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Downregulation of Carnitine palmitoyltransferase-2 (CPT2) has been shown to be highly associated with the progression of several cancers, but little known about its expression, biological functions and mechanisms in colorectal cancer (CRC).Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets was used to explore the expression of CPT2, the relationship between CPT2 expression and clinicopathologic features, as well as the overall survival of CRC. Cox's proportional hazards regression model was used to analyze independent prognostic factors of CRC. In vitro, CRC tissues were analyzed by RT-qPCR, IHC, IF and western blotting to verify CPT2 expression. Colony formation, CCK-8, cell cycle, apoptosis, transwell and wound healing assays were performed to examine the functions of CPT2 in CRC. In vivo, nude mouse xenograft experiment was used to further examine the effect of CPT2 on tumorigenesis. Furthermore, gene set enrichment analysis (GSEA) was conducted to explore the downstream pathway of CPT2. The regulation of p53 pathway by CPT2 was verified by RT-qPCR and Western blotting.CPT2 expression was frequently downregulated in CRC and correlated with poor prognosis. Low CPT2 expression was significantly associated with age, lymph node metastasis, distant metastasis and TMN stage. Univariate and multivariate analysis indicated that low CPT2 expression was an independent prognostic factor for poorer overall survival. Functionally, overexpression of CPT2 in CRC cells induced growth suppression, cell cycle arrest at the G1 phase, enhanced apoptosis and reduced cell migration and invasion. Conversely, knockdown of CPT2 contributed to cell proliferation, migration and invasion, increased the proportion of S phase cells, decreased the proportion of G1 phase cells and inhibited apoptosis. Mechanistically, we found that CPT2 overexpression can increase p53 expression by activating p-p53, leading to p21, Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP activation and Bcl2, MDM2 deactivation, thereby inhibiting tumor proliferation and promoting apoptosis. CPT2 knockdown yielded opposite results.These findings suggest that CPT2 may be a novel prognostic marker of CRC and downregulation of CPT2 can promote proliferation and inhibit apoptosis through p53 pathway in CRC. Strategies targeting CPT2 may be developed as therapies for CRC.

The effect of tumor necrosis factor superfamily member 9 (TNFSF9) on the metastasis of pancreatic cancer (PC) and the underlying mechanism remain unclear. We studied the expression of TNFSF9 in pancreatic cancer and its relationship with immune cells. We further explored the effect of TNFSF9 on pancreatic cancer metastasis by inducing macrophage polarization, and evaluated the expression of Src/FAK/p-Akt/IL-1β signals in macrophages after knocking down TNFSF9. The data shows that TNFSF9 expression is elevated in pancreatic cancer and is related to the poor prognosis of patients with pancreatic cancer. In addition, TNFSF9 may induce the M2 polarization of macrophages through Src/FAK/p-Akt/IL-1β signals, thereby promoting the migration of pancreatic cancer cells. In conclusion, our data reveals that TNFSF9 may become a predictive biomarker of pancreatic cancer and provides a new intervention target for the immunotherapy of pancreatic cancer.

Stroke is a major global health problem, with the prevalence and economic burden predicted to increase due to aging populations in western society. Following stroke, numerous biochemical alterations occur and damage can spread to nearby tissue. This zone of “at risk” tissue is termed the peri-infarct zone (PIZ). As the PIZ contains tissue not initially damaged by the stroke, it is considered by many as salvageable tissue. For this reason, much research effort has been undertaken to improve the identification of the PIZ and to elucidate the biochemical mechanisms that drive tissue damage in the PIZ in the hope of identify new therapeutic targets. Despite this effort, few therapies have evolved, attributed in part, to an incomplete understanding of the biochemical mechanisms driving tissue damage in the PIZ. Magnetic resonance imaging (MRI) has long been the gold standard to study alterations in gross brain structure, and is frequently used to study the PIZ following stroke. Unfortunately, MRI does not have sufficient spatial resolution to study individual cells within the brain, and reveals little information on the biochemical mechanisms driving tissue damage. MRI results may be complemented with histology or immuno-histochemistry to provide information at the cellular or sub-cellular level, but are limited to studying biochemical markers that can be successfully “tagged” with a stain or antigen. However, many important biochemical markers cannot be studied with traditional MRI or histology/histochemical methods. Therefore, we have developed and applied a multi-modal imaging platform to reveal elemental and molecular alterations that could not previously be imaged by other traditional methods. Our imaging platform incorporates a suite of spectroscopic imaging techniques; Fourier transform infrared imaging, Raman spectroscopic imaging, Coherent anti-stoke Raman spectroscopic imaging and X-ray fluorescence imaging. This approach does not preclude the use of traditional imaging techniques, and rather it should be use to complement traditional methods such as MRI or histology and immunohistochemistry, to gain a greater insight into disease mechanisms. We demonstrate the potential of this approach by characterizing biochemical alterations within the PIZ 24 h after the induction of photothrombotic stroke in mice. Substantial molecular and elemental alterations were identified in the PIZ 24 h after stroke that are consistent with tissue swelling and edema, but not oxidative stress. This reveals important mechanistic information, that could not previously be obtained, which should be considered in future studies aimed at developing therapeutic intervention from this model.