The topical application of lactic acid bacteria (LAB) is recognized as a useful approach to improve skin health. This work aims to characterize by a multidisciplinary approach, the wound healing, anti-inflammatory, anti-pathogens and proteomic effects of six LAB lysates, belonging to the genus Lactobacillus. Our results demonstrated that the lysates of tested LAB stimulated the proliferation of keratinocytes, and that L. plantarum SGL 07 and L. salivarius SGL 19 accelerated the re-epithelization by inducing keratinocyte migration. The bacterial lysates also reduced the secretion of specific pro-inflammatory mediators from keratinocytes. Furthermore, viable L. salivarius SGL 19 and L. fermentum SGL 10 had anti-pathogenic effects against S. aureus and S. pyogenes, while L. brevis SGL 12 and L. paracasei SGL 04 inhibited S. aureus and S. pyogenes, respectively. The tested lactobacilli lysates also induced specific proteome modulation of the exposed keratinocytes, involving dysregulation of proteins (such as interleukin enhancer-binding factor 2 and ATP-dependent RNA helicase) and pathways (such as cytokine, NF-kB, Hedgehog, and RUNX signaling) associated with their specific wound healing and anti-inflammatory effects. This study indicates the different potential of selected lactobacilli, suggesting that they may be successfully used in the future together with conventional therapies to bring relief from skin disorders. Abbreviations LAB Lactic acid bacteria TNF-α Tumor necrosis factor-alpha IFN-γ Interferon-gamma PBS Phosphate buffered saline DMEM Dulbecco's modified Eagle's medium MCP-1 Monocyte chemoattractant protein-1 RANTES Regulated on activation, normal T cell expressed and secreted LC-MS/MS Liquid chromatography-tandem mass spectrometry SWATH Sequential window acquisition of all theoretical mass spectra The skin, considered the largest organ of the body, is involved in a variety of functions and acts primarily as a protective barrier preventing the entry of potential pathogens. In particular, skin homeostasis is regulated by microorganisms, the so called skin microbiota, which act on keratinocytes and on their cytokine release, ensuring

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Pancreatic ductal adenocarcinoma (PDAC) is typically characterized by high chemoresistance and metastatic spread, features mainly attributable to cancer stem cells (CSCs). It is of central interest the characterization of CSCs and, in particular, the study of their metabolic features in order to selectively identify their peculiarities for an efficient therapeutic approach. In this study, CSCs have been obtained by culturing different PDAC cell lines with a specific growth medium. Cells were characterized for the typical stem/mesenchymal properties at short-, medium-, and long-term culture. Metabolomics, proteomics, analysis of oxygen consumption rate in live cells, and the effect of the inhibition of lactate transporter on cell proliferation have been performed to delineate the metabolism of CSCs. We show that gradually de-differentiated pancreatic cancer cells progressively increase the expression of both stem and epithelial-to-mesenchymal transition markers, shift their metabolism from a glycolytic to an oxidative one, and lastly gain a quiescent state. These quiescent stem cells are characterized by high chemo-resistance, clonogenic ability, and metastatic potential. Re-differentiation reverts these features, re-activating their proliferative capacity and glycolytic metabolism, which generally correlates with high aggressiveness. These observations add an important piece of knowledge to the comprehension of the biology of CSCs, whose metabolic plasticity could be exploited for the generation of promising and selective therapeutic approaches for PDAC patients.

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SUMMARYIn this paper, we propose a novel current-mode solution suitable for the square waveform generation. The designed oscillator, which utilizes only two positive second-generation current conveyors as active blocks, six resistors and a capacitor, is based on a current differentiation, instead of voltage integration, typical of developed solutions both in voltage-mode and in current-mode approaches, so avoiding circuit limitations due to the node saturation effects. The proposed circuit has been designed, as an integrated solution at transistor level, in a standard CMOS technology, with low-voltage (±1 V) and low-power (430 W) characteristics. Simulation results have confirmed the good circuit behaviour, also for working temperature drifts, showing good linearity in a wide oscillation frequency range, which can be independently adjusted through either capacitive (in the range pF− F) or resistive (in the range M -G ) external passive components. Waiting for the chip fabrication, preliminary measurements have been performed using a laboratory breadboard employing the CCII with AD844 commercial component and sample capacitors and resistors. The experimental results have shown good agreement with both simulations and theoretical expectations.