Tania Fiaschi - Academia.edu (original) (raw)

Papers by Tania Fiaschi

Molecular Reproduction and Development, 2020

Among the follicular fluid (FF) components promoting the development of the oocyte are included g... more Among the follicular fluid (FF) components promoting the development of the oocyte are included glycoproteins, several fatty acids, and steroid hormones synthesized by the dominant follicle. For this, the analysis of the metabolites present in FF can determine the quality of the oocyte. FF composition is in part determined by local follicular metabolic processes and in part a plasma transudate. Since the causes of impaired fertility may be due to a metabolic imbalance, metabolomics is useful to identify low molecular weight metabolites. Oxidative stress is involved in human infertility and the use of metabolomics can be crucial to identify which other metabolites besides reactive oxygen species are involved in oxidative stress correlated to infertility. To obtain new information on the study of signaling molecules in FF, the knowledge of the lipid content will be important to improve information on the understanding of follicular development. The objective of this study is to identi...

Biochemical Journal, 1997

The organ common-type (CT) isoenzyme of acylphosphatase is inactivated by Woodward's reagent ... more The organ common-type (CT) isoenzyme of acylphosphatase is inactivated by Woodward's reagent K (WRK) (N-ethyl-5-phenylisoxazolium-3ʹ-sulphonate) at pH 6.0. The inactivation reaction follows apparent pseudo first-order kinetics. The dependence of the reciprocal of the pseudo first-order kinetic constant (kobs) on the reciprocal WRK concentration reveals saturation kinetics, suggesting that the WRK forms a reversible complex with the enzyme before causing inactivation. Competitive inhibitors, such as inorganic phosphate and ATP, protect the enzyme from WRK inactivation, suggesting that this reagent acts at or near to the enzyme active site. The reagent-enzyme adduct, which elicits a strong absorption band with λmax at 346 nm, was separated from unreacted enzyme by reverse phase HPLC and the modified protein was cleaved with endoproteinase Glu-C to produce fragments. The HPLC fractionation gave two reagent-labelled peptides (peak 1 and peak 2) that were analysed by ion-spray MS and...

Cells, 2022

Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscl... more Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscle, has insulin-sensitizing and anti-inflammatory properties. Sphingosine 1-phosphate (S1P) is reported to act as effector of diverse biological actions of Adn in different tissues. S1P is a bioactive sphingolipid synthesized by the phosphorylation of sphingosine catalyzed by sphingosine kinase (SK) 1 and 2. Consolidated findings support the key role of S1P in the biology of skeletal muscle. Methods and Results: Here we provide experimental evidence that S1P signalling is modulated by globular Adn treatment being able to increase the phosphorylation of SK1/2 as well as the mRNA expression levels of S1P4 in C2C12 myotubes. These findings were confirmed by LC-MS/MS that showed an increase of S1P levels after Adn treatment. Notably, the involvement of S1P axis in Adn action was highlighted since, when SK1 and 2 were inhibited by PF543 and ABC294640 inhibitors, respectively, not only the elec...

Biomedicines, 2021

Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipy... more Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, dis...

Molecular Reproduction and Development, 2020

Research has been focused on determining the follicular microenviroment produced by the theca and... more Research has been focused on determining the follicular microenviroment produced by the theca and granulosa cells since the molecular characterisation of this body fluid could lead to the understanding of several fertility problems. Oxidative stress may be one of the factors involved in female infertility since it plays a key role in the modulation of oocyte maturation and finally pregnancy. An increase in oxidative stress is correlated with inflammation and intense research was developed to understand the interaction between inflammation and adiponectin, based on the fact that many adipokines are inflammation related proteins linked to reactive oxygen species production. The aim of this study is to investigate the correlation between total adiponectin levels and oxidative stress amount in the serum and follicular fluid (FF) of women who undergone in vitro fertilization. Moreover we verified the expression of adiponectin in granulosa and cumulus cells. To clarify the predictive valu...

Medicinal Research Reviews, 2021

Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthri... more Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity observed both in vitro and in vivo tumor models. In this review, we analysed studies in which Auranofin was used as a single drug or in combination with other molecules to enhance their anticancer activity or to overcome chemoresistance. The analysis of different targets/pathways affected by this drug in different cancer types has allowed us to highlight several interesting targets and effects of Auranofin besides the already well-known inhibition of thioredoxin reductase. Among these targets, inhibitory-κB kinase, deubiquitinates, protein kinase C iota have been frequently suggested. To rationalize the effects of Auranofin by a system biology-like approach, we exploited transcriptomic data obtained from a wide range of cell models, extrapolating the data deposited in the Connectivity Maps website and we attempted to provide a general conclusion and discussed the major points that need further investigation.

