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Cinnamic acid and its derivatives represent attractive building blocks for the development of pharmacological tools. A series of piperoniloyl and cinnamoyl‐based amides (6‐9 a‐f) have been synthesized and assayed against a wide panel of colorectal cancer (CRC) cells, with the aim of finding promising anticancer agents. Among all twenty‐four synthesized molecules, 7a, 7e‐f, 9c, and 9f displayed the best antiproliferative activity. The induced G1 cell cycle arrest and the increase in apoptotic cell death was seen in FACS analysis and western Blotting in the colon tumor cell lines HCT116, SW480, LoVo, and HT29, but not in the nontumor cell line HCEC. In particular, 9f overcame the resistance of HT29 cells, which have a mutant p53 and BRAF. Furthermore, 9f, amide of piperonilic acid with the 3,4‐dichlorobenzyl substituent upregulated p21, which is involved in cell cycle arrest as well as in apoptosis induction. Cinnamic acid derivatives might be potential anticancer compounds, useful for the development of promising anti‐CRC agents. [ABSTRACT FROM AUTHOR]

Summary: An innovative functional food with symbiotic and functional potential was produced by combining probiotic milk kefir, and white grape‐seed pomace obtained by UAE (ultrasound‐assisted extraction) rich in catechin and glycosylated flavonoids. The milk kefir was fortified by adding, after 24 h of fermentation, a polymer of inulin grafted with seed extract. The inulin/grape extract‐enriched polymer showed a higher antioxidant profile (P < 0.05). Simulated in vitro digestion demonstrated that 50 g of the kefir product would result in the delivery of antioxidants equivalent to 300 mg of ascorbic acid. The integrity of the intestinal barrier functions was not compromised by kefir treatments (at 10 μg mL‐1). [ABSTRACT FROM AUTHOR]

Prompt diagnosis of complex phenotypes is a challenging task in clinical genetics. Whole exome sequencing has proved to be effective in solving such conditions. Here, we report on an unpredictable presentation of Werner Syndrome (WRNS) in a 12‐year‐old girl carrying a homozygous truncating variant in RECQL2, the gene mutated in WRNS, and a de novo activating missense change in PTPN11, the major Noonan syndrome gene, encoding SHP2, a protein tyrosine phosphatase positively controlling RAS function and MAPK signaling, which have tightly been associated with senescence in primary cells. All the major WRNS clinical criteria were present with an extreme precocious onset and were associated with mild intellectual disability, severe growth retardation and facial dysmorphism. Compared to primary fibroblasts from adult subjects with WRNS, proband's fibroblasts showed a dramatically reduced proliferation rate and competence, and a more accelerated senescence, in line with the anticipated WRNS features occurring in the child. In vitro functional characterization of the SHP2 mutant documented its hyperactive behavior and a significantly enhanced activation of the MAPK pathway. Based on the functional interaction of WRN and MAPK signaling in processes relevant to replicative senescence, these findings disclose a unique phenotype likely resulting from negative genetic interaction. [ABSTRACT FROM AUTHOR]

Summary: Olive pomaces from Southern Italy autochthonous cultivars (Carolea, Nocellara and Roggianella) were eco‐friendly extracted to reach value‐added ingredients for the production of fortified pear beverages. Chemical composition of the extracts was carried out by 1H‐NMR analysis, while antioxidant features were in vitro evaluated. The extracts displayed remarkable scavenger properties against DPPH (IC50 values in the range 0.051–0.171 mg mL−1) and ABTS (IC50 values in the range 0.035–0.047 mg mL−1) radical species. Reactive species in the extracts and inulin chains were involved in an eco‐friendly radical process by grafting reaction to obtain macromolecular conjugates with outstanding antioxidant features, in terms of both antioxidant and scavenging performances, representing an attractive source in the design of functional foods. In this context, the conjugates were employed to enrich pear juice, to achieve reinforced beverages displaying remarkable antioxidant properties in comparison with its non‐functional counterparts, as well as its maintenance over time (20 days). [ABSTRACT FROM AUTHOR]

The hybrid molecule Quercetin‐3‐oleate (AV2), accommodates within the binding pocket for allosteric full GPR40 agonists. AV2 endorses skin wound healing acting as a promoter of keratinocytes proliferation and overcomes immunosuppressive conditions in vitro. AV2 stimulated HaCaT wound healing by 51% compared to the untreated control, at the concentration of 1 μM with slight TGF‐β production and MMP‐9 release. Pretreatment with the known GPR40 antagonist DC260126 abolished its wound healing power. Docking simulations suggested that both molecules share the same binding site. [ABSTRACT FROM AUTHOR]

Summary: Seeds and skins from grape pomaces of Pecorello and Mantonico cv underwent extraction (ultrasound–assisted or maceration), in order to obtain added‐value ingredients for the production of a functional pear jam. The antioxidant features of the extracts were tested by in vitro colorimetric assays. Among seeds, Mantonico by maceration (MSC) showed the best results, as well as Mantonico by ultrasound‐assisted extraction (MBs) among skin extracts. The selected extracts were fully characterised by NMR and MS techniques, confirming the presence of many polyphenols, flavonoids and tannins among others. Pectin was then derivatised by the grafting procedure with the active molecules of MBs and MSC. The latter produced the best antioxidant polymer also without toxicity evaluated using Caco‐2 cells and was used for the jam preparation. The functional pear jam showed improved antioxidant performances in comparison with its non‐functional counterparts as well as its maintenance over time (15 days). [ABSTRACT FROM AUTHOR]

Estrogens exert their action mainly by binding three receptors, namely estrogen receptors α and β (ERα and ERβ) and GPER-1 (G-protein coupled estrogen receptor 1). While the patho-physiological role of both ERα and ERβ has been deeply investigated, the role of GPER-1 in estrogens' signaling has not been clearly defined yet. Unfortunately, only few GPER-1 selective ligands were discovered so far, and the real efficiency of such compounds is still matter of debate. To better understand the physiological relevance of GPER-1, new selective chemical probes are higly needed. In this scenario, we report herein the generation and validation of a three-dimensional (3-D) GPER-1 homology model by means of docking studies and molecular dynamics simulations. The model thus generated was employed to ( i) decipher the structural basis underlying the ability of estrogens and some Selective Estrogen Receptor Modulators (SERMs) to bind GPER-1 and classical ERα and ERβ, and ( ii) generate a reliable G1/GPER-1 complex useful in rationalizing the pharmacological profile of G1 reported in the literature. The G1/GPER-1 complex herein reported could be further exploited in drug design approaches aimed at improving the pharmacological profile of G1 or at identifying new chemical entities (NCEs) as potential modulators of GPER-1. [ABSTRACT FROM AUTHOR]