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Bioactive sphingolipid profile in a xenograft mouse model of head and neck squamous cell carcinoma

provided laboratory space for Lipidomics Facility in MUSC?s Children?s Research Institute. Author Contributions Conceptualization: Aiping Bai, Yusuf A. Hannun. Formal analysis: Aiping Bai, Jacek Bielawski ... . Funding acquisition: Yusuf A. Hannun. Investigation: Aiping Bai, Xiang Liu. Resources: Aiping Bai, Jacek Bielawski, Yusuf A. Hannun. Supervision: Jacek Bielawski, Yusuf A. Hannun. Writing ? original

Anticancer actions of lysosomally targeted inhibitor, LCL521, of acid ceramidase

Acid ceramidase, which catalyzes ceramide hydrolysis to sphingosine and free fatty acid mainly in the lysosome, is being recognized as a potential therapeutic target for cancer. B13 is an effective and selective acid ceramidase inhibitor in vitro, but not as effective in cells due to poor access to the lysosomal compartment. In order to achieve targeting of B13 to the lysosome...

Extracellular ATP mediates inflammatory responses in colitis via P2 × 7 receptor signaling

ScholarSearch for Yuan Guo in:Nature Research journals • PubMed • Google ScholarSearch for Aiping Bai in:Nature Research journals • PubMed • Google Scholar Contributions A.B. and X.L. convinced and designed the ... declare no competing financial interests. Corresponding author Correspondence to Aiping Bai. Supplementary information PDF files1.Supplementary Information Rights and permissions This work is

AMPK Inhibition Blocks ROS-NFκB Signaling and Attenuates Endotoxemia-Induced Liver Injury

Background AMP-activated protein kinase (AMPK) is an important enzyme in regulation of cellular energy homeostasis. We have previously shown that AMPK activation by 5-aminoimidazole-4-carboxamide (AICAR) results in suppression of immune responses, indicating the pivotal role of AMPK in immune regulation. However, the cellular mechanism underpinning AMPK inhibition on immune...

Characterization of Human CD39+ Th17 Cells with Suppressor Activity and Modulation in Inflammatory Bowel Disease

Induced regulatory T-cells (iT-reg) and T helper type 17 (Th17) in the mouse share common CD4 progenitor cells and exhibit overlapping phenotypic and functional features. Here, we show that human Th17 cells endowed with suppressor activity (supTh17) can be derived following exposure of iT-reg populations to Th17 polarizing conditions. In contrast to “pathogenic” Th17, supTh17...

P2X7 Integrates PI3K/AKT and AMPK-PRAS40-mTOR Signaling Pathways to Mediate Tumor Cell Death

Background Extracellular adenosine triphosphate (ATP) functions as a novel danger signal that boosts antitumor immunity and can also directly kill tumor cells. We have previously reported that chronic exposure of tumor cells to ATP provokes P2X7-mediated tumor cell death, by as yet incompletely defined molecular mechanisms. Methodology/Principal Findings Here, we show that acute...

Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression

Background Ceramide is a bioeffector that mediates various cellular processes, including apoptosis. However, the mechanism underlying ceramide function in apoptosis is apparently cell type-dependent and is not well-understood. We aimed at identifying molecular targets of ceramide in metastatic human colon and breast cancer cells, and determining the efficacy of ceramide analog in...

Seasonality in Flares and Months of Births of Patients with Ulcerative Colitis in a Chinese Population

Background and Aims Reports on seasonality in flares or months of births of inflammatory bowel disease patients have been inconsistent, but little data are available in a Chinese population. The aim of this study was to determine whether symptom flares and births of ulcerative colitis (UC) patients follow a seasonal pattern. Methods Patients with a diagnosis of UC established...