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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>
Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
( Meng Chieh Wu ),( Hsin Kai Huang ),( Chun Cheng Zhang ),( Li Sheng Chang ),( Yung Ze Cheng ),( Chien Chin Hsu ),( Kao Chang Lin ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: Emergency department (ED) overcrowding is a problem in many countries including Taiwan. Access block refers to a situation where patients in the emergency department requiring inpatient care are unable to gain access to appropriate hospital beds within a reasonable time frame (more than 8 hours total time in the emergency department). Access block is one major reason of ED overcrowding. Methods: A new holistic care unit was established in our medical center in Taiwan in July 2012, with the attending physicians including internal medicine physicians and a neurologist. The patients who required hospitalized treatment were referred to internal medicine physicians in the emergency department. The new department was comprised of seven experienced medical attending physician to take care of the patients directly, with 8-hour duty work shifts within 24 hours, in collaboration with emergency physicians, radiologists, nurses, social workers and case managers to form a team. This team had similar three-shift work duty, education and training programs, and they shared medical devices and resources. If beds in the intensive care unit or ward are not available immediately, procedures and treatment can be performed in the holistic care unit. The pediatric patients were excluded from this study. Results: In total, 26,623 patients were admitting to ward from our emergency department from August 2011 to July 2012, and 23,790 patients from August 2012 to July 2013. The rate of access block decreased from 55.29% to 50.01% ( p < 0.01) after holistic care unit was established. The mean time of ED length of stay was also improved from 18.04 hours to 15.43 hours ( p < 0.01). Conclusions: The newly established holistic care unit in our hospital improved the quality of medical care, not only physiologically but also psychologically.
Entomopathogenic fungi-mediated biological control of the red palm weevil Rhynchophorus ferrugineus
Yang Tzu-Hao,Wu Li-Hsin,Liao Chung-Ta,LIDONGWEI,Young Shin Tae,Jae Su Kim,Nai Yu-Shin 한국응용곤충학회 2023 Journal of Asia-Pacific Entomology Vol.26 No.1
The red palm weevil (RPW), Rhynchophorus ferrugineus, is an important pest of palms, and difficult to control by conventional methods. Therefore, microbial control is an alternative strategy for controlling RPW. Herein, a total of 15 entomopathogenic fungi (EPFs) were subjected to primary pathogenicity screening against last stage of RPW larvae. The preliminary data showed that four Beauveria bassiana isolates (JEF-484, 158, 462 and 507) and one Isaria fumosorosea isolate (JEF-014) resulted in 100 % mortality within 5–10 days post inoculation (d.p.i.), respectively. According to the time required for RPW mortality, JEF-484, 158, 462 and 014 were further sub jected to bioassays using 10 7 conidia/ml suspensions by spraying method. Based on the results, JEF-484 showed the highest mortality and shortest LT 50 on the last stage of RPW larvae, followed by JEF-158. The two isolates also showed good conidial production and high thermal stability compared to the other isolates. Therefore, JEF-484 and JEF-158 were selected for bioassays against RPW egg and the last larval stage with different concen trations of 10 5 , 10 6 and 10 7 conidia/ml conidial suspensions by spraying method. For the bioassay at the egg stage, JEF-158 showed a significantly higher ovicidal effect than JEF-484. In the larval bioassay, both EPF isolates showed a dosage-dependent effect on the RPW larvae. JEF-484 caused higher mortality in RPW larvae than JEF-158. In summary, the combination of the 2 promising EPF isolates might provide an opportunity for the practical microbial control of RPW at different life stages in palm tree fields.
APMP.QM-K111-propane in nitrogen
Lin, Tsai-Yin,Liu, Hsin-Wang,Huang, Chiung-Kun,Kang, Namgoo,Bae, Hyun Kil,Woo, Jin Chun,Bi, Zhe,Zhou, Zeyi,Sinweeruthai, Ratirat,Wongjuk, Arnuttachai,Li, Hou,Keat, Teo Beng,Hui, Liu,Wu, Thomas,Ann, Ch BUREAU INTERNATIONAL DES POIDS ET MESURES 2018 METROLOGIA -BERLIN- Vol.55 No.1
Dual-Mode Liquid Crystal Devices with Switchable Memory and Dynamic Modes
I-An Yao,Jin-Jei Wu,Jia-Hsin Li,Hsiao-Ti Koub,Jia-Hsin Lib, 한국정보디스플레이학회 2009 Journal of information display Vol.10 No.4
A liquid crystal device with switchable dynamic and memory modes was investigated and developed. The proposed device reveals the splay, π-twist, and bend states via selective switching among them. In the dynamic mode, thedevice is operated in the bend state, which exhibits a wide viewing-angle and a fast-response-time due to its self-compensated bend structure and flow-accelerated fast response time, respectively. In the memory mode, the permanent memory characteristics in the splay and π-twist sates are obtained, respectively. The switching mechanisms of the tristate device are also proposed.
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.