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Biomedical subjects

Hui Sun

Publications and source records attributed to Hui Sun.

At least 73 records · Page 4Linked to original sources

[Effects of c-myc antisense oligodeoxynucleotide on the telomerase activity and the induction of apoptosis in HL-60 cells].

To investigate the effects of c-myc antisense oligodeoxynucleotide (ASODN) on the telomerase activity and the induction of apoptosis in HL-60 cells, and to explore the relationship between the telomerase activity and the expression of c-myc gene in HL-60 cells, after treatment by c-myc ASODN, the expression of c-myc was detected by RT-PCR, the apoptosis, cell cycle were detected with agarose gel electrophoresis and flow cytomety, and the telomerase activity was determined with TRAP-ELISA. The results showed that after blocking c-myc gene with ASODN for 72 hours, it is obvious that the expression of c-myc gene was inhibited. The percentage of S phase HL-60 cells decreased from 55.6% to 30%, the early apoptosis peak appeared (the percentage of apoptosis cells were 25.2%) and the DNA ladders were shown. OD(450 - 690) were 2.648 +/- 0.42, 2.324 +/- 0.36, 2.162 +/- 0.38, 1.952 +/- 0.14, 1.805 +/- 0.40, 1.616 +/- 0.41 and 2.466 +/- 0.29, respectively, as the cells were treated with 0, 1, 2, 3, 4, 5 micromol/L ASODN and 5 micromol/L SODN for 72 hours. The difference was significant when compared 3, 4, 5 micromol/L groups with 0 micromol/L ASODN group respectively (P < 0.05), but the difference was no significant when compared 1, 2 micromol/L ASODN and 5 micromol/L SODN groups with 0 micromol/L ASODN group (P > 0.05). It is concluded that the c-myc gene ASODN may induce the apoptosis of cells, inhibit cells from G(1) phase into S phase and regulate the telomerase activity down in HL-60 cells by blocking the expression of c-myc gene.

Apoptosis↗

[Pharmacokinetic study of intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles].

OBJECTIVE: To analyze the pharmacokinetics of intraperitoneal chemotherapy with mitomycin C (MMC) bound to activated carbon particles. METHODS: A nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by i.v. or intraperitoneal (i.p.) injections, or given i.p. MMC bound to activated carbon particles (MMC-CH). Pharmacokinetic assays were carried out at different time points (0.5, 1, 2, 3, 6, 12 and 24 h) in 7 mice per each time point, to compare the MMC concentrations revealed by the above mentioned methods. RESULTS: The MMC concentration in peritoneal exudate, omentum and lymph nodes of MMC-CH group was significantly higher than that of MMC solution i.p. group and MMC i.v. group (P < 0.001). On the other hand, the MMC level in serum was significantly lower than that in two control groups (P < 0.001). High MMC level was maintained longer than 24 hours in the MMC-CH group. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in serum, peritoneal exudates and lymph nodes, and only a transient high level of MMC in the omentum. After i.v. administration, a significantly higher level of MMC concentration occurred in the serum, but only a shortly increased concentration of MMC in the omentum, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups (P < 0.001). CONCLUSION: High concentration of MMC in peritoneal exudate, omentum and lymph nodes maintained longer than 24 hours and a significantly lower MMC serum concentration can be achieved by administration of intraperitoneal administration of MMC bound to activated carbon particles.

Animals↗

[Chemical constituents from rhizome of Pulsatilla dahurica].

OBJECTIVE: To study the chemical constituents from rhizome of Pulsatilla dahurica. METHOD: The constituents were isolated and purified by various chromatographic methods. AR compounds were identified on the basis of spectral analysis and physico-chemical characters. RESULT: Six compounds were isolated from the 70% alcohol extract of the rhizome identified as hederagenin ( I ), hederagenin 3-O-alpha-L-arabinopyranoside (II), hederagenin 3-O-beta-D-glucopyranosyl(1-->2)-alpha-L-arabinopyranoside (III), hederagenin 3-O-beta-D-glucopyranosyl(1 -->2) [beta-D-glucopyranosyl(1-->4)]-alpha-L-arabinopyranoside (IV), beta-sitosterol (V) and daucosterol (VI), respectively. CONCLUSION: Compounds I approximately VI were isolated from this plant for the first time.

Oleanolic Acid↗

Highly effective expression of glutamine synthetase genes GS1 and GS2 in transgenic rice plants increases nitrogen-deficiency tolerance.

