Review of Animal Models of Colorectal Cancer in Different Carcinogenesis Pathways.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract with increasing morbidity and mortality. Exploring the factors affecting colorectal carcinogenesis and controlling its occurrence at its root is as important as studying post-cancer treatment and management. Establishing ideal animal models of CRC is crucial, which can occur through various pathways, such as adenoma-carcinoma sequence, inflammation-induced carcinogenesis, serrated polyp pathway and de-novo pathway. This article aims to categorize the existing well-established CRC animal models based on different carcinogenesis pathways, and to describe their mechanisms, methods, advantages and limitations using domestic and international literature sources. This will provide suggestions for the selection of animal models in early-stage CRC research.

Inhibition of tissue transglutaminase attenuates lipopolysaccharide-induced inflammation in glial cells through AKT/mTOR signal pathway.

AIM: In view of the facts that tTG protein expression level and its enzyme activity increase in AD brains of both individuals and transgenic animals and compelling evidence of the involvement of inflammation in AD pathogenesis, tTG could be involved in the inflammation responses in the brain. In the present study, we examined the effects of the irreversible and the competitive inhibitor of tTG on the condition of lipopolysaccharide-induced mimic inflammation models in glial cells. METHODS: Western blot and tTG enzyme activity assay were applied to detect tTG and isopeptide protein levels and tTG enzyme activity. The production of nitric oxide and the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were determined by Griess Reagents and Western blot respectively to assess anti-inflammatory effects. Moreover, the activation of AKT/mTOR signaling pathway was determined to evaluate the underlying mechanism of anti-inflammatory response. RESULTS: Irreversible and competitive inhibitor of tTG could ameliorate LPS-induced neuroinflammation in glial cells without cytotoxicity. Moreover, AKT/mTOR pathway may be involved in the anti-inflammatory response of tTG inhibitors. Therefore, NTU283 and Cystamine may alleviate inflammatory response in glial cells, probably through, at least partially, inhibiting the activation of AKT/mTOR signaling pathway. CONCLUSION: Our study provided some clues that tTG inhibitors NTU283 and Cystamine might be potential candidates for the treatments of neuroinflammation-related diseases, although more studies needed for further exploration.

Inhibition of tissue transglutaminase promotes Aß-induced apoptosis in SH-SY5Y cells.

AIM: Tissue transglutaminase (tTG) catalyzes proteins, including ß-amyloid (Aß), to cross-link as a γ-glutamyl-ε-lysine structure isopeptide, which is highly resistant to proteolysis. Thus, tTG plays an important role in protein accumulation in Alzheimer's disease (AD). In the present study, we examined the effect of an irreversible tTG inhibitor, NTU283, on Aß mimic-induced AD pathogenesis in SH-SY5Y cells. METHODS: Western blot and in-cell Western analyses were used to detect tTG and isopeptide (representing the enzyme activity of tTG) protein levels. Moreover, Hoechst and PI co-staining was performed, and caspase-3 and caspase-7 activities and the Bax/Bcl-2 ratio were determined to evaluate the effects of NTU283 on apoptosis. RESULTS: The results confirmed that tTG activity was inhibited by NTU283 20-500 µmol/L in a concentration-dependent manner in SH-SY5Y cells. Contrary to our expectations, however, the isopeptide bonds were increased when cells were co-treated with Aß and NTU283. In addition, NTU283 alone did not induce apoptosis in SH-SY5Y cells. However, when co-applied with Aß, NTU283 promoted rather than inhibited Aß-induced apoptosis. Consistent with the apoptotic rate, pretreating cells with different concentrations of NTU283 and Aß significantly increased the activities of caspase-3 and caspase-7 as well as the ratio of Bax/Bcl-2. CONCLUSION: Irreversible inhibition of tTG activity did not block but rather promoted Aß-induced apoptosis, which indicated that tTG has complex functions in AD pathogenesis.