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    Piero Sestili

    Cannabis sativa var. Kompolti, a variety routinely used for food production purposes, is characterized by a low concentration of psychoactive molecules, although containing many other biologically attractive metabolites in all parts of... more
    Cannabis sativa var. Kompolti, a variety routinely used for food production purposes, is characterized by a low concentration of psychoactive molecules, although containing many other biologically attractive metabolites in all parts of the plant, including the roots. In the present work, we evaluate the specific biological activities of the roots’ extract from plants cultivated through aeroponics, an affordable and reliable method facilitating the isolation and processing of roots, with the advantage of being suitable for industrial scale-up. Furthermore, aeroponics results in an increased net accumulation of the most biologically attractive constituents (β-sitosterol, friedelin and epi-friedelanol) found in the roots. The ethanolic extract of the aeroponic roots of C. sativa (APEX) and its separate components are studied to evaluate their anti-inflammatory (modulation of the expression level of specific markers upon LPS stimulation in U937 cells, such as IL-6, IL-8, TNF-α, IkB-α, i...
    The 14th 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... more
    The 14th 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 Based on selection from submitted abstracts, participants presented their novel, unpublished results in seven oral communication and two poster sessions.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...
    We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to... more
    We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized ...
    Social isolation has adverse effects on mental health, physical exercise, and dietary habits. This longitudinal observational study aimed to investigate the effects of mood states and exercise on nutritional choices, on 176 college... more
    Social isolation has adverse effects on mental health, physical exercise, and dietary habits. This longitudinal observational study aimed to investigate the effects of mood states and exercise on nutritional choices, on 176 college students (92 males, 84 females; 23 ± 4 years old) during the COVID-19 lockdown. During 21 days, nutrition and exercise were daily monitored, and the mood states assessed. A factor analysis was used to reduce the number of nutritional variables collected. The relationships between exercise, mood and nutrition were investigated using a multivariate general linear model and a mediation model. Seven factors were found, reflecting different nutritional choices. Exercise was positively associated with fruit, vegetables and fish consumption (p = 0.004). Depression and quality of life were, directly and inversely, associated with cereals, legumes (p = 0.005; p = 0.004) and low-fat meat intake (p = 0.040; p = 0.004). Exercise mediated the effect of mood states on ...
    Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a... more
    Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0–5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP...
    Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the... more
    Heterocyclic aromatic amines (HAAs) are potent carcinogenic compounds induced by the Maillard reaction in well-done cooked meats. Free amino acids, protein, creatinine, reducing sugars and nucleosides are major precursors involved in the production of polar and non-polar HAAs. The variety and yield of HAAs are linked with various factors such as meat type, heating time and temperature, cooking method and equipment, fresh meat storage time, raw material and additives, precursor’s presence, water activity, and pH level. For the isolation and identification of HAAs, advanced chromatography and spectroscopy techniques have been employed. These potent mutagens are the etiology of several types of human cancers at the ng/g level and are 100- to 2000-fold stronger than that of aflatoxins and benzopyrene, respectively. This review summarizes previous studies on the formation and types of potent mutagenic and/or carcinogenic HAAs in cooked meats. Furthermore, occurrence, risk assessment, and...
    Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous,... more
    Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed...
    COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill... more
    COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.
    ABSTRACT Introduction Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different... more
    ABSTRACT Introduction Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation, and downregulation of specific signaling pathways. Areas covered The goal of this article is to critically review recent evidence on association between coffee and prevention of different types of cancer, with particular emphasis on the molecular mechanisms and the bioactive compounds involved in its anticancer activity. Expert opinion Coffee is a mixture of different compounds able to decrease the risk of many types of cancer. However, its potential anticancer activity is not completely understood. Hundreds of biologically active components such as caffeine, chlorogenic acid, diterpenes are contained in coffee. Further research is needed to fully elucidate the molecular mechanisms underlying the anticancer effects of coffee and fully understand the role of different confounding factors playing a role in its reported anticancer activity.
    The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new... more
    The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nig...
    The killing of Escherichia coli cells by H2O2 is higher when exposure to the oxidant is performed in a complete culture medium, as compared to saline. Whereas MgSO4, CaCl2, thiamine or glucose, added separately or in combination with the... more
    The killing of Escherichia coli cells by H2O2 is higher when exposure to the oxidant is performed in a complete culture medium, as compared to saline. Whereas MgSO4, CaCl2, thiamine or glucose, added separately or in combination with the saline, had no effect on the cytotoxic response to H2O2, the cytotoxicity appeared highly dependent upon the presence of the casamino acids in the incubation medium. One of these amino acids, histidine, was found to greatly augment the toxicity of H2O2 in E. coli. This effect of histidine was also observed in mammalian cells. In fact, both the cytoxicity and the DNA damage produced by H2O2 in Chinese hamster ovary (CHO) cells were significantly increased by this amino acid.
    The DNA synthesis inhibitory effect of hydrogen peroxide is more pronounced when treatments are performed at 37°C than at 4°C and in low density rather than high density cultures. Recovery from DNA synthesis inhibition appears to be rapid... more
    The DNA synthesis inhibitory effect of hydrogen peroxide is more pronounced when treatments are performed at 37°C than at 4°C and in low density rather than high density cultures. Recovery from DNA synthesis inhibition appears to be rapid in cells challenged with the oxidant at 4°C, whereas no recovery (for up to 6 hours) was apparent in cells treated at 37°C. These results correlate well with our previous data, indicating that different types of lesions are produced by hydrogen peroxide at the two different temperatures, and suggest an explanation for the lower toxicity elicited by the oxidant at 4°C, as compared to the physiological temperature of 37°C.
    The COVID-19 pandemic is posing an unprecedented sanitary threat. In the absence of specific vaccines and anti-SARS-CoV-2 drugs, medicines that may assist in tackling the emergency and limiting the high number of fatalities are urgently... more
    The COVID-19 pandemic is posing an unprecedented sanitary threat. In the absence of specific vaccines and anti-SARS-CoV-2 drugs, medicines that may assist in tackling the emergency and limiting the high number of fatalities are urgently needed. The repositioning of available drugs to treat COVID-19 is the only and rapid option in the face of the lack of direct antiviral agents and vaccines available. In this light it is important to focus on available drugs, which, based on their pharmacodynamics, could plausibly attenuate viral growth as well as COVID-19’s worst complications. This is the case of chloroquine and tocilizumab which seem to limit virus replication and the severity of interstitial pneumonia, respectively. However, these treatments, particularly those aimed at containing inflammation, are still reserved for the most severe cases. This commentary elaborates on the pharmacological rationale of repositioning the mast cell stabilizer chromones as an adjunctive treatment for SARS‐CoV‐2 infection, and proposes their practical clinical testing as an early, safe, and cost-effective anti-inflammatory intervention in COVID-19 to limit the eventual secondary progression toward life-threatening respiratory complications.
    A healthy lifestyle is based on a correct diet and regular exercise. Little is known about the effect of different types of exercise on dietary preferences. To address the question of whether high-intensity interval training (HIIT) could... more
    A healthy lifestyle is based on a correct diet and regular exercise. Little is known about the effect of different types of exercise on dietary preferences. To address the question of whether high-intensity interval training (HIIT) could modulate spontaneous food choices, an experimental study was carried out on 32 young, healthy normal-weight subjects. The spontaneous diet of each subject has been monitored over nine weeks of indoor-cycling training, divided into three mesocycles with an incremental pattern: total energy intake, macronutrients and micronutrients have been analysed. A two-way mixed model has been used to assess differences in dietary variables; a principal factor analysis has been performed to identify sample subgroups. An increased energy intake (+17.8% at T3; p < 0.01) has been observed, although macronutrients’ proportions did not vary over time, without differences between sexes. An increase of free fat mass was found in the last mesocycle (+3.8%), without an...
