Activation of Stress Kinases in the Brain of Mucopolysaccharidosis IIIB mice

The accumulation of heparan sulfate (HS) in lysosomes is the primary consequence of the enzyme defect (α-N-acetylglucosaminidase) in mucopolysaccharidosis type IIIB. This accumulation triggers a cascade of pathological events that progressively leads to CNS pathology. Here we examined the activation of the three major stress kinases in the neuronal tissue of a murine model of the disease. ERK1/2 was significantly higher in the cortex of 1–2-month-old affected animals compared with wild-type (Wt) littermates. Similarly, ERK1/2 was stimulated in neurons cultured from MPS IIIB mice. SAPK/JNK was also found to be activated in the cortex of 1–2-month-old affected animals compared with Wt subjects, and the same was found for cultured neurons. In contrast, the active form of p38MAPK was lower in the cortex of 1-month-old MPS IIIB mice compared with Wt animals, but no significant difference was found between the two p38MAPK analyzed in normal and affected neurons cultured in vitro. These data indicate the possible involvement of MAPK dysregulation in the early stage of MPS IIIB brain disease. © 2011 Wiley-Liss, Inc

Anti-VEGF Therapy in Breast and Lung Mouse Models of Cancers

Cancer is the second leading cause of death in the world after cardiovascular diseases. Some types of cancer cells often travel to other parts of the body through blood circulation or lymph vessels, where they begin to grow. This process is recognized as metastasis. Angiogenesis is the formation of new blood vessels from existing vessel. Normally angiogenesis is a healthy process, that helps the body to heal wounds and repair damaged body tissues, whereas in cancerous condition this process supports new blood vessels formation that provide a tumor with its own blood supply, nutrients and allow it to grow. The most important proximal factor for angiogenesis is the vascular endothelial growth factor VEGF. Angioinhibition is a form of targeted therapy that uses drugs to stop tumors from making new blood vessels. Therefore, in this paper we analyse the importance of VEGF as target of cancer therapy, analysing murine models

Late diagnosis of Fabry disease caused by a de novo mutation in a patient with end stage renal disease.

BACKGROUND: We present the case of a white 35-year-old male with a diagnosis of Fabry disease and negative family history. CASE PRESENTATION: At the age of 31, he underwent a renal biopsy with a diagnosis of hypertension-induced nephroangiosclerosis. At the age of 35, he was referred to our hospital and started dialysis: the unusual finding of left ventricular hypertrophy with a normal ejection fraction and of myocardial fibrosis at the cardiac magnetic resonance suggested a diagnosis of Fabry disease, although there was no apparent family history—so extensive tests were subsequently undertaken. The patient had low plasma levels of α-galactosidase A and the genetic analysis showed a single nucleotide point mutation in hemizygosis at nucleotide c.901 C>T in exon 6 of the GLA gene, confirming the diagnosis of Fabry disease. We extended the genetic analysis to all family members of the patient (mother, sister and brothers) and none of them had any alteration in the GLA gene, suggesting a de novo mutation in the patient. CONCLUSIONS: In a family, it is rare to find only one Fabry disease affected subject with a de novo mutation. These findings emphasize the importance of early diagnosis, genetic counseling and studying the genealogical tree of suspicious patients, even in absence of a typical family history

Finding aquaporins in annelids : An evolutionary analysis and a case study

Funding Information: This research was funded by PRIN2017 Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale 2017 (grant # 2017J92TM5) by Italian MUR to G.C. and by the Molecular Bio-diversity Laboratory of the Italian node of Lifewatch (CNR, Consiglio Nazionale delle Ricerche) to C.G.Peer reviewedPublisher PD

Persistent photoconductivity in 2-dimensional electron gases at different oxide interfaces