Gold and ruthenium compounds hold today great promise as new metallodrugs for treatment of human ... more Gold and ruthenium compounds hold today great promise as new metallodrugs for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on their molecular mechanisms in previous studies we performed proteomic analysis in the A2780 human ovarian cancer cell line, after treatment with four different gold and two ruthenium compounds. To gain a better interpretation of their cellular effects we reported here the bioinformatic analysis of proteomic data that confirmed the action of these metallodrugs on previously identified signaling pathways such as glucose metabolism, protein folding, and cell division cycle and apoptosis. In addition, this new study pointed out the involvement of novel pathways such as synthesis and degradation of purine/pyrimidine nucleotides as well mitochondrial energy metabolism. These findings strengthen the idea of energy metabolism and mitochondrial function as possible target of both gold and ruthenium compound in...

Objective: Abdominal aortic aneurysm (AAA) affects up to 9% of adults, and the incidence of asymp... more Objective: Abdominal aortic aneurysm (AAA) affects up to 9% of adults, and the incidence of asymptomatic and ruptured AAA currently accounts for 1–2% of male deaths. A number of studies have applied classical proteomics methodology to identify plasma biomarkers of AAA. The use of a systems biology protein-protein interaction network analysis on proteomics results can reveal novel mechanisms. Methods: We performed a bioinformatics analysis on a compiled set of proteins previously identified in multiple proteomics studies. Results from a total of nine papers were identified and included in the analysis. The 64 proteins related to AAA were first analyzed by over-representation analysis (ORA) using Webgestalt. Afterwards, the same input list was submitted to BioProfiling. This portal used statistical methodology for the network based interpretation of the protein list (Rspider, PPIspider). The networks obtained by both Reactome and PPI analysis were further analyzed by ORA using the JEP...

iScience, 2021

Summary Development of biological tissues in vitro is not a trivial task and requires the correct... more Summary Development of biological tissues in vitro is not a trivial task and requires the correct maturation of the selected cell line. To this aim, many attempts were done mainly by mimicking the biological environment using micro/nanopatterned or stimulated scaffolds. However, the obtainment of functional tissues in vitro is still far from being achieved. In contrast with the standard methods, we here present an easy approach for the maturation of myotubes toward the reproduction of muscular tissue. By using liquid crystalline networks with different stiffness and molecular alignment, we demonstrate how the material itself can give favorable interactions with myoblasts helping a correct differentiation. Electrophysiological studies demonstrate that myotubes obtained on these polymers have more adult-like morphology and better functional features with respect to those cultured on standard supports. The study opens to a platform for the differentiation of other cell lines in a simple and scalable way.

Journal of Cell Science, 2002

Uncontrolled activation of receptor tyrosine kinases (RTKs) is implicated in the proliferation of... more Uncontrolled activation of receptor tyrosine kinases (RTKs) is implicated in the proliferation of cancerous cells, and deficiencies in RTKs results in pathological conditions such as developmental abnormalities and immunodeficiencies. Tight regulation of RTK cascades is therefore critical for eliciting an appropriate type and level of response to external stimuli. The aim of this work is to compare different RTK downregulation mechanisms, such as ligandinduced internalisation, ubiquitin-mediated proteolysis and dephosphorylation by protein phosphotyrosine phosphatase (PTPs). We choose platelet-derived growth factor receptor (PDGF-r) in NIH3T3 cells as a model of RTK. Our data suggest that PDGF-r internalisation could be mainly considered as a positive signaling system, as it is involved in MAPK activation rather than a downregulation of the mitotic signal. Inhibition of receptor ubiquitination does not result in regulation of PDGF-r tyrosine phosphorylation and does not lead to vari...

