Multidimensional Assessment of Sarcopenia and Sarcopenic Obesity in Geriatric Patients: Creatinine/Cystatin C Ratio Performs Better than Sarcopenia Index.

The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI) are novel indicators for sarcopenia, but their accuracy may depend on various confounders. To assess CCR and SI diagnostic accuracy, we studied the clinical and biophysical parameters associated with sarcopenia or sarcopenic obesity. A total of 79 elderly patients (65-99 yrs, 33 females) underwent clinical, anthropometric, body composition, geriatric performance, and blood chemistry evaluation. The CCR and SI accuracy were assessed to identify sarcopenia. Sarcopenia was confirmed in 40.5%, and sarcopenic obesity in 8.9% of the subjects. Sarcopenic patients showed an increased Charlson comorbidity index, cardiovascular disease (CVD) rates and frailty, and decreased physical performance than non-sarcopenic subjects. Patients with sarcopenic obesity had increased body fat and inflammatory markers compared to obese subjects without sarcopenia. Sarcopenia was associated with a decreased CCR and SI. However, when the logistic regression models were adjusted for possible confounders (i.e., age, gender, Charlson comorbidity index, presence of CVD, and frailty score), a significant OR was confirmed for the CCR (OR 0.021, 95% CI 0.00055-0.83) but not for the SI. The AUC for the CCR for sarcopenia discrimination was 0.72. A higher performance was observed in patients without chronic kidney diseases (CKD, AUC 0.83). CCR, more than the SI, is a useful, non-invasive, and cost-effective tool to predict sarcopenia, irrespective of the potential confounders, particularly in subjects without CKD.

Comprehensive Strategies for Metabolic Syndrome: How Nutrition, Dietary Polyphenols, Physical Activity, and Lifestyle Modifications Address Diabesity, Cardiovascular Diseases, and Neurodegenerative Conditions.

Several hallmarks of metabolic syndrome, such as dysregulation in the glucose and lipid metabolism, endothelial dysfunction, insulin resistance, low-to-medium systemic inflammation, and intestinal microbiota dysbiosis, represent a pathological bridge between metabolic syndrome and diabesity, cardiovascular, and neurodegenerative disorders. This review aims to highlight some therapeutic strategies against metabolic syndrome involving integrative approaches to improve lifestyle and daily diet. The beneficial effects of foods containing antioxidant polyphenols, intestinal microbiota control, and physical activity were also considered. We comprehensively examined a large body of published articles involving basic, animal, and human studie, as well as recent guidelines. As a result, dietary polyphenols from natural plant-based antioxidants and adherence to the Mediterranean diet, along with physical exercise, are promising complementary therapies to delay or prevent the onset of metabolic syndrome and counteract diabesity and cardiovascular diseases, as well as to protect against neurodegenerative disorders and cognitive decline. Modulation of the intestinal microbiota reduces the risks associated with MS, improves diabetes and cardiovascular diseases (CVD), and exerts neuroprotective action. Despite several studies, the estimation of dietary polyphenol intake is inconclusive and requires further evidence. Lifestyle interventions involving physical activity and reduced calorie intake can improve metabolic outcomes.

Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options.

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and, finally, "metabolic dysfunction-associated steatotic liver disease" (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut-liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Gender-specific insights into the irritable bowel syndrome pathophysiology. Focus on gut dysbiosis and permeability.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder involving the brain-gut interaction. IBS is characterized by persistent abdominal pain and changes in bowel habits. IBS exerts significant impacts on quality of life and imposes huge economic costs. Global epidemiological data reveal variations in IBS prevalence, both globally and between genders, necessitating comprehensive studies to uncover potential societal and cultural influences. While the exact pathophysiology of IBS remains incompletely understood, the mechanism involves a dysregulation of the brain-gut axis, leading to disturbed intestinal motility, local inflammation, altered intestinal permeability, visceral sensitivity, and gut microbiota composition. We reviewed several gender-related pathophysiological aspects of IBS pathophysiology, by focusing on gut dysbiosis and intestinal permeability. This perspective paves the way to personalized and multidimensional clinical management of individuals with IBS.

Early and accurate diagnosis of steatotic liver by artificial intelligence (AI)-supported ultrasonography.

