Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia

Background: Cachexia, a multifactorial syndrome affecting more than 50% of patients with advanced cancer and responsible for ~20% of cancer-associated deaths, is still a poorly understood process without a standard cure available. Skeletal muscle atrophy caused by systemic inflammation is a major clinical feature of cachexia, leading to weight loss, dampening patients' quality of life, and reducing patients' response to anticancer therapy. RAGE (receptor for advanced glycation end-products) is a multiligand receptor of the immunoglobulin superfamily and a mediator of muscle regeneration, inflammation, and cancer. Methods: By using murine models consisting in the injection of colon 26 murine adenocarcinoma (C26-ADK) or Lewis lung carcinoma (LLC) cells in BALB/c and C57BL/6 or Ager−/− (RAGE-null) mice, respectively, we investigated the involvement of RAGE signalling in the main features of cancer cachexia, including the inflammatory state. In vitro experiments were performed using myotubes derived from C2C12 myoblasts or primary myoblasts isolated from C57BL/6 wild type and Ager−/− mice treated with the RAGE ligand, S100B (S100 calcium-binding protein B), TNF (tumor necrosis factor)α±IFN (interferon) γ, and tumour cell- or masses-conditioned media to analyse hallmarks of muscle atrophy. Finally, muscles of wild type and Ager−/− mice were injected with TNFα/IFNγ or S100B in a tumour-free environment. Results: We demonstrate that RAGE is determinant to activate signalling pathways leading to muscle protein degradation in the presence of proinflammatory cytokines and/or tumour-derived cachexia-inducing factors. We identify the RAGE ligand, S100B, as a novel factor able to induce muscle atrophy per se via a p38 MAPK (p38 mitogen-activated protein kinase)/myogenin axis and STAT3 (signal transducer and activator of transcription 3)-dependent MyoD (myoblast determination protein 1) degradation. Lastly, we found that in cancer conditions, an increase in serum levels of tumour-derived S100B and HMGB1 (high mobility group box 1) occurs leading to chronic activation/overexpression of RAGE, which induces hallmarks of cancer cachexia (i.e. muscle wasting, systemic inflammation, and release of tumour-derived pro-cachectic factors). Absence of RAGE in mice translates into reduced serum levels of cachexia-inducing factors, delayed loss of muscle mass and strength, reduced tumour progression, and increased survival. Conclusions: RAGE is a molecular determinant in inducing the hallmarks of cancer cachexia, and molecular targeting of RAGE might represent a therapeutic strategy to prevent or counteract the cachectic syndrome

Tenchini’s legacy as a starting point for the reconstruction of the history of a criminal in the 19th century|L’eredità del Tenchini come punto di partenza per la ricostruzione della storia di un criminale del XIX secolo

Late in the 19th century, physician Lorenzo Tenchini undertook a study of criminal subjects and psychiatric patients. One of these was B.A., a 22-year-old soldier who committed suicide after attempting to kill his lover, a prostitute named G.I. The starting points of this study were the analysis of the subject's biography – data which resulted from the autopsy – and several observations on his brain and skull in accordance with the phrenological doctrine of that time. The goal of this work was to shed new light on an Italian criminal of the late 19th century and on Tenchini's work, combining the material collected by the doctor himself with sources of the period and modern medical knowledge

Patterns of CT lung injury and toxicity after stereotactic radiotherapy delivered with helical tomotherapy in early stage medically inoperable NSCLC

To evaluate toxicity and patterns of radiologic lung injury on CT images after hypofractionated image-guided stereotactic body radiotherapy (SBRT) delivered with helical tomotherapy (HT) in medically early stage inoperable non-small-cell lung cancer (NSCLC)

Investigation on the topological optimization of cooling channels for extrusion dies

During the extrusion process, high temperatures are generated, due to friction and deformation works, potentially leading to profile and die defects. Among the suggested solutions aimed at controlling the thermal field of the process, the most accredited one involves the manufacturing of cooling channels at the mating face between the die and a third plate. Despite the proven efficiency of well-designed channels, the main drawback lies in the managing of the many variables involved that strongly affect the cooling efficiency and balancing. In this frame, aim of the work is to investigate the applicability of the topological optimization tool, proposed by COMSOL Multiphysics software, for the design of cooling channels in extrusion dies. To validate the tool, an industrial case study has been selected and results compared between not optimized and optimized cooling solutions

Extrusion Benchmark 2023: Effect of Die Design on Profile Speed, Seam Weld Quality and Microstructure of Hollow Tubes

