Pancreatic Ductal Adenocarcinoma and Nutrition: Exploring the Role of Diet and Gut Health.

The incidence of pancreatic cancer is increasing worldwide. The most common form is represented by pancreatic ductal adenocarcinoma (PDAC) which has been shown to be linked to chronic inflammation. Notably, the gut microbiota has emerged as a critical player in regulating immune responses and inflammation. Indeed, intestinal dysbiosis, characterized by an imbalance in the gut microbiota composition, can contribute to the initiation of chronic inflammation. Sterile chronic inflammation can occur, probably activated by the translocation of bacterial components, such as lipopolysaccharide (LPS), the major component of Gram-negative microbiota, with the consequent induction of innate mucosal immunity, through the activation of Toll-like receptors (TLRs). Furthermore, the interaction between LPS and TLRs could enhance cancer progression. Recent research has shed light on the pivotal role of nutrition, as a modifiable risk factor, in PDAC immunological processes, particularly focusing on the immuno-modulatory effects of the gut microbiota. Different dietary regimens, fiber intake, immunonutrients, and antioxidants have the potential to either exacerbate or mitigate chronic inflammation, thereby influencing the pathogenesis and natural history of PDAC. These dietary components may affect the gut microbiota composition and, consequently, the level of inflammation, either promoting or protecting against PDAC. In this review of reviews, we discuss the modulatory role of nutrition and the gut microbiota in PDAC's immunological processes to explore a translational therapeutic approach that could improve the survival and quality of life of these patients.

Nutrition for Prevention and Control of Chronic Degenerative Diseases and COVID-19.

Chronic degenerative diseases (CDD) are non-infectious, slow-progressing, and long-lasting diseases such as diabetes, heart disease, obesity, chronic respiratory diseases, neurodegenerative diseases, and cancer [...].

The Pharmaceutical Formulation Plays a Pivotal Role in Hydroxytyrosol Pharmacokinetics.

Current evidence supports the use of extra virgin olive oil (EVOO) and its minor components such as hydroxytyrosol or 3,4-dihydroxyphenyl ethanol (DOPET), to improve cardiovascular and metabolic health. Nevertheless, more intervention studies in humans are needed because some gaps remain in its bioavailability and metabolism. The aim of this study was to investigate the DOPET pharmacokinetics on 20 healthy volunteers by administering a hard enteric-coated capsule containing 7.5 mg of bioactive compound conveyed in EVOO. The treatment was preceded by a washout period with a polyphenol and an alcohol-free diet. Blood and urine samples were collected at baseline and different time points, and free DOPET and metabolites, as well as sulfo- and glucuro-conjugates, were quantified by LC-DAD-ESI-MS/MS analysis. The plasma concentration versus time profiles of free DOPET was analyzed by a non-compartmental approach, and several pharmacokinetic parameters (Cmax, Tmax, T1/2, AUC0-440 min, AUC0-∞, AUCt-∞, AUCextrap_pred, Clast and Kel) were calculated. Results showed that DOPET Cmax (5.5 ng/mL) was reached after 123 min (Tmax), with a T1/2 of 150.53 min. Comparing the data obtained with the literature, the bioavailability of this bioactive compound is about 2.5 times higher, confirming the hypothesis that the pharmaceutical formulation plays a pivotal role in the bioavailability and pharmacokinetics of hydroxytyrosol.

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.

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.

Diet, Nutrition and Chronic Degenerative Diseases.

Chronic degenerative diseases (CDDs), represented mainly by obesity, cardiovascular disease (CVD), diabetes, chronic kidney disease (CKD), inflammatory bowel diseases, osteoporosis, sarcopenia, neurodegenerative diseases such as Huntington's disease (HD), rheumatoid arthritis (RA), chronic respiratory diseases, and many cancers, have been, up to now, the most frequent causes of prolonged disability and death worldwide [...].

Lockdown of Breast Cancer Screening for COVID-19: Possible Scenario.

