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.

Effects of electromagnetic field and asymmetric Gaussian potential on low energy state energy of bound polaron in quantum well

Wang Ying-Hao,Chen Ying-Jie,Shao Feng-Lan 한국물리학회 2020 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.77 No.7

In this article, effects of electromagnetic field and asymmetric Gaussian potential (AGP) on the bound polaron's low energy state in quantum well are explored theoretically by the Lee-Low-Pines unitary transformation and Pekar type variational method. The variation of the ground state energy and the first excited state energy of the polaron with the Coulomb bound potential (CBP) strength at different electron-phonon coupling (EPC) constants, electric field (EF) strengths, heights and ranges of the AGP and magnetic field adjustment lengths are obtained. Our numerical results indicate that the polaron's low energy state depends on the EPC constant, the EF strength, the AGP's height and range and the CBP strength.

Hydration, Compressive Strength and Durability of Eco-friendly Cement Mortars Containing Recycled Brick Powder and Metakaolin

Hao Wang,Liang Wang,Xin Qian,Ke Cao,Ying Xu,Yi Fang,Liyun Cui 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.9

Grinding brick waste into powder for use as a supplementary cementitious material has shown to be a promising recycling method for the reuse of construction and demolition waste.However, the strength and durability of concrete containing recycled brick powder (RBP) will significantly decrease due to the poor pozzolanic activity of RBP, limiting its wider applications. This study attempted to overcome these defects through metakaolin (MK) addition. The hydration, compressive strength, durability, and environmental impact of eco-friendly mortars containing RBP and MK were investigated. The results showed that MK promoted the early-stage hydration of cement, creating a suitable hydration environment for the hydration of RBP at a later age. As a result, the volume fractions of low-density calcium silicate hydrate (C-S-H) and high-density C-S-H increased according to the nanoindentation test results. In addition, the strength, chloride penetration resistance, and reinforcement bar corrosion resistance of the blended mortars obviously improved due to the synergistic effect of RBP and MK. Lastly, we achieved CO2 emissions that were 22.1 – 30.2% lower and energy consumption that was 21.4 – 27.0% lower by incorporating 20% RBP and 5 – 15% MK.

LiFePO₄ quantum-dots composite synthesized by a general microreactor strategy for ultra-high-rate lithium ion batteries

Wang, Bo,Xie, Ying,Liu, Tong,Luo, Hao,Wang, Bin,Wang, Chunhui,Wang, Lei,Wang, Dianlong,Dou, Shixue,Zhou, Yu Elsevier 2017 Nano energy Vol.42 No.-

<P><B>Abstract</B></P> <P>Due to the relatively slow, diffusion-controlled faradaic reaction mechanisms of conventional LiFePO<SUB>4</SUB> (LFP) materials, which is hard to deliver satisfied capacity for high rate applications. In this work, ultrafine LFP quantum dots (LFP-QDs) co-modified by two types of carbonaceous materials - amorphous carbon and graphitized conductive carbon (graphene) have been successfully synthesized through a novel microreactor strategy. Because of the very limited area constructed by the dual-carbon microreactor for the growth of LFP crystal, it's demension was furthest suppressed to a very small level (~ 6.5nm). Such a designed nano-composite possesses a large specific surface area for charge adsorption and abundant active sites for faradaic reactions, as well as ideal kinetic features for both electron and ion transport, and thus exhibits ultra-fast, surface-reaction-controlled lithium storage behavior, mimicking the pseudocapacitive mechanisms for supercapacitor materials, in terms of extraordinary rate capability (78mAhg<SUP>−1</SUP> at 200C) and remarkable cycling stability (~ 99% over 1000 cycles at 20C). On the other side, due to the quasi-2D structure of the synthesized LFP-QDs composite, which can be used as the basic unit to further fabricate free-standing film, aerogel and fiber electrode without the addition of binder and conductive agent for different practical applications. In addition, to deeper understand its electrochemical behavior, a combined experimental and density functional theoretical (DFT) calculation study is also introduced.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A general microreactor strategy has been developed for structure-optimized Li-contained electrode materials. </LI> <LI> Ultrafine LiFePO<SUB>4</SUB> quantum dots are first reported through the designed microreactor strategy. </LI> <LI> The synthesized G/LFP-QDs@C exhibits ultra-fast, surface-reaction-controlled Li storage behavior. </LI> <LI> A combined experimental and DFT calculation study is introduced to reveal the energy storage mechanism of G/LFP-QDs@C. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Ultrafine LiFePO<SUB>4</SUB> quantum dots (~ 6.5nm) co-modified by two types of carbonaceous materials - amorphous carbon and graphitized conductive carbon (graphene) have been successfully synthesized through a novel microreactor strategy, which exhibit ultra-fast, surface-reaction-controlled energy storage behavior, mimicking the pseudocapacitive mechanisms for supercapacitor materials, in terms of excellent rate capability and outstanding cycling stability.</P> <P>[DISPLAY OMISSION]</P>

