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.

Effects of gas flow on particulate deposition in EGR coolers

Xun Zhang,Jihui Li,Zhiqiang Han,Xunshun Wu,Wei Tian 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.1

This paper presents the test approach to investigate the effects of gas flow rate on particulate deposition inside the exhaust gas recirculation (EGR) coolers. The tests were carried out on a diesel engine equipped with the EGR cooler that a given total gas flow rate passed through and that contained pluggable exchanger tubes to adjust the flow rate in the tubes. Test results show that under the given coolant temperature and EGR gas temperature, the lower flow rate in the exchanger tube is and the longer tubes are, the more particulate with D p > 50 nm deposit in the cooler. With the given total gas flow rate passing through the cooler, the lower flow rate in the exchanger tube is and the longer tubes are, the larger deposit mass is inside the cooler. In the cases of longer tubes, the effects of gas flow rate on the deposit mass are depends on the effects of gas velocity on the particulate deposition, rather than the effects of flow rate on the particulate number passing through the heat exchanger tube per minute.

Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D₂ in the beating rat atrium

Zhang, Ying,Li, Xiang,Liu, Li-Ping,Hong, Lan,Liu, Xia,Zhang, Bo,Wu, Cheng-Zhe,Cui, Xun The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

Effects of coolant temperature on particulate deposition and cooling efficiency of EGR coolers

Xun Zhang,Wei Tian,Jinhui Li,Zhiqiang Han,Xueshun Wu 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.7

Porous fouling layers formed by particulate deposition in the EGR cooler tubes degrade the cooling efficiency of the EGR coolers. This research has investigated the changes of the particulate concentration under varied coolant temperature conditions and the effects of the coolant temperature on the cooling efficiency of the cooler tubes by measuring the particulate concentration and size distribution at the cooler inlet and outlet. The experiment results indicate that for the particulates of different sizes, the thermophoretic force acting on them and the regeneration vary under the same experiment conditions, presenting distinctive effects on the particulate concentration distribution in the exhaust gas and causing concentrations of nuclear particulates and aggregated particulates to change, respectively. The mass of fouling layers inside the cooler tubes increases as the coolant temperature decreases. Decreasing the coolant temperature not only increases the quantity of fouling particulates but also forms more particulates of big sizes, causing cooling efficiency of the cooler tube per unit length to decrease with the decrease of coolant temperature and the increase of the tube length.

Comparisons of Curative and Side Effects of Chemoradiotherapy among Xinjiang Han, Uigur and Kazakh Esophageal Carcinoma Patients

Zhang, Li,Ma, Li-Li,Zhang, Jian-Qing,Yang, Mei,Xun, Tu-Er,Li, Ai Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Objective: This study aimed to explore the differences in the curative and side effects of chemoradiotherapy on esophageal cancer (EC) among Xinjiang Han, Uigur and Kazakh patients. Methods: 170 patients with IIA stage-IV of esophageal squamous cell carcinoma were analyzed retrospectively. Based on different nationalities, they were divided into the Han, Uigur and Kazakh groups. The 1-, 2- and 3-year survival rates, incidence of the side effects (including hematological toxicities, radioactive esophagitis and percutaneous reactions) and application of antibiotics and harmonics were compared among the groups. There was no significant difference in the short-term curative effects among the Han, Uigur and Kazakh groups. The 1- 2- and 3-year survival rates of the three groups were 84%, 40%, 26%; 78%, 27%, 18%; and 60%, 21%, 12% ($x^2$=14.497, P<0.05). The incidence rate of hamatological toxicity ${\geq}$Grade 2 in the Kazakh group was significantly lower than that in the Han or Uigur group. Results: The incidence rates of radioactive esophagitis and percutaneous reactions Grade 2 in the Han group were significantly higher than those in the Uigur or Kazakh group. There was no significant difference in the types of applied antibiotics among the groups, but there were significant differences in the days of antibiotic application and proportion of patients receiving harmonics between the Hans and either of other groups. Conclusion: Chemoradiotherapy shows a better effect in the long-term survival rate among Han EC patients compared with Uigur or Kazakh EC patients. Uigur and Kazakh patients show a better tolerance to the side effects of chemoradiotherapy compared with Hans.

Anomalous magnetization jumps in granular Pb superconducting films

Zhang An-Lei,Jiang Wan-Yan,Chen Xing-Hong,Zhang Xiao-Ke,Lu Wen-Lai,Chen Fei,Feng Zhen-Jie,Cao Shi-Xun,Zhang Jin-Cang,Ge Jun-Yi 한국물리학회 2022 Current Applied Physics Vol.35 No.-

In granular superconductors, the grain boundaries are closely related to the vortex dynamics and the macroscopic superconducting properties. In our research, Pb films with different grain sizes were prepared by tuning the substrate temperature. With the grain size decreasing, Pb films are prone to feature the anomalous magnetization jumps in the M − T curves, while in the M − H curves flux avalanche happens. Both phenomena appear in the same region of the H − T phase diagram and thus are considered to have the same origin. The further theoretical analysis shows that with grain size decreasing the pinning mechanism evolves from a mixed δTc and δl pinning to the δl pinning mechanism. The results shed light on the study of pinning mechanism for granular superconductors and is beneficial to the potential application of manipulating vortex pinning by regulation of intrinsic defects.

