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Biomedical subjects

Xuan Zhang

Publications and source records attributed to Xuan Zhang.

At least 91 records · Page 5Linked to original sources

Involvement of ERK1/2 pathway in TGF-beta1-induced VEGF secretion in normal human cytotrophoblast cells.

Transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in the angiogenesis during the development of placenta, but the intracellular signaling mechanism by which TGF-beta1 stimulates this process remains poorly understood. In this article, we demonstrated that exposure of normal human cytotrophoblast cells to TGF-beta1 stimulated the secretion of the VEGF gene encoding vascular endothelial growth factor, which is a key factor in angiogenesis. Meanwhile, treatment of normal human cytotrophoblast cells with TGF-beta1-induced expression of HIF-1a, the regulated subunit of hypoxia-inducible factor 1, a known transactivator of the VEGF gene. Our data indicated that TGF-beta1 induced extracellular signal- regulated kinase (ERK) 1/2 phosphorylation in normal human cytotrophoblast cells. Moreover, treating cells with PD98059, an inhibitor of ERK1/2 signaling, inhibited TGF-beta1 stimulation of VEGF secretion and HIF-1a protein expression. These data indicated that in normal human cytotrophoblast cells, TGF-beta1 induced HIF-1a-mediated VEGF secretion, and TGF-beta1-stimulated-ERK1/2 activation may be involved in this process.

Humans↗

Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis.

The aim of this study was to determine the influence of a glutamate receptor antagonist or a protein kinase C (PKC) inhibitor on the central visceral nociceptive amplification process present in an experimental pancreatitis model. The acute pancreatitis model was produced by combining intraductal infusion of an irritative bile salt, glycodeoxycholic acid (GDOC), with intraperitoneal injection of a CCK analogue, caerulein, in male Sprague-Dawley rats. Exploratory activities were measured with an automated photobeam activity system and compared among different treatment groups. To confirm the inflammation, the pancreas was weighed and compared histologically with those taken from naive rats. Exploratory activity changed significantly in rats with experimental pancreatitis (i.e., rearing events, rearing time, active time, distance traveled, and total activity all were decreased; whereas resting time was increased). The inflamed pancreatic tissues were edematous, with moderate to marked acinar atrophy and inflammatory infiltrate. Intrathecal administration (at the T7-T9 spinal levels) of an NMDA receptor antagonist (D-AP5, 1 microg) or a selective PKC inhibitor (GF109203X, 0.15 microg) significantly reversed the changes in exploratory activity when compared with the vehicle-treated group of rats with experimental pancreatitis. Our results demonstrate that pancreatitis pain is the result of central pain processes that play a role in the amplification of responses to peripheral visceral input through NMDA receptor activation and PKC phosphorylation signaling pathways.

Acute Disease↗

Expression of Smad2 and Smad4, transforming growth factor-beta signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation.

SMADs are intracellular signaling molecules that transmit signals elicited by members of transforming growth factor-beta (TGF-beta) superfamily. To decipher the mechanism of TGF-beta signaling during the estrous cycle and implantation, we performed in situ hybridization to investigate the expression patterns of mRNAs for Smad2 and Smad4 in rat endometrium during the estrous cycle and on Days 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 of pregnancy. Intense epithelial expression of Smad2 mRNA at diestrus and proestrus was reduced at estrus and metaestrus, while Smad4 maintained its constitutive expression during the estrous cycle. During pre-implantation, both Smads were accumulated in the luminal epithelium and the glandular epithelium. Contrary to the dramatic Smad4 expression, Smad2 was highly down-regulated on Day 2.5 and was increased on Day 3.5. During peri-implantation, both Smads were expressed in the luminal epithelium, subepithelial stroma, and the primary decidual zone. Smad4 was down-modulated on Day 5.5. These results suggest that (a) both Smads are involved in the tissue remodeling of cycling and pregnant rat uteri; (b) TGF-beta signaling functions mainly in the epithelium during pre-implantation and Smad2 is involved in the endometrial switch from the neutral phase to the receptive phase; (c) TGF-beta signaling is down-regulated at the time when trophoblast invasion begins and both Smads are involved in the formation of the primary decidual zone.

Animals↗

Is NOTCH4 associated with schizophrenia?

