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Biomedical subjects

Jian Sun

Publications and source records attributed to Jian Sun.

At least 55 records · Page 3Linked to original sources

[Comparison between antitumor effect and chemical constituents of Huanglian Jiedu decoction and that of serum containing Huanglian Jiedu decoction].

OBJECTIVE: To make a comparison between the antitumor effect and the chemical constituents of Huanglian Jiedu decoction (HLJDT) and that of serum containing HLJDT. METHOD: Based on the established chromatographic fingerprint of HLJDT, analysis and comparison were made between the HPLC fingerprints of rat serum samples obtained after orally taking HLJDT and those of control rat serum samples. The different effects on NCI-H446 and Bel-74024 cancer cells from human were investigated in vitro using HLJDT and its serum. The inhibitory effects of HLJDT and its serum were observed by MTT assay. RESULT: Ten compounds of HLJDT and some metabolites were detected after oral administration of HLJDT, and however some main compounds of HLJDT were not detected in serum. Both HLJDT and its serum in different dosage groups could inhibit the proliferation of NCI-H446 and Bel-7402 cancer cells from human in a dose-dependent manner, but inhibitory grade was different in the two cancer cell lines. HLJDT had more inhibitory effect on Bel-7402 than on NCI-H446, on the other hand serum containing HLJDT had the same inhibitory effect on Bel-7402 and NCI-H446. CONCLUSION: The reason for inhibitory grade change was that the proportion of concentration of many compounds in serum containing HLJDT was different to that in HLJDT, which should be subject to thorough investigation so as to illuminate the pharmacology and active mechanism of HLJDT.

Animals↗

[Diagnosis and management for early hepatic artery thrombosis after liver transplantation].

OBJECTIVE: To explore the diagnosis and management of early hepatic artery thrombosis (HAT) after liver transplantation. METHODS: Routine examination of Color Doppler Imagine (CDI) was used to detect hepatic artery flow after liver transplantation in 220 cases from April 2001 to November 2004. Suspected patients were further confirmed by immediate hepatic artery angiography, and continuous infusion of urokinase through hepatic artery with catheter was performed to the patients with HAT. RESULTS: HAT was identified in 6 patients (2.7%), occurring 5.5 days (2 - 19 days) after liver transplantation. Hepatic artery recanalization was obtained in 6 cases. One patient died from lung infection 2 months after liver transplantation. One patient underwent the second liver transplantation because of the recurrence of HAT 6 months after the first transplantation, but died from multiple system organ failure 2 months after the operation. The other 4 cases have been surviving well disease-freely. CONCLUSIONS: CDI is useful for the diagnosis of early HAT after liver transplantation. Contributes to recovery of the hepatic artery flow, continuous infusion of urokinase through hepatic artery with catheter may be the first choice of the therapy for early HAT.

Adult↗

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

Computer Simulation↗

Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts.

Our current study was to test the hypothesis that the extract of Herba leonuri (HL) would have antioxidant and cardioprotective effects on ischemic myocardium. The extract of HL (400 mg/kg/day) was administered orally (daily) starting from 1 week before and continuing until 3 weeks after myocardial infarction (MI). Surviving rats were sacrificed at different time points to obtain left ventricles for biochemical assays. Our study demonstrates for the first time that HL does have antioxidant effects both in vitro and in vivo. The antioxidant effects of HL are exerted only under the condition of oxidative stress, by selectively preserving the activities of superoxide dismutase and glutathione peroxidase, as well as depressing the formation of malondialdehyde, especially in the acute phase of acute MI. Its effects of scavenging free radicals and inhibiting the formation of reactive oxygen species may play a key role in protecting the endogenous antioxidant system from oxidative stress in vivo.

Animals↗

Histone deacetylase inhibitor Trichostatin A reduces anti-DNA autoantibody production and represses IgH gene transcription.

Systemic lupus erythematosus is characterized by the presence of autoantibodies and hypergammaglobulinemia. To investigate the role of histone deacetylases (HDACs) in the production of autoantibody and immunoglobulin, we examined the effect of Trichostatin A (TSA), a specific inhibitor of HDACs, on anti-DNA autoantibody production and IgH gene transcription. Our results showed that inhibition of HDAC activity by TSA markedly reduced anti-DNA autoantibody production by T347 cells either by inducing apoptosis or in an apoptosis-independent manner, suggesting that TSA might be useful for treating certain autoimmune diseases. Moreover, we found that TSA strongly inhibited germline and post-switch immunoglobulin transcripts in T347 cells and in primary splenic B cells of MRL-lpr mice. Reporter gene analysis demonstrated that both Emu and 3'-IgH enhancer activities were repressed significantly by TSA-mediated HDAC inhibition. Furthermore, we observed that HDAC1 was recruited to the 3'-IgH enhancer hs1,2 as determined by chromatin immunoprecipitation assays. Over-expression of HDAC1 increased the activity of IgH enhancers, especially 3'-IgH enhancers. These findings implicate HDAC in the IgH gene transcription via activation of 3'-IgH enhancers.