    Background Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although... more
    Background Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although the topic is still open to debate. The aim of the present study was to determine whether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer’s recommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning (1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approach integrating the determination of psychometric, performance, metabolic and blood biochemical parameters. Methods This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults (20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue in the participant...
    The adult gut microbiota contains trillions of microorganisms of thousands of different species. Only one third of gut microbiota are common to most people; the rest are specific and contribute to enhancing genetic variation. Gut... more
    The adult gut microbiota contains trillions of microorganisms of thousands of different species. Only one third of gut microbiota are common to most people; the rest are specific and contribute to enhancing genetic variation. Gut microorganisms significantly affect host nutrition, metabolic function, immune system, and redox levels, and may be modulated by several environmental conditions, including physical activity and exercise. Microbiota also act like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with training; in turn, exercise has been demonstrated to increase microbiota diversity, consequently improving the metabolic profile and immunological responses. On the other side, adaptation to exercise might be influenced by the individual gut microbiota that regulates the energetic balance and participates to the control of inflammatory, redox, and hydration status. Intense endurance exercise causes physiological and biochemical demands,...
    Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee... more
    Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren–Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS...
    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... more
    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 ...
    Myogenic differentiation is triggered, among other situations, in response to muscle damage for regenerative purposes. It has been shown that during myogenic differentiation, myotubes release extracellular vesicles (EVs) which participate... more
    Myogenic differentiation is triggered, among other situations, in response to muscle damage for regenerative purposes. It has been shown that during myogenic differentiation, myotubes release extracellular vesicles (EVs) which participate in the signalling pattern of the microenvironment. Here we investigated whether EVs released by myotubes exposed or not to mild oxidative stress modulate the behaviour of targeted differentiating myoblasts and macrophages to promote myogenesis. We found that EVs released by oxidatively challenged myotubes (H₂O₂-EVs) are characterized by an increased loading of nucleic acids, mainly DNA. In addition, incubation of myoblasts with H₂O₂-EVs resulted in a significant decrease of myotube diameter, myogenin mRNA levels and myosin heavy chain expression along with an upregulation of proliferating cell nuclear antigen: these effects collectively lead to an increase of recipient myoblast proliferation. Notably, the EVs from untreated myotubes induced an oppo...
    The need for express screening of the DNA damaging potential of chemicals has progressively increased over the past 20 years due to the wide number of new synthetic molecules to be evaluated, as well as the adoption of more stringent... more
    The need for express screening of the DNA damaging potential of chemicals has progressively increased over the past 20 years due to the wide number of new synthetic molecules to be evaluated, as well as the adoption of more stringent chemical regulations such as the EU REACH and risk reduction politics. In this regard, DNA diffusion assays such as the microelectrophoretic comet assay paved the way for rapid genotoxicity testing. A more significant simplification and speeding up of the experimental processes was achieved with the fast halo assay (FHA) described in the present chapter. FHA operates at the single cell level and relies on radial dispersion of the fragments of damaged DNA from intact nuclear DNA. The fragmented DNA is separated by diffusion in an alkaline solvent and is stained, visualized, and finally quantified using computer-assisted image analysis programs. This permits the rapid assessment of the extent of DNA breakage caused by different types of DNA lesions. FHA h...
    Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional... more
    Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB. Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety. Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions. From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded tha...
    In this research, fatty acid profile and polyphenolic content of an ethanolic extract of walnut from Juglans regia L. collected in Central Italy, were characterized. The potential antioxidant and anti-inflammatory effects of the extract... more
    In this research, fatty acid profile and polyphenolic content of an ethanolic extract of walnut from Juglans regia L. collected in Central Italy, were characterized. The potential antioxidant and anti-inflammatory effects of the extract were investigated in the human keratinocytes cell line. Fatty acid profile was determined by gas chromatography/mass spectrometry analysis, total phenolic content by Folin-Ciocalteu method and aluminum chloride colorimetric method was used for determination of total flavonoids. Kertatinocytes were exposed to t-butyl hydroperoxide or Tumor Necrosis Factor alfa in the absence or presence of extract. Reduced glutathione was determined by Sedlak method; lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances. t-butyl hydroperoxide and Tumor Necrosis Factor alfa-induced intracellular reactive oxygen species were monitored by fluorescent probes. The expression of some genes related to the inflammatory process (IL-6, IL-8, ikB, ...