Glutamine synthetase (GS, EC6.3.1.2) is a key enzyme in ammonia assimilation both in plants and in Gram-negative microorganisms. It plays an important role in efficient use of nitrogen sources and nitrogen metabolism in organisms. Two groups of GS isoenzymes, plastidic (GS2) and cytosolic (GS1), have been identified in higher plants. A plant constitutive expression vector p2GS harboring GS1 and GS2 under the control of rice actin 1 (Act1) and maize ubiquitin (Ubi) promoters was constructed for the first time in a single plasmid, and 3 rounds of ligation and transformation were performed. There has been no report about studies on rice transformation with the two GS enzymes (GS1 and GS2). The p2GS thus constructed was introduced into rice var. Zhonghua 10 by Agrobacterium-mediated transfer method, and transgenic plants with resistance to hygromycin (Hyg) were obtained. Results of PCR and Southern blot analysis showed that the foreign genes have been integrated into the rice genome. The transcription of GS1-GS2 genes in the transformants was also confirmed by Northern blot analysis. The transgenic rice plants thus obtained can grow well in an MS medium in which the nitrogen source was replaced by (NH(4))(2)SO(4) 0.7 mmol/L, and fresh weight of the transformants was significantly higher than the control rice plants. The result suggests that expression of p2GS makes the transgenic rice plants tolerant to nitrogen-deficiency.

Adaptation, Physiological↗

[Successful treatment of agammaglobulinemia by HLA-mismatched unrelated cord blood stem cell transplantation--the first case report].

OBJECTIVE: To evaluate cord blood stem cell transplantation (CBT) in the treatment of X-linked agammaglobulinemia, and observe the courses of the hematopoietic and immune reconstitution. METHODS: A 14-year-old male patient with agammaglobulinemia received CBT from a 1/6 HLA-mismatched unrelated cord blood. The conditioning regimen was Bu/Cy/anti-CD3 antibody. CsA was given together with MMF and MTX for prophylaxis of GVHD. The patient received 0.42 x 10(8) nucleated cells/kg, containing 0.35 x 10(6) CD34(+) cells/kg. RESULTS: The recipient showed hematopoietic reconstitution on day 30 post-transplantation when ANC was 0.5 x 10(9)/L and BPC 20 x 10(9)/L. Sex chromosome analysis showed engraftment (donor 46, XX/recipient 46, XY = 4:1) on day 45. The recipient's blood group changed from AB to O, IgG from 1.1 g/L to 3.5 g/L, sex chromosome from 46, XY to full 46, XX, and mature B cells in peripheral blood from 0 to 5% on day 100, indicating immune reconstitution. At the last follow-up of 360 days, the patient without acute or chronic GVHD showed normal hemogram and myelogram, IgG 13.5 g/L and 10% mature B cells in peripheral blood, indicating the hematopoiesis and immune persistent reconstitution. No acute or chronic GVHD was developed. CONCLUSION: This is the first case report of successful treatment of X-linked agammaglobulinemia by HLA-mismatched unrelated CBT.

Adolescent↗

The growth characteristics and ginsenosides isolation of suspension-cultured crown gall of Panax quinquefolium.

The growth characteristics and ginsenosides isolation of the suspension-cultured crown gall of Panax quinquefolium were studied. The result showed that the maximum biomass of cultures was 18.6 g/L (dry weight) and the content of ginsenosides reached its maximum level of 620.4 mg/L on the 27th day. The utilization rates of sugar, phosphorus, nitrogen in NH4+ and nitrogen in NO3- were 91.8%, 100%, 81% and 97%, respectively. Four compounds were isolated from the suspension-cultured crown gall and their structures were elucidated as pseudoginsenoside F11 (I), ginsenoside Rd (II), ginsenoside Rb1 (llI) and ginsenoside Rb3 (IV).

Culture Media↗

[Plasma activated coagulation factor VII and Msp I polymorphism in elderly patients with coronary heart disease].

