Site-specific PEGylated TRAIL with improved pharmacokinetic properties and in vivo antitumor efficacy in mouse model of colon cancer

Jiang Hai Hua,KIM Tae Hyung,LIM Sung Mook,LEE Kang Choon 대한약학회 2012 大韓藥學會 總會 및 學術大會 Vol.2012 No.1

Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

Rapid Detection and Monitoring Therapeutic Efficacy of Mycobacterium tuberculosis Complex Using a Novel Real-Time Assay

( Jiang Li Juan ),( Wen Juan Wu ),( Hai Wu ),( Son Sik Ryang ),( Jian Zhou ),( Wei Wu ),( Tao Li ),( Jian Guo ),( Hong Hai Wang ),( Shui Hua Lu ),( Yao Li ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.9

We combined real-time RT-PCR and real-time PCR (R/P) assays using a hydrolysis probe to detect Mycobacterium tuberculosis complex (MTBC)-specific 16S rRNA and its rRNA gene (rDNA). The assay was applied to 28 nonrespiratory and 207 respiratory specimens from 218 patients. Total nucleic acids (including RNA and DNA) were extracted from samples, and results were considered positive if the repeat RT-PCR threshold cycle was ≤35 and the ratio of real-time RT-PCR and real-time PCR load was ≥1.51. The results were compared with those from existing methods, including smear, culture, and real-time PCR. Following resolution of the discrepant results between R/P assay and culture, the overall sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of all samples (including nonrespiratory and respiratory specimens) were 98.2%, 97.2%, 91.7%, and 99.4%, respectively, for R/P assay, and 83.9%, 89.9%, 72.3%, and 94.7%, respectively, for real-time PCR. Furthermore, the R/P assay of four patient samples showed a higher ratio before treatment than after several days of treatment. We conclude that the R/P assay is a rapid and accurate method for direct detection of MTBC, which can distinguish viable and nonviable MTBC, and thus may guide patient therapy and public health decisions.

Down-regulation of Protease-activated Receptor 4 in Lung Adenocarcinoma is Associated with a More Aggressive Phenotype

Jiang, Ping,Yu, Guo-Yu,Zhang, Yong,Xiang, Yang,Hua, Hai-Rong,Bian, Li,Wang, Chun-Yan,Lee, Wen-Hui,Zhang, Yun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

The role of protease-activated receptors (PARs) in lung tumors is controversial. Although PAR4 is preferentially expressed in human lung tissues, its possible significance in lung cancer has not been defined. The studies reported herein used a combination of clinical observations and molecular methods. Surgically resected lung adenocarcinomas and associated adjacent normal lung tissues were collected and BEAS-2B and NCI-H157 cell lines were grown in tissue culture. PAR4 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. The results showed that PAR4 mRNA expression was generally decreased in lung adenocarcinoma tissues as compared with matched noncancerous tissues (67.7%) and was associated with poor differentiation (p=0.017) and metastasis (p=0.04). Western blotting and immunohistochemical analysis also showed that PAR4 protein levels were mostly decreased in lung adenocarcinoma tissues (61.3%), and were also associated with poor differentiation (p=0.035) and clinical stage (p=0.027). Moreover, PAR4 expression was decreased in NCI-H157 cells as compared with BEAS-2B cells. In conclusion, PAR4 expression is significantly decreased in lung adenocarcinoma, and down-regulation of PAR4 is associated with a more clinically aggressive phenotype. PAR4 may acts as a tumor suppressor in lung adenocarcinoma.

Lack of Association between Hsa-Mir-499 rs3746444 Polymorphism and Cancer Risk: Meta-analysis Findings

Jiang, Sheng-Gao,Chen, Lin,Tang, Jin-Hai,Zhao, Jian-Hua,Zhong, Shan-Liang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Epidemiologic findings concerning the association between the hsa-mir-499 rs3746444 A>G polymorphism and cancer risk have yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies. We searched PubMed and EMBASE for studies published up to November 2014, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. The Benjamini-Hochberg (BH) method was used to correct the p values for multiple comparisons. We included 39 studies, including 14,136 cases and 16,937 controls. The results of overall meta-analysis suggested a borderline association between hsa-mir-499 rs3746444 polymorphism and cancer susceptibility (AG+GG vs. AA: OR=1.15, 95% CI=1.04-1.26, corrected p value=0.04). After removing studies not conforming to Hardy-Weinberg equilibrium (HWE), however, this association disappeared (AG+GG vs AA: OR=1.18, 95% CI=1.03-1.34, corrected p value=0.21). When stratified analysis by ethnicity, cancer type or HWE in controls, although some associations between hsa-mir-499 rs3746444 polymorphism and cancer susceptibility were detected, these associations no longer existed after adjustment using BH method. In conclusion, our meta-analysis suggests that hsa-mir-499 rs3746444 A>G polymorphism is not associated with risk of cancer based on current evidence.

Abortions and Breast Cancer Risk in Premenopausal and Postmenopausal Women in Jiangsu Province of China

Jiang, Ai-Ren,Gao, Chang-Ming,Ding, Jian-Hua,Li, Su-Ping,Liu, Yan-Ting,Cao, Hai-Xia,Wu, Jian-Zhong,Tang, Jin-Hai,Qian, Yun,Tajima, Kazuo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

To evaluate the relationship between abortions and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The results have revealed that induced abortion was related to increased risk of breast caner. Premenopausal women who had ${\geq}3$ times of induced abortion were at increased crude OR (2.41, 95%CI: 1.09-5.42) and adjusted-OR (1.55, 95%CI: 1.15-5.68). Postmenopausal women with a previous induced abortion were at increased crude OR (2.04, 95%CI: 1.48-2.81) and adjusted-OR (1.82, 95%CI: 1.30-2.54), and there was a significant increase trend in OR with number of induced abortions (p for trend: 0.0001). Overall, spontaneous abortion did not significantly alter the risk of breast cancer, but postmenopausal women who had history of spontaneous abortion were at increased OR. These results suggested that relationship between breast cancer and abortions may depend on menopausal status and induced abortion may played an important role in the development of breast cancer in Jiangsu' women of China.