Animals↗

Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction.

In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage. After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.

Analysis of Variance↗

Liver transplantation for patients with hepatocellular carcinoma at the Liver Cancer Institute of Fudan University, China.

BACKGROUND: Selection of patients with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT) remains controversial. Since there is a trend to expand the transplant criteria for HCC patients, we reviewed the data of patients with HCC who had received OLT at our institute to determine their survival and prognostic factors. METHODS: A total of 67 patients with HCC who had undergone OLT from April 2001 through December 2003 were reviewed retrospectively. Selection OLT candidates with HCC was dependent on the anatomical characteristics and/or the severity of underlying liver cirrhosis. The 67 patients were followed up for more than 6 months after transplantation. Their survival rate was calculated by the Kaplan-Meier method. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed to reveal the factors affecting the survival rate. RESULTS: No perioperative death occurred in this series. The 1- and 2-year cumulative survival rates were 90.0% and 65.6%, and the disease-free survival (DFS) rates were 77.5% and 62.5% respectively. Univariate analysis revealed the tumor size, portal vein tumor thrombus (PVTT), serum alpha-fetoprotein level, bilobular distribution of tumors, pTNM stage and histological differentiation were statistically significant factors affecting the DFS (P < 0.05). Multivariate analysis showed tumor size and PVTT were independent and statistically significant factors affecting the DFS (P = 0.005 and 0.010, respectively). In this series, all but 2 received systemic chemotherapy, among them 13 had tumor recurrence within 8 months after OLT. CONCLUSIONS: OLT is indicated for patients with HCC, even for some patients with end-stage liver disease who may survive longer without tumor recurrence. Adjuvant chemotherapy may decrease the recurrence of HCC after OLT.

Adult↗

Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area.

BACKGROUND/AIMS: The acquisition of hepatitis B virus (HBV) infection following organ transplantation from donors with occult HBV infection is an important cause of morbidity and mortality. The aim of this study is to determine the prevalence of occult HBV in allogeneic hematopoietic stem cell (HSC) transplantation donors. METHODS: We performed a retrospective study on 124 consecutive hepatitis B surface antigen negative HSC donors. Their serum samples were analyzed by PCR for the pre-S/S, pre-core/core and X regions of the virus. Samples reactive by at least two PCR assays were considered HBV-DNA positive. RESULTS: Nineteen of the 124 HSC donors (15.3%) had occult HBV infection. Sixteen of these 19 donors with occult HBV infection (84.2%) tested positive for hepatitis B core antibody while 78 of 105 subjects (74.3%) without occult HBV infection were also positive (P=0.56). Fourteen of the 19 donors (73.7%) with occult HBV infection tested positive for hepatitis B surface antibody while 67 of the 105 subjects without occult HBV infection were also positive (P=0.45). CONCLUSIONS: The prevalence of occult HBV infection among HSC donors in Hong Kong is high. Anti-HBc and anti-HBs status had no significant correlation with the presence of occult HBV infection.

Adult↗

Clinical and virological characteristics of lamivudine resistance in chronic hepatitis B patients: a single center experience.

We have investigated the characteristics of lamivudine-resistant strains in patients with chronic hepatitis B in Guangdong, China, where the predominant genotypes are B and C. Two hundred forty-seven patients treated with lamivudine in Nanfang Hospital were followed-up. Patients with hepatitis B e antigen (HBeAg) positive and hepatitis B virus (HBV)-DNA levels over 7.5 x 10(6) copies/ml at baseline had a shorter time to the selection of YMDD mutant (P = 0.02 and 0.00, respectively). The detection of YMDD mutant precedes HBV-DNA breakthrough and alanine transaminase (ALT) flare in about 2 and 3 months, respectively. The ALT flare after the appearance of YMDD mutants was more evident in HBeAg positive patients than HBeAg negative patients (P = 0.02). After emergence of YMDD mutant, the HBV-DNA level was significantly higher in genotype C patients compared with genotype B patients (P = 0.02). No significant difference of YMDD mutant pattern was found between patients with genotype B and C. Four kinds of new mutants were found in over two patients including rtL80I, rtG172E, rtG174C, and rtG172E/rtG174C. In vitro transfection and real-time analysis showed that rtG172E, rtG174C, and rtG172E/rtG174C mutants had a decreased replication competence compared with wild type (33%, 27%, and 15% of the wild type HBV, respectively). Our result suggest that genotypic monitoring of YMDD mutant is important for the management of patients treated with lamivudine.

