Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an “ideal bridge”, linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05–5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:10⁵–1:10⁴ v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.

Despite its possible therapeutic potential against COVID-19, the exact mechanism(s) by which palmitoylethanolamide (PEA) exerts its beneficial activity is still unclear. PEA has demonstrated analgesic, anti-allergic, and anti-inflammatory activities. Most of the anti-inflammatory properties of PEA arise from its ability to antagonize nuclear factor-κB (NF-κB) signalling pathway via the selective activation of the PPARα receptors. Acting at this site, PEA can downstream several genes involved in the inflammatory response, including cytokines (TNF-α, Il-1β) and other signal mediators, such as inducible nitric oxide synthase (iNOS) and COX2. To shed light on this, we tested the anti-inflammatory and immunomodulatory activity of ultramicronized(um)-PEA, both alone and in the presence of specific peroxisome proliferator-activated receptor alpha (PPAR-α) antagonist MK886, in primary cultures of murine alveolar macrophages exposed to SARS-CoV-2 spike glycoprotein (SP). SP challenge caused a significant concentration-dependent increase in proinflammatory markers (TLR4, p-p38 MAPK, NF-κB) paralleled to a marked upregulation of inflammasome-dependent inflammatory pathways (NLRP3, Caspase-1) with IL-6, IL-1β, TNF-α over-release, compared to vehicle group. We also observed a significant concentration-dependent increase in angiotensin-converting enzyme-2 (ACE-2) following SP challenge. um-PEA concentration-dependently reduced all the analyzed proinflammatory markers fostering a parallel downregulation of ACE-2. Our data show for the first time that um-PEA, via PPAR-α, markedly inhibits the SP induced NLRP3 signalling pathway outlining a novel mechanism of action of this lipid against COVID-19.

Gastroesophageal Reflux Disease (GERD) is multifactorial pathogenesis characterized by the abnormal reflux of stomach contents into the esophagus. Symptoms are worse after the ingestion of certain foods, such as coffee. Hence, a randomized pilot study conducted on 40 Italian subjects was assessed to verify the effect of standard (SC) and dewaxed coffee (DC) consumption on gastroesophageal reflux symptoms and quality of life in patients with gastrointestinal diseases. The assessment of patient diaries highlighted a significant percentage reduction of symptoms frequency when consuming DC and a significant increase in both heartburn-free and regurgitation-free days. Consequentially, patients had a significant increase of antacid-free days during the DC assumption. Moreover, the polyphenolic profile of coffee pods was ascertained through UHPLC-Q-Orbitrap HRMS analysis. Chlorogenic acids (CGAs) were the most abundant investigated compounds with a concentration level ranging between 7.316 (DC) and 6.721 mg/g (SC). Apart from CGAs, caffeine was quantified at a concentration level of 5.691 mg/g and 11.091 for DC and SC, respectively. While still preliminary, data obtained from the present pilot study provide promising evidence for the efficacy of DC consumption in patients with GERD. Therefore, this treatment might represent a feasible way to make coffee more digestible and better tolerated.

Crohn’s disease (CD) is a chronic inflammatory gastrointestinal disorder requiring lifelong medications. The currently approved drugs for CD are associated with relevant side effects and several studies suggest an increased use of nutraceuticals among CD patients, seeking for what is perceived as a more “natural” approach in controlling this highly morbid condition. Nutraceuticals are foods or foods’ components with beneficial health properties that could aid in CD treatment for their anti-inflammatory, analgesic and immunoregulatory activities that come along with safety, high tolerability, easy availability and affordability. Depending on their biological effect, nutraceuticals’ support could be employed in different subsets of CD patients, both those with active disease, as adjunctive immunomodulatory therapies, and/or in quiescent disease to provide symptomatic relief in patients with residual functional symptoms. Despite the increasing interest of the general public, both limited research and lack of education from healthcare professionals regarding their real clinical effectiveness account for the increasing number of patients turning to unconventional sources. Professionals should recognize their widespread use and the evidence base for or against their efficacy to properly counsel IBD patients. Overall, nutraceuticals appear to be safe complements to conventional therapies; nonetheless, little quality evidence supports a positive impact on underlying inflammatory activity.

Obesity is a risk factor for several diseases present worldwide. Currently, dietary changes and physical activity are considered the most effective treatment to reduce obesity and its associated comorbidities. To promote weight loss, hypocaloric diets can be supported by nutraceuticals. The aim of this study was to evaluate the effects of a hypocaloric diet associated with Cinchona succirubra supplementation on satiety, body weight and body composition in obese subjects. Fifty-nine overweight/obese adults, were recruited, randomized into two groups and treated for 2 months. The first group (32 adults) was treated with a hypocaloric diet plus cinchona supplementation (the T-group); the second one (27 adults) was treated with a hypocaloric diet plus a placebo supplementation (the P-group). Anthropometric-measurements as well as bioimpedance analysis, a Zung test and biochemical parameters were evaluated at baseline and after 60 days. T-group adults showed significant improvement in nutritional status and body composition compared to those at the baseline and in the P-group. Moreover, T-group adults did not show a reduction in Cholecystokinin serum levels compared to those of P-group adults. In conclusion, our data demonstrate that a hypocaloric diet associated with cinchona supplementation is effective in inducing more significant weight loss and the re-establishment of metabolic parameters than those obtained with a hypocaloric diet.

Background: The sense of taste is involved in food behavior and may drive food choices, likely contributing to obesity. Differences in taste preferences have been reported in normal-weight as compared to obese subjects. Changes in taste perception with an increased sweet-induced sensitivity have been reported in surgically treated obese patients, but data regarding the perception of basic tastes yielded conflicting results. We aimed to evaluate basic taste identification, induced perception, and pleasantness in normal-weight controls and obese subjects before and after bariatric surgery. Methods: Severe obese and matched normal weight subjects underwent a standardized spit test to evaluate sweet, bitter, salty, umami, and sour taste identification, induced perception, and pleasantness. A subset of obese subjects were also studied before and 12 months after sleeve gastrectomy. Results: No significant differences in basic taste-induced perceptions were observed, although a higher number of controls correctly identified umami than did obese subjects. Sleeve-gastrectomy-induced weight loss did not affect the overall ability to correctly identify basic tastes but was associated with a significant increase in taste intensities, with higher scores for sour and bitter, and a significantly reduced bitter-induced pleasantness. Conclusions: The perception of basic tastes is similar in normal-weight and severely obese subjects. Sleeve-gastrectomy-induced weight loss significantly increases basic taste-induced intensity, and selectively reduces bitter-related pleasantness without affecting the ability to identify the tastes. Our findings reveal that taste perception is influenced by body mass index changes, likely supporting the hypothesis that centrally mediated mechanisms modulate taste perception in severe obesity.