We report on the transport characterization in dark and under light irradiation of three different interfaces: LaAlO3/SrTiO3, LaGaO3/SrTiO3, and the novel NdGaO3/SrTiO3 heterostructure. All of them share a perovskite structure, an insulating nature of the single building blocks, a polar/non- polar character and a critical thickness of four unit cells for the onset of conductivity. The interface structure and charge confinement in NdGaO3/SrTiO3 are probed by atomic-scale- resolved electron energy loss spectroscopy showing that, similarly to LaAlO3/SrTiO3, extra electronic charge confined in a sheet of about 1.5 nm in thickness is present at the NdGaO3/SrTiO3 interface. Electric transport measurements performed in dark and under radiation show remarkable similarities and provide evidence that the persistent perturbation induced by light is an intrinsic peculiar property of the three investigated oxide-based polar/non-polar interfaces. Our work sets a framework for understanding the previous contrasting results found in literature about photoconductivity in LaAlO3/SrTiO3 and highlights the connection between the origin of persistent photoconductivity and the origin of conductivity itself. An improved understanding of the photo- induced metastable electron-hole pairs might allow to shed a direct light on the complex physics of this system and on the recently proposed perspectives of oxide interfaces for solar energy conversion.Comment: 11 pages, 7 figure

Contribution of vitamin D3 and thiols status to the outcome of COVID-19 disease in Italian pediatric and adult patients

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), was declared a global pandemic by the World Health Organization (WHO) on March 2020, causing unprecedented disease with million deaths across the globe, mostly adults. Indeed, children accounted for only a few percent of cases. Italy was the first Western country struck by the COVID-19 epidemic. Increasing age, which is one of the principal risk factors for COVID-19 mortality, is associated with declined glutathione (GSH) levels. Over the last decade, several studies demonstrated that both vitamin D (VD) and GSH have immunomodulatory properties. To verify the association between VD, GSH and the outcome of COVID-19 disease, we conducted a multicenter retrospective study in 35 children and 128 adult patients with COVID-19. Our study demonstrated a hypovitaminosis D in COVID-19 patients, suggesting a possible role of low VD status in increasing the risk of COVID-19 infection and subsequent hospitalization. In addition, we find a thiol disturbance with a GSH depletion associated to the disease severity. In children, who fortunately survived, both VD and GSH levels at admission were higher than in adults, suggesting that lower VD and thiols levels upon admission may be a modifiable risk factor for adverse outcomes and mortality in hospitalized patients with COVID-19

Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization.

"Abstract. Transcriptional silencing by CpG island hypermethylation plays a critical role in endometrial carcinogenesis. In a collection of benign, premalignant and malignant endometrial lesions, a methylation profile of a complete gene panel, such steroid receptors (ERα, PR), DNA mismatch repair (hMLH1), tumor-suppressor genes (CDKN2A\/P16 and CDH1\/E-CADHERIN) and WNT pathway inhibitors (SFRP1, SFRP2, SFRP4, SFRP5) was investigated in order to demonstrate their pathogenetic role in endometrial lesions. Our results indicate that gene hypermethylation may be an early event in endometrial endometrioid tumorigenesis. Particularly, ERα, PR, hMLH1, CDKN2A\/P16, SFRP1, SFRP2 and SFRP5 revealed a promoter methylation status in endometrioid carcinoma, whereas SFRP4 showed demethylation in cancer. P53 immunostaining showed weak-focal protein expression level both in hyperplasic lesions and in endometrioid cancer. Non-endometrioid cancers showed very low levels of epigenetic methylations, but strong P53 protein positivity. Fisher exact test revealed a statistically significant association between hMLH1, CDKN2A\/P16 and SFRP1 genes methylation and endometrioid carcinomas and between hMLH1 gene methylation and peritumoral endometrium (p < 0.05). Our data confirm that the methylation profile of the peritumoral endometrium is different from the altered molecular background of benign endometrial polyps and hyperplasias. Therefore, our findings suggest that the methylation of hMLH1, CDKN2A\/P16 and SFRP1 may clearly distinguish between benign and malignant lesions. Finally, this study assessed that the use of an epigenetic fingerprint may improve the current diagnostic tools for a better clinical management of endometrial lesions.