Microwave-assisted Solvent-free Synthesis of Some Dimethine Cyanine Dyes, Spectral Properties and TD-DFT/PCM Calculations

Zhang, Xiang-Han,Wang, Lan-Ying,Zhai, Gao-Hong,Wen, Zhen-Yi,Zhang, Zu-Xun Korean Chemical Society 2007 Bulletin of the Korean Chemical Society Vol.28 No.12

A series of dimethine cyanine dyes were synthesized in a fast, efficient and high yield by the condensation of quaternary salts with 1H-indole-3-carbaldehyde in the presence of piperidine under solvent-free microwave irradiation. The products were identified by 1H NMR, IR, UV-Vis spectra and elemental analysis. The absorption and fluorescence properties of these dyes were investigated both experimentally and theoretically. Calculations performed at a combination of time-dependent density functional theory (TD-DFT) and the polarizable continuum model (PCM) reproduced the π-π* type absorption bands of the dyes. Regression analysis was used for studying theoretical results of the absorption maxima in different solvents. Compared with experimental counterparts, estimated overall uncertainties in the absorption maxima were about ±2%.

NSM00158 Specifically Disrupts the CtBP2-p300 Interaction to Reverse CtBP2-Mediated Transrepression and Prevent the Occurrence of Nonunion

Chen, Xun,Zhang, Wentao,Zhang, Qian,Song, Tao,Yu, Zirui,Li, Zhong,Duan, Ning,Dang, Xiaoqian Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.6

Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

Neurotrophic Effects of Schwann Cell Secretions from Wallerian Degenerating Facial Nerves on Neonatal Rats Facial Motoneurons in vitro

Ma, Xun,Yu, Guang-Yan,Zhang, Zhen-Kang,Li, Sheng-Lin,Fu, Jia,Zhang, Kui-Hua Korean Academy of Oral Biology and the UCLA Dental 2001 International Journal of Oral Biology Vol.26 No.3

Regeneration and functional recovery of facial nerves after injury are still far from satisfaction. Studies on whether Schwann cells of injured facial nerves could secrete neurotrophic factors to promote nerve regeneration are rare, and that is the pbjective of this study. Schwann cells from Wallerian degenerating segments of rats facial nerves were isolated and cultured in conditioned culture medium, collected, concentrated and fractionated by ultra-filtration. The neurotrophic bioactivity of the soluble secretions from cultured Schwann cells were examined on an established neuron culture model. Dil fluorescence labeling facial motoneurons from neonatal rats, MTT assay, and image analysis for survival of facial motoneurons were used. The results show that facial motoneuron survival activity in Schwann cell culture medium containing a molecular weight larger than 30 kDa component, was significantly higher than in medium with and without serum (p<0.05 and p<0.01 respectively). The effect could be extinguished by either boiling or trypsinizing. At the 2nd, 4th and 7th days after conditioned culture, mean perikaryon area and neurite length of facial motoneurons in a medium containing molecular weight larger than 30kDa component, were significantly larger than in serum containing medium. The results show that Schwann cells from Wallerian degenerating facial nerves in serum-free and neurite re-growth of facial motoneurons in vitro. The results also suggest that the neurotrophic effect might be derived from protein(s) or peptide(s) with molecular weight larger than 30 kDa component of the soluble secretions. It may be potent for functional repair of facial verve and other neural disorders.

The complete mitochondrial genome of Hemigrapsus sinensis (Brachyura, Grapsoidea, Varunidae) and its phylogenetic position within Grapsoidea

Jin Xun,Guo Xingle,Chen Jian,Li Jiasheng,Zhang Shufei,Zheng Sixu,Wang Yunpeng,Peng Ying,Zhang Kun,Liu Yifan,Liu Bingjian 한국유전학회 2023 Genes & Genomics Vol.45 No.3

Background In this study, the complete mitogenome of Hemigrapsus sinensis was the first identified and analyzed. Objective The complete mitochondrial genome of Hemigrapsus sinensis (Brachyura, Grapsoidea, Varunidae) and its phylogenetic position within Grapsoidea. Methods The sample of Hemigrapsus sinensis was collected and DNA was extracted. After sequencing, NOVOPlasty was used for sequence assembly. Annotate sequences with MITOS WebServer, tRNAscan-SE2.0, and NCBI database. MEGA was used for sequence analysis and Phylosuite was used for phylogenetic tree construction. DnaSP was used to calculate Ka/Ks. Results This mitochondrial genome shows that it was 15,900 bp and encoded 13 PCGs, 22 tRNA genes, two rRNA genes, and one control region. The genome composition tends to A + T (74.34%) and presents a negative GC-skew (− 0.22) and AT-skew (− 0.03). The PCGs initiation codon was the typical ATN and termination codon was the typical TAN, incomplete T or missing. The ML and BI trees showed that H. sinensis was most closely related to Hemigrapsus and clustered together with the Varunidae. And our phylogenetic trees provide proof that Ocypodoidea and Grapsoidea may be of common origin. Meanwhile, in the phylogenetic tree, parallel mixing of Chiromantes and Orisarma raised doubts over the traditional classification system. Besides, Incomplete Lineage sorting (ILS) was observed in Varunidae. In the subsequent analysis of evolution rate, we found that all of the PCGs (NAD4 was not calculated) had undergone negative selections, indicating the conservation of mitochondrial genes of H. sinensis during the evolution. Conclusion Therefore, researching the complete mitogenome of H. sinensis would be contributing to molecular taxonomy, phylogenetic relationship, and breeding optimization within the Grapsoidea superfamily.