryonic brain development.
- Published
- 2011
21. Green tea catechins and their oxidative protection in the rat eye
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Ching Yan Chu, Wai Ying Li, Chi Chiu Wang, Chi Pui Pang, Kwong Wai Choy, Kai On Chu, Kwok Ping Chan, and Michael S. Rogers
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genetic structures ,Flavonoid ,Green tea extract ,Eye ,Antioxidants ,Catechin ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Oral administration ,Cornea ,medicine ,Gallocatechin ,Animals ,chemistry.chemical_classification ,Chromatography ,Aqueous humour ,Plant Extracts ,General Chemistry ,eye diseases ,Rats ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Polyphenol ,sense organs ,General Agricultural and Biological Sciences ,Oxidation-Reduction - Abstract
Catechins, active constituents of green tea, are well-known antioxidative natural products. It was proposed that green tea extract (GTE) consumption could benefit the eye, and the pharmacokinetics of catechins and oxidation status in rat eye were investigated after oral administration. Sprague-Dawley rats were fed GTE and sacrificed at different time intervals. Their eyes were dissected into cornea, lens, retina, choroid-sclera, vitreous humor, and aqueous humor for analysis of catechins and 8-epi-isoprostane by HPLC-ECD and GC-NCI-MS, respectively. Catechins were differentially distributed in eye tissues. Gallocatechin was present at the highest concentration in the retina, 22729.4 +/- 4229.4 pmol/g, and epigallocatechin in aqueous humor at 602.9 +/- 116.7 nM. The corresponding area-under-curves were 207,000 pmol x h/g and 2035.0 +/- 531.7 nM x h, respectively. The time of maximum concentration of the catechins varied from 0.5 to 12.2 h. Significant reductions in 8-epi-isoprostane levels were found in the compartments except the choroid-sclera or plasma, indicating antioxidative activities of catechins in these tissues.
- Published
- 2010
22. Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model
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W.T. Lui, Ching Yan Chu, P.S. Ng, H. Xu, Michael S. Rogers, and Chi Chiu Wang
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Pathology ,medicine.medical_specialty ,Angiogenesis ,Endometriosis ,Angiogenesis Inhibitors ,Mice, SCID ,Epigallocatechin gallate ,Biology ,Endometrium ,Catechin ,Neovascularization ,chemistry.chemical_compound ,Mice ,Peritoneum ,medicine ,Animals ,Humans ,Vitamin E ,Microvessel ,Cell Proliferation ,Neovascularization, Pathologic ,Tea ,Microcirculation ,Rehabilitation ,Obstetrics and Gynecology ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Disease Models, Animal ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Female ,medicine.symptom - Abstract
The development of new blood vessels plays an essential role in growth and survival of endometriosis. Epigallocatechin gallate (EGCG) from green tea has powerful anti-angiogenic properties and our aim was to evaluate these properties in experimental endometriosis.Eutopic endometrium from endometriosis patients was transplanted s.c. to severely compromised immunodeficient mice, randomly treated i.p. with EGCG (anti-angiogenic and -oxidant), Vitamin E (a non-angiogenic antioxidant) or saline for 2 weeks. The endometrial implant, including adjacent host outer skin and subcutaneous layers plus inner abdominal muscle and peritoneum, was collected. New microvessels were determined by species-specific immunohistochemistry. Angiogenic factors in lesions and abdominal muscle were detected by quantitative real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling and quantitative real-time PCR. In saline control, endometrial implants developed new blood vessels with proliferating glandular epithelium and were tightly adhered to host subcutaneous and abdominal muscle layers. After EGCG, endometriotic lesions were smaller than control (P0.05), and glandular epithelium was smaller and eccentrically distributed. Angiogenesis in lesions from the implant and adjacent tissues was under-developed, and microvessel size and density were lower (both P0.01) than control. mRNA for angiogenic vascular endothelial growth factor A, but not hypoxia inducible factor 1, alpha subunit, was significantly down-regulated in lesions after EGCG (P0.05). In addition, apoptosis in the lesions was more obvious, and nuclear factor kappa B and mitogen activated protein kinase 1 mRNA levels were up-regulated (P0.05) after EGCG treatment. No differences were observed with Vitamin E treatment.EGCG significantly inhibits the development of experimental endometriosis through anti-angiogenic effects.
