Oleuropein Aglycone Peracetylated (3,4-DHPEA-EA(P)) Attenuates H2O2-Mediated Cytotoxicity in C2C12 Myocytes via Inactivation of p-JNK/p-c-Jun Signaling Pathway.

Oleuropein, a glycosylated secoiridoid present in olive leaves, is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 µM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant.

Rapid Detection and Identification of Antimicrobial Peptide Fingerprints of Nasal Fluid by Mesoporous Silica Particles and MALDI-TOF/TOF Mass Spectrometry: From the Analytical Approach to the Diagnostic Applicability in Precision Medicine.

BACKGROUND: Antimicrobial peptides (AMP) play a pivotal role in innate host defense and in immune response. The delineation of new MS-based profiling tools, which are able to produce panels of AMP of the nasal fluid (NF), may be attractive for the discovery of new potential diagnostic markers of respiratory disorders. METHODS: Swabs collected NF from healthy patients and from patients with respiratory disorders. We used a fast procedure based on mesoporous silica particles (MPS) to enrich NF in its AMP component in combination with MALDI-TOF/TOF MS as a key tool for rapidly analyzing clinical samples. RESULTS: Reproducible MS peptide fingerprints were generated for each subject and several AMP were detected including (Human Neutrophil Peptides) HNPs, Statherin, Thymosin-ß4, Peptide P-D, II-2, ß-MSP, SLPI, Lysozyme-C, and their proteo-forms. In particular, Statherin, Thymosin-ß4, and Peptide P-D were accurately identified by direct MS/MS sequencing. Examples of applicability of this tool are shown. AMP fingerprints were obtained before and after a nasal polypectomy as well as before and post-treatment with azelastine/fluticasone in one case of allergic rhinitis. CONCLUSION: The potential of our platform to be implemented by new mesoporous materials for capturing a wider picture of AMP might offer an amazing opportunity for diagnostic clinical studies on individual and population scales.

Impact of legumes and plant proteins consumption on cognitive performances in the elderly.

BACKGROUND: Numerous studies have investigated the role of the dietary factors in the prevention of cognitive decline but the short-term effects of foods choice on cognitive performances in the elderly are poorly explored. Our aim was to investigate the choice of foods among elderly Italian individuals and the association with cognitive function. METHODS: In this longitudinal study, the participants were 214 individuals aged ≥65 years with a score >20 at the Mini Mental State Examination. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. Food choices was measured by a combination of a 24-h recall and a seven-day diet record and Principal Components Analysis. RESULTS: The Principal Components Analysis identified four food and four nutrient patterns. MMSE and ADAS-cog score after 1 year were found to be associated with legumes pattern (B = 0.25, p = 0.007; 95% CI 0.07/0.44; and B = -0.10, p = 0.006; CI -0.79/-0.30, respectively). A dietary pattern including plant proteins was independently associated with an improved ADAS-cog after 1 year (B = 0.584, p = 0.04; OR 1.79, CI 0.04-0.42). CONCLUSIONS: The Principal Components Analysis is useful to investigate the choice of foods and nutrients in the elderly. We demonstrated an association between legumes pattern with cognitive performances.

Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis.

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986-2016) were included. Nine studies were included (3 retrospective cohort and 6 case-control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means = -5.42 years, 95% CI -7.19 to -3.66, p < 0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means = 0.45, 95% CI -0.01 to 0.91, p = 0.054). No differences were observed in sex distribution (OR = 0.94, 95% CI 0.51-1.72, p = 0.83) and clinical form (OR = 1.03, 95% CI 0.33-3.21, p = 0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR = 7.06, 95% CI 2.39-20.8; p < 0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR = 2.6, 95% CI 1.0-6.5; p = 0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures.

Evidences of a New Psychobiotic Formulation on Body Composition and Anxiety.

BACKGROUND: Gut microbiota is implied in obesity, because of its ability to harvest energy from diet, and in the regulation of behavior. Given the link between gut microbiota, body composition, obesity, and anxiety, the aim of this study was to evaluate the effects of a new psychobiotic formulation. METHODS: Eligible patients were randomly divided into three groups: psychobiotics oral suspension group (POSG); dietary treatment group (DTG); combined treatment group (CTG). All subjects underwent body composition and psychological profile evaluation. RESULTS: Significant changes in body composition parameters in each group were relieved after all treatments. Hamilton anxiety rating scale (HAM-A) highlighted a significant reduction of the total score for all study population after treatments in POSG (p = 0.01) and CTG (p = 0.04). A reduction of HAM-A total score in anxious subjects in POSG or CTG and a significant reduction of positive subjects for HAM-A in POSG (p = 0.03) and in CDG (p = 0.01) were shown. DISCUSSION: Three-week intake of selected POS represents a good approach to solve problems related to obesity and behavior disorders. However, new clinical trials need to be performed on a larger population and for a longer period of treatment before definitive conclusions can be made. This trial is registered with NCT01890070.

