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.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

Wang Lu,Dai Ying-Jie,Cui Yu,Zhang Hong,Jiang Chang-Hao,Duan Ying-Jie,Zhao Yong,Feng Ye-Fang,Geng Shi-Mei,Zhang Zai-Hui,Lu Jiang,Zhang Ping,Zhao Li-Wei,Zhao Hang,Ma Yu-Tong,Song Cheng-Guang,Zhang Yi,Ch 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; <i>P</i>=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, <i>P</i>=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

NANOSEEDING EFFECT IN ZSM-5CRYSTALLIZATION PROCESS

YI LU,NAI-QIAN ZHANG,JIN-KU LIU,QIN TONG,DAN-JING HONG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2013 NANO Vol.8 No.3

ZSM-5 zeolites were hydrothermally synthesized in three different seeding pathways under the direction of tetrapropylammonium bromide (TPABr) template. In order to investigate the seeding effect in ZSM-5 crystallization process, ZSM-5 crystals and pre-fabricated MFI-type nanoseeds were added into the original self-induction system, respectively. The final ZSM-5 zeolites were systematically investigated based on XRD (X-ray diffraction), SEM (scanning electron micrograph), TEM (transmission electron micrograph), nitrogen adsorption characterizations and NH3-TPD (ammonia-temperature programmed desorption). The self-induction system produced ca. 20 μm ZSM-5 zeolite displaying hexagonally uniform prisms. After the addition of ZSM-5 crystal seeds, the crystal sizes were decreased greatly to ca. 5 μm. When MFI-type nanoseeds were adopted, irregular aggregate particles consisting of 20–50 nm primary particles were rapidly synthesized. The varied hydrothermal crystallization kinetics of the three synthesis system was also explored. Adjusting the seed agents alone, ZSM-5 crystals with diverse structural, morphological, textural and hydrothermal behaviors could be fabricated conveniently. The three ZSM-5 zeolites loaded by 0.05 wt.% Pt were assessed for the xylene isomerization reaction to investigate the particle size effect on the catalytic properties.

Residential Radon and Lung Cancer Risk: An Updated Meta-analysis of Case-control Studies

Zhang, Zeng-Li,Sun, Jing,Dong, Jia-Yi,Tian, Hai-Lin,Xue, Lian,Qin, Li-Qiang,Tong, Jian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Background: Numbers of epidemiological studies assessing residential radon exposure and risk of lung cancer have yielded inconsistent results. Methods: We therefore performed a meta-analysis of relevant published case-control studies searched in the PubMed database through July 2011 to examine the association. The combined odds ratio (OR) were calculated using fixed- or random-effects models. Subgroup and dose-response analyses were also performed. Results: We identified 22 case-control studies of residential radon and lung cancer risk involving 13,380 cases and 21,102 controls. The combined OR of lung cancer for the highest with the lowest exposure was 1.29 (95% CI 1.10-1.51). Dose-response analysis showed that every 100 Bq/$m^3$ increment in residential radon exposure was associated with a significant 7% increase in lung cancer risk. Subgroup analysis displayed a more pronounced association in the studies conducted in Europe. Studies restricted to female or non-smokers demonstrated weakened associations between exposure and lung cancer. Conclusions: This meta-analysis provides new evidence supporting the conclusion that residential exposure to radon can significantly increase the risk of lung cancer in a dose-response manner.

Diagnostic Value of Rectal Bleeding in Predicting Colorectal Cancer: a Systematic Review

Tong, Gui-Xian,Chai, Jing,Cheng, Jing,Xia, Yi,Feng, Rui,Zhang, Lu,Wang, De-Bin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

