Chrysophanol-induced Necrotic-like Cell Death through an Impaired Mitochondrial ATP Synthesis in Hep3B Human Liver Cancer Cells

Chien-Hang Ni,Jing-Gung Chung,Po-Yuan Chen,Hsu-Feng Lu,Jai-Sing Yang,Hui-Ying Huang,Shin-Hwar Wu,Siu-Wan Ip,Chin-Tung Wu,Su-Yin Chiang,Jaung-Geng Lin,W. Gibson Wood 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.

Grain Refinement and Strengthening Mechanisms of In-situ Follow-up Hammering-Assisted Wire Arc Additive Manufacturing for Hydraulic Turbine Blade Repairing

Xiaochen Xiong,Xunpeng Qin,Lin Hua,Gang Wan,Shilong Wei,Mao Ni,Zeqi Hu 대한금속·재료학회 2023 METALS AND MATERIALS International Vol.29 No.6

An in-situ follow-up hammering-assisted (FH) wire arc additive manufacturing (WAAM) process is proposed for hydraulicturbine blade repairing. With different hammering intervention temperatures above the austenite recrystallization temperature(Tre-γ), the influence and mechanism of the process on the grain size of prior austenite grains and room-temperaturemartensite, as well as the texture of 0Cr13Ni5Mo deposited layers are systematically studied. The OM, SEM and EBSD areused for characterization. The repairing layer of large-sized blade is dominated with the coarse columnar grains with severalmillimeters in length, and the grain size is rated as grade 0. After the FH process, the prior austenite grains are significantlyrefined to grade 8. As the hammering temperature increases, the recrystallized austenite grains gradually grow and coarsenowing to the higher ambient temperature. FH at 950 ℃, a temperature slightly higher than the Tre-γ can achieve the austenitegrains with excellent grain refinement effect. Meanwhile, thanks to microstructure inheritance, the room-temperature martensiticis also refined from 4.69 to 2.47 μm, and the typical < 100 > fibre texture content in the deposited layer is obviouslyreduced with the texture intensity reduced from 6.68 to 2.95. Furthermore, the yield strength is increased by about 200 MPa. The main strengthening mechanisms are grain refinement strengthening and dislocation strengthening, and the contributionsto the yield strength are 96.1 MPa and 79 MPa respectively. Additionally, the FH process is also expected to simultaneouslyimprove the formability of the blade repaired layer.

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.

Bioinformatics Analysis Reveals Connection of Squamous Cell Carcinoma and Adenocarcinoma of the Lung

Fan, Wei-Dong,Zhang, Xian-Quan,Guo, Hui-Lin,Zeng, Wei-Wei,Zhang, Ni,Wan, Qian-Qian,Xie, Wen-Yao,Cao, Jin,Xu, Chang-Hua Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Squamous cell carcinoma and adenocarcinoma are the major histological types of non-small cell lung cancer. Because they differ on the basis of histopathological and clinical characteristics and their relationship with smoking, their etiologies may be different; for example, different tumor suppressor genes may be related to the genesis of each type. We used microarray data to construct three regulatory networks to identify potential genes related to lung adenocarcinoma and squamous cell carcinoma and investigated the similarity and specificity of them. In the network, some of the observed transcription factors and target genes had been previously proven to be related to lung adenocarcinoma and squamous cell carcinoma. We also found some new transcription factors and target genes related to SCC. The results demonstrated that regulatory network analysis is useful in connection analysis between lung adenocarcinoma and squamous cell carcinoma.

Pathophysiological Mechanisms Underlying Unilateral Vocal Fold Paralysis in Female Patients: An Ultrasonographic Study

Yi-An Lu,Tuan-Jen Fang,Yu-Cheng Pei,Yun-Chen Tsai,Wan-Ni Lin 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal foldparalysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFPpatients to investigate the pathophysiologic mechanisms of UVFP. Methods. In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measuredusing B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. Results. Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA)muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respec-tively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side,as observed through LEMG, correlated with the VF length during the resting phase (R =0.368, P =0.050) and CDVLvalues (R =0.627, P =0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlatedwith the normalized phonatory vocal length change (nPLC; R =0.621, P =0.041) on the paralyzed side. Conclusion. CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFPcases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The find-ings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngealnerve injury and offer valuable insights into the pathophysiology of UVFP.