University of Brescia

About: University of Brescia is a education organization based out in Brescia, Italy. It is known for research contribution in the topics: Population & Heart failure. The organization has 8090 authors who have published 24576 publications receiving 780862 citations. The organization is also known as: Università degli Studi di Brescia & Universita degli Studi di Brescia.

Polymorphisms of the Interleukin-1β Gene Affect the Risk of Myocardial Infarction and Ischemic Stroke at Young Age and the Response of Mononuclear Cells to Stimulation In Vitro

Abstract: Objectives— To investigate the role of interleukin-1β (IL-1β) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. Methods and Results— A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the −511C/T IL-1β polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect ( P =0.0020 in MI; P =0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1β and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1β during cell stimulation resulted in a marked reduction of tissue factor activity expression. Conclusions— -511C/T IL-1β gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.

Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types

Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the add ...

Review: Parkinson's disease: from synaptic loss to connectome dysfunction

Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder with prominent loss of nigro-striatal dopaminergic neurons. The resultant dopamine (DA) deficiency underlies the onset of typical motor symptoms (MS). Nonetheless, individuals affected by PD usually show a plethora of nonmotor symptoms (NMS), part of which may precede the onset of motor signs. Besides DA neuron degeneration, a key neuropathological alteration in the PD brain is Lewy pathology. This is characterized by abnormal intraneuronal (Lewy bodies) and intraneuritic (Lewy neurites) deposits of fibrillary aggregates mainly composed of α-synuclein. Lewy pathology has been hypothesized to progress in a stereotypical pattern over the course of PD and α-synuclein mutations and multiplications have been found to cause monogenic forms of the disease, thus raising the question as to whether this protein is pathogenic in this disorder. Findings showing that the majority of α-synuclein aggregates in PD are located at presynapses and this underlies the onset of synaptic and axonal degeneration, coupled to the fact that functional connectivity changes correlate with disease progression, strengthen this idea. Indeed, by altering the proper action of key molecules involved in the control of neurotransmitter release and re-cycling as well as synaptic and structural plasticity, α-synuclein deposition may crucially impair axonal trafficking, resulting in a series of noxious events, whose pressure may inevitably degenerate into neuronal damage and death. Here, we provide a timely overview of the molecular features of synaptic loss in PD and disclose their possible translation into clinical symptoms through functional disconnection.

The oxysterol–CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils

Abstract: Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs. We report that tumor-derived oxysterols recruit protumor neutrophils in a liver X receptor (LXR)–independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression. We demonstrate that interfering with the oxysterol–CXCR2 axis delays tumor growth and prolongs the overall survival of tumor-bearing mice. These results identify an unanticipated protumor function of the oxysterol–CXCR2 axis and a possible target for cancer therapy.