The NOTCH4 locus was reported to be associated with schizophrenia in our previous study but the subsequent replication by other workers has been inconsistent. To find out possible reasons for the poor replication, the present work was undertaken to analyse four functional single nucleotide polymorphisms (SNPs) (rs367398, rs915894, rs520692 and rs422951) at the NOTCH4 locus among 141 schizophrenic family trios of Chinese Han descent. Of these four SNPs, rs520692 was the only one associated with schizophrenia (P = 0.017); the other three, however, did not show any association with the illness, including rs367398 located in the promoter region, which had shown a strong association with the illness in our previous study conducted with British samples. Although these four SNPs analysed lie within a less than 4 kb segment of genomic DNA, the pattern of linkage disequilibrium between them was unexpected. The strongest linkage disequilibrium was shown only between rs367398 and rs520692 and between rs520692 and rs422951 in both parent and patient groups. This study raises the possibility that there might be two or more disease-underlying variants at the NOTCH4 locus or at a nearby locus, and that the allelic or locus heterogeneity may be one of the possible reasons for the poor replication of the NOTCH4 finding.

Adult↗

[Experimental study on prevention and treatment of focal segmental glomerulosclerosis with heparin].

OBJECTIVE: To observe the preventive and therapeutic feasibility of heparin calcium injection in rats with focal segmental glomerulosclerosis (FSGS). METHODS: Eighteen male Wistar rats were divided into three groups: Normal control group (A, n=6), heparin-treated rats (B, n=6) and model group (C, n=6). Rat model of FSGS was constructed with low-dose adriamycin, metaraminol and high lipid feed method. Group B was treated with heparin. 24-hour urinary protein was measured at the 0, 2nd, 4th, 6th and 12th week. Serum total protein, albumin, cholesterol, blood urea nitrogen (BUN) and serum creatinine (SCr) were determined at 0, 2nd, 6th and 12th week. Renal cortex blood flow was performed at the 12th week. Renal pathology changes were evaluated at the 12th week as well. RESULTS: 24-hour urinary protein was decreased in heparin treatment group after 6th week. The serum cholesterol level in heparin treatment group was lower than that in model group at 12th week. Renal cortex blood flow was increased significantly in heparin -treated group. Glomerular sclerotic index (SI) and glomerular extracellular matrix (ECM)/glomerular area (GA) were decreased significantly in heparin treatment group. Electron microscopy revealed that there was no glomerular capillary cavities obstruction in heparin -treated group, basement membrane change and foot precesses fusion were markedly alleviated in comparison with model group. CONCLUSION: Heparin may be play a valuable role in the prevention and treatment of FSGS.

Albumins↗

[Study of HLA polymorphism in the 6965 Han bone marrow registry donors].

OBJECTIVE: To analyze human leukocyte antigen (HLA) polymorphism and search for new alleles in Chinese Han population bone marrow registry donors. METHODS: DNA-based HLA genotyping methods were used including PCR-SSP, BST and molecular cloning. RESULTS: A total of 6965 unrelated donors, 4707 from South China origin and 2258 from north, were typed for HLA-A, B, and DRB1 loci. Seventy-two specificities of HLA alleles were identified. The HLA-A25, A34, A74, B41, B42, B53, B73 and B81 that were rarely reported in previously Chinese population studies were identified in this study. Estimation of gene frequency indicated that the blank gene frequency was less than 0.2% for HLA-A, 0.25% for HLA-B and 0.70% for HLA-DRB1 loci. Three novel alleles were identified and officially assigned by the World Health Organization (WHO) Nomenclature Committee as A*0253N, A*1114 and B*5610. CONCLUSION: Large-scale DNA-based HLA genotyping used in bone marrow registry donors is highly accurate and reliable for estimating gene frequency and searching for new alleles. The discrepancy of HLA gene distribution between South and North China Han population showed the necessity of setting the more regions in South and North China to screen the bone marrow registry donors for bone marrow transplant.

Bone Marrow Transplantation↗

[BAY11-7082 and Lactacystein in CD154-induced NF-kappaB activation].