OBJECTIVES: Steatotic liver disease is the most frequent chronic liver disease worldwide. Ultrasonography (US) is commonly employed for the assessment and diagnosis. Few information is available on the possible use of artificial intelligence (AI) to ameliorate the diagnostic accuracy of ultrasonography. MATERIALS AND METHODS: An AI-based algorithm was developed using a dataset of US images. We prospectively enrolled 134 patients for algorithm validation. Patients underwent abdominal US and Proton Density Fat Fraction MRI scans (MRI-PDFF), assumed as reference technique. The hepatorenal index was manually calculated (HRIM) by 4 operators. An automatic hepatorenal index (HRIA) was obtained by the algorithm. The accuracy of HRIA to discriminate steatosis grades was evaluated by ROC analysis using MRI-PDFF cut-offs. RESULTS: Overweight was 40 % of subjects (BMI 26.4 kg/cm2). The median HRIA was 1.11 (IQR 0.32) and the average of 4 manually calculated HRIM was 1.08 (IQR 0.26), with a 15 % inter-operator variability. Both HRIA (R = 0.79, P < 0.0001) and HRIM (R = 0.69, P < 0.0001) significantly correlated with liver fat percentage (MRI-PDFF). According to MRI-PDFF, 32 % of enrolled subjects had steatosis. Discrimination capacity by AUC between patient with steatosis and patient without steatosis was better for HRIA than HRIM (AUC: 0.87 vs. 0.82, respectively). ROC analysis showed an AUC = 0.98 for HRIA with 1.64 cut-off in distinguishing between mild and moderate/severe groups. CONCLUSIONS: The use of AI improves accuracy and speed of ultrasonography in the diagnosis of liver steatosis. Further studies should evaluate the routine use of this technique in the management of liver steatosis at high cardio-metabolic risk.

Nutritional and Physiological Properties of Thymbra spicata: In Vitro Study Using Fecal Fermentation and Intestinal Integrity Models.

(Poly)phenolic-rich Mediterranean plants such as Thymbra spicata have been associated with several health-promoting effects. The nutritional value, as well as physiological interaction of T. spicata with the gastrointestinal tract, has not been investigated before. The nutritional composition of T. spicata leaves was here characterized by standard analytical methods. T. spicata leaves were subjected to ethanolic extraction, simulated gastrointestinal digestion, and anaerobic microbial gut fermentation. Phenols/flavonoid contents and radical scavenging activity were assessed by colorimetric methods. The volatile organic compounds (VOCs) were detected by gas chromatography coupled with mass spectrometry. The effect on intestinal integrity was evaluated using a Caco-2 monolayers mounted in a Ussing chamber. T. spicata contains a high amount of fiber (12.3%) and unsaturated fatty acids (76% of total fat). A positive change in VOCs including short-chain fatty acids was observed without significant change in viable microbe. T. spicata and carvacrol (main phenolic compound) enhanced ionic currents in a concentration-dependent manner without compromising the Caco-2 monolayer's integrity. These effects were partially lost upon simulated digestion and completely abolished after colonic fermentation in line with polyphenols and carvacrol content. Conclusion: T. spicata represents a promising nutrient for the modulation of gut microbiota and the gut barrier. Further studies must better define its mechanisms of action.

Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients.

BACKGROUND: Long COVID symptoms are widely diffused and have a poorly understood pathophysiology, with possible involvement of inflammatory cytokines. MATERIALS AND METHODS: A prospective follow-up study involved 385 unvaccinated patients, started 1 month after SARS-CoV-2 infection and continued for up to 12 months. We compared circulating biomarkers of neutrophil degranulation, endothelial and metabolic dysfunction in subjects with long COVID symptoms and in asymptomatic post-COVID controls. RESULTS: The highest occurrence of symptoms (71%) was after 3 months from the infection, decreasing to 62.3% and 29.4% at 6 and 12 months, respectively. Compared to controls, long COVID patients had increased levels of the neutrophilic degranulation indices MMP-8 and MPO, of endothelial dysfunction indices L-selectin and P-selectin. Among indices of metabolic dysfunction, leptin levels were higher in long COVID patients than in controls. CONCLUSION: In unvaccinated patients, symptoms may persist up to 1 year after acute COVID infection, with increased indices of neutrophil degranulation, endothelial and metabolic dysfunction. The clinical implications of specific inflammatory biomarkers require further attention, especially in individuals with fatigue and long COVID-linked cognitive dysfunctions.

