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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 Indications for Spinal Endoscopic Surgery and Potential for Future Expansion
Kuo-Tai Chen,김진성,Abel Po-Hao Huang,Martin Hsiu-Chu Lin,Chien-Min Chen 대한척추신경외과학회 2023 Neurospine Vol.20 No.1
Endoscopic spine surgery (ESS) has evolved as a safe, effective, and efficient alternative for minimally invasive spine surgery (MISS). The innovation of full-endoscopic systems makes definitive decompression surgery through different approaches feasible. The approach can be determined according to the location of the target lesion or the surgeon's preference. During the past 2 decades, ESS has expanded its indications from lumbar to cervical spines. Except for decompression, endoscopy-assisted fusion surgery is also developing. However, ESS is still evolving and has a steep learning curve. The revolution of technologies and ESS techniques will enable surgeons to treat various spinal diseases more practically. In recent years, the application of the computer-assisted navigation system and augmented reality have reformed imaging quality and interpretation. The endoscopic rhizotomy techniques have opened a new way for MISS of chronic low back pain. This review introduces the current indications of ESS and its potential future expansion.