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.

Current Evidence on the Association between rs3757318 of C6orf97 and Breast Cancer Risk: a Meta-Analysis

Hong, Yuan,Chen, Xue-Qin,Li, Jiao-Yuan,Liu, Cheng,Shen, Na,Zhu, Bei-Bei,Gong, Jing,Chen, Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. Materials and Methods: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. Results: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. Conclusions: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms.

Rapid and Visual Detection of Vibrio parahaemolyticus in Aquatic Foods Using blaC_ARB-17 Gene-Based Loop-Mediated Isothermal Amplification with Lateral Flow Dipstick (LAMP-LFD)

( Yuan-qing Hu ),( Xian-hui Huang ),( Li-qing Guo ),( Zi-chen Shen ),( Lin-xue Lv ),( Feng-xia Li ),( Zan-hu Zhou ),( Dan-feng Zhang ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.12

Vibrio parahaemolyticus is recognized as one of the most important foodborne pathogens responsible for gastroenteritis in humans. The bla_CARB-17 gene is an intrinsic β-lactamase gene and a novel species-specific genetic marker of V. parahaemolyticus. In this study, a loop-mediated isothermal amplification (LAMP) assay combined with a lateral flow dipstick (LFD) was developed targeting this bla_CARB-17 gene. The specificity of LAMP-LFD was ascertained by detecting V. parahaemolyticus ATCC 17802 and seven other non-V. parahaemolyticus strains. Finally, the practicability of LAMP-LFD was confirmed by detection with V. parahaemolyticus-contaminated samples and natural food samples. The results showed that the optimized reaction parameters of LAMP are as follows: 2.4 mmol/l Mg²⁺, 0.96 mmol/l dNTPs, 4.8 U Bst DNA polymerase, and an 8:1 ratio of inner primer to outer primer, at 63℃ for 40 min. The optimized reaction time of the LFD assay is 60 min. Cross-reactivity analysis with the seven non-V. parahaemolyticus strains showed that LAMP-LFD was exclusively specific for V. parahaemolyticus. The detection limit of LAMP-LFD for V. parahaemolyticus genomic DNA was 2.1 × 10^-4 ng/μl, corresponding to 630 fg/reaction and displaying a sensitivity that is 100-fold higher than that of conventional PCR. LAMP-LFD in a spiking study revealed a detection limit of approximately 6 CFU/ml, which was similar with conventional PCR. The developed LAMP-LFD specifically identified the 10 V. parahaemolyticus isolates from 30 seafood samples, suggesting that this LAMP-LFD may be a suitable diagnostic method for detecting V. parahaemolyticus in aquatic foods.

Raman signature from brain hippocampus could aid Alzheimer's disease diagnosis.

Chen, Pu,Shen, Aiguo,Zhao, Wei,Baek, Seong-Joon,Yuan, Hua,Hu, Jiming Optical Society of America 2009 Applied Optics Vol.48 No.24

<P>Micro-Raman spectroscopy (MRS) is used for the first time to our knowledge to investigate brain hippocampus tissue from Alzheimer's disease (AD) infected rats. In situ Raman analysis of tissue sections provides distinct spectra useful for distinguishing AD from normal state. The biochemical changes of brain hippocampus tissue including the deposit of beta-amyloid (Abeta) protein, the increase of cholesterol, and hyperphosphorylated tau are observed through MRS when AD occurs. A more convincing multi-Raman criterion based on single Raman peaks, and further in combination with statistical analysis of the entire Raman spectrum, is found capable of classifying brain hippocampus tissues with different pathological features. This study demonstrates the brain hippocampus is an important candidate for considering the early pathological state of AD, and Raman signatures from the brain hippocampus could aid AD diagnosis. In addition, Raman results undoubtedly confirm simultaneous changes of cholesterol and Abeta in the progression of AD.</P>

Clinical Study of Thalidomide Combined with Dexamethasone for the Treatment of Elderly Patients with Newly Diagnosed Multiple Myeloma

Chen, Hai-Fei,Li, Zheng-Yang,Tang, Jie-Qing,Shen, Hong-Shi,Cui, Qing-Ya,Ren, Yong-Ya,Qin, Long-Mei,Jin, Ling-Juan,Zhu, Jing-Jing,Wang, Jing,Ding, Jie,Wang, Ke-Yuan,Yu, Zi-Qiang,Wang, Zhao-Yue,Wu, Tian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Objective: To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). Methods: Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. Results: A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). Conclusions: The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.

Flux Sliding-mode Observer Design for Sensorless Control of Dual Three-phase Interior Permanent Magnet Synchronous Motor

Shen, Jian-Qing,Yuan, Lei,Chen, Ming-Liang,Xie, Zhen The Korean Institute of Electrical Engineers 2014 Journal of Electrical Engineering & Technology Vol.9 No.5

A novel equivalent flux sliding-mode observer (SMO) is proposed for dual three-phase interior permanent magnet synchronous motor (DT-IPMSM) drive system in this paper. The DT-IPMSM has two sets of Y-connected stator three-phase windings spatially shifted by 30 electrical degrees. In this method, the sensorless drive system employs a flux SMO with soft phase-locked loop method for rotor speed and position estimation, not only are low-pass filter and phase compensation module eliminated, but also estimation accuracy is improved. Meanwhile, to get the regulator parameters of current control, the inner current loop is realized using a decoupling and diagonal internal model control algorithm. Experiment results of 2MW-level DT-IPMSM drives system show that the proposed method has good dynamic and static performances.