Biomedicines, 2021

Cachexia is a disorder associated with several pathologies, including cancer. In this paper, we d... more Cachexia is a disorder associated with several pathologies, including cancer. In this paper, we describe how cachexia is induced in myotubes by a metabolic shift towards fermentation, and the block of this metabolic modification prevents the onset of the cachectic phenotype. Cachectic myotubes, obtained by the treatment with conditioned medium from murine colon carcinoma cells CT26, show increased glucose uptake, decreased oxygen consumption, altered mitochondria, and increased lactate production. Interestingly, the block of glycolysis by 2-deoxy-glucose or lactate dehydrogenase inhibition by oxamate prevents the induction of cachexia, thus suggesting that this metabolic change is greatly involved in cachexia activation. The treatment with 2-deoxy-glucose or oxamate induces positive effects also in mitochondria, where mitochondrial membrane potential and pyruvate dehydrogenase activity became similar to control myotubes. Moreover, in myotubes treated with interleukin-6, cachectic ph...

International Journal of Molecular Sciences, 2020

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The h... more Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study i...

Free Radical Research, 2019

The evidence about the health benefits of regular physical activity is well established. Exercise... more The evidence about the health benefits of regular physical activity is well established. Exercise intensity is a significant variable and structured high-intensity interval training (HIIT) has been demonstrated to improve both whole-body and skeletal muscle metabolic health in different populations. Conversely, fatigue accumulation, if not resolved, leads to overwork, chronic fatigue syndrome (CFS), overtraining syndrome up to alterations of endocrine function, immune, systemic inflammation, and organic diseases with health threat. In response to temporary increases in stress during training, some athletes are unable to maintain sufficient caloric intake, thus suffering a negative energy balance that causes further stress. The regulation of the energy balance is controlled by the central nervous system through an elaborate interaction of the signaling that involves different tissues such as leptin, adiponectin and ghrelin whose provide important feedback to the hypothalamus to regulate the energy balance. Although exercise-induced reactive oxygen species are required for normal force production in muscle, high levels of ROS appear to promote contractile dysfunction. However, a high level of oxidative stress in may induce a rise in inflammatory markers and a disregulation in expression of adiponectin, leptin and grelin.

The Journal of Sports Medicine and Physical Fitness, 2019

BACKGROUND Several authors reported evidences for postactivation potentiation (PAP) but so far, f... more BACKGROUND Several authors reported evidences for postactivation potentiation (PAP) but so far, few studies suggested suitable methods for use it to improve performance. On the other hand, it is well known that a fatiguing exercise can leads to a temporary imbalance between the production of reactive oxygen species (ROS) and their disposal. The purpose of our research was to evaluate the effects on performance and plasma oxidative stress of a specific program of conditioning in replacement of traditional sequences of warm-up. METHODS We proposed a protocol of specific conditioning exercises and the effect on performance is evaluated by measuring leg power using the counter movement jump performed at different time after the protocol in athletes trained for different sports. Moreover, we measured the antioxidant capacity and the plasma levels of reactive oxygen metabolites before and at different times after the conditioning. RESULTS Considering the evaluation of explosive force of athletes subdivided for the different sports we noticed that the swimmer and tennis players do not show a significant improvement in it after conditioning while the soccer and rugby players shown a significant prolongation of the effect. Moreover, the analysis of oxidative stress shows that it is not influenced by the PAP protocol used. CONCLUSIONS We can conclude that our specific protocol seems effective in improving performance in athletes who used training methods able to affect their explosive strength like soccer players. On the contrary, in our proposed program this effect seems to be less evident in athletes who used resistance-training programs.

International Journal of Molecular Sciences, 2019

Adiponectin, the most abundant secreted adipokine, has received great attention from the scientif... more Adiponectin, the most abundant secreted adipokine, has received great attention from the scientific community since its discovery [...]

Journal of Molecular Medicine, 2019

International Journal of Molecular Sciences, 2019

In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, ant... more In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, anti-inflammatory, insulin-sensitizing to regenerative roles. Despite the important functions exerted by adiponectin, the study of the hormone in myopathies is still marginal. Myopathies include inherited and non-inherited/acquired neuromuscular pathologies characterized by muscular degeneration and weakness. This review reports current knowledge about adiponectin in myopathies, regarding in particular the role of adiponectin in some hereditary myopathies (as Duchenne muscular dystrophy) and non-inherited/acquired myopathies (such as idiopathic inflammatory myopathies and fibromyalgia). These studies show that some myopathies are characterized by decreased concentration of plasma adiponectin and that hormone replenishment induces beneficial effects in the diseased muscles. Overall, these findings suggest that adiponectin could constitute a future new therapeutic approach for the improvement...

