Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages

Yuan-Shen Chen,Wei-Chu Chuang,Hsiu-Ni Kung,Ching-Yuan Cheng,Duen-Yi Huang,Ponarulselvam Sekar,Wan-Wan Lin 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.4

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

Construction of Z-scheme W18O49/NiAl-LDH heterojunction with photothermal effect for photocatalytic reduction of CO2

Cheng Xia,Rui-Tang Guo,Zhen-rui Zhang,Chen-yuan Fan,Yu-zhe Liu,Yu-cheng Lin,Chu-fan Li,Wei-Guo Pan 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.128 No.-

Recently, the photocatalytic CO2 reduction technology is an effective solution to remit the energy crisis. Inorder to improve the photocatalytic performance, Z-scheme W18O49/NiAl-LDH composite catalysts wereprepared by hydrothermal method. Fortunately, the prepared catalysts revealed excellent photocatalyticperformance under the simulated sunlight, and CO and CH4 could be detected in the reduction products. WO/LDH-0.5 catalyst possessed the optimal activity, with CO and CH4 yield of 37.09 and 8.01 lmol g-1h1separately, which were 7.9 and 3.6 times that of NiAl-LDH monomer. In addition, W18O49 endowedW18O49/NiAl-LDH catalysts with photothermal effect, which raised the surface temperature andfacilitated the catalytic reaction. Meanwhile, the Z-scheme heterojunction composed of flower-likeNiAl-LDH and urchin-like W18O49 accelerated the separation of photoexcited carriers and enhanced theredox ability. Through a series of characterizations and investigations, this work is promising to breaknew ground for the design of photocatalysts with photothermal effect.

Evolutionary Studies of Weedy and Cultivated Rice Using Chloroplast Genome Sequencing

Lin Cheng,Yuan Cao,Rungnapa Phitaktansakul,Kyaw Myo Aung,Myeong-Hyun Min,Jungrye Nam,Eul Jai Myung,Sang-Ho Chu,Kyu-Won Kim,Yong-Jin Park 한국잡초학회 2019 한국잡초학회 별책(학술대회 초록집) Vol.39 No.1

Real-World Effectiveness and Safety of SOF/LDV for Pa-tients with Chronic Hepatitis C in Taiwan

( Ching-chu Lo ),( Pin-nan Cheng ),( Chi-yi Chen ),( Chung-feng Huang ),( Hsing-tao Kuo ),( Kuo-chih Tseng ),( Yi-hsiang Huang ),( Chi-ming Tai ),( Cheng-yuan Peng ),( Ming-jong Bair ),( Chien-hung Ch 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Distinctive Endophytic Fungal Assemblage in Stems of Wild Rice (Oryza granulata) in China with Special Reference to Two Species of Muscodor (Xylariaceae)

Zhi-lin Yuan,Zhen-zhu Su,Li-juan Mao,Yang-qing Peng,Guan-mei Yang,Fu-cheng Lin,Chu-long Zhang 한국미생물학회 2011 The journal of microbiology Vol.49 No.1

Ecological niches in the rhizosphere and phyllosphere of grasses capable of sustaining endophytes have been extensively studied. In contrast, little information regarding the identity and functions of endophytic fungi in stems is available. In this study, we investigated the taxonomic affinities, diversity, and host specificities of culturable endophytes in stems of wild rice (Oryza granulata) in China. Seventy-four isolates were recovered. Low recovery rate (11.7%) indicated that there were relatively few sites for fungal infection. Identification using morphology, morphospecies sorting, and molecular techniques resulted in classification into 50 taxa, 36 of which were recovered only once. Nucleotide sequence similarity analysis indicated that 30% of the total taxa recovered were highly divergent from known species and thus may represent lineages new to science. Most of the taxa were classified as members of the classes Sordariomycetes or Dothideomycetes (mainly in Pleosporales). The presence of Arthrinium and Magnaporthaceae species, most often associated with poaceous plants, suggested a degree of host specificity. A polyphasic approach was employed to identify two Muscodor taxa based on (i) ITS and RPB2 phylogenies, (ii) volatile compounds produced, and (iii)an in vitro bioassay of antifungal activity. This to our knowledge is only the second report regarding the isolation of Muscodor spp. in China. Therefore, we hypothesize that wild plants represent a huge reservoir of unknown fungi. The prevalence, novelty, and species-specificity of unique isolates necessitate a reevaluation of their contribution to ecosystem function and fungal biodiversity.

