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Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

Skeletal muscle regeneration entails a multifaceted process marked by distinct phases, encompassing inflammation, regeneration, and remodeling. The coordination of these phases hinges upon precise intercellular communication orchestrated by diverse cell types and signaling molecules. Recent focus has turned towards extracellular vesicles (EVs), particularly small EVs, as pivotal mediators facilitating intercellular communication throughout muscle regeneration. Notably, injured muscle provokes the release of EVs originating from myofibers and various cell types, including mesenchymal stem cells, satellite cells, and immune cells such as M2 macrophages, which exhibit anti-inflammatory and promyogenic properties. EVs harbor a specific cargo comprising functional proteins, lipids, and nucleic acids, including microRNAs (miRNAs), which intricately regulate gene expression in target cells and activate downstream pathways crucial for skeletal muscle homeostasis and repair. Furthermore, EVs foster angiogenesis, muscle reinnervation, and extracellular matrix remodeling, thereby modulating the tissue microenvironment and promoting effective tissue regeneration. This review consolidates the current understanding on EVs released by cells and damaged tissues throughout various phases of muscle regeneration with a focus on EV cargo, providing new insights on potential therapeutic interventions to mitigate muscle-related pathologies.

The human zinc finger protein 521 (ZNF521) is a co-transcriptional factor with multiple recognized regulatory functions in a range of normal, cancer and stem cell compartments. ZNF521 regulates proliferation, progression and CSC (cancer stem cell) compartments in human ovarian cancer (hOC), which is a very aggressive and late-diagnosed female tumor. Two other important regulators of hOC are the NRF2 and NOTCH signaling pathways. In the present paper, the mRNA and protein levels of ZNF521 were correlated with those of the NRF2-NOTCH signaling components in two different hOC cell lines and in a public dataset of 381 hOC patients. The data show that high levels of ZNF521 significantly increase NRF2-NOTCH signaling expression; conversely, the silencing of ZNF521 impairs NRF2-NOTCH signaling. This experimental work shows that, in hOC, different levels of ZNF521 modulate the NRF2-NOTCH signaling pathway and also influences hOC CSC properties.

Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats (p < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group (p < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle–bone crosstalk and to identify new strategies to prevent osteosarcopenia.

Oleuropein plays a key role as a pro-oxidant as well as an antioxidant in cancer. In this study, the activity of oleuropein, in an in vitro model of ovarian (OCCs) and breast cancer cells (BCCs) was investigated. Cell viability and cell death were analyzed. Oxidative stress was measured by CM-H2DCFDA flow cytometry assay. Mitochondrial dysfunction was evaluated based on mitochondrial reactive oxygen species (ROS) and GPX4 protein levels. Further, the effects on iron metabolism were analyzed by measuring the intracellular labile iron pool (LIP). We confirmed that high doses of oleuropein show anti-proliferative and pro-apoptotic activity on HEY and MCF-7 cells. Moreover, our results indicate that low doses of oleuropein impair cell viability without affecting the mortality of cells, and also decrease the LIP and ROS levels, keeping them unchanged in MCF-7 cells. For the first time, our data show that low doses of oleuropein reduce erastin-mediated cell death. Interestingly, oleuropein decreases the levels of intracellular ROS and LIP in OCCs treated with erastin. Noteworthily, we observed an increased amount of ROS scavenging enzyme GPX4 together with a consistent reduction in mitochondrial ROS, confirming a reduction in oxidative stress in this model.

The application of imaging to cardiovascular diseases fosters the diagnosis, clinical management, and risk stratification of patients, thus leading to the early detection of cardiac and vascular diseases [...]

The maintenance of the physiological values of blood pressure is closely related to unchangeable factors (genetic predisposition or pathological alterations) but also to modifiable factors (dietary fat and salt, sedentary lifestyle, overweight, inappropriate combinations of drugs, alcohol abuse, smoking and use of psychogenic substances). Hypertension is usually characterized by the presence of a chronic increase in systemic blood pressure above the threshold value and is an important risk factor for cardiovascular disease, including myocardial infarction, stroke, micro- and macro-vascular diseases. Hypertension is closely related to functional changes in the endothelium, such as an altered production of vasoconstrictive and vasodilator substances, which lead to an increase in vascular resistance. These alterations make the endothelial tissue unresponsive to autocrine and paracrine stimuli, initially determining an adaptive response, which over time lead to an increase in risk or disease. The gut microbiota is composed of a highly diverse bacterial population of approximately 1014 bacteria. A balanced intestinal microbiota preserves the digestive and absorbent functions of the intestine, protecting from pathogens and toxic metabolites in the circulation and reducing the onset of various diseases. The gut microbiota has been shown to produce unique metabolites potentially important in the generation of hypertension and endothelial dysfunction. This review highlights the close connection between hypertension, endothelial dysfunction and gut microbiota.

Sarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles.

Overactivation of the c-MET/HGF system is a feature of many cancers. We previously reported that type II testicular germ cell tumor (TGCT) cells express the c-MET receptor, forming non-seminomatous lesions that are more positive compared with seminomatous ones. Notably, we also demonstrated that NT2D1 non-seminomatous cells (derived from an embryonal carcinoma lesion) increase their proliferation, migration, and invasion in response to HGF. Herein, we report that HGF immunoreactivity is more evident in the microenvironment of embryonal carcinoma biopsies with respect to seminomatous ones, indicating a tumor-dependent modulation of the testicular niche. PI3K/AKT is one of the signaling pathways triggered by HGF through the c-MET activation cascade. Herein, we demonstrated that phospho-AKT increases in NT2D1 cells after HGF stimulation. Moreover, we found that this pathway is involved in HGF-dependent NT2D1 cell proliferation, migration, and invasion, since the co-administration of the PI3K inhibitor LY294002 together with HGF abrogates these responses. Notably, the inhibition of endogenous PI3K affects collective cell migration but does not influence proliferation or chemotactic activity. Surprisingly, LY294002 administered without the co-administration of HGF increases cell invasion at levels comparable to the HGF-administered samples. This paradoxical result highlights the role of the testicular microenvironment in the modulation of cellular responses and stimulates the study of the testicular secretome in cancer lesions.

Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities, and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-4, IL-5 and IL-13 and IgE. Antibodies targeting these cytokines or receptors represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in chronic rhinosinusitis (CRS) patients is associated with remodeling transition, a process in which epithelial cells lose their typical phenotype, acquiring a mesenchymal-like aspect. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these signaling pathways are able to interfere with the process; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells, which can be isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to the delineating inflammatory process underlying the development of nasal polyps.

Evidence has been accumulated demonstrating that heavy metals may accumulate in various organs, leading to tissue damage and toxic effects in mammals. In particular, the Central Nervous System (CNS) seems to be particularly vulnerable to cumulative concentrations of heavy metals, though the pathophysiological mechanisms is still to be clarified. In particular, the potential role of oligodendrocyte dysfunction and myelin production after exposure to subtoxic concentration I confirmed. It is ok of heavy metals is to be better assessed. Here we investigated on the effect of sub-toxic concentration of several essential (Cu2 +, Cr3 +, Ni2 +, Co2+) and non-essential (Pb2 +, Cd2+, Al3+) heavy metals on human oligodendrocyte MO3.13 and human neuronal SHSY5Y cell lines (grown individually or in co-culture). MO3.13 cells are an immortal human–human hybrid cell line with the phenotypic characteristics of primary oligodendrocytes but following the differentiation assume the morphological and biochemical features of mature oligodendrocytes. For this reason, we decided to use differentiated MO3.13 cell line. In particular, exposure of both cell lines to heavy metals produced a reduced cell viability of co-cultured cell lines compared to cells grown separately. This effect was more pronounced in neurons that were more sensitive to metals than oligodendrocytes when the cells were grown in co-culture. On the other hand, a significant reduction of lipid component in cells occurred after their exposure to heavy metals, an effect accompanied by substantial reduction of the main protein that makes up myelin (MBP) in co-cultured cells. Finally, the effect of heavy metals in oligodendrocytes were associated to imbalanced intracellular calcium ion concentration as measured through the fluorescent Rhod-2 probe, thus confirming that heavy metals, even used at subtoxic concentrations, lead to dysfunctional oligodendrocytes. In conclusion, our data show, for the first time, that sub-toxic concentrations of several heavy metals lead to dysfunctional oligodendrocytes, an effect highlighted when these cells are co-cultured with neurons. The pathophysiological mechanism(s) underlying this effect is to be better clarified. However, imbalanced intracellular calcium ion regulation, altered lipid formation and, finally, imbalanced myelin formation seem to play a major role in early stages of heavy metal-related oligodendrocyte dysfunction.

Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders.

The maintenance of physiological levels of nitric oxide (NO) produced by eNOS represents a key element for vascular endothelial homeostasis. On the other hand, NO overproduction, due to the activation of iNOS under different stress conditions, leads to endothelial dysfunction and, in the late stages, to the development of atherosclerosis. Oxidized LDLs (oxLDLs) represent the major candidates to trigger biomolecular processes accompanying endothelial dysfunction and vascular inflammation leading to atherosclerosis, though the pathophysiological mechanism still remains to be elucidated. Here, we summarize recent evidence suggesting that oxLDLs produce significant impairment in the modulation of the eNOS/iNOS machinery, downregulating eNOS via the HMGB1-TLR4-Caveolin-1 pathway. On the other hand, increased oxLDLs lead to sustained activation of the scavenger receptor LOX-1 and, subsequently, to NFkB activation, which, in turn, increases iNOS, leading to EC oxidative stress. Finally, these events are associated with reduced protective autophagic response and accelerated apoptotic EC death, which activates atherosclerotic development. Taken together, this information sheds new light on the pathophysiological mechanisms of oxLDL-related impairment of EC functionality and opens new perspectives in atherothrombosis prevention.

The exchange of solutes between the blood and the nerve tissue is mediated by specific and high selective barriers in order to ensure the integrity of the different compartments of the nervous system. At peripheral level, this function is maintained by the Blood Nerve Barrier (BNB) that, in the presence, of specific stressor stimuli can be damaged causing the onset of neurodegenerative processes. An essential component of BNB is represented by the endothelial cells surrounding the sub-structures of peripheral nerves and increasing evidence suggests that endothelial dysfunction can be considered a leading cause of the nerve degeneration. The purpose of this review is to highlight the main mechanisms involved in the impairment of endothelial cells in specific diseases associated with peripheral nerve damage, such as diabetic neuropathy, erectile dysfunction and inflammation of the sciatic nerve.

The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons, and oligodendrocytes as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital components of the BBB able to preserve the brain homeostasis. These cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: (1) the presence of junction proteins and (2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. This review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.

Leukemias derived from the MLL-AF9 rearrangement rely on dysfunctional transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. Here, we demonstrate that ZNF521 mRNA levels correlate with specific genetic aberrations: in particular, the highest expression is observed in AMLs bearing MLL rearrangements, while the lowest is detected in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. In cord blood-derived CD34+ cells, enforced expression of ZNF521 provides a significant proliferative advantage and enhances MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome analysis of primary CD34+ cultures displayed subsets of genes up-regulated by MLL-AF9 or ZNF521 single transgene overexpression as well as in MLL-AF9/ZNF521 combinations, at either the early or late time points of an in vitro leukemogenesis model. The silencing of ZNF521 in the MLL-AF9 + THP-1 cell line coherently results in an impairment of growth and clonogenicity, recapitulating the effects observed in primary cells. Taken together, these results underscore a role for ZNF521 in sustaining the self-renewal of the immature AML compartment, most likely through the perturbation of the gene expression landscape, which ultimately favors the expansion of MLL-AF9-transformed leukemic clones.

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 μg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 μg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena.

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p < 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF < 57% and FMD value < 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

The neurodegenerative process is characterized by the progressive ultrastructural alterations of selected classes of neurons accompanied by imbalanced cellular homeostasis, a process which culminates, in the later stages, in cell death and the loss of specific neurological functions. Apart from the neuronal cell impairment in selected areas of the central nervous system which characterizes many neurodegenerative diseases (e.g., Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, etc.), some alterations may be found in the early stages including gliosis and the misfolding or unfolding accumulation of proteins. On the other hand, several common pathophysiological mechanisms can be found early in the course of the disease including altered oxidative metabolism, the loss of cross-talk among the cellular organelles and increased neuroinflammation. Thus, antioxidant compounds have been suggested, in recent years, as a potential strategy for preventing or counteracting neuronal cell death and nutraceutical supplementation has been studied in approaching the early phases of neurodegenerative diseases. The present review will deal with the pathophysiological mechanisms underlying the early stages of the neurodegenerative process. In addition, the potential of nutraceutical supplementation in counteracting these diseases will be assessed.

Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation. The present study is aimed at determining the effects of ZNF521 on the osteoblastic differentiation of hADSCs to clarify whether it can influence their osteogenic commitment. The enforced expression or silencing of ZNF521 in hADSCs was achieved by lentiviral vector transduction. Cells were cultured in a commercial osteogenic medium for up to 20 days. The ZNF521 enforced expression significantly reduced osteoblast development as assessed by the morphological and molecular criteria, resulting in reduced levels of collagen I, alkaline phosphatase, osterix, osteopontin, and calcium deposits. Conversely, ZNF521 silencing, in response to osteoblastic stimuli, induced a significant increase in early molecular markers of osteogenesis and, at later stages, a remarkable enhancement of matrix mineralization. Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in hADSCs and suggest that its expression may contribute to maintaining the immature properties of hADSCs.