Molecular Reproduction and Development, 2020

Among the follicular fluid (FF) components promoting the development of the oocyte are included g... more Among the follicular fluid (FF) components promoting the development of the oocyte are included glycoproteins, several fatty acids, and steroid hormones synthesized by the dominant follicle. For this, the analysis of the metabolites present in FF can determine the quality of the oocyte. FF composition is in part determined by local follicular metabolic processes and in part a plasma transudate. Since the causes of impaired fertility may be due to a metabolic imbalance, metabolomics is useful to identify low molecular weight metabolites. Oxidative stress is involved in human infertility and the use of metabolomics can be crucial to identify which other metabolites besides reactive oxygen species are involved in oxidative stress correlated to infertility. To obtain new information on the study of signaling molecules in FF, the knowledge of the lipid content will be important to improve information on the understanding of follicular development. The objective of this study is to identi...

Biochemical Journal, 1997

The organ common-type (CT) isoenzyme of acylphosphatase is inactivated by Woodward's reagent ... more The organ common-type (CT) isoenzyme of acylphosphatase is inactivated by Woodward's reagent K (WRK) (N-ethyl-5-phenylisoxazolium-3ʹ-sulphonate) at pH 6.0. The inactivation reaction follows apparent pseudo first-order kinetics. The dependence of the reciprocal of the pseudo first-order kinetic constant (kobs) on the reciprocal WRK concentration reveals saturation kinetics, suggesting that the WRK forms a reversible complex with the enzyme before causing inactivation. Competitive inhibitors, such as inorganic phosphate and ATP, protect the enzyme from WRK inactivation, suggesting that this reagent acts at or near to the enzyme active site. The reagent-enzyme adduct, which elicits a strong absorption band with λmax at 346 nm, was separated from unreacted enzyme by reverse phase HPLC and the modified protein was cleaved with endoproteinase Glu-C to produce fragments. The HPLC fractionation gave two reagent-labelled peptides (peak 1 and peak 2) that were analysed by ion-spray MS and...

Cells, 2022

Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscl... more Background: Adiponectin (Adn), released by adipocytes and other cell types such as skeletal muscle, has insulin-sensitizing and anti-inflammatory properties. Sphingosine 1-phosphate (S1P) is reported to act as effector of diverse biological actions of Adn in different tissues. S1P is a bioactive sphingolipid synthesized by the phosphorylation of sphingosine catalyzed by sphingosine kinase (SK) 1 and 2. Consolidated findings support the key role of S1P in the biology of skeletal muscle. Methods and Results: Here we provide experimental evidence that S1P signalling is modulated by globular Adn treatment being able to increase the phosphorylation of SK1/2 as well as the mRNA expression levels of S1P4 in C2C12 myotubes. These findings were confirmed by LC-MS/MS that showed an increase of S1P levels after Adn treatment. Notably, the involvement of S1P axis in Adn action was highlighted since, when SK1 and 2 were inhibited by PF543 and ABC294640 inhibitors, respectively, not only the elec...

Biomedicines, 2021

Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipy... more Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, dis...

Molecular Reproduction and Development, 2020

Research has been focused on determining the follicular microenviroment produced by the theca and... more Research has been focused on determining the follicular microenviroment produced by the theca and granulosa cells since the molecular characterisation of this body fluid could lead to the understanding of several fertility problems. Oxidative stress may be one of the factors involved in female infertility since it plays a key role in the modulation of oocyte maturation and finally pregnancy. An increase in oxidative stress is correlated with inflammation and intense research was developed to understand the interaction between inflammation and adiponectin, based on the fact that many adipokines are inflammation related proteins linked to reactive oxygen species production. The aim of this study is to investigate the correlation between total adiponectin levels and oxidative stress amount in the serum and follicular fluid (FF) of women who undergone in vitro fertilization. Moreover we verified the expression of adiponectin in granulosa and cumulus cells. To clarify the predictive valu...

Medicinal Research Reviews, 2021

Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthri... more Auranofin is an oral gold(I) compound, initially developed for the treatment of rheumatoid arthritis. Currently, Auranofin is under investigation for oncological application within a drug repurposing plan due to the relevant antineoplastic activity observed both in vitro and in vivo tumor models. In this review, we analysed studies in which Auranofin was used as a single drug or in combination with other molecules to enhance their anticancer activity or to overcome chemoresistance. The analysis of different targets/pathways affected by this drug in different cancer types has allowed us to highlight several interesting targets and effects of Auranofin besides the already well-known inhibition of thioredoxin reductase. Among these targets, inhibitory-κB kinase, deubiquitinates, protein kinase C iota have been frequently suggested. To rationalize the effects of Auranofin by a system biology-like approach, we exploited transcriptomic data obtained from a wide range of cell models, extrapolating the data deposited in the Connectivity Maps website and we attempted to provide a general conclusion and discussed the major points that need further investigation.

