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Biomedical subjects

Jing Zhao

Publications and source records attributed to Jing Zhao.

At least 127 records · Page 7Linked to original sources

Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol.

Previous work has shown that the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H(2)S) pathway participates in the regulation of cardiac contraction. We hypothesized that the pathway might participate in the pathophysiological regulation of ischemic heart disease. Isoproterenol injection of rat hearts induced a myocardial ischemic injury model, with reduced myocardial and plasma H(2)S levels, decreased CSE activity, and upregulated CSE gene expression. Exogenous administration of the H(2)S donor NaHS reduced the mortality rate; increased left-ventricular pressure development and left-ventricular-end systolic pressure; and decreased left-ventricular-end diastolic pressure (LVEDP) and subendocardial necrosis, capillary dilatation, leukocytic infiltration, fibroblast swelling, and fibroblastic hyperplasia. As well, production of lipid peroxidation, including myocardial malondialdehyde (MDA), and plasma MDA and conjugated diene, was reduced. Oxidative stress injury is an important mechanism of isoproterenol-induced myocardial injury. In vitro experiments revealed that NaHS might antagonize myocyte MDA production by oxygen-free radicals and that NaHS directly scavenged hydrogen peroxide and superoxide anions. Our results suggest that the endogenous CSE/H(2)S pathway contributes to the pathogenesis of isoproterenol-induced myocardial injury. Administration of exogenous H(2)S effectively protects myocytes and contractile activity, at least by its direct scavenging of oxygen-free radicals and reducing the accumulation of lipid peroxidations.

Alkenes↗

Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length.

Human LPTS/PinX1 is a telomerase-inhibitory protein, which binds to the telomere protein Pin2/TRF1 and the catalytic subunit hTERT of telomerase. To explore the proteins that might be involved in the telomerase pathway, we performed a yeast two-hybrid screening with LPTS/PinX1 as the bait. A novel gene, MCRS2, encoding for an isoform of MCRS1/p78 and MSP58 was isolated. The expression of MCRS2 protein is cell-cycle dependent, accumulating in the very early S phase. MCRS2 interacts with LPTS/PinX1 in vitro, in vivo and colocalizes with LPTS/PinX1 in cells. MCRS2 and its amino terminus inhibit telomerase activity in vitro and long-term overexpression of MCRS2 in SMMC-7721 cells results in a gradual and progressive shortening of telomeres. Our findings suggest that MCRS2 might be a linker between telomere maintenance and cell-cycle regulation.

Base Sequence↗

Secreted antibody/granzyme B fusion protein stimulates selective killing of HER2-overexpressing tumor cells.

Targeted cell killing is required for effective treatment of cancers. We previously described the generation of a chimeric immunocasp-3 protein and its potent selective antitumor activity (Jia, L. T., Zhang, L. H., Yu, C. J., Zhao, J., Xu, Y. M., Gui, J. H., Jin, M., Ji, Z. L., Wen, W. H., Wang, C. J., Chen, S. Y., and Yang, A. G. (2003) Cancer Res. 63, 3257-3262). Here we extend the repertoire of another chimeric pro-apoptotic protein immunoGrB, which comprises an anti-HER2 single-chain antibody, a Pseudomonas exotoxin A translocation domain and active granzyme B. Human lymphoma Jurkat cells transfected with the immunoGrB gene expression vector were able to produce and secrete the chimeric protein. The immunoGrB molecule selectively recognized and destroyed HER2-overexpressing tumor cells both in vitro and in nude mouse after intramuscular injection of the immunoGrB expression plasmid. Further in vivo study showed that intravenous administration of immunoGrB gene-modified lymphocytes led to suppression of HER2-overexpressing tumor growth and prolonged animal survival because of continuous secretion of immunoGrB molecules into blood and lymph fluid. These results demonstrate that the chimeric immunoGrB molecule, which is capable of antibody-directed targeting and granzyme B-mediated killing, has therapeutic potential against HER2 tumors, especially in cases in which caspase-dependent apoptosis is inhibited.

Animals↗

H2S generated by heart in rat and its effects on cardiac function.

