miR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction.

BACKGROUND: Cardiac fibrosis represents a key element in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a condition highly prevalent amongst geriatric patients, especially if diabetic. The microRNA 181c (miR-181c) has been shown to be associated with the response to exercise training in HFpEF patients and has been also linked to diabetic cardiovascular complications. However, the underlying mechanisms have not been fully elucidated. OBJECTIVE: To measure circulating miR-181c in elderly patients with HFpEF and diabetes mellitus (DM) and identify gene targets pathophysiologically relevant in HFpEF. METHODS: We quantified circulating miR-181c in frail older adults with a confirmed diagnosis of HFpEF and DM, and, as control, we enrolled age-matched subjects without HFpEF and without DM. We validated in human cardiac fibroblasts the molecular mechanisms linking miR-181c to a pro-fibrotic response. RESULTS: 51 frail patients were included :34 patients with DM and HFpEF and 17 age-matched controls. We observed that miR-181c was significantly upregulated (p < 0.0001) in HFpEF patients vs controls. We confirmed in vitro that miR-181c is targeting PRKN and SMAD7. CONCLUSIONS: We demonstrate that miR-181c levels are significantly increased in frail elderly adults with DM and HFpEF and that miR-181c targets PRKN and SMAD7 in human cardiac fibroblasts.

Acute coronary syndrome and renal impairment: a systematic review.

BACKGROUND: Coronary artery disease (CAD) and chronic kidney disease (CKD) may reciprocally influence each other. Patients with CAD and CKD have an increased risk of both ischemic and hemorrhagic events. METHODS: In the present review, we summarize the existing literature focusing on the relationship between kidney dysfunction and acute coronary syndromes (ACS) in terms of risk factors, complications, and prognosis. We discuss also about the best evidence-based strategies to prevent deterioration of renal function in patients with CAD. RESULTS: Patients with CKD less frequently receive an invasive management (percutaneous or surgical revascularization) and potent antithrombotic drugs. Nevertheless, recent evidence suggests they would benefit from a selective invasive management, especially in case of ACS. CONCLUSION: Patients with CKD and CAD represent a challenging population, more randomized controlled trials and meta-analyses are needed to better define the best therapeutic strategy during an ACS episode.

Renal Involvement in COVID-19: A Review of the Literature.

Kidney injury may be a severe complication of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to worsen the prognosis. Various pathophysiological mechanisms can contribute to organ damage and impair renal function, proving the complexity of the virus activity and the resulting immunity response. We summarized the evidence of the literature on the prevalence of kidney involvement, on the pathogenic pathways and on its management.

Anticoagulant treatment in COVID-19: a narrative review.

The actual Coronavirus Disease (COVID 19) pandemic is due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the coronavirus family. Besides the respiratory involvement, COVID 19 patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. It is common to observe diffuse microvascular thrombi in multiple organs, mostly in pulmonary microvessels. Thrombotic risk seems to be directly related to disease severity and worsens patients' prognosis. Therefore, the correct understanding of the mechanisms underlying COVID-19 induced prothrombotic state can lead to a thorough assessment of the possible management strategies. Hence, we review the pathogenesis and therapy of COVID 19-related thrombosis disease, focusing on the available evidence on the possible treatment strategies and proposing an algorithm for the anticoagulation strategy based on disease severity.

Repositioning of Immunomodulators: A Ray of Hope for Alzheimer's Disease?

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid ß plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain's pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.

Cardiovascular System in COVID-19: Simply a Viewer or a Leading Actor?

As of January 2020, a new pandemic has spread from Wuhan and caused thousands of deaths worldwide. Several studies have observed a relationship between coronavirus disease (COVID-19) infection and the cardiovascular system with the appearance of myocardial damage, myocarditis, pericarditis, heart failure and various arrhythmic manifestations, as well as an increase in thromboembolic risk. Cardiovascular manifestations have been highlighted especially in older and more fragile patients and in those with multiple cardiovascular risk factors such as cancer, diabetes, obesity and hypertension. In this review, we will examine the cardiac involvement associated with SARS-CoV-2 infection, focusing on the pathophysiological mechanism underlying manifestations and their clinical implication, taking into account the main scientific papers published to date.

