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Biomedical subjects

Yi Zhao

Publications and source records attributed to Yi Zhao.

At least 55 records · Page 3Linked to original sources

Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation.

The angiotensin type 2 (AT2) receptor has been previously demonstrated to exert neuroprotective actions possibly by inducing neuronal cell differentiation involving neurite outgrowth. The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is an important transcriptional regulator of cell differentiation. The aim of the present study was to clarify whether PPARgamma is involved in AT2-receptor-mediated morphological neuronal cell differentiation. To investigate AT2-receptor-mediated morphological neuronal cell differentiation, rat pheochromocytoma cells (PC12W cells) expressing AT2 but not AT1 receptors, were stimulated with angiotensin II (Ang II, 100 nmol/L) +/- the PPARgamma antagonists GW9662 (3 micromol/L) and bisphenol A diglycidyl ether (BADGE, 1 micromol/L), and neurite outgrowth of these cells was assessed. Ang II induced neurite outgrowth by 19 +/- 1.6-fold (p < 0.01). Antagonizing PPARgamma activity by GW9662 or BADGE potently blocked Ang II-induced neurite outgrowth (Ang II + GW9662: 6.6 +/- 1.5-fold, p < 0.05; Ang II + BADGE: 1.3 +/- 0.7-fold, p < 0.01). AT2 receptor activation by Ang II markedly induced mRNA and protein expression of the PPARgamma2 isoform and enhanced ligand-induced PPARgamma activity in transactivation assays. In conclusion, the present study demonstrates that Ang II induces PPARgamma expression and ligand-mediated PPARgamma activity via AT2 receptor activation, which appears to be a crucial process in AT2 receptor mediated neurite outgrowth. AT2 receptor/PPARgamma-dependent neurite outgrowth may play an important role during neuroprotective processes.

Angiotensin II↗

ANG III induces expression of inducible transcription factors of AP-1 and Krox families in rat brain.

In addition to rapid responses comprising increases in blood pressure, drinking, and stimulation of natriuresis, ANG II induces the expression of transcription factors (TF) in the central nervous system. The ANG II metabolite ANG III (ANG 2-8) has been demonstrated to exert physiological effects similar to those of ANG II. We aimed to determine 1) whether ANG III induces TF expression in the brain, 2) which ANG II (AT) receptor subtype is involved, and 3) whether the two peptides, ANG II and ANG III, differ in their efficacy to stimulate TF expression. ANG II (100 pmol), ANG III (100 pmol), or vehicle was injected into the lateral brain ventricle of conscious rats alone or in combination with the AT(1) receptor antagonist losartan (10 nmol), the AT(2) receptor antagonist PD-123319 (5 nmol), or the aminopeptidase inhibitor amastatin (10 nmol). Similar to ANG II, ANG III induced the expression of c-Fos, c-Jun, and Krox-24 in four brain regions, subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus of the hypothalamus, with the same efficacy. This effect was AT(1) receptor mediated. Pretreatment with amastatin reduced the expression of TF in response to ANG II, indicating that this expression is partly mediated by ANG III. Interestingly, the AT(2) receptor antagonist PD-123319 alone slightly enhanced the expression of c-Fos, c-Jun, and Krox-24 in different populations of neurons of the paraventricular nucleus. These data indicate that different populations of neurons in the paraventricular nucleus are tonically inhibited by AT(2) receptors under physiological conditions.

Angiotensin II↗

Gene expression profile of murine long-term reconstituting vs. short-term reconstituting hematopoietic stem cells.

The hematopoietic stem cell (HSC) compartment is composed of long-term reconstituting (LTR) and short-term reconstituting (STR) stem cells. LTR HSC can reconstitute the hematopoietic system for life, whereas STR HSC can sustain hematopoiesis for only a few weeks in the mouse. Several excellent gene expression profiles have been obtained of the total hematopoietic stem cell population. We have used five-color FACS sorting to isolate separate populations of LTR and STR stem cell subsets. The LTR HSC has the phenotype defined as Lin- Sca+ Kit+ 38+ 34-; two subsets of STR HSC were obtained with phenotypes of Lin- Sca+ Kit+ 38+ 34+ and Lin- Sca+ Kit+ 38- 34+. The microarray profiling study reported here was able to identify genes specific for LTR functions. In the interrogated genes (approximately 12,000 probe sets corresponding to 8,000 genes), 210 genes are differentially expressed, and 72 genes are associated with LTR activity, including membrane proteins, signal transduction molecules, and transcription factors. Hierarchical clustering of the 210 differentially expressed genes suggested that they are not bone marrow-specific but rather appear to be stem cell-specific. Transcription factor-binding site analysis suggested that GATA3 might play an important role in the biology of LTR HSC.