Polyphenol-enriched extracts of Sarcopoterium spinosum fruits for counteracting lipid accumulation and oxidative stress in an in vitro model of hepatic steatosis.

Sarcopoterium spinosum (L.) Spach is a Rosaceae shrub employed in the folk medicine in the Eastern Mediterranean basin. The previous few studies have focused on the S. spinosum roots, while the fruits have been poorly investigated. The present study aims to assess the biological properties of S. spinosum fruits collected in Lebanon and subjected to ethanolic, water or boiling water extraction. The extracts were compared for the phenol and flavonoid contents, and for the in vitro radical scavenging ability. The ethanolic extract (SEE) was selected and characterized by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) showing a phenolome rich in tannins (ellagitannins), flavonoids (quercetin derivatives), and triterpenes. The biological activity of SEE was tested on a cellular model of moderate steatosis consisting of lipid-loaded hepatic cells treated with increasing concentrations of SEE (1-25 µg/mL), or with corilagin or quercetin as comparison. In steatotic hepatocytes the SEE was able (i) to ameliorate the hepatosteatosis; (ii) to counteract the excess ROS and lipid peroxidation; (iii) to restore the impaired catalase activity. The results indicate that the ethanolic extract from S. spinosum fruits is endowed with relevant antisteatotic and antioxidant activities and might find application as nutraceutical product.

Gut microbes in metabolic disturbances. Promising role for therapeutic manipulations?

The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.

The interaction of bile acids and gut inflammation influences the pathogenesis of inflammatory bowel disease.

Bile acids (BA) are amphipathic molecules originating from cholesterol in the liver and from microbiota-driven biotransformation in the colon. In the gut, BA play a key role in fat digestion and absorption and act as potent signaling molecules on the nuclear farnesoid X receptor (FXR) and membrane-associated G protein-coupled BA receptor-1 (GPBAR-1). BA are, therefore, involved in the maintenance of gut barrier integrity, gene expression, metabolic homeostasis, and microbiota profile and function. Disturbed BA homeostasis can activate pro-inflammatory pathways in the gut, while inflammatory bowel diseases (IBD) can induce gut dysbiosis and qualitative and/or quantitative changes of the BA pool. These factors contribute to impaired repair capacity of the mucosal barrier, due to chronic inflammation. A better understanding of BA-dependent mechanisms paves the way to innovative therapeutic tools by administering hydrophilic BA and FXR agonists and manipulating gut microbiota with probiotics and prebiotics. We discuss the translational value of pathophysiological and therapeutic evidence linking BA homeostasis to gut inflammation in IBD.

Self-reported symptoms after COVID-19 vaccination. Distinct sex, age, and geographical outcomes in Lebanese and Italian cohorts.

Following the COVID-19 discovery in December 2019, different vaccines were authorized in 2021 in Italy and Lebanon, but side effects and the impact of sex and age remained partly explored. We designed a web-based "Google Form" questionnaire to record self-reported systemic and local side effects up to 7 days after 1st and 2nd dose of the vaccine in two distinct Italian and Lebanese cohorts. Twenty-one questions in Italian and Arabic languages explored the prevalence and severity of 13 symptoms. Results were compared with respect to living country, timing, sex, and age classes. A total of 1,975 Italian subjects (age 42.9 ± SD16.8 years; 64.5% females) and 822 Lebanese subjects (age 32.5 ± SD15.9 years; 48.8% females) joined the study. The most common symptoms in both groups were injection site pain, weakness, and headache after the 1st and 2nd doses. The rate of post-vaccinal symptoms and the severity score were significantly higher in females than in males and progressively decreased with increasing age following both doses. We find that among two populations from the Mediterranean basin, the anti-COVID-19 vaccine generates mild age and sex-dependent adverse effects, with ethnic differences and prevalent symptoms rate and severity in females.

Genetic and clinical features of familial mediterranean fever (FMF) in a homogeneous cohort of patients from South-Eastern Italy.

