The expression analysis of mouse interleukin-6 splice variants argued against their biological relevance

Alternative splicing generates several interleukin-6 (IL-6) isoforms; for them an antagonistic activity to the wild-type IL-6 has been proposed. In this study we quantified the relative abundance of IL-6 mRNA isoforms in a panel of mouse tissues and in C2C12 cells during myoblast differentiation or after treatment with the Ca2+ ionophore A23187, the AMP-mimetic AICAR and TNF-alpha. The two mouse IL-6 isoforrns identified, IL-6 delta 5 (deletion of the first 58 bp of exon 5) and IL-6 delta 3 (lacking exon 3), were not conserved in rat and human, did not exhibit tissue specific regulation, were expressed at low levels and their abundance closely correlated to that of full-length IL-6. Species-specific features of the IL-6 sequence, such as the presence of competitive 3' acceptor site in exon 5 and insertion of retrotransposable elements in intron 3, could explain the production of IL-6 delta 5 and IL-6 delta 3. Our results argued against biological significance for mouse IL-6 isoforms

Sarcopenia ed esercizio fisico

In questo articolo viene descritto il ruolo dell’esercizio fisico nel migliorare la funzionalità e la dinamicità mitocondriale e nel favorire una buona qualità dell’invecchiamento muscolare; si tratta di un’area della ricerca bioenergetica che pone i mitocondri al centro delle teorie sull’invecchiamento

Use of Streptococcus salivarius K12 in supporting the mucosal immune function of active young subjects: A randomised double-blind study

Introduction: Upper respiratory tract infections (URTI) are the most common illnesses affecting athletes, causing absences from training and competition. Salivary immunoglobulin A (sIgA) is the main immune factor in saliva, and a consistent association between low concentrations of sIgA and an increased incidence of URTIs has been reported. The oral probiotic Streptococcus salivarius K12 has been suggested to have the potential to improve oral diseases and mucosal barrier function. However, the effects of this probiotic on active young subjects performing a high-intensity training (HIT) program have not been investigated. Methods: Active young students were randomised into a treated group (S. salivarius K12) and a control (placebo) group and asked to take the product daily for 30 days. After this period, participants performed a graded exercise test and five HIT sessions, all within 3 days. They were also asked to complete the Wisconsin Upper Respiratory Symptom Survey daily to monitor URTI's presence. Before and after the 30 days, and at 0h, 24h and 72h after the last training session, saliva samples were collected to quantify sIgA level, secretion rate, and flow. The effect of S. salivarius K12 intake on these parameters was tested using an ANOVA for repeated measures. Results: Twenty (M = 14, F = 6) young subjects (23.5 ± 2.3 years old) participated in the study. The total accumulated training load (sRPE) in the supplementation period was similar in the two groups (treated: 4345 ± 3441 AU; control: 4969 ± 4165 AU; p > 0.05). Considering both sIgA level and secretion rate, significant time (F(4,15) = 3.38; p = 0.037; F(4,15) = 6.00; p = 0.004) and time×group interactions (F(4,15) = 2.49; p = 0.049; F(4,15) = 5.01; p = 0.009) were reported, with the treated group showing higher sIgA levels at 72h post-exercise and increased secretion rate both at 0h and 72h. The number of URTI episodes was similar in the treated and control groups (χ² = 1.83; p > 0.05). Conclusion: This study demonstrates that relatively short-term S. salivarius K12 supplementation increased sIgA level and secretion in healthy subjects performing a demanding exercise-training programme composed of HIT sessions

Muscle releases alpha-sarcoglycan positive extracellular vesicles carrying miRNAs in the bloodstream