- Published
- 2008
23. High isoprostane level in cardinal ligament-derived fibroblasts and urine sample of women with uterine prolapse
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YM Liu, WT Lui, Rogers, MW Pang, Kwong Wai Choy, Chi Chiu Wang, Ching Yan Chu, L. L. Lee, and Shing-Kai Yip
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Adult ,medicine.medical_specialty ,Isoprostane ,Urinary system ,Uterus ,Urology ,Urine ,Isoprostanes ,chemistry.chemical_compound ,Uterine Prolapse ,Medicine ,Humans ,Gynecology ,Ligaments ,business.industry ,Obstetrics and Gynecology ,Uterine prolapse ,Fibroblasts ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Matrix Metalloproteinase 9 ,In utero ,Cardinal ligament ,Case-Control Studies ,Biomarker (medicine) ,Matrix Metalloproteinase 2 ,Female ,business - Abstract
We studied the isoprostane level, a well-recognised biomarker of oxidative stress, from women with uterine prolapse and age-matched female controls without prolapse. Cardinal ligament-derived fibroblasts explanted from women with prolapse showed a significant increased level of isoprostane production (P < 0.05) compared with those derived from controls. This concurs with elevated urinary isoprostane levels identified among women with prolapse (P < 0.001) compared with controls. In addition, the matrix metalloproteinase 2 mRNA was significantly increased (P= 0.004) among women with uterine prolapse. Parallel findings of increased isoprostane in cardinal ligament and urine sample among women with prolapse suggest that oxidative stress might be involved in the development of uterine prolapse.
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- 2008
24. Metabolomic and bioinformatic analyses in asphyxiated neonates
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Ching Yan Chu, L. K. Law, Xiao Guang Zhou, Chi Chiu Wang, Xin Xiao, Tze Kin Lau, Chi Pui Pang, Tai Fai Fok, and Michael S. Rogers
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Neonatal intensive care unit ,Urinary system ,Clinical Biochemistry ,Carboxylic Acids ,Gestational Age ,Urine ,Biology ,Bioinformatics ,Sensitivity and Specificity ,Metabolomics ,Predictive Value of Tests ,Pregnancy ,medicine ,Cluster Analysis ,Humans ,Clinical significance ,Asphyxia ,Asphyxia Neonatorum ,Infant, Newborn ,Computational Biology ,Ethylmalonate ,General Medicine ,Obstetrics ,ROC Curve ,Case-Control Studies ,Female ,medicine.symptom ,Morbidity ,Maternal Age - Abstract
Objectives: We tested the application of bioinformatic algorithms in studying the metabolomic profiles of neonatal urine samples with clinical evidence of severe asphyxia at birth and subsequent neurodevelopmental handicap. Design and methods: The clinical outcomes of 256 newborns that required direct admission to neonatal intensive care unit for respiratory support or did not require direct admission were studied. Urinary metabolite profiles were measured by high throughput mass spectrometry and analyzed by bioinformatic methods. Results: We found a positive relationship between suppressed biochemical networks involved in macromolecular synthesis and birth asphyxia associated with significant neonatal oxidative stress and morbidity. The metabolomic discriminators between good neonatal outcome and poor neonatal outcome were established using hierarchical clustering analysis. Concentrations of eight urinary organic acids in distinct biochemical pathways were elevated and significantly associated with the prognosis of neurodevelopmental handicap with high sensitivity and specificity: ethylmalonate, 3-hydroxy-3-methylglutarate, 2-hydroxy-glutarate and 2-oxo-glutarate were associated with good neonatal outcome, whereas glutarate, methylmalonate, 3-hydroxy-butyrate and orotate were associated with poor outcome. Conclusions: The data demonstrated the potential application of bioinformatics methods in this metabolomic study and proved its clinical relevance.