BACKGROUND/AIM: Coronavirus disease is spreading worldwide. Due to fast transmission and high fatality rate drastic emergency restrictions were issued. During the lockdown, only urgent medical services are guaranteed. All non-urgent services, as breast cancer (BC) screening, are temporarily suspended. The potential of breast cancer screening programs in increasing the survival rate and decreasing the mortality rate has been widely confirmed. Suspension could lead to worse outcomes for breast cancer patients. Our study aimed to analyse the data and provide estimates regarding the temporary BC screening suspension. PATIENTS AND METHODS: Data regarding breast cancer and respective screening programs were achieved through literature research and analysis. RESULTS: Considering three different scenarios with respect to the lockdown's impact on breast cancer screening, we estimate that approximately 10,000 patients could have a missed diagnosis during these 3 months. Considering a 6-month period, as suggested by the Imperial college model, the number of patients who will not receive a diagnosis will rise to 16,000. CONCLUSION: Breast cancer screening should be resumed as soon as possible in order to avoid further breast cancer missed diagnosis and reduce the impact of delayed diagnosis.

PI3Kδ Inhibition as a Potential Therapeutic Target in COVID-19.

The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1ß, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.

Body Composition Findings by Computed Tomography in SARS-CoV-2 Patients: Increased Risk of Muscle Wasting in Obesity.

Obesity is a characteristic of COVID-19 patients and the risk of malnutrition can be underestimated due to excess of fat: a paradoxical danger. Long ICU hospitalization exposes patients to a high risk of wasting and loss of lean body mass. The complex management precludes the detection of anthropometric parameters for the definition and monitoring of the nutritional status. The use of imaging diagnostics for body composition could help to recognize and treat patients at increased risk of wasting with targeted pathways. COVID-19 patients admitted to the ICU underwent computed tomography within 24 hours and about 20 days later, to evaluate the parameters of the body and liver composition. The main results were the loss of the lean mass index and a greater increase in liver attenuation in obese subjects. These could be co-caused by COVID-19, prolonged bed rest, the complex medical nutritional therapy, and the starting condition of low-grade inflammation of the obese. The assessment of nutritional status, with body composition applied to imaging diagnostics and metabolic profiles in COVID-19, will assist in prescribing appropriate medical nutritional therapy. This will reduce recovery times and complications caused by frailty.

Eating habits and lifestyle changes during COVID-19 lockdown: an Italian survey.

BACKGROUND: On December 12th 2019, a new coronavirus (SARS-Cov2) emerged in Wuhan, China, sparking a pandemic of acute respiratory syndrome in humans (COVID-19). On the 24th of April 2020, the number of COVID-19 deaths in the world, according to the COVID-Case Tracker by Johns Hopkins University, was 195,313, and the number of COVID-19 confirmed cases was 2,783,512. The COVID-19 pandemic represents a massive impact on human health, causing sudden lifestyle changes, through social distancing and isolation at home, with social and economic consequences. Optimizing public health during this pandemic requires not only knowledge from the medical and biological sciences, but also of all human sciences related to lifestyle, social and behavioural studies, including dietary habits and lifestyle. METHODS: Our study aimed to investigate the immediate impact of the COVID-19 pandemic on eating habits and lifestyle changes among the Italian population aged ≥ 12 years. The study comprised a structured questionnaire packet that inquired demographic information (age, gender, place of residence, current employment); anthropometric data (reported weight and height); dietary habits information (adherence to the Mediterranean diet, daily intake of certain foods, food frequency, and number of meals/day); lifestyle habits information (grocery shopping, habit of smoking, sleep quality and physical activity). The survey was conducted from the 5th to the 24th of April 2020. RESULTS: A total of 3533 respondents have been included in the study, aged between 12 and 86 years (76.1% females). The perception of weight gain was observed in 48.6% of the population; 3.3% of smokers decided to quit smoking; a slight increased physical activity has been reported, especially for bodyweight training, in 38.3% of respondents; the population group aged 18-30 years resulted in having a higher adherence to the Mediterranean diet when compared to the younger and the elderly population (p < 0.001; p < 0.001, respectively); 15% of respondents turned to farmers or organic, purchasing fruits and vegetables, especially in the North and Center of Italy, where BMI values were lower. CONCLUSIONS: In this study, we have provided for the first time data on the Italian population lifestyle, eating habits and adherence to the Mediterranean Diet pattern during the COVID-19 lockdown. However, as the COVID-19 pandemic is ongoing, our data need to be confirmed and investigated in future more extensive population studies.

Obesity and Body Composition in Man and Woman: Associated Diseases and the New Role of Gut Microbiota.

