Interplay between FGFR2b-induced autophagy and phagocytosis: role of PLCγ-mediated signalling

Signalling of the epithelial splicing variant of the fibroblast growth factor receptor 2 (FGFR2b) induces both autophagy and phagocytosis in human keratinocytes. Here, we investigated, in the cell model of HaCaT keratinocytes, whether the two processes might be related and the possible involvement of PLCγ signalling. Using fluorescence and electron microscopy, we demonstrated that the FGFR2b-induced phagocytosis and autophagy involve converging autophagosomal and phagosomal compartments. Moreover, the forced expression of FGFR2b signalling mutants and the use of specific inhibitors of FGFR2b substrates showed that the receptor-triggered autophagy requires PLCγ signalling, which in turn activates JNK1 via PKCδ. Finally, we found that in primary human keratinocytes derived from light or dark pigmented skin and expressing different levels of FGFR2b, the rate of phagocytosis and autophagy and the convergence of the two intracellular pathways are dependent on the level of receptor expression, suggesting that FGFR2b signalling would control in vivo the number of melanosomes in keratinocytes, determining skin pigmentation

Remission of Kimura disease with carotid hypervascularization after cyclosporine treatment

No abstract available

Extracorporeal Shock Wave Treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs)

Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury

PANIC DISORDER, ANXIETY, AND CARDIOVASCULAR DISEASES

Different data indicate that psychological and/or emotional disorders may play an important role in the natural history of heart diseases. Although the major evidence is that related to depression, epidemiological data would indicate that anxiety and panic disorders are highly represented in cardiac patient, thus influencing mortality and morbidity. The diagnosis of panic disorder in patients with chest pain is crucial to a correct therapeutic approach, as well as to reduce the risks and costs of inappropriate treatments. Anxiety and panic may accelerate different direct and indirect processes involved in the pathogenesis of cardiovascular diseases: lifestyle risk factors, arterial hypertension, myocardial perfusion, autonomic nervous system or hypothalamus-pituitary-adrenal axis, platelet activation, and inflammation processes. Panic disorder seems to correlate particularly with sudden death: this suggests that it may be considered one of the main inducers of life-threatening arrhythmias, rather than to be linked to the development and progression of coronary atherosclerosis. Beyond hard outcomes, panic disorders produce negative effects on both global adjustment and life quality that may impair the course of the cardiac diseases. Interestingly, specific antipanic and anxiolytic agents seem to be particularly effective upon life quality. In any case, adequate controlled clinical trials are necessary in order to confirm the possibility of cardiovascular risk reduction by means of anxiety and panic disorder treatment

Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF. In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF

Predicting LVOT Obstruction in Transcatheter Mitral Valve Replacement for Failed Surgical Annuloplasty

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Fluorescein-guided surgery for intradural spinal tumors: A single-center experience

•Gross total removal has a pivotal role in surgical treatment of intradural spinal tumors.•Sodium fluorescein prevents vascular injuries also preserving pial vessels in posterior myelotomy.•Fluorescence before the durotomy helps to distinguishing tumor from healthy tissue in intradural lesions.•Intraoperative fluorescence is safe and effective, also preserving functional anatomy in tumor removal

Expression of miRNA-33 and miRNA-155 in symptomatic and asymptomatic carotid artery stenosis

Background: The aim of this study was to evaluate miRNA-33 and miRNA-155 expression in Peripheral Blood Mononuclear Cells (PBMC) and carotid specimens of patients affected by Critical Carotid Artery stenosis (CAS). Material and Methods: We selected 17 asymptomatic (CAS-A group) and 10 symptomatic (CAS-S group) patients with CAS. Ten patients with traditional cardiovascular risk factors (RF group), matched for age and sex, were used as control group. Results: A significant increase in miRNA-33 expression was observed both in peripheral blood and in carotid specimens of CAS-A patients (p 0.04) in comparison with CAS-S and RF, whereas no significant difference were found among the groups regarding miRNA-155 expression both in peripheral blood and in carotid specimens. Conclusions: This is to our knowledge the first report on miRNAs expression in human PBMCs from CAS patients. Results of this study suggest that miRNA-33 in involved in the process underling plaque formation and growth, but not is plaque instability and ischemic brain damage, whereas miRNA-155 is expressed during all the phases of atherosclerotic disease

In vitro characterization of mitochondrial function and structure in rat and human cells with a deficiency of the NADH:ubiquinone oxidoreductase Ndufc2 subunit

Ndufc2, a subunit of the NADH:ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure-function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke

Comparative studies of the Pschorr reaction in the pyrazole series. Access to the new dibenzo(e,g)pyrazolo(1,5-a)(1,3)diazocine system of pharmaceutical interest

The diazonium tetrafluoroborate 11 obtained from 2-amino-N-methyl-N-(1-phenyl-3-methylpyrazol-5-yl)benzamide was transformed in dry acetonitrile via an ionic or radical pathway. Diferences were observed with respect to ionic or radical transformations in aqueous media of the analogous diazonium hydrogen sulfate 1 derived from the same amine. In acetonitrile solution, the ionic pathway was characterized by an increased yield of 1,4-dimethyl-3-phenyl-pyrazolo[3,4-c]isoquinolin-5-one 4 and by the formation of its isomer, the new derivative 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]diazocin-10(9H)-one 12. When the reaction folowed a radical pathway, the pyrazolo[3,4-c]isoquinoline derivative 4 and N-methyl-2-(1-phenyl-3-methylpyrazol-5-yl)benzamide 17, the later due to a 1,4-pyrazolyl transfer proces, were isolated in low yields. Decomposition of the solid diazonium tetrafluoroborate at its melting point gave compounds 4, 12 and the N-(1-phenyl-3-methylpyrazol-5-yl)-2-fluorobenzamide 17. The crystal structure of compound 12 was also determined