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Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, prion diseases such as Creutzfeldt–Jakob’s disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer’s disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.

Background Extracellular Vesicles (EVs) are sub-micrometer lipid-bound particles released by most cell types. They are considered a promising source of cancer biomarkers for liquid biopsy and personalized medicine due to their specific molecular cargo, which provides biochemical information on the state of parent cells. Despite this potential, EVs translation process in the diagnostic practice is still at its birth, and the development of novel medical devices for their detection and characterization is highly required. Results In this study, we demonstrate mid-infrared plasmonic nanoantenna arrays designed to detect, in the liquid and dry phase, the specific vibrational absorption signal of EVs simultaneously with the unspecific refractive index sensing signal. For this purpose, EVs are immobilized on the gold nanoantenna surface by immunocapture, allowing us to select specific EV sub-populations and get rid of contaminants. A wet sample-handling technique relying on hydrophobicity contrast enables effortless reflectance measurements with a Fourier-transform infrared (FTIR) spectro-microscope in the wavelength range between 10 and 3 µm. In a proof-of-principle experiment carried out on EVs released from human colorectal adenocarcinoma (CRC) cells, the protein absorption bands (amide-I and amide-II between 5.9 and 6.4 µm) increase sharply within minutes when the EV solution is introduced in the fluidic chamber, indicating sensitivity to the EV proteins. A refractive index sensing curve is simultaneously provided by our sensor in the form of the redshift of a sharp spectral edge at wavelengths around 5 µm, where no vibrational absorption of organic molecules takes place: this permits to extract of the dynamics of EV capture by antibodies from the overall molecular layer deposition dynamics, which is typically measured by commercial surface plasmon resonance sensors. Additionally, the described metasurface is exploited to compare the spectral response of EVs derived from cancer cells with increasing invasiveness and metastatic potential, suggesting that the average secondary structure content in EVs can be correlated with cell malignancy. Conclusions Thanks to the high protein sensitivity and the possibility to work with small sample volumes—two key features for ultrasensitive detection of extracellular vesicles- our lab-on-chip can positively impact the development of novel laboratory medicine methods for the molecular characterization of EVs. Graphical Abstract

Introduction: Neuropeptides are frequently identified as potential drugs for the development of new therapeutics or for the study of a variety of human cerebral diseases. Due to their instability when injected proteins and peptides need specific delivery systems, to stretch the biodisponibility. Nanocarriers can be a solution to solve the problem of transport to the central nervous system. Material and method: We performed a data literature analysis from PubMed. We analyze data from multiple studies, reporting that nanovectors are a possible drug delivery system (DDS) in the central nervous system (CNS). Results: We found that several studies are developing nanocarriers for neuropeptides delivery through intranasal route or injected. With this strategy it is possible to deliver efficiently several drugs with different natures such as small polar molecules, peptides, and proteins, and also the large proteins, polysaccharides, and even neuropeptides entering the CNS. Conclusions: We can conclude that the developments of the nanocarriers as DDS for neuropeptides and the transport through the nasal passages are a promising strategy for the delivery of neuropeptides in CNS.

Introduction: Metabolic syndrome (MS) includes a various factors such as hyperglycemia, high blood pressure and hypercholesterolemia that predispose individuals to the development of cardiovascular disease and diabetes. Furthermore, MS is strongly associated with obesity, indeed, it is well know that abdominal and/or visceral adipose tissue accumulation is a contributory cause of MS development. These diseases are associated with multiple metabolic toxicities resulting from the oxidative stress, which are the product of reactive oxygen species. In this scenario, a corrected nutrition and adequate physical activity are important measures against MS, obesity, aging and prevention of cardiovascular disease and cancer. In this regards, the healthy lifestyle, and in particular correct physical activity, represents one the epigenetic strategies against MS, having beneficial and anti-inflammatory effects, reducing the production of free radicals and the risk to development cardiovascular diseases and diabetes. The aim of this review is to discuss on physical activity and its role in modification of lyfestile inducing beneficial effect on health status. Material and method: We performed a data literature analysis from PubMed. We analyze data from multiple studies reporting that physical activity decreases body adiposity and the physical exercise reduces the fat mass in a dose dependent. Physical activity decreases abdominal visceral and subcutaneous fat indipendently of changes in dietary energy intake in healthy, overweight and obese man and women, suggesting that training is critical in the treatment, or prevention, of MS. Also, it induces the expression of a many genes involved in the repair of cellular damage and reduces the expression of genes involved in the mechanisms of oxidative stress and inflammation, activating numerous metabolic pathways and down-regulating the production of mediators of inflammation and ROS production. Conclusion: the physical activity can be an efficient therapeutic approach in MS, promoting weight loss in obesity and reducing cardiovascular disease and diabetes risks.

Introduction: Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles. The composition is influenced by the cellular origin and the cellular processes starting their formation. The MPs have various biochemical composition, depending on the site in which they originate: from platelets or endothelium, MPs are involved in many disease, in particular in cardiovascular disease but also in cancer and in central nervous system disease. They are involved in many cellular processes and in particular in apoptosis and in cellular rearrangement. MPs could promote the recruitment of more immune cells in vascular inflammatory areas. Material and method: We performed a data literature analysis from PubMed. We analyze data from multiple studies, reporting that in central nervous system (CNS), the MPs have an important biological role, they can be derived from platelets, endothelial cells, neurons or glial cells. RESULT: We found that the CNS cells in the neurovascular unit, including the endothelial lining and neural cells are also subject to stress by a variety of stimuli such as oxygen radicals and inflammation. Indeed, it is induced membrane shedding in vascular cells. For these reasons, it is possible that the shedding in the neurovascular network may be linked not only to the development and progression of various CNS diseases, but also to the physiological development of the nervous system. In fact, the MPs attend, also, to a regeneration and repair of nerve injury. The MPs are involved in neuroimmune response, indeed, during the various negative stimuli, the microglial release a MPs containing pro-inflammatory cytokines. The MPs can be considered as a biomarkers from a specific tissue undergoing activation or damage. The plasma membrane is considerate as a sensor of cell interactions with the microenvironment. Conclusion: Given these evidences, we can conclude that the releasing of MPs is an indicator of a physiological and/ or pathophysiological activation in CNS, and then these vesicles are strongly involved in various CNS disease such as stoke, multiple sclerosis and Alzheimer’s disease.

The study of erythrocyte membrane protein concentration by polyacrylamide gel electrophoresis (PAGE) is the first step in approaching the primary molecular defect in hereditary spherocytosis (HS). Normal or greater than normal protein 2.1 levels were found in ten unrelated HS patients showing the inactivation of one ankyrin allele. Erythrocyte membranes from the same patients, once splenectomized, showed a homogeneous degree of protein 2.1 reduction. Thus protein 2.1 levels could misleadingly appear normal due to the high number of circulating reticulocytes. To calculate the true ankyrin level using PAGE and consequently to avoid mistakes in studying a mutated gene, a simple equation, based on the number of reticulocytes, was developed.

The case of a female patient with a normal mammography of first level screening and a control mammography showing the presence of a cluster of microcalcifications, is discussed. The case history is carefully examined also based on previous investigations. The patient decided to undergo stereotactic vacuum-assisted biopsy (mammotome biopsy) that was performed elsewhere. Indications, advantages and possible complications of the procedure are analyzed.

In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or severe symptoms with the latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing the development of many complementary approaches to identify candidate cellular pathways involved in disease progression. Host lipids play a critical role in the virus life, being the double-membrane vesicles a key factor in coronavirus replication. Moreover, lipid biogenesis pathways affect receptor-mediated virus entry at the endosomal cell surface and modulate virus propagation. In this study, targeted lipidomic analysis coupled with proinflammatory cytokines and alarmins measurement were carried out in serum of COVID-19 patients characterized by different severity degree. Serum IL-26, a cytokine involved in IL-17 pathway, TSLP and adiponectin were measured and correlated to lipid COVID-19 patient profiles. These results could be important for the classification of the COVID-19 disease and the identification of therapeutic targets.

Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.

Background: Lung cancer is a leading cause of mortality. The most common cancer subtype, non small cell lung cancer (NSCLC), accounts for 85-90 % all cases and is mainly caused by environmental and genetic factors. Mechanisms involved in lung carcinogenesis include deregulation of several kinases and molecular pathways affecting cell proliferation, apoptosis and differentiation. Despite advances in lung cancer detection, diagnosis and staging, survival rate still remains poor and novel biomarkers for both diagnosis and therapy need to be identified. In the present study, we have explored the potential of novel specific biomarkers in the diagnosis of NSCLC, and the over-expression/activation of several kinases involved in disease development and progression. Method: Lung tumor tissue specimens and adjacent cancer-free tissues from 8 NSCLC patients undergoing surgery were collected. The differential activation status of ERK1/2, AKT and IKB alpha/NF-kappa beta was analyzed. Subsequently, protein expression profile of NSCLC vs normal surrounding tissue was compared by a proteomic approach using LC-MS MS. Subsequently, MS/MS outputs were analyzed by the Protein Discoverer platform for label-free quantitation analysis. Finally, results were confirmed by western blotting analysis. Results: This study confirms the involvement of ERK1/2, AKT, IKB alpha and NF-kappa beta proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Furthermore, we found significant differential expression of 20 proteins (R-sc >= 1.50 or

Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for adiponectin-receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of T-cadherin receptor. In addition, the loss of T-cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this work explores their possible contribution to the down-regulation of T-cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target miRNA sites within the 3' UTR of T-cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the T-cadherin sequence, and thus down-regulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of T-cadherin in CRC, the regulatory circuit highlighted in this work may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets. This article is protected by copyright. All rights reserved.

Adiponectin (Acrp30) and leptin, adipokines produced and secreted mainly by the adipose tissue, are involved in human carcinogenesis. Thyroid carcinomas are frequent endocrine cancers, and several evidences suggest that they are correlated with obesity. In this study, we first analyzed the expression levels and prognostic values of Acrp30, leptin, and their receptors in thyroid cancer cells. Then, we investigated the role of Acrp30 and leptin in proliferation, migration, and invasion. We found that Acrp30 treatment alone inhibits cell proliferation and cell viability in a time and dose-dependent manner; leptin alone does not influence thyroid cancer cells (BCPAP and K1) proliferation, but the combined treatment reverts Acrp30-induced effects on cell proliferation. Additionally, through wound healing and Matrigel Matrix invasion assays, we unveiled that Acrp30 inhibits thyroid cancer cell motility, while leptin induces the opposite effect. Importantly, in the combined treatment, Acrp30 and leptin exert antagonizing effects on papillary thyroid cancer cells’ migration and invasion in both BCPAP and K1 cell lines. Highlights of these studies suggest that Acrp30 and leptin could represent therapeutic targets and biomarkers for the management of thyroid cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s13105-021-00789-x.

Obesity is characterized by an energy imbalance and by the accumulation of visceral adipose tissue. The energy balance is controlled by a complex set of balanced physiological systems that provide hunger and satiety signals to the brain and regulate the body’s ability to consume energy. The central nervous system controls the metabolic state, influencing the activity of other systems and receiving information from them. Heart rate variability (HRV) is the natural variability of the heart rate in response to several factors. HRV is related to the interaction between the SNS and the parasympathetic. In the light of this evidence, the aim of this study is to investigate the possible effects of the two different dietary regimens such as very low-calorie ketogenic diet (VLCKD) vs. low caloric diet (LCD), on the functions of the nervous system, with particular attention to the autonomous control of heart rate variability (HRV). A total of 26 obese subjects underwent diet therapy in order to reduce body weight; they were also randomly divided into two groups: the VLCKD group and the LCD group. Our results showed that in both groups, there is a reduction in heart rate as an indicator of sympathetic activity; we found a statistically significant variation only in the VLCKD group. Therefore, this study supports the notion that the sympathovagal balance can be modulated by a specific diet, but further studies are needed to clarify the molecular pathway undergoing this modulation.

Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome. The relationship between central obesity and the development of insulin resistance is widely verified. Adipose tissue excess and the coexistent dysregulation of adipocyte functions directly contribute to the pathogenesis of the metabolic complications observed in women with PCOS. In the light of these evidence, the most therapeutic option prescribed to obese women with PCOS, regardless of the phenotype e from the severity of clinical expression, is lifestyle correction by diet and physical activity. The aim of this study is to evaluate the beneficial effects of ketogenic diet in 17 obese women with PCOS. Our results showed that the ketogenic diet inducing therapeutic ketosis, improves the anthropometric and many biochemical parameters such as LH, FSH, SHBG, insulin sensitivity and HOMA index. In addition, it induces a reduction in androgenic production, whereas the contextual reduction of fat mass reduced the acyclic production of estrogens deriving from the aromatization in the adipose tissue of the androgenic excess, with an improvement of the LH/FSH ratio. This is the first study on the effects of the ketogenic diet on PCOS, however, further studies are needed to elucidate the mechanism underlying ketogenic diet effects.