Hydrogen sulfide (H2S), which was considered as a novel gasotransmitter, is produced endogenously from L-cysteine in mammalian brain and vessels, and might be a physiological function regulator to these organs. Here, we showed that mRNA for H2S producing enzyme, cystathionine gamma-lyase, was expressed in myocardial tissues and H2S could endogenously be produced in myocardial tissues. Negative inotropic effect of H2S was proved in present study in vitro and in vivo experiments, and the effect could partly be blocked by glibenclamide, a KATP channel blocker. An intravenous bolus injection of NaHS provoked a decrease in central venous pressure. The present findings suggested that H2S could be endogenously produced by heart tissues, as a physiological cardiac function regulator, mediated by KATP channel pathway.

Animals↗

Reorganization of specific chromosomal domains and activation of silent genes in plant cells acquiring pluripotentiality.

The transition from leaf cells to protoplasts (plant cells devoid of cell walls) confers pluripotentiality coupled with chromatin reorganization. Here, we sought to identify remodeled chromosomal domains in Arabidopsis protoplasts by tracking DNA sequences undergoing changes in DNA methylation and by identifying up-regulated genes. We observed a reduction in DNA methylation at a pericentromeric region of chromosome 1, and up-regulation of several members of the NAC (NAM/ATAF1/CUC2) domain family, two of which are located near the telomeric region of chromosome 1. Fluorescence in situ hybridization (FISH) analysis demonstrated that both pericentromeric and telomeric subdomains underwent chromatin decondensation. This decondensation is subdomain-specific inasmuch as centromeric repeats remained largely unchanged, whereas the 18S rDNA underwent condensation. Within the pericentromeric subdomain, VIP1, a gene encoding a b-Zip nuclear protein required for Agrobacterium infectivity, was transcriptionally activated. Overexpression of this gene in tobacco resulted in growth retardation and inhibition of differentiation and shoot formation. Altogether, our data indicate that acquisition of pluripotentiality involves changes in DNA methylation pattern and reorganization of specific chromosomal subdomains. This change leads to activation of silent genes whose products are involved in acquisition or maintenance of pluripotentiality and/or the ensuing fate of the cell.

Blotting, Northern↗

Neutrophils are stimulated by syncytiotrophoblast microvillous membranes to generate superoxide radicals in women with preeclampsia.

OBJECTIVE: This study was undertaken to determine whether syncytiotrophoblast microvillous membranes (STBMs) stimulate maternal neutrophils to produce superoxide radicals in women with preeclampsia. STUDY DESIGN: Serum levels of tissue polypeptide antigen (TPA), which is a marker for STBM, were measured in 25 nulliparous women (10 with mild preeclampsia, 6 with severe preeclampsia, and 9 controls). Superoxide production by maternal neutrophils from cases and controls and by donor neutrophils cocultured with the STBMs from cases and controls was measured spectrophotometrically by reduction of ferricytochrome C. RESULTS: Maternal TPA levels were significantly greater among cases than controls (P=.005). Superoxide production by maternal neutrophils and donor neutrophils cultured with STBM from cases of preeclampsia was greater than controls (P values.006 and.019, respectively), and dose-response relationships were observed. Superoxide production by maternal leukocytes was correlated with superoxide induction by STBMs in culture (P=.007). CONCLUSION: STBMs in maternal blood induce neutrophils to generate superoxide radicals that may cause endothelial dysfunction in women with preeclampsia.

Adult↗

Photoregulation of in vitro transcription/translation of GFP by tethering an azobenzene to T7 promoter.

Based on a previous study of photo-regulation of transcription by T7 RNA polymerase, the regulatory effect of azobenzene on in vitro green fluorescent protein (GFP) production was studied by introduction of a D-threoninol-tethered p-azobenzene into the non template strand of the T7 promoter in a GFP template. By measurement of the resulting GFP fluorescence intensity after the in vitro transcription/translation coupled reaction, it is found that photo-regulation of GFP gene expression can be achieved in a position-dependent manner by trans-cis isomerization of azobenzene upon UV irradiation.

Azo Compounds↗

Effects of taurine and homocysteine on calcium homeostasis and hydrogen peroxide and superoxide anions in rat myocardial mitochondria.

