Biomedical subjects

Yan Yang

Publications and source records attributed to Yan Yang.

121 records · Page 7Linked to original sources

PubMed2002

CEACAM1 regulates insulin clearance in liver.

We hypothesized that insulin stimulates phosphorylation of CEACAM1 which in turn leads to upregulation of receptor-mediated insulin endocytosis and degradation in the hepatocyte. We have generated transgenic mice over-expressing in liver a dominant-negative, phosphorylation-defective S503A-CEACAM1 mutant. Supporting our hypothesis, we found that S503A-CEACAM1 transgenic mice developed hyperinsulinemia resulting from impaired insulin clearance. The hyperinsulinemia caused secondary insulin resistance with impaired glucose tolerance and random, but not fasting, hyperglycemia. Transgenic mice developed visceral adiposity with increased amounts of plasma free fatty acids and plasma and hepatic triglycerides. These findings suggest a mechanism through which insulin signaling regulates insulin sensitivity by modulating hepatic insulin clearance.

Animals↗

PubMed2002

Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus.

BACKGROUND & AIMS: The aim of this study was to determine whether expression of hepatitis C virus proteins alters hepatic morphology or function in the absence of inflammation. METHODS: Transgenic C57BL/6 mice with liver-specific expression of RNA encoding the complete viral polyprotein (FL-N transgene) or viral structural proteins (S-N transgene) were compared with nontransgenic littermates for altered liver morphology and function. RESULTS: FL-N transcripts were detectable only by reverse-transcription polymerase chain reaction, and S-N transcripts were identified in Northern blots. The abundance of viral proteins was sufficient for detection only in S-N transgenic animals. There was no inflammation in transgenic livers, but mice expressing either transgene developed age-related hepatic steatosis that was more severe in males. Apoptotic or proliferating hepatocytes were not significantly increased. Hepatocellular adenoma or carcinoma developed in older male animals expressing either transgene, but their incidence reached statistical significance only in FL-N animals. Neither was ever observed in age-matched nontransgenic mice. CONCLUSIONS: Constitutive expression of viral proteins leads to common pathologic features of hepatitis C in the absence of specific anti-viral immune responses. Expression of the structural proteins enhances a low background of steatosis in C57BL/6 mice, while additional low level expression of nonstructural proteins increases the risk of cancer.

Animals↗

PubMed2002

Apolipoprotein B mRNA editing and the reduction in synthesis and secretion of the atherogenic risk factor, apolipoprotein B100 can be effectively targeted through TAT-mediated protein transduction.

Hepatic very-low-density lipoprotein particles (VLDL) containing full-length apolipoprotein B100 are metabolized in the blood stream to low-density lipoprotein (LDL) particles, whose elevated levels increase the risk of atherosclerosis. Statins and bile-acid sequestrants are effective LDL-lowering therapies for many patients. Development of alternative therapies remains important for patients with adverse reactions to conventional therapy, with defects in the LDL receptor-dependent lipoprotein uptake pathway and for intervention in children. Editing of apoB mRNA by the enzyme APOBEC-1 changes a glutamine codon to a stop codon, leading to the synthesis and secretion of apoB48-containing VLDL, which are rapidly cleared before they can be metabolized to LDL. Human liver does not edit apoB mRNA because it does not express APOBEC-1. Although initially promising, enthusiasm for apobec-1 gene therapy for hypercholesterolemia was blunted by the finding that uncontrolled transgenic expression of APOBEC-1 led to nonspecific editing of mRNAs and pathology. We demonstrate that APOBEC-1 fused to TAT entered primary hepatocytes, where it induced a transient increase in mRNA editing activity and enhanced synthesis and secretion of VLDL containing apoB48. Protein transduction of APOBEC-1 transiently stimulated high levels of apoB mRNA editing in a dose-dependent manner without loss of fidelity. These results suggested that apoB mRNA editing should be re-evaluated as a LDL-lowering therapeutic target in the new context of protein transduction therapy.

