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Biomedical subjects

Xiang Wang

Publications and source records attributed to Xiang Wang.

At least 73 records · Page 4Linked to original sources

Adjustment of lipiodol dose according to tumor blood supply during transcatheter arterial chemoembolization for large hepatocellular carcinoma by multidetector helical CT.

AIM: To work out an individualized lipiodol dose in transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma (HCC) according to its blood supply evaluated by CT. METHODS: One hundred patients with large HCC (more than 8 cm in diameter) were studied by multidetector helical CT. Patterns of blood supply of HCC were divided into sufficient blood supply, poor blood supply, mixed blood supply and arteriovenous (A-V) shunt. The dose of ultra-fluid lipiodol was determined by diameter and blood supply type of HCC. Patients were divided into two groups (50 cases each): lipiodol perfusion group and iodized oil perfusion group according to tumor diameter and the blood supply type of tumor. RESULTS: The confirmation and effective rates were 82%, 84% in the first group and 36%, 46% in the second group (P<0.01). CONCLUSION: A relatively individualized lipiodol dose may be determined according to the blood supply pattern and the tumor diameter by CT imaging.

Adult↗

Human liver specific transcriptional factor TCP10L binds to MAD4.

A human gene T-complex protein 10 like (TCP10L) was cloned in our lab. A previous study showed that it expressed specifically in the liver and testis. A transcription experiment revealed that TCP10L was a transcription factor with transcription inhibition activity. In this study, the human MAD4 was identified to interact with TCP10L by a yeast two-hybrid screen. This finding was confirmed by immunoprecipitation and subcellular localization experiments. As MAD4 is a member of the MAD family, which antagonizes the functions of MYC and promotes cell differentiation, the biological function of the interaction between TCP10L and MAD4 may be to maintain the differentiation state in liver cells. Also, we propose that the up-regulation of Myc is caused by the down-regulation of TCP10L in human hepatocarcinomas.

Animals↗

Inhibition of NOS2 ameliorates cardiac remodeling, improves heart function after myocardial infarction in rats.

OBJECTIVE: Previous studies have shown increased expression of nitric oxide synthase 2 (NOS2) in rat heart several weeks after myocardial infarction (MI). The aim of this study was to examine the effect of chronic administration of S-methylisothiourea (SMT), a selective NOS2 inhibitor, commenced one week after MI on hemodynamic parameters and left ventricular (LV) remodeling in rats. METHODS: Rats with MI induced by left coronary ligation were given SMT (0.5 mg/kg/d) or saline by gavage starting one week after MI. After chronic administration for five weeks, hemodynamic and cardiac morphologic studies were performed, and lung water content, plasma NO(x) concentration, NOS2 protein level, myocyte size and collagen volume fraction of noninfarct LV area were quantified. RESULTS: The NO(x) concentration in plasma and the NOS2 protein level in noninfarct myocardium in MI rats were higher than controls. When compared with the MI rats receiving saline, chronic administration of SMT reduced myocyte size (15.1 +/- 1.6 microm vs 16.9 +/- 2.3 microm, P < 0.05), collagen volume fraction of noninfarct LV area (4.4% +/- 1.1% vs 5.7% +/- 1.2%, P < 0.01) and lung water content (77.4% +/- 1.4% vs 79.3% +/- 0.9%, P < 0.01), without affecting infarct size. Administration of SMT had no significant effect on heart rate and mean arterial pressure, but decreased LV end-diastolic pressure (8.7 +/- 2.1 mmHg vs 13.4 +/- 3.1 mmHg, P < 0.01), central venous pressure (0.9 +/- 0.3 mmHg vs 1.5 +/- 0.5 mmHg, P < 0.01) and inner LV diameter (6.9 +/- 0.3 mm vs 7.2 +/- 0.3 mm, P < 0.05) in the MI rats. Plasma level of NO(x) in the MI rats receiving SMT was reduced to control level. CONCLUSIONS: Chronic administration of SMT had beneficial effects on LV remodeling and cardiac dysfunction in MI rats, suggesting the possibility that inhibition of NOS2 could be a therapeutic tool for cardiac dysfunction after MI.

Animals↗

Platinum-catalyzed intramolecular alkylation of indoles with unactivated olefins.

