Deubiquitinating enzyme Josephin-2 stabilizes PHGDH to promote a cancer stem cell phenotype in hepatocellular carcinoma

Wang Ying,Li Ze-Xin,Wang Jian-Guo,Li Lu-Hao,Shen Wen-Long,Dang Xiao-Wei 한국유전학회 2023 Genes & Genomics Vol.45 No.2

Background Deubiquitinating enzymes (DUBs) have been shown to be possible targets for hepatocellular carcinoma (HCC) treatment. Objective This study was designed to reveal the effect and underlying mechanism of Josephin-2, a relatively newly defined DUB, in HCC progression. Methods SNU-387 and PLC/PRF/5 cells were used for in vitro functional assays. The levels of Josephin-2 and phosphoglycerate dehydrogenase (PHGDH) were determined using RT-qPCR and western blotting. Cell proliferation, migration and invasion were assessed by CCK-8, colony formation and Transwell. Spheroid-forming assay was performed to assess the cancer stem cell (CSC)-phenotype of HCC cells. A xenograft mice model was applied to verify the effect of Josephin-2 on HCC cell growth in vivo. Results Herein, we showed that Josephin-2 expression was negatively correlated with HCC patient survival in data from the online database. Cell experiments indicated that knockdown of Josephin-2 attenuated HCC cell malignant biological behaviors. Besides, Josephin-2 silencing also decreased the spheroid-formation while inhibited the expression of CSC biomarkers (CD133, OCT4, SOX2 and EpCAM) in HCC cells. Mechanistically, Josephin-2 had a deubiquitinating activity towards the regulation of PHGDH protein, the rate-limiting enzyme in the first step of serine biosynthesis pathway. Depletion of Josephin-2 enhanced the ubiquitination degradation of PHGDH and ultimately inhibited the proliferation and CSC-phenotype of HCC in vitro and in vivo. Conclusion Our work uncovered the regulatory effects of Josephin-2 on PHGDH protein stability and profiled its contribution in HCC malignant progression, which might provide a potential therapeutic target for HCC.

Finding Blue Tracks in Gephyrocharax melanocheir Fish Similar to the Locations of Acupuncture Meridians after Injecting Alcian Blue

Ze Wang,Wei-Bo Zhang,Shuyong Jia,Yu-Ying Tian,Guang-Jun Wang,Hongyan Lin 사단법인약침학회 2015 Journal of Acupuncture & Meridian Studies Vol.8 No.6

This study investigated whether a meridian-like distribution of Alcian blue (AB) existed after it was injected into a fish's body and suggested a new animal model for meridian study. Twenty Gephyrocharax melanocheir fish with translucent bodies were injected with AB at a point near the spinal column or the dorsal fin. Distribution of AB was observed using a digital camera and a stereomicroscope. Three or more obvious blue tracks were found: one along the spinal column, another along the posterior margin of the abdomen extending to the superior margin of the anal fin, and a third along both sides of the dorsal fin. They were similar to the locations of the governor, conceptual vessel, and urinary bladder meridians, respectively, on the human body according to the classic theory of traditional Chinese medicine. A few other blue tracks were also found, which apparently did not correspond to any known meridians. The results show that the tracks of AB share important similarities with the locations of classically described meridians and that they are mainly distributed in the interstitial space around bones and blood vessels and inside muscular interstices. This study may provide a new experimental animal model for exploring acupuncture meridians.

