Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma

Li Xun,Zhang Cheng-Cheng,Lin Xiao-Tong,Zhang Jie,Zhang Yu-Jun,Yu Hong-Qiang,Liu Ze-Yu,Gong Yi,Zhang Lei-Da,Xie Chuan-Ming 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

Li, Xing,Dong, Min,Wen, Jing-Yun,Wei, Li,Ma, Xiao-Kun,Xing, Yan-Fang,Deng, Yun,Chen, Zhan-Hong,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wang, Tian-Tian,Wu, Dong-Hao,Liu, Xu,Hu, Hai-Tao,Lin, Jia-Yu,Li, Zhu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

Lack of Association between the COMT rs4680 Polymorphism and Ovarian Cancer Risk: Evidence from a Meta-analysis of 3,940 Individuals

Du, Jin-Ze,Dong, Yu-Ling,Wan, Guo-Xing,Tao, Lin,Lu, Li-Xia,Li, Feng,Pang, Li-Juan,Jia, Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.

Recent advances of bioactive proteins/polypeptides in the treatment of breast cancer

Qi-Zhang Li,Ze-Rong Zhou,Cui-Yu Hu,Xian-Bin Li,Yu-Zhou Chang,Yan Liu,Yu-Liang Wang,Xuan-Wei Zhou 한국식품과학회 2023 Food Science and Biotechnology Vol.32 No.3

Proteins do not only serve as nutrients to fulfill the demand for food, but also are used as a source of bioactive proteins/polypeptides for regulating physical functions and promoting physical health. Female breast cancer has the highest incidence in the world and is a serious threat to women’s health. Bioactive proteins/polypeptides exert strong anti-tumor effects and exhibit inhibition of multiple breast cancer cells. This review discussed the suppressing effects of bioactive proteins/polypeptides on breast cancer in vitro and in vivo, and their mechanisms of migration and invasion inhibition, apoptosis induction, and cell cycle arrest. This may contribute to providing a basis for the development of bioactive proteins/polypeptides for the treatment of breast cancer.

Photoluminescence properties of a new orange–red emitting Sm³⁺-doped Y₂Mo₄O₁₅ phosphor

Deng, Huajuan,Zhao, Ze,Wang, Jing,Hei, Zhoufei,Li, Mengxue,Noh, Hyeon Mi,Jeong, Jung Hyun,Yu, Ruijin Elsevier 2015 Journal of solid state chemistry Vol.228 No.-

<P><B>Abstract</B></P> <P>A series of novel Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:<I>x</I>Sm<SUP>3+</SUP> ( (0.01 ≤ <I>x</I> ≤ 0.20) phosphors for white light-emitting (W-LEDs) were successfully prepared by the solid state reaction technology at 973K for 12h. X-ray diffraction and photoluminescence spectra were utilized to characterize the structure and luminescence properties of the as-synthesized phosphors. The emission spectra of the Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:Sm<SUP>3+</SUP> phosphors consisted of some sharp emission peaks of Sm<SUP>3+</SUP> ions centered at 565nm, 605nm, 650nm, and 712nm. The strongest one is located at 605nm due to <SUP>4</SUP> <I>G</I> <SUB>5/2</SUB>–<SUP>6</SUP> <I>H</I> <SUB>7/2</SUB> transition of Sm<SUP>3+</SUP>, generating bright orange–red light. The optimum dopant concentration of Sm<SUP>3+</SUP> ions in Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:<I>x</I>Sm<SUP>3+</SUP> is around 5mol% and the critical transfer distance of Sm<SUP>3+</SUP> is calculated as 23.32Å. The CIE chromaticity coordinates of the Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:0.05Sm<SUP>3+</SUP> phosphors were located in the orange reddish region. The Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:Sm<SUP>3+</SUP> phosphors may be potentially used as red phosphors for white light-emitting diodes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An orange–red emitting Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:Sm<SUP>3+</SUP> phosphor has been firstly synthesized. </LI> <LI> Their structures, luminescent properties have also been investigated. </LI> <LI> The optical absorption edge for the molybdate lies around 325nm. </LI> <LI> The CIE chromaticity coordinates were located in the orange reddish region. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>The excitation spectrum of Y<SUB>2</SUB>Mo<SUB>4</SUB>O<SUB>15</SUB>:Sm<SUP>3+</SUP> is composed of a broad band and some sharp <I>f</I>–<I>f</I> transitions. Under 407nm excitation, the phosphor presents some sharp emission peaks of Sm<SUP>3+</SUP> ions.</P> <P>[DISPLAY OMISSION]</P>

The Data Processing and Remote Transmission Technologies for On-Line Monitoring Of Eurytopic Distributed

Yu-rong Deng,Qiu-li Wu,Wei Zhang,Ze-cheng Lv 보안공학연구지원센터 2015 International Journal of Grid and Distributed Comp Vol.8 No.5

Aiming at the provincial level within the grid wide-area distributed substation equipment on-line monitoring various types, processing of large amount of data and communication standard is not unified. Optimization of the structure of communication between the various levels, researched open communication format specification, established data interaction integration model. The paper studied the wide-area distributed on-line monitoring comprehensive processing unit of end stations with provincial level network of on-line monitoring system for the main platform of communication technology. Application shows that systems runs stability and meet online monitoring data collection, processing, transmission, and other functions, and has good maintainability and extensibility, adapt to various on-line monitoring in province level the development trend of the main platform for centralized management.