Gold and ruthenium compounds hold today great promise as new metallodrugs for treatment of human ... more Gold and ruthenium compounds hold today great promise as new metallodrugs for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on their molecular mechanisms in previous studies we performed proteomic analysis in the A2780 human ovarian cancer cell line, after treatment with four different gold and two ruthenium compounds. To gain a better interpretation of their cellular effects we reported here the bioinformatic analysis of proteomic data that confirmed the action of these metallodrugs on previously identified signaling pathways such as glucose metabolism, protein folding, and cell division cycle and apoptosis. In addition, this new study pointed out the involvement of novel pathways such as synthesis and degradation of purine/pyrimidine nucleotides as well mitochondrial energy metabolism. These findings strengthen the idea of energy metabolism and mitochondrial function as possible target of both gold and ruthenium compound in...

Objective: Abdominal aortic aneurysm (AAA) affects up to 9% of adults, and the incidence of asymp... more Objective: Abdominal aortic aneurysm (AAA) affects up to 9% of adults, and the incidence of asymptomatic and ruptured AAA currently accounts for 1–2% of male deaths. A number of studies have applied classical proteomics methodology to identify plasma biomarkers of AAA. The use of a systems biology protein-protein interaction network analysis on proteomics results can reveal novel mechanisms. Methods: We performed a bioinformatics analysis on a compiled set of proteins previously identified in multiple proteomics studies. Results from a total of nine papers were identified and included in the analysis. The 64 proteins related to AAA were first analyzed by over-representation analysis (ORA) using Webgestalt. Afterwards, the same input list was submitted to BioProfiling. This portal used statistical methodology for the network based interpretation of the protein list (Rspider, PPIspider). The networks obtained by both Reactome and PPI analysis were further analyzed by ORA using the JEP...

iScience, 2021

Summary Development of biological tissues in vitro is not a trivial task and requires the correct... more Summary Development of biological tissues in vitro is not a trivial task and requires the correct maturation of the selected cell line. To this aim, many attempts were done mainly by mimicking the biological environment using micro/nanopatterned or stimulated scaffolds. However, the obtainment of functional tissues in vitro is still far from being achieved. In contrast with the standard methods, we here present an easy approach for the maturation of myotubes toward the reproduction of muscular tissue. By using liquid crystalline networks with different stiffness and molecular alignment, we demonstrate how the material itself can give favorable interactions with myoblasts helping a correct differentiation. Electrophysiological studies demonstrate that myotubes obtained on these polymers have more adult-like morphology and better functional features with respect to those cultured on standard supports. The study opens to a platform for the differentiation of other cell lines in a simple and scalable way.

Journal of Cell Science, 2002

Uncontrolled activation of receptor tyrosine kinases (RTKs) is implicated in the proliferation of... more Uncontrolled activation of receptor tyrosine kinases (RTKs) is implicated in the proliferation of cancerous cells, and deficiencies in RTKs results in pathological conditions such as developmental abnormalities and immunodeficiencies. Tight regulation of RTK cascades is therefore critical for eliciting an appropriate type and level of response to external stimuli. The aim of this work is to compare different RTK downregulation mechanisms, such as ligandinduced internalisation, ubiquitin-mediated proteolysis and dephosphorylation by protein phosphotyrosine phosphatase (PTPs). We choose platelet-derived growth factor receptor (PDGF-r) in NIH3T3 cells as a model of RTK. Our data suggest that PDGF-r internalisation could be mainly considered as a positive signaling system, as it is involved in MAPK activation rather than a downregulation of the mitotic signal. Inhibition of receptor ubiquitination does not result in regulation of PDGF-r tyrosine phosphorylation and does not lead to vari...

