Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

Zhang, Ling-Qiang,Zhang, Xiu-De,Xu, Jia,Wan, Yong,Qu, Kai,Zhang, Jing-Yao,Wang, Zhi-Xin,Wei, Ji-Chao,Meng, Fan-Di,Tai, Ming-Hui,Zhou, Lei,Liu, Chang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

Interval Observer-based Output Feedback Control for a Class of Interconnected Systems with Uncertain Interconnections

Zhi-Hui Zhang,Shujiang Li,Hua Yan 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.4

This paper studies the output feedback controller design problem for a class of interconnected systemswith uncertain interconnections. First, the interval observers are built to guarantee the interval property betweenthe system states and their estimations. Then, the state feedback controller is designed for each observer systemother than output feedback controller for original system. A cyclic-small-gain condition is used to deal with thebound functions of the uncertain interconnections. The original closed-loop system is robust stable since that theinterval properties are satisfied. The non-convex conditions caused by traditional observer-based output feedbackare avoided by transforming the output to state feedback problem. Finally, the main results are demonstrated bynumerical simulations.

Immunization of BALB/c mice with Brucella abortus 2308DwbkA confers protection against wild-type infection

Zhi-qiang Li,Dan Gui,Zhi-hua Sun,Jun-bo Zhang,Wen-zhi Zhang,Hui Zhang,Fei Guo,Chuangfu Chen 대한수의학회 2015 Journal of Veterinary Science Vol.16 No.4

Brucellosis is a zoonotic disease that causes animal and human diseases. Vaccination is a major measure for prevention of brucellosis, but it is currently not possible to distinguish vaccinated animals from those that have been naturally infected. Therefore, in this study, we constructed the Brucella (B.) abortus 2380 wbkA mutant (2308DwbkA) and evaluated its virulence. The survival of 2308DwbkA was attenuated in murine macrophage (RAW 264.7) and BALB/c mice, and it induced high protective immunity in mice. The wbkA mutant elicited an anti-Brucella-specific immunoglobulin G response and induced the secretion of gamma interferon. Antibodies to 2308DwbkA could be detected in sera from mice, implying the potential for use of this protein as a diagnostic antigen. The WbkA antigen would allow serological differentiation between infected and vaccinated animals. These results suggest that 2308DwbkA is a potential attenuated vaccine against 16M. This vaccine will be further evaluated in sheep.

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

Zhang, Chen-Guang,Wang, Hui,Niu, Zhi-Guo,Zhang, Jing-Jing,Yin, Ming-Mei,Gao, Zhi-Tao,Hu, Li-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in $Tax^+$-T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into $Tax^-$-T cells (TaxN, Jurkat) and $Tax^+$-T cells (TaxP). We found that promoter activity in $Tax^+$-T cells to be higher than that in $Tax^-$-T cells, indicating a significant increase in pHLuc6. Bay11-7082 (NF-${\kappa}B$ inhibitor) treatment did not block the enhancing effect. Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1 promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the fragment in question. Mutation of cis-elements for C/EBP reduced significant HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances the expression of HMGB1 gene at the transcriptional level, possibly by interacting with C/EBP.

Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study

Zhi-Hui Zhang,Jiang-Feng Ke,Jun-Xi Lu,Yun Liu,Ai-Ping Wang,Lian-Xi Li 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.1

Background: The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM.Methods: This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed.Results: After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients.Conclusion: Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Patients with Spontaneously Ruptured Hepatocellular Carcinoma Benefit from Staged Surgical Resection after Successful Transarterial Embolization

Zhang, Dong-Zhi,Zhang, Ke,Wang, Xiao-Peng,Cai, Hui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Surgical resection of spontaneously ruptured hepatocellular carcinoma (HCC) after successful transarterial embolization (TAE) remains controversial. The aim of this study was to investigate its efficacy in a series of cases. Materials and Methods: We retrospectively examined ruptured HCC cases from Jan 2000 to Dec 2008; all of these 126 cases received TAE as the initial therapy. Subsequently, 74 cases received staged surgical resection, and the remaining 52 cases underwent repeated TACE. The baseline demographic data, tumor characteristics, and long term survival were recorded and compared. Results: The demographic and baseline characteristics were comparable between the hepatic resection and TACE groups; furthermore, no significant difference in the tumor characteristics was detected between the two groups. The differences in in-hospital, 30-day and 90-day mortality between the two groups were not significant (P>0.05). However, the 1-, 3-, and 5-year overall survival rates were 85.1%, 63.5%, and 37.8%, respectively, in the hepatic resection group, which were significantly higher than those in the TACE group (69.2%, 46.2%, and 17.3%, respectively, P=0.004). Univariate and multivariate analyses indicated that these patients benefitted from hepatic resection compared with TACE with respect to long-term outcomes. Conclusions: Staged hepatic resection after TAE is an effective treatment that results in superior long-term survival to repeated TACE.