Reaction of 1-methy-2-(4-pentenyl)indole (1) with a catalytic amount of PtCl2 (2 mol %) in dioxane that contained a trace of HCl (5 mol %) at 60 degrees C for 24 h led to the isolation of 4,9-dimethyl-2,3,4,9-tetrahydro-1H-carbazole (2) in 92% yield. Platinum-catalyzed cyclization of 2-(4-pentenyl)indoles tolerated substitution at each position of the 4-pentenyl chain. Furthermore, the protocol was applicable to the synthesis of tetrahydro-beta-carbolinones and was effective for cyclization of unprotected indoles. 2-(3-Butenyl)indoles underwent platinum-catalyzed cyclization with exclusive 6-endo-trig regioselectivity. Mechanistic studies established a mechanism for the platinum-catalyzed cyclization of 2-alkenyl indoles involving nucleophilic attack of the indole on a platinum-complexed olefin.

Alkenes↗

Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation.

DNA damage-induced S phase (S) checkpoint includes inhibition of both replicon initiation and chain elongation. The precise mechanism for controlling the two processes remains unclear. In this study, we showed that Hus1-deficient mouse cells had an impaired S checkpoint after exposure to DNA strand break-inducing agents such as camptothecin (CPT) (>or=1.0 micro M), or ionizing radiation (IR) (>or=15 Gy). The Hus1-dependent S checkpoint contributes to cell resistance to CPT. This impaired S checkpoint induced by CPT or IR in Hus1-deficient cells reflected mainly the chain elongation step of DNA replication and was correlated with the reduction of dissociation of PCNA from DNA replication foci. Although Hus1 is required for Rad9 phosphorylation following exposure of cells to CPT or IR, Hus1-deficient cells showed normal activation of ATR/CHK1 and ATM kinases at doses where the checkpoint defects were manifested, suggesting that Hus1 is not a component of the sensor system for activating these pathways in S checkpoint induced by CPT or IR.

Animals↗

Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks.

We recently reported that two Chinese hamster mutants deficient in the RAD51 paralogs XRCC2 and XRCC3 show reduced radiosensitization after treatment with caffeine, thus implicating homology-directed repair (HDR) of DNA double-strand breaks (DSBs) in the mechanism of caffeine radiosensitization. Here, we investigate directly the effect of caffeine on HDR initiated by DSBs induced by a rare cutting endonuclease (I-SceI) into one of two direct DNA repeats. The results demonstrate a strong inhibition by caffeine of HDR in wild-type cells, and a substantial reduction of this effect in HDR-deficient XRCC3 mutant cells. Inhibition of HDR and cell radiosensitization to killing shows similar dependence on caffeine concentration suggesting a cause-effect relationship between these effects. UCN-01, a kinase inhibitor that effectively abrogates checkpoint activation in irradiated cells, has only a small effect on HDR, indicating that similar to radiosensitization, inhibition of checkpoint signaling is not sufficient for HDR inhibition. Recombination events occurring during treatment with caffeine are characterized by rearrangements reminiscent to those previously reported for the XRCC3 mutant, and immunofluorescence microscopy demonstrates significantly reduced formation of IR-specific RAD51 foci after caffeine treatment. In summary, our results identify inhibition of HDR as a significant contributor to caffeine radiosensitization.

Animals↗

Expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF > or = 6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74 +/- 19 U vs sinus rhythm: 32 +/- 24 U, P < 0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150% in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.

Adult↗

Angiogenic potency of bone marrow stromal cells improved by ex vivo hypoxia prestimulation.

To study the angiogenic potency of hypoxia-prestimulated bone marrow stromal cells (BMSCs) when transplanted into acute myocardial infarction models of rats. BMSCs were cultured under hypoxia condition for 24 h. Their expression of VEGF was investigated. The rat acute myocardial infarction models were made by coronary artery ligation and divided into 3 groups at random. In normoxia group, twice-passaged BMSCs were labeled with Bromodeoxyuridine (BrdU) and then implanted into the infarction regions and ischemic border of the recipients in 4 weeks. The rats in hypoxia group were implanted with hypoxia-prestimulated BMSCs. In control group, the model rats received only DMEM medium injection. Six-weeks after AMI, the infarction regions were examined to identify the angiogenesis and the expression of the VEGF. Our results showed that viable cells labeled with BrdU could be identified in the host hearts. The infarction regions in normoxia and hypoxia groups had a greater capillary density and increased VEGF expression than the regions in control group. The capillary density and VEGF expression in hypoxia group were higher than in normoxia group. It is concluded that the enhanced expression of VEGF in BMSCs could be induced by ex vivo hypoxia stimulation. BMSCs implantation promoted the angiogenesis in myocardial infarction tissue via supplying exogenic VEGF. Angiogenic potency of bone marrow stromal cells was improved by ex vivo hypoxia prestimulation though the enhanced VEGF expression.

