Mario F Tecce | University of Salerno (original) (raw)
Papers by Mario F Tecce
International Journal of Molecular Sciences, Dec 31, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Cellular Physiology, Sep 28, 2017
† This article has been accepted for publication and undergone full peer review but has not been ... more † This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Polyunsaturated fatty acids (PUFA) are nutrients with relevant biological activities and preventi... more Polyunsaturated fatty acids (PUFA) are nutrients with relevant biological activities and preventive effects of cardiovascular and neoplastic diseases and therefore it is important to characterize the molecular processes involved in their action. On this purpose, we evaluated the effect of PUFA on Stearoyl-CoA Desaturase 1 (SCD1), the rate limiting enzyme in PUFA biosynthesis and on Sterol Regulatory Element Binding Protein (SREBP-1c), a transcription factor which directly modulate its expression. SCD1, introducing a double bond in fatty acyl-CoA substrates, is of particular interest since alterations of its activity seem to be involved in several dyslipidemic conditions. Considering that Liver X Receptor (LXR) activation induces lipogenic pathways also trough SREBP-1c regulation, we analyzed the effect of a specific LXR agonist molecule, T0901317, on a human hepatoma cell line (HepG2). Our data show a significant induction of SREBP-1c and SCD1 by T0901317. In addition, we analyzed some putative transcription factor binding sites within SCD1 gene promoter sequence. Using chromatin immunoprecipitation (ChIP) assay, we identified a functional binding site (-789/-659 SRE1 region). Data show an increased SREBP-1c binding after LXR activation. We analyzed the effects of individual PUFA on this mechanism. Results show that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) are able to reduce SREBP-1c binding on SRE1 region, while a saturated stearic acid (SA) did not give any effect. To further understand if PUFA produce these effects through a direct interaction with LXR, we have also carried out a surface plasmon resonance (SPR) analysis which showed a direct binding of DHA, EPA and AA on LXR transcription factor, while no interaction was found with saturated SA, indicating that these effects are specific. We conclude that analyzed PUFA selectively down-regulate lipogenic pathways through LXR inhibition and consequent SREBP-1c and SCD1 expression down-regulation
International Conference Bio & Food Electrotechnologies BFE 2012, 2012
European Journal of Medicinal Chemistry, 2022
The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression an... more The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression and exacerbation of different aggressive tumors such as glioblastoma, hepatocarcinoma, pancreas, bone, and triple-negative breast cancer. Few chemotypes are currently available as selective GLS-1 inhibitors, and still, fewer of them are at the clinical stage. In the present paper, starting from a naturally-inspired antitumor compound library, metabolomics has been used to putatively identify the molecular mechanism underlying biological activity. GLS-1 was identified as a potential target. Biochemical analysis confirmed the hypothesis leading to the identification of a new hit compound acting as a GLS-1 selective inhibitor (IC50 = 3.96 ± 1.05 μM), compared to the GLS-2 isoform (IC50 = 12.90 ± 0.87 μM), with remarkable antitumor potency over different aggressive tumor cell lines. Molecular modelling studies revealed new insight into the drug-target interaction providing robust SAR clues for the rational hit-to-lead development. The approach undertaken underlines the wide potential of metabolomics applied to drug discovery, particularly in target identification and hit discovery following phenotype screening.
There are many evidence in scientific literature that relate to causal nutrition and risk of dise... more There are many evidence in scientific literature that relate to causal nutrition and risk of disease. The concept that proper nutrition can be a significant protective factor that can significantly affect the risk of cardiovascular and neoplastic diseases is widely demonstrated by scientific literature. Evidence has been shown at an epidemiological level first: it has been shown that a certain qualitative and quantitative composition of nutritional support can be both a protective factor that can reduce the incidence of pathologies and, in other dietary formulations, a a causal factor that can increase its etiopathogenetic effect. It is well known, for example, how the incidence of cardiovascular disease is closely related to the lifestyle of the person, and in particular the excess energy and / or lipids, particularly saturated. Likewise, the characteristics of the diet also significantly affect the incidence of neoplastic diseases. It is believed that on the combination of neoplastic and cardiovascular diseases, which then represent the first two causes of death in the most developed countries, at least one-third of case histories recognize diet as the main causal factor. While the first evidence of nutrition and health relationship has come from epidemiological data on populations, subsequent research is progressively identifying the molecular pathophysiological mechanisms at the basis of the observed effects. The evidence that they are showing shows significant mechanisms involved in nutrition. Nutrients, ie molecules absorbed within the body by the digestive tract, are classically divided into energetic and structural, wanting to indicate with what food-derived molecules can or give the energy needed for various metabolic processes or become part of the cellular and tissue structures of the body. The study of the relationship between nutrition and health has recently added to those categories that of chemiopreventive or bioactive nutrients. With this term we want to point out those molecules made by the diet, for which, regardless of their role as nutritional energy or structural, it is noticed how the magnitude of their representation in the diet is associated with a reduction in the risk of pathologies, sometimes being also known explanations of the molecular mechanism with which this occurs. For example, polyunsaturated omega-3fatty acids derived from diet seem to be the basis of the mechanism for which epidemiology has shown that a diet with various weekly fish portions significantly reduces cardiovascular risk. Many other substances, often with protective power against the mechanisms of oxidative cell damage, are increasingly placed under careful attention to explain the relationship between nutrition and health at the molecular level.