Hypoxia-inducible Factor 1 Alpha (HIF-1α) as a Prognostic Indicator in Patients with Gastric Tumors: A Meta-analysis

Zhang, Zhi-Gang,Zhang, Qiu-Ning,Wang, Xiao-Hu,Tian, Jin-Hui Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background and Objective: Though researched for years, the prognostic role of hypoxia-inducible factor 1 alpha (HIF-$1{\alpha}$) in gastric cancer is still controversial. We thus undertook a systematic review to assess the relationship. Method: A systematically literature search of Pubmed, Embase, Web of Science, China Biological Medicine Disc and Cochrane Library was undertaken in February 2013, and the reference lists of articles were retrieved. Results: 12 trials (1,555 participants) were included to assess the association between HIF-$1{\alpha}$ expression and survival. Summary hazard ratios (HRs) were calculated. HIF-$1{\alpha}$ expression was significantly correlated with poor overall survival of gastric cancer patients (HR=1.34, 95%CI: 1.13-1.58; P=0.0009), but not with poor disease free survival of gastric cancer patients (HR=1.67, 95%CI: 0.99-2.82; P=0.06). Conclusion: HIF-$1{\alpha}$ was associated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF-$1{\alpha}$ with OS and DFS in non-Asian gastric cancer patients appear needed.

북한 안보정책과 한반도 위기 북핵문제를 중심으로

장혜지 ( Hui Zhi Zhang ) 동국대학교 북한학연구소(구 동국대학교 안보연구소) 2014 북한학연구 Vol.10 No.2

북핵문제는 한반도위기와 밀접하게 연결되어 있다. 그러나 지금까지 북한을 둘러싼 주변국들은 북핵문제를 해결할 방법을 찾고 있지 못하다. 본 논문은 북한의 안보정책을 중심으로 북한이 핵을 개발하는 원인을 분석하고 북핵문제의 해결주도자는 누구이며, 그 해법은 어떠한 방향으로 나아가야 하는지를 탐구하였다. 그 결과, 한반도 정세가 위기상태를 벗어나고 있지 못한 작금의 상황이지만 김정은 체제 이후 최근의 북한은 미국을 위시한 주변 각국에 대해 적극적인 외교공세를 실시하고 있으며, 주변 각국들 또한 기본원칙을 견지하면서도 북핵위기를 타개하기 위한 대화의 유연성을 보여주는 양손정책(兩手政策)을 펼치고 있다고 분석했다. 때문에 향후 북한의 안보수요를 만족시키는 실질적 해법을 통해 현재의 한반도 위기를 대화와 해결의 기회로 전환시키기 위한 적극적 노력이 요구된다 하겠다. The DPRK nuclear issue is often related to the serious situation on the Korean peninsula but it has still not found a way to resolve it. The research is focus on the DPRK security policy and analysis why DPRK develop its nuclear program, who is the leading of the DPRK nuclear issue among China, U.S, or DPRK and ROK. Now the situation on the Korean Peninsula is serious again. On the other hand, DPRK is taking a diplomatic offensive, the neighboring countries insist on “DPRK abandons its nuclear aspirations” principle, at the same time, also reflect flexibilityso there still has a Potential Opportunity to change the crisis.

A Potent Brucella abortus 2308 Δery Live Vaccine Allows for the Differentiation between Natural and Vaccinated Infection

Junbo Zhang,Shuanghong Yin,Fei Guo,Ren Meng,Chuangfu Chen,Hui Zhang,Zhi-qiang Li,Qiang Fu,Huijun Shi,Shengwei Hu,Wei Ni,Tiansen Li,Ke Zhang 한국미생물학회 2014 The journal of microbiology Vol.52 No.8

Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. However, the current Brucella abortus vaccines (S19 and RB51) are deficient; they can cause abortion in pregnant animals. Moreover, when the vaccine S19 is used, tests cannot differentiate natural from vaccinated infection. Therefore, a safer and more potent vaccine is needed. A Brucella abortus 2308 ery promoter mutant (Δery) was constructed to overcome these drawbacks. The growth of the Δery mutant was significantly attenuated in macrophages and mice and induced high protective immunity in mice. Moreover, Δery induced an anti-Brucellaspecific IgG (immunoglobulin G) response and stimulated the expression of interferon-gamma (INF-γ) and interleukin-4 (IL-4). Furthermore, the expression of EryA antigen allowed for the serological differentiation between natural and vaccinated infection in mice. These results indicate that the Δery mutant is a potential attenuated live vaccine candidate against virulent Brucella abortus 2308 (S2308) infection.

Ginseng berry polysaccharides on infl ammation-associated colon cancer: inhibiting T-cell differentiation, promoting apoptosis, and enhancing the effects of 5-fl uorouracil

Chong-Zhi Wang,Lifei Hou,Jin-Yi Wan,Haiqiang Yao,Jinbin Yuan,Jinxiang Zeng,Chan Woong Park,Su Hwan Kim,Dae Bang Seo,Kwang-Soon Shin,Chun-Feng Zhang,Lina Chen,Qi-Hui Zhang,Zhi Liu,Clara Sava-Segal,Chun 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In thisproject, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC andrelated immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharideportion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper celldifferentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cellcycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation,inhibited CD4þIFN-gþ cell (Th1) differentiation, and decreased CD4þFoxP3þ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggestingthat it has an important role in antiinflammation, whereas Treg cells hinder the body’s immuneresponse against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at variousdegrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility inmanaging enteric inflammation and suppressing CRC through immunomodulation mechanisms.