Nutrients, herbal bioactive derivatives and commensal microbiota as tools to lower the risk of SARS-CoV-2 infection.

The SARS-CoV-2 outbreak has infected a vast population across the world, causing more than 664 million cases and 6.7 million deaths by January 2023. Vaccination has been effective in reducing the most critical aftermath of this infection, but some issues are still present regarding re-infection prevention, effectiveness against variants, vaccine hesitancy and worldwide accessibility. Moreover, although several old and new antiviral drugs have been tested, we still lack robust and specific treatment modalities. It appears of utmost importance, facing this continuously growing pandemic, to focus on alternative practices grounded on firm scientific bases. In this article, we aim to outline a rigorous scientific background and propose complementary nutritional tools useful toward containment, and ultimately control, of SARS-CoV-2 infection. In particular, we review the mechanisms of viral entry and discuss the role of polyunsaturated fatty acids derived from α-linolenic acid and other nutrients in preventing the interaction of SARS-CoV-2 with its entry gateways. In a similar way, we analyze in detail the role of herbal-derived pharmacological compounds and specific microbial strains or microbial-derived polypeptides in the prevention of SARS-CoV-2 entry. In addition, we highlight the role of probiotics, nutrients and herbal-derived compounds in stimulating the immunity response.

Interleukin-18 Is a Potential Biomarker Linking Dietary Fatty Acid Quality and Insulin Resistance: Results from a Cross-Sectional Study in Northern Italy.

Dietary lipids are pivotal in modulating metabolic inflammation. Among the inflammatory mediators characterizing metabolic inflammation, interleukin 18 (IL-18) has been consistently associated with obesity and insulin resistance. This study aims to evaluate whether the quality of lipid intake impacts upon IL-18 plasma levels and the implications on insulin resistance computed by the homeostatic model assessment for insulin resistance (HOMA-IR). Using a cross-sectional design, this study confirmed that IL-18 correlated positively with insulin resistance and individuals with a HOMA-IR ≥ 2.5 displayed higher circulating IL-18 levels compared with their insulin-sensitive counterparts. In terms of the effect of the quality of dietary lipids on IL-18 circulating levels, the ratio between monounsaturated, omega-3, polyunsaturated and saturated fatty acids as well as the intake of eicosapentaenoic and docosahexaenoic acids correlated negatively with IL-18. Despite this, IL-18 circulating levels, but not dietary fatty acid quality, predicted insulin resistance. Nevertheless, the ratio between omega 3 and saturated fatty acids was a predictor of IL-18 plasma levels. Thus, the downregulation of IL-18 may underpin, at least partially, the beneficial metabolic effects of substituting omega 3 for saturated fatty acids with this cytokine potentially representing a biomarker linking dietary lipids and metabolic outcomes.

Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides.

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.

New Insights on the Role of Bioactive Food Derivatives in Neurodegeneration and Neuroprotection.

Over the last three decades, neurodegenerative diseases have received increasing attention due to their frequency in the aging population and the social and economic burdens they are posing. In parallel, an era's worth of research in neuroscience has shaped our current appreciation of the complex relationship between nutrition and the central nervous system. Particular branches of nutrition continue to galvanize neuroscientists, in particular the diverse roles that bioactive food derivatives play on health and disease. Bioactive food derivatives are nowadays recognized to directly impact brain homeostasis, specifically with respect to their actions on cellular mechanisms of oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and autophagy. However, ambiguities still exist regarding the significance of the influence of bioactive food derivatives on human health. In turn, gut microbiota dysbiosis is emerging as a novel player in the pathogenesis of neurodegenerative diseases. Currently, several routes of communication exist between the gut and the brain, where molecules are either released in the bloodstream or directly transported to the CNS. As such, bioactive food derivatives can modulate the complex ecosystem of the gut-brain axis, thus, targeting this communication network holds promises as a neuroprotective tool. This review aims at addressing one of the emerging aspects of neuroscience, particularly the interplay between food bioactive derivatives and neurodegeneration. We will specifically address the role that polyphenols and omega-3 fatty acids play in preventing neurodegenerative diseases and how dietary intervention complements available pharmacological approaches.