    Nuclear factor (erythroid-derived-2)-like 2 is one of the most efficient cytoprotective rheostats against exogenous or endogenous oxidative insults. At present, the modulation of the Nrf2 pathway represents an interesting and highly... more
    Nuclear factor (erythroid-derived-2)-like 2 is one of the most efficient cytoprotective rheostats against exogenous or endogenous oxidative insults. At present, the modulation of the Nrf2 pathway represents an interesting and highly explored strategy in the oncological area. Area covered: In this review, we present and discuss the different modulation of the Nrf2 pathway by some natural compounds with a well demonstrated anticancer activity, and critically analyze the challenges associated with the development of an Nrf2-based anticancer strategy. Expert opinion: Many natural compounds with a well-defined anticancer activity are able to modulate this pathway. Both Nrf2 inducers and inhibitors can be useful as anticancer strategy. However, since Nrf2 modulates many networks potentially involved in the detoxification process of anticancer drugs, its activation in cancer cells could lead to chemoresistance. The switch between a beneficial or detrimental role of Nrf2 in cancer cells essentially depends on the tight control of its activity, the specific conditions of tumor microenvironment, and cell type. In line with the paucity of clear data related to the mechanisms underpinning the role of Nrf2 in cancer development and chemoresistance, discovery and development of Nrf2-based strategies is one of the most critical and challenging assignments for fighting cancers.
    Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and... more
    Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS) production and decreased antioxidant (AO) defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to...
    To investigate how the viscoelastic characteristics of muscles (non-neural tone, elasticity and stiffness) vary as a function of age and gender in a sample of track and field master athletes. To compare these findings with data on related... more
    To investigate how the viscoelastic characteristics of muscles (non-neural tone, elasticity and stiffness) vary as a function of age and gender in a sample of track and field master athletes. To compare these findings with data on related sedentary subjects in literature. A total of 390 athletes (aged 35-99) were assessed during the European Master Athletics Indoor Championship 2016. A non-invasive measurement device called MyotonPro was used to measure tone, stiffness, and elasticity in the biceps brachii and rectus femoris muscles at rest. Linear regression analysis was used to assess the correlation between age and the measured parameters. To compare our results with previously reported data, we stratified participants according to gender and age. Tone was found to not be dependent on age, whereas stiffness was found to be age dependent. Elasticity was found to be both physical activity and age dependent. Tone (only for men), elasticity, and stiffness were lower in master athlete...
    In professional road cyclists, the majority of overuse injuries affect the lower limbs and are mostly represented by contractures or muscle shortening, characterized by an increase of tone and stiffness and a variation of elasticity.... more
    In professional road cyclists, the majority of overuse injuries affect the lower limbs and are mostly represented by contractures or muscle shortening, characterized by an increase of tone and stiffness and a variation of elasticity. Treatment and prevention of these specific conditions may include physical, supplementary, and pharmacologic support. The aim of this real-life study was to determine: first, the alterations of tone, stiffness, elasticity, and soreness of rectus femoris (RF) and biceps femoris (BF) in top class cyclists engaged in 3 multistage races, and second, whether any variable in the management of the athletes may affect the prevention and/or reduction of such alterations.Twenty-three professional cyclists competing in 3 international, cycling stage races were assessed. Athletes could receive, upon the approval of the medical staff, physical, dietary, and/or pharmacological management which could include treatments with topical over-the-counter myorelaxants to pre...