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- 2005
25. In vitro exposure to carbon dioxide induces oxidative stress in human peritoneal mesothelial cells
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Michael S. Rogers, Angela M. Bentes de Souza, Chi Chiu Wang, Ching Yan Chu, Christopher J. Haines, and Christine Briton-Jones
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Adult ,Biology ,medicine.disease_cause ,Dinoprost ,Helium ,Toxicology ,chemistry.chemical_compound ,Peritoneum ,medicine ,Humans ,Viability assay ,Cells, Cultured ,Rehabilitation ,Obstetrics and Gynecology ,In vitro exposure ,Epithelial Cells ,Carbon Dioxide ,Hydrogen-Ion Concentration ,Molecular biology ,In vitro ,Culture Media ,Oxidative Stress ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Carbon dioxide ,Female ,Oxidative stress ,Mesothelial Cell - Abstract
BACKGROUND The objective of this study was to verify whether in vitro exposure of human peritoneal mesothelial cells to carbon dioxide (CO(2)) influences the levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a marker of oxidative stress. METHODS Mesothelial cells were exposed to either: (i). 100% CO(2) for 4 h; (ii). 100% helium (an alternative gas with which to create hypoxic conditions) for 4 h; (iii). 100% CO(2) for 24 h; or (iv). standard conditions (control). After gas exposure, mesothelial cells were returned to standard conditions and harvested immediately (T(0)), and at 1-(T(1)) and 3 (T(3)) h afterwards. Cell viability and culture medium pH were monitored throughout the experiments. 8-iso-PGF(2alpha) was assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS Exposure to CO(2) decreased the culture medium pH whereas helium increased the pH. 8-iso-PGF(2alpha) levels in all treated groups were significantly higher than in the control group: in the 4 h CO(2) group at T(1); in the 24 h CO(2) group at T(0) and T(1); and in the 4 h helium group at T(0), T(1) and T(3). 8-iso-PGF(2alpha) levels following 4 h CO(2) exposure were significantly lower than after 24 h CO(2) exposure at T(1), and lower than following 4 h helium exposure at all time points. CONCLUSIONS Exposure to both CO(2) and helium induces oxidative stress in mesothelial cells. Hypoxia-reoxygenation may play a role in this process.
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- 2004
26. Determination of catechins and catechin gallates in tissues by liquid chromatography with coulometric array detection and selective solid phase extraction
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Kai On, Chu, Chi Chiu, Wang, Ching Yan, Chu, Michael Scott, Rogers, Kwong Wai, Choy, and Chi Pui, Pang
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Brain Chemistry ,Reproducibility of Results ,Reference Standards ,Kidney ,Catechin ,Rats ,Rats, Sprague-Dawley ,Liver ,Calibration ,Electrochemistry ,Animals ,Female ,Indicators and Reagents ,Tissue Distribution ,Chromatography, High Pressure Liquid ,Spleen - Abstract
Catechins levels in organ tissues, particularly liver, determined by published methods are unexpectedly low, probably due to the release of oxidative enzymes, metal ions and reactive metabolites from tissue cells during homogenization and to the pro-oxidant effects of ascorbic acid during sample processing in the presence of metal ions. We describe a new method for simultaneous analysis of eight catechins in tissue: (+)-catechin (C), (-)-epicatechin (EC), (-)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), (-)-gallocatechin gallate (GCG) and (-)-epigallocatechin gallate (EGCG) (Fig. 1). The new extraction procedure utilized a methanol/ethylacetate/dithionite (2:1:3) mixture during homogenization for simultaneous enzyme precipitation and antioxidant protection. Selective solid phase extraction was used to remove most interfering bio-matrices. Reversed phase HPLC with CoulArray detection was used to determine the eight catechins simultaneously within 25 min. Good linearity (0.9922) was obtained in the range 20-4000 ng/g. The coefficients of variance (CV) were less than 5%. Absolute recovery ranged from 62 to 96%, accuracy 92.5 +/- 4.5 to 104.9 +/- 6%. The detection limit was 5 ng/g. This method is capable for determining catechins in rat tissues of liver, brain, spleen, and kidney. The method is robust, reproducible, with high recovery, and has been validated for both in vitro and in vivo sample analysis.
