Effect of PD98059, a selective MAPK3/MAPK1 inhibitor, on acute lung injury in mice.

The aim of the present study is to evaluate the contribution of mitogen-activated protein kinase 1–3 (MAPK3/MAPK1) in a model of acute lung inflammation in mice. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent adhesion molecule expression (I-CAM and P-selectin), lipid peroxidation, and increased production of tumour necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced lung apoptosis (Bax and Bcl-2 expression) as well as nitrotyrosine formation, NF-κB activation, and pJNK expression, as determined by immunohistochemical analysis of lung tissues and the degree of lung inflammation and tissue injury (histological score). Administration of PD98059, an inhibitor of MAPK3/MAPK1 (10 mg/kg) 1 h after carrageenan caused a reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that inhibitors of the MAPK3/MAPK1 signaling pathways, such as PD98059, may be useful in the treatment of various inflammatory diseases

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury:

Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice

Molecular interactions, characterization and photoactivity of Chlorophyll a/chitosan/2-HP-β-cyclodextrin composite films as functional and active surfaces for ROS production

Novel photosensitizing film based on the natural hybrid polymer Chitosan/2-hydroxy-propyl-β-Cyclodextrin (CH/CD) is synthesized introducing Chlorophyll a (CH/CD/Chla) as a photoactive agent for possible application in antimicrobial photodynamic therapy (PDT). The polymer absorbs visible light, in turn able to generate reactive oxygen species (ROS) and, therefore it can be used as environmental friendly and biodegradable polymeric photosensitizer (PS). The modified film is characterized by means of different spectroscopic, calorimetric, diffraction techniques and microscopic imaging methods including time-resolved absorption spectroscopy. UV–Vis, FTIR-ATR and X-ray Photoelectron Spectroscopy (XPS) analyses suggest that Chla shows a strong affinity toward Chitosan introducing interactions with amino groups present on the polymer chains. Nanosecond laser flash photolysis technique provides evidence for the population of the excited triplet state of Chla. Photogeneration of singlet oxygen is demonstrated by both direct detection by using infrared luminescence spectroscopy and chemical methods based on the use of suitable traps. Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Differential Scanning Calorimetry (DSC) analyses confirm also the occurrence of structural changes both on the film surface and within the film layer induced by the insertion of the pigment. Moreover, X-ray Diffraction data (XRD) shows the existence of an amorphous phase for the chitosan films in all the compared conditions

Photo-thermal effects in gold nanorods/DNA complexes

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Role of PPAR-δ in the development of zymosan-induced multiple organ failure: an experiment mice study

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor (PPAR)-beta/delta is a nuclear receptor transcription factor that regulates gene expression in many important biological processes. It is expressed ubiquitously, especially white adipose tissue, heart, muscle, intestine, placenta and macrophages but many of its functions are unknown. Saturated and polyunsaturated fatty acids activate PPAR-beta/delta, but physiological ligands have not yet been identified. In the present study, we investigated the anti-inflammatory effects of PPAR-beta/delta activation, through the use of GW0742 (0,3 mg/kg 10% Dimethyl sulfoxide (DMSO) i.p), a synthetic high affinity ligand, on the development of zymosan-induced multiple organ failure (MOF).</p> <p>Methods</p> <p>Multiple organ failure (MOF) was induced in mice by administration of zymosan (given at 500 mg/kg, i.p. as a suspension in saline). The control groups were treated with vehicle (0.25 ml/mouse saline), while the pharmacological treatment was the administration of GW0742 (0,3 mg/kg 10% DMSO i.p. 1 h and 6 h after zymosan administration). MOF and systemic inflammation in mice was assessed 18 hours after administration of zymosan.</p> <p>Results</p> <p>Treatment with GW0742 caused a significant reduction of the peritoneal exudate formation and of the neutrophil infiltration caused by zymosan resulting in a reduction in myeloperoxidase activity. The PPAR-beta/delta agonist, GW0742, at the dose of 0,3 mg/kg in 10% DMSO, also attenuated the multiple organ dysfunction syndrome caused by zymosan. In pancreas, lung and gut, immunohistochemical analysis of some end points of the inflammatory response, such as inducible nitric oxide synthase (iNOS), nitrotyrosine, poly (ADP-ribose) (PAR), TNF- and IL-1as well as FasL, Bax, Bcl-2 and apoptosis, revealed positive staining in sections of tissue obtained from zymosan-injected mice. On the contrary, these parameters were markedly reduced in samples obtained from mice treated with GW0742</p> <p>Conclusions</p> <p>In this study, we have shown that GW0742 attenuates the degree of zymosan-induced non-septic shock in mice.</p