Familial Mediterranean Fever (FMF) is linked with the MEFV gene and is the commonest among monogenic autoinflammatory diseases, with high prevalence in the Mediterranean basin. Although the clinical presentation of FMF has a major role in diagnosis, genotype/phenotype correlations and the role of "benign" gene variants (as R202Q) appear highly variable and incompletely clear, making difficult to select the most effective strategy in the management of patients. Aim of the present study was to investigate the clinical presentation and the genetic background in a homogenous cohort of patients from Apulia (south eastern Italy). We investigated 217 patients with a clinical suspect of autoinflammatory diseases, who were characterized for the occurrence of specific symptoms and with next generation sequencing by a 4-gene panel including MEFV, MVK, NLRP3 and TNFRSF1A. A genetic change was identified in 122 (53.7%) patients, with 161 different MEFV variants recorded in 100 individuals, 10 variants in NLRP3, and 6 each in TNFRSF1A and MVK. The benign variant R202Q was largely prevalent (41.6% of all MEFV variants). When patients were selected according the number of pathogenic MEFV variants (0, 1, or 2 pathogenic variants), results failed to show significant links between the frequency of symptoms and the number of pathogenic variants. Only family history and Pras score (indicative for severity of disease) predicted the presence of pathogenic variants, as compared with carriers of variants considered of uncertain significance or benign. Fever >38 °C and arthralgias appeared more frequently in R202Q-positive patients than in non-R202Q carriers. These two subgroups showed comparable duration of fever, occurrence of myalgia, abdominal and chest pain, Pras, and IFFS scores. In conclusion, results confirm that FMF manifests in mild form in non-middle eastern patients. This possibility partly affects the reliability of clinical criteria/scores. Furthermore, the presence of the R202Q variant might not be completely neutral in selected groups of patients.

Ramadan intermittent fasting reduces visceral fat and improves gastrointestinal motility.

BACKGROUND: Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility. METHODS: In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis. RESULTS: Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H2 peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn. CONCLUSIONS: RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.

Contribution of the microbiome for better phenotyping of people living with obesity.

Obesity has reached epidemic proportion worldwide and in all ages. Available evidence points to a multifactorial pathogenesis involving gene predisposition and environmental factors. Gut microbiota plays a critical role as a major interface between external factors, i.e., diet, lifestyle, toxic chemicals, and internal mechanisms regulating energy and metabolic homeostasis, fat production and storage. A shift in microbiota composition is linked with overweight and obesity, with pathogenic mechanisms involving bacterial products and metabolites (mainly endocannabinoid-related mediators, short-chain fatty acids, bile acids, catabolites of tryptophan, lipopolysaccharides) and subsequent alterations in gut barrier, altered metabolic homeostasis, insulin resistance and chronic, low-grade inflammation. Although animal studies point to the links between an "obesogenic" microbiota and the development of different obesity phenotypes, the translational value of these results in humans is still limited by the heterogeneity among studies, the high variation of gut microbiota over time and the lack of robust longitudinal studies adequately considering inter-individual confounders. Nevertheless, available evidence underscores the existence of several genera predisposing to obesity or, conversely, to lean and metabolically health phenotype (e.g., Akkermansia muciniphila, species from genera Faecalibacterium, Alistipes, Roseburia). Further longitudinal studies using metagenomics, transcriptomics, proteomics, and metabolomics with exact characterization of confounders are needed in this field. Results must confirm that distinct genera and specific microbial-derived metabolites represent effective and precision interventions against overweight and obesity in the long-term.

Effect of channel density, inverse solutions and connectivity measures on EEG resting-state networks reconstruction: A simulation study.

Along with the study of brain activity evoked by external stimuli, the past two decades witnessed an increased interest in characterizing the spontaneous brain activity occurring during resting conditions. The identification of connectivity patterns in this so-called "resting-state" has been the subject of a great number of electrophysiology-based studies, using the Electro/Magneto-Encephalography (EEG/MEG) source connectivity method. However, no consensus has been reached yet regarding a unified (if possible) analysis pipeline, and several involved parameters and methods require cautious tuning. This is particularly challenging when different analytical choices induce significant discrepancies in results and drawn conclusions, thereby hindering the reproducibility of neuroimaging research. Hence, our objective in this study was to shed light on the effect of analytical variability on outcome consistency by evaluating the implications of parameters involved in the EEG source connectivity analysis on the accuracy of resting-state networks (RSNs) reconstruction. We simulated, using neural mass models, EEG data corresponding to two RSNs, namely the default mode network (DMN) and dorsal attentional network (DAN). We investigated the impact of five channel densities (19, 32, 64, 128, 256), three inverse solutions (weighted minimum norm estimate (wMNE), exact low-resolution brain electromagnetic tomography (eLORETA), and linearly constrained minimum variance (LCMV) beamforming) and four functional connectivity measures (phase-locking value (PLV), phase-lag index (PLI), and amplitude envelope correlation (AEC) with and without source leakage correction), on the correspondence between reconstructed and reference networks. We showed that, with different analytical choices related to the number of electrodes, source reconstruction algorithm, and functional connectivity measure, high variability is present in the results. More specifically, our results show that a higher number of EEG channels significantly increased the accuracy of the reconstructed networks. Additionally, our results showed significant variability in the performance of the tested inverse solutions and connectivity measures. Such methodological variability and absence of analysis standardization represent a critical issue for neuroimaging studies that should be prioritized. We believe that this work could be useful for the field of electrophysiology connectomics, by increasing awareness regarding the challenge of variability in methodological approaches and its implications on reported results.