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Experimental compressive behavior of novel composite wall with different width-to-thickness ratios

Ying Qin,Xin Chen,Xing-Yu Zhu,Wang Xi,Yuan-Ze Chen 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.36 No.2

Double skin composite wall system owns several structural merits in terms of high load-carrying capacity, large axial stiffness, and favorable ductility. A recently proposed form of truss connector was used to bond the steel plates to the concrete core to achieve good composite action. The structural behavior of rectangular high walls under compression and T-shaped high walls under eccentric compression has been investigated by the authors. Furthermore, the influences of the truss spacings, the wall width, and the faceplate thickness have been previously studied by the authors on short walls under uniform compression. This paper experimentally investigated the effect of width-to-thickness ratio on the compressive behavior of short walls. Compressive tests were conducted on three short specimens with different width-to-thickness ratios. Based on the test results, it is found that the composite wall shows high compressive resistance and good ductility. The walls fail by local buckling of steel plates and crushing of concrete core. It is also observed that width-to-thickness ratio has great influence on the compressive resistance, initial stiffness, and strain distribution across the section. Finally, the test results are compared with the predictions by modern codes.

Compressive behavior of rectangular sandwich composite wall with different truss spacings

Ying Qin,Xin Chen,Wang Xi,Xing-Yu Zhu,Yuan-Ze Chen 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.34 No.6

Steel-concrete-steel sandwich composite wall is composed of two external steel plates and infilled concrete core. Internal mechanical connectors are used to enhance the composite action between the two materials. In this paper, the compressive behavior of a novel sandwich composite wall was studied. The steel trusses were applied to connect the steel plates to the concrete core. Three short specimens with different truss spacings were tested under compressive loading. The boundary columns were not included. It was found that the failure of walls started from the buckling of steel plates and followed by the crushing of concrete. Global instability was not observed. It was also observed that the truss spacing has great influence on ultimate strength, buckling stress, ductility, strength index, lateral deflection, and strain distribution. Three modern codes were introduced to calculate the capacity of walls. The comparisons between test results and code predictions show that AISC 360 provides significant underestimations while Eurocode 4 and CECS 159 offer overestimated predictions.

Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells

( Ze Min Huang ),( Jun Wu ),( Zheng Cai Jia ),( Yi Tian ),( Jun Tang ),( Yan Tang ),( Ying Wang ),( Yu Zhang Wu ),( Bing Ni ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.6

The retinoid-related orphan nuclear receptor gamma (RORγ) plays critical roles in regulation of development, immunity and metabolism. As transcription factor usually forms a protein complex to function, thus capturing and dissecting of the RORγ protein complex will be helpful for exploring the mechanisms underlying those functions. After construction of the recombinant tandem affinity purification (TAP) plasmid, pMSCVpuro RORγ-CTAP(SG), the nuclear localization of RORγ-CTAP(SG) fusion protein was verified. Following isolation of RORγ protein complex by TAP strategy, seven candidate interacting proteins were identified. Finally, the heat shock protein 90 (HSP90) and receptor-interacting protein 140 (RIP140) were confirmed to interplay with RORγ by co-immunoprecipitation. Interference of HSP90 or/and RIP140 genes resulted in dramatically decreased expression of CYP2C8 gene, the RORγ target gene. Data from this study demonstrate that HSP90 and RIP140 proteins interact with RORγ protein in a complex format and function as co-activators in the RORγ-mediated regulatory processes of HepG2 cells. [BMB Reports 2012; 45(6): 331-336]

Dietary inflammatory index and risk of gynecological cancers: a systematic review and meta-analysis of observational studies

Ze-ying Liu,Xu-ping Gao,Sui Zhu,Yan-hua Liu,Li-jun Wang,Chun-xia Jing,Fang-fang Zeng 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.3