    The toxicity of a short-term exposure to tert-butylhydroperoxide in U937 cells was markedly reduced by chemically or experimentally induced respiratory deficiency. Rotenone mitigated the lethal effects of the hydroperoxide over the same... more
    The toxicity of a short-term exposure to tert-butylhydroperoxide in U937 cells was markedly reduced by chemically or experimentally induced respiratory deficiency. Rotenone mitigated the lethal effects of the hydroperoxide over the same concentration-range in which the complex I inhibitor inhibited oxygen utilization. U937 cells that were made respiration deficient by growing them in the presence of either chloramphenicol or ethidium bromide, were in both circumstances highly resistant to tert-butylhydroperoxide. The improved survival was not a direct consequence of the absence of electron transport, but rather was attributable to the large amounts of NADH which accumulate in the mitochondria of chemically hypoxic or respiration-deficient cells. Indeed, the toxicity elicited by tert-butylhydroperoxide was also abolished by supplementation with either of two different NADH-linked substrates, namely pyruvate or beta-hydroxybutyrate. Accumulation of intramitochondrial NADH, and the resulting cytoprotective effects, was associated with prevention of the loss of nonprotein sulphydryls and mitochondrial membrane potential. Neither rotenone nor pyruvate reduced the toxicity of tert-butylhydroperoxide in thiol-depleted cells. Taken together, these results indicate that depletion of mitochondrial NADH is a critical event in the cytotoxic response to tert-butylhydroperoxide since this pyridine nucleotide prevents mitochondrial dysfunction and cell death caused by the hydroperoxide. As a consequence, in hydroperoxide-treated cells electron transport is highly detrimental since it consumes mitochondrial NADH.
    The in vitro antifungal activity was determined of an ethanolic extract of Vitis vinifera L. tendrils (TVV) against ten plant pathogenic fungi, using the agar dilution method; activity was shown against all tested fungi. Fusarium species... more
    The in vitro antifungal activity was determined of an ethanolic extract of Vitis vinifera L. tendrils (TVV) against ten plant pathogenic fungi, using the agar dilution method; activity was shown against all tested fungi. Fusarium species were the most sensitive with MIC values ranging from 250 to 300 ppm, while the basidiomycete fungus Rhizoctonia solani was the most resistant, with a MIC value of 500 ppm. Electrospray ionization tandem mass spectrometry (ESI-MS(n)) was used to obtain qualitative information on the main components of TVV. The high amount of polyphenolic compounds contained in TVV is likely to contribute significantly to its antifungal activity.
    Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role in muscle biochemistry and physiology not limited to its ergogenic role. Indeed Cr has been shown to exert pleiotropic effects, which promote protein... more
    Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role in muscle biochemistry and physiology not limited to its ergogenic role. Indeed Cr has been shown to exert pleiotropic effects, which promote protein accretion, muscle-specific protein synthesis, growth in cultured myogenic cells and favour the myogenic process either in normal or stressing conditions. This review focuses on the effects of Cr supplementation on cellular and mitochondrial biochemistry and function in the course of skeletal muscle differentiation, either in normal or oxidatively stressing conditions, and on the ensuing nutraceutical/therapeutic perspectives.
    According to recent estimates, cancer continues to remain the second leading cause of death and is becoming the leading one in old age. Failure and high systemic toxicity of conventional cancer therapies have accelerated the... more
    According to recent estimates, cancer continues to remain the second leading cause of death and is becoming the leading one in old age. Failure and high systemic toxicity of conventional cancer therapies have accelerated the identification and development of innovative preventive as well as therapeutic strategies to contrast cancer-associated morbidity and mortality. In recent years, increasing body ofin vitroandin vivostudies has underscored the cancer preventive and therapeutic efficacy of the isothiocyanate sulforaphane. In this review article, we highlight that sulforaphane cytotoxicity derives from complex, concurring, and multiple mechanisms, among which the generation of reactive oxygen species has been identified as playing a central role in promoting apoptosis and autophagy of target cells. We also discuss the site and the mechanism of reactive oxygen species’ formation by sulforaphane, the toxicological relevance of sulforaphane-formed reactive oxygen species, and the deat...