The Impact of Za'atar Antioxidant Compounds on the Gut Microbiota and Gastrointestinal Disorders: Insights for Future Clinical Applications.

Since the gut microbiota plays a pivotal role in host homeostasis and energy balance, changes in its composition can be associated with disease states through the promotion of immune-mediated inflammatory disorders and increasing intestinal permeability, ultimately leading to the impairment of intestinal barrier function. Za'atar is one of the most popular plant-based foods in the Eastern Mediterranean region. Za'atar is a mixture of different plant leaves, fruits, and seeds and contains hundreds of antioxidant compounds, especially polyphenols, and fiber, with pre-clinical and clinical evidence suggesting health-promoting effects in cardiovascular and metabolic disease. Za'atar compounds have also been studied from a gastrointestinal perspective, concerning both gut microbiota and gastrointestinal diseases. Antioxidants such as Za'atar polyphenols may provide beneficial effects in the complex interplay between the diet, gut microbiota, and intestinal permeability. To our knowledge, no studies have reported the effects of the whole Za'atar mixture, however, based on the pre-clinical studies published on components and single compounds found in Za'atar, we provide a clinical overview of the possible effects on the gastrointestinal tract, focusing mainly on carvacrol, rosmarinic acid, gallic acid, and other polyphenols. We also cover the potential clinical applications of Za'atar mixture as a possible nutraceutical in disorders involving the gastrointestinal tract.

Gender-dependent impact of COVID-19 lockdown on metabolic and psychological aspects.

The first COVID-19 lockdown resulted in enforced quarantine of heavily affected areas with social isolation and related measures by several governments to slow the spread of the disease. The general population experienced several mental and lifestyle changes. Herein, we aimed to evaluate the metabolic and psychological effects induced by lifestyle changes during COVID-19 self-isolation among an Apulian overweight/obese cohort with metabolic disturbances. The study assessed anthropometric data (weight, abdominal circumferences), dietary habits (adherence to the Mediterranean diet, junk food score), lifestyle habits (i.e., smoking, and physical activity), levels of stress and anxiety, and depression. Subjects underwent bioumoral exams before and after self-isolation to monitor glycemic and lipid profiles. A total of 245 subjects (M:F = 118:127) have been included in the study. After lockdown, the number of obese subjects significantly increased in both sexes, and was higher in females than in males (P < 0.0001). Glycemic and lipid profiles worsened, with higher levels of insulinemia, lower levels of HDL cholesterol, and higher levels of triglycerides in females than in males. Adherence to the Mediterranean diet and consumption of junk foods were altered in both groups, especially in females. Psychological aspects were significantly higher in females than in males. Finally, work activities and familial status strongly affected the metabolic and psychological profile. In conclusion, COVID-19 self-isolation induced changes in lifestyle and dietary habits with psychological distress and detrimental effects on metabolic patterns, which were more pronounced in female gender.

Prevention of Oxidative Stress and Diseases by Antioxidant Supplementation.

Excessive and uncontrolled oxidative stress can damage biomacromolecules, such as lipids, proteins, carbohydrates, and DNA, by free radical and oxidant overproduction. In this review, we critically discuss the main properties of free radicals, their implications in oxidative stress, and specific pathological conditions. In clinical medicine, oxidative stress can play a role in several chronic noncommunicable diseases, such as diabetes mellitus, cardiovascular, inflammatory, neurodegenerative diseases, and tumours. Antioxidant supplements can theoretically prevent or stop the progression of diseases, but a careful literature analysis finds that more evidence is needed to dissect the ultimate beneficial effect of antioxidants versus reactive oxygen species in several diseases.

Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling.

Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/ß-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.