OBJECTIVE: To investigate the inhibition mechanisms of BAY11-7082 (IkappaB-alpha phosphorylation inhibitor) and Lactacystein (proteosome inhibitor) in CD154-induced NF-kappaB activation. METHODS: We used recombinant CD154 to stimulate EBV/LMP1 negative Ramos B cell and observed the effects of BAY11-7082 and Lactacystein in CD154-induced NF-kappaB luciferase activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of p65, and nuclear translocation of NF-kappaB subunits upon CD154 stimulation. RESULTS: Both BAY11-7082 and Lactacystein abrogated CD154-induced NF-kappaB luciferase activation in Ramos cells. While CD154-induced phosphorylation of p65, phosphorylation and degradation of IkappaB-alpha, and nuclear translocation of p50, p65, and c-Rel were all blocked by BAY11-7082; Lactacystein only inhibited degradation of IkappaB-alpha and p65 nuclear translocation. CONCLUSION: BAY11-7082 and Lactacystein inhibit CD154-induced NF-kappaB activation through different mechanisms.

Acetylcysteine↗

[Genetic polymorphisms of 6 Y-chromosome specific STR loci in the southern Chinese Han population and its application in forensic science].

To study the genetic polymorphisms of six Y-chromosome specific STR loci in the southern Chinese Han population and apply it in forensic science, six Y-STR loci were amplified by multiple PCR and the PCR products were detected by using ABI Prism 377 Sequencer. The haplotype frequencies at 6 Y-STR loci were determined in a total of 204 unrelated males from southern Han population of China. Ninety-three father/son pairs with demonstrated paternity and thirty-eight non-paternity father/son pairs were detected by using our Y-STR system. As a result, the number of alleles for DYS393, DYS19, DYS389 II, DYS390, DYS391 and DYS385 were 5, 6, 8, 6, 4 and 44, respectively. A total of 176 haplotypes at 6 Y-STR loci were found. Two father/son pairs with single Y-STR mutation were observed in the 93 father/son pairs with demonstrated paternity. Among the 38 non-paternity father/son pairs, one case with one Y-STR exclusion of paternity, one case with two Y-STR exclusions and 35 cases with 3 or more Y-STR exclusions were observed. Non-exclusion of paternity at 6 Y-STR loci was found only in one case. This result indicated that the six Y-STR loci were highly polymorphic and are suitable for personal identification and paternity testing.

Asian People↗

[Preparation of cyclosporine A pH sensitive nanoparticles and oral pharmacokinetics in rats].

AIM: To study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles. METHODS: The CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing (250 +/- 20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg x kg(-1) by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles. RESULTS: The blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion, the relative bioavailability of CyA was 94.8%, 115.2%, 113.6% and 132.5% for CyA-E100, CyA-L100, CyA-L100-55 and CyA-S100 nanoparticles respectively. CONCLUSION: CyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion (P < 0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore, this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

Administration, Oral↗

Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice.

Tissue inhibitors of metalloproteinases (TIMPs) are expressed within the uteri of virtually all species where they are postulated to control extracellular matrix turnover, cellular apoptosis, and proliferation. The objective of the current study was to examine the steroidal regulation of uterine TIMP expression and to determine the potential role of the TIMP-1 gene product in this regulation. To accomplish these goals, ovariectomized female TIMP-1 wild-type and null mice were treated with estradiol, progesterone, or estradiol and progesterone and killed at various times after steroid administration. Estradiol induced a significant reduction in uterine TIMP-3 expression in wild-type mice at 8 and 24 h post-steroid administration, but the ability of this steroid to decrease TIMP-3 expression was impaired in the uteri of TIMP-1 null mice. Further, estrogen-induced uterine wet-weight gain/edema was enhanced in the TIMP-1 null mice, and the antiestrogen compound ICI 182780 or progesterone could only partially block this estrogenic effect. It is concluded from this study that steroidal modulation of uterine TIMP-3 expression and regulation of wet-weight gain/edema are altered in TIMP-1 null mice. These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema.

Animals↗

Effect of ubiquitin-proteasome pathway on mouse blastocyst implantation and expression of matrix metalloproteinases-2 and -9.