In the past few years, skeletal muscle has emerged as an important secretory organ producing soluble factors, called myokines, that exert either autocrine, paracrine or endocrine effects. Moreover, recent studies have shown that muscle releases microRNAs into the bloodstream in response to physical exercise. These microRNAs affect target cells, such as hormones and cytokines. The mechanisms underlying microRNA secretion are poorly characterized at present. Here, we investigated whether muscle tissue releases extracellular vesicles (EVs), which carry microRNAs in the bloodstream under physiological conditions such as physical exercise. Using density gradient separation of plasma from sedentary and physically fit young men we found EVs positive for TSG101 and alpha-sarcoglycan (SGCA), and enriched for miR-206. Cytometric analysis showed that the SGCA+ EVs account for 1-5% of the total and that 60-65% of these EVs were also positive for the exosomal marker CD81. Furthermore, the SGCA-immuno captured sub-population of EVs exhibited higher levels of the miR-206/miR16 ratio compared to total plasma EVs. Finally, a significant positive correlation was found between the aerobic fitness and muscle-specific miRNAs and EV miR-133b and -181a-5p were significantly up-regulated after acute exercise. Thus, our study proposes EVs as a novel means of muscle communication potentially involved in muscle remodeling and homeostasis

Looking at the role of disordered E-tails of IGF-1

Intrinsically disordered proteins (IDPs) encompass signalling and regulatory functions and altered expression of IDPs is associated with many diseases and imbalance in signalling pathways, transcriptional regulation, and splicing. Interest in insulin-like growth factor (IGF) – 1 isoforms on muscle homeostasis, regeneration, differentiation, and diseases has increased significantly. Inclusion or exclusion of exon 5 into the IGF-1 mRNA gives rise to three transcripts, IGF-1Ea, IGF-1Eb and IGF-1Ec, which yield three different C-terminal extensions called Ea, Eb and Ec peptides. Protein-coding sequences of exon 5 showed low rate of synonymous mutations and contain disorder-promoting amino acids, suggesting a regulatory role for these domains (Annibalini et al. 2016). To setup the analysis, the supernatants of HEK293 cells transfected with the specific IGF-1 isoform constructs as described in (De Santi et al. 2016) were studied by limited proteolysis combined with mass spectrometry (MS) using a Q-TOF microTM MS/MS (Micromass, Manchester, UK). Preliminary data showed that the C-terminal region of IGF-1Ea has lower resistance to trypsin digestion compared to the mature IGF-1 demonstrating IDRs in the Ea peptide. MS analyses to the detection of IGF-1E isoforms allowed us to identify both mature IGF-1 and IGF-1Ea isoform in transfected HEK293 cell culture supernatant. Analytical methods to correctly detect and quantify the IGF-1 isoforms are not currently available. In fact, the current existing methods rely on the use of antibodies that primarily recognize the mature IGF-1 peptide, thereby underestimate the isoforms. This finding could provide evidence allowing the detection and identification of the “E-tails” of IGF-1 and targeting these regulatory elements may represent a new strategy to control IGF-1 bioavailability in physio-pathological conditions. 1. Annibalini G, et al. MIR retroposon exonization promotes evolutionary variability and generates species-specific expression of IGF-1 splice variants BBAGRM 2016;1859:757-68. 2. De Santi M, et al. Cell Oncol (Dordr) 2016;39:149-59

Muscle and bone health in postmenopausal women: Role of protein and vitamin d supplementation combined with exercise training

Menopause is an age-dependent physiological condition associated with a natural decline in oestrogen levels, which causes a progressive decrease of muscle mass and strength and bone density. Sarcopenia and osteoporosis often coexist in elderly people, with a prevalence of the latter in elderly women. The profound interaction between muscle and bone induces a negative resonance between the two tissues affected by these disorders worsening the quality of life in the postmenopausal period. It has been estimated that at least 1 in 3 women over age 50 will experience osteoporotic fractures, often requiring hospitalisation and long-term care, causing a large financial burden to health insurance systems. Hormonal replacement therapy is effective in osteoporosis prevention, but concerns have been raised with regard to its safety. On the whole, the increase in life expectancy for postmenopausal women along with the need to improve their quality of life makes it necessary to develop specific and safe therapeutic strategies, alternative to hormonal replacement therapy, targeting both sarcopenia and osteoporosis progression. This review will examine the rationale and the effects of dietary protein, vitamin D and calcium supplementation combined with a specifically-designed exercise training prescription as a strategy to counteract these postmenopausal-associated disorders

