Figure - available from: The Journal of International Medical Research
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The levels of apoptosis as measured using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of tissue sections of intestinal type of gastric cancer from patients (n = 55) categorized based on the degree of differentiation (a). Scale bar 100 µm. The mean ± SD apoptosis index for each corresponding differentiation status (b). *P < 0.01 compared with the well differentiated tissues; #P < 0.05 compared with the moderately differentiated tissues; data were compared using one-way analysis of variance. DAPI, 4′,6-diamino-2-phenylindole. The colour version of this figure is available at:http://imr.sagepub.com.
Source publication
Objective
To investigate the effect of the casein kinase 2 interacting protein 1 (CKIP-1) on the apoptosis of the intestinal type of gastric cancer (GC).
Methods
The levels of CKIP-1 protein and the rates of apoptosis were measured in tissue samples of the intestinal type of GC and human GC cell lines. The rate of apoptosis and the protein levels...
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Citations
... Interestingly, these two members have adverse functions in cell death regulation. In contrast to PLEKHO2, PLEKHO1 promotes apoptosis [19,20] and inhibits cell proliferation [18,21]. So the interaction and regulation relationship of these two members should be investigated in future studies. ...
Receptor interaction protein kinase 1 (RIPK1) plays a diverse role in tumor necrosis factor α (TNFα) signalings. The ubiquitination of RIPK1 is essential for NF-κB activation, whereas its kinase activity promotes apoptosis and necroptosis. However, the mechanisms underlying have not been fully illuminated. Here we report that PH domain-containing family O member 2 (PLEKHO2) inhibits RIPK1-dependent cell death and is necessary for NF-κB activation in response to TNFα. Cells of PLKEHO2 deficiency are more susceptible to TNF-α induced apoptosis and necroptosis with increased RIPK1 activation, which is consistent with the observation that the susceptibility of PLEKHO2−/− cells is effectively prevented by treatment of RIPK1 kinase inhibitor. Moreover, PLEKHO2 deficient cells exhibit compromised RIPK1 ubiquitination and NF-κB activation in response to TNFα. Ultimately, PLEKHO2-deficient mice display greatly increased hepatotoxicity and lethality after TNFα-induced hepatitis. In summary, our study revealed that PLEKHO2 is a novel inhibitor of apoptosis and necroptosis, which plays a key role in regulating RIPK1 ubiquitination and activation
Li‐Zhong‐Xiao‐Pi (LZXP) granule is effective for treating gastric precancerous lesions (GPL) in traditional Chinese medicine. However, the active compounds of LZXP and their potential therapeutic mechanism in GPL remained unclarified. The purpose of this study is to investigate the chemical composition and potential targets of LZXP, which is clinically applied in the treatment of GPL. Based on the accurate masses, ion fragments, and literature data, a total of 128 compounds were identified in the LZXP sample using ultra‐performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) in both positive and negative ion modes, and 28 of these compounds were exactly determined by comparison with authentic reference standards. Meanwhile, 11 typical components were quantified via UPLC during a 24‐min period. The linearity, accuracy, stability and recovery of the method were all proven. Through the network pharmacological analysis, six chemicals (quercetin, 4'‐hydroxywogonin, sinensetin, 5, 7, 8, 3', 4'‐pentamethoxyflavanone, 8‐gingerdione and quercetin) were identified as the active ingredients, and five LZXP targets (AKT1, CYP1B1, PTGS2, MMP9, and EGFR) were found to be the crucial molecules in the treatment of GPL. This study provides a systematic and applicable method for the rapid screening and identification of the chemical constituents from LZXP, and an effective understanding the mechanism of LZXP in the treatment of GPL.
