Regulation of Inflammation by Short Chain Fatty Acids

The short chain fatty acids (SCFAs) acetate (C2), propionate (C3) and butyrate (C4) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted

Dietary Factors Modulating Colorectal Carcinogenesis

The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies

A Secure and Efficient Group Key Management Scheme for Clusters of String Inverters

A string inverter converts the low voltage direct current coming from the string of its Photovoltaic (PV) panels into alternating current to be exported to the grid. In today Smart Grid’s context, PV plants feature clusters of cooperating smart string inverters that exchange information in a multicast fashion (typically) over the Internet Protocol (IP). However, IP multicast does not provide any mechanism to limit the access to multicast data to authorized subjects only. A security infringement may cause a cluster either into exporting no energy into the grid (zero energy attack) or more energy than the limit set (energy overflow attack). Both the attacks can lead to potential severe consequences. In this regard, we are the first addressing those issues. Particularly, we propose a Key Management Service (KMS) for group key generation and distribution. The KMS provides forward secrecy and periodic refresh. We implement a prototype on a cluster of Power-One Italy S.p.A. a member of FIMER Group smart string inverters and evaluate the performance. Experimental results indicate that the scheme scales up to clusters composed of 50 inverters with an efficiency of 90.5% in terms of latency for group key distribution and 99% in terms of memory overhead

Low Vitamin K and Vitamin D Dietary Intake in Patients with Inflammatory Bowel Diseases

The inadequate dietary intake of Vitamin D and Vitamin K is an easily reversible factor favoring IBD-associated bone loss, but data on Vitamin K are lacking. A 28-item quantitative food frequency questionnaire was administered to 193 IBD patients (89 Crohn’s disease and 104 ulcerative colitis), and 199 controls. Patients’ demographics, clinical and laboratory findings were analyzed in relation to recommended daily allowances. VitD intake was inadequate both in the IBD and control patients (8.3 ± 4.5 µg/day in IBD, 53.1% RDA, and 9.7 ± 5.9 µg/day, 63.2% RDA, respectively). Conversely, the mean ViK intake was less than adequate in IBD, at 116.7 ± 116.3 µg/day (78.7% RDA), and high in controls, at 203.1 ± 166.9 µg/day (138.8% RDA). Nonetheless, due to marked inter-individual differences, diets were severely lacking VitK in 40% of UC and 49% of CD patients, more so in females and those with active disease. The intake of Vit D was non-significantly lower in colitis than that in Crohn’s disease (7.9 vs. 8.7 µg/day). The opposite was observed for VitK (123.5 vs. 107.0 µg/day). Thus, the diet lacks the micronutrients involved in bone wellbeing in a large proportion of IBD patients. While VitD supplementation is the rule, VitK shortages need proactive nutritional intervention

Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged

Association of Colonic Diverticula with Colorectal Adenomas and Cancer

Background and Objectives: Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. Materials and Methods: All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyperplastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. Results: During the study period, 1490 patients were enrolled; 37.2% (n = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% (n = 183) patients presented only diverticula, 13.7% (n = 204) only polyps or cancer, 11.3% (n = 168) both diseases, and 62.7% (n = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27–3.47, p < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90–5.14, p < 0.0001). Conclusions: A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population

Association of colonic diverticula with colorectal adenomas and cancer

Background and Objectives: Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. Materials and Methods: All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyper-plastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. Results: During the study period, 1490 patients were enrolled; 37.2% (n = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% (n = 183) patients presented only diverticula, 13.7% (n = 204) only polyps or cancer, 11.3% (n = 168) both diseases, and 62.7% (n = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27–3.47, p \u3c 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90–5.14, p \u3c 0.0001). Conclusions: A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population