Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes.

Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions.

Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet.

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms.

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.

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.

Left Ventricular Mass Reduction by a Low-Sodium Diet in Treated Hypertensive Patients.

Objective: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction.

Patients And Methods: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread.

Diabetes promotes invasive pancreatic cancer by increasing systemic and tumour carbonyl stress in Kras mice.

Background: Type 1 and 2 diabetes confer an increased risk of pancreatic cancer (PaC) of similar magnitude, suggesting a common mechanism. The recent finding that PaC incidence increases linearly with increasing fasting glucose levels supports a central role for hyperglycaemia, which is known to cause carbonyl stress and advanced glycation end-product (AGE) accumulation through increased glycolytic activity and non-enzymatic reactions. This study investigated the impact of hyperglycaemia on invasive tumour development and the underlying mechanisms involved.

Aortic Valve Replacement for Aortic Stenosis in Low-, Intermediate-, and High-Risk Patients: Preliminary Results From a Prospective Multicenter Registry.

Objective: To evaluate current results of surgical aortic valve replacement (SAVR) ± coronary artery bypass grafting surgery.

Design: Independent, multicenter, prospective registry.

Setting: Tertiary university hospitals.

Sodium Intake and Target Organ Damage in Hypertension-An Update about the Role of a Real Villain.

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk.

Low-Salt Intake Suggestions in Hypertensive Patients Do not Jeopardize Urinary Iodine Excretion.

A low-sodium diet is an essential part of the treatment of hypertension. However, some concerns have been raised with regard to the possible reduction of iodine intake during salt restriction. We obtained 24-h urine collections for the evaluation of iodine (UIE) and sodium excretion (UNaV) from 136 hypertensive patients, before and after 9 ± 1 weeks of a simple low-sodium diet.

The advanced glycation end-product N -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes-associated risk and its prevention.

Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs.

Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice.

Objective: Galectin-3 is constitutively expressed in bone cells and was recently shown to modulate osteogenic transdifferentiation of vascular smooth muscle cells and atherosclerotic calcification. However, the role of galectin-3 in bone physiology is largely undefined. To address this issue, we analyzed (1) the skeletal features of 1-, 3- and 6-month-old galectin-3 null (Lgals3) and wild type (WT) mice and (2) the differentiation and function of osteoblasts and osteoclasts derived from these animals.

Langmuir-Blodgett nanotemplates for protein crystallography.

The new generation of synchrotrons and microfocused beamlines has enabled great progress in X-ray protein crystallography, resulting in new 3D atomic structures for proteins of high interest to the pharmaceutical industry and life sciences. It is, however, often still challenging to produce protein crystals of sufficient size and quality (order, intensity of diffraction, radiation stability). In this protocol, we provide instructions for performing the Langmuir-Blodgett (LB) nanotemplate method, a crystallization approach that can be used for any protein (including membrane proteins).

Dietary interventions to contrast the onset and progression of diabetic nephropathy: A critical survey of new data.

This article is a critical overview of recent contributions on the dietary corrections and the foods that have been claimed to delay or hinder the onset of diabetic nephropathy (DN) and its progression to end-stage renal disease. Innovative dietary and behavioral approaches to the prevention and therapy of DN appear to be the most captivating in consideration of the rather well-established protocols for glucose and blood pressure control in use. In addition to restricted caloric intake to contrast obesity and the metabolic syndrome, adjustments in the patient's macronutrients intake, and in particular some degree of reduction in protein, have been long considered in the prevention of DN progression.

Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis.

Galectin-3 is an important modulator of several biological functions. It has been implicated in numerous disease conditions, particularly in the long-term complications of diabetes because of its ability to bind the advanced glycation/lipoxidation end products that accumulate in target organs and exert their toxic effects by triggering proinflammatory and prooxidant pathways. Recent evidence suggests that galectin-3 may also participate in the development of obesity and type 2 diabetes.

Galectin-3: an emerging all-out player in metabolic disorders and their complications.

Galectin-3 has been increasingly recognized as an important modulator of several biological functions, by interacting with several molecules inside and outside the cell, and an emerging player in numerous disease conditions. Galectin-3 exerts various and sometimes contrasting effects according to its location, type of injury or site of damage. Strong evidence indicates that galectin-3 participates in the pathogenesis of diabetic complications via its receptor function for advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs).

Results differ between transaortic and open surgical aortic valve replacement in women.