Previous studies have documented that ubiquitin-related proteins are present in human, baboon, rhesus monkey, cow, sheep, and mouse pregnant uteri, indicating that the ubiquitin-proteasome pathway (UPP) may be involved in the extensive uterine remodeling during mammalian early pregnancy, but there is still no direct evidence. A mouse intrauterine injection model was employed to study the direct effect of the UPP on mouse embryo implantation and its possible mechanisms. On Day 3 of pregnancy in each mouse, one of the uterine horns in each mouse was injected with different concentrations of lactacystin, a specific proteasome inhibitor, or anti-ubiquitin antibody, and the other side was used as a control. On days 5, 6, and 7, the number of implanted embryos was counted and the expression and gelatinolytic activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 were studied. Results presented here illustrate that injection of lactacystin and anti-ubiquitin antibody significantly inhibited mouse embryo implantation. Further investigations by reverse transcription-polymerase chain reaction and gelatin zymography showed that MMP-2 and MMP-9 mRNA expression, as well as the gelatinolytic activity of MMP-9 in the lactacystin-treated uterine horn, significantly decreased, whereas the activity of MMP-2 was not significantly affected. The results obtained from this study, together with previous reports, suggest that the UPP is involved in mouse embryo implantation, and UPP's effect on embryo implantation is achieved at least in part by regulating MMP-2 and MMP-9 mRNA expression and the gelatinolytic activity of MMP-9.

Acetylcysteine↗

Development of fluorescent sensing of anions under excited-state intermolecular proton transfer signaling mechanism.

[reaction: see text] A substantially red-shifted fluorescence emission in 3-hydroxyl-2-naphthanilide in acetonitrile was developed and drastically enhanced upon addition of anions such as F(-), AcO(-), and H(2)PO(4)(-), with the enhancement depending on anion basicity. Excited-state intermolecular proton transfer in the sensor-anion hydrogen-bonding complex was suggested to be the signaling mechanism.

Journal Article↗

Intramolecular charge transfer with N-benzoylaminonaphthalenes. 1-Aminonaphthalene versus 2-aminonaphthalene as electron donors.

N-(substituted-benzoyl)-1-aminonaphthalenes and N-(substituted-benzoyl)-2-aminonaphthalenes (1-NBAs and 2-NBAs) with varied substituents at the para- or meta-position of benzoyl phenyl ring were prepared to probe the difference between 1-aminonaphthalene (1-AN) and 2-aminonaphthalene (2-AN) as electron donors, using benzanilide-like charge transfer as a probe reaction. An abnormal long-wavelength emission was found for all of the prepared aminonaphthalene derivatives in cyclohexane and was assigned to the CT state by the observation of a substantial red shift with increasing solvent polarity or with increasing electron-withdrawing ability of the substituent. The CT emission energies were found to follow a linear relationship with the Hammett constant of the substituent and the value of the linear slope for 1-NBAs (-0.45 eV) was higher than that of 2-NBAs (-0.35 eV), the latter being close to that of the aniline derivatives (BAs, -0.345 eV). This pointed to a higher extent of charge separation in the CT state of 1-NBAs in which a full charge separation was established by the reduction potential dependence of the CT emission energy with a linear slope of -1.00. The possible contribution of the difference in the steric effect and the electron donating ability of the donors in 1-NBAs and 2-NBAs was ruled out by the observation that the corresponding linear slopes of benzoyl-substituted BAs remained unchanged when para-, meta-, ortho-, or ortho,ortho-methyls were introduced into the aniline moiety. It was therefore concluded that 1-AN enhanced the charge transfer in 1-NBAs and the proximity of its 1La and 1Lb states was suggested to be responsible. Results showed that the charge transfers in 1-NBAs and 2-NBAs were not the same and 1-AN and 2-AN as electron donors were different not only in electron donating ability but in shaping the charge transfer pathway as well.

Journal Article↗

The effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following intradermal injection of capsaicin.

