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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>
( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
Degradation of polyvinyl alcohol in aqueous solutions using UV/oxidant process
Chia-Chang Lin,Li-Ting Lee 한국공업화학회 2015 Journal of Industrial and Engineering Chemistry Vol.21 No.1
This study evaluates the effectiveness of the UV/S2O82 and UV/H2O2 processes in degrading polyvinylalcohol (PVA) in aqueous solutions. The effects of pH, oxidant dosage, and initial PVA concentration onthe efficiency of degradation of PVA were examined. Under acidic conditions, the efficiencies ofdegradation of PVA by the UV/S2O82 and UV/H2O2 processes exceeded those under alkaline conditions. The efficiencies of degradation of PVA by the UV/S2O82 and UV/H2O2 processes increased with oxidantdosage, but fell as the initial PVA concentration was increased. In the UV/S2O82 process, adding salts(Na2SO4, NaNO3, and NaCl) reduced the efficiency and rate of degradation of PVA. However, in the UV/H2O2 process, adding Na2SO4 and NaNO3 did not influence the degradation of PVA, whereas adding NaClweakened the degradation of PVA to a greater extent than in the UV/S2O82 process. At pH 3 with anoxidant dosage of 0.25 mM and an initial PVA concentration of 20 mg/L, the degradation efficiencies ofthe UV/S2O82 and UV/H2O2 processes, as measured after 5 min, were 100 and 58%, respectively. Thecorresponding observed degradation rate constants of the UV/S2O82 and UV/H2O2 processes were1.5509 and 0.2052 min 1, respectively. This result is attributable to the fact that SO4 was better able todegrade PVA than was OH . Therefore, the UV/S2O82 process was more effective than the UV/H2O2 process in degrading PVA.
Human-Oriented Recognition for Intelligent Interactive Office Robot
Chia-Ming Wang,Shin-Huan Tseng,Pei-Wen Wu,Yuan-Han Xu,Chien-Ke Liao,Yu-Chi Lin,Yi-Shiu Chiang,Chung-Dial Lim,Ting-Sheng Chu,Li-Chen Fu 제어로봇시스템학회 2013 제어로봇시스템학회 국제학술대회 논문집 Vol.2013 No.10
This paper presents our new intelligent interactive robot, which is constructed to eagerly provide multi-functional services in an office environment. In order to endow a full interactive capability of our robots for realizing so-called human-robot interaction (HRI), we propose sensor fusion based human detection and tracking system and human pose estimation to deal with a number of situations which may take place in the office environment. Not only by these perceptions, human interact with the robot also by some natural way, such as touching the interface screen and talking with the robot through microphone. Finally, the effectiveness of the proposed work is tested and validated by some of experiments.
Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes
Chia-Jung Hsieh,Chun-Yu Wu,Yen-Heng Lin,Yu-Cheng Huang,Wen-Chi Yang,Tom Wei-Wu Chen,Wei-Li Ma,Wei-Hsin Lin,Feng-Ming Hsu,Furen Xiao,Shih-Hung Yang,Dar-Ming Lai,Chang-Mu Chen,Shin-Yi Chao,Fon-Yih Tsuan 대한척추신경외과학회 2023 Neurospine Vol.20 No.4
Objective: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.
Image Watermarking Scheme Based on Scale-Invariant Feature Transform
( Wan-li Lyu ),( Chin-chen Chang ),( Thai-son Nguyen ),( Chia-chen Lin ) 한국인터넷정보학회 2014 KSII Transactions on Internet and Information Syst Vol.8 No.10
In this paper, a robust watermarking scheme is proposed that uses the scale-invariant feature transform (SIFT) algorithm in the discrete wavelet transform (DWT) domain. First, the SIFT feature areas are extracted from the original image. Then, one level DWT is applied on the selected SIFT feature areas. The watermark is embedded by modifying the fractional portion of the horizontal or vertical, high-frequency DWT coefficients. In the watermark extracting phase, the embedded watermark can be directly extracted from the watermarked image without requiring the original cover image. The experimental results showed that the proposed scheme obtains the robustness to both signal processing and geometric attacks. Also, the proposed scheme is superior to some previous schemes in terms of watermark robustness and the visual quality of the watermarked image.
Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease
Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4
Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
Wu, Chia-Shan,Bongmba, Odelia Y. N.,Yue, Jing,Lee, Jong Han,Lin, Ligen,Saito, Kenji,Pradhan, Geetali,Li, De-Pei,Pan, Hui-Lin,Xu, Allison,Guo, Shaodong,Xu, Yong,Sun, Yuxiang MDPI AG 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.4
<P>Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (<I>AgRP-Cre</I>;<I>Ghsr<SUP>f/f</SUP></I>). Our data showed that GHS-R in AgRP neurons is required for ghrelin’s stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO.</P>