Guglielmo Sorci - Academia.edu (original) (raw)

Papers by Guglielmo Sorci

Journal of Cachexia, Sarcopenia and Muscle, Mar 11, 2020

Background Cachexia, a multifactorial syndrome affecting more than 50% of patients with advanced ... more 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 À/À (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 À/À 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 À/ À 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.

The 14 th Meeting of the Interuniversity Institute of Myology (IIM), October 12-15, 2017-Assisi, ... more The 14 th Meeting of the Interuniversity Institute of Myology (IIM), October 12-15, 2017-Assisi, Italy gathered together researchers from Italy, European and North-American countries to discuss recent results on muscle research. The program showcased keynote lectures from world-renowned international speakers presenting advances in muscle physiology, bioengineering, metabolism and therapeutics. Based on selection from submitted abstracts, participants presented their novel, unpublished results in seven oral communication and two poster sessions. Particular emphasis was devoted to young trainees. For example, trainees where directly involved in organizing a scientific session and three round tables tailored to the interests of their peers. The meeting attracted a broad audience from Italy, various European countries and from North America. It offered a unique opportunity to all researchers involved in the field of muscle biology to exchange ideas and foster scientific collaborations to better understand the causative mechanisms of muscular diseases and to improve the design of more efficient therapeutic strategies. The friendly and inclusive atmosphere promoted the active participation of junior scientists to exciting discussions, which allowed to identify emerging areas of myology research and encouraged scientific cross-fertilization to facilitate exchanges between different laboratories in different countries. The meeting was a success and this community will continue to deliver major contributions to our understanding of muscle development and function, the pathogenesis of muscle diseases and the development of novel therapeutic approaches. Here, we report abstracts of the meeting discussing recent results of basic, translational and early clinical studies confirming that the field of Myology is strong and articulated, maturing toward clinical development for the treatment of muscle diseases.

Row data related to Fig. 1 and Fig. 2 of the manuscript "Microencapsulated Sertoli cells sus... more Row data related to Fig. 1 and Fig. 2 of the manuscript "Microencapsulated Sertoli cells sustain myoblast proliferation without affecting the myogenic potential. In vitro data" received by Data in Brief.

This article is distributed under the terms of the Creative Commons Attribution Noncommercial Lic... more This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Cellular and Molecular Life Sciences, Jul 30, 2019

Obesity is an endemic pathophysiological condition and a comorbidity associated with hypercholest... more Obesity is an endemic pathophysiological condition and a comorbidity associated with hypercholesterolemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, and cancer. The adipose tissue of obese subjects shows hypertrophic adipocytes, adipocyte hyperplasia, and chronic low-grade inflammation. S100 proteins are Ca 2+-binding proteins exclusively expressed in vertebrates in a cell-specific manner. They have been implicated in the regulation of a variety of functions acting as intracellular Ca 2+ sensors transducing the Ca 2+ signal and extracellular factors affecting cellular activity via ligation of a battery of membrane receptors. Certain S100 proteins, namely S100A4, the S100A8/S100A9 heterodimer and S100B, have been implicated in the pathophysiology of obesity-promoting macrophage-based inflammation via toll-like receptor 4 and/ or receptor for advanced glycation end-products ligation. Also, serum levels of S100A4, S100A8/S100A9, S100A12, and S100B correlate with insulin resistance/type 2 diabetes, metabolic risk score, and fat cell size. Yet, secreted S100B appears to exert neurotrophic effects on sympathetic fibers in brown adipose tissue contributing to the larger sympathetic innervation of this latter relative to white adipose tissue. In the present review we first briefly introduce S100 proteins and then critically examine their role(s) in adipose tissue and obesity.

International Journal of Andrology, Mar 30, 2018

Sertoli cells are located in the testes where they control several key functions in spermatogenes... more Sertoli cells are located in the testes where they control several key functions in spermatogenesis. Over the past 30 years, Sertoli cells have been upgraded from a simple scaffold-like structural system to a dynamic functional system of intercellular support that delivers potent immunomodulatory and trophic factors. Since the discovery of new Sertoli cell secretory products, these cells have been utilized in experimental cell transplantation and co-transplantation protocols aimed at treating both chronic inflammatory and degenerative disorders. For these reasons, this work reviews the application of both naked and microencapsulated Sertoli cells used in cell transplantation studies of several chronic or autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne muscular dystrophy and in studies aimed at the prevention of skin allograft rejection.

Journal of Cachexia, Sarcopenia and Muscle, Nov 30, 2018

Primary sarcopenia is a condition of reduced skeletal muscle mass and strength, reduced agility, ... more Primary sarcopenia is a condition of reduced skeletal muscle mass and strength, reduced agility, and increased fatigability and risk of bone fractures characteristic of aged, otherwise healthy people. The pathogenesis of primary sarcopenia is not completely understood. Herein, we review the essentials of the cellular and molecular mechanisms of skeletal mass maintenance; the alterations of myofiber metabolism and deranged properties of muscle satellite cells (the adult stem cells of skeletal muscles) that underpin the pathophysiology of primary sarcopenia; the role of the Ca 2+-sensor protein, S100B, as an intracellular factor and an extracellular signal regulating cell functions; and the functional role of S100B in muscle tissue. Lastly, building on recent results pointing to S100B as to a molecular determinant of myoblast-brown adipocyte transition, we propose S100B as a transducer of the deleterious effects of accumulation of reactive oxygen species in myoblasts and, potentially, myofibers concurring to the pathophysiology of sarcopenia.

European Journal of Translational Myology, Feb 23, 2016

Italian journal of anatomy and embryology, 1994

Cellular and Molecular Life Sciences, Feb 18, 2020

Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathi... more Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/ NAD + ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2-the master regulator of the antioxidant response-, consequent in most cases to defective autophagy, can lead to reductive stress. In addition, hyperglycemia-induced activation of the polyol pathway can lead to increased NADH/NAD + ratio, which might translate into increased levels of hydrogen sulfide-via enhanced activity of cystathionine β-synthase-that would fuel reductive stress through inhibition of mitochondrial complex I. Reductive stress may be either a potential weapon against cancer priming tumor cells to apoptosis or a cancer's ally promoting tumor cell proliferation and making tumor cells resistant to reactive oxygen species-inducing drugs. In non-cancer pathological states reductive stress is definitely harmful paradoxically leading to reactive oxygen species overproduction via excess NADPH oxidase 4 activity. In face of the documented occurrence of reductive stress in several heart diseases, there is much less information about the occurrence and effects of reductive stress in skeletal muscle tissue. In the present review we describe relevant results emerged from studies of reductive stress in the heart and review skeletal muscle conditions in which reductive stress has been experimentally documented and those in which reductive stress might have an as yet unrecognized pathophysiological role. Establishing whether reductive stress has a (patho)physiological role in skeletal muscle will hopefully contribute to answer the question whether antioxidant supplementation to the general population, athletes, and a large cohort of patients (e.g. heart, sarcopenic, dystrophic, myopathic, cancer, and bronco-pulmonary patients) is harmless or detrimental.

European Journal of Translational Myology, 2017