Animals↗

Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury.

Several lines of clinical and experimental evidence suggest an important role of the renin-angiotensin system in ischemic brain injury although the cellular regulation of the angiotensin AT1 and AT2 receptors and their potential relevance in this condition have not yet been clearly defined. We first assessed the regulation of brain AT1 and AT2 receptors in response to transient unilateral medial cerebral artery occlusion in rats by real-time RT-PCR, Western blot, and immunofluorescence labeling. AT2 receptors in the peri-infarct zone were significantly upregulated 2 days after transient focal cerebral ischemia. Increased AT2 receptors, which were abundantly distributed in a large number of brain regions adjacent to the infarct area including cerebral frontal cortex, piriform cortex, striatum, and hippocampus, were exclusively expressed in neurons. By contrast, AT1 receptors, which remained unaltered, were mainly expressed in astrocytes. In neurons of ischemic striatum, increased AT2 receptors were associated with intense neurite outgrowth. Blockade of central AT2 receptors with PD123177 abolished the neuroprotective effects of central AT1 receptor blockade with irbesartan on infarct size and neurological outcome. In primary cortical neurons, stimulation of AT2 receptors supported neuronal survival and neurite outgrowth. Our data indicate that cerebral AT2 receptors exert neuroprotective actions in response to ischemia-induced neuronal injury, possibly by supporting neuronal survival and neurite outgrowth in peri-ischemic brain areas.

Angiotensin II↗

NONCODE: an integrated knowledge database of non-coding RNAs.

NONCODE is an integrated knowledge database dedicated to non-coding RNAs (ncRNAs), that is to say, RNAs that function without being translated into proteins. All ncRNAs in NONCODE were filtered automatically from literature and GenBank, and were later manually curated. The distinctive features of NONCODE are as follows: (i) the ncRNAs in NONCODE include almost all the types of ncRNAs, except transfer RNAs and ribosomal RNAs. (ii) All ncRNA sequences and their related information (e.g. function, cellular role, cellular location, chromosomal information, etc.) in NONCODE have been confirmed manually by consulting relevant literature: more than 80% of the entries are based on experimental data. (iii) Based on the cellular process and function, which a given ncRNA is involved in, we introduced a novel classification system, labeled process function class, to integrate existing classification systems. (iv) In addition, some 1100 ncRNAs have been grouped into nine other classes according to whether they are specific to gender or tissue or associated with tumors and diseases, etc. (v) NONCODE provides a user-friendly interface, a visualization platform and a convenient search option, allowing efficient recovery of sequence, regulatory elements in the flanking sequences, secondary structure, related publications and other information. The first release of NONCODE (v1.0) contains 5339 non-redundant sequences from 861 organisms, including eukaryotes, eubacteria, archaebacteria, virus and viroids. Access is free for all users through a web interface at http://noncode.bioinfo.org.cn.

Base Sequence↗

Effect of MDR1 haplotype on risk of Parkinson disease.

BACKGROUND: MDR1, a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. OBJECTIVE: To determine whether specific haplotypes formed by SNPs e21/2677 and e26/3435 may protect against Parkinson disease (PD) among ethnic Chinese in Hong Kong. DESIGN: Case-control study. SETTING: Tertiary referral centers in Hong Kong. SUBJECTS: One hundred eighty-five patients with PD and 206 control subjects. INTERVENTIONS: The two SNPs were amplified in a single multiplex polymerase chain reaction. Five other SNPs that span 100 kilobases of the gene were also analyzed. MAIN OUTCOME MEASURES: Haplotypes frequencies, degree of haplotype association with the disease status, and estimated odds ratio for each haplotype with associated 95% confidence intervals. RESULTS: In addition to 2677 G-->T/A (exon 21) and 3435 C-->T (exon 26), the other SNPs that were analyzed were -41 A-->G (intron -1), -145 C-->G (exon 1), -129 T-->C (exon 1), 1236 T-->C (exon 12), and 4036 A-->G (exon 28). Haplotypes containing SNPs e21/2677 and e26/3435 were found to be significantly associated with risk of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P<.001; chi(2) = 14.521; odds ratio, 0.33; 95% confidence interval, 0.19-0.59). CONCLUSIONS: An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.

Adult↗

Alpha-synuclein mRNA expression in sporadic Parkinson's disease.