Nanostructured Photoelectrochemical Biosensing Platform for Cancer Biomarker Detection

The innovative photoelectrochemical properties of multifunctional nanomaterials are here investigated for the development of biosensing platforms for rapid and sensitive detection of a class of cancer biomarker candidates, known as microRNAs. Many different transducers have been proposed, so far, for microRNA detection. Recently, with the emergence of novel photoelectrochemically active species and new detection schemes, photoelectrochemistry has received increasing attention. Gold nanostructures have been, here, used to modify TiO2 electrodes. The surface of the nanostructured platform has been modified by nucleic acid capture probes (CPs). Biotinylated target miRNAs have been recognized by the specific CPs. The biosensing platform has been incubated with streptavidin alkaline phosphatase and exposed to a proper substrate. The product of the enzymatic reaction has been photoelectrochemically monitored. A compact and hand-held analytical device has been developed in order to have a final prototype in line with the concept of point of care testing. (C) 2017 The Authors. Published by Elsevier Ltd

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration

Bone regeneration represents still a challenge, in particular for calvarium defects. Recently, the development of biomaterials with the addiction of stem cells is giving promising results for the treatment of bone defects. In particular, it was demonstrated that scaffolds enriched with mesenchymal stem cells (MSCs) and/or their derivatives, such as conditioned medium (CM) and extracellular vesicles (EVs), may improve bone regeneration. Moreover, given the deep link between osteogenesis and angiogenesis, a successful approach must also take into consideration the development of vascularization. In this work we evaluated the bone regeneration capacity of a collagen membrane (3D-COL) enriched with human periodontal-ligament stem cells (hPDLSCs) and CM or EVs or EVs engineered with polyethylenimine (PEI-EVs) in rats subjected to a calvarial defect. We evaluated also their capacity to induce angiogenic factors. At first, in vitro results showed an increased expression of osteogenic markers in hPDLSCs cultured with the 3D-COL and PEI-EVs, associated also with the increased protein levels of Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2). The increased expression of these proteins was confirmed also in vivo in rats implanted with the 3D-COL enriched with hPDLSCs and PEI-EVs. Moreover, histological examination evidenced in this group of rats the activation of bone regeneration and of the vascularization process. Also MicroCT imaging with morphometric analysis confirmed in rats transplanted with 3D-COL enriched with hPDLSCs and PEI-EVs an important regenerative process and a better integration level. All together, these results evidenced that the 3D-COL enriched with hPDLSCs and PEI-EVs may promote bone regeneration of calvaria defects, associated also with an increased vascularization

Treatment with green tea extract attenuates secondary inflammatory response in an experimental model of spinal cord trauma

In this study, we evaluated the effect of green tea extract (that was administered 25 mg/kg intraperitoneal at 1 and 6 h after injury) in experimental animal model of spinal cord injury. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5–T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterised by oedema, neutrophilic infiltration and apoptosis. Also, immunohistochemical examination demonstrated a marked increase in immune reactivity for nitrotyrosine. All parameters of inflammation were attenuated by green tea extract. The degree of spinal cord inflammation, nitrotyrosine, poli (ADP-ribosio) synthetase (PARS) and neutrophilic infiltration was markedly reduced. Green tea extract significantly ameliorated the recovery of limb function. Values shown are mean ± SE mean of ten mice for each group. *p < 0.01 versus sham, °p < 0.01 versus spinal cord injury. Taken together, our results clearly demonstrate that green tea extract treatment ameliorates spinal cord injury oxidative stress

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection