Group V Secreted Phospholipase A2 Induces the Release of Proangiogenic and Antiangiogenic Factors by Human Neutrophils

Secreted phospholipases A2 (sPLA2s) are extracellular enzymes that catalyze the release of free fatty acids and lysophospholipids from membrane phospholipids and also bind to different receptors (e.g., PLA2R1 or integrins). To date, 12 mammalian sPLA2s have been identified, which play a critical role in pathophysiological processes including inflammation and cancer. sPLA2s activate immune cells such as human neutrophils (PMNs) by enzymatic activity- or receptor-mediated mechanisms. In addition, human PMNs synthesize and store human group V (hGV) and human group X (hGX) sPLA2s in their granules, but only the former is released upon cellular activation. We investigated the effects of sPLA2s on the release of proangiogenic and antiangiogenic factors by PMNs. We found that exogenous hGV and hGX sPLA2s induce the release of vascular endothelial growth factor (VEGF)-A, angiopoietin 1 (Ang1), and CXCL8/IL-8. Only hGV induces the secretion of the antiangiogenic isoform of VEGF-A, namely, VEGF-A165b. While the release of VEGF-A, Ang1, and CXCL8/IL-8 was likely mediated by hGV enzymatic activity and/or binding to PLA2R1 and heparan sulfate proteoglycans, the release of VEGF-A165b requires the interaction with αVβ3 and α4β1 integrins. We also provide evidence that endogenous hGV released by N-formyl-met-leu-phe (fMLF)-activated PMNs is involved in the release of angiogenic factors. The translational relevance of these data is supported by our findings that hGV expression is increased in human samples of lung cancer which are infiltrated by PMNs. Overall, our results suggest that the hGV-neutrophil axis may play a relevant role in the modulation of cancer-related inflammation and angiogenesis

A genic and epigenetic combination therapy for liver cancer

Results: Cell cycle analysis was achieved on HepG2 cells transfected with TRAIL-GFP and pEGFP-p53 recombinant protein. Results were analysed with Cell-Quest and ModIFit software. Data shown the re-expression of selected recombinant proteins in over than 30% cells post 24 h from transfection. The transfected cells were treated post 24 h with MS-275 for other 8 h and the cells were collected. The total protein extract was analysed by Western blot and the apoptosis pathways were evaluated via caspase activation proteins. In details we detect the relative bands for caspase 8 and caspase 9 full lengths and activated form in transfected cells and post MS-275 treatment. Conclusion: Results showed the possibility to restore the expression of pro-apoptotic gene TRAIL and p53 in a liver cancer model HepG2. Moreover, the treatment with epigenetic modulators MS-275 enhanced the pro-apoptotic effect mediated by the re-expression of those silenced genes

A genic and epigenetic combination therapy for liver cancer

Results: Cell cycle analysis was achieved on HepG2 cells transfected with TRAIL-GFP and pEGFP-p53 recombinant protein. Results were analysed with Cell-Quest and ModIFit software. Data shown the re-expression of selected recombinant proteins in over than 30% cells post 24 h from transfection. The transfected cells were treated post 24 h with MS-275 for other 8 h and the cells were collected. The total protein extract was analysed by Western blot and the apoptosis pathways were evaluated via caspase activation proteins. In details we detect the relative bands for caspase 8 and caspase 9 full lengths and activated form in transfected cells and post MS-275 treatment. Conclusion: Results showed the possibility to restore the expression of pro-apoptotic gene TRAIL and p53 in a liver cancer model HepG2. Moreover, the treatment with epigenetic modulators MS-275 enhanced the pro-apoptotic effect mediated by the re-expression of those silenced genes

In Vitro Antimicrobial and Antibiofilm Properties and Bioaccessibility after Oral Digestion of Chemically Characterized Extracts Obtained from <i>Cistus</i> × <i>incanus</i> L., <i>Scutellaria lateriflora</i> L., and Their Combination

Periodontal diseases are oral inflammatory diseases ranging from gingivitis to chronic periodontitis. Porphyromonas gingivalis is one of the major pathogens responsible for severe and chronic periodontitis. Plant extracts with antimicrobial activity could be considered possible alternatives to chlorhexidine, an antiseptic substance used in oral hygiene thatcan cause bacteria resistance. Here, two commercial extracts obtained from Cistus × incanus L. and Scutellaria lateriflora L. were chemically characterized usingUltra-High-Performance Liquid Chromatography (UHPLC) coupled with a Q-Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. The extracts were studied for their bioaccessibility after simulated in vitro oral digestion, their antimicrobial activity against P. gingivalis, their protective effects against cellular invasion by P. gingivalis, and their antibiofilm activity. The extracts were found to contain very complex mixtures of polyphenols, which were quite stable after in vitro simulated oral digestion and demonstrated mild, dose-dependent inhibitory activity against P. gingivalis growth. This activity increased with the combination of the two extracts. Moreover, the combination of the extracts induced a reduction in P. gingivalis HaCaT invasiveness, and the reduction in biofilm came to around 80%. In conclusion, a combination of C. incanus and S. lateriflora showed promising effects useful in the treatment of gingivitis