OBJECTIVE: To investigate the association of activated coagulation factor VII(F7a) and its gene Msp I polymorphism with coronary heart disease in elderly patients. METHODS: This was a case-control study, and the method of candidate gene was adopted. F7 genotypes were identified with polymerase chain reaction amplified genomic deoxyribonulieic acid (DNA) and Msp I restriction fragment length polymorphism analysis, and the level of plasma F7a was detected with recombinant tissue factor method for 108 elderly patients with coronary heart disease and 120 sex- and age-matched healthy control subjects. RESULTS: (1) Plasma F7a levels was significantly higher in elderly patients with coronary heart disease than in healthy control subjects (2.88 +/- 0.62 vs 2.58 +/- 0.60 microg/L, P < 0.05), and was significantly higher in old myocardial infarction than in stable angina pectoris (3.12 +/- 0.62 vs 2.76 +/- 0.60, P < 0.05). F7a was shown to be a risk factor for coronary heart disease in elderly patients by Logistic regression analysis (OR=1.21 P < 0.05). (2) The allelic frequencies were in accordance with Hardy-Weinberg equilibrium. The results suggested that the distribution of genotype and allelic frequencies in the groups displayed no significant difference, and there was no difference between the subgroups of coronary heart disease in elderly patients, either (P > 0.05). (3) F7a level was significantly higher in RR genotype than in Q allele carriers (2.72 +/- 0.60 vs 1.98 +/- 0.59 microg/L, P < 0.05) and was associated with F7 gene polymorphism. CONCLUSION: Plasma F7a level may be an independent risk factor of coronary heart disease in elderly patients, and it may be influenced by the Msp I polymorphism of F7 gene.

Aged↗

Metabolic effects of IGF-I deficiency: lessons from mouse models.

Insulin and insulin-like growth factors (IGFs) belong to the most biologically characterized family of peptides involved in metabolism, growth and development. The cellular responses to the IGFs are mediated primarily by the IGF-I receptor. The IGF-I receptor is a member of the family of tyrosine kinase growth factor receptors, and is highly homologous (70%) to the insulin receptor, especially in the tyrosine kinase domain (84%) ADDIN. Upon ligand binding to the extracellular region, the intrinsic tyrosine kinase domain of the receptor is activated. In the past it was believed that insulin activates primarily metabolic processes while IGFs promote cell growth and differentiation. However, in the last two decades many animal models of IGFI deficiency and excess revealed the importance of IGF-I in carbohydrate and lipid metabolism and now it is clear that these peptide hormones together with growth hormone (GH) work in a coordinate and interdependent manner. In the circulation, IGFs are bound in a binary complex with a family of high affinity IGF-binding proteins (IGFBPs) ADDIN. However, most of the circulating IGF-I associates with a high molecular weight complex approximately 150 KDa consisting of IGFBP-3 and the acid labile subunit (ALS) ADDIN. Once the ternary complex dissociates, the binary complexes of IGFBP-IGFs are removed from the circulation and by crossing the endothelium to reach the target tissues and to interact with cell surface receptors. In the present review we will summarize the role of GH and IGF in somatic growth and focus on the metabolic effects of IGF-I deficiency as assessed in various mouse models.

Animals↗

[Study on the collecting method of constituents absorbed into the blood from anti-V capsule].

OBJECTIVE: Aim To establish the condition and parameters for collecting the effective constituents of Anti-V capsule. METHOD: Based on HPLC, using chlorogenic acid and baicalin which are the main constituents absorbed in the blood as the marker substance, the best technical process of macropore absorbed resin was evaluated by the quantity of two compounds in the collected part. RESULT: After the abstraction of the capsule, the collection method of NKA-2 macropore absorbed resin as sorbent and 5 bed volume 50% ethanol as mobile phase was definited as the best craftwork. In the collected part, the content of chlorogenic acid and baicalin was five times than in the capsule. CONCLUSION: In guide of serum pharmacochemistry, macropore absorbed resin is the effective method to collect the constituents absorbed in blood of Anti-V capsule. At the same time, this method provides a way to research other Compound medicine.

Animals↗

[Abnormal expression of hMSH2 mRNA and mutation P53 protein in acute lymphoblastic leukemia].

In order to investigate the mechanism of acute lymphoblastic leukemic cell malignant proliferation, the expressions of hMSH2 mRNA and mutation P53 (mtP53) protein in bone marrow cells of de novo acute lymphoblastic leukemia (ALL) were determined by in situ hybridization and immunocytochemical methods. The results showed the that percentage of positive cell with hMSH2 mRNA expression was (32.88 +/- 11.46)% in the de novo ALL group and (64.22 +/- 8.51)% in the control group. The percentage of positive cell with mtP53 protein expression was (29.25 +/- 9.45)% in the de novo ALL group, and (12.63 +/- 6.66)% in the control group. There was a significant negative correlation between the positive percentages of hMSH2 mRNA expression and mtP53 protein expression (r = -0.45, P < 0.05). It is concluded that defective MSH2 mRNA expression plays an important role in the pathogenesis of acute lymphoblastic leukemia, mtP53 protein mutation plays an important role in the development of acute lymphoblastic leukemia, the hMSH2 mRNA defect can lead to accumulation of the mutant P53 protein in acute lymphoblastic leukemia, and both jointly promote the pathogenesis of ALL.