BACKGROUND: Obesity is now recognized as a worldwide health issue and has reached epidemic proportions, affecting both developed and developing countries. The World Obesity Federation stated that "Obesity is a chronic relapsing disease process": as a result, obesity has been recognized internationally as a chronic disease. The primary cause of the metabolic syndrome and increase of the cardiovascular risk have been identified in "sick fat", a condition then defined as adiposopathy. Heart attacks, strokes and renal failures are pathologies that have mid-risk factors such as dyslipidemia, hypertension and diabetes, which in turn are caused by obesity, whose primary risk factor is represented by the diet. The aim of the present review is to consider the importance of body composition, together with chronic inflammation and a new gut microbiota data that may turn out to be crucial elements of some target treatment of human obesity. METHODS: In this review, we performed research using PubMed database reviewing the evidence in the literature of evidence information regarding the link between obesity and body composition in the development of metabolic disease via inflammation markers and in particular, the new role exerted by gut microbiota. RESULTS: Several papers were evaluated searching for differences in fat mass and disease risk. We also identified the same papers dealing with differences in body composition and metabolic syndrome. Our attention focuses also on a new frontier of gut microbiota composition in the body weight decrease and anti-inflammatory effects. CONCLUSION: To the saving of lean mass, for the prevention of cardiometabolic diseases, also considering the relationship with obesity, it is necessary to reduce the inflammatory state, acting on the gut-microbiota and on the intestinal permeability. To improve the health of the intestinal flora, we propose a 4P medicine and treatment with probiotics, prebiotics, postbiotics, and polyphenols.

Why primary obesity is a disease?

Obesity must be considered a real pathology. In the world wide, obesity represent one of the major public health issue associated with increased morbidity and mortality. Overweight or obesity, in fact, significantly increases the risk of contracting diseases, such as: arterial hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, cerebral vasculopathy, gallbladder lithiasis, arthropathy, ovarian polycytosis, sleep apnea syndrome, and some neoplasms. Despite numerous informative campaigns, unfortunately, the fight against obesity does not seem to work: in the last years, the prevalence continued to increase. The progressive and rapid increase in the incidence of obesity, which has characterized most of the economically advanced countries in the last decade, has been the main stimulus for the research of the mechanisms underlying this pathology and the related disorders. The aims of this review is to provide a revision of the literature in order to define obesity as diseases, secondly to highlight the limits and the inaccuracy of common tools used for the diagnosis of obesity, and as a third thing to strengthen the concept of the complexity of obesity as a disease among political health care providers. Obesity may be viewed as a multifactorial pathology and chronic low-grade inflammatory disease. In fact, people affected by obesity have greater risk of developing comorbility and morbility, respect to healthy. Hence, the absolute therapeutic benefit is directly proportional to the basic risk. So, internationally interest on early diagnosis of obesity is growing to avoid under- and overdiagnosis consequences. Therefore, the consequences are an aggravation of the disease and an increase in obesity related pathology like diabetes, cardiovascular disease, and cancer. The most widely used parameter for diagnosis, body mass index (BMI) is not suitable for assessing the body fat. In fact, several studies demonstrate that BMI alone cannot define obesity, which consists not so much in weight gain as in excess fat mass. The use of suitable tools for the assessment of fat mass percentage combined with clinical and genetic analysis allowed to identify different phenotypes of obesity, which explain the various paradoxes of obesity. It is essential to adopt all possible strategies to be able to combat obesity, ameliorate the suffering of patients, and reduce the social and treatment costs of obesity.

Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial.

Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed. Oxidation biomarkers like thiol group (p = 0.001), total antioxidant status (TAS) (p = 0.001), superoxide dismutase 1 (SOD1) (2-ΔΔCt = 3.7), and plasma concentration of HT (2.83 µg·mL-1) were significantly increased, while nitrite (p = 0.001), nitrate (p = 0.001), and malondialdehyde (MDA) (p = 0.02) were drastically reduced after HTT. A significant reduction of body fat mass percentage (p = 0.01), suprailiac skinfold (p = 0.01), and weight (p = 0.04; Δ% = -0.46%) was observed after HTT. This study shows that regular intake of 15 mg/day of HT changed body composition parameters and modulated the antioxidant profile and the expression of inflammation and oxidative stress-related genes. However, it is advisable to personalize HT doses in order to exert its health benefits in CVD prevention and protection of LDL-C particles from oxidative damage. This trial is registered with ClinicalTrials.gov NCT01890070.