The Extrusion Benchmark 2023 was focused on the evaluation of different die design strategies for the manufacturing of AA6082 hollow tubes (40 mm external diameter and 4 mm thickness) through a porthole die with 3 openings. The extrusion process was monitored in industrial environment in terms of press load, profiles’ speed, profiles’ exit temperature, and die temperatures under different processing conditions (air quenching, water quenching, nitrogen die cooling). Extruded profiles were then analyzed in terms of seam weld quality, charge weld extension and microstructure evolution for both air/water quench and the presence/absence of nitrogen cooling. The results of the study are aimed at validating FEM simulation outputs in the context of the International Conference on Extrusion and Benchmark (ICEB)

Experimental analysis and modeling of the recrystallization behaviour of a AA6060 extruded profile

The microstructure of Al-Mg-Si alloys is gaining nowadays an increasing industrial interest because it influences the strength, crash, corrosion and esthetic properties of the extruded profiles. In order to investigate and predict the recrystallization behaviour in the extrusion of 6XXX aluminum alloys, experimental and numerical activities are still needed. In this work, the extrusion of an industrial-scale AA6060 aluminum alloy hollow profile was carried out. An innovative recrystallization model was developed and optimized by comparing the microstructural data experimentally acquired with the outputs of the simulation performed using the Finite Element commercial code Qform Extrusion. A good correlation between numerical prediction and experimental data was found, thus proving the reliability of the proposed AA6060 recrystallization model

Advancements in extrusion and drawing: a review of the contributes by the ESAFORM community

The present review paper would celebrate the 25 years anniversary of the ESAFORM association by summarizing the studies performed by the delegates of the ESAFORM conference series within mini-symposium “Extrusion and Drawing” and of the papers published in the International Journal of Material Forming in the same fields. The 160 analyzed papers have been divided in four main categories corresponding to the paper main chapters (Hot Metal Extrusion, Cold Metal Extrusion, Polymer Extrusion and Drawing) then further divided in sub-chapters in order to group them in more specific research subjects. The aim of this review paper is then to provide to the reader a complete overview of the investigated topics and of the research trends over the years within the ESAFORM associate researchers

Recent Trends in Nitrogen Cooling Modelling of Extrusion Dies

Nitrogen cooling has been identified as a powerful industrial solution for the hot extrusion process to remove heat in the die and in the profile. The complexity involved in the design of cooling channels depends on many factors, including the cooling path, its position with respect to the hottest zones as well as the nitrogen phase-change that strongly affects the heat removal capacity. However, the industrial approach is still stuck in the empirical and based-experience practices that too often strongly limit the possibilities of obtaining a performing cooling solution. In this context, this work intends to summarize and discuss the advanced recent trends in the design of cooling channels for extrusion dies proposed by the authors based on the numerical approaches, with the final aim to propose possible solutions to fill the current gaps of the suboptimal industrial approaches

Brazilian banana crop: current situation and research challenges.

Brazil is the worlds fifth largest producer of bananas, with 7.3 million Mg, 503 thousand ha and average yield of 14.6 Mg ha-1. The country also holds an important market with unique characteristics. In the Northern and Northeastern regions, AAB varieties such as Pacovan, Dwarf Prata and Terra dominate. In the Southeastern region, AAB Prata, Dwarf Prata and Maçã and AAA Cavendish type, in that order. In the Southern region, Cavendish varieties and the Prata type, and, in the Midwest, Prata type and Maçã. In the main banana producing centers of the country, in general, the climatic conditions are suitable, except for water limitation in the North of Minas Gerais, Medium and Submedium São Francisco in Bahia, Submedium São Francisco at Pernambuco, Jaguaribe-Apodi in Ceará and Mossoró/Açú in Rio Grande do Norte, overcome with the use of irrigation; and low temperatures in São Paulo and in the South. Research with the crop began in 1925 in São Paulo, and became more consistent after the 1970s. The Brazilian system of agricultural research is constituted by the Brazilian Agricultural Research Company, state research companies, federal and state universities and other research, teaching and extension institutions. More than a fifth of the 453 articles published in leading scientific journals in Brazil, in the last 20 years, developed the theme improved genotypes. The Brazilian Banana Breeding Program, coordinated by Embrapa Cassava and Fruits, began in 1983 and made available to farmers several genotypes, since 1995. In the North of the country, where black Sigatoka is present and there are climatic conditions favorable to the pathogen, there was greater adoption the new genotypes. The banana crop in Brazil has evolved greatly in recent decades, due to the generation, adaptation and diffusion of technology, but also the organization of banana growers. Some highly technified production centers emerged, especially in irrigated areas, disseminating information and functioning as showcases positive for producers