The “Journal of Functional Morphology and Kinesiology” Journal Club Series: Highlights on Recent Papers in Physical Activity and Sedentary Behavior

We are glad to introduce the sixth Journal Club. This edition is focused on several relevant studies published in the last years in the field of physical activity and sedentary behavior, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the sport seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture

Protective Role of Italian Juglans Regia L. Nut Ethanolic Extract in Human Keratinocytes under Oxidative and Inflammatory Stress

In this research, fatty acid profile and polyphenolic content of an ethanolic extract of walnut from Juglans regia L. collected in Central Italy, were performed. The potential antioxidant and anti-inflammatory effects of the extract were investigated in the human keratinocytes cell line

Mutual Interactions among Exercise, Sport Supplements and Microbiota

The adult gut microbiota contains trillions of microorganisms of thousands of differentspecies. Only one third of gut microbiota are common to most people; the rest are specific andcontribute to enhancing genetic variation. Gut microorganisms significantly affect host nutrition,metabolic function, immune system, and redox levels, and may be modulated by several environmentalconditions, including physical activity and exercise. Microbiota also act like an endocrine organ andis sensitive to the homeostatic and physiological changes associated with training; in turn, exercisehas been demonstrated to increase microbiota diversity, consequently improving the metabolic profileand immunological responses. On the other side, adaptation to exercise might be influenced bythe individual gut microbiota that regulates the energetic balance and participates to the control ofinflammatory, redox, and hydration status. Intense endurance exercise causes physiological andbiochemical demands, and requires adequate measures to counteract oxidative stress, intestinalpermeability, electrolyte imbalance, glycogen depletion, frequent upper respiratory tract infections,systemic inflammation and immune responses. Microbiota could be an important tool to improveoverall general health, performance, and energy availability while controlling inflammation andredox levels in endurance athletes. The relationship among gut microbiota, general health, trainingadaptation and performance, along with a focus on sport supplements which are known to exertsome influence on the microbiota, will be discussed

Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study

Purpose: Circulating insulin-like growth factor-1 (IGF-1) is positively associated with the risk of BC recurrence, and is more frequently dysregulated in older people, especially in those with metabolic syndrome (MetS) and obesity. This study aimed to analyze the association between IGF-1 levels and indices of MetS and insulin resistance in BC survivors. Methods: Baseline data of 563 BC survivors enrolled in the DIet and ANdrogen-5 (DIANA-5; NCT05019989) study were analyzed. Results: Lower circulating IGF-1 levels in subjects with MetS than in those without MetS were found. After stratification of the patients according to the diagnosis of MetS, we highlighted that the insulin was the main predictor of elevated IGF-1 levels only in subjects without MetS. Moreover, we found an interaction between high-density lipoprotein cholesterol (HDL-C), glycemia, and IGF-1 levels, showing a positive correlation between HDL-C and IGF-1, especially in subjects with higher values of glycemia and without a diagnosis of MetS. Conclusions: While IGF-1 levels appear to be much more impaired in subjects diagnosed with MetS, in non-MetS subjects, IGF-1 levels may respond better to metabolic parameters and lifestyle changes. Further studies are needed to analyze the role of physical activity and/or dietary intervention in modulating IGF-1 concentrations in BC survivors. Implications for cancer survivors: These results could have important clinical implications for planning customized strategies aimed at modulating IGF-1 levels in BC survivors. In fact, while the IGF-1 system seems to be much more compromised in subjects with a diagnosis of MetS, in noMetS subjects, IGF-1 levels could better respond to lifestyle changes