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.

Cell-Target-Specific Anti-Inflammatory Effect of Empagliflozin: In Vitro Evidence in Human Cardiomyocytes.

The antidiabetic sodium-glucose cotransporter type 2 inhibitor (SGLT2i) empagliflozin efficiently reduces heart failure (HF) hospitalization and cardiovascular death in type 2 diabetes (T2D). Empagliflozin-cardioprotection likely includes anti-inflammatory effects, regardless glucose lowering, but the underlying mechanisms remain unclear. Inflammation is a primary event in diabetic cardiomyopathy (DCM) and HF development. The interferon (IFN)γ-induced 10-kDa protein (IP-10/CXCL10), a T helper 1 (Th1)-type chemokine, promotes cardiac inflammation, fibrosis, and diseases, including DCM, ideally representing a therapeutic target. This preliminary study aims to explore whether empagliflozin directly affects Th1-challenged human cardiomyocytes, in terms of CXCL10 targeting. To this purpose, empagliflozin dose-response curves were performed in cultured human cardiomyocytes maintained within a Th1-dominant inflammatory microenvironment (IFNγ/TNFα), and CXCL10 release with the intracellular IFNγ-dependent signaling pathway (Stat-1) was investigated. To verify possible drug-cell-target specificity, the same assays were run in human skeletal muscle cells. Empagliflozin dose dependently inhibited CXCL10 secretion (IC50 = 76,14 × 10-9 M) in association with Stat-1 pathway impairment only in Th1-induced human cardiomyocytes, suggesting drug-selective cell-type-targeting. As CXCL10 plays multifaceted functions in cardiac remodeling toward HF and currently there is no effective method to prevent it, these preliminary data might be hypothesis generating to open new scenarios in the translational approach to SGLT2i-dependent cardioprotection.

Effects of Fatty Acids on Hematological Neoplasms: A Mini Review.

Hematological neoplasias are the fourth cause of death in the world. All of them are responsible of bad quality of life, due to heavy therapies administration and a lot of side effects correlated to. It arises a new concept of "multitherapy", in which fatty acids availment is used to contrast and reduce toxic effects and ameliorate chemotherapeutic agents asset. In Vitro studies have confirmed that fatty acids, in particular ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are able to help canonical therapies to contrast cancer cell expansion and proliferation. In clinical trials it is also almost clear that fatty acids are useful to build new personalized therapies for a better condition of life. In this review we have summarized most recent studies on cancer cell lines and clinical trials on patients with fatty acids supplementation in diet therapies. We have found that fatty acids could be useful to contrast side effects during chemotherapeutic drugs therapies; they are also able to block cancer cell metabolic pathways for proliferation and contrast adverse effects, even when they are used in combination with traditional therapies or innovative, like monoclonal antibodies or CAR-T therapy. These aspects are crucial for better health condition of patients.

Cariogenic Risk and COVID-19 Lockdown in a Paediatric Population.

The Severe Acute Respiratory Syndrome Coronavirus 2 disease COVID-19 pandemic caused several lifestyle changes, especially among younger people. The study aimed to describe the impact of eating habits, lifestyle, and home oral hygiene during the COVID-19 pandemic, on the cariogenic risk in the Italian paediatric population, by using an online survey. The survey was conducted through a virtual questionnaire divided into four parts: child personal and anthropometric data; oral health; child dietary habits (KIDMED test); and child lifestyle, before and during COVID-19 lockdown. During the lockdown, only 18.6% of the participants had high adherence to a Mediterranean diet, recording an increase in sweets consumption and the number of meals (p < 0.001). In terms of lifestyle, the percentage of moderately and vigorously active children decreased (41.4% and 5.0%, respectively) (p = 0.014). The percentage of children sleeping more than 9 h increased (p < 0.001). They watched more television programs (p < 0.001). Regarding oral hygiene, children did not change their brushing habits (p = 0.225). The percentage of children using non-fluoridated toothpaste was higher (6.4%), and no changes were observed (p > 0.05). In some cases, dental pain and abscesses were declared (10% and 2.7%, respectively). This study confirms the need for campaigns to promote hygiene and dental care in combination with food education for a correct habit and promotion of a healthy and sustainable dietary style.

Psychological Aspects and Eating Habits during COVID-19 Home Confinement: Results of EHLC-COVID-19 Italian Online Survey.

The COVID-19 pandemic has had a huge impact on the population with consequences on lifestyles. The aim of the study was to analyse the relationship between eating habits, mental and emotional mood. A survey was conducted online during social isolation, from 24 April to 18 May 2020, among the Italian population. A total of 602 interviewees were included in the data analysis. A high percentage of respondents experienced a depressed mood, anxious feelings, hypochondria and insomnia (61.3%, 70.4%, 46.2% and 52.2%). Almost half of the respondents felt anxious due to the fact of their eating habits, consumed comfort food and were inclined to increase food intake to feel better. Age was inversely related to dietary control (OR = 0.971, p = 0.005). Females were more anxious and disposed to comfort food than males (p < 0.001; p < 0.001). A strength of our study was represented by the fact that the survey was conducted quickly during the most critical period of the Italian epidemic lockdown. As the COVID-19 pandemic is still ongoing, our data need to be confirmed and investigated in the future with larger population studies.

Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism.

The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. Here, we show that cyclin D3 also performs a novel function, regulating muscle fiber type-specific gene expression. Mice lacking cyclin D3 display an increased number of myofibers with higher oxidative capacity in fast-twitch muscle groups, primarily composed of myofibers that utilize glycolytic metabolism. The remodeling of myofibers toward a slower, more oxidative phenotype is accompanied by enhanced running endurance and increased energy expenditure and fatty acid oxidation. In addition, gene expression profiling of cyclin D3-/- muscle reveals the upregulation of genes encoding proteins involved in the regulation of contractile function and metabolic markers specifically expressed in slow-twitch and fast-oxidative myofibers, many of which are targets of MEF2 and/or NFAT transcription factors. Furthermore, cyclin D3 can repress the calcineurin- or MEF2-dependent activation of a slow fiber-specific promoter in cultured muscle cells. These data suggest that cyclin D3 regulates muscle fiber type phenotype, and consequently whole body metabolism, by antagonizing the activity of MEF2 and/or NFAT.