European Journal of Medicinal Chemistry, 2021
Acta Diabetologica, 2020
Aims Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key f... more Aims Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key features of diabetes mellitus, being both diagnostic parameters and pathogenetic mechanisms. Vascular endothelial growth factor (VEGF) is importantly implicated in the physiology and pathology of blood vessels, including diabetic vascular damage. Methods These factors certainly affect endothelial cells, and to evaluate mechanisms involved, we took advantage of telomerase-immortalized human microvascular endothelial (TIME) cells. TIME cells were exposed to different glucose concentrations and to VEGF treatments. Culture conditions also included the use of basement membrane extract, as an in vitro differentiation model. Cell morphology was then evaluated in the different conditions, and cellular proteins were extracted to analyze specific protein products by Western blot. Results High glucose concentrations and VEGF did substantially affect neither morphology nor growth of cultured TIME cells, while both considerably increased differentiation into "capillary-like" structures when cells were cultured on basement membrane extract. Conclusions Under these conditions, high glucose concentration and VEGF also produced a short-term increase in pERK1/2 and p85 proteins, while total and phosphorylated AKT were not affected. These data suggest a direct angiogenetic effect of glucose, affecting intracellular transduction mechanisms with an action similar to that of VEGF. This effect on endothelial cell proliferation and differentiation could be part of pathogenetic mechanisms producing diabetic microvascular alterations.
PLOS ONE, 2020
Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease.... more Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutarylcoenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.
Integrative Food, Nutrition and Metabolism, 2017
Nutrigenomics will therefore be an individual genomic analysis aimed at examining the genome and ... more Nutrigenomics will therefore be an individual genomic analysis aimed at examining the genome and its expression in relation to the effects of nutrients derived from the diet. The different individual susceptibility to the effect of nutrients can however result in the fact that the effect of diet on gene expression is partly subject to variability [16-22]. Figure 1 wants to schematically represent how the relationship between exposure to bioactive nutrients in relation to the state of nutrition, which however concerns the development of nutritional situations in the long term and not individual moments, comes to affect the health of an individual, acting on the magnitude of the risk of disease. This effect, however, is carried out through a series of mechanisms that can greatly affect the characteristics. The bioactive nutrient can be variable absorbed as well as subsequently variably activated or inactivated. His biological activity will thus expose on specific molecular "targets" which may also be variable or modulable in relation to the genomic characteristics of the individual affecting its quality and quantity [22-25].
Journal of Cellular Physiology, May 26, 2015
Serum composition is linked to metabolic diseases not only to understand their pathogenesis but a... more Serum composition is linked to metabolic diseases not only to understand their pathogenesis but also for diagnostic purposes. Quality and quantity of nutritional intake can affect disease risk and serum composition. It is then possible that diet derived serum components directly affect pathogenetic mechanisms. To identify involved factors, we evaluated the effect on gene expression of direct addition of dyslipidemic human serum samples to cultured human hepatoma cells (HepG2). Sera were selected on the basis of cholesterol level, considering this parameter as mostly linked to dietary intake. Cells were treated with 32 sera from hypercholesterolemic and normocholesterolemic subjects to identify differentially regulated mRNAs using DNA microarray analysis. We identified several mRNAs with the highest modulations in cells treated with dyslipidemic sera versus cells treated with normal sera. Since the two serum groups had variable polyunsaturated fatty acids (PUFAs) contents, selected mRNAs were further assessed for their regulation by docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA). Four genes resulted both affected by serum composition and PUFAs: 3‐hydroxy‐3‐methylglutaryl‐CoenzymeA synthase 2 (HMGCS2), glutathione S‐transferase alpha 1 (GSTA1), liver expressed antimicrobial peptide 2 (LEAP2) and apolipoprotein M (ApoM). HMGCS2 expression appears the most relevant and was also found modulated via transcription factors peroxysome proliferator activated receptor α (PPARα) and forkhead box O1 (FoxO1). Our data indicate that expression levels of the selected mRNAs, primarily of HMGCS2, could represent a reference of nutritional intake, PUFAs effects and dyslipidemic diseases pathogenesis. J. Cell. Physiol. 230: 2059–2066, 2015. © 2015 Wiley Periodicals, Inc.