Background: Despite the well-known impact of female sex on outcome after surgical aortic valve replacement (sAVR), few studies investigated its role after transcatheter aortic valve replacement (TAVR).

Methods: After propensity-matching for age, baseline comorbidities, previous interventions, priority, frailty score, New York Heart Association class, left ventricular function and associated cardiac diseases, hospital mortality, and procedure-related morbidities of 388 women (194 TAVR versus 194 sAVR)-of 5,231 patients enrolled in 70 centers participating in this prospective multicenter national registry-were analyzed at a central management unit of the Italian National Institute of Health.

Results: Although hospital mortality was comparable (4.

Analysis of a multiple nuclear dots pattern in a large cohort of dermatological patients.

Background: Anti-multiple nuclear dots (MND) antibodies are the markers of primary biliary cirrhosis (PBC), but can also be found in patients with other autoimmune diseases.

Methods: We looked for MND in 9189 sera belonging to 6240 patients stored for autoimmune diseases with prevalent cutaneous features.

Results: Fifty sera proved anti-MND-positive and came from 15 different patients: 6 had lupus erythematosus, 2 dermatomyositis, 2 lichen planus, 1 stroke, 1 telogen effluvium, 1 autoimmune thrombocytopenia, and 2 undifferentiated connective tissue disease.

Thirty-five years of biliopancreatic diversion: notes on gastrointestinal physiology to complete the published information useful for a better understanding and clinical use of the operation.

Background: In the attempt to complete the available information on biliopancreatic diversion (BPD) use and mechanisms of action, some data and observations are presented that for different reasons were never published before.

Methods: These pieces of information derive from minute efforts of gastrointestinal physiology research or from rigorous but preliminary and incomplete collection of data, combined with the daily input from clinical use of BPD.

Result: They essentially regard intestinal limbs, gastric volume, and their interactions in affecting energy and protein intestinal absorption in BPD.

The effects of biliopancreatic diversion on type 2 diabetes mellitus in patients with mild obesity (BMI 30-35 kg/m2) and simple overweight (BMI 25-30 kg/m2): a prospective controlled study.

Background: Beneficial effects of BPD on T2DM in BMI >35 kg/m(2) patients are far better than those in patients with BMI 25-35. This study was aimed at investigating if a similar difference exists between patients with mild obesity (OB, BMI 30-35) or simple overweight (OW, BMI 25-30).

Methods: Fifteen OB (six M) and 15 OW (13 M), diabetic for ≥ 3 years, with HbA1c ≥ 7.

sHLA-I Contamination, a novel mechanism to explain ex vivo/in vitro modulation of IL-10 synthesis and release in CD8(+) T lymphocytes and in neutrophils following intravenous immunoglobulin infusion.

Background: Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.

Materials And Methods: Ex vivo analysis of cells from ten IVIG recipients showed significant increase of IL-10 mRNA and intra-cellular IL-10 molecules in both leukotypes.

Results: In vitro comparable results were obtained incubating CD8(+) T lymphocytes and neutrophils from healthy donors with IVIG.

sHLA-I contaminating molecules as novel mechanism of ex vivo/in vitro transcriptional and posttranscriptional modulation of transforming growth factor-beta in CD8+ T lymphocytes and neutrophils after intravenous immunoglobulin treatment.

Background: Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders. Among others' data, an in vitro increase of intracellular TGF-beta expression when culturing CD4+ T lymphocytes in the presence of IVIG has been reported. As IVIG infusion involves administration of soluble contaminants likewise all hemoderivative preparations, we hypothesized that, besides several other immunomodulatory proposed mechanisms, the clinical effects of IVIG therapy might be, at least partly, due to contaminating soluble HLA Class I (sHLA-I) molecules capable to exert pleiotropic immunomodulatory effects among which TGF-beta(1) modulation.

A comparison of a personal series of biliopancreatic diversion and literature data on gastric bypass help to explain the mechanisms of resolution of type 2 diabetes by the two operations.

Background: Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) are highly beneficial operations for type 2 diabetes mellitus (T2DM) in obese patients, leading to complete T2DM resolution in 75-90 and 97-99% of cases, respectively. In both RYGBP and BPD, the foregut is excluded from the food stream and the distal small bowel receives the food stimulation, while following BPD fat intestinal absorption is also extremely limited. This study was carried out to identify clinical features that could give insight on the different mechanisms of action on diabetes resolution.