APOBEC-1 Deaminase↗

PubMed2002

Sequence requirements for viral RNA replication and VPg uridylylation directed by the internal cis-acting replication element (cre) of human rhinovirus type 14.

Until recently, the cis-acting signals required for replication of picornaviral RNAs were believed to be restricted to the 5' and 3' noncoding regions of the genome. However, an RNA stem-loop in the VP1-coding sequence of human rhinovirus type 14 (HRV-14) is essential for viral minus-strand RNA synthesis (K. L. McKnight and S. M. Lemon, RNA 4:1569-1584, 1998). The nucleotide sequence of the apical loop of this internal cis-acting replication element (cre) was critical for RNA synthesis, while secondary RNA structure, but not primary sequence, was shown to be important within the duplex stem. Similar cres have since been identified in other picornaviral genomes. These RNA segments appear to serve as template for the uridylylation of the genome-linked protein, VPg, providing the VPg-pUpU primer required for viral RNA transcription (A. V. Paul et al., J. Virol. 74:10359-10370, 2000). Here, we show that the minimal functional HRV-14 cre resides within a 33-nucleotide (nt) RNA segment that is predicted to form a simple stem-loop with a 14-nt loop sequence. An extensive mutational analysis involving every possible base substitution at each position within the loop segment defined the sequence that is required within this loop for efficient replication of subgenomic HRV-14 replicon RNAs. These results indicate that three consecutive adenosine residues (nt 2367 to 2369) within the 5' half of this loop are critically important for cre function and suggest that a common RNNNAARNNNNNNR loop motif exists among the cre sequences of enteroviruses and rhinoviruses. We found a direct, positive correlation between the capacity of mutated cres to support RNA replication and their ability to function as template in an in vitro VPg uridylylation reaction, suggesting that these functions are intimately linked. These data thus define more precisely the sequence and structural requirements of the HRV-14 cre and provide additional support for a model in which the role of the cre in RNA replication is to act as template for VPg uridylylation.

Base Sequence↗

PubMed2002

[The effect of vitamin C in oxidative modification of low-density lipoprotein induced by macrophage and copperion].

OBJECTIVE: To study the effect of vitamin C on preventing oxidative modification of low density lipoprotein cholesterol (LDL) in vitro. METHODS: Different levels of vitamin C were added to two different systems of lipid peroxidation of LDL induced by either Cu(2+) or macrophage. The level of VC in systems induced by Cu(2+) were 10, 50, 100 and 200 micromol/L respectively and by macrophage were 50, 100, 200 micromol/L respectively. Vitamin E (200 micromol/L) and VC(0) (0 micromol/L) were served as positive and negative control respectively. The content of TBARS, Ox-LDL, fluorescent compounds, electrophoretic mobility of LDL and the lag-phage of oxidation of LDL were measured. RESULTS: In the oxidative systems induced by Cu(2+), the groups with higher levels of VC (100, 200 micromol/L) reduced the levels of TBARS, Ox-LDL at 3, 6, and 9 hour after adding Cu(2+), but low dose groups (10, 50 micromol/L) had no the effects. In the macrophage systems, higher levels of VC (100, 200 micromol/L) significantly reduced levels of fluorescent compounds and TBARS, and also lowered electrophoretic mobility of LDL and increased the lag-phage of oxidation of LDL. CONCLUSION: Vitamin C has dual effect on oxidation of LDL. Low dose treatment enhanced oxidation of LDL, but high doses has anti-oxidative effects on LDL.

Animals↗

PubMed2002

[Effects of ectogenous FHIT gene on reversing malignant phenotype of human lung adenocarcinoma cells A549].

