Enhancing mucosal immunity in mice by recombinant adenovirus expressing major epitopes of porcine circovirus-2 capsid protein delivered with cytosine-phosphate-guanosine oligodeoxynucleotides

Hong-tao Chang,Xiu-yuan He,Yu-Feng Liu,Lu Chen,Quan-hai Guo,Qiu-ying Yu,Jun Zhao,Xin-wei Wang,Xia Yang,Chuan-qing Wang 대한수의학회 2014 Journal of Veterinary Science Vol.15 No.3

A recombinant replication-defective adenovirus expressingthe major epitopes of porcine circovirus-2 (PCV-2) capsidprotein (rAd/Cap/518) was previously constructed and shownto induce mucosal immunity in mice following intranasaldelivery. In the present study, immune responses induced byintranasal immunization with a combination of rAd/Cap/518and cytosine-phosphate-guanosine oligodeoxynucleotides(CpG ODN) were evaluated in mice. The levels ofPCV-2-specific IgG in serum and IgA in saliva, lung, andintestinal fluids were significantly higher in the groupimmunized with rAd/Cap/518 and CpG ODN than animalsimmunized with rAd/Cap/518 alone. The frequencies ofIL-2-secreting CD4+ T cells and IFN-γ-producing CD8+ T cellswere significantly higher in the combined immunizationgroup than mice immunized with rAd/Cap/518 alone. Thefrequencies of CD3+, CD3+CD4+CD8−, and CD3+CD4−CD8+T cells in the combined immunization group were similar tothat treated with CpG ODN alone, but significantly higherthan mice that did not receive CpG ODN. PCV-2 load afterchallenge in the combined immunization group wassignificantly lower than that in the phosphate-buffered salineplacebo group and approximately 7-fold lower in the grouptreated with CpG ODN alone. These results indicate thatrAd/Cap/518 combined with CpG ODN can enhance systemicand local mucosal immunity in mice, and represent apromising synergetic mucosal vaccine against PCV-2.

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Wang, Xue-Jian,Duan, Yu,Li, Zong-Tao,Feng, Jin-Hong,Pan, Xiang-Po,Zhang, Xiu-Rong,Shi, Li-Hong,Zhang, Tao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.

Pharmacokinetic Behavior of Gentiopicroside From Decoction of Radix Gentianae, Gentiana Macrophylla After Oral Administration in Rats: a Pharmacokinetic Comaprison with Gentiopicroside after Oral and Intravenous Administration Alone

Wang, Chang-Hong,Cheng, Xue-Mei,He, Yu-Qi,White, Kenneth N.,Bligh, S.W.Annie,Branford-White, Christopher J.,Wang, Zheng-Tao 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.9

The pharmacokinetics in rats of gentiopicroside (GPS) from orally administered decoctions of Radix Gentianae (DRG) and Gentiana macrophlla (DGM) were compared with that of GPS alone administered at 150 mg/kg orally and 30 mg/kg intravenously. The metabolic profile of GPS after intravenous injection could be fitted to two-compartment model whereas oral administration decoctions DRG or DGM, or GPS alone, could all be fitted to a one-compartment model. After oral administration of GPS alone, GPS was absorbed quickly and reached a maximum plasma concentration ($C_{max}$) value, 5.78 ${\pm}$ 2.24 ${\mu}g/mL$ within 0.75 ${\pm}$ 0.62 h. The plasma level of GPS declined with a $T_{1/2ke}$, 3.35 ${\pm}$ 0.76 h. After oral administration of decoctions DRG and DGM, GPS was absorbed and reached significantly higher maximum concentrations of 10.53 ${\pm}$ 3.20 ${\mu}g/mL$ (p < 0.01) and 7.43 ${\pm}$ 1.64 ${\mu}g/mL$ (p < 0.05) at later time points 1.60 ${\pm}$ 0.76 (p < 0.01) and 2.08${\pm}$0.74 h (p < 0.05), for DRG and DGM respectively, compared with oral GPS alone. Significantly larger AUC values were found for decoctions of GPS (83.49 ${\pm}$ 20.8 ${\mu}g{\cdot}h/mL$ for DRG and 59.43 ${\pm}$ 12.9 ${\mu}g{\cdot}h/mL$ for DGM) compared with oral GPS alone (32.67 ${\pm}$ 12.9 ${\mu}g{\cdot}h/mL$. The results demonstrate that the bioavailability of GPS was markedly improved when administered as a decoction than as purified GPS. The decoction from Radix Gentianae provided 2.5 times better bioavailability and that from Gentiana macrophlla 1.8 times higher. The study confirms the importance of careful pharmacokinetic analysis in the characterization of herbal medicines when applied for future clinical applications.

Isolation and Cloning of Porcine SLC27A2 Gene and Detection of Its Polymorphism Associated with Growth and Carcass Traits

Wang, Tao,Liu, Chang,Xiong, Yuan-Zhu,Deng, Chang-Yan,Zuo, Bo,Xie, Hong-Tao,Xu, De-Quan Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.8

The protein encoded by SLC27A2 gene is an isozyme of long-chain fatty-acid-coenzyme A ligase family, and it converts free long-chain fatty acids into fatty acyl-CoA esters, and thereby plays a key role in lipid biosynthesis and fatty acid degradation. In the present study, SLC27A2 located on human chromosome 15 was selected as candidate gene and we isolated and cloned partial fragments of mRNA sequence and genomic fragments of porcine SLC27A2 gene. The coding region of the gene as determined by alignments shared 90% and 82% identity with human and mouse cDNAs, respectively. Detection in LargeWhite and Meishan breeds showed that a single nucleotide polymorphism (SNP) ($A{\rightarrow}G$) existed in exon 7, which caused corresponding amino acid changed for encoding. In LargeWhite pigs it encoded for Val while in Meishan pigs it encoded for Ile, so we developed the PCR-RFLP genotype method for detection of this polymorphism. Association study in 135 $F_2$ reference family indicated that significant correlation existed between the polymorphism and growth and carcass traits.

