Antioxidant and Anti-Inflammatory Activities of Flavanones from Glycyrrhiza glabra L. (licorice) Leaf Phytocomplexes: Identification of Licoflavanone as a Modulator of NF-kB/MAPK Pathway

Inflammation represents an adaptive response generated by injuries or harmful stimuli. Natural remedies represent an interesting alternative to traditional therapies, involving several biochemical pathways. Besides, the valorization of agrochemical wastes nowadays seems to be a feasible way to reduce the health spending and improve the accessibility at bioactive natural compounds. In this context, the chemical composition of three Glycyrrhiza glabra L. (licorice) leaf extracts, obtained through maceration or ultrasound-assisted method (fresh and dried leaves) was investigated. A guided fractionation obtained three main components: pinocembrin, glabranin and licoflavanone. All the extracts showed similar antioxidant properties, evaluated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Diammonium Salt (ABTS) assay, while, among the isolated compounds, licoflavanone exhibited the best antioxidant activity. The anti-inflammatory activity of the extracts and the purified compounds was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Extract C and licoflavanone showed a good anti-inflammatory activity without affecting cell viability, as they decreased nitrite levels even when used at 12.5 μg/mL (p < 0.005) and 50 μM concentration (p < 0.001), respectively. Interestingly, licoflavanone markedly decreased pro-inflammatory cytokines and cyclooxygenase 2/inducible nitric oxide synthase (COX-2/iNOS) expression levels (p < 0.001). A modulation of nuclear factor kappa B/mitogen-activated protein kinases (NF-kB/MAPK) pathway underlay such behavior, highlighting the potential of this natural compound as a new scaffold in anti-inflammatory drug research

A System to Filter Unwanted Messages from OSN User Walls

This paper proposes a system allowing OSN users to have a direct control on the messages posted on their walls. This is achieved through a flexible rule-based system, that allows users to customize the filtering criteria to be applied to their walls, and a Machine Learning based soft classifier automatically labeling messages in support of content-based filtering

Improved extractability of carotenoids from tomato peels as side benefits of PEF treatment of tomato fruit for more energy-efficient steam-assisted peeling

Abstract The combination of steam blanching (SB) with Pulsed Electric Fields (PEF) treatments of whole tomatoes, in addition to reducing the energy required for tomato peeling, can significantly contribute to the recovery of carotenoids from the peels. In this work, PEF (0.25-0-75 kV/cm, 1 kJ/kg) and SB (1 min at 50–70 °C), as pre-treatment prior to hand peeling, were investigated to assess their ability, separately and in combination, to induce the cell permeabilization of tomato peels, and hence to improve the carotenoids extraction in acetone (4 h at 25 °C). PEF and SB, by inducing significant damages at the cuticular level, caused the increase of the yield in total carotenoids (up to 188% for PEF and 189% for SB) and antioxidant power (up to 372% for PEF and 305% for SB) with respect to the peels from untreated tomatoes. The application of a combined treatment (PEF + SB) significantly increased the carotenoid content and the antioxidant power of the extracts, with a synergistic effect observed already at 60 °C (37.9 mg/100 g fresh weight tomato peels). HPLC analyses revealed that lycopene was the main carotenoid extracted and that neither PEF nor SB caused any selective release or degradation of lycopene. Results obtained from this study demonstrate that the integration of PEF in the processing line of tomato fruits prior to SB contributes to the valorization of tomato processing by-products

Cepstral Peak Prominence Smoothed distribution as discriminator of vocal health in sustained vowel

This paper focuses on Cepstral Peak Prominence Smoothed (CPPS) as a possible indicator of vocal health status, considering individual CPPS distribution and its descriptive statistics. 31 voluntary patients and 22 control subjects performed the same protocol, which includes the simultaneous acquisition of three repetitions of the sustained vowel /a/ with a microphone in air and a contact sensor, the perceptual assessment of voice and the videolaringoscopy examination. The best logistic regression models have been applied and preliminary results showed that the fifth percentile and the standard deviation of CPPS distributions are the best parameters that discriminate healthy and unhealthy voice for the microphone in air and the contact sensor, respectively. The Area Under Curve (AUC) revealed the diagnostic precision of the selected CPPS parameters: AUC of 0.96 and 0.83 have been found for the microphone in air and the contact sensor, showing strong to moderate discrimination power, respectively. The repeatability of the selected CPPS parameters has been also estimated. For each selected CPPS parameter, the Monte Carlo method has been implemented in order to evaluate the uncertainty of the threshold, which was identified by means of the Receiver Operating Curve analysis

Constraints on Kerr-Newman black holes from merger-ringdown gravitational-wave observations

