Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress

none10noChronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.openMatacchione, Giulia; Valli, Debora; Silvestrini, Andrea; Giuliani, Angelica; Sabbatinelli, Jacopo; Giordani, Chiara; Coppari, Sofia; Rippo, Maria Rita; Albertini, Maria Cristina; Olivieri, FabiolaMatacchione, Giulia; Valli, Debora; Silvestrini, Andrea; Giuliani, Angelica; Sabbatinelli, Jacopo; Giordani, Chiara; Coppari, Sofia; Rippo, Maria Rita; Albertini, Maria Cristina; Olivieri, Fabiol

Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia

Background: Nutraceutical combinations (NCs) against hypercholesterolemia are increasing in the marketplace. However, the availability of NCs without monacolin K is scarce even though the statin-intolerant population needs it. Methods: This study is a parallel-group, randomized, placebo-controlled, double-blind trial. We evaluated the effects of the NC containing phytosterols, bergamot, olive fruits, and vitamin K2 on lipid profile and inflammatory biomarkers in 118 subjects (mean age ± SD, 57.9 ± 8.8 years; 49 men and 69 women) with hypercholesterolemia (mean total cholesterol ± SD, 227.4 ± 20.8 mg/dL) without clinical history of cardiovascular diseases. At baseline and 6 and 12 weeks of treatment, we evaluated lipid profile (total, LDL and HDL cholesterol, and triglycerides), safety (liver, kidney, and muscle parameters), and inflammatory biomarkers such as hs-CRP, leukocytes, interleukin-32, and interleukin-38 and inflammatory-microRNAs (miRs) miR-21, miR-126, and miR-146a. Results: Compared to the placebo, at 6 and 12 weeks, NC did not significantly reduce total cholesterol (p = 0.083), LDL cholesterol (p = 0.150), and triglycerides (p = 0.822). No changes were found in hs-CRP (p = 0.179), interleukin-32 (p = 0.587), interleukin-38 (p = 0.930), miR-21 (p = 0.275), miR-126 (p = 0.718), miR-146a (p = 0.206), myoglobin (p = 0.164), and creatine kinase (p = 0.376). Among the two reported, only one adverse event was probably related to the nutraceutical treatment. Conclusions: The evaluated nutraceutical combination did not change serum lipid profile and inflammatory parameters, at least not with the daily dose applied in the present study

Socio-economic disparities in the appropriateness of diabetes care in an Italian region: findings of AEQUITAS study

Background: To evaluate socio-economic disparities in diabetes prevalence and care in Marches (a region of central Italy) in 2003-2010 through a cross-sectional study. Methods: The databases of 52 general practitioners were mined for people with diabetes (age ≥20 years). These data were linked with records from other regional administrative databases. Healthcare disparities, specifically potentially preventable hospitalizations (PPH) related to diabetes and its complications, were analysed using participants’ gender, age, and education data and the Italian Deprivation Index. Crude, age-specific and gender-specific diabetes prevalence was estimated for each year of observation. A time-trend analysis was performed. Admissions that might have been prevented according to Agency for Healthcare Research and Quality criteria were used to calculate the PPH rate for each level of social condition indicators. Rate ratios and 95% confidence intervals were estimated with a multiple Poisson regression model. Results: The search found 6,494 participants with diabetes mellitus aged ≥20 years. Disease prevalence ranged from 5.4% (2003) to 7.8% (2010), with a significant 0.31% positive trend. Those aged ≤44 years were at significantly higher risk of PPH than older people. A significant PPH excess was found among people living in socio-economically disadvantaged areas. Education and gender did not significantly affect PPH. Conclusion. People with diabetes seem to use primary care services appropriately irrespective of socio-economic status. Outpatient services are not equally distributed on the regional territory; this may increase disease severity and/or the risk of diabetes complications and affect appropriateness of diabetes care

Adherence to Herpes Zoster (Shingles) Catch-Up Campaign at the Romagna Local Health Authority (Italy), a Multi-Center Retrospective Observational Study

: Herpes Zoster (shingles) is an infection that occurs when varicella-zoster virus reactivates from the latent state. Incidence and severity of Herpes Zoster disease increase with age. Antiviral drugs are the elective treatment; however, prevention of disease reactivation through effective and safe vaccines is available in Italy out-of-pocket from age 65 onwards. The Romagna Local Health Authority (northern Italy) administered catch-up vaccinations in March-May 2022 for immunizations not performed during the COVID-19 pandemic. In this study, adherence rates to the catch-up campaign and recall activities adopted in two centers were investigated. The uptakes for only the catch-up vaccinations were 11.4% and 12.4%. Having suffered from Herpes Zoster or having family members who suffered from it would not seem to be drivers of increased uptake. Although sending text-messages to all involved patients was the main motivation for vaccine uptake (85.7-95.1%), word of mouth and web/news advertising also contributed to adoption in Center No. 2. In both centers, the need for greater synergy between public health departments and general practitioners to engage their patients emerged, as did the need for additional recall measures. Studying the main drivers of vaccine hesitancy, especially at the local level, can help in targeting campaigns and catch-up activities in order to achieve widespread acceptance

