The concept of “type 3 diabetes” has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD).
Novel evidence suggests that ...changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aβ) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state. As the pathophysiological role of Aβ1–40 in patients with cardiovascular disease has attracted attention due to its involvement in plaque formation and destabilization, it is of great interest to explore whether a paradigm similar to that in AD exists in the cardiovascular field. Therefore, this review aims to elucidate the intricate interplay between insulin resistance, IGF-1, and Aβ1–40 in the cardiovascular system and assess the applicability of the type 3 diabetes concept. Understanding these relationships may offer novel therapeutic targets and diagnostic strategies to mitigate cardiovascular risk in patients with insulin resistance and dysregulated IGF-1 signaling.
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•Relationship between Diabetes and Alzheimer's disease is called Type 3 diabetes.•Molecular changes in Diabetes Mellitus influence Aβ production.•Diabetes Mellitus-dependent Aβ production is suggested in patients with CVDs.•Aβ has pro-atherosclerotic and pro-thrombotic characteristics.•Aβ is potentially harmful in ischemia reperfusion injury in AMI patients.
The dietary methionine (Met) and total sulfur amino acid (TSAA) requirements of European sea bass (Dicentrarchus labrax) (initial body weight 13.4 (SD 0.2) g) were estimated in a 12-week ...dose-response experiment. Seven isonitrogenous (7.6 % DM) and isoenergetic (gross energy, 21.2 MJ/kg DM) diets, based on soya protein and crystalline L-amino acids containing graded levels of L-Met (1.6-16.2 g/kg) at a constant cysteine (4 g/kg) level and a fish meal-based diet, were fed each to triplicate groups of fifty fish kept in 250 litre tanks in a thermoregulated (23 +/- 0.5 degrees C) seawater system. The Met and TSAA-deficient diet resulted in higher mortality, impaired feed intake and growth relative to the other treatments (P < 0.01). No signs of lens opacity due to limiting Met intake were observed and no feed intake or growth depression occurred at the highest level of dietary TSAA. Met and TSAA requirements for optimal N deposition or weight gain as fitted with the broken-line model resulted in estimated values of 8.0 and 12.0 g/kg diet (for example, 1.8 and 2.7 % dietary protein) and 9.1 and 13.1 g/kg diet (for example, 2.0 and 3.0 % dietary protein), respectively. Plasma levels of Met, homocysteine and cysteine increased in response to excess dietary TSAA, corroborating requirement estimates from growth data. N gain resulted in a linear function of TSAA consumption at marginal Met (TSAA) intake. The TSAA intake needed to maintain N balance resulted in a value of 20.0 mg TSAA/kg average body weight0.75 per d, which represents 23 % of the total (maintenance+accretion) requirement.
Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this ...context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known. In this study, we applied high-resolution proteomics to murine and human iRhom2-deficient macrophages for a systematic identification of substrates, and therefore functions, of the iRhom2/ADAM17 proteolytic complex. We found that iRhom2 loss suppressed the release of a group of transmembrane proteins, including known (e.g. CSF1R) and putative novel ADAM17 substrates. In the latter group, shedding of major histocompatibility complex class I molecules (MHC-I) was consistently reduced in both murine and human macrophages when iRhom2 was ablated. Intriguingly, it emerged that in addition to its shedding, iRhom2 could also control surface expression of MHC-I by an undefined mechanism. We have demonstrated the biological significance of this process by using an in vitro model of CD8
+
T-cell (CTL) activation. In this model, iRhom2 loss and consequent reduction of MHC-I expression on the cell surface of an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line dampened activation of autologous CTLs and their cell-mediated cytotoxicity. Taken together, this study uncovers a new role for iRhom2 in controlling cell surface levels of MHC-I by a dual mechanism that involves regulation of their surface expression and ectodomain shedding.
The effects of feeding two complete extruded diets differing in protein source (fish meal-FM vs. vegetable proteins-VP) over 30 weeks and subsequent 30 days of starvation on biometry, fillet ...composition and liver IGF-I mRNA were studied in large rainbow trout. At the end of the feeding period, the dietary protein source little affected major biometry traits, dressing out yields and overall adiposity (P<0.05) but fish given the VP diet resulted in higher content of PUFA n-6 fatty acids in muscle (0.46 vs. 0.22 g/100g fillet, P<0.05). Regardless of the previous diet, 30 days of starvation resulted in increased carcass yield (P<0.05), in a slight reduction in adiposity (P<0.05) and of all fatty acids in fillet (P<0.05), except DHA. Liver IGF-I mRNA content was little affected by the test diet and starvation.