Study on host plants for reproduction of Chilo suppressalis

Wei-Hua Jiang,Hai-Dong Li,Xiong-Feng Cheng,Jian-Ren Ye,Yong-Bin Feng,Zhao-Jun Han 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.3

The rice stem borer, Chilo suppressalis, is generally considered to be a polyphagous pest. The current study challenges this view by investigating its oviposition preference, larval survival and development on different host plants under both laboratory and field conditions. Rice and water-oat populations of the borer inhabiting on corresponding plants respectively have partial reproductive isolation based on previous studies. In a laboratory multiple-choice test, C. suppressalis adults from rice population laid most of eggs on water-oat (46.5% of total eggs) and rice (43.8%), with very fewlaid onwheat (3.6%), sugarcane (4.0%) andmaize (2.0%). Field surveys supported the laboratory study and found no egg on the plants other than rice and water-oat. Neonate inoculation experiments performed in field and laboratory showed that larval survival rate was much higher on rice (49.1%–51.2%) and wheat (36.5%–44.1%) than that on water-oat (10.7%–10.8%), maize (1.2%–7.2%), sugarcane (0–1.5%) and weeds (2.4%). These results were discussed with the data reported from water-oat population and it was concluded that C. suppressalis is not a typical polyphagous pest. Rice population mainly reproduces on rice and use water-oat only as minor host, and water-oat population breeds better on water-oat than on rice as reported. Neither population could thrive on the other recorded host plants, which are used for the supplementary nutrition sources of larvae. These findings provide useful information for the development of control strategies to prevent C. suppressalis laying eggs on rice seedlings in early spring, hence effectively reducing population density of this pest in rice fields.

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

Wang, Yong-Hua,Cao, Yan-Wei,Yang, Xue-Cheng,Niu, Hai-Tao,Sun, Li-Jiang,Wang, Xin-Sheng,Liu, Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

Morphology and transcriptome differences between the haploid and diploid drones of Apis cerana

Wei-Yu Yan,Hai-Yan Gan,Shu-Yun Li,Jing-Hua Hu,ZilongWang,Xiaobo Wu,Zhi Jiang Zeng 한국응용곤충학회 2016 Journal of Asia-Pacific Entomology Vol.19 No.4

In general, drone honey bees are haploid and develop from unfertilized eggs. However, a diploid drone can arise in an inbred colony. In this study, the morphological characteristics and gene expression profile of the haploid and diploid drones of Apis cerana were analyzed to reveal the differences between them. The ploidy level of the droneswas identified by FlowCytometry (FCM). The characters of the forewings,wetweight of reproductive organs and of newly emerged drones, were investigated. Then, a high throughput transcriptomic analysis was performed using RNA-seq in diploid and haploid drones. The results showed that the wet weight and reproductive organs of diploid droneswere significantly lighter than those of haploid drones. About 201 million high-quality reads were generated from RNA-seq, and 75.99–78.12% of the data weremapped to Apis cerana genome. 360 genes were differentially expressed between diploid and haploid drone, with 152 up-regulated and 208 downregulated in the diploid drones. Functional analysis identified that these genes were significantly enriched in 28 pathways. Comparative transcriptomic analysis detected several differentially expressed genes, which lay a foundation for future studies on molecular mechanisms underlying biology difference in drones in Apis cerana.

Preparation and characterization of Apo2L/TNF‐related apoptosis‐inducing ligand–loaded human serum albumin nanoparticles with improved stability and tumor distribution

Kim, Tae Hyung,Jiang, Hai‐,Hua,Youn, Yu Seok,Park, Chan Woong,Lim, Sung Mook,Jin, Cheng‐,Hao,Tak, Kyung Kook,Lee, Hye Suk,Lee, Kang Choon Wiley Subscription Services, Inc., A Wiley Company 2011 Journal of Pharmaceutical Sciences Vol.100 No.2

<P><B>Abstract</B></P><P>Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half‐life and rapid renal clearance, and an inability to form a homotrimeric structure. In this research, we attempted to develop a sustained release nanoparticle (NP) formulation that stabilizes Apo2L/TRAIL and preserves its antitumor activity. Apo2L/TRAIL‐loaded human serum albumin (HSA) NPs were prepared using a desolvation technique optimized by particle size, zeta‐potential, and entrapment efficiency. Apo2L/TRAIL in HSA‐NPs continuously released over 24 h at 37°C in phosphate buffered saline and rat plasma condition, and the biological activity of Apo2L/TRAIL‐HSA‐NPs was preserved (IC<SUB>50</SUB> = 67.2 ng/mL versus Apo2L/TRAIL IC<SUB>50</SUB> = 55.4 ng/mL) with negligible activity loss. Furthermore, <I>in vivo</I> pharmacokinetic profiles and tumor distribution demonstrated the superiority of Apo2L/TRAIL‐HSA‐NPs over Apo2L/TRAIL. The circulating half‐life period was significantly prolonged from 9.8 to 90.7 min (9.2‐fold enhancement), and drug bioavailability was clearly enhanced on the basis of area under the curve analysis (2.7‐fold). And tumor distribution of Apo2L/TRAIL‐HSA‐NPs was also increased at 1 h after injection, which was about 14‐fold (1‐h point) over that of Apo2L/TRAIL. These results show that Apo2L/TRAIL‐loaded HSA‐NPs should be considered as potential long‐acting cancer agents. © 2010 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:482–491, 2011</P>