Animals↗

Development of Taqman RT-nested PCR system for clinical SARS-CoV detection.

Severe acute respiratory syndrome (SARS) is an acute newly emerged infectious respiratory illness. The etiologic agent of SARS was named 'SARS-associated coronavirus' (SARS-CoV) that can be detected with reverse transcription-polymerase chain reaction (RT-PCR) assays. In this study, 12 sets of nested primers covering the SARS-CoV genome have been screened and showed sufficient sensitivity to detect SARS-CoV in RNA isolated from virus cultured in Vero 6 cells. To optimize further the reaction condition of those nested primers sets, seven sets of nested primers have been chosen to compare their reverse transcribed efficiency with specific and random primers, which is useful to combine RT with the first round of PCR into a one-step RT-PCR. Based on the sensitivity and simplicity of results, the no. 73 primer set was chosen as the candidate primer set for clinical diagnoses. To specify the amplicon to minimize false positive results, a Taqman RT-nested PCR system of no. 73 nested primer set was developed. Through investigations on a test panel of whole blood obtained from 30 SARS patients and 9 control persons, the specificity and sensitivity of the Taqman RT-nested PCR system was found to be 100 and 83%, respectively, which suggests that the method is a promising one to diagnose SARS in early stages.

Adolescent↗

Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis.

The bromodomain, an evolutionarily conserved motif that binds acetyl-lysine on histones, is found in many chromatin-associated proteins, transcription factors, and in nearly all known histone acetyltransferases. The BET subclass of bromodomain-containing proteins contains two bromodomains and one ET domain and consists of at least four members in mouse and human, Brd2, Brd3, Brd4, and Brdt. We isolated mouse cDNAs for these genes and studied their expression patterns with particular focus on the testis. Northern hybridization revealed that Brd3 is most abundant in testis, ovary, placenta, uterus, and brain; that Brd4 is rather ubiquitously expressed but is most abundant in mid-gestation embryo, testis, ovary, and brain; and that Brdt is specifically expressed in testis. In situ hybridization and immunostaining on histological sections of mouse testes revealed a strikingly specific and dynamic change of cellular specificity in the germ line during the progression of spermatogenesis. Brd4 is expressed in spermatogonia, Brdt is only expressed in mid- to late-spermatocytes, Brd2 is expressed in diplotene spermatocytes and round spermatids and at low levels in spermatogonia, and Brd3 is expressed in round spermatids. This unique expression pattern suggests that genes in this subclass are not simply redundant. Rather, their expression is tightly regulated in the male germ cell lineage, suggesting that they likely have specific roles in different developmental stages and/or cell types.

Animals↗

Preparation of on-axis cylindrical trabecular bone specimens using micro-CT imaging.

The Orientation of trabecular bone specimens for mechanical testing must be carefully controlled. A method for accurately preparing on-axis cylindrical specimens using high-resolution micro-CT imaging was developed. Sixteen cylindrical specimens were prepared from eight bovine tibiae. High-resolution finite element models were generated from micro-CT images of parallelepipeds and used to determine the principal material coordinate system of each parallelepiped. A cylindrical specimen was then machined with a diamond coring bit. The resulting specimens were scanned again to evaluate the orientation. The average deviation between the principal fabric orientation and the longitudinal axis of the cylindrical specimen was only 4.70 +/- 3.11 degrees.

Animals↗

[Effects of atorvastatin on the function of dendritic cells in patients with unstable angina pectoris].

