Anticancer activity of "Trigno M", extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models

Abstract In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style : a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35%) as compared to the chemotherapy treatment with 5-fluorouracil (80%) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8%) and a low level of necrotic fraction (6.7%) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma

Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

Background: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. Methods: We performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. Results: We did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071). Conclusions: Our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts

[Occupational therapy in rheumatoid arthritis: short term prospective study in patients treated with anti-TNF-alpha drugs].

Objective: to assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti- TNF-alpha drugs in a short-term open controlled prospective study. Methods: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15- 432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). Results: at baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. Conclusion: our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment

Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms.

Metabolic diseases harm brain health and cognitive functions, but whether maternal metabolic unbalance may affect brain plasticity of next generations is still unclear. Here, we demonstrate that maternal high fat diet (HFD)-dependent insulin resistance multigenerationally impairs synaptic plasticity, learning and memory. HFD downregulates BDNF and insulin signaling in maternal tissues and epigenetically inhibits BDNF expression in both germline and hippocampus of progeny. Notably, exposure of the HFD offspring to novel enriched environment restores Bdnf epigenetic activation in the male germline and counteracts the transmission of cognitive impairment to the next generations. BDNF administration to HFD-fed mothers or preserved insulin sensitivity in HFD-fed p66Shc KO mice also prevents the intergenerational transmission of brain damage to the progeny. Collectively, our data suggest that maternal diet multigenerationally impacts on descendants' brain health via gametic mechanisms susceptible to lifestyle