This study aimed at summarizing published study findings on the diagnostic value of rectal bleeding (RB) and informing clinical practice, preventive interventions and future research areas. We searched Medline and Embase for studies published by September 13, 2013 examining the risk of colorectal cancer in patients with RB using highly inclusive algorithms. Data for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and positive predictive value (PPV) of RB were extracted by two researchers and analyzed applying Meta-Disc (version 1.4) and Stata (version 11.0). Methodological quality of studies was assessed according to QUADAS. A total of 38 studies containing 5,626 colorectal cancer patients and 73,174 participants with RB were included. The pooled sensitivity and specificity were 0.47 (95% CI: 0.45-0.48) and 0.96 (95% CI: 0.96-0.96) respectively. The overall PPVs ranged from 0.01 to 0.21 with a pooled value of 0.06 (95% CI: 0.05-0.08). Being over the age of 60 years, change in bowel habit, weight loss, anaemia, colorectal cancer among first-degree relatives and feeling of incomplete evacuation of rectum appeared to increase the predictive value of RB. Although RB greatly increases the probability of diagnosing colorectal cancer, it alone may not be sufficient for proposing further sophisticated investigations. However, given the high specificity, subjects without RB may be ruled out of further investigations. Future studies should focus on strategies using RB as an "alarm" symptom and finding additional indications to justify whether there is a need for further investigations.

Binary Structured Polypropylene/Polyethylene Glycol Micronanofibrous Membranes with Enhanced Water and Air Permeability

Heng Zhang,Qi Zhen,Jing-Qiang Cui,Huan-Wei Sun,Rang-Tong Liu,Yi-Feng Zhang,Yong Liu 한국섬유공학회 2021 Fibers and polymers Vol.22 No.1

As a stable chemical material, polypropylene (PP) micro-nanofibrous membranes are widely used in medical andhealth care. However, PP fibrous membranes with single nano scale diameter are conducive to high packing density, whichresults in large flow resistance across the membrane. Therefore, to improve the material’s water and air permeability,polyethylene glycol (PEG), an incompatible polymer with PP, was introduced by blending in a modified method using a meltblowing process. This proposed approach allows large 10 μm diameter fibers to be entangled with fine 300 nm diameterfibers to produce highly porous binary structured fibrous membranes with small pore size. Because of its binary structure, theair permeability in the material reached 569.56 mm/s and the water vertical velocity was 70.15 mm/s. Additionally, the threedimensionalnumerical calculations suggested that the high porosity and binary structure were key to enhancing waterpermeability in the fibrous membranes. These binary structured micro-nanofibrous membranes are expected to be used forfiltration, separation, health care, oil/water separation, medical wound dressings, and other applications.

Microstructure and corrosion resistance of Ni-based alloy laser coatings with nanosize CeO₂ addition

Hong Zhang, Shi,Xi Li, Ming,Hong Yoon, Jae,Yul Cho, Tong,Zhu He, Yi,Gyu Lee, Chan Elsevier 2008 SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS Vol.9 No.3

<P>Micron-size Ni-base alloy (NBA) powders were mixed with both 1.5 wt.% (hereinafter %) micron-size CeO<SUB>2</SUB> (<I>m</I>-CeO<SUB>2</SUB>) and also 1.5% and 3.0% nano-size CeO<SUB>2</SUB> (<I>n</I>- CeO<SUB>2</SUB>) powders. These mixtures were coated on low-carbon steel (Q235) by 2.0 kW CO<SUB>2</SUB> laser cladding. The effects on the microstructures, phases and electrochemical corrosion of the coatings upon the addition of <I>m</I>- and <I>n</I>- CeO<SUB>2</SUB> powders to NBA (<I>m</I>- and <I>n</I>- CeO<SUB>2</SUB> /NBA) have been investigated. The results showed that a smooth coating was prepared under suitable processing parameters (<I>P</I>= 2.0 kW, <I>V</I>= 180 mm min<SUP>- 1</SUP>) by adding 1.5% <I>n</I>- CeO<SUB>2</SUB>. In addition to the primary phases of γ-Ni, Cr<SUB>23</SUB> C<SUB>6</SUB> and Ni<SUB>3</SUB> B in the Ni-base alloy coating, CeNi<SUB>3</SUB> was formed in Ni-base alloy coatings with both <I>n</I>- CeO<SUB>2</SUB> and <I>m</I>-CeO<SUB>2</SUB> particles, and CeNi<SUB>5</SUB> appeared in the coating upon decreasing the size of CeO<SUB>2</SUB> particles. Well-developed dendrites were observed in the Ni-base alloy coating; directional dendrites grew at the interface in the coating upon the addition of <I>m</I>-CeO<SUB>2</SUB>, whereas fine and multioriented dendrites grew upon decreasing the size of CeO<SUB>2</SUB> particles to the nanoscale. Actinomorphic dendrites and compact equiaxed dendrites grew from the interface to near the surface upon increasing the content of <I>n</I>- CeO<SUB>2</SUB> from 1.5 to 3.0%. In strongly acidic HNO<SUB>3</SUB> solution, the severe corrosion of dendrites occurred and there were many corrosion pits in the Ni-base alloy coating; intercrystalline corrosion also has a dominant role upon the addition of <I>m</I>-CeO<SUB>2</SUB>, whereas uniform corrosion occurs in the coating as the size of CeO<SUB>2</SUB> particles is decreased to nanoscale.</P>