OBJECTIVE: To investigate the function of dendritic cells (DC) in patients with unstable angina pectoris (UAP) and the effects of atorvastatin on it. METHODS: 27 patients with UAP were divided into two groups treated respectively with regular pharmacotherapy and regular pharmacotherapy plus atorvastatin. PBMC from the UAP patients (before and 2 weeks after the treatment) and 11 healthy subjects were incubated and induced to mature DC in a completed medium containing GM-CSF and IL-4. Flow cytometric analysis was used to detect the expression of co-stimulating factor CD86 (B7-2) on DC. The stimulating capacity of DC was determined in allogenic mixed lymphocyte reaction (MLR). ELISA was used to analyze the level of cytokines (IL-1beta, IL-6, IL-10 and TNF-alpha) in the medium of MLR. Relationship of expression of CD86 to risk factors and blood CRP level was also analyzed. RESULTS: When compared with normal group, CD86 on DC was much more expressed in UAP patients; the stimulating capacity of DC in MLR was higher; T lymphocytes in MLR secreted higher levels of pro-inflammation cytokines (IL-1beta, IL-6 and TNF-alpha) and lower level of anti-inflammation cytokine (IL-10). Blood LDL-C before treatment was positively related to the expression of CD86. Atorvastatin inhibited the function of DC and lowered blood level of CRP and CD86, the levels of which were significantly positively correlated. CONCLUSIONS: DC in UAP are activated, which may play an important role in initiating immune reaction in the plaque. LDL-C may be one of the activators of DC; inhibitory effect of atorvastatin on inflammation in UAP may be due to its inhibition on DC.

Adult↗

[Compariative study of mitochondrial tRNA gene sequence and secondary structure among fifteen Predatory birds].

Three major clusters of mitochondrial tRNA genes (tRNA(Ile) -tRNA(Gln) -tRNA(Met), tRNA(Trp)- tRNA(Ala) -tRNA(Asn)- tRNA(CYs) -tRNA(Tyr) and tRNA(His) tRNA(Ser)(AGY) -tRNA(Leu)(CUN) from 13 species of Predatory birds were amplified and sequenced. The length of these tRNA clusters was similar among species (212 approximately 214 bp, 353 approximately 362 bp, 205 approximately 208 bp, respectively), and 47% of the sequences were variable, 67% of which were involved in the loop regions. The stem regions were relatively conserved, and the variable base pairs were under the restriction of compensatory changes or G-U wobble pairing which could be regarded as mechanisms for maintaining a stable secondary structure. Maximum-parsimony (MP) and Neighbor joining (NJ) phylogenetic trees were constructed using all the tRNA gene sequences or stein-forming nucleotides with Caprimulgus indicus as outgroup. We found that the bootstrap values for branches of trees using the tRNA sequences were commonly higher than the others, therefore the phylogenetic relationship of Predatory birds reflected by these data may be closer to the truth. Phylogenetic analyses indicated that Accipitridae was closer to Strigidae instead of Falconidae, and the classification of Tytonidae was different from the conclusion from the previously morphological and DNA-DNA hybridization studies. By comparing the secondary structure among taxa we found that the characters of nucleotide insertions and deletions in some tRNA genes have synapomorphies, suggesting that these characters may be useful for resolving the phylogenetic relationship of different families in Predatory birds with higher phylogenetic performance.

Animals↗

Palladium-catalyzed intramolecular hydroalkylation of unactivated olefins with dialkyl ketones.

[reaction: see text] Treatment of 3-butenyl heptyl ketone with substoichiometric amounts of PdCl(2)(CH(3)CN)(2) (10 mol %), HCl (0.1 equiv), and CuCl(2) (0.3 equiv) in dioxane at 70 degrees C for 12 h in a sealed tube formed 2-hexylcyclohexanone in 77% isolated yield. A number of alkyl 3-butenyl ketones underwent hydroalkylation under these conditions to form 2-substituted cyclohexanones in moderate to good yield.

Journal Article↗

Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat.

BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778 and FK779) monotherapy and combination therapy were examined in prevention of acute heart and kidney allograft rejection and reversal of ongoing acute heart allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and kidney transplantation models. Immunosuppressants were administered orally from day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after transplantation for the reversal of ongoing acute rejection. RESULTS: In the prevention of acute heart rejection model, recipient rats treated with monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related prolongation of mean survival time (MST) compared with naive control rats (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and FK778 indicated that an additive to synergistic interaction was produced when compared with the respective monotherapies (combination index [CI]=0.631-1.022). These results were reproducible with tacrolimus and FK779 combination therapy (CI=0.572-0.846). Furthermore, similar results were also found in the prevention of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal of ongoing acute heart allograft rejection, combination therapy of tacrolimus and FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of acute heart and kidney rejection and reversal of ongoing heart allograft rejection in the rat.

Acute Disease↗