The expression of alpha-synuclein gene can be influenced by the genomic load and/or epigenetic factors. By using quantitative real-time polymerase chain reaction techniques, we demonstrated that the alpha-synuclein gene mRNA expression in sporadic PD did not differ from healthy controls (median [range] 0.110 ]0.012-0.628] vs. 0.120 [0.028-0.447]; P = 0.15). There was no difference in the alpha-synuclein gene dosage between PD patients with high and low mRNA expression. Multivariate analysis did not reveal age, gender, or cigarette smoking as confounding variables. Our study suggests that there was no significant alteration of alpha-synuclein mRNA expression in our sporadic PD patients compared to controls. However, the role of alpha-synuclein mRNA expression in select groups of sporadic PD patients and its interaction with environmental agents need to be further determined.

DNA Primers↗

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

OBJECTIVE: Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. MATERIALS AND METHODS: Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. RESULTS: Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. CONCLUSION: Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Animals↗

The intracerebral application of the PPARgamma-ligand pioglitazone confers neuroprotection against focal ischaemia in the rat brain.

The present study addresses the neuroprotective function of intracerebroventricular (i.c.v.) application of pioglitazone, a selective ligand of the peroxisome proliferator-activated receptor gamma (PPARgamma) in the rat brain after ischaemia. Pioglitazone or vehicle were i.c.v. infused via osmotic minipumps over a 5-day period before, and 2 days after transient middle cerebral artery occlusion (MCAO) for 90 min. This i.c.v. application of pioglitazone in the brain significantly reduced the infarct size and brain oedema, and attenuated in the peri-infarct cortical regions the invasion of activated microglia and macrophages. Moreover, pioglitazone improved the recovery of sensory deficits 48 h after MCAO. Our data demonstrate for the first time that it is the activation of intracerebral PPARgamma that can confer neuroprotection, anti-inflammatory and neurological improvement following ischaemic injury.

Animals↗

FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers.

Hepatic ischemia-reperfusion injury is an inevitable consequence during liver surgery. The outcome is particularly poor in cirrhotic livers, which are more prone to hepatic ischemia-reperfusion injury. We aim to study whether FTY720 could attenuate hepatic ischemia-reperfusion injury both in normal and in cirrhotic livers. We applied a 70% liver-ischemia (60 min) model in rats with normal or cirrhotic livers. FTY720 was given 20 min before ischemia and 10 min before reperfusion (1 mg/kg, i.v.). Liver tissues and blood were sampled at 20 min, 60 min, 90 min, 6 h and 24 h after reperfusion for detection of MAPK-Egr-1, Akt pathways and caspase cascade. Hepatic ultrastructure and apoptosis were also compared. FTY720 significantly improved liver function in the rats with normal and cirrhotic livers. Akt pathway was activated at 6 and 24 h after reperfusion. FTY720 significantly down-regulated Egr-1, ET-1, iNOS and MIP-2 accompanied with up-regulation of A20, IL-10, HO-1 and Hsp70. MAPK (Raf-MEK-Erk) pathway was down-regulated. Hepatic ultrastructure was well maintained and fewer apoptotic liver cells were found in the FTY720 groups. In conclusion, FTY720 attenuates ischemia-reperfusion injury in both normal and cirrhotic livers by activation of cell survival Akt signaling and down-regulation of Egr-1 via Raf-MEK-Erk pathway.

Animals↗

Equivalence between "feeling the pulse" on the human wrist and the pulse pressure wave at fingertip.

Feeling the pulse on the wrist is the regular diagnostic method in traditional Chinese medicine. However it is natural to ask whether there is any difference between feeling the pulse on the wrist or at any other part of the body: such as the fingertips at which it is easily measured by electronic devices. We employ a series of neural networks to model blood pressure propagation from the wrist to the fingertip. In order to avoid the problem of over-fitting we apply information theoretic criterion to determine the optimal model in these networks and then apply surrogate data method to the residuals in this model. We demonstrate the application of this method to recordings of human pulse in six subjects. Our result indicates that there is no significant difference between pulse waveform measure on the lateral arterial artery (wrist) and at the fingertip.

Blood Pressure↗

Role of Cdx-2 in insulin and proglucagon gene expression: a study using the RIN-1056A cell line with an inducible gene expression system.