We construct a template to model the post-merger phase of a binary black hole coalescence in the presence of a remnant $U(1)$ charge. We include the quasi-normal modes typically dominant during a binary black hole coalescence, $(\ell,m,n) = \{(2,2,0), (2,2,1)\}$ and also present analytical fits for the quasinormal mode frequencies of a Kerr-Newman black hole in terms of its spin and charge, here also including the $(3,3,0)$ mode. Aside from astrophysical electric charge, our template can accommodate extensions of the Standard Model, such as a dark photon. Applying the model to LIGO-Virgo detections, we find that we are unable to distinguish between the charged and uncharged hypotheses from a purely post-merger analysis of the current events. However, restricting the mass and spin to values compatible with the analysis of the full signal, we obtain a 90th percentile bound $\bar{q} < 0.33$ on the black hole charge-to-mass ratio, for the most favorable case of GW150914. Under similar assumptions, by simulating a typical loud signal observed by the LIGO-Virgo network at its design sensitivity, we assess that this model can provide a robust measurement of the charge-to-mass ratio only for values $\bar{q} \gtrsim 0.5$; here we also assume that the mode amplitudes are similar to the uncharged case in creating our simulated signal. Lower values, down to $\bar{q} \sim 0.3$, could instead be detected when evaluating the consistency of the pre-merger and post-merger emission.Comment: 21 pages, 11 figures, 4 tables. Matches published versio

Bioinspired negatively charged calcium phosphate nanocarriers for cardiac delivery of MicroRNAs

Aim: To develop biocompatible and bioresorbable negatively charged calcium phosphate nanoparticles (CaP-NPs) as an innovative therapeutic system for the delivery of bioactive molecules to the heart. Materials & methods: CaP-NPs were synthesized via a straightforward one-pot biomineralization-inspired protocol employing citrate as a stabilizing agent and regulator of crystal growth. CaP-NPs were administered to cardiac cells in vitro and effects of treatments were assessed. CaP-NPs were administered in vivo and delivery of microRNAs was evaluated. Results: CaP-NPs efficiently internalized into cardiomyocytes without promoting toxicity or interfering with any functional properties. CaP-NPs successfully encapsulated synthetic microRNAs, which were efficiently delivered into cardiac cells in vitro and in vivo. Conclusion: CaP-NPs are a safe and efficient drug-delivery system for potential therapeutic treatments of polarized cells such as cardiomyocytes

Telerehabilitation for Lee Silverman Voice Treatment (Tele-LSVT)-Loud on voice intensity and voice use in daily living in people with multiple sclerosis: A protocol for a feasibility and pilot randomized controlled study

Objective: Alterations in voice intensity and quality may constitute a social life limitation in people with multiple sclerosis (MS), but only 2% of cases receive speech therapy. Especially the Lee Silverman Voice Treatment (LSVT)-Loud is a highly effective intensive method for voice intensity, requiring subjects’ repeated attendance at the clinic. Telerehabilitation may represent a feasible solution to bypass potential barriers related to speech therapy attendance, scaling up the beneficial effects of the treatment to a broader population. The proposed protocol aims to test the feasibility and the pilot efficacy of the LSVT-Loud delivered in telerehabilitation (Tele-LSVT-Loud), compared to the same treatment delivered in the clinic (LSVT-Loud). Methods: A single-blinded, parallel, two-arm, pilot randomized (1:1 ratio) controlled trial will be performed involving 20 people with MS. Patients will be allocated to 4 weeks of Tele-LSVT-Loud by accessing a telerehabilitation platform at home or LSVT-Loud conventionally delivered in the clinic. Feasibility and pilot effectiveness will be evaluated three times: before (T0), after the treatment (T1), and 3-month follow-up (T2). Feasibility measures will include adherence, adverse events, user experience, motivation, engagement, and acceptability. Vocal intensity during a 1-minute monologue will be the primary outcome measure. Secondary outcome measures will be the vocal quality during a 1-minute monologue, sustained /a/ voice intensity, quality and stability, voice use in daily life, voice subjective perception in daily life, and quality of life. Results: Expected results will be (1) high feasibility of Tele-LSVT-Loud and (2) a non-inferiority effect of Tele-LSVT-Loud compared with face-to-face treatment delivery on voice intensity and quality outcomes. Conclusions: Tele-LSVT-Loud may be a feasible intervention for MS alteration in voice intensity and quality with a non-inferior effect compared to LSVT-Loud

Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure

It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH2attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Ce, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gαsand cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy

265Generation of iPSC-based cardiomyocytes for investigating mechanisms of dilated cardiomyopathy due to Lamin A/C mutations

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New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells

Nowadays, the beneficial role of a healthy lifestyle, particularly emphasizing the quality of foods and cancer management, is accepted worldwide. Polyphenols and oleic acid play a key role in this context, but are still scarcely used as anti-cancer agents due to their bio-accessibility limits. Therefore, we aimed to synthesize a set of new oleoyl-hybrids of quercetin, morin, pinocembrin, and catechin to overcome the low bioavailability of polyphenols, throughout a bio-catalytic approach using pancreatic porcine lipase as a catalyst. The in vitro assays, using a wide panel of human cancer cell lines showed, mainly for two novel regioisomer oleoyl-hybrids of quercetin, a remarkable increase in apoptotic cell populations. We suggested that the DNA damage shown as ɣH2AX signals might be the major cause of apoptotic cell death. Finally, we demonstrated convincing data about two novel polyphenol-based hybrids displaying a highly selective anti-cancer cytotoxicity and being superior compared to their reference/parental compounds