An Outlook on Uterine Neoplasms: From Hormonal and DNA Damaging to Cervical and Endometrial Cancer Development and Minimally Invasive Management.

Uterine neoplasms are common tumors, formed by endometrial and cervical cancers; endometrial cancer is the fourth most frequently diagnosed cancer in developed countries and the eighth leading cause of cancer death in women, and cervical cancer is the second most common cancer in women worldwide and is a leading cause of cancer-related death in women in underdeveloped countries. Cervical cancer arises by HPV DNA damaging; in fact cervical cancer starts in the cells on the surface of the cervix, exposed to viral infective agents, as HPV, founded in 80% of patients affected by cervical cancer. Thus, more than 99% of cervical uterine cancer cases show HPV presence. Nevertheless, Endometrial cancer involves cancerous growth of the endometrium, and increasing evidence indicates that different biological and genetic factors play relevant roles its onset so as carcinogenesis generally develops by hormonal modifications. Both tumors can be safely and feasibly managed from minimally invasive surgical techniques till to endoscopic radical operations, such as hysterectomy, bilateral salpingo- oophorectomy, pelvic and para-aortic lymphadenectomy for surgical treatment. The authors reviewed several excellent reviews and studies in the area of hormonal, viral and genetical risk factors associated with endometrial and cervical cancer risk and development, analyzing the area of biologic markers, all papers dealing with serum and plasma markers involved in uterine cancer detection, development, progression and minimally invasive treatment

RGS4 negatively modulates Nociceptin/Orphanin FQ opioid receptor signaling: implication for L-Dopa induced dyskinesia

Background and purpose Regulator of G-protein signal 4 (RGS4) is a signal transduction protein that accelerates intrinsic GTPase activity of Gαi/o and Gαq subunits, suppressing GPCR signaling. Here we investigate whether RGS4 modulates nociceptin/orphanin FQ (N/OFQ) opioid (NOP) receptor signaling and this modulation has relevance for L-Dopa-induced dyskinesia. Experimental approach HEK293T cells transfected with NOP, NOP/RGS4 or NOP/RGS19 were challenged with N/OFQ and the small molecule NOP agonist AT-403, using D1-stimulated cAMP levels as a readout. Primary rat striatal neurons and adult mouse striatal slices were challenged with N/OFQ or AT-403 in the presence of the experimental RGS4 chemical probe, CCG-203920, and D1-stimulated cAMP or phosphorylated extracellular signal regulated kinase 1/2 (pERK) responses were monitored. In vivo, CCG-203920 was co-administered with AT-403 and L-Dopa to 6-hydroxydopamine hemilesioned rats, and dyskinetic movements, striatal biochemical correlates of dyskinesia (pERK and pGluR1 levels) and striatal RGS4 levels were measured. Key results RGS4 expression reduced NOFQ and AT-403 potency and efficacy in HEK293T cells. CCG-203920 increased N/OFQ potency in primary rat striatal neurons, and potentiated AT-403 response in mouse striatal slices. CCG-203920 enhanced AT-403 mediated inhibition of dyskinesia and its biochemical correlates, without compromising its motor-improving effects. Unilateral dopamine depletion caused bilateral reduction of RGS4 levels, which was reversed by L-Dopa. L-Dopa acutely upregulated RGS4 in the lesioned striatum. Conclusions and Implications RGS4 physiologically inhibits NOP receptor signaling. CCG-203920 enhanced NOP responses and improved the antidyskinetic potential of NOP receptor agonists, mitigating the effects of striatal RGS4 upregulation occurring during dyskinesia expression

Diritti umani e Mediterraneo nel Human Rights Data Project

Analisi dei dati del Human Rights Data Project applicata ai Paesi del Mediterraneo

Introduzione

I quaderni editoriali Eunomia raccolgono alcuni fra i più meritevoli lavori finali svolti nelle materie del Diritto internazionale e dei Diritti umani dagli iscritti al C.d.L. in Scienze Politiche e delle Relazioni Internazionali dell'Università del Salento

Molecular and imaging prodromal markers of dopamine neuron degeneration in animal models of Parkinson’s disease: pathophysiology and clinical perspectives

The target of the proposal is to identify pre-degenerative/premotor molecular and cellular alterations, that initiate and contribute to early structural synaptic and axonal dopaminergic damage in the Caudate-Putamen (CPu) of mice that model Parkinson’s disease (PD)-like pathology, in order to delineate new diagnostic and therapeutic strategies that can be translated to the clinic to healing dopaminergic neurodegeneration. To achieve this target, we will use classical neuropathological and functional investigations and advanced microscopy techniques to correlate molecular/structural imaging with data obtained from MRI and PET analysis. This strategy will help to clarify whether and how key events involved in PD pathogenesis, such as alpha-synuclein (AS) pathology, neuroinflammation and mitochondrial derangement, can trigger synaptic and axonal damage detectable by brain imaging to provide very early diagnostic markers of PD. The project will also evaluate the effects of novel neuroprotective compounds (some of them under patent), which may be used to counteract the neuronal demise underlying PD. The deliverables of this project own great potential of scientific and technological advancement in PD research, with significant social and economic impact