Cientificidade e aceitabilidade dos métodos e técnicas em linguística forense: um estudo sobre o caso "Qanon"

Este artigo propõe-se a discutir a cientificidade dos métodos e técnicas utilizados na área da Linguística Forense, baseando-se em uma matéria da Folha de S.Paulo acerca do caso QAnon. Trabalhos como os de Japiassu (1994), Fourez (1995), Okasha (2002), McMenamin (2002) e Almeida (2015) foram consultados para a fundamentação da discussão em torno dos procedimentos adotados em atribuição de autoria, observando quais são considerados mais (ou menos) científicos. Tendo em vista o exposto, foi realizada uma revisão da literatura e estudo de casos. Ao longo da discussão, foi possível perceber o prestígio que a objetividade e a quantificação de dados costumam receber por parte das autoridades jurídicas e acadêmicas. Desta forma, a partir do caso investigado, pôde-se inferir a valorização das análises quantitativas em detrimento das qualitativas

Integrated multidisciplinary ecological analysis from the Uluzzian settlement at the Uluzzo C Rock Shelter, south-eastern Italy

open20siThe Middle to Upper Palaeolithic transition, between 50 000 and 40 000 years ago, is a period of important ecological and cultural changes. In this framework, the Rock Shelter of Uluzzo C (Apulia, southern Italy) represents an important site due to Late Mousterian and Uluzzian evidence preserved in its stratigraphic sequence. Here, we present the results of a multidisciplinary analysis performed on the materials collected between 2016 and 2018 from the Uluzzian stratigraphic units (SUs) 3, 15 and 17. The analysis involved lithic technology, use-wear, zooarchaeology, ancient DNA of sediments and palaeoproteomics, completed by quartz single-grain optically stimulated luminescence dating of the cave sediments. The lithic assemblage is characterized by a volumetric production and a debitage with no or little management of the convexities (by using the bipolar technique), with the objective to produce bladelets and flakelets. The zooarchaeological study found evidence of butchery activity and of the possible exploitation of marine resources, while drawing a picture of a patchy landscape, composed of open forests and dry open environments surrounding the shelter. Ancient mitochondrial DNA from two mammalian taxa were recovered from the sediments. Preliminary zooarchaeology by mass spectrometry results are consistent with ancient DNA and zooarchaeological taxonomic information, while further palaeoproteomics investigations are ongoing. Our new data from the re-discovery of the Uluzzo C Rock Shelter represent an important contribution to better understand the meaning of the Uluzzian in the context of the Middle/Upper Palaeolithic transition in south-eastern Italy.First published: 13 July 2021openSARA SILVESTRINI, MATTEO ROMANDINI, GIULIA MARCIANI, SIMONA ARRIGHI, LISA CARRERA, ANDREA FIORINI, JUAN MANUEL LÓPEZ-GARCÍA, FEDERICO LUGLI, FILOMENA RANALDO, VIVIANE SLON, LAURA TASSONI, OWEN ALEXANDER HIGGINS, EUGENIO BORTOLINI, ANTONIO CURCI, MATTHIAS MEYER, MICHAEL CHRISTIAN MEYER, GREGORIO OXILIA, ANDREA ZERBONI, STEFANO BENAZZI, SPINAPOLICE ENZA ELENASARA SILVESTRINI, MATTEO ROMANDINI, GIULIA MARCIANI, SIMONA ARRIGHI, LISA CARRERA, ANDREA FIORINI, JUAN MANUEL LÓPEZ-GARCÍA, FEDERICO LUGLI, FILOMENA RANALDO, VIVIANE SLON, LAURA TASSONI, OWEN ALEXANDER HIGGINS, EUGENIO BORTOLINI, ANTONIO CURCI, MATTHIAS MEYER, MICHAEL CHRISTIAN MEYER, GREGORIO OXILIA, ANDREA ZERBONI, STEFANO BENAZZI, SPINAPOLICE ENZA ELEN

An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow

IntroductionRecent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.MethodsWe report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.ResultsWe demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.DiscussionOur model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role