2,5-Hexanedione induces apoptosis via a mitochondriamediated pathway in PC12 cells

Yuan Qi,Shuang-yue Li,Feng-yuan Piao,Zhe-min Wang,Ruo-lin Chen,Shuang Liu,Jing-shun Shen 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.1

2,5-Hexanedione (HD) is the main active metabolite of n-hexane and mediates the neurotoxicity of the parent compound. Studies suggested that apoptosis involved in HD neurotoxicity. However, the mechanism of HD-induced neuronal apoptosis remains unknown. To explore its underlying mechanism, we treated PC12 cells with 5, 10 and 20 mM HD for 24 h, respectively. We found that HD induced apoptotic death in PC12 cells in a dose-dependent manner. Moreover, HD down-regulated Bcl-2 expression, up-regulated Bax expression and Bax/Bcl-2 ratio, promoted the disruption of mitochondrial transmembrane potential, induced the release of cytochrome c from mitochondria, and increased the activity of caspase-3 in PC12 cells, which were all the key regulators of intrinsic apoptotic pathway. These results indicate that HD induces apoptosis via a mitochondria- mediated pathway in PC12 cells.

The Energy Efficiency of China’s Regional Construction Industry Based on the Three-stage DEA Model and the DEA-DA Model

Yuan Chen,Bingsheng Liu,Yinghua Shen,Xueqing Wang 대한토목학회 2016 KSCE Journal of Civil Engineering Vol.20 No.1

China’s construction industry has constantly been confronted with the problems, such as high resource consumption, serious pollution and low energy efficiency. Thus, improving the energy efficiency of the construction industry and reducing its energy consumption can not only promote the sustainable development of the socio-economy and eco-economy, but also enhance the overall development level of the construction industry. In the context, the objectives are to put forward a set of systematic methodologies for measuring the energy efficiency of the regional construction industry and analyzing its change trends. First, the energy efficiency index system of the construction industry and its influencing factors are constructed through the literature review. Second, two research methods (the three-stage Data Envelopment Analysis (DEA) model and the Data Envelopment Analysis-Discriminant Analysis (DEA-DA) model) are applied to analyze the energy efficiency in 30 provinces of China and the change trends from 2003 to 2011. The results indicate that after eliminating the influence of the environment factors and random errors, the energy efficiency values of the construction industry in most of the provinces were improved. The mean of China’s energy efficiency of the construction industry in each year was approximately 0.92. Except Shandong with the lowest values, the mean of the other provinces was over 0.8, which reflected that the energy management and utilization levels in the construction industry were relative mature. However, the energy efficiency in most of provinces fluctuated constantly during these nine years, with the peak in 2004 and a downward trend in the overall efficiency after 2004. From the regional aspect, the energy efficiency of the construction industry in the eastern, central and western regions decreased successively; as the development level of the local economy had less significant effects on the energy efficiency, the gaps among the three regions were not obvious.

Structural and functional properties of Maillard-reacted casein phosphopeptides with different carbohydrates

Meng Yuan,Yu Cao,Haoyang Zheng,Kunlin Chen,Yuping Lu,Jing Wang,Liqin Zhu,Ming Chen,Zhipeng Cai,Yonggen Shen 한국식품과학회 2024 Food Science and Biotechnology Vol.33 No.7

This study used glucose, fructose, maltose and dextran to explore the effects of different carbohydrates on the Maillard reaction of casein phosphopeptides (CPP). The color parameter results showed that heating time from 1 to 5 h led to brown color, which was consistent with the observed increased in browning intensity. Fourier transform infrared spectroscopy results verified that four carbohydrates reacted with CPP to produce Maillard conjugates. Fluorescence spectroscopy showed that the Maillard reaction changed the tertiary structure of CPP by decreasing the intrinsic fluorescence intensity and surface hydrophobicity compared with the CPP-carbohydrate mixture. At the same time, the Maillard reaction effectively improved the emulsifying properties, reducing power and DPPH radical scavenging activity of CPP. Furthermore, this study also found that glucose and fructose improved CPP more than maltose and dextran. Therefore, monosaccharides have good potential in modifying CPP via the Maillard reaction.

Enhancement of the Polar Coercive Force for Annealed Co/Ir(111) Ultrathin Films

Wen-Yuan Chan,Du-Cheng Tsai,Wei-Hsiang Chen,Cheng-Hsun-Tony Chang,Jyh-Shen Tsay 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.12

The alloy formation and the magnetic properties of Co/Ir(111) ultrathin films have been investigated. As the temperature is increased above 400 K, interdiffusion of Co and the Ir substrate occurs. Due to a compositional change in the surface layers, the polar coercive force is greatly enhanced. At temperatures above 600 K, magnetic hysteresis appears only in the polar configuration. Thisshows that the easy axis of the magnetization of Co/Ir(111) may be stabilized in the direction ofthe surface normal by thermal-annealing treatments. From systematic investigations of Co/Ir(111)ultrathin films thinner than 4 monolayers, a magnetic phase diagram has been established. Accordingto the compositional changes and related magnetic properties, the phase diagram can beseparated into three regions. In region I at temperatures below 400 K, Co films are ferromagnetic. In region II where atomic interdiffusion occurs in the surface layers, an enhanced polar coerciveforce is observed. The phase transition from phase I to II is related to the interdiffusion betweenthe Co overlayer and the iridium substrate. In region III for low coverage or at high temperatures,a nonferromagnetic behavior is observed. The phase transition from phase II to III is mainly dueto the reduced atomic percent of cobalt in the Co-Ir alloy and to the lowered Curie temperaturecaused by a reduction in the thickness of the magnetic layers.