Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance

The growing global epidemic of obesity and type 2 diabetes mellitus has de-termined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the West-ern world and a leading cause of liver transplan-tation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close as-sociation between insulin resistance (IR), dys-biosis, and steatosis. However, all the mecha-nisms that lead to impaired permeability, inflam- mation, and fibrosis have not been fully clari- fied. Recently, new possible treatment modali- ties have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (poly -phenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NA-FLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the thera-peutic strategies currently in use

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5(+)) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5(+), or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5(+) administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5(+) inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5(+) significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5(+) may be able to counteract adipogenesis and then obesity by inducing fat browning

Il naturalismo oggi. Abbozzo di una mappa e alcune riflessioni

This paper tries to draw a map of the various versions of naturalism to which the current philosophical debate aims – from the most radical, or ‘hard’ ones, to the mild-est, or liberal ones – and of the different projects of naturalization that are associated to them. In particular, in the first paragraphs, the present article will consider Timothy Williamson’s and Penelope Maddy’s attempts to inherit the demands of naturalism with-out declaring to be a naturalist (Williamson), or without making naturalism an empty slogan or a kind of masked first philosophy (Maddy). In the second part, the connec-tions between epistemological naturalism and ontological or metaphysical naturalism will be analysed. The questions will be: (1) is it possible to be naturalist with regard to epistemology without being naturalist with regard to ontology?; (2) is it possible to be ontologically naturalist without being epistemologically naturalist

Psychosocial Predictors of Colorectal Cancer Screening Intention: An Experiment on the Invitation Letter

Background: In Italy, attendance rates for colorectal cancer (CRC) screening are suboptimal. The present work analysed cognitive and emotional predictors of CRC screening intention and tested an intervention on a real invitation letter to improve CRC screening intention, both directly and in interaction with the predictors of our model. Methods: Our model included variables from the theory of planned behaviour and the emotional barriers to bowel screening scale. We applied six changes to an invitation letter used in Italy to avoid the repetition of words like ‘faeces’, ‘blood’, or ‘occult’ and reduce the prompting of disgust. The 228 participants were randomly assigned to a between-participants design (original letter vs. manipulated letter). Results: Disgust hindered CRC screening intention, while embarrassment, fear, and subjective norms (i.e., perception of the social pressures to attend CRC screening) were not associated with intention to screen. More positive attitudes towards CRC screening were associated with a higher intention to screen. The positive association between perceived behavioural control and CRC screening intention was stronger for participants who read the letter with fewer (vs. more) references to bodily waste. Letter manipulation did not affect intention to screen. Conclusions: The disgust associated with faecal matter is a critical factor in determining CRC screening attendance, and it should be acknowledged as such in public policies. Until new screening tests avoiding the activation of this emotional reaction are concretely available, public campaigns should improve CRC screening participation by boosting both positive attitudes towards screening and patients’ perceived behavioural contro

Computational design of S-Duct intakes for distributed propulsion

Purpose: The purpose of this paper is to identify efficient methods and tools for the design of distributed propulsion architectures

Simultaneous determination of water-soluble organic tracers in atmospheric aereosol using silyl-derivatization and GC-MS analysis

A GC-MS analysis method has been developed for the simultaneous determination of water-soluble organic tracers in atmospheric aereosol. The method, based on silyl-derivatization, has been successfully applied in PM monitoring campaigns to evaluate air quality in Northen Italy regions