Deubiquitination and Stabilization of PD-L1 by CSN5

Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6

<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Coal dust exposure induces proliferation and migration of human bronchial epithelial cells

Li Amin,Zhang Yinci,Wang Ruikai,Xu Ruyue,Ma Yongfang,Song Li,Cao Weiya,Xiaolong Tang 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.2

Background Coal dust exposure has caused a variety of lung diseases. In addition to genotoxicity and cytotoxicity, other biological changes caused by coal dust (CD) exposure need further study. Objective To observe the cellular transformation eff ects of CD exposure and explore its underlying molecular mechanism, human bronchial epithelial cells (BEAS-2B) were cultured with continuous CD exposure. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, colony formation assay, wound healing assay, next-generation sequencing (NGS) and western blotting were performed to observe the cell proliferation, migration, genomic transcription and pathological signaling pathways. Results We demonstrated that BEAS-2B cells with long-term chronic CD exposure show accelerated proliferation rate and enhanced migration ability, and have altered gene expression profi les and aberrant activation of EGFR/Raf/ERK and PI3K/ AKT/mTOR pathways. Conclusions The results indicate that chronic CD exposure could induce abnormal proliferation and migration of BEAS-2B cells, lead to the transformation potential of human bronchial epithelial cells.

A Novel Approach to Synthesize Nitrogen-Deficient g-C3N4 for the Enhanced Photocatalytic Contaminant Degradation and Electrocatalytic Hydrogen Evolution

Xiaoxiao Li,Kailian Zhang,Man Zhou,Kai Yang,Shi Yang,Xiaoshuai Ma,Changlin Yu,Yu Xie,Weiya Huang,Qizhe Fan 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2020 NANO Vol.15 No.02

Graphitic carbon nitride with nitrogen vacancies was successfully synthesized by the three-step method for the calcination of melamine, following urea-assisted hydrothermal and jacjoin calcination approach. The structural, surface, optical and electric properties were characterized by XRD, FT-IR, SEM, TEM, UV–Vis DRS, PL, N2 physical adsorption/desorption and electrochemical methods, which proved that this strategy of modifying g-C3N4 by nitrogen vacancies not only increased the specific surface area, exposed more active sites, but also inhibited the recombination of photogenerated carriers on the surface of photocatalysts, resulting in the enhancement of photocatalytic and electrocatalytic performances. The photocatalytic activities were measured under visible light irradiation ( λ > 420 nm), and their degradation efficiencies could be achieved for 99.8%, 55%, 100% and 99.7% corresponding to that of rhodamine B, acid orange II, methyl orange and methylene blue, respectively. The trapping experiments demonstrated that ·O2- played an important role in the degradation process. In addition, being an active electrocatalyst, nitrogen-deficient g-C3N4 showed a lower Tafel slope, smaller overpotential and the more effective electrochemical surface area compared with that of bare g-C3N4 in neutral media. This work underlines the importance of defect engineering to promote catalytic performance, which can provide a simple and efficient way for modifying g-C3N4 and other N-based catalysts.

Licochalcone A, a Natural Inhibitor of c-Jun <i>N</i>-Terminal Kinase 1

Yao, Ke,Chen, Hanyong,Lee, Mee-Hyun,Li, Haitao,Ma, Weiya,Peng, Cong,Song, Nu Ry,Lee, Ki Won,Bode, Ann M.,Dong, Ziming,Dong, Zigang American Association for Cancer Research 2014 Cancer Prevention Research Vol.7 No.1

<P>The c-<I>Jun N</I>-terminal kinases (JNK) play an important role in many physiologic processes induced by numerous stress signals. Each JNK protein appears to have a distinct function in cancer, diabetes, or Parkinson's disease. Herein, we found that licochalcone A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity but had little effect on JNK2 <I>in vitro</I> activity. Although licochalcone A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both <I>ex vivo</I> and <I>in vitro</I> systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expressed compared with normal cell lines. In cancer cell lines, treatment with licochalcone A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. The inhibition resulted in G<SUB>1</SUB> phase arrest and apoptosis. Moreover, an <I>in vivo</I> xenograft mouse study showed that licochalcone A treatment effectively suppressed the growth of HCT116 xenografts, without affecting the body weight of mice. These results show that licochalcone A is a selective JNK1 inhibitor. Therefore, we suggest that because of the critical role of JNK1 in colon cancer and pancreatic carcinogenesis, licochalcone A might have preventive or therapeutic potential against these devastating diseases. <I>Cancer Prev Res; 7(1); 139–49. ©2013 AACR</I>.</P>

A heat transfer tube wear reliability analysis method based on first-order reliability method

Xiao Chen,Xing He,Lichen Tang,Yuebing Li,Mingjue Zhou,Weiya Jin,Zengliang Gao 한국CDE학회 2020 Journal of computational design and engineering Vol.7 No.6

The heat transfer tube is one of the most essential components of the nuclear power plant as the boundary between the first and second circuit pressures. The wear between the heat transfer tube and the support plate or the anti-vibration strip is one of the essential reasons for its failure. Based on a heat transfer tube wear analysis method, combined with the reliability analysis theory, the calculation scheme of tube wear failure probability is proposed in this paper. In the analysis and calculation process, the key factors affecting the reliability are determined, including the baffle thickness B and the aperture difference Ce. In the manufacturing process, these key factors can be controlled, which is instructive for engineering practice.

Correlation between red blood cell distribution width/platelet count and prognosis of newly diagnosed diffuse large B-cell lymphoma

Xiaobo Liu,Yanliang Bai,Ying Liu,Weiya Li,Yabin Cui,Jinhui Xu,Xingjun Xiao,Xiaona Niu,Kai Sun 대한혈액학회 2023 Blood Research Vol.58 No.4

Background Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL). Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (<0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P < 0.05). A survival analysis showed that progression-free survival (PFS) (P =0.003) and overall survival (OS) (P <0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P <0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P <0.05). Conclusion A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.