1. Taurine and homocysteine are metabolites of methionine. Hyperhomocysteinaemia is one of the risk factors for cardiovascular disease. Although taurine may be a cardiovascular cytoprotective substance, we hypothesized that it may antagonize the effects of homocysteine on myocardial mitochondrial function. 2. We studied the effects of taurine and homocysteine on [(45)Ca] uptake, Ca(2+)-ATPase activity and generation of hydrogen peroxide and superoxide anions in vitro in rat isolated myocardial mitochondria. 3. Results showed that the inhibition of mitochondrial [(45)Ca] uptake by homocysteine (0.1, 0.5 and 1.0 mmol/L) was concentration dependent. Taurine (5, 10 and 20 mmol/L) promoted [(45)Ca] uptake in a concentration-dependent manner, as well as concentration dependently reducing the homocysteine (0.5 mmol/L)-induced inhibition of mitochondrial [(45)Ca] uptake. 4. Homocysteine significantly inhibited mitochondrial Ca(2+)-ATPase activity, whereas taurine had a diphasic action on this activity. Taurine, at 5 and 10 mmol/L, increased Ca(2+)-ATPase activity (P < 0.01), but 20 mmol/L taurine inhibited Ca(2+)-ATPase activity (P < 0.05). Taurine attenuated the inhibitory effect of homocysteine on Ca(2+)-ATPase activity. 5. Homocysteine stimulated the generation of hydrogen peroxide and superoxide anions. Taurine had no effect on the generation of the anions, but inhibited their homocysteine-stimulated generation. 6. These results indicate that taurine and homocysteine have opposite effects in myocardial mitochondria with regard to [(45)Ca] uptake, Ca(2+)-ATPase activity and the generation of hydrogen peroxide and superoxide anions. Our results may show an important mechanism for the cardiovascular protective effects of taurine.

Animals↗

Percutaneous imaging-guided radiofrequency ablation in patients with colorectal pulmonary metastases: 1-year follow-up.

BACKGROUND: We assessed the safety and evidence of efficacy of radiofrequency ablation (RFA) for colorectal lung metastases with follow-up to 1 year. METHODS: Twenty-three patients had percutaneous RFA for 52 colorectal pulmonary metastases under fluoro-computed tomography (CT). Patients received intravenous conscious sedation and local analgesia with routine hospitalization and monitoring for 24 hours after RFA. Patients had CT scanning at 1 month and then every 3 months, with serum carcinoembryonic antigen assessment monthly and every 3 months. RESULTS: All ablations were technically successful. Tumor diameter ranged from.3 to 4.2 cm. Pneumothorax occurred in 43% (10 of 23) of patients. Six patients required intercostal chest drain placement. Six patients had a second RFA, four for new lesions and two for re-treatment of a previously treated lesion. The median admission was 2.0 days (range, 1-9 days). The median follow-up was 428 days (range, 173-829 days); data are reported to 1 year in this article. Five patients died at 5, 6, 8, 8, and 12 months after RFA from extrapulmonary (n = 1) or widespread (n = 4) disease. One patient developed a malignant pleural effusion at 6 months after RFA. Cavitation was seen in nine treated lesions (17%); all resolved with scar tissue contraction by 12 months. Eighteen patients with CT scan follow-up at 1 year have 40 lesions classified as disappeared (n = 17), decreased (n = 5), stable/same size (n = 4), or increased (n = 14). CONCLUSIONS: Percutaneous imaging-guided RFA of multiple colorectal pulmonary metastases is a minimally invasive treatment option with modest morbidity. A significant proportion of patients show good evidence of successful local control at 1 year.

Adult↗

New triterpenoid saponins from the roots of Sinocrassula asclepiadea.

Five new triterpenoid monodesmosides (sinocrassulosides I-V, 1-5) and six bisdesmosides (sinocrassulosides VI-XI, 6-11), in which 2-11 possess different acyl groups in the glycosidic moieties, were isolated from the roots of Sinocrassula asclepiadea FRANCH. Sinocrassulosides VI (4) and V (5) also contained a novel A-seco aglycone in their structures. All of the structures were determined on the basis of spectroscopic and physicochemical evidence.

Caryophyllaceae↗

[Studies on the biotransformation of escin Ia by human intestinal bacteria and the anti-tumor activities of desacylescin I].