- Published
- 2004
27. The effect of intra-abdominal pressure on the generation of 8-iso prostaglandin F2alpha during laparoscopy in rabbits
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Ching Yan Chu, Ângela M. Bentes de Souza, Michael S. Rogers, Chi Chiu Wang, and Po Mui Lam
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medicine.medical_specialty ,Time Factors ,Urology ,Prostaglandin ,Adhesion (medicine) ,Tissue Adhesions ,Abdominal cavity ,Dinoprost ,Peritoneal Diseases ,chemistry.chemical_compound ,Peritoneum ,Pneumoperitoneum ,medicine ,Pressure ,Animals ,Postoperative Period ,Laparoscopy ,Tissue Adhesion ,medicine.diagnostic_test ,business.industry ,Rehabilitation ,Obstetrics and Gynecology ,Abdominal Cavity ,Carbon Dioxide ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Abdomen ,Female ,Rabbits ,business ,Pneumoperitoneum, Artificial - Abstract
BACKGROUND: Carbon dioxide pneumoperitoneum induces peritoneal oxidative stress. The aim of this study was to verify the effect of intra-abdominal pressure on oxidative stress in the peritoneum and on post-operative adhesion formation. METHODS: Forty-one rabbits underwent laparoscopic surgery: either gasless, or with CO2-pneumoperitoneum at pressures of 5, 10 or 15 mmHg. Serial parietal peritoneal biopsies were taken at various time-points: immediately after reaching the abdominal cavity, 30, 60, 90 and 120 min afterwards, and 15 min after abdominal desufflation. 8-iso prostaglandin F2a (8-iso PGF2a), a marker of oxidative stresss, was assayed by enzyme immunoassay and adhesion formation was scored by second-look laparoscopy on day 14. RESULTS: The gasless group showed no significant changes in 8-iso PGF2a. Conversely, significant changes occurred in CO2-pneumoperitoneum in a time- and pressure-dependent manner. Adhesions developed only in the CO2-pneumoperitoneum groups, and total adhesion score was correlated with the amount of CO2 insufflated and intra-abdominal pressure, but not with 8-iso PGF2a, which was correlated with intra-abdominal pressure. CONCLUSION: Intra-abdominal pressure increased 8-iso PGF2a in the parietal peritoneum in a graded fashion, whilst gasless laparoscopy had no impact. It also influenced the frequency and severity of adhesion formation, but no causal link was found between 8-iso PGF2a and post-operative adhesion formation.
- Published
- 2003
28. Effects of Different Inspired Oxygen Fractions on Lipid Peroxidation During General Anesthesia for Elective Cesarean Section
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Floria F. Ng, W.D. Ngan Kee, Michael S. Rogers, Lester A. H. Critchley, Ching Yan Chu, C.C. Wang, Wing Hung Tam, and Kim S. Khaw
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Lipid peroxidation ,chemistry.chemical_compound ,medicine.medical_specialty ,chemistry ,Elective cesarean section ,business.industry ,Anesthesia ,medicine ,chemistry.chemical_element ,business ,Oxygen ,Surgery - Published
- 2011
29. Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo
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Tina N. Davis, Robert J. D'Amato, Amy E. Birsner, Wai Ting Lui, Christian M. Becker, Hui Xu, Andrew L. Kung, Ching Yan Chu, Gene Chi Wai Man, and Chi Chiu Wang
- Subjects
Adult ,medicine.medical_specialty ,Angiogenesis ,Vascular Endothelial Growth Factor C ,Endometriosis ,complex mixtures ,Catechin ,Receptor tyrosine kinase ,Neovascularization ,Mice ,Random Allocation ,Internal medicine ,medicine ,Animals ,Humans ,heterocyclic compounds ,Cells, Cultured ,Neovascularization, Pathologic ,Tea ,biology ,food and beverages ,Obstetrics and Gynecology ,Kinase insert domain receptor ,Vascular Endothelial Growth Factor Receptor-2 ,Mice, Inbred C57BL ,Endothelial stem cell ,Vascular endothelial growth factor A ,Endocrinology ,Gene Expression Regulation ,Reproductive Medicine ,Vascular endothelial growth factor C ,biology.protein ,Cancer research ,Female ,sense organs ,Signal transduction ,medicine.symptom ,Signal Transduction - Abstract