Although the homeobox gene Cdx-2 was initially isolated from the pancreatic beta cell line HIT-T15, no examination of its role in regulating endogenous insulin gene expression has been reported. To explore further the role of Cdx-2 in regulating both insulin and proglucagon gene expression, we established an ecdysone-inducible Cdx-2 expression system. This report describes a study using the rat insulinoma cell line RIN-1056A, which abundantly expresses both insulin and proglucagon (glu), and relatively high amounts of endogenous Cdx-2. Following the introduction of the inducible Cdx-2 expression system into this cell line and the antibiotic selection procedure, we obtained novel cell lines that displayed dramatically reduced expression of endogenous Cdx-2, in the absence of the inducer. These novel cell lines did not express detectable amounts of glu mRNA or the glucagon hormone, while their insulin expression was not substantially affected. In the presence of the inducer, however, transfected Cdx-2 expression was dramatically increased, accompanied by stimulation of endogenous Cdx-2 expression. More importantly, activated Cdx-2 expression was accompanied by elevated insulin mRNA expression, and insulin synthesis. Cdx-2 bound to the insulin gene promoter enhancer elements, and stimulated the expression of a luciferase reporter gene driven by these enhancer elements. Furthermore, Cdx-2 and insulin gene expressions in the wild-type RIN-1056A cells were stimulated by forskolin treatment, and forskolin-mediated activation on insulin gene expression was attenuated in the absence of Cdx-2. We suggest that Cdx-2 may mediate the second messenger cAMP in regulating insulin gene transcription.

Animals↗

[Effect of tongxinluo capsule on plasma endothelin in patients with diabetic nephropathy].

OBJECTIVE: In order to explore the therapeutic effect of tongxinluo capsule (TXLC) on diabetic nephropathy, the influence on plasma endothelin (ET-1) level of the drug was observed. METHODS: All the 63 patients enrolled were randomly divided into the treatment group and control group. They were all treated with low protein diabetic diet, oral administration of hypoglycemic or injection of insulin, calcium antagonist according to level of blood pressure and supportive symptomatic treatment. To the treated group, 2 capsules of TXLC were given additionally three times a day. The efficacy was evaluated after 8 weeks' treatment. The chief indices observed before and after treatment were endogenous creatinine clearance rate (CCr), urinary albumin excretion rate (UAER), urinary beta2-microglobulin (beta2-MG), fasting blood-glucose (FBG) and ET-1. RESULTS: Before treatment, no significant difference was shown in all the tested indices between the treated group and the control group. After treatment, levels of CCr, UAER, beta2-MG, ET-1 and FBG significantly changed in the treated group, showing significant difference as compared with those before treatment (P < 0.05). Moreover, comparison of these indices in the two groups after treatment, excepting FBG, also showed statistical significance (P < 0.01). CONCLUSION: TXLC shows obvious effect in reducing plasma ET-1 and UAER, it is definitely effective in repairing the renal tubular interstitial damage, and effectively delay the progress of diabetic nephropathy, improve the renal function, and is favorable to ameliorate hyperglycemia auxiliarily.

Albuminuria↗

[Analysis of anthropometry on head and eye for stipulating of children's spectacle frames].

OBJECTIVE: To investigate the normal value of six parameters of head and eye in Chinese children, including interorbit distance (IOD), interpupillary distance (IPD), superior otobasion-ectocochion distance (obs-ec), intersuperior otobasion distance (obs-obs), exophthalmos and nasal basis angle, for stipulating the sizes of children spectacle frames. METHODS: The value of these six parameters in 10 171 children ages 5 to 17 years old were measured with caliper in four cities and the results were analyzed. RESULTS: The IOD, IPD, obs-ec and obs-obs were increased and positively correlated with the age. The differences of these parameters among different ages were statistically significant (F = 0.97, P < 0.01), especially in IPD before 15, IOD before 13, obs-ec and obs-obs before 12 and exophthalmos before 12 years old. The fastest growth age in IPD, IOD, exophthalmos, obs-ec and obs-obs was 10, 11, 5, 7 and 11 years old, respectively. The growth period of IPD, IOD, exophthalmos, obs-ec and obs-obs was 5 - 15, 5 - 13, 5 - 8, 5 - 12 and 5 - 15 years old. The difference of these six parameters among children in 4 cities were statistically significant (t = 3.1, P < 0.01). CONCLUSIONS: The most active growth period of IPD, IOD, obs-obs, obs-ec and exophthalmos lies between 5-15 years old in Chinese children 5-17 years old. Although the differences of these six parameters between male and female and among children in four cities are statistically significant, practically they are not important for stipulating the sizes of children's spectacle frames.

Adolescent↗

Effect of inhibitors on macroscopical oxidation kinetics of calcium sulfite.

