Propofol Prevents the Growth, Migration, Invasion, and Glycolysis of Colorectal Cancer Cells by Downregulating Lactate Dehydrogenase Both In Vitro and In Vivo.

Colorectal cancer (CRC) is one of the most frequently diagnosed gastrointestinal malignancies worldwide and has high rates of morbidity and mortality. Propofol has been reported to have certain anticancer properties. However, the role and mechanism of propofol in CRC are not entirely clear. CRC cells were treated with propofol and/or LDH-overexpression plasmids, and a mouse xenograft model of CRC was also established and treated with propofol. Cell viability, migration, and invasion were evaluated by CCK-8, wound healing, and transwell assays; the expression of related proteins was confirmed by western blotting; indexes of the glycolytic pathway were analyzed using specialized kits; tumor growth in mice was measured; pathological tissue structure was assessed by H&E staining; and 8-OHDG expression was determined by an immunochemistry assay. Our results verified that propofol could effectively prevent the malignant behaviors of CRC cells by suppressing cell viability, migration, and invasion and accelerating apoptosis. We also discovered that propofol could attenuate the glycolytic pathway in CRC cells. Moreover, we proved that lactate dehydrogenase (LDH) was required for the inhibitory effects of propofol on the growth of CRC cells, including glycolysis in CRC cells. Furthermore, our results showed that propofol could not only significantly inhibit tumor growth and glycolysis, but also ameliorate the pathological structure of CRC tumors. The current results proved that propofol could attenuate the malignant progression of CRC by preventing LDH activity, suggesting that propofol might be an effective therapeutic agent for CRC.

Maresin-2 alleviates allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome, Th2 type immune response and oxidative stress.

Asthma is a chronic inflammatory disease of the respiratory system. Maresin-2 (MaR2) is biosynthesized from docosahexaenoic acid (DHA) by macrophages, display strong anti-inflammatory and pro-resolving activity. To investigate the therapeutic effect and mechanism of MaR2 on asthmatic mice induced by ovalbumin (OVA) in conjunction with the adjuvant aluminum hydroxide. Twenty four female BALB/c mice were randomly divided into control, OVA, OVA + MaR2, and OVA + dexamethasone (Dexa) groups. MaR2 or Dexa were given as a treatment for OVA-induced asthma. Serum, bronchoalveolar alveolar lavage fluid (BALF) and lung tissue were collected for further analysis. The Pathological changes of lung tissue, proportion of inflammatory cells in BALF, levels of inflammatory cytokines in BALF or serum, oxidative stress indices, and the protein concentration of ASC, MPO, Ly-6G, ICAM-1, NLRP3 and Caspase-1 in lung tissues were evaluated. Compared with the OVA group, both OVA + MaR2 and OVA + Dexa group had reduced inflammation and mucus secretion in lung tissue, number of inflammatory cells in BALF, levels of related inflammatory cytokines in serum or BALF, and expressions of ASC, MPO, Ly-6G, ICAM-1, NLRP3 and Caspase-1 proteins in lung tissue. In addition, the oxidative stress was alleviated as indicated by decreased MDA, and elevated SOD and GSH. MaR2 has an obvious protective effect on OVA-induced bronchial asthma in mice, in a similar manner as Dexa. The mechanism may be related to the inhibition of the Th2 type immune response, the NLRP3 inflammasome activation and oxidative stress.

Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism.

OBJECTIVE: This study examined whether the immunomodulator fingolimod (FTY720) could alleviate renal ischemia/reperfusion (I/R)-induced lung injury and explored the potential mechanisms. METHODS: Renal I/R was established in a rat model, and FTY720 (0.5, 1, or 2 mg/kg) was injected intraperitoneally after 15 minutes of ischemia. Pro-inflammatory cytokine levels, oxidative stress, apoptosis, and the mRNA expression of the sphingosine-1-phosphate (S1P)-related signaling pathway genes sphingosine kinase-1 (SphK1) and sphingosine kinase-2 were analyzed in lung tissue. RESULTS: Increased pro-inflammatory cytokine levels; decreased total superoxide dismutase, catalase, and glutathione peroxidase levels; increased apoptosis; and increased S1P lyase and SphK1 expression were observed following renal I/R. FTY720 reversed renal I/R-induced changes and effectively attenuated lung injury. CONCLUSION: FTY720 protected against acute lung injury in rats subjected to renal I/R by decreasing pulmonary inflammation and apoptosis, increasing oxidative stress, and modulating S1P metabolism.

The effect of FTY720 at different doses and time-points on LPS-induced acute lung injury in rats.

We sought to assess the protective effect of different doses of Fingolimod (FTY720) in a rat model of acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) and explored the underlying mechanisms. The ALI model was established in rats and different doses of FTY720 (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, or 2 mg/kg) were injected intraperitoneally. Lung computed tomography and blood gas analyses were performed at 6 h, 24 h, and 48 h after intraperitoneal injection, and the lung tissues were extracted to prepare paraffin sections for histopathological examination. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) were detected by ELISA, and the expressions of inflammatory pathway proteins in each group were measured by Western blot analysis. A single intraperitoneal injection of FTY720 inhibited LPS-induced NF-κB activation, reduced the level of inflammatory cytokines, and decreased the infiltration of inflammatory cells. Moreover, it alleviated lung tissue injury, as shown by marked attenuation of pulmonary oedema and improved arterial partial pressure of oxygen (PaO2) and the general condition of ALI rats. In conclusion, our results demonstrate the protective effect of FTY720 against LPS-induced ALI. The underlying mechanism of the protective effect may involve inhibition of LPS-induced activation of NF-κB and regulation of the inflammatory pathway to alleviate barrier dysfunction of alveolar capillaries.