Objective To investigate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo. Design Animal studies. Setting University laboratory. Animal(s) Human endometrium from women with endometriosis (n = 10) was transplanted into immunocompromised mice. Intervention(s) Mice (n = 30) were randomly treated with EGCG, vitamin E (antioxidant control), or vehicle (negative control) for microvessel imaging. Main Outcome Measure(s) Endometriotic implants were collected for angiogenesis microarray and pathway analysis. Differentially expressed angiogenesis molecules were confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Effects of EGCG on angiogenesis signal transduction were further characterized in a human endothelial cell line. Microvessel parameters and the angiogenesis signaling pathway in endometriotic implants and endothelial cells were studied. Result(s) EGCG, but not vitamin E, inhibited microvessels in endometriotic implants. EGCG selectively suppressed vascular endothelial growth factor C (VEGFC) and tyrosine kinase receptor VEGF receptor 2 (VEGFR2) expression. EGCG down-regulated VEGFC/VEGFR2 signaling through c-JUN, interferon-γ, matrix metalloproteinase 9, and chemokine (C-X-C motif) ligand 3 pathways for endothelial proliferation, inflammatory response, and mobility. EGCG also suppressed VEGFC expression and reduced VEGFR2 and ERK activation in endothelial cells. VEGFC supplementation attenuated the inhibitory effects by EGCG. Conclusion(s) EGCG inhibited angiogenesis and suppressed VEGFC/VEGFR2 expression and signaling pathway in experimental endometriosis in vivo and endothelial cells in vitro.
- Published
- 2011
30. Association of Hemopexin in Tear Film and Conjunctival Macrophages With Vernal Keratoconjunctivitis
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Ching Yan Chu, Dennis S.C. Lam, Jeffrey Chiu Fai Pong, Srinivas K Rao, Lu Li, Ling Yin Tang, Wai Ting Lui, Chi Pui Pang, Wai Ying Li, Terence C.W. Poon, and Chi Chiu Wang
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Conjunctiva ,Adolescent ,Proteome ,Enzyme-Linked Immunosorbent Assay ,Lacrimal apparatus ,Mass Spectrometry ,Pathogenesis ,Mice ,Young Adult ,Hemopexin ,Edema ,medicine ,Animals ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Child ,Eye Proteins ,Keratoconjunctivitis ,Conjunctivitis, Allergic ,business.industry ,Macrophages ,medicine.disease ,eye diseases ,body regions ,Ophthalmology ,medicine.anatomical_structure ,Tears ,Immunology ,Female ,medicine.symptom ,business ,Vernal keratoconjunctivitis - Abstract
Objective Vernal keratoconjunctivitis (VKC) is a chronic allergic inflammatory disease with unclear etiology and pathogenesis. We investigated the tear film proteome of patients with VKC to understand the pathologic characteristics of VKC. Methods Tear samples were collected from healthy volunteers and patients with VKC. Electrophoresis was performed to display the tear proteomic profiles according to VKC severity. The identities of differentially expressed proteins were analyzed by mass spectrometry and quantified by enzyme-linked immunosorbent assay. Impression cytology was performed on VKC conjunctival samples to demonstrate the cellular protein expression. Allergic sensitization was performed in mice to study the pathologic role of these proteins in VKC. Results Hemopexin, an inflammatory protein, was elevated in the tear film of patients with VKC. The increased hemopexin concentration in VKC tears was significantly associated with disease severity. Impression cytology showed specific high hemopexin expression in dekeratinized conjunctival epithelium and necrotic macrophages in patients with VKC. Immunohistochemical examination of normal lacrimal tissues from mice showed that hemopexin was not expressed in any lacrimal apparatus. Under systemic and topical sensitization and challenge using hemopexin in mice, the affected eye had mild to moderate bead discharge, chemosis, and edema with excessive macrophage infiltration and conjunctival necrosis. Conclusion An association exists between tear hemopexin and the development and pathologic effects of VKC. Clinical Relevance Increased hemopexin may have a role in the development of VKC.
