1.A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells.
Dachuan HUANG ; Sylvia LIM ; Rong Yuan Ray CHUA ; Hong SHI ; Mah Lee NG ; Siew Heng WONG
Protein & Cell 2010;1(3):291-306
MHC class II expression is controlled mainly at transcriptional level by class II transactivator (CIITA), which is a non-DNA binding coactivator and serves as a master control factor for MHC class II genes expression. Here, we describe the function of a novel splice-isoform of CIITA, DC-expressed caspase inhibitory isoform of CIITA (or DC-CASPIC), and we show that the expression of DCCASPIC in DC is upregulated upon lipopolysaccharides (LPS) induction. DC-CASPIC localizes to mitochondria, and protein-protein interaction study demonstrates that DC-CASPIC interacts with caspases and inhibits its activity in DC. Consistently, DC-CASPIC suppresses caspases-induced degradation of nitric oxide synthase-2 (NOS2) and subsequently promotes the synthesis of nitric oxide (NO). NO is an essential regulatory molecule that modulates the capability of DC in stimulating T cell proliferation/activation in vitro; hence, overexpression of DC-CASPIC in DC enhances this stimulation. Collectively, our findings reveal that DC-CASPIC is a key molecule that regulates caspases activity and NO synthesis in DC.
Alternative Splicing
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Amino Acid Sequence
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Animals
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Base Sequence
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CARD Signaling Adaptor Proteins
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genetics
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metabolism
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Cell Line
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Dendritic Cells
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drug effects
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immunology
;
metabolism
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Humans
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In Vitro Techniques
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Lipopolysaccharides
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pharmacology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mitochondria
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metabolism
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Molecular Sequence Data
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Nitric Oxide
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biosynthesis
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Nitric Oxide Synthase Type II
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metabolism
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Nuclear Proteins
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genetics
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metabolism
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Protein Isoforms
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genetics
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metabolism
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RNA, Messenger
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genetics
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metabolism
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T-Lymphocytes
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immunology
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metabolism
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Trans-Activators
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genetics
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metabolism
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Up-Regulation
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drug effects
2.Multimodal prerehabilitation for elderly patients with sarcopenia in colorectal surgery
Jingting WU ; Hannah CHI ; Shawn KOK ; Jason M.W. CHUA ; Xi-Xiao HUANG ; Shipin ZHANG ; Shimin MAH ; Li-Xin FOO ; Hui-Yee PEH ; Hui-Bing LEE ; Phoebe TAY ; Cherie TONG ; Jasmine LADLAD ; Cheryl H.M. TAN ; Nathanelle KHOO ; Darius AW ; Cheryl X.Z. CHONG ; Leonard M.L. HO ; Sharmini S. SIVARAJAH ; Jialin NG ; Winson J.H. TAN ; Fung-Joon FOO ; Bin-Tean TEH ; Frederick H. KOH
Annals of Coloproctology 2024;40(1):3-12
Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.