ONYX-II: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + Ribavirin in HCV Genotype 1b-Infected Patients with Compensated Cirrhosis from South Korea and Taiwan

( Seung Woon Paik ),( Chi-jen Chu ),( Yan Luo ),( Kwang-hyub Han ),( Jia-horng Kao ),( Jeong Heo ),( Cheng-yuan Peng ),( Yoon Jun Kim ),( Ting-tsung Chang ),( Young-suk Lim ),( Ming Lung Yu ),( Linda 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Chronic hepatitis C virus (HCV) infection is associated with development of complications including hepatocellular carcinoma, liver failure and cirrhosis. Patients with cirrhosis are historically more difficult to cure. In southeastern Asia, the most prevalent HCV genotype (GT) is GT1b. In western populations, the 3 direct-acting antiviral (3-DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by AbbVie and Enanta) and dasabuvir (DSV) ± ribavirin (RBV) demonstrated sustained virologic response (SVR) at post-treatment week 12 (SVR12) rates of 99% in patients with GT1b infection and compensated cirrhosis regardless of prior treatment experience. The regimen, however, has not been investigated in southeastern Asian populations. The ONYX-II study is evaluating the efficacy and safety of this regimen in Asian patients with HCV GT1b infection and compensated cirrhosis. Methods: Treatment-naive and interferon-based therapy-experienced patients with HCV GT1b-infection and compensated cirrhosis were enrolled in South Korea, Taiwan, and China, and received 12 weeks of OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) with RBV (weight-based). Patients will be followed for 48 weeks after the last dose of study drugs. The primary objectives are to compare the SVR12 rate to the known SVR rate of telaprevir + peg-interferon (IFN) + RBV therapy, and to assess the safety of OBV/PTV/r + DSV + RBV. Results: Twenty-one and 20 subjects were enrolled in South Korea and Taiwan, respectively. Of South Korean patients, 52% were male and 71% were treatment-experienced; of Taiwanese patients, 45% were male and 65% were treatment-experienced. Safety data and SVR at post-treatment week 4 (SVR4) will be available for presentation. Conclusions: The ONYX-II study evaluates the 3-DAA regimen of OBV/PTV/r + DSV with RBV for Asian patients with compensated cirrhosis and HCV GT1b infection. Resultant data may provide evidence for treatment guidelines for HCV GT1b in this population.

Threshold-based Filtering Buffer Management Scheme in a Shared Buffer Packet Switch

Yang, Jui-Pin,Liang, Ming-Cheng,Chu, Yuan-Sun The Korea Institute of Information and Commucation 2003 Journal of communications and networks Vol.5 No.1

In this paper, an efficient threshold-based filtering (TF) buffer management scheme is proposed. The TF is capable of minimizing the overall loss performance and improving the fairness of buffer usage in a shared buffer packet switch. The TF consists of two mechanisms. One mechanism is to classify the output ports as sctive or inactive by comparing their queue lengths with a dedicated buffer allocation factor. The other mechanism is to filter the arrival packets of inactive output ports when the total queue length exceeds a threshold value. A theoretical queuing model of TF is formulated and resolved for the overall packet loss probability. Computer simulations are used to compare the overall loss performance of TF, dynamic threshold (DT), static threshold (ST) and pushout (PO). We find that TF scheme is more robust against dynamic traffic variations than DT and ST. Also, although the over-all loss performance between TF and PO are close to each other, the implementation of TF is much simpler than the PO.

ONYX-I: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir in South Korean and Taiwanese Patients with HCV Genotype 1b Infection and without Cirrhosis

( Jeong Heo ),( Wan-Long Chuang ),( Yan Luo ),( Mong Cho ),( Chi-Jen Chu ),( Kwang-Hyub Han ),( Jia-Horng Kao ),( Seung Woon Paik ),( Chun-Yen Lin ),( Jin-Woo Lee ),( Cheng-Yuan Peng ),( Young-Suk Lim 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Approximately 45-50% of Hepatitis C virus (HCV) infections in South Korea and Taiwan are genotype (GT) 1b. Previous phase 3 studies demonstrated that the direct-acting antiviral (DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by Abbvie and Enanta) and dasabuvir (DSV) was well tolerated and achieved sustained virologic response at post-treatment week 12 (SVR12) in 99% of treatment-naive and 100% of treatment- experienced patients with HCV GT1b. ONYX-I (NCT02517515) was designed to evaluate efficacy and safety in Asian patients with HCV GT1b infection without cirrhosis. Methods: Treatment-naive and IFN-based therapy-experienced patients with HCV GT1b infection in South Korea, Taiwan, and China were randomized 1:1 to receive either OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) or placebo for 12 weeks during the double-blind (DB) period. Patients in the placebo arm subsequently received OBV/PTV/r + DSV for 12 weeks during the open-label period. Patients will be followed for 48 weeks after last dose of study drugs. The primary objectives are to compare the SVR12 rates for the treatment-naive and -experienced patients to corresponding historical SVR rates of telaprevir + peg-interferon and ribavirin therapy, and assess the safety of the OBV/PTV/r + DSV regimen. Presented are results from the South Korean and Taiwanese populations. Results: In both South Korea and Taiwan, 120 patients were randomized and treated. Of South Korean patients, 45% were male, 33% were treatment-experienced and 89% had F0-F1 fibrosis. Of Taiwanese patients, 39% were male, 33% were treatment-experienced, and 87% had F0-F1 fibrosis. Safety data and SVR at post-treatment week 4 will be presented. Conclusions: The ONYX-I study is evaluating the safety and efficacy of DAA regimen, OBV/PTV/r + DSV, in Southeast Asian patients without cirrhosis infected with HCV GT1b. Resultant data may help inform treatment guidelines for HCV GT1b in this population.

Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)