Preclinical and clinical evidence of nephro- and cardiovascular protective effects of glycosaminoglycans

Despite advances in pharmacological treatment, diabetic nephropathy is still the leading cause of end-stage renal disease and an important cause of morbidity and mortality in diabetics. Glycosaminoglycans are long, unbranched mucopolysaccharides that play an important role in establishing a charge-selective barrier that restricts the passage of negatively charged molecules, such as albumin and other proteins, at the level of the glomerular basal membrane. Their loss is associated with loss of selectivity and proteinuria. Extensive preclinical evidence and some clinical trials suggest that glycosaminoglycans replacement is associated with improvement of glomerular selectivity and of proteinuria. Sulodexide could also have some other effects, potentially useful to reduce the renal damage and the cardiovascular disease associated with proteinuria, such as improvement of haemorheological and blood lipid parameters, an endothelium protective effect and anti-inflammatory action. This review will discuss the evidence supporting the potential nephroprotective effects of sulodexide and other glycosaminoglycans

Tuning the potential drop at graphene/protic ionic liquid interface by molecular structure engineering

Ionic liquids (ILs) have been extensively employed in many applications involving interfaces with carbon-based electrodes, such as energy storage devices (batteries or supercapacitors) or electrocatalytic devices, where the way each ion of the IL interacts with the electrode has a strong impact on the overall performance of the device. For instance, the amount of potential difference between the electrode and the bulk of the IL is highly sensitive to the IL composition and it is directly related to the device capacitance. The selection of the most suited pair of ions often proceeds by time-consuming and costly trial-and-error approaches. It is necessary to understand the atomistic features of the interface to determine the effect of each ion on the potential drop. By classical molecular dynamics simulations, we show that it is possible to quickly infer the interface potential arising at the carbon electrode by carefully inspecting the molecular structure of the IL. The ion orientation at the interface is, in fact, determined by the distribution of charges within the molecules. Depending on where charges are located, ions can either lie flat or perpendicular to the interface to minimize the surface energy. The interface potential is found to be mainly determined by ion-ion interactions dictating the interface energy minimization process, whereas ion-electrode interactions are found to enforce higher ordering and charge layers stacking but not to induce selective adsorption of an ion over the other

An Evolving Definition of a “Healthy Diet”

Throughout life, most of us eat at least three meals a day for 365 days a year. It follows that, in a 90-year life, everyone is potentially exposed to food constituents (i.e., nutrients, bioactives, and other chemical compounds) more than 95 thousand times; therefore, dietary habits are a relevant determinant of health status. In daily clinical practice, we usually discourage patients from eating foods deemed unhealthy, such as highly processed items. Even more rarely do we recommend that patients consume healthy foods, except as an alternative to junk foods. Nevertheless, it is well known that a healthy diet prevents several chronic and degenerative diseases and is the key to a healthy and long life. However, what is a healthy diet and how do we define it? Recently, a large number of epidemiological studies have attempted to identify which dietary factors correlate with negative health outcomes, including death, loss of function, and lack of well-being. Determinants of positive health outcomes have been more rarely investigated, on the contrary

Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and -most importantly-with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders

Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer

Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hundred and twenty patients with MCRC were enrolled in this study. The median PFS of the first-, second-, and third-lines of treatment and the OS were evaluated. The correlation between the time to progression and the OS was analyzed. The median PFS of the three lines of treatment were 8.5, 5, and 3 months, respectively. Results: The median OS was 32.4 months. A modest correlation was found between the PFS to the first-line treatment with Folfox\u2013avastin and OS. Similar data were obtained with the second-line treatment. However, no correlation was found between the PFS and OS during the third-line treatment. The regression analysis revealed that PFS is predictive of OS. Conclusion: In brief, the PFS of the first- and second-lines of treatment could be a good candidate as a surrogate endpoint of OS in patients with MCRC

Short-term evolocumab-induced tendon xanthomas regression in an elderly patient with homozygous familial hypercholesterolemia

Homozygous Familial Hypercholesterolemia (HoFH) is a rare inherited disorder affecting 1 in 160,000 to 1 in 300,000 individuals and resulting in extremely elevated low-densitym lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Manifestations of ASCVD most notably include fatal and non-fatal myocardial infarction (MI) and occlusive vascular disease requiring surgical or percutaneous revascularization. Deposits of cholesterol in the skin or tendons, or both, called xanthomas, are the hallmark of the disease

The Gut Microbiota and Vascular Aging: A State-of-the-Art and Systematic Review of the Literature

The gut microbiota is a critical regulator of human physiology, deleterious changes to its composition and function (dysbiosis) have been linked to the development and progression of cardiovascular diseases. Vascular ageing (VA) is a process of progressive stiffening of the arterial tree associated with arterial wall remodeling, which can precede hypertension and organ damage, and is associated with cardiovascular risk. Arterial stiffness has become the preferred marker of VA. In our systematic review, we found an association between gut microbiota composition and arterial stiffness, with two patterns, in most animal and human studies: a direct correlation between arterial stiffness and abundances of bacteria associated with altered gut permeability and inflammation; an inverse relationship between arterial stiffness, microbiota diversity, and abundances of bacteria associated with most fit microbiota composition. Interventional studies were able to show a stable link between microbiota modification and arterial stiffness only in animals. None of the human interventional trials was able to demonstrate this relationship, and very few adjusted the analyses for determinants of arterial stiffness. We observed a lack of large randomized interventional trials in humans that test the role of gut microbiota modifications on arterial stiffness, and take into account BP and hemodynamic alterations