Eucaloric diets enriched in palm olein, cocoa butter, and soybean oil did not differentially affect liver fat concentration in healthy participants: a 16-week randomized controlled trial.

BACKGROUND: Effects of dietary fat quality on liver fat remain to be elucidated. Inconsistent evidence may be influenced by fatty acid saturation, chain-length, and regio-specificity within triacylglycerol (TAG) molecules. OBJECTIVES: We aimed to compare eucaloric diets enriched in palm olein (POo), cocoa butter (COB), and soybean oil (SBO) on liver fat concentration in healthy participants. Secondary outcomes included visceral (VAT) and abdominal subcutaneous (aSCAT) adipose tissue, plus other obesity and cardiometabolic health outcomes. METHODS: Eighty-three healthy participants (20-45 y, BMI 18.5-27.5 kg/m2) commenced and 64 completed a 16-wk randomized parallel intervention, preceded by a 2-wk run-in. Participants consumed identical eucaloric background diets differing in test fats [contributing 20% total energy intake (%E)], providing 33%E total fat with the following ratios for PUFAs/SFAs/MUFAs: POo, 4.2/13.5/15%E; SBO, 14.4/8.8/9.4%E; COB, 2.3/19.5/11%E. Liver fat and abdominal adiposity were measured at weeks 0 and 16 using 1H-magnetic resonance spectroscopy/imaging; all other outcomes were measured at 0, 4, 8, 12, and 16 wk. RESULTS: Fat quality did not affect liver fat concentration, VAT, aSCAT, obesity indexes, blood pressure, liver enzymes, leptin, or fasting glucose. Body fat mass decreased with SBO and COB compared with POo. SBO decreased serum total cholesterol (TC), LDL cholesterol, and TC:HDL cholesterol relative to POo [estimated marginal mean (95% CI) differences: -0.57 (-0.94, -0.20) mmol/L; -0.37 (-0.68, -0.07) mmol/L; and -0.42 (-0.73, -0.11) mmol/L, respectively]. No diet differences were observed on HDL cholesterol, TAG, apoA1, apoB, apoB:apoA1, or fecal free fatty acids (FFAs), except for lower FFA pentadecanoic acid (15:0) with COB than with SBO and POo. CONCLUSIONS: In healthy adults, when consumed as part of eucaloric typical Australian diets, 3 different dietary fat sources did not differentially affect liver fat concentration and amounts of adipose tissue. Effects on serum lipids were inconsistent across lipid profiles. The findings must be confirmed in metabolically impaired individuals before recommendations can be made.

The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review.

The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions.

Palmitic acid triggers inflammatory responses in N42 cultured hypothalamic cells partially via ceramide synthesis but not via TLR4.

A high-fat diet induces hypothalamic inflammation in rodents which, in turn, contributes to the development of obesity by eliciting both insulin and leptin resistance. However, the mechanism by which long-chain saturated fatty acids trigger inflammation is still contentious. To elucidate this mechanism, the effect of fatty acids on the expression of the pro-inflammatory cytokines IL-6 and TNFα was investigated in the mHypoE-N42 hypothalamic cell line (N42). N42 cells were treated with lauric acid (LA) and palmitic acid (PA). PA challenge was carried out in the presence of either a TLR4 inhibitor, a ceramide synthesis inhibitor (L-cycloserine), oleic acid (OA) or eicosapentaenoic acid (EPA). Intracellular ceramide accumulation was quantified using LC-ESI-MS/MS. PA but not LA upregulated IL-6 and TNFα. L-cycloserine, OA and EPA all counteracted PA-induced intracellular ceramide accumulation leading to a downregulation of IL-6 and TNFα. However, a TLR4 inhibitor failed to inhibit PA-induced upregulation of pro-inflammatory cytokines.In conclusion, PA induced the expression of IL-6 and TNFα in N42 neuronal cells independently of TLR4 but, partially, via ceramide synthesis with OA and EPA being anti-inflammatory by decreasing PA-induced intracellular ceramide build-up. Thus, ceramide accumulation represents one on the mechanisms by which PA induces inflammation in neurons.

Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity.

Diet-induced hypothalamic inflammation, which leads to hypothalamic dysfunction and a loss of regulation of energy balance, is emerging as a potential driver of obesity. Excessive intake of long-chain saturated fatty acids is held to be the causative dietary component in hypothalamic inflammation. This review summarizes current evidence on the role of long-chain saturated fatty acids in promoting hypothalamic inflammation and the related induction of central insulin and leptin insensitivity. Particularly, the present review focuses on the molecular mechanisms linking long-chain saturated fatty acids and hypothalamic inflammation, emphasizing the metabolic fate of fatty acids and the resulting lipotoxicity, which is a key driver of hypothalamic dysfunction. In conclusion, long-chain saturated fatty acids are key nutrients that promote hypothalamic inflammation and dysfunction by fostering the build-up of lipotoxic lipid species, such as ceramide. Furthermore, when long-chain saturated fatty acids are consumed in combination with high levels of refined carbohydrates, the proinflammatory effects are exacerbated via a mechanism that relies on the formation of advanced glycation end products.

The Effects of Dietary Polyphenols on Circulating Cardiovascular Disease Biomarkers and Iron Status: A Systematic Review.

The prevalence of cardiovascular disease (CVD) is rising worldwide, remaining the major cause of death in developed countries. Polyphenols have been shown to have cardioprotective properties; however, their impact on iron bioavailability and potential impact on other aspects of health is unclear. A systematic review was undertaken to evaluate the current status of the relationship between habitual polyphenol consumption, iron status, and circulating biomarkers of CVD. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines, searches were performed across 5 electronic databases (PubMed, Cochrane Library, Scopus, Web of Science, and CINAHL) to identify randomized controlled trials which investigated the effects of polyphenol consumption on inflammatory markers, serum lipid profile, and iron absorption and bioavailability. In total, 1174 records were identified, with only 7 studies meeting the inclusion criteria. The selected studies involved 133 participants and used a variety of foods and supplements, including olive oil and cherries, rich in polyphenols including hydroxytyrosol, quercetin, and resveratrol, as well as catechin enriched drinks. The duration of the studies ranged from between 56 and 145 days, with total polyphenolic content of the food items and supplements ranging from 45 to 1015 mg (per 100 g). Polyphenols did not appear to interfere with iron status, and most studies reported improvements in inflammatory markers and lipid profile. While these results are promising, the limited number of studies and considerable heterogeneity across the interventions support the need for more extensive trials assessing the relationship between polyphenol intake, iron bioavailability, and CVD risk.

The beneficial health effects of green tea amino acid l-theanine in animal models: Promises and prospects for human trials.

l-Theanine (l-THE) is a nonproteinogenic amino acid derived from green tea (Camellia sinensis), which exhibits strong antioxidant-like properties and contributes to the favourable umami taste sensation. Several studies have reported that the consumption of this amino acid has many therapeutic effects, including improvements in brain and gastrointestinal function, cancer drug therapeutic efficacies, antihypertensive effects, and improved immune function. Considering the recent Western commercialisation and popularity of green tea consumption as a nootropic agent in humans, the aims of this review were to consolidate the existing knowledge from ex vivo and in vitro animal models and attempt to highlight the applicability of l-THE towards the human clinical trials. Considering the anti-inflammatory and antioxidants effects of l-THE presented in the current review, further research must translate the existing knowledge gained from animal and cell models to exploring the potential metabolic health benefits and moderating effects on the pathogenesis of conditions such as obesity, arthritis, depression, and type 2 diabetes in human trials. This will bridge the gap in literature and provide more insights into the mechanisms driving pathologies characterised by the inflammatory response and oxidative stress.

Anthropometric, metabolic and molecular determinants of human epidermal growth factor receptor 2 expression in luminal B breast cancer.