    The effect of the OH radical, generated in a Fenton-like reaction, on DNA structure and function was studied in a monkey kidney cell line (Vero). DNA single strand breaks were detected following exposure to 10- 100 microM concentrations... more
    The effect of the OH radical, generated in a Fenton-like reaction, on DNA structure and function was studied in a monkey kidney cell line (Vero). DNA single strand breaks were detected following exposure to 10- 100 microM concentrations of H2O2 on ice. These breaks were repaired very rapidly, and addition of the poly (ADP-ribose) transferase inhibitor, 3-aminobenzamide, resulted in an accumulation of breaks. DNA synthesis was inhibited at concentrations as high as 1- 30 mM, this effect also being reversible in approximately 60 min. 3-aminobenzamide did not affect the rate of DNA synthesis inhibition by H2O2.
    The cytotoxic effects of the essential oils obtained from the flowering aerial parts (APO) and ripe fruits (RFO) of Echinophora spinosa L. (Apiaceae) from central Italy toward human U937 promonocytoid cells were studied; the contribution... more
    The cytotoxic effects of the essential oils obtained from the flowering aerial parts (APO) and ripe fruits (RFO) of Echinophora spinosa L. (Apiaceae) from central Italy toward human U937 promonocytoid cells were studied; the contribution of each of the major constituents to the whole cytotoxic activity of either APO or RFO was also characterized. The major components of APO were beta-phellandrene (34.7%), myristicin (16.5%), p-cymene (16.3%), delta3-carene (12.6%), alpha-pinene (6.7%) and alpha-phellandrene (6.2%); those of RFO p-cymene (50.2%), myristicin (15.3%), alpha-pinene (15.1%) and alpha-phellandrene (8.1%). Both oils tested were toxic to U937 cells, but RFO was much more cytotoxic: indeed, the IC50 values calculated from the linear regression curves of RFO and APO were 14.5 +/- 0.85 and 43.4 +/- 2.81 microg/mL, respectively. alpha-Pinene and alpha-phellandrene were identified as the most toxically relevant constituents: however, they did not completely account for the toxic...
    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... more
    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 Ca(2+) ionophore A23187, the AMP-mimetic AICAR and TNF-α. The two mouse IL-6 isoforms identified, IL-6δ5 (deletion of the first 58 bp of exon 5) and IL-6δ3 (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-6δ5 and IL-6δ3. Our results argued against biological significance for mouse IL-6 isoforms.
    In contrast to damage of genomic DNA and despite its potential to affect cell physiology, RNA damage is a poorly examined field in biomedical research. Potential triggers of RNA damage as well as its pathophysiological implications remain... more
    In contrast to damage of genomic DNA and despite its potential to affect cell physiology, RNA damage is a poorly examined field in biomedical research. Potential triggers of RNA damage as well as its pathophysiological implications remain largely unknown. While less lethal than mutations in genome, such non-acutely lethal insults to cells have been recently associated with underlying mechanisms of several human chronic diseases. We investigated whether RNA damage could be related to the exposure of particular xenobiotics by testing the RNA-damaging activity of a series of chemicals with different mechanisms of action. Cultured human T-lymphoblastoid cells were treated with ethyl methanesulfonate (EMS), H(2)O(2), doxorubicin, spermine, or S-nitroso-N-acetylpenicillamine (SNAP). Furthermore, we studied the potential protective activity of a pomegranate extract against RNA damage induced by different chemicals. Special attention has been paid to the protective mechanisms of the extract...