Antioxidant-Enriched Diet on Oxidative Stress and Inflammation Gene Expression: A Randomized Controlled Trial.

The Mediterranean Diet (MedDiet) is associated with beneficial effects against chronic non-communicable diseases (CNCDs). In particular, the content of micronutrients leads to an improvement of the oxidative and inflammatory profiles. A randomized, parallel, controlled study, on 24 subjects, was conducted to evaluate if 2-week supplementation with a mixed apple and bergamot juice (MAB juice), had a positive impact on the body composition, the biochemical profile, and oxidative and inflammatory gene expression (Superoxide dismutase (SOD1), Peroxisome Proliferator-Activated Receptor γ (PPARγ), catalase (CAT), chemokine C-C motif ligand 5 (CCL5), Nuclear Factor Kappa B Subunit 1 (NFKB1), Vitamin D Receptor (VDR), and Macrophage Migration Inhibitory Factor (MIF)), respect to a MedDiet. Body composition evaluation analysis showed a gain in lean mass (p < 0.01). Moreover, a significant reduction in total cholesterol/HDL index (p < 0.01) was pointed out between the two groups. Gene expression analysis highlighted an increase in MIF (p ≤ 0.05), PPARγ (p < 0.001), SOD1 (p ≤ 0.05), and VDR (p ≤ 0.05) expressions when comparing MedDiet and MedDiet + MAB juice groups. These data based on the nutrigenomics approach demonstrated that supplementing 2 weeks of MAB juice to the MedDiet could contribute to a reduction in the risk of CNCDs.

Evaluation of Citrus aurantifolia peel and leaves extracts for their chemical composition, antioxidant and anti-cholinesterase activities.

BACKGROUND: The replacement of synthetic antioxidants by safe natural antioxidants fosters research on the screening of vegetables and food as sources of new antioxidants. Moreover, oxidative degeneration of cells is associated with neurodegenerative diseases such as Alzheimer's disease. On the basis of these considerations this work aimed to investigate the antioxidant properties [by using the diphenyl picryl hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric reducing ability of plasma assays, and the ß-carotene bleaching test] and the anti-cholinesterase activity of Citrus aurantifolia peel and leaves from different areas of growth. RESULTS: Methanol extracts of the peel and leaves demonstrated the strongest radical scavenging activity. A similar trend was observed with the reducing ability, with values from 112.1 to 146.0 µmol L(-1) Fe(II) g(-1). The relationship between phenol and flavonoid contents and antioxidant activity was statistically investigated. Based on analysis by high-performance liquid chromatography, the most abundant flavonoids found in C. aurantifolia extracts were apigenin, rutin, quercetin, kaempferol and nobiletin. n-Hexane fractions of both peel and leaves showed a good acetylcholinesterase inhibitory activity with IC(50) values in the range 91.4-107.4 µg mL(-1). Gas chromatography-mass spectrometry analysis revealed the presence of monoterpenes and sesquiterpenes as most common components. CONCLUSION: The findings of this study suggest a potential use of C. aurantifolia peel and leaves for supplements for human health.

Exploring the Sustainable Benefits of Adherence to the Mediterranean Diet during the COVID-19 Pandemic in Italy.

This study aimed to identify adherence to the Mediterranean diet (MedDiet) and its effect on health and environmental and socioeconomic sustainability during the COVID-19 pandemic among a sample of the Italian population. Notably, it intended to assess the effect of adherence to the MedDiet on ecological footprints and food expenditure. A survey was conducted from the 5th to the 24th of April 2020 on Google Forms. The MEDAS questionnaire was used to determine the level of adherence to the MedDiet. The carbon footprint (CO2), water footprint (H2O), and food cost were calculated. In total, 3353 participants completed the questionnaire, ranging from 18 to 86 years old. A statistically significant difference was observed in the CO2 and H2O among BMI groups (p < 0.001). The low- and medium-MEDAS groups showed higher CO2 (p < 0.001). The food cost (EUR/week) resulted in statistically significant differences among the MEDAS groups. The CO2 results were significantly lower in organic-market buyers compared to non-organic-market buyers (p < 0.001). Public health must promote awareness of how adhering to a healthy lifestyle and making appropriate food choices can positively impact our health and social and economic well-being.