- Published
- 2011
31. Association of Hemopexin in Tear Film and Conjunctival Macrophages With Vernal Keratoconjunctivitis.
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Jeffrey Chiu Fai Pong, Ching Yan Chu, Wai Ying Li, Ling Yin Tang, Lu Li, Wai Ting Lui, Terence Chuen Wai Poon, Rao, Srinivas K., Shun Chiu Lam, Dennis, Chi Chiu Wang, and Chi Pui Pang
- Abstract
Objective: Vernal keratoconjunctivitis (VKC) is a chronic allergic inflammatory disease with unclear etiology and pathogenesis. We investigated the tear film proteome of patients with VKC to understand the pathologic characteristics of VKC. Methods: Tear samples were collected from healthy volunteers and patients with VKC. Electrophoresis was performed to display the tear proteomic profiles according to VKC severity. The identities of differentially expressed proteins were analyzed by mass spectrometry and quantified by enzyme-linked immunosorbent assay. Impression cytology was performed on VKC conjunctival samples to demonstrate the cellular protein expression. Allergic sensitization was performed in mice to study the pathologic role of these proteins in VKC. Results: Hemopexin, an inflammatory protein, was elevated in the tear film of patients with VKC. The increased hemopexin concentration in VKC tears was significantly associated with disease severity. Impression cytology showed specific high hemopexin expression in dekeratinized conjunctival epithelium and necrotic macrophages in patients with VKC. Immunohistochemical examination of normal lacrimal tissues from mice showed that hemopexin was not expressed in any lacrimal apparatus. Under systemic and topical sensitization and challenge using hemopexin in mice, the affected eye had mild to moderate bead discharge, chemosis, and edema with excessive macrophage infiltration and conjunctival necrosis. Conclusion: An association exists between tear hemopexin and the development and pathologic effects of VKC. Clinical Relevance: Increased hemopexin may have a role in the development of VKC. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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32. Serotonin Receptor 6 Mediates Defective Brain Development in Monoamine Oxidase A-deficient Mouse Embryos.
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Chi Chiu Wang, Chi Wai Man, Gene, Ching Yan Chu, Borchert, Astrid, Ugun-Klusek, Aslihan, Billett, E. Ellen, Kühn, Hartmut, and Ufer, Christoph
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- *
MONOAMINE oxidase , *SEROTONIN receptors , *MITOCHONDRIAL membranes , *BIOGENIC amines , *CENTRAL nervous system physiology , *NEURAL development , *GENETICS - Abstract
Monoamine oxidases A and B (MAO-A and MAO-B) are enzymes of the outer mitochondrial membrane that metabolize biogenic amines. In the adult central nervous system, MAOs have important functions for neurotransmitter homeostasis. Expression of MAO isoforms has been detected in the developing embryo. However, suppression of MAO-B does not induce developmental alterations. In contrast, targeted inhibition and knockdown of MAO-A expression (E7.5-E10.5) caused structural abnormalities in the brain. Here we explored the molecular mechanisms underlying defective brain development induced by MAO-A knockdown during in vitro embryogenesis. The developmental alterations were paralleled by diminished apoptotic activity in the affected neuronal structures. Moreover, dysfunctional MAO-A expression led to elevated levels of embryonic serotonin (5-hydroxytryptamine (5-HT)), and we found that knockdown of serotonin receptor-6 (5-Htr6) expression or pharmacologic inhibition of 5-Htr6 activity rescued the MAO-A knockdown phenotype and restored apoptotic activity in the developing brain. Our data suggest that excessive 5-Htr6 activation reduces activation of caspase-3 and -9 of the intrinsic apoptotic pathway and enhances expression of antiapoptotic proteins Bcl-2 and Bcl-XL. Moreover, we found that elevated 5-HT levels in MAO-A knockdown embryos coincided with an enhanced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and a reduction of proliferating cell numbers. In summary, our findings suggest that excessive 5-HT in MAO-A-deficient mouse embryos triggers cellular signaling cascades via 5-Htr6, which suppresses developmental apoptosis in the brain and thus induces developmental retardations. [ABSTRACT FROM AUTHOR]
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- 2014
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33. Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats.