The search for novel exopolysaccharides (EPS) with targeted functionalities is currently a topic of great interest. This study aimed to investigate the chemical characteristics and technological ...properties of a novel EPS (named EPS_O) from Leuconostoc mesenteroides. EPS_O was a high-molecular-weight dextran (>6.68 × 105 g/mol) characterized by high water-holding capacity (785 ± 73%) and high water solubility index (about 99%). EPS_O in water (<30 mg/mL) formed viscous solutions, whereas at concentrations >30 mg/mL, it formed weak gels. Notably, lower concentrations (4–5 mg/mL) exhibited antimicrobial activity against various foodborne pathogens, antibiofilm activity against Listeria monocytogenes, and radical-scavenging activity. These properties are significant for maintaining food quality and promoting health. Based on these findings, EPS_O presents itself as a promising food ingredient that could elevate food quality and confer health benefits to consumers.
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•Leuconostoc mesenteroides DSA_O produced a high-molecular-weight dextran (EPS_O).•EPS_O displayed strong antimicrobial and antibiofilm activity.•The dextran exhibited radical scavenging ability.•Weak gels were formed by EPS_O at concentration > 3%.•The properties of EPS_O may be exploited in functional foods.
The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the ...lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH) model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid profile, transaminases, HOMA-IR, steatosis, inflammation, fibrosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic life style changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a significant improvement in glycemia, visceral fat, lipid profile, and liver fibrosis. Moreover, it reduced (both in vitro and in vivo) ALT, hepatic inflammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the beneficial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH.
We report the case of a 28-year-old Caucasian patient symptomatic for low-threshold angina. Coronary angiography ruled out significant coronary stenosis. He was diagnosed with familial ...hypercholesterolemia and severe aortic stenosis in a setting of bicuspid valve disease. Preoperative evaluation showed diffuse atheromatous disease and severe calcification of the ascending aorta. The patient was treated by endarterectomy of the ascending aorta, non-coronary sinus enlargement patch and aortic valve replacement. This case report emphasizes the role of aortic valve disease in patients with familial hypercholesterolemia and highlights the complexity of surgical management of this condition.
•The reduction of fat content in food is a timely issue.•The plasticizing properties of lipids could be exploited to develop low-fat spreads.•Mathematical predictive tools could be useful to develop ...new formulations.
The research was addressed to develop mathematical predictive models to be applied in the formulation of low-fat chocolate spreads. To this purpose, fats (palm oil, palm kernel fat and their blends) and oils (sunflower oil and extra virgin olive oil) with different physical properties were considered. The effect of lipid type and content on spread firmness and physical stability was assessed by measuring mechanical properties and oil release. Results were described by opportune mathematical models defined by using best-fitting analysis. The effectiveness of the models was finally validated considering the formulation of a chocolate spread having defined firmness and physical stability. The developed mathematical tools could support the choice of the lipid nature and concentration allowing the preparation of chocolate spreads with tailored nutritional properties. In the attempt to reduce fat content, the minimum lipid concentration required to obtaining a homogeneous spread can be predicted by the developed mathematical models.
Mental disorders are a major public health problem. However, over the last few years, there have been few studies aimed at evaluating their diffusion. Therefore, this study aimed at evaluating: the ...prevalence of the most frequent psychiatric disorders in the general population residing in Tuscany using a clinical scale administered by trainee in psychiatry.
The study was carried out on a representative sample of the general population aged > 18 years, randomly extracted from the register of patients in the Tuscany region, adopting a proportional sampling method stratified by gender, age group and Local Health Units (LHU). Each person was contacted by letter followed by a phone call from an operator who makes an appointment with the trainee in psychiatry. The diagnostic interview conducted was the Mini-International Neuropsychiatric Interview (MINI). Point and lifetime prevalence by gender and age group were calculated. Differences and associations were considered statistically significant if their p-values were less than 0.05.
Of the 408 people involved, 390 people were enrolled (of which 52.6% female). The 28.5% of the sample had been affected by a psychiatric disorder during their lifetime. In their lifetime, the most represented psychiatric disorders were major depressive episode (20.4%), major depressive disorder (17.0%) and panic disorder (10.3%), more frequent in the female than the male group. Current conditions were predominantly major depressive episode (3.1%) and agoraphobia (2.8%). A 5.9% rate of current suicidal ideation was also found.
In the general population, 28.5% of people reported a psychiatric disorder during their lifetime. This prevalence is considerably higher than that reported in a previous study carried out in central Italy.
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