Adult↗

[Study on the compliance and safety of the oral antifungal agents for the treatment of onychomycosis].

OBJECTIVE: To explore the rate of compliance, influencing factors and the safety of patients with onychomycosis under treatment of oral antifungal agents. METHODS: According to the scoring clinical index of onychomycosis (SCIO), 330 patients with onychomycosis, their target nail's integral of the SCIO were calculated and randomly divided into three groups under the baseline of the SCIO integral range. Patients were treated with intermittent pulse itraconazole (A group), continuous terbinafine (B group) and intermittent terbinafine (C group) respectively. Self-administered questionnaire was applied in the survey on every onychomycosis patient. RESULTS: The average rate of compliance was 55.15%. The cure rate for those compliance with doctors' order was 89.01%, while it was only 30.41% for those noncompliant patients The overall non-compliant rate was 44.85%. Among the noncompliant ones, 29.73% were worried about the side effects of medicine, 22.30% thought that they had already been cured, 15.54% was due to economic reasons and 12.16% could not bear the side effects of medicine. It was found that the compliant rates were significantly correlated to ageing, position of the target nails, the integral of the SCIO and the therapy scheme (P < 0.05), while no significant correlations were seen between male and female, culture degree and course (P > 0.1). The frequency of adverse incident of A, B, C groups were 22.73%, 21.43%, 23.15% respectively, but without statistical significance (P > 0.1). Majority of the adverse incidents happened during the first month of therapy but were mild and reversible. CONCLUSION: Our results showed that the overall compliance was low which exerted a significant influence on the curative effect of onychomycosis patients. Factors as ageing, position of the target nail, integral of the SCIO and the therapy scheme had an influence on the compliant rate. When treating onychomycosis with oral itraconazole, the results seemed to be just as safe as when using terbinafine.

Administration, Oral↗

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).

Base Sequence↗

GluR4c, an alternative splicing isoform of GluR4, is abundantly expressed in the adult human brain.

We report the cloning of human GluR4c, an alternative splicing isoform of GluR4. Similar to rodent and chick GluR4c mRNA, human GluR4c had a 113-bp insert containing a stop codon, resulting in a short C terminus. The expression of human GluR4c was widespread in the brain, and was upregulated with development in the cerebellum and cerebral cortex where the level of it was about 30% of total GluR4 mRNA in adult stage. The GluR4 subunit may play a pivotal role in regulating channel properties as well as trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in the adult human brain.

Adult↗

The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte contractility via a direct inhibition of Ik,slow currents.

OBJECTIVE: Phosphoinositide 3-kinase (PI3K) is a key component in regulating myocardial growth, survival and contractility. LY294002 and wortmannin are two PI3K inhibitors used widely to establish the role of PI3K. The goal of this study was to examine the effects of acute application of LY294002 and wortmannin on cardiac myocyte contractility and underlying mechanisms. METHODS: Patch-clamp, indo-1 epifluorescence and video-edge detection techniques were used to measure outward K(+) currents, action potentials (AP), Ca(2+) transients and shortening of myocytes isolated from mouse left ventricular free wall. RESULTS: In field-stimulated myocytes, LY294002 (10 micromol/l) increased Ca(2+) transient amplitude by 23%, and cell shortening amplitude by 60% in the absence or presence of wortmannin, while wortmannin alone had no effect. LY294002 (but not wortmannin) prolonged AP duration by specifically inhibiting slowly inactivating K(+) currents (i.e., the 4-aminopyrydine-sensitive I(k,slow1) and the tetraethylammonium-sensitive I(k,slow2)), leading to an increase in sarcoplasmic reticular Ca(2+) levels. It appeared that the AP prolongation was responsible for elevated contractility since AP-clamp of myocytes with prolonged APs (recorded in LY294002-treated myocytes) induced a 29% increase in cell shortening compared with control APs, while LY294002 application did not increase contractility in voltage-clamp studies using either step or AP depolarizations. CONCLUSIONS: The putative PI3K inhibitor LY294002 increases Ca(2+) release and myocyte contractility via direct inhibition of cardiac I(k,slow) and AP prolongation, thus limiting the usefulness of this agent in the analyses of the role of PI3K in heart function.