In the presence of inhibitors, the macroscopical oxidation kinetics of calcium sulfite, the main byproduct in wet limestone scrubbing, was studied for the first time by adding different inhibitors and varying pH, concentration of calcium sulfite, oxygen partial pressure, concentration of inhibitors and temperature. The mathematical model about the general oxidation reaction was established, which was controlled by three steps involving dissolution of calcium sulfite, mass transfer of oxygen and chemical reaction in the solution. It was concluded that the general reaction was controlled by mass transfer of oxygen under uncatalyzed conditions, while it was controlled by dissolution of calcium sulfite after adding three kinds of inhibitors. Thus, the theory was provided for investigating the mechanism and oxidation kinetics of sulfite. The beneficial references were also supplied for design of oxidation technics in the wet limestone scrubbing.

Antioxidants↗

Conditionally replicative adenovirus vector carrying TRAIL gene for enhanced oncolysis of human hepatocellular carcinoma.

Conditionally replicative adenovirus (CRAd) mediated tumor specific gene therapy based on transcriptional control is considered a new direction for the treatment of cancer. Our previous studies showed that an HS4 insulator increased the alpha-fetoprotein (AFP) promoter-driven expression in the context of an adenovirus (Ad) vector, while retaining the highly specific gene expression in hepatoma cells in vitro and in vivo. In this study, we constructed two HS4-AFP promoter based CRAd vectors (Ad.HS4.AFP.E1a/TRAIL and Ad.HS4.AFP.E1a) with and without the expression cassette of TNF-related apoptosis-inducing ligand (TRAIL). The TRAIL-expressing virus vector, Ad.HS4.AFP.E1a/TRAIL, exhibited more obvious oncolytic effect than Ad.HS4.AFP.E1a in both high-AFP-producing HCC cell lines (Hep3B and HUH7) and a low-AFP-producing HCC cell line (PLC/PRF/5) examined, indicating endogenous TRAIL over-expression increased CRAd potency. The enhanced hepatoma cell death was mainly mediated through apoptotic mechanism, as evidenced by the activation of caspase-3, binding of annexin V and inhibition by caspase inhibitor z-vad-fmk. In s.c. xenograft of low-AFP-producing PLC/PRF/5 hepatoma model, the administration of Ad.HS4.AFP.E1a/TRAIL resulted in a more potent oncolytic effect compared with the same dose of Ad.HS4.AFP.E1a 28 days after virus exposure. This study demonstrated that the TRAIL in the context of a CRAd vector was able to increase the oncolytic activity in low-AFP-producing HCC cells in vitro and in vivo. Considering that oncolytic viruses destroy tumor cells expressing low levels of the tumor marker is a clinical concern, TRAIL might be a useful tool to improve the efficacy of these vectors.

Adenoviridae↗

[A prospective study of risk factors in pregnant women with abnormal glucose metabolism].

OBJECTIVE: To evaluate the risk factors for gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: A prospective case-control study was performed in 85 women with GDM, 63 cases with GIGT and 125 cases as control recruited from Feb 2004 to Aug 2004 in Peking University First Hospital. Univariate analysis and multivariate logistic regression were used to identify risk factors of GDM and GIGT. RESULTS: (1) The mean age, and body mass index (BMI) before pregnancy and larger maternal weight gains during pregnancy were significantly different between GDM/GIGT and control group (P < 0.05). (2) More intakes of fruits and carbohydrate per day increased the incidence of GDM and GIGT (P < 0.05). (3) There was a higher proportion of women with family history of diabetes among the GDM (42.2%) and GIGT (36.5%) compared with control group (19.2%). Irregular menses (16.5%, 23.8%), and polycystic ovary syndrome (PCOS) (5.9%, 3.2%) were more prevalent in the GDM, GIGT groups versus control subjects (6.4%, 0). The incidence of vulvovaginal candidiasis (VVC) was significantly higher in pregnant women with GDM and GIGT (15.3% and 17.4%) than in control group (7.2%). (4) Multivariate logistic regression showed that age, irregular menses, BMI before pregnancy, history of spontaneous abortion, educational level and VVC all were independent factors for GDM or GIGT. CONCLUSIONS: Maternal age, irregular menses, obesity before gestation, rapid weight gains during pregnancy, history of spontaneous abortion as well as VVC are independent risk factors for GDM or GIGT. PCOS and family history of diabetes increase the incidence of GDM and GIGT but these are not independent risk factors for GDM and GIGT.

Blood Glucose↗