Consensus guidelines for the detection of immunogenic cell death

none82siApoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.Kepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong-Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean-Ehrland; Riganti, Chiara; Rovere-Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei-Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, LorenzoKepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean Ehrland; Riganti, Chiara; Rovere Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenz

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Osteosarcopenia: A Narrative Review on Clinical Studies

Osteosarcopenia (OS) is defined by the concurrent presence of osteopenia/osteoporosis and sarcopenia. The pathogenesis and etiology of OS involve genetic, biochemical, mechanical, and lifestyle factors. Moreover, an inadequate nutritional status, such as low intake of protein, vitamin D, and calcium, and a reduction in physical activity are key risk factors for OS. This review aims to increase knowledge about diagnosis, incidence, etiology, and treatment of OS through clinical studies that treat OS as a single disease. Clinical studies show the relationship between OS and the risk of frailty, falls, and fractures and some association with Non-communicable diseases (NCDs) pathologies such as diabetes, obesity, and cardiovascular disease. In some cases, the importance of deepening the related mechanisms is emphasized. Physical exercise with adequate nutrition and nutritional supplementations such as proteins, Vitamin D, or calcium, represent a significant strategy for breaking OS. In addition, pharmacological interventions may confer benefits on muscle and bone health. Both non-pharmacological and pharmacological interventions require additional randomized controlled trials (RCT) in humans to deepen the synergistic effect of exercise, nutritional interventions, and drug compounds in osteosarcopenia

Study of the influence of triacylglycerol composition on DSC cooling curves of extra virgin olive oil by chemometric data processing

In this work, a coupled high-pressure liquid chromatography-differential scanning calorimetry-partial least square (HPLC-DSC-PLS) procedure was applied to clarify the influence of triacylglycerol composition on the shape of cooling curves for extra virgin olive oil (EVOo), as chemometric processing of digitized DSC curves was previously reported to be an attractive alternative to the application of the common procedure of parameter extrapolation for the analysis of thermal transition. 69 samples of EVOo were analysed to obtain triacylglycerol (TAG) composition by means of HPLC and DSC cooling profiles. Results obtained by the application of PLS algorithm on TAG concentration (%) and digitized DSC curves showed that cooling transitions were markedly influenced by OOO, OLO and OOP + SLO that are the most representative TAG for EVOo. Other TAG as LLP + OLnO, LLL + LLPo and POPo developed good PLS models, appearing to influence EVOo cooling curve, although less markedly than the further. Otherwise, the other identified TAG did not render appropriate models. Finally, grouping TAG according to different unsaturation degree, high correlation coefficients (>0.80) and low relative standard deviations (<11 %) were found for sum of tri-unsaturated triacylglycerols in both calibration and validation sets. Starting from these encouraging results, this new and fast coupled approach may be applied to a wider set of EVOo samples to tentatively discriminate among oils according to different geographical and/or botanical origins taking into account relation established among TAG and cooling curves.Fil: Maggio, Ruben Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Barnaba, Carlo. Instituto Tecnológico y de Estudios Superiores de Occidente; MéxicoFil: Cerretani, Lorenzo. Universidad de Bologna; ItaliaFil: Paciulli, Maria. Università di Parma; ItaliaFil: Chiavaro, Emma. Università di Parma; Itali

Microwave heating of different commercial categories of olive oil: Part II. Effect on thermal properties

The effect of microwave heating of commercial categories of olive oil for human consumption (extra virgin olive oil [EVOo], olive–pomace oil [Po] and olive oil [Oo]) on DSC thermal properties was evaluated at different times of microwave treatment. Marked changes of DSC cooling profiles were found for EVOo and Po subjected to microwaving, with the major exotherm that shifted towards lower temperature and decreased height with increasing treatment time. Thermal properties (during DSC cooling analysis) changed in all samples: crystallisation enthalpy significantly decreased and the phase transition developed over a larger temperature range, due to more heterogeneous chemical composition of all oils that resulted from triacylglycerol lysis to the formation of lipid oxidation products. Heating profiles of EVOo and Po were also modified by microwave treatment, as the minor endotherm progressively disappeared, significantly shifting offset temperature of transition towards lower temperature. Oo did not exhibit such changes of thermal properties and phase transition profiles as described for EVOo and Po. This may be mainly related to its lower water content although the simultaneous presence of small amounts of antioxidant molecules (polyphenols) may have contributed to partially prevent thermal degradation of this oil in comparison with the others. These preliminary results suggest that DSC can be useful, not only for monitoring modifications of chemical composition with increasing microwave treatment time, but also to discriminate amongst olive oils according to their response to microwave exposure

Physical Activity Assessment in an Italian Adult Population using the International Physical Activity Questionnaire

Introduction: The international physical activity questionnaire (IPAQ) was developed as an instrument for cross-national monitoring of physical activity (PA) and inactivity. The aim of this study was to determine the PA level in a sample of Italian population. Methods: In total 957 adults (56% women) aged 19-65 years were randomly recruited. PA was assessed using the long form of the IPAQ (IPAQ-L). Lifestyle, body weight and height were obtained by questionnaire. Results: The total PA was 1610 MET-min/week: subjects were physically more active in the domestic and garden domain, contrary to transportation and leisure domain. Classifying the activities on the basis of the intensity, significant differences between sexes were detected for moderate and vigorous activities; moreover subjects aged 18-30 years had the lowest levels of PA, while subjects aged >50 had the highest levels. The 86% of the examined population spent at least 30 minutes of moderate PA on 5 days of the week, adhering to the international recommendations. Conclusions: Differences in PA between sexes and among age groups were observed. Strategies for increasing PA should be addressed especially to the young adults

Total and Plant Protein Consumption: The Role of Inflammation and Risk of Non-Communicable Disease

Background: Inflammatory cytokine levels are associated with Non-Communicable Diseases (NCDs) and can be influenced by a person&rsquo;s macronutrient profile. This work aims to evaluate the relationship between the compliance with the age-specific recommended protein intake and the levels of inflammatory markers related to the risk of NCDs. Methods: The study participants included 347 participants (119 men and 228 women), ages 18 to 86 years. Cardio-metabolic risk evaluations, including an assessment of the prevalence of Metabolic Syndrome, were performed. Leptin, IL-15, IL-6, and TNF-&alpha; levels were measured. Results: The adequacy of the total protein (TP) intake was lower in old people compared to individuals aged &lt;60 years, and only few volunteers consumed the suggested 50% plant protein (PP) for a healthy and sustainable diet. A lower risk of NCDs with a PP consumption above at least 40% was observed only in old individuals. A differential effect on TNF-&alpha; and IL-6 was observed for both TP and PP intake by gender and age class, whereas for leptin and IL-15 only significant interactions among sex and the class of age were found. Conclusion: Although our data suggest that consuming more than 40% of PP can reduce the risk of NCDs, the effect of gender differences on cytokine levels should be considered in larger studies