OBJECTIVE: To study Biotransformation of escin Ia by the crude enzymes of human intestinal bacteria and Lactobacillus brevis, determine the structures of biotransformation products and assay the inhibitory effect of desacylescin I on the tumor cell growth. METHODS: The escin Ia was incubated with crude enzymes of human intestinal bacteria and Lactobacillus brevis in vitro, respectively. The biotransformation products were isolated and purified by the chromatographic methods and the structures were determined by the spectroscopic techniques. RESULTS: Escin Ia was converted into isoescin Ia, desacylescin I, 21beta-O-tigloylprotoaescigenin and protoaescigenin by crude enzymes of human intestinal bacteria and Lactobacillus brevis. Desacylescin I showed potentially inhibitory effects on tumor cell growth of mouse sarcoma-180, hepatic carcinoma H(22) and lung carcinoma in vivo. CONCLUSION: The results suggest that Escin Ia was a prodrug and its structure can be converted by human intestinal bacteria and Lactobacillus brevis. Desacylescin I as a biotransformation product showed potentially inhibitory effects on mouse tumor, and a potential candidate for anti tumor agents.

Animals↗

Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells.

AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS)--hydrogen peroxide (H2O2) and superoxide anion (O2(-*)) were measured with luminol or lucigenin chemiluminescence method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocysteine, was increased (P<0.01 vs control), and it was markedly inhibited when co-incubated with taurine (P<0.01). Homocysteine induced H2O2 generation from VSMC in a concentration dependent manner (P<0.01 vs control). However, taurine (5, 10, and 20 mmol/L) significantly antagonized 0.5 mmol/L homocysteine-induced H2O2 generation in VSMC in a concentration dependent manner (P<0.01 vs homocysteine alone group), although taurine itself did not alter the H2O2 generation in VSMC (P>0.05 vs control). In this study, the superoxide anion in VSMC was not detectable by chemiluminescence method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition, co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

Animals↗

Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017.

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca(2+)-related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC(50) was 11.5 micromol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 micromol/L in KH solution (phase 1), Ca(2+) free KH solution ( phase 2), and by addition of CaCl(2) into Ca(2+)-free KH solution (phase 3) were observed. The IC(50) to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 micromol/L and 16.3 micromol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca(2+) entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively. CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

Animals↗

[The cloning and expression of the truncated human bid gene and its pro-apoptotic effect on Hela cells].

AIM: To explore the expression of the truncated bid gene and its pro-apoptotic effect on Hela cells. METHODS: A full-length human bid gene was cloned by RT-PCR and confirmed by sequence analysis. By deleting the 60 amino acids of N-terminal the truncated bid (tbid) gene was obtained and then inserted into the eukaryotic expression vector pIRES2-EGFP. After the tbid gene was transfected into Hela cells under lipofectamine mediation, the effect of target gene expression on morphology and growth of Hela cells were observed under fluorescence and electron microscopes and analysed by TUNEL staining. RESULTS: pIRES2-EGFP containing tbid gene was constructed successfully. After Hela cells were transfected with GFP expression vector of tbid gene, tbid was expressed which was followed by decreased cell fluorescence intensity, poor cell growth, and cell death. Cell shrinkage and nuclear condensation, typical apoptotic characteristics, were observed by electron microscope observation and Tunel staining. CONCLUSION: The expression of tbid can effectively induce apoptosis of Hela cells.

Apoptosis↗

[Clinical analysis of 91 cases with articulation error].