    Over the past three decades the development of methods for visualizing at the cell level the extent of DNA breakage significantly contributed to genotoxicity testing: their availability greatly improved the knowledge in the field of... more
    Over the past three decades the development of methods for visualizing at the cell level the extent of DNA breakage significantly contributed to genotoxicity testing: their availability greatly improved the knowledge in the field of genetic toxicology. These procedures are based on the separation and visualization of DNA fragments resulting from cleavage of nuclear DNA. The separation process can be obtained either electrically (comet assay, linear migration of DNA fragments) or chemically (alkaline dispersion assays, radial diffusion of DNA fragments). Once separated and stained, intact and fragmented DNA can be observed with fluorescence or light microscope. Appropriate computer-assisted image analysis allows quantitative determination of the extent of DNA breakage. These procedures have been proven to be sensitive, flexible, and reliable, and, as compared to former methods, they are simpler, are less time and money consuming, and have the unique capability of detecting DNA damage at the single cell level. This last feature has the additional advantage of allowing the identification of cellular subpopulations characterized by different sensitivity to the damaging agent. The fast halo assay (FHA) is currently the simplest and quickest nuclear dispersion assay; recent modifications of FHA have further improved the assay and pave the way to a full exploitation of its analytical potential. In this chapter the development, procedures, applications, and limits of these dispersion assays, with a particular focus on FHA, will be illustrated.
    The toxicity of a short-term exposure to tert-butylhydroperoxide in U937 cells was markedly reduced by chemically or experimentally induced respiratory deficiency. Rotenone mitigated the lethal effects of the hydroperoxide over the same... more
    The toxicity of a short-term exposure to tert-butylhydroperoxide in U937 cells was markedly reduced by chemically or experimentally induced respiratory deficiency. Rotenone mitigated the lethal effects of the hydroperoxide over the same concentration-range in which the complex I inhibitor inhibited oxygen utilization. U937 cells that were made respiration deficient by growing them in the presence of either chloramphenicol or ethidium bromide, were in both circumstances highly resistant to tert-butylhydroperoxide. The improved survival was not a direct consequence of the absence of electron transport, but rather was attributable to the large amounts of NADH which accumulate in the mitochondria of chemically hypoxic or respiration-deficient cells. Indeed, the toxicity elicited by tert-butylhydroperoxide was also abolished by supplementation with either of two different NADH-linked substrates, namely pyruvate or beta-hydroxybutyrate. Accumulation of intramitochondrial NADH, and the res...
    We have isolated and conducted preliminary characterization of a cell line derived from the Chinese hamster ovary cell line AA8, which we have designated AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately... more
    We have isolated and conducted preliminary characterization of a cell line derived from the Chinese hamster ovary cell line AA8, which we have designated AG8 and which is highly resistant to the cytotoxic effects of H2O2 (approximately 17-fold when the H2O2 treatment was at 37 degrees; approximately 11-fold when the H2O2 treatment was at 4 degrees). AG8 cells were moderately (but significantly; P < 0.05) cross-resistant to CdCl2 (approximately 4-fold), NaAsO2 (approximately 2.3-fold), t-butyl hydroperoxide (approximately 2.9-fold), cumene hydroperoxide (approximately 3-fold), menadione (approximately 1.7-fold) and HgCl2 (approximately 1.5-fold), but were not significantly cross-resistant to hyperthermia (43 degrees), 254 nm UV light, 137Cs gamma-rays, and 42-MeV (p-->Be+) fast neutrons. As regards their biochemical status, AG8 and AA8 cells contain similar non-protein sulfhydryl levels per milligram of protein. Catalase activity (assessed by both spectrophotometry and polarogr...
    Treatment of cultured mammalian cells with three different carcinogens, namely methylmethane sulphonate (MMS), chromate and 254 U.V. radiation, produces DNA single strand breaks (SSB) in cultured mammalian cells. The rate of removal of... more
    Treatment of cultured mammalian cells with three different carcinogens, namely methylmethane sulphonate (MMS), chromate and 254 U.V. radiation, produces DNA single strand breaks (SSB) in cultured mammalian cells. The rate of removal of these lesions is not affected by exposure to 50 Hz electric (0.2 - 20 kV/m), magnetic (0.0002-0.2 mT), or combined electric and magnetic fields. These results indicate that, under the experimental conditions utilized in this study, 50 Hz electric, magnetic and electromagnetic fields (over a wide range of intensities) do not affect the machinery involved in the repair of DNA SSBs generated by different carcinogens in three different cultured mammalian cell lines, making it unlikely that field exposure enhances the ability of these carcinogens to induce transformation via inhibition of DNA repair.
