Diabetes and pancreatic cancer-a dangerous liaison relying on carbonyl stress

Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals

Diabetic complications and oxidative stress: A 20‐year voyage back in time and back to the future

Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect. This twenty‐year journey focuses on the most relevant literature regarding the main sources of ROS generation in diabetes and their role in the pathogenesis of cell dysfunction and diabetic complications. To identify future research directions, this review discusses the evidence in favor and against oxidative stress as an initial event in the cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl stress and the Warburg effect, linking glucose and lipid excess, mitochondrial dysfunction, and the activation of alternative pathways of glucose metabolism leading to vascular cell injury and inflammation

The Megamaser Cosmology Project. X. High Resolution Maps and Mass Constraint for SMBHs

We present high resolution (sub-mas) VLBI maps of nuclear H2O megamasers for seven galaxies. In UGC6093, the well-aligned systemic masers and high-velocity masers originate in an edge-on, flat disk and we determine the mass of the central SMBH to be M_SMBH = 2.58*10^7Msun(+-7%). For J1346+5228, the distribution of masers is consistent with a disk, but the faint high-velocity masers are only marginally detected, and we constrain the mass of the SMBH to be in the range 1.5-2.0*10^7Msun. The origin of the masers in Mrk1210 is less clear, as the systemic and high-velocity masers are misaligned and show a disorganized velocity structure. We present one possible model in which the masers originate in a tilted, warped disk, but we do not rule out the possibility of other explanations including outflow masers. In NGC6926, we detect a set of redshifted masers, clustered within a pc of each other, and a single blueshifted maser about 4.4pc away, an offset that would be unusually large for a maser disk system. Nevertheless, if it is a disk system, we estimate the enclosed mass to be M_SMBH<4.8*10^7 Msun . For NGC5793, we detect redshifted masers spaced about 1.4pc from a clustered set of blueshifted features. The orientation of the structure supports a disk scenario as suggested by Hagiwara et al.(2001). We estimate the enclosed mass to be M SMBH<1.3*10^7 Msun. For NGC2824 and J0350-0127, the masers may be associated with pc or sub-pc scale jets or outflows.Comment: Accepted by Ap

Growth induction and low-oxygen apoptosis inhibition of human CD34 + progenitors in collagen gels

Various reports have indicated low survival of injected progenitors into unfavorable environments such as the ischemic myocardium or lower limb tissues. This represents a major bottleneck in stem-cell-based cardiovascular regenerative medicine. Strategies to enhance survival of these cells in recipient tissues have been therefore sought to improve stem cell survival and ensure long-term engraftment. In the present contribution, we show that embedding human cord blood-derived CD34+ cells into a collagen I-based hydrogel containing cytokines is a suitable strategy to promote stem cell proliferation and protect these cells from anoxia-induced apoptosis

Plasduino: an inexpensive, general purpose data acquisition framework for educational experiments

Based on the Arduino development platform, Plasduino is an open-source data acquisition framework specifically designed for educational physics experiments. The source code, schematics and documentation are in the public domain under a GPL license and the system, streamlined for low cost and ease of use, can be replicated on the scale of a typical didactic lab with minimal effort. We describe the basic architecture of the system and illustrate its potential with some real-life examples.Comment: 11 pages, 10 figures, presented at the XCIX conference of the Societ\`a Italiana di Fisic

Ultrasound as first line step in anaemia diagnostics

This review covers the role of ultrasonography as an essential non-invasive diagnostic approach when facing patients with anaemia, a common clinical problem. Abdomen ultrasound is well recognised as a first-line examination in the setting of blood loss, both acute and chronic. Less is clear about the additional opportunities, given by ultrasound in anaemia, due to the many other possible causes. Here we provide information on the utility of ultrasound in different contexts and a practical guide for clinicians facing anaemic patients