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Kai On Chu, Chi Chiu Wang, Ching Yan Chu, Kwok Ping Chan, Rogers, Michael Scott, Kwong Wai Choy, and Chi Pui Pang
- Subjects
- *
PHARMACOKINETICS , *DRUG metabolism , *POLYPHENOLS , *CATECHIN , *GREEN tea - Abstract
We carried out a pharmacokinetic study to determine the levels and profiles of catechins in pregnant rats and their fetuses after ingestion of green tea extract (GTE). We measured total catechin levels after enzyme digestions. Dams, at 15.5 days of gestation, were fed with GTE and catechins were measured in the maternal plasma, placenta, and fetus 0, 0.5, 1, 2, 3, 5, 8, 10, 12, 16, and 20 h after maternal GTE intake. The pharmacokinetic changes were analyzed by non compartmental models. We found that maternal plasma concentrations of catechins were about 10 times higher than in placenta and 50–100 times higher than in the fetus. AUC and Cmax levels of (-)-epicatechin (EC) were the highest in plasma while the levels of (-)-epigallocatechin gallate (EGCG) were the highest in the placenta and the fetus. The exposure level of catechin derivatives was higher than the gallate derivatives in maternal plasma after normalization but reversed in the placenta and fetus. The absorption of epi-isomers in plasma was found to be more favorable than their non epi-isomer counterparts. EGCG had the highest level of exposure (AUC) and the highest Cmax in the fetus, implying it may have potential for in utero antioxidant protection. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1372–1381, 2006 [ABSTRACT FROM AUTHOR]
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- 2006
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34. Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis.
- Author
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Chi Chiu Wang, Borchert, Astrid, Ugun-Klusek, Aslihan, Ling Yin Tang, Wai Ting Lui, Ching Yan Chu, Billett, Ellen, Kuhn, Hartmut, and Ufer, Christoph
- Subjects
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MONOAMINE oxidase , *METALLOENZYMES , *APOPTOSIS , *CELL death , *GENE expression - Abstract
Monoamine oxidases (MAO-A, MAO-B) metabolize biogenic amines and have been implicated in neuronal apoptosis. Although apoptosis is an important process in embryo development, the role of MAO isoenzymes has not been investigated in detail. We found that expression of MAO-A and MAO-B can be detected early on during embryo development. Expression levels remained constant until around midgestation but then dropped to almost undetectable levels toward birth. Similar expression kinetics were observed in the brain. Isoform-specific expression silencing of MAO-A mediated by siRNA during in vitro embryogenesis induced developmental defects, as indicated by a reduction of the crown rump length and impaired cerebral development. These alterations were paralleled by elevated serotonin levels. Similar abnormalities were observed when embryos were cultured in the presence of the MAO-A inhibitor clorgyline or when the transcriptional inhibitor of MAO-A expression R1 was overexpressed. In contrast, no such alterations were detected when expression of MAO-B was knocked down. To explore the underlying mechanisms for the developmental abnormalities in MAO-A knockdown embryos, we quantified the degree of developmental apoptosis in the developing brain. MAO-A knockdown reduced the number of apoptotic cells in the neuroepithelium, which coincided with impaired activation of caspases 3 and 9. Moreover, we observed reduced cyclin D1 levels as an indicator of impaired cell proliferation in MAO-A knockdown embryos. This data highlights MAO-A as a vital regulator of embryonic brain development. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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