Combined transcriptomic and proteomic analysis of flubendiamide resistance in Plutella xylostella

Li Jing‐Jing,Jin Ming‐Hui,Wang Nian‐Meng,Yu Qi‐Tong,Shang Ze‐Yu,Xue Chao‐Bin 한국곤충학회 2020 Entomological Research Vol.50 No.10

Diamondback moth (DBM), Plutella xylostella, is an important pest of crucifers worldwide. The extensive use of diamide insecticides has led to DBM resistance in the world, and this presents a serious threat to vegetable production. In the present study, transcriptomic and proteomic analyses were combined to investigate the potential flubendiamide‐resistance mechanism in DBM. The lab‐selected (Rh) and field‐collected (Rb) flubendiamide‐resistant lines of P. xylostella with resistance ratios of 1889.92‐fold and 1250.97‐fold, respectively, were used, as well as a lab‐reared flubendiamide‐susceptible line (S). Compared with the S group, the transcriptomic analysis revealed 151 upregulated and 287 downregulated gene messengers in the Rh group and 432 upregulated and 565 downregulated gene messengers in the Rb group. The most frequently enriched pathways of differentially expressed genes (DEGs) were mainly involved in metabolic pathways. Metabolism related genes, including two P450, two ABC transporters, and three trypsins, were upregulated in the Rh line. Additionally, some P450 genes, trypsin, juvenile hormone (JH), and mucin genes were also upregulated in the Rb line. In proteomic analysis comparisons with the S group, there were 78 upregulated and 90 downregulated proteins in the Rh group and 221 upregulated and 155 downregulated proteins in the Rb group. Further analyses found that three CYP and 11 CYP proteins were over‐expressed in Rh and Rb lines, respectively. Four glutathione S‐transferase (GST) and four UGTs were over‐expressed in Rb line. So, we deduced that the detoxification metabolism may be the main mechanism of flubendiamide resistance in P. xylostella.

Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats

Ze-Hua Zhao,Feng-Zhi Xin,Yaqian Xue,Zhimin Hu,Yamei Han,Fengguang Ma,Da Zhou,Xiao-Lin Liu,Aoyuan Cui,Zhengshuai Liu,Yuxiao Liu,Jing Gao,Qin Pan,Yu Li,Jian-Gao Fan 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Microbial metabolites have emerged as critical components that mediate the metabolic effects of the gut microbiota. Here, we show that indole-3-propionic acid (IPA), a tryptophan metabolite produced by gut bacteria, is a potent anti-non-alcoholic steatohepatitis (NASH) microbial metabolite. Here, we demonstrate that administration of IPA modulates the microbiota composition in the gut and inhibits microbial dysbiosis in rats fed a high-fat diet. IPA induces the expression of tight junction proteins, such as ZO-1 and Occludin, and maintains intestinal epithelium homeostasis, leading to a reduction in plasma endotoxin levels. Interestingly, IPA inhibits NF-κB signaling and reduces the levels of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6, in response to endotoxin in macrophages to repress hepatic inflammation and liver injury. Moreover, IPA is sufficient to inhibit the expression of fibrogenic and collagen genes and attenuate diet-induced NASH phenotypes. The beneficial effects of IPA on the liver are likely mediated through inhibiting the production of endotoxin in the gut. These findings suggest a protective role of IPA in the control of metabolism and uncover the gut microbiome and liver cross-talk in regulating the intestinal microenvironment and liver pathology via a novel dietary nutrient metabolite. IPA may provide a new therapeutic strategy for treating NASH.

Radioactive gas diffusion simulation and inhaled effective dose evaluation during nuclear decommissioning

Li-qun Yang,Yong-kuo Liu,Min-jun Peng,Abiodun Ayodeji,Zhi-tao Chen,Ze-yu Long 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.1

During the decommissioning of the nuclear facilities, the radioactive gases in pressure vessels may leakdue to the demolition operations. The decommissioning site has large space, slow air circulation, andmany large nuclear facilities, which increase the difficulty of workers' inhalation exposure assessment. Inorder to dynamically evaluate the activity distribution of radionuclides and the committed effective dosefrom inhalation in nuclear decommissioning environment, an inhalation exposure assessment methodbased on the modified eddy-diffusion model and the inhaled dose conversion factor is proposed in thispaper. The method takes into account the influence of building, facilities, exhaust ducts, etc. on thedistribution of radioactive gases, and can evaluate the influence of radioactive gases diffusion on workersduring the decommissioning of nuclear facilities.