OBJECTIVE: To explore the role of fragile histidine triad(FHIT) gene in the proliferation, apoptosis and tumorigenesis of human lung cancer cells. METHODS: FHIT gene packaged with lipofectin was transfected into the cells of a human lung adenocarcinoma cell line (A549), which stably expressed ectogenous FHIT gene. The FHIT mRNA and protein expression of A549-FHIT, A549-vector and A549 cell were detected by reverse transcription-PCR(RT-PCR), Western blot and immunocytochemical methods. The cell cycle pattern and apoptosis were assayed by using flow cytometry. RESULTS: After transfection of FHIT gene, cell growth was obviously inhibited (P<0.01). The apoptosis index of A549-FHIT (8.42%) was significantly higher than that of A549-vector (5.45%) and A549 cells (5.71%)(P<0.01). The clone-formation rate of A549-FHIT cell (21.84%) was significantly lower than that of A549-vector (28.70%) and A549 cells (31.68%, P<0.01). Compared with control cell lines, larger scale of A549-FHIT cells accumulated in G0/G1, presenting that the proportion of the cells in G0/G1 phase was obviously increased from 67.78 % to 82.35 %. Tumorigenicity of the A549 cells in nude mice was greatly inhibited by expression of ectogenous FHIT gene, the weight and volume of A549-FHIT(1.61 g/1.37 cm(3)) were significantly lower than that of A549-vector (2.45 g/1.99cm(3)) and A549 cells (2.77 g/2.27 cm(3))(P<0.05). CONCLUSION: Expression of ectogenous FHIT gene can obviously inhibit the proliferation and tumorigenesis of A549 cells, and can induce A549 cells into programmed cell death. The result of this study suggests that FHIT gene may be a tumor suppressor gene in human lung cancer cells.

Acid Anhydride Hydrolases↗

PubMed2002

[Clinical research of patients with acute or chronic hepatic failure treated with molecular adsorbent recirculating system].

OBJECTIVE: To summarize the experience of a single treatment using molecular adsorbent recirculating system (MARS) in patients with acute-on-chronic liver failure. METHODS: Twenty-five eases treated by MARS-artificial liver were followed up and reviewed. RESULTS: The levels of serum total bilirubin, non-conjugated bilirubin and blood ammonia were significantly decreased from (618.51 200.68) mmol/L to (390.81 146.02) mmol/L (t=2.729, P<0.01), (490.03 163.39) mmol/L to (303.28 113.06) mmol/L (t =2.516, P<0.01), and (152.44 82.62)mmol/L to (84.80 13.30)mmol/L (t=2.174, P<0.05), respectively. Prothrombin activity was significantly increased from 70.55% 32.39% to 93.63% 14.20% (t=1.728, P<0.05) in patients during a single 6 h treatment with MARS. No difference was presented in the markers of liver zymogram, serum protein, kidney function, electrolyte, blood routine and blood gas analysis before and after the MARS. Thirteen of 17 patients have been cured or improved, 4 died, and the survival rate was 76.5%. CONCLUSIONS: MARS is a safe and an effective treatment for patients with liver failure.

Adult↗

PubMed2002

[Changes of proinflammatory cytokines and their receptors in serum from patients with pulmonary tuberculosis].

OBJECTIVE To investigate the characteristics and clinical value of serum tumor necrosis factor-alpha (TNF-alpha) and its receptor (sTNF-R), interleukin-1beta(IL-1beta) and its receptor(IL-1R), interleukin-6(IL-6) and its receptor(IL-6R) in patients with pulmonary tuberculosis, and to evaluate their role in the immunopathogenesis of tuberculosis. METHODS The serum levels of TNF-alpha, sTNF-R Iota IL-1beta,IL-1R, IL-6 and IL-6R were measured using the sandwich ABC-ELISA method in 41 cases of active tuberculosis, 21 cases of inactive tuberculosis and 20 normal controls. The serum levels of the cytokines in 17 cases of active tuberculos is were followed. RESULTS The serum levels of TNF-alpha sTNF-RIota IL-1beta,IL-1R, IL-6 IL-6R and the TNF-alpha/sTNF-RIota ratio were significantly higher in both the active and the inactive tuberculosis groups than those in normal controls (P <0.01 approximately 0.05). The TNF-alpha sTNF-R Iota IL-1 beta, IL-1R, IL-6 IL-6R levels and the TNF-alpha/sTNF-R Iota ratio in the active tuberculosis group were significantly higher than those in the inactive tuberculosis(P <0.01 approximately 0.05). The serum levels of TNF-alpha sTNF-R Iota, IL-1beta and IL-6 and the TNF-alpha,/sTNF-R Iota ratio were significantly lower in cavernous tuberculosis than those in non- cavernous tuberculosis (P < 0.01 approximately 0.05). After 2 months' antituberculosis treatment, the serum levels of TNF-alpha,sTNF-R Iota IL-1 beta, IL-1R,IL-6, IL-6R and the TNF-alpha/sTNF-R Iota ratio in 15(15/17) cases were significantly lower than those before treatment(P < 0.01 approximately 0.05). CONCLUSIONS TNF-alpha, IL-1 beta, IL-6 and their receptors may be involved in the immunopathogenesis of tuberculosis. Measuring the serum levels of proinflammatory cytokines and their receptors may be useful in evaluating the activity, the clinical pattern, and the prognosis of the disease and monitoring the clinical effect of antituberculous therapy.