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines

Shen, Tao,Li, Wei,Wang, Yan-Yan,Zhong, Qing-Qing,Wang, Shu-Qi,Wang, Xiao-Ning,Ren, Dong-Mei,Lou, Hong-Xiang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with $IC_{50}$ values ranging from 2.90 to $4.15{\mu}M$. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.

Development and Validation of Nomograms to Provide Individualized Predictions of Sur-vival Benefits from Surgery in Patients with Intermediate/Advanced Hepatocel-lular Carcinoma

( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.

Pharmacokinetic Behavior of Gentiopicroside From Decoction of Radix Gentianae,

Chang-hong Wang,Xue-mei Cheng,Yu-qi He,Kenneth N. White,S. W. Annie Bligh,Christopher J. Branford-White,Zheng-tao Wang 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.9

The pharmacokinetics in rats of gentiopicroside (GPS) from orally administered decoctions of Radix Gentianae (DRG) and Gentiana macrophlla (DGM) were compared with that of GPS alone administered at 150 mg/kg orally and 30 mg/kg intravenously. The metabolic profile of GPS after intravenous injection could be fitted to two-compartment model whereas oral administration decoctions DRG or DGM, or GPS alone, could all be fitted to a one-compartment model. After oral administration of GPS alone, GPS was absorbed quickly and reached a maximum plasma concentration (Cmax) value, 5.78 ± 2.24 µg/mL within 0.75 ± 0.62 h. The plasma level of GPS declined with a T1/2ke, 3.35 ± 0.76 h. After oral administration of decoctions DRG and DGM, GPS was absorbed and reached significantly higher maximum concentrations of 10.53 ± 3.20 µg/mL (p < 0.01) and 7.43 ± 1.64 µg/mL (p < 0.05) at later time points 1.60 ± 0.76 (p < 0.01) and 2.08±0.74 h (p < 0.05), for DRG and DGM respectively, compared with oral GPS alone. Significantly larger AUC values were found for decoctions of GPS (83.49 ± 20.8 µg·h/mL for DRG and 59.43 ± 12.9 µg·h/mL for DGM) compared with oral GPS alone (32.67 ± 12.9 µg·h/mL). The results demonstrate that the bioavailability of GPS was markedly improved when administered as a decoction than as purified GPS. The decoction from Radix Gentianae provided 2.5 times better bioavailability and that from Gentiana macrophlla 1.8 times higher. The study confirms the importance of careful pharmacokinetic analysis in the characterization of herbal medicines when applied for future clinical applications.

MiR-421 Regulates Apoptosis of BGC-823 Gastric Cancer Cells by Targeting Caspase-3

Wu, Jian-Hong,Yao, Yong-Liang,Gu, Tao,Wang, Ze-You,Pu, Xiong-Yong,Sun, Wang-Wei,Zhang, Xian,Jiang, Yi-Biao,Wang, Jian-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.

Composition and abundance of microbiota in the pharynx in patients with laryngeal carcinoma and vocal cord polyps

Hongli Gong,Boyan Wang,Yi Shi,Yong Shi,Xiyan Xiao,Pengyu Cao,Lei Tao,Yuezhu Wang,Liang Zhou 한국미생물학회 2017 The journal of microbiology Vol.55 No.8

The pharynx is an important site of microbiota colonization, but the bacterial populations at this site have been relatively unexplored by culture-independent approaches. The aim of this study was to characterize the microbiota structure of the pharynx. Pyrosequencing of 16S rRNA gene libraries was used to characterize the pharyngeal microbiota using swab samples from 68 subjects with laryngeal cancer and 28 subjects with vocal cord polyps. Overall, the major phylum was Firmicutes, with Streptococcus as the predominant genus in the pharyngeal communities. Nine core operational taxonomic units detected from Streptococcus, Fusobacterium, Prevotella, Granulicatella, and Veillonella accounted for 21.3% of the total sequences detected. However, there was no difference in bacterial communities in the pharynx from patients with laryngeal cancer and vocal cord polyps. The relative abundance of Firmicutes was inversely correlated with Fusobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes. The correlation was evident at the genus level, and the relative abundance of Streptococcus was inversely associated with Fusobacterium, Leptotrichia, Neisseria, Actinomyces, and Prevotella. This study presented a profile for the overall structure of the microbiota in pharyngeal swab samples. Inverse correlations were found between Streptococcus and other bacterial communities, suggesting that potential antagonism may exist among pharyngeal microbiota.

Design of a Modular Green Closed Internal Cooling Turning Tool for Applications

Tao Wu,Tianjian Li,Xiaohong Ding,Hong Chen,Lei Wang 한국정밀공학회 2018 International Journal of Precision Engineering and Vol.5 No.2

Green machining has been aggressively pursued in the manufacturing industry in recent years. Dry or clean cutting without the hazards of cooling liquid, and their abilities to monitor thermal impact on turning tools in real time have been very appealed to the manufacturing industries. In this study, a modular green closed internal cooling turning tool is presented, in which coolant channel is designed only between an insert and an adaptor. The insert is grouped with the adaptor and designed as a Plug-and-Play component in cooling circuit. Thermal-fluid-structural coupling analysis is employed to evaluate the effects of the internal cooling system with machining process constraints. The numerical simulation results demonstrate that the newly designed internal cooing turning tool could effectively decrease the tool temperature. Preliminary experiments have further proved the effectiveness of the modular green closed internal cooling turning tool system. The study has potentially great significance in improving tooling performance, as well as achieving environmental friendly, economical and sustainable machining.