Impact of COVID-19 on the Destiny of Bariatric Patients.

Obese patients reported worse outcomes of COVID-19 related to prothrombotic and low-grade inflammation status. During the SARS-CoV-2 outbreak, all non-elective surgeries were postponed, including bariatric surgery (BS). This umbrella review wants to underline obesity as a condition provoking low-grade chronic inflammation, and increasing severe COVID-19 risk; to relaunch the prioritization of BS. The literature search was conducted in March 2022 via Pubmed (MEDLINE) and focused on reviews, systematic reviews, and meta-analyses published in peer-reviewed journals. Terms "bariatric surgery" OR "obesity surgery" OR "metabolic surgery" were analyzed with "COVID-19" OR "SARS-CoV-2" using the AND modifier. Only 13 studies of the 406 screened met the objective. The procrastination of BS over the past two years determined a delay in obesity treatment and severe consequences. The COVID-19 pandemic has had a huge impact on economic costs. Although BS has high costs, a lifetime cost advantage over conventional weight loss methods was demonstrated. As the pandemic continues, health policies must recognize obesity as a disease-predisposing factor for SARS-CoV-2 infection, considering COVID-19 as a new comorbidity mitigable by BS. Care pathways for obese patients in COVID/post-COVID era should be revitalized and the concept of elective surgery attributed to BS should be reformulated.

In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines.

In the course of recent efforts to identify new potential antiproliferative active principles, Salvia leriifolia extracts and isolated constituents were evaluated for their cytotoxic activity against a panel of human cancer cell lines, including renal adenocarcinoma (ACHN), amelanotic melanoma (C32), colorectal adenocarcinoma (Caco-2), lung large cell carcinoma (COR-L23), malignant melanoma (A375), lung carcinoma (A549), and hepatocellular carcinoma (Huh-7D12) cells. The hexane and CH(2) Cl(2) extracts showed the strongest cytotoxic activity against the C32 cell line with IC(50) values of 11.2 and 13.6 µg/ml, respectively, and the AcOEt extract was the most active extract against the COR-L23 cell line (IC(50) of 20.9 µg/ml). Buchariol, a sesquiterpene obtained by biofractionation of the CH(2) Cl(2) extract, exhibited a higher activity than the positive control vinblastine against the C32 and A549 cell lines (IC(50) values of 2.1 and 12.6 µM, resp.). Interesting results were also obtained for naringenin, a flavonoid isolated from the AcOEt extract, which exhibited a strong cytotoxic activity against the C32, LNCaP, and COR-L23 cell lines (IC(50) values of 2.2, 7.7, and 33.4 µM, resp.), compared to vinblastine (IC(50) values of 3.3, 32.2, 50.0 µM, resp.). None of the tested compounds affected the proliferation of skin fibroblasts (142BR), suggesting a selective activity against tumor cells.

Presenilin enhancer-2 gene: identification of a novel promoter mutation in a patient with early-onset familial Alzheimer's disease.

UNLABELLED: γ-Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid-ß (Aß) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer-2 gene (PEN-2) is a necessary component of the γ-Secretase complex. Recently, it has been shown that PEN-2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN-2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty-two subjects (FAD: 97; CONTROLS: 355) were recruited for this study. We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early-FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN-2 gene. Although the effective role of the PEN-2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role.

Lack of association between G-protein coupled receptor kinase 5 gene and Parkinson's disease.

The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's disease (PD) is α-synuclein, most prominently phosphorylated at serine 129. G-protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate α-synuclein in vitro, enhancing the α-synuclein toxicity to dopaminergic neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD patients. A genetic association study performed in the Japanese population revealed haplotypic association of the GRK5 gene with susceptibility to sporadic PD. We aimed at investigating whether four polymorphisms within the GRK5 gene (rs871196, rs2420616, rs7069375, rs4752293) could represent a risk factor for sporadic PD in Southern Italy. We genotyped 446 patients with PD and 450 controls for these markers and did not find any significant association with the disease at allelic, genotypic and haplotypic level. Our results indicate that the GRK5 gene does not confer risk to sporadic PD in our sample from Southern Italy.