OBJECTIVE: To study classification of the articulation errors, find the related factors which affect the therapy effect, and compare the therapy effect in the different patterns of the phonemic errors and build up a clinical model of the speech therapy on the basis of more than 4 years speech therapy in the clinic. METHOD: After excluding the organic articulation disorders, 91 cases of consonant phonemic errors were classified into different patterns according to the phonemic placement errors. The 91 cases were divided into two groups as effective one and ineffective one depending on whether the symptoms disappeared or not after the speech therapy. Ten factors including sex, age, oral-motor function problem, developmental delay, history of language development delay, history of middle ear affection, lingua frenata, mental retardation, the therapy frequency and times, were analyzed. The statistics software SPSS (SPSS Inc, 1997) was applied to show the factors related to the therapy effect by logistic multiple stepwise regression analysis. The therapy effect was compared between the single pattern (phonemic error < 2 groups) and multiple pattern (phonemic errors > or = 2 groups). RESULTS: The 91 cases with consonant phonemic errors were classified into four groups. The multiple pattern of the articulation errors was the most common (37 cases, 41%) among the 4 groups, followed by velar errors (33 cases, 36%). The third one was the apico-dental errors (12 cases, 13%) and the last one was the linguo-alveolar errors (8 cases, 9%). Only one case had labiodental error (/f/). The logistic multiple stepwise regression analysis showed that the history of the positive developmental delay, language delay and the frequency of the speech therapy were related to the therapy effect. The effective rate of the speech therapy in the single pattern of the phonemic error was as high as 87% while the one in the multiple pattern group was only 2.7%. The difference was significant (P < 0.000 1) when the therapy effect in these two groups was compared. The clinical model of the speech therapy included speech assessment, designing of the goal, choice of the target sound, sound production and oral-motor functional training. CONCLUSION: The consonant phonemic errors in the clinic represent four groups. The developmental delay, the language delay and frequency of the speech therapy influence the therapy effect. The frequency of the speech therapy should be increased every week, for example not less two times a week. The therapy effect of the single pattern of the phonemic errors is much better than that of the multiple pattern. The primary model of the speech therapy has been built in the clinics.

Articulation Disorders↗

[Construction, expression and cell growth inhibition of translocating peptide/granzyme B fusion protein gene].

AIM: To investigate the inhibitory effect of translocating peptide/granzyme B fusion protein on cell growth. METHODS: The translocating peptide gene of Pseudomonas exotoxin A (PE) was fused with active granzyme B gene by recombinant PCR to construct PE II-GrBa fusion protein gene. PE II-mGrBa with a mutation of serine to cystein at active center of GrB was used as negative control. The resulting PE II-GrBa and PE II-mGrBa genes were transiently transfected into mammalian cells via lipofectamine mediation. The effects of expression of PE II-GrBa gene on morphology and growth of transfected cells were detected by MTT colorimetry, TUNEL assay and indirect immunofluorescence staining. RESULTS: Transient expression of PE II-GrBa resulted in cytoskeleton abnormality, cell growth inhibition, and apoptosis in some cells. CONCLUSION: Expression of PE II-GrBa fusion protein can inhibit cell growth.

Apoptosis↗

Ghrelin protects myocardium from isoproterenol-induced injury in rats.

AIM: To investigate the cardiac protective effects of ghrelin in rat with myocardial injury induced by isoproterenol (ISO). METHODS: Rats were subcutaneously injected ISO 40 mg/kg/d with or without ghrelin 1 or 10 nmol/kg/d for 2 d. Hemodynamic parameters including mean arterial blood pressure and left ventricular pressure were measured at 12 h after the last injection with ISO and/or ghrelin. Plasma lactate dehydrogenase (LDH) activity, plasma and myocardial contents of malondialdehyde (MDA), and conjugated diene were measured. Plasma ghrelin and endothelin-1 levels were assayed using radioimmunoassay methods. Endothelin-1 and ghrelin mRNA were determined using RT-PCR. RESULTS: About 45 % (5/11) of rats after treatment with ISO alone died during experimental periods. However, no rats died after administration with ghrelin 10 nmol/kg/d (0/11, P<0.05). Ghrelin also obviously ameliorated the hemodynamic disturbance in rats induced by ISO. The plasma LDH activity, contents of myocardial and plasma MDA, and conjugated diene level in plasma in ISO+G10 nmol/kg/d group were decreased by 28 %, 34 %, 73 %, and 38 % compared with those of ISO group (all P<0.01) respectively. ISO-induced endothelin-1 mRNA over-expression was inhibited and endothelin-1 level in plasma were inhibited by ghrelin 1 and 10 nmol/kg/d. The ghrelin levels in plasma and ghrelin mRNA in myocardium were increased in the rats after injection of ISO. The plasma ghrelin level was further increased after ghrelin administration. CONCLUSION: Ghrelin has a protective effect against ISO-induced myocardial injury.

Animals↗