    Pharmacologically attainable concentrations of ascorbic acid are highly toxic for U937 cells (a human promyelocytic cell line), and this response appears to be mediated by H2O2. This inference finds experimental support in the following... more
    Pharmacologically attainable concentrations of ascorbic acid are highly toxic for U937 cells (a human promyelocytic cell line), and this response appears to be mediated by H2O2. This inference finds experimental support in the following observations: 1) toxic levels of H2O2 are readily generated upon dissolution of survival-range concentrations of ascorbic acid in the culture medium; 2) the lethal effects elicited by ascorbic acid or reagent H2O2 are prevented by the addition of either catalase or the intracellular iron chelator o-phenanthroline and are characterized by similar temporal dependence; 3) U937 cells resistant to hydrogen peroxide are cross-resistant to ascorbic acid; 4) under the conditions utilized in this study, H2O2 and ascorbate promote similar modes of cell death (i.e., necrosis); and 5) cell killing provoked by H2O2 or ascorbate is an inverse function of cell density and is suppressed by coculturing U937 target cells with human erythrocytes (at a density far below...
    Exposure of cultured mammalian cells to 50 Hz electric (0.2-20 kV/m), magnetic (0.002-2 G), or combined electric and magnetic fields did not affect the rate of repair of DNA single strand breaks (SSB) induced by hydrogen peroxide. The... more
    Exposure of cultured mammalian cells to 50 Hz electric (0.2-20 kV/m), magnetic (0.002-2 G), or combined electric and magnetic fields did not affect the rate of repair of DNA single strand breaks (SSB) induced by hydrogen peroxide. The same lack of effect was observed on the repair of both DNA SSBs and DNA double strand breaks (DSBs) in cells treated with the cocktail hydrogen peroxide/L-Histidine. These results indicate that exposure to electric and/or magnetic fields does not affect the machinery involved in the repair of DNA lesions in oxidatively injured cells thus suggesting that it is unlikely that field exposure might induce changes in the response of the cells to the tumor promoting or carcinogenic effects elicited by reactive oxygen species.
    Structural analogues of benzamide (BA) containing a sulfur atom were tested for their ability to inhibit the enzyme poly(ADP-ribose)transferase (ADPRT) in cultured Chinese Hamster Ovary (CHO) cells. These compounds were benzene... more
    Structural analogues of benzamide (BA) containing a sulfur atom were tested for their ability to inhibit the enzyme poly(ADP-ribose)transferase (ADPRT) in cultured Chinese Hamster Ovary (CHO) cells. These compounds were benzene sulfonamide (BSA), thiobenzamide (TB) and 3-thiophene carboxamide (TCA) and their activity was compared with that of benzamide in a number of experimental systems. Results have shown that substitution of the carboxamide function with a sulfonamide group produces an almost complete loss of the enzyme inhibiting activity. Also inactive was TB which however was found to display inhibition of the DNA damaging effect of hydrogen peroxide, thus suggesting a hydroxyl radical scavenging effect of TB. TCA, an isostere of BA, produced some inhibition of ADPRT, although its activity was markedly lower than that of the parental drug. Therefore, these results indicate that: 1) ADPRT inhibiting activity is inverse function of dipole moments, hydrogen bonding strength and s...
    The effect of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser... more
    The effect of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser extent than in normal cells, as might have been expected since H2O2 is a radiomimetic agent. On the contrary, 4 AT cell lines displayed a higher sensitivity to the inhibitory effect of H2O2 on DNA synthesis than 2 normal cell lines. Comparable levels of cytotoxicity were detected in cell viability studies. Furthermore, neither the level of DNA breakage produced by H2O2, nor the rate of repair of these lesions was significantly different in normal and AT cells. Together, these results indicate that the AT cell lines utilized in this study are not hypersensitive to the oxidant. It is suggested that H2O2 may not induce lethality via the direct action of the hydroxyl radical (OH.).

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