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (

Unusual long-lasting cutaneous complete response to lapatinib and capecitabine in a heavily pretreated HER2-positive plurimetastatic breast cancer patient.

Lapatinib, in combination with capecitabine, has shown clinical activity in both first-line and refractory disease in patients with HER2-positive advanced breast cancer. Herein we describe the case of a plurimetastatic, heavily pretreated, HER2-positive breast cancer patient who experienced multiple cutaneous metastases successfully treated with lapatinib and capecitabine. An early complete response was obtained on all skin lesions, and no evidence of disease progression at other metastatic sites was observed for 22 months. The treatment was well tolerated, without dose-reductions or delays. In advanced breast cancer patients with skin metastases overexpressing HER2, previously treated with anthracyclines, taxanes and trastuzumab, lapatinib and capecitabine may represent a very active, safe and well-tolerated treatment option.

Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer.

The role of aromatase inhibitors combined with gonadotropin-releasing hormone analog in metastatic male breast cancer patients remains unknown. In this retrospective study we evaluated the activity of letrozole combined with a gonadotropin-releasing hormone analog as a first- or second-line therapy for metastatic male breast cancer patients. 19 men entered the study. We did not observe any grade 3 or 4 adverse events. 2 patients (10.5 %) had complete response, 7 patients (36.8 %) experienced a partial response, 7 patients (36.8 %) had stable disease lasting ≥ 6 months, and 3 patients (15.8 %) had progressive disease. Overall, the disease control rate was 84.2 %. Median progression-free survival was 12.5 months (95 % CI 8.2-16.9), median overall survival was 35.8 months (95 % CI 24.4-49.2), 1- and 2-year survival rates were 89.5 and 67 %, respectively. Interestingly, 3 out of 4 patients treated with the combination following disease progression while on aromatase inhibitor monotherapy confirmed or improved the best overall response observed in the first-line setting. The combination of letrozole and gonadotropin-releasing hormone analog is effective and safe in hormone-receptor positive, metastatic male breast cancer patients.

Vitamin D supplementation and breast cancer prevention: a systematic review and meta-analysis of randomized clinical trials.

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the "Related Article" feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I(2) test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74-1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23-1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54-1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.

Impact of continuous intracardiac ST-segment monitoring on mid-term outcomes of ICD-implanted patients with coronary artery disease. Early results of a prospective comparison with conventional ICD outcomes.

BACKGROUND: Although myocardial ischaemia monitored by some implantable cardioverter-defibrillators (ICDs) might improve patient care, the clinical usefulness of this technology has not yet been validated. OBJECTIVE: To investigate the potential impact of ICD-based ischaemia monitoring on clinical care and patient management of ICD recipients. DESIGN: Prospective, controlled, non-randomised study. SETTING: Single-centre, university hospital. PATIENTS: Consecutive patients with known coronary artery disease, followed up for at least 6 months. INTERVENTIONS: Patients implanted with either an ICD providing continuous intracardiac ST monitoring (n=53; ST group) or with an ICD without this capability (n=50). MAIN OUTCOME MEASURES: Major cardiovascular events, appropriateness of ST-shift episodes and unscheduled device-related visits. RESULTS: During follow-up (15.4±8.4 months), one patient experienced ST-shift events confirmed by angiography to be related to myocardial ischaemia. Myocardial infarction was a rare event and occurred in one patient (ST group) who had an ST-elevation myocardial infarction 3 weeks after the implant, but at this time the algorithm had not yet been activated. In the ST group, seven patients had one or more episodes of false-positive ST events (median 9, range 1-90). The programmable features of the device helped overcome the problem in six patients. Among patients with a remote monitoring system, unscheduled outpatient visits were significantly increased in the ST group (17 vs 4; p=0.032). CONCLUSIONS: Although, this study was underpowered by the small number of acute ischaemic events, ICD-based ST monitoring failed to provide a benefit over ICDs without this capability and increased unscheduled evaluations in patients with remote follow-up. The sensitivity and specificity of the algorithm still require validation.