Transcript Profiling of Toll-Like Receptor mRNAs in Selected Tissues of Mink (Neovison vison)

( Mingwei Tong ),( Li Yi ),( Yuening Cheng ),( Miao Zhang ),( Zhigang Cao ),( Jianke Wang ),( Hang Zhao ),( Peng Lin ),( Yong Yang ),( Shipeng Cheng ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.12

Toll-like receptors (TLRs) can recognize conserved molecular patterns and initiate a wide range of innate and adaptive immune responses against invading infectious agents. The aim of this study was to assess the transcript profile of mink TLRs (mTLRs) in mink peripheral blood mononuclear cells (PBMCs) and a range of tissues, and to explore the potential role of mTLRs in the antiviral immune response process. The results indicated that the mTLR partial nucleotide sequences had a high degree of nucleotide identity with ferret sequences (95-98%). Phylogenetic analysis showed that mammalian TLRs grouped into five TLR families, with a closer relationship of the mTLRs with those of ferret than the other mammalian sequences. Moreover, all the mTLRs were ubiquitously expressed in lymphoid organs (spleen and lymph nodes) and PBMCs. Interestingly, the mTLR expression patterns in lung, uterus, and heart showed quite a lot of similarity. Another remarkable observation was the wide expression of mTLR1-3 mRNAs in all tissues. Among the analyzed tissues, skeletal muscle was revealed to being the lowest repertoire of mTLR expression. Additionally, mink PBMCs exposed to the canine distemper virus revealed significant upregulation of mTLR2, mTLR4, mTLR7, and mTLR8 mRNAs, indicating that mTLRs have a role in innate immunity in the mink. Collectively, our results are the first to establish the basic expression patterns of mTLRs and the relationship between mTLRs and a virus, which will contribute to better understanding of the evolution and the functions of mTLRs in the innate immune system in minks.

Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis

Shu Yi Wang,Wei Sen Zhang,Chao Qiang Jiang,Ya Li Jin,Tong Zhu,Feng Zhu,Lin Xu 대한당뇨병학회 2024 Diabetes and Metabolism Journal Vol.48 No.1

Background: Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.Methods: Participants (<i>n</i>=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.Results: During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.Conclusion: Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Entropic Image Thresholding Segmentation Based on Gabor Histogram

( Sanli Yi ),( Guifang Zhang ),( Jianfeng He ),( Lirong Tong ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.4

Image thresholding techniques introducing spatial information are widely used image segmentation. Some methods are used to calculate the optimal threshold by building a specific histogram with different parameters, such as gray value of pixel, average gray value and gradient-magnitude, etc. However, these methods still have some limitations. In this paper, an entropic thresholding method based on Gabor histogram (a new 2D histogram constructed by using Gabor filter) is applied to image segmentation, which can distinguish foreground/background, edge and noise of image effectively. Comparing with some methods, including 2D-KSW, GLSC-KSW, 2D-D-KSW and GLGM-KSW, the proposed method, tested on 10 realistic images for segmentation, presents a higher effectiveness and robustness.