Action Potentials↗

A TM2 residue in the beta1 subunit determines spontaneous opening of homomeric and heteromeric gamma-aminobutyric acid-gated ion channels.

Gamma-aminobutyric acid type A (GABAA) receptors are major inhibitory neurotransmitter-gated ion channels in the central nervous system. GABAA receptors consist of multiple subunits and exhibit distinct pharmacological and channel properties. Of all GABAA receptor subunits, the beta subunit is thought to be a key component for the functionality of the receptors. Certain types of GABAA receptors have been found to be constitutively active. However, the molecular basis for spontaneous opening of channels of these receptors is not totally understood. In this study, we showed that channels that contain the beta1 but not beta3 subunits opened spontaneously when these subunits were expressed homomerically or co-expressed with other types of GABAA receptor subunits in Xenopus oocytes. Using subunit chimeras and site-directed mutagenesis, we localized a key amino acid residue, a serine at position 265, that is critical in conferring an open state of the beta1 subunit-containing GABAA receptors in the absence of agonist. Moreover, some point mutations of Ser-265 also produced constitutively active channels. The magnitude of spontaneous activity of these receptors was correlated with the molecular volume of the residue at 265 for both homomeric and heteromeric GABAA receptors, suggesting that the spontaneous activity of the beta1 subunit-containing GABAA receptors may be mediated through a similar molecular mechanism that is dependent on the molecular volume of the residue at 265.

Animals↗

Glutamate receptors: RNA editing and death of motor neurons.

The aetiology of sporadic amyotrophic lateral sclerosis (ALS), a fatal paralytic disease, is largely unknown. Here we show that there is a defect in the editing of the messenger RNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by ALS. This failure to swap an arginine for a glutamine residue at a crucial site in the subunit, which occurs normally in the affected brain areas of patients with other neurodegenerative diseases, will interfere with the correct functioning of the glutamate receptors and may be a contributory cause of neuronal death in ALS patients.

Amyotrophic Lateral Sclerosis↗

Regulation of glutamate receptor RNA editing and ADAR mRNA expression in developing human normal and Down's syndrome brains.

In human brain, developmental up-regulation in RNA editing at the Q/R site was evident in GluR5 and GluR6, but GluR2 editing in the white matter was down-regulated. Each ADAR mRNA expression was up-regulated in the gray matter, whereas differently regulated in the white matter. ADAR2 mRNA was not overexpressed in the brains of Down's syndrome subjects, nor was there any evidence of changes in the RNA editing efficiency of their GluRs.

Adenosine Deaminase↗

The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease.

Phosphoinositide-3 kinases (PI3Ks) are a family of evolutionary conserved lipid kinases that mediate many cellular responses in both physiologic and pathophysiologic states. Class I PI3K can be activated by either receptor tyrosine kinase (RTK)/cytokine receptor activation (class I(A)) or G-protein-coupled receptors (GPCR) (class I(B)). Once activated PI3Ks generate phosphatidylinositols (PtdIns) (3,4,5)P(3) leading to the recruitment and activation of Akt/protein kinase B (PKB), PDK1 and monomeric G-proteins (e.g. Rac-GTPases), which then activate a range of downstream targets including glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR), p70S6 kinase, endothelial nitric oxide synthase (eNOS) and several anti-apoptotic effectors. Class I(A) (PI3Kalpha, beta and delta) and class I(B) (PI3Kgamma) PI3Ks mediate distinct phenotypes in the heart and under negative control by the 3'-lipid phosphatase, phosphatase and tensin homolog on chromosome ten (PTEN) which dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(4,5)P(2). PI3Kalpha, gamma and PTEN are expressed in cardiomyocytes, fibroblasts, endothelial cells and vascular smooth muscle cells where they modulate cell survival/apoptosis, hypertrophy, contractility, metabolism and mechanotransduction. Several transgenic and knockout models support a fundamental role of PI3K/PTEN signaling in the regulation of myocardial contractility and hypertrophy. Consequently the PI3K/PTEN signaling pathways are involved in a wide variety of diseases including cardiac hypertrophy, heart failure, preconditioning and hypertension. In this review, we discuss the biochemistry and molecular biology of PI3K (class I isoforms) and PTEN and their critical role in cardiovascular physiology and diseases.

Animals↗