Objective: There has been growing body of literatures showing that chronic inflammation might play an important role in cancer development. This meta-analysis aimed to assess the association between the dietary inflammation index (DII) score and gynecological cancers. Methods: A systematic search of PubMed, EMBASE and Web of Science up until October 20, 2018 was carried out to retrieve all related cohort and case-control studies. The summary risk assessments were pooled using random-effects models. The dose-response relationship was estimated by linear relationship model. Results: Twelve case-control studies (10,774 cases/15,958 controls) and six prospective cohort studies (330,363 participants/23,133 incident cases) were included in this meta-analysis. The pooled adjusted relative risk (RR) of gynecological cancers for the highest DII category compared to the lowest category was 1.38, (95% confidence intervals [CIs], 1.21–1.56, p<0.001]. A positive dose-response relationship was also noticed. Stratified by study design indicated that, the pooled RRs was significantly higher for case-control studies than cohort studies (p for interaction<0.001), for studies conducted among participants with body mass index (BMI) ≥25 kg/m2 than participants with BMI <25 kg/m2 (p for interaction=0.026), among participants with ovarian cancer and endometrial cancer than participants with breast cancer (p for interaction = 0.038). Meta-regression analysis further confirmed that study design significantly contributed to inter-study heterogeneity (p<0.001). Conclusion: This meta-analysis suggests that elevated DII is independently associated with a higher risk of gynecological cancers, especially patients with ovarian cancer and endometrial cancer and among obese participants.

Risk Assessment of Breast Cancer in Guangdong, China: A Community-based Survey

Lin, Ying,Shao, Nan,Zhang, Yun-Jian,Wu, Zhuang-Hong,Li, Zhi-Bin,Ren, Ze-Fang,Wang, Shen-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objectives: Compared with Western countries, the incidence rates for breast cancer in China are still low. However, breast cancer appears to be hitting Chinese women at a much younger age, with a peak between 40 and 50 years. Furthermore, breast tumors of Asian women have molecular and genetic characteristics that are different from those of Caucasian women. Methods: A community-based study was designed to evaluate the relationship between lifestyles and breast cancer risk in Chinese women residing in Guangzhou. 16,314 subjects completed the questionnaire. Potential confounding factors included sociodemographic characteristics. Results: 33 individuals reported a history of breast cancer, yielding a prevalence rate of 202.3/100000. Associations between subjects' demographic and breast cancer risk factors were assessed. Breast cancer is associated with family history of breast cancer, X-rays received, benign breast disease and hyperlipoidemia or hypercholesteremia with elevated odds ratios. Conclusions: Family history of breast cancer, X-ray received benign breast disease and hyperlipoidemia or hypercholesteremia were significantly associated with risk of breast cancer and may havepotential for breast cancer risk assessment.

Research of liquid-solid two phase flow in centrifugal pump with crystallization phenomenon

Liu, Dong,Wang, Ya-Yun,Wang, Ying-Ze,Wang, Chun-Lin,Yang, Min-Guan Korean Society for Fluid machinery 2014 International journal of fluid machinery and syste Vol.7 No.2

Particle Image Velocimetry combined with developed image processing method is adopted to study the liquid-solid two phase flow in the centrifugal pump impeller with crystallization phenomenon. The tracer particle is used to follow the liquid phase, which has the diameter between 8 to $12{\mu}m$. The crystal particle precipitates from the sodium sulfate solution does change the wavelength of the laser, and which has great laser scattering characteristics. The diameter of the crystal particle is larger than $20{\mu}m$. Through calculating the diameter of the particles in the image, the tracer particle and the crystal particle can be distinguished. By analyzing the experimental result, the following conclusion has been obtained. During the delay period, there is not any crystal particle and the pump performance has not been changed. As the crystallization process begins, the crystal nuclei appears from the supersaturation solution and grows larger with temperature decreasing, which has the tendency of moving towards the pressure side. The characteristics of liquid-solid two phase flow with crystallization phenomenon in the pump are obtained according to analysis of experimental results, and some guiding advices are presented to mitigate the crystallization phenomenon in pump impeller.

Smads, p38 and ERK1,2 are involved in BMP9-induced osteogenic differentiation of C3H10T1,2 mesenchymal stem cells

( Dao Jing Xu ),( Ying Ze Zhao ),( Jin Wang ),( Juan Wen He ),( Ya Guang Weng ),( Jin Yong Luo ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.4

Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells. [BMB reports 2012; 45(4): 247-252]