Adolescent↗

PubMed2002

[Distribution of CSF1PO TPOX and TH01 loci in five minority populations in Yunnan of China].

OBJECTIVE: To investigate the distribution of CSF1PO, TPOX and TH01 in 5 minority populations only resided in Yunnan province. METHODS: DNA extraction from bloods and multiplex amplification of CSF1PO, TPOX and TH01 were carried out. The technique of denaturing polyacrylamide gel electrophoresis and silver staining method were used. RESULTS: The data on the distribution of allele frequencies of 3 loci(CSF1PO, TPOX and TH01) in Achang Deang Bulang Pumi and Jino were collected and analyzed. CONCLUSION: The allele distribution of the loci were in good agreement with the Hardy-Weinberg equibrium. A satisfactory result was obtained and some significant genetics differences were noticed in different populations.

Alleles↗

PubMed2002

Effect of superior fiber complex on insulin sensitivity index and blood lipids in non-insulin dependent diabetes mellitus rats.

OBJECTIVE: To explore the factors affected insulin sensitivity index (ISI) and the effects of superior fiber complex (SFC) on ISI and blood lipids in non-insulin dependent diabetes mellitus (NIDDM) rats. METHODS: Twenty-six male Wistar rats were injected with low dose of streptozotocin and fed a diet with high calorie and high fat for ten weeks and glucose tolerance (GTT), fasting insulin (FINS), total cholesterol (TC) and triglyceride (TG) were measured while area under curve (AUC) and insulin sensitivity index (ISI) were also calculated. The results were compared with those from 7 normal control rats. Multi-factor regression analysis was used to analyze those factors affected ISI. In the same experiment, 13 rats with diabetes mellitus were treated with Superior Fiber Complex (SFC) for 8 weeks and the results were compared with the pre-treated data. RESULTS: Compared with the control group, AUC in the diabetic group was larger, and FINS, TC and TG were higher; but ISI was lower. Therefore, The TG and AUC was the major factor affected ISI. TC and TG were lowered and AUC was reduced and ISI increased. CONCLUSION: High TG and impaired glucose tolerance (IGT) are main risk factors of ISI in the rat model, and SFC could increase ISI, decrease high blood lipids and prevent IGT.

Animals↗

PubMed2002

[The role of hyperhomocysteinemia on atherosclerosis in patients with chronic renal failure].