Gut Microbiota in Alzheimer's Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress.

Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer's disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer's disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.

A Quartz Crystal Microbalance Immunosensor for Stem Cell Selection and Extraction.

A cost-effective immunosensor for the detection and isolation of dental pulp stem cells (DPSCs) based on a quartz crystal microbalance (QCM) has been developed. The recognition mechanism relies on anti-CD34 antibodies, DPSC-specific monoclonal antibodies that are anchored on the surface of the quartz crystals. Due to its high specificity, real time detection, and low cost, the proposed technology has a promising potential in the field of cell biology, for the simultaneous detection and sorting of stem cells from heterogeneous cell samples. The QCM surface was properly tailored through a biotinylated self-assembled monolayer (SAM). The biotin-avidin interaction was used to immobilize the biotinylated anti-CD34 antibody on the gold-coated quartz crystal. After antibody immobilization, a cellular pellet, with a mixed cell population, was analyzed; the results indicated that the developed QCM immunosensor is highly specific, being able to detect and sort only CD34+ cells. Our study suggests that the proposed technology can detect and efficiently sort any kind of cell from samples with high complexity, being simple, selective, and providing for more convenient and time-saving operations.

Regio- and enantioselective friedel-crafts reactions of indoles to epoxides catalyzed by graphene oxide: a green approach.

Graphene oxide efficiently promotes high regio- and enantioselective ring opening reactions of aromatic epoxides by indoles addition, in solvent- and metal-free conditions. The Friedel-Crafts products were obtained with enantioselectivity up to 99 % ee. The complete inversion of stereochemistry indicates the occurrence of SN 2-type reaction, which assures high level of enantioselectivity.

Experimental evidence of a buoyant mass difference between bovine spermatozoa bearing X- and Y-chromosomes using a micromechanical resonator.

Flow cytometry is to date the only commercially viable technique for sex preselection of mammalian spermatozoa, measuring the different DNA content in X- and Y-chromosome bearing spermatozoa. Here we present experimental evidence of a measurable difference between bovine spermatozoa bearing X- and Y-chromosomes based on their buoyant mass. Single cells of two populations of flow-cytometrically sorted spermatozoa were analyzed by means of a micromechanical resonator, consisting of a suspended doubly-clamped microcapillary. Spermatozoa buoyant mass is related to the transitory variation in vibration phase lag, caused by the passage through the sensitive area of a single sperm cell suspended in a fluid. Data analysis shows two well-separated distributions and provides evidence of the sensor capabilities to detect the buoyant mass of single cells with such accuracy to distinguish X- and Y-chromosome bearing spermatozoa. These preliminary results suggest the possibility to develop an intriguing technique alternative to flow cytometry in the field of sperm sorting.

Clay exfoliation and polymer/clay aerogels by supercritical carbon dioxide.

Supercritical carbon dioxide (scCO2) treatments of a montmorillonite (MMT) intercalated with ammonium cations bearing two long hydrocarbon tails (organo-modified MMT, OMMT) led to OMMT exfoliation, with loss of the long-range order in the packing of the hydrocarbon tails and maintenance of the long-range order in the clay layers. The intercalated and the derived exfoliated OMMT have been deeply characterized, mainly by X-ray diffraction analyses. Monolithic composite aerogels, with large amounts of both intercalated and exfoliated OMMT and including the nanoporous-crystalline δ form of syndiotactic polystyrene (s-PS), have been prepared, by scCO2 extractions of s-PS-based gels. Also for high OMMT content, the gel and aerogel preparation procedures occur without re-aggregation of the exfoliated clay, which is instead observed for other kinds of polymer processing. Aerogels with the exfoliated OMMT have more even dispersion of the clay layers, higher elastic modulus and larger surface area than aerogels with the intercalated OMMT. Extremely light materials with relevant transport properties could be prepared. Moreover, s-PS-based aerogels with exfoliated OMMT could be helpful for the handling of exfoliated clay minerals.