Selection of Reference Genes for Gene Expression Studies in Porcine Whole Blood and Peripheral Blood Mononuclear Cells under Polyinosinic:Polycytidylic Acid Stimulation

Wang, Jiying,Wang, Yanping,Wang, Huaizhong,Hao, Xiaojing,Wu, Ying,Guo, Jianfeng Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.4

Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation.

Exploring the role and mechanisms of diallyl trisulfide and diallyl disulfide in chronic constriction-induced neuropathic pain in rats

( Gang Wang ),( Yan Yang ),( Chunfeng Wang ),( Jianzhong Huang ),( Xiao Wang ),( Ying Liu ),( Hao Wang ) 대한통증학회 2020 The Korean Journal of Pain Vol.33 No.3

Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H₂S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall-Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H₂S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Coadministration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H₂S levels. Conclusions: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H₂S-BDNF-Nrf2 signaling pathway.

RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells

Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

Nausea and Vomiting after Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: Incidence and Risk Factor Analysis

Wang, Shi-Ying,Zhu, Wen-Hao,Vargulick, Sonya,Lin, Sam Bill,Meng, Zhi-Qiang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: Nausea and vomiting after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) are common in clinical practice, but few studies have reported the incidence and risk factors of such events. Objective: The purpose of this study was to analyze the incidence and risk factors of nausea and vomiting after TACE for HCC. Methods: This study was a single-center retrospective analysis of a prospectively maintained database. Between May 2010 and October 2012, 150 patients with HCC were analyzed for incidence and preprocedural risk factors. Results: The incidence of postembolization nausea and vomiting was 38.8% and 20.9%, respectively, in patients with HCC. Patients who developed nausea had lower levels (<100 IU/L) of serum alkaline phosphatase (ALP) compared to those without nausea ($123.04{\pm}69.38$ vs. $167.41{\pm}138.95$, respectively, p=0.044). Female gender correlated to a higher incidence of nausea as well (p=0.024). Patients who developed vomiting, compared to those who did not, also had lower levels (<100 IU/L) of serum ALP ($112.52{\pm}62.63$ vs. $160.10{\pm}127.80$, respectively, p=0.010), and serum alanine transferase (ALT) ($35.61{\pm}22.87$ vs. $4.97{\pm}29.62$, respectively, p=0.045). There were no statistical significances in the incidences of nausea and vomiting between male patients over 50 years old and female patients who have entered menopause (p=0.051 and p=0.409, respectively). Multivariate analysis by logistic regression analysis demonstrated that female gender and ALP>100 IU/L were the most independent predictive factors of postembolization nausea (odds ratio (OR): 3.271, 95% CI: 1.176-9.103, p=0.023 and OR: 0.447, 95% CI: 0.216-0.927, p=0.030, respectively). ALP>100 IU/L was also the most independent predictive risk factor of postembolization vomiting (OR: 0.389, 95% CI: 0.159-0.952, p=0.039). Conclusions: Postembolizaiton nausea and vomiting are common in patients with HCC. Recognition of the risk factors presented above before TACE is important for early detection and proper management of postembolization nausea and vomiting. Nevertheless, future studies are required.

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.

Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice

Wang, Ai-Guo,Lee, Dong-Seok,Moon, Hyung-Bae,Kim, Jin-Man,Cho, Kyung-Hyun,Choi, Soo-Ho,Ha, Hye-Lin,Han, Ying-Hao,Kim, Dae-Ghon,Hwang, Soon B.,Yu, Dae-Yeul John Wiley Sons, Ltd. 2009 The Journal of pathology Vol.219 No.2

<P>Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV-induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co-localized with apolipoprotein A-I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF-κB and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>