Biomedicines, 2021

Cachexia is a disorder associated with several pathologies, including cancer. In this paper, we d... more Cachexia is a disorder associated with several pathologies, including cancer. In this paper, we describe how cachexia is induced in myotubes by a metabolic shift towards fermentation, and the block of this metabolic modification prevents the onset of the cachectic phenotype. Cachectic myotubes, obtained by the treatment with conditioned medium from murine colon carcinoma cells CT26, show increased glucose uptake, decreased oxygen consumption, altered mitochondria, and increased lactate production. Interestingly, the block of glycolysis by 2-deoxy-glucose or lactate dehydrogenase inhibition by oxamate prevents the induction of cachexia, thus suggesting that this metabolic change is greatly involved in cachexia activation. The treatment with 2-deoxy-glucose or oxamate induces positive effects also in mitochondria, where mitochondrial membrane potential and pyruvate dehydrogenase activity became similar to control myotubes. Moreover, in myotubes treated with interleukin-6, cachectic ph...

International Journal of Molecular Sciences, 2020

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The h... more Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study i...

Free Radical Research, 2019

The evidence about the health benefits of regular physical activity is well established. Exercise... more The evidence about the health benefits of regular physical activity is well established. Exercise intensity is a significant variable and structured high-intensity interval training (HIIT) has been demonstrated to improve both whole-body and skeletal muscle metabolic health in different populations. Conversely, fatigue accumulation, if not resolved, leads to overwork, chronic fatigue syndrome (CFS), overtraining syndrome up to alterations of endocrine function, immune, systemic inflammation, and organic diseases with health threat. In response to temporary increases in stress during training, some athletes are unable to maintain sufficient caloric intake, thus suffering a negative energy balance that causes further stress. The regulation of the energy balance is controlled by the central nervous system through an elaborate interaction of the signaling that involves different tissues such as leptin, adiponectin and ghrelin whose provide important feedback to the hypothalamus to regulate the energy balance. Although exercise-induced reactive oxygen species are required for normal force production in muscle, high levels of ROS appear to promote contractile dysfunction. However, a high level of oxidative stress in may induce a rise in inflammatory markers and a disregulation in expression of adiponectin, leptin and grelin.

The Journal of Sports Medicine and Physical Fitness, 2019

BACKGROUND Several authors reported evidences for postactivation potentiation (PAP) but so far, f... more BACKGROUND Several authors reported evidences for postactivation potentiation (PAP) but so far, few studies suggested suitable methods for use it to improve performance. On the other hand, it is well known that a fatiguing exercise can leads to a temporary imbalance between the production of reactive oxygen species (ROS) and their disposal. The purpose of our research was to evaluate the effects on performance and plasma oxidative stress of a specific program of conditioning in replacement of traditional sequences of warm-up. METHODS We proposed a protocol of specific conditioning exercises and the effect on performance is evaluated by measuring leg power using the counter movement jump performed at different time after the protocol in athletes trained for different sports. Moreover, we measured the antioxidant capacity and the plasma levels of reactive oxygen metabolites before and at different times after the conditioning. RESULTS Considering the evaluation of explosive force of athletes subdivided for the different sports we noticed that the swimmer and tennis players do not show a significant improvement in it after conditioning while the soccer and rugby players shown a significant prolongation of the effect. Moreover, the analysis of oxidative stress shows that it is not influenced by the PAP protocol used. CONCLUSIONS We can conclude that our specific protocol seems effective in improving performance in athletes who used training methods able to affect their explosive strength like soccer players. On the contrary, in our proposed program this effect seems to be less evident in athletes who used resistance-training programs.

International Journal of Molecular Sciences, 2019

Adiponectin, the most abundant secreted adipokine, has received great attention from the scientif... more Adiponectin, the most abundant secreted adipokine, has received great attention from the scientific community since its discovery [...]

Journal of Molecular Medicine, 2019

International Journal of Molecular Sciences, 2019

In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, ant... more In skeletal muscle, adiponectin has varied and pleiotropic functions, ranging from metabolic, anti-inflammatory, insulin-sensitizing to regenerative roles. Despite the important functions exerted by adiponectin, the study of the hormone in myopathies is still marginal. Myopathies include inherited and non-inherited/acquired neuromuscular pathologies characterized by muscular degeneration and weakness. This review reports current knowledge about adiponectin in myopathies, regarding in particular the role of adiponectin in some hereditary myopathies (as Duchenne muscular dystrophy) and non-inherited/acquired myopathies (such as idiopathic inflammatory myopathies and fibromyalgia). These studies show that some myopathies are characterized by decreased concentration of plasma adiponectin and that hormone replenishment induces beneficial effects in the diseased muscles. Overall, these findings suggest that adiponectin could constitute a future new therapeutic approach for the improvement...