OBJECTIVE: To determine whether atherosclerosis may be accelerated by hyperhomocysteinemia in patients with chronic renal failure (CRF). METHODS: One hundred and ninety-seven CRF patients and 53 healthy volunteers were included in this study. Plasma total homocysteine (tHcy) levels were measured by using fluorescence polarization immunoassay. Intima-media thickness (IMT) and prevalence atherosclerotic plaques of the extracranial common carotid artery were determined by high-resolution B-mode ultrasonography. The changes in brachial artery diameter during reactive hyperemia (D(h)) and after administration of sublingual nitroglycerin (D(n)) were analyzed during ultrasonic examination. RESULTS: The prevalence of hyperhomocysteinemia was 84.4% in the CRF patients. The mean level of tHcy (23.56 +/- 11.91) micro mol/L was significantly higher in the CRF patients than that in the healthy controls (7.97 +/- 2.65) micro mol/L (P < 0.01). The prevalence of atherosclerotic plaques and the mean IMT value of carotid artery were significantly increased in CRF patients compared with that in age-matched controls. Furthermore, arterial dilating function sush as D(h) and D(n) was significantly decreased in CRF patients [(D(h)) (4.05 +/- 3.81)% and (D(n)) (4.94 +/- 4.28)%] compared with that in controls [(D(h)) (8.81 +/- 6.15)% and (D(n)) (11.72 +/- 7.64)%] (P < 0.01). The levels of plasma tHcy were coherent with intensity of atherosclerosis in the CRF patients. Multiple stepwise regression analysis showed that in CRF patients, independent risk factors associated with value of IMT were level of tHcy, age, and duration of dialysis (RR = 0.484, P < 0.001), while those associated with D(h) arterial dilatation were plasma tHcy level, age, duration of dialysis and total cholesterol (RR = 0.263, P < 0.001) and those associated with D(n) were age and tHcy level (RR = 0.211, P < 0.001). CONCLUSION: The results indicate that atherosclerosis and dysfunction of arterial vasodilation in CRF patients are associated with increase of plasma tHcy. Hyperhomocysteinemia may be an independent risk factor for atherosclerosis seen in CRF patients.

Adult↗

PubMed2002

[A study on apoptosis of nasopharyngeal carcinoma cell line induced by Tanshinone II A and its molecular mechanism].

OBJECTIVE: To assess effect of Tanshinone II A on the apoptosis of human nasopharyngeal carcinoma (NPC) cell line CNE-1 and inquire into the mechanism there in involved. METHODS: The CNE-1 cells cultured in vitro were treated with 0.5 microgram/ml Tanshinone II A for 4 days. The morphology of the cells was observed by microscopy. The cell growth and proliferation were measured by cell counting. The DNA break was examined by gel electrophoresis. The cell cycle, apoptosis index (AI) and the expression of apoptosis associated gene were analysed by flow cytometry. RESULTS: 0.5 microgram/ml Tanshinone II A could induce the apoptosis of CNE-1 cells. In the treatment group, the morphologic characteristics of apoptotic cells were observed, the DNA of cells presented "ladder" break, the cell growth and proliferation were inhibited obviously, and the AI was 16.9% (the AI of control group was 6.4%). The cells were arrested in G0/G1 phase and cellular DNA synthesis was inhibited. The expressions of apoptosis associated gene fas, bax, p53 and p21 were up-regulated; the expression of bcl-2 was down-regulated. CONCLUSION: Tanshinone II A can induce apoptosis of human nasopharyngeal carcinoma cells. Its molecular mechanism may relate to modulation of the apoptosis associated gene expression.

Abietanes↗

PubMed2002

[Expression of VEGF and VEGF-C in laryngeal carcinoma and their clinical significance].

OBJECTIVE: To study the gene expression of Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor C (VEGF-C) in laryngeal carcinoma and their relation with clinic pathologic features. METHOD: VEGF and VEGF C gene expression in 20 cases of fresh laryngeal carcinoma, cutting edge and normal tissue were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULT: The gene expression of VEGF and VEGF-C is different among laryngeal carcinoma, cutting edge and normal tissue in the same patient. In laryngeal carcinoma, the gene expression of VEGF, VEGF-C were not associated with age, sex, site, T stage and histological grade of differentiation. Expression of VEGF, VEGF-C in laryngeal carcinoma was significantly higher in lymph node positive group than in lymph node negative group. CONCLUSION: VEGF, VEGF-C have prognostic significance in laryngeal carcinoma.

Adult↗