The functions of crucial proteins in the nervous system are modulated by kinases and phosphatases which catalyze opposing reactions of phosphorylation and dephosphorylation. During spinal cord central sensitization, serine/threonine protein phosphatase 2A (PP2A) may play an important role in determining the excitability of nociceptive neurons in the spinal cord by modulating the phosphorylation state of some critical proteins. The effects of a general inhibitor of PP2A, okadaic acid (OA), and a specific inhibitor, fostriecin, on the behavioral responses of rats following capsaicin injection were investigated in this study. Hyperalgesia was initiated by injection of capsaicin into the plantar surface of the hindpaw of rats. An intrathecal catheter was previously implanted into the subarachnoid space of the spinal cord for the administration of a variety of drugs. Rats were tested for responses to mechanical stimuli using von Frey filaments of different bending forces applied at a site outside the area of injection. Responses to heat stimuli were detected from a site near the injection area. The responses were recorded before and after injection of capsaicin with the perfusion of ACSF, OA negative control, OA or fostriecin at different time points. The results demonstrated that secondary mechanical hyperalgesia and allodynia can be induced by the intradermal injection of capsaicin. Compared to administration of ACSF or the OA negative control, infusion of the phosphatase inhibitor OA or of fostriecin into the subarachnoid space enhanced the secondary mechanical hyperalgesia and allodynia by making the intradermal capsaicin-induced hyperalgesia and allodynia last longer.

Animals↗

High performance liquid chromatographic fingerprint evaluation of the quinolizidine alkaloids from commercial Radix Sophorae Flavescentis.

Fifteen commercial samples of Radix Sophorae Flavescentis were collected from different parts of China. HPLC analysis showed that the commercial samples all contained quinolizidine alkaloids and a total of nine chromatographic peaks were identified by referring to standard compounds, HPLC/MS analysis and comparison of the physicochemical data of the isolated peak with the literature. The contents of the major alkaloids were determined and the ratio of the major alkaloids contents was shown to be correlated with their source of origin. The commercial samples from China gave a distinct HPLC pattern showing the main alkaloids contents. The sample preparations were researched and the extraction conditions of the alkaloids were optimized. Reproducible HPLC fingerprints can be obtained for the quinolizidine alkaloids under the well-controlled extraction conditions. The HPLC fingerprint analysis method is suitable for the quality control of the Radix Sophorae Flavescentis and the standardization of phytomedicines.

Alkaloids↗

Prospective cohort study of comprehensive prevention to gastric cancer.

AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically. METHODS: Stratified sampling and cluster sampling were applied to define the intervention group and the control group. The prospective cohort study was used for evaluating the effect of preventing gastric cancer. The relative risk (RR) and attributable risk percent (AR %) of intervention on gastric cancer death were calculated. Potential years of life lost (PLYY) of the disease was analyzed, and the RR and AR % of PYLL were calculated. Survival analysis was applied among the screened patients. RESULTS: In the first 4 years after intervening, the relative risk (RR) of intervention on death was 0.5059 (95 % CI: 0.3462-0.7392, P<0.05) with significance statistically. AR % of the intervention on death was 49.41 %. The RR of intervention on cumulative PYLL was 0.6778 (95 % CI: 0.5604-0.8198, P<0.05) with statistic significance. AR % of the intervention on cumulative PYLL was 30.32 %. The four-year survival rate of the screened patients was 0.6751 (95 % CI: 0.5298-0.9047). CONCLUSION: The initiative intervention results showed that the intervention approach used in the trial was effective, it reduced mortality and increased survival rate, and alleviated the adverse effect of gastric cancer on the health and life of screened population.

Cohort Studies↗

[Quantitative analysis of resveratrol from grape seeds and grape skins by high performance liquid chromatography method].

In order to perform a quantitative analysis of resveratrol from grape seeds, grape skins and waste residue of grape winery, acetonitrile-water (26:74) was applied as the fluxion phase. The detective wave-length (lambda) was 303 nm. Colume temperature was 35 degrees C. The type of chrimato pattern colume was SupelcosiLTMLC-18 (250 mm x 4.6 mm, 5 microns). Results showed that the contents of resveratrol from grape skins were higher than those of grape seeds. Among different kinds of grape skins, resveratrol contents varied. The reserveratrol content of Suo Suo grape skin was the lowest (0.9850 microgram/g). Among the same kinds of grape skins from the same production area, the resveratrol content was highest in the skin of waste residue of grape winery followed by the fresh grape skin and the old grape skin ranked thirdly, and the differences of resveratrol contents were statistically significant.

Chromatography, High Pressure Liquid↗