A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis

Fei-yu Wang,Yu-qing Zhang,Xin-min Wang,Chan Wang,Xiao-fang Wang,Jiang-dong Wu,Fang Wu,Wan-jiang Zhang,Le Zhang 한국미생물학회 2016 The journal of microbiology Vol.54 No.4

Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.

Prevalence and Risk Factors of Cerebral Small Vessel Disease in a Chinese Population-Based Sample

Fei Han,Fei-Fei Zhai,Quan Wang,Li-Xin Zhou,Jun Ni,Ming Yao,Ming-Li Li,Shu-Yang Zhang,Li-Ying Cui,Zheng-Yu Jin,Yi-Cheng Zhu 대한뇌졸중학회 2018 Journal of stroke Vol.20 No.2

Background and Purpose Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies. Methods This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression. Results Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations. Conclusions A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.

Risk of Treatment-related Mortality with Sorafenib in Patients with Cancer

Zhang, Xin-Ji,Zhang, Tian-Yi,Yu, Fei-Fei,Wei, Xin,Li, Ye-Sheng,Xu, Feng,Wei, Li-Xin,He, Jia Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

Security Analysis of Speech Perceptual Hashing Authentication Algorithm

Zhang Qiu-yu,Ren Zhan-wei,Xing Peng-fei,Huang Yi-bo,Yu Shuang 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.1

Speech perceptual hashing authentication algorithm is an efficient method for content integrity authentication and identity authentication. But the algorithm becomes transparent under the principle of Kerckhoffs which makes the algorithm unsafe. In this paper, the algorithm is encrypted under the principle of Kerckhoffs to protect the security of the algorithm. Then the specific link that won’t affect the performance of the algorithm is identified through the experiments. Next, this paper analyzes the security of the encrypted algorithm based on the concept of Shannon unicity distance. The unicity distance is figured out finally based on the experiments. That is to say, the algorithm loses its security even though the algorithm has been encrypted. Under this circumstances, the most important thing is to continue keeping the safety of the algorithm. Therefore, this paper proposed an efficient random secret key method to guarantee the safety of the algorithm after the unicity distance is figured out.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

Zhang, Yu-Rong,Xu, Yong,Yang, Kuo,Liu, Ming,Wei, Dong,Zhang, Yao-Guang,Shi, Xiao-Hong,Wang, Jian-Ye,Yang, Fan,Wang, Xin,Liang, Si-Ying,Zhao, Cheng-Xiao,Wang, Fei,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Zh Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

Macrophages Promote Coal Tar Pitch Extract-induced Tumorigenesis of BEAS-2B Cells and Tumor Metastasis in Nude Mice Mediated by AP-1

Zhang, Peng,Jin, Yue-Fei,Zhang, Qiao,Wu, Yi-Ming,Wu, Wei-Dong,Yao, Wu,Wu, Yong-Jun,Li, Zhi-Tao,Zhao, Yong,Liu, Yu,Feng, Fei-Fei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.

GRAPHENE AS TUNABLE STATIONARY PHASE ADDITIVE FOR ENANTIOSEPARATION

FEI-YUE TU,LIN-YAN YU,JIN-GANG YU,XIAOQING CHEN,QIANG FU,FEI-PENG JIAO,ZHI-GUANG PENG,TING ZHANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2013 NANO Vol.8 No.6

Graphene-based biosensor and chiral sensor have made significant progress in recent years. Because of the similarity of the optical enantiomers, enantioseparation is perhaps the most subtle to achieve. Developing more effectively chiral separation techniques based on graphene is highly desirable. Herein, pristine graphene was prepared and then applicated to assist resolution of two racemic drugs of propranolol and ofloxacin using thin-layer chromatography (TLC). In comparison with TLC chiral separation by only using pure D-(-)-tartaric acid as a selector with relatively low degree of separation, a mixture of graphene and D-(-)-tartaric acid is more attractive, efficient and ready available. The high specific resolution ability for racemic compounds aided by graphene might allow its potential application in future chiral separation technologies.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression

Jiajia Zhang,Feize Li,Yuzhen Yin,Ning Liu,Mengqin Zhu,Han Zhang,Weihao Liu,Mengdie Yang,Shanshan Qin,Xin Fan,Yuanyou Yang,Kun Zhang,Fei Yu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. Methods: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzymelinked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. Results: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. Conclusions: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TATCDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

Genetic Analysis of the Liver Putative Tumor Suppressor (LPTS) Gene in Gastric Cancer

Hai Bing Zhang,Qu Zhang,Li Sa Wang,Fei Yan,Yun Lu,Zhi Qiang Wang,Jing Li,Liang Liang Zhang,Ying Yan Yu,Zheng Gang Zhu,Xiang Yin Kong,Lan Dian Hu 한국유전학회 2005 Genes & Genomics Vol.27 No.4

Branched polymeric prodrug/programmed cell death 4 complexes for combinational cancer therapy

Yu‑Jing He,Lei Xing,Peng‑Fei Cui,Jia‑Liang Zhang,Jian‑Bin Qiao,Cheng‑Qiong Luo,Ge Jiang,Hu‑Lin Jiang 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.2

Here, we demonstrate a co-delivery system constructed by integrating chemotherapeutic molecules into branched polymeric prodrug which can condense nucleic acids. Demethylcantharidate (DCA) was chosen as a model drug and premodified through nucleophilic substitution reaction by its two carboxylic groups with allyl chloride. The synthesized intermediate (DCA-dially) was then used to polymerize with tris (2-aminoethyl) amine (TAEA) through progressively ammonolysis reaction. The obtained poly (DCA-alt-TAEA) (DCAT) was used to pack PDCD4 into spherical-like nanoparticles through electrostatic interaction. Gel retardation assays implied that DCAT could integrate DNA at the weight ratio of 1 and protect it from digestion by nuclease. Acid-base titration experiments showed that DCAT obtained preferable buffering capability which was beneficial for the endosomal escape of DCAT/PDCD4 complexes. Cellular tests involving gene transfection efficiency and cytotoxicity indicated that DCA and PDCD4 co-delivered by the complexes significantly and synergistically suppressed the viability of SMMC-7721 cells. These results suggest that integrating chemotherapeutic molecules into nucleic acid-packing polymeric prodrug as cationic polymer/PDCD4 complexes is a highly efficient way to co-deliver chemotherapeutic drugs and nucleic acids for cancer therapy.