Central nervous system agents in medicinal chemistry, Jun 1, 2010
Bioelectromagnetics, Nov 23, 2010
Low-frequency (LF) electric fields (EFs) are currently used in clinical therapies of several bone... more Low-frequency (LF) electric fields (EFs) are currently used in clinical therapies of several bone diseases to increase bone regenerative processes. To identify possible molecular mechanisms involved in these processes, we evaluated the effects on cell cultures of 1 h exposures to the signal generated by an apparatus of current clinical use (frequency 60 kHz, frequency of the modulating signal 12.5 Hz, 50% duty cycle, peak-to-peak voltage 24.5 V). Two different human cell lines, bone SaOS-2 and liver HepG2, were used. Exposures significantly increased alkaline phosphatase (ALP) enzymatic activity in both cell lines. The increase was about 35% in SaOS-2 cells and about 80% in HepG2 cells and occurred in the first 4 h after exposure and decreased to almost no change by 24 h. Since ALP represents a typical marker of bone regeneration, these results represent a first molecular evidence of biological effects from 60 kHz EF exposures. The finding of similar effects in cells derived from two different tissues more likely indicates the effective operation of the mechanism in living organisms.
BENTHAM SCIENCE PUBLISHERS eBooks, Aug 18, 2010
Diseases and disorders, 2017
Histone acetyltransferase inhibitors are able to induce neuroprotection because of their antioxid... more Histone acetyltransferase inhibitors are able to induce neuroprotection because of their antioxidant properties, so, their therapeutic use in limiting neurological damage is strongly supported. Histone acetyltransferase inhibitors treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression and to repair the damaged structures. The acetylation and deacetylation of histones are involved in the regulation of gene expression and the regular function of histone acetyltransferases (HATs) and deacetylases (HDACs) provide regulatory steps for gene expression and cell cycle. Functional defects of these enzymes may lead to several diseases, including neurodegenerative disorders. The studies reported in the present review support the view that the histone acetyltransferase inhibitors may be a key modulatory element in the control of neurodegenerative disorders. This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data. Furthermore, these studies support the idea of developing novel pharmacotherapies with histone acetyltransferase inhibitors that selectively target specific area of CNS.
International Journal of Molecular Sciences, Dec 31, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Cellular Physiology, Sep 28, 2017
† This article has been accepted for publication and undergone full peer review but has not been ... more † This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Polyunsaturated fatty acids (PUFA) are nutrients with relevant biological activities and preventi... more Polyunsaturated fatty acids (PUFA) are nutrients with relevant biological activities and preventive effects of cardiovascular and neoplastic diseases and therefore it is important to characterize the molecular processes involved in their action. On this purpose, we evaluated the effect of PUFA on Stearoyl-CoA Desaturase 1 (SCD1), the rate limiting enzyme in PUFA biosynthesis and on Sterol Regulatory Element Binding Protein (SREBP-1c), a transcription factor which directly modulate its expression. SCD1, introducing a double bond in fatty acyl-CoA substrates, is of particular interest since alterations of its activity seem to be involved in several dyslipidemic conditions. Considering that Liver X Receptor (LXR) activation induces lipogenic pathways also trough SREBP-1c regulation, we analyzed the effect of a specific LXR agonist molecule, T0901317, on a human hepatoma cell line (HepG2). Our data show a significant induction of SREBP-1c and SCD1 by T0901317. In addition, we analyzed some putative transcription factor binding sites within SCD1 gene promoter sequence. Using chromatin immunoprecipitation (ChIP) assay, we identified a functional binding site (-789/-659 SRE1 region). Data show an increased SREBP-1c binding after LXR activation. We analyzed the effects of individual PUFA on this mechanism. Results show that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) are able to reduce SREBP-1c binding on SRE1 region, while a saturated stearic acid (SA) did not give any effect. To further understand if PUFA produce these effects through a direct interaction with LXR, we have also carried out a surface plasmon resonance (SPR) analysis which showed a direct binding of DHA