Adolescent↗

Characteristics of the beta myosin heavy chain gene Ala26Val mutation in a Chinese family with hypertrophic cardiomyopathy.

BACKGROUND: Genotype-phenotype studies have suggested that some mutations of genes encoding various components of the cardiac sarcomere cause hypertrophic cardiomyopathy (HCM) and are associated with the prognosis of patients with HCM. The aims of this study were to investigate the gene mutations of exons in the cardiac beta myosin heavy chain (MYH7) gene, the troponin T (TNNT2) gene, and the brain natriuretic peptide (BNP) gene, as well as to assess the effect of these mutations on the clinical features of Chinese patients with HCM. METHODS: Five unrelated Chinese families with HCM were studied. Exons 3 and 18 in the MYH7 gene, exon 9 in the TNNT2 gene, and all three exons in the BNP gene were screened with the polymerase chain reaction (PCR) for genomic DNA amplification. Further study included purification of PCR products and direct sequencing of PCR fragments by fluorescent end labeling. RESULTS: A C-to-T transition in codon 26 of exon 3 in the MYH7 gene was found in one family (including four patients and five carriers), resulting in an amino acid substitution of valine (Val) for alanine (Ala). The Ala26Val mutation was of incomplete dominance (penetrance 44%). This mutation was not seen in the other four families or in the control group. Moreover, the association between the gene mutations of exon 18 in MYH7, of exon 9 of TNNT2, and of all three exons in BNP and HCM was not found in the populations we studied. CONCLUSIONS: The missense mutation Ala26Val found in this one Chinese family was associated with a mild phenotype of HCM. The genetic and phenotypic heterogeneity of HCM exists in the Chinese population. It suggests that genetic and environmental factors may be involved in the pathogenesis of HCM.

Journal Article↗

Circadian rhythm in dihydropyrimidine dehydrogenase activity and reduced glutathione content in peripheral blood of nasopharyngeal carcinoma patients.

Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Glutathione (GSH) is a tripeptide involved in platinum complex detoxification. This study explored the circadian rhythms of DPD activity and GSH concentration in the peripheral blood of 16 patients with histologically proven nasopharyngeal carcinoma (NPC) in order to guide the establishment of chronotherapeutic schedules for this cancer. DPD activity and GSH concentration were determined by high performance liquid chromatography (HPLC). Both variables displayed significant circadian rhythms (Cosinor analysis: p = 0.009 and 0.012, respectively). Peak DPD activity occurred at about 02:30 h; whereas, peak GSH concentration occurred around 12:40 h. The differences between the peak and nadir mean values were 25.5% and 38.7%, respectively. The study showed that the circadian rhythms in DPD activity and GSH concentration in Chinese NPC are similar to those reported for western patients with colorectal cancer, despite the differences in race and kinds of cancer. These findings imply that the chronotherapeutic schedule of 5-FU and platinum used to treat European colorectal cancer patients probably is applicable to Chinese NPC patients.

Adult↗

Effectiveness of prophylactic Anti-HBV therapy in allogeneic hematopoietic stem cell transplantation with HBsAg positive donors.

Use of hepatitis B surface antigen (HBsAg) positive donors for allogeneic hematopoietic stem cell transplantation (HSCT) causes serious hepatitis B virus (HBV)-related liver morbidity and mortality in the recipient. We compared the effectiveness of anti-HBV therapy in 29 recipients who underwent HSCT using HBsAg positive marrow (group I) against a historical control group of 25 patients who received HBsAg positive marrow without pre-HSCT prophylaxis (group II). Anti-HBV therapy consisted of lamivudine for HBsAg-positive donors and all recipients (n = 29) as well as HBV vaccination to all HBsAg-negative recipients (n = 10) before HSCT. After transplantation, HBV-related hepatitis was significantly higher in group II than group I recipients [12 of 25 recipients (48%) vs. 2 of 29 recipients (6.9%), p = 0.002] and in recipients whose donors had detectable serum HBV DNA by Digene Hybrid Capture II assay [8 of 14 recipients (57.1%) vs. 6 of 40 recipients (15.0%), p = 0.02]. Six recipients in group II and none in group I died of HBV-related hepatic failure (24.0% vs. 0%, p = 0.01). By multivariate Cox analysis, anti-HBV therapy effectively reduces post-HSCT HBV-related hepatitis (p = 0.01, adjusted hazards ratio 7.27, 95%CI 1.62-32.58). Our data support the use of prophylactic therapy in preventing HBV-related hepatitis after allogeneic HSCT from HBsAg-positive donor.

Adult↗

Construction of phospholamban antisense RNA recombinant adeno-associated virus vector and its effects in rat cardiomyocytes.

AIM: To construct a recombinant adeno-associated virus (rAAV) vector containing gene encoding phospholamban antisense RNA (asPLB), and analyse its effect on expression of PLB, expression and activity of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), and the change of intracellular free Ca2+ concentration ([Ca2+]i) in rat cardiomyocytes. METHODS: The target gene encoding PLB antisense RNA was inserted inversely into the adeno-associated virus plasmid pAAV-MCS digested by corresponding restricted endonuclease enzyme. The recombinant plasmid and pAAV-RC and pHelper were co-transfected into 293 cell. At the same time, a viral production positive control (rAAV-LacZ) and negative control were performed. The recombinant viruses were used to transfect the cultured rat cardiomyocytes. Site beta-Galactosidase staining were performed to observe the transfer efficiency. Reverse transcription-PCR and Western blot were used to determine the mRNA and protein expression of PLB and SERCA. The activity of SERCA and the [Ca2+]i were measured. RESULTS: The rAAV vectors were constructed successfully and were transfected into rat cardiomyocytes effectively. The PLB mRNA and protein expression were reduced in rat cardiomyocytes transfected by rAAV-asPLB compared with controls. The activity of SERCA was increased. In rest state, the level of [Ca2+]i in the rAAV-asPLB transfected group decreased. The level of [Ca2+]i increased when induced by isoproterenol. CONCLUSION: AAV-asPLB vector was constructed successfully, which disrupted the expression of PLB, enhanced the activity of SERCA, reduced the resting [Ca2+]i, and improved the cardiac function.

Animals↗

Diphasic effects of Astragalus membranaceus BUNGE (Leguminosae) on vascular tone in rat thoracic aorta.

This study was designed to investigate the effects of the aqueous ethanol extract of Astragalus membranaceus BUNGE (Leguminosae) on rat thoracic aorta. Isometric tension was recorded in response to drugs in organ bath. In endothelium-intact aortic rings, A. membranaceus extract induced a significant dose-dependent relaxation of the rings precontracted by phenylephrine, which could be inhibited by preincubation with L-N(omega)-nitro-arginine methyl ester or methylthioninium chloride. In endothelium-denuded ones, the extract could dose-dependently relax the rings contracted by phenylephrine, not by KCl; and it could also attenuate contractile response to phenylephrine, not to caffeine or phorbol-12,13-diacetate in Ca(2+)-free medium; but it failed to affect the CaCl(2)-induced enhancement of contractile response to phenylephrine in Ca(2+)-free medium. These results indicate that nitric oxide signaling and Ca(2+)-handling pathway are involved in the A. membranaceus extract-induced vasodilatation.

Animals↗

[Cloning, expression and sequence analysis and tissue distribution of angiotensin-converting enzyme 2 (ACE2) gene in adult mice].

OBJECTIVE: o clone angiotensin-converting enzyme 2(ACE2) gene, to analyze its amino acids and nucleotides sequence and to investigate tissue distribution of ACE2 in adult mice. METHODS: The full-length ACE2 encoding sequence was amplified from the RNA of mice kidney tissue by RT-PCR technique, cloned into plasmid pGEM-T easy, then subcloned into plasmid pcDNA3.1+. After identification of DNA sequence, the recombinant plasmid pmACE2 was transfected into Cos7 cells with lipofectin reagent. The transient expression of ACE2 molecule was detected by SDS-PAGE. Sequence analysis was conducted with CLUSTALX program. Tissue distribution of ACE2 in mice was detected by RT-PCR. RESULTS: A fragment about 2.6 kb was amplified and the recombinant plasmid pmACE2 was confirmed by two-enzyme digesting and DNA sequencing. The cloned DNA sequence was consistent with that previously reported, except for 3 variations: A701G, T1102C and T1330C. SDS-PAGE proved that expression of a soluble, truncated products form of ACE2 was a glycoprotein of approximately 80 kD in Cos7 cells. The predicted mice ACE2 sequence contained an N-terminal signal sequence (amino acid residues 1-18), a single HHEMGHIQ zinc-binding domain (amino acid residues 373-380) and C-terminal membrane anchor (amino acid residues 738-765). Mice ACE2 showed 84 % identity with that of human, and 90 % identity with that of rat. Expression of ACE2 was the greatest in lungs, hearts and kidneys, and moderate levels were also detected in testes and livers. CONCLUSION: Mice ACE2 gene has been cloned and successfully expressed in vitro. The tissue-specific expression of ACE2 in different species is not identical.

Amino Acid Sequence↗