Arsenic and chromium levels in hair correlate with actinic keratosis/non-melanoma skin cancer: results of an observational controlled study.

BACKGROUND: The role of heavy metals in carcinogenetic process has been widely established; however, information on the most common environmental metals that serve as major risk factors for actinic keratosis (AK)/non-melanoma skin cancer (NMSC) are still lacking. The aim of this study was to evaluate levels of the most common environmental heavy metals in hair of patients with AK/NMSC as compared to healthy controls. METHODS: Thirty-one patients diagnosed with AK/NMSC and 34 healthy controls were enrolled. Patients were interviewed for heavy metals exposure and underwent hair analysis for detection of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb). Continuous variables were analyzed using Wilcoxon Non-Parametric Rank Test and proportions were compared by Fisher's Exact Test. Statistical significance was determined by P<0.05. RESULTS: In our cohort we observed 48.4% patients had AKs, 16.1% basal cell carcinoma (BCC), 9.7% squamous cell carcinoma (SCC) and 25.9% of patients presented with a combination of these lesions. There were significantly elevated levels of As and Cr in AK-NMSC group as compared to controls. CONCLUSIONS: We identified a strong positive correlation between As and Cr concentration and AK/NMSC adding new clues to the scenery of NMSC risk factors that should be taken under consideration in exposed populations.

Gut Microbiota and Obesity: A Role for Probiotics.

Nowadays, obesity is one of the most prevalent human health problems. Research from the last 30 years has clarified the role of the imbalance between energy intake and expenditure, unhealthy lifestyle, and genetic variability in the development of obesity. More recently, the composition and metabolic functions of gut microbiota have been proposed as being able to affect obesity development. Here, we will report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature, searching for the following keywords: metabolism, gut microbiota, dysbiosis, obesity. There is evidence for the association between gut bacteria and obesity both in infancy and in adults. There are several genetic, metabolic, and inflammatory pathophysiological mechanisms involved in the interplay between gut microbes and obesity. Microbial changes in the human gut can be considered a factor involved in obesity development in humans. The modulation of the bacterial strains in the digestive tract can help to reshape the metabolic profile in the human obese host as suggested by several data from animal and human studies. Thus, a deep revision of the evidence pertaining to the use probiotics, prebiotics, and antibiotics in obese patients is conceivable.

Anti-tumor Activity and Epigenetic Impact of the Polyphenol Oleacein in Multiple Myeloma.

Olive oil contains different biologically active polyphenols, among which oleacein, the most abundant secoiridoid, has recently emerged for its beneficial properties in various disease contexts. By using in vitro models of human multiple myeloma (MM), we here investigated the anti-tumor potential of oleacein and the underlying bio-molecular sequelae. Within a low micromolar range, oleacein reduced the viability of MM primary samples and cell lines even in the presence of bone marrow stromal cells (BMSCs), while sparing healthy peripheral blood mononuclear cells. We also demonstrated that oleacein inhibited MM cell clonogenicity, prompted cell cycle blockade and triggered apoptosis. We evaluated the epigenetic impact of oleacein on MM cells, and observed dose-dependent accumulation of both acetylated histones and α-tubulin, along with down-regulation of several class I/II histone deacetylases (HDACs) both at the mRNA and protein level, providing evidence of the HDAC inhibitory activity of this compound; conversely, no effect on global DNA methylation was found. Mechanistically, HDACs inhibition by oleacein was associated with down-regulation of Sp1, the major transactivator of HDACs promoter, via Caspase 8 activation. Of potential translational significance, oleacein synergistically enhanced the in vitro anti-MM activity of the proteasome inhibitor carfilzomib. Altogether, these results indicate that oleacein is endowed with HDAC inhibitory properties, which associate with significant anti-MM activity both as single agent or in combination with carfilzomib. These findings may pave the way to novel potential anti-MM epi-therapeutic approaches based on natural agents.

Role of Personalized Nutrition in Chronic-Degenerative Diseases.

Human nutrition is a branch of medicine based on foods biochemical interactions with the human body. The phenotypic transition from health to disease status can be attributed to changes in genes and/or protein expression. For this reason, a new discipline has been developed called "-omic science". In this review, we analyzed the role of "-omics sciences" (nutrigenetics, nutrigenomics, proteomics and metabolomics) in the health status and as possible therapeutic tool in chronic degenerative diseases. In particular, we focused on the role of nutrigenetics and the relationship between eating habits, changes in the DNA sequence and the onset of nutrition-related diseases. Moreover, we examined nutrigenomics and the effect of nutrients on gene expression. We perused the role of proteomics and metabolomics in personalized nutrition. In this scenario, we analyzed also how dysbiosis of gut microbiota can influence the onset and progression of chronic degenerative diseases. Moreover, nutrients influencing and regulating gene activity, both directly and indirectly, paves the way for personalized nutrition that plays a key role in the prevention and treatment of chronic degenerative diseases.

Rosmarinic Acid as Potential Anti-Inflammatory Agent.

Rosmarinus officinalis L. (Lamiaceae), popularly known as rosemary, is used for food flavoring, and in folk medicine, as an antispasmodic, analgesic, anti-rheumatic, diuretic, and antiepileptic agent. Rosemary is an herb widely used in folk medicine, cosmetics, and phytotherapy and for flavoring of food products. Studies have focused on various biological activities of the secondary metabolites of this plant, such as rosmarinic acid, which have powerful antioxidant, hepato-protective, antimicrobial, anti-nociceptive, and anti-inflammatory properties.

New equations to estimate resting energy expenditure in obese adults from body composition.

AIMS: The aims of this study were: to develop new equations for predicting resting energy expenditure (REE) in obese Italian subjects according to body composition parameters; to compare them with predicted values estimated by other REE prediction equations; and to cross-validate our equations using a validation set cohort. METHODS: Four hundred patients were enrolled and divided into three groups. Besides anthropometry and REE (indirect calorimetry), total body fat and lean were evaluated by dual X-ray absorptiometry, and fat mass and fat-free mass by bioelectrical impedance analysis. RESULTS: The subjects eligible to participate were 330. Group 1 (n = 174) was used to develop (R 2 = 0.79) and (R 2 = 0.77). Group 2 (n = 115) was used to generate (R 2 = 0.85) and (R 2 = 0.81). Group 3 (n = 41) was used to cross-validate the equations. CONCLUSION: Equations 1 and 3 are reliable to measure REE from calorimetry and better than other equations that use anthropometric variables as predictors of REE. Further analysis in different populations is required before it can be applied in clinical practice.

Development and cross-validation of predictive equation for estimating total body lean in children.

AIM: To develop and cross-validate a predictive equation for estimating lean body mass (LBM) in children, based on bioelectrical impedance analysis (BIA) and anthropometric parameters, and to compare our equation with other predictive methods. METHODS: We evaluated body composition of 155 children (age 5-14 years) by BIA and dual energy X-ray absorptiometry (DXA). Children were divided in two groups: developing set and cross-validation set. Statistical analysis as multiple regression and Bland-Altman methods were performed. RESULTS: From developing set (105 children) a predictive LBM (kg) equation was created. From the cross-validated set (35 children), our equation was seen to agree with LBM (kg) by DXA. On the contrary, LBM predicted by Schaefer's equation and BIA did not agree with the criterion measure. CONCLUSIONS: This cross-validated equation can be useful in epidemiological studies and also in clinical practice, permitting a better definition and follow up of children's body composition.

Indole and 2,4-Thiazolidinedione conjugates as potential anticancer modulators.

BACKGROUND: Thiazolidinediones (TZDs), also called glitazones, are five-membered carbon ring molecules commonly used for the management of insulin resistance and type 2 diabetes. Recently, many prospective studies have also documented the impact of these compounds as anti-proliferative agents, though several negative side effects such as hepatotoxicity, water retention and cardiac issues have been reported. In this work, we synthesized twenty-six new TZD analogues where the thiazolidinone moiety is directly connected to an N-heterocyclic ring in order to lower their toxic effects. METHODS: By adopting a widely applicable synthetic method, twenty-six TZD derivatives were synthesized and tested for their antiproliferative activity in MTT and Wound healing assays with PC3 (prostate cancer) and MCF-7 (breast cancer) cells. RESULTS: Three compounds, out of twenty-six, significantly decreased cellular viability and migration, and these effects were even more pronounced when compared with rosiglitazone, a well-known member of the TZD class of antidiabetic agents. As revealed by Western blot analysis, part of this antiproliferative effect was supported by apoptosis studies evaluating BCL-xL and C-PARP protein expression. CONCLUSION: Our data highlight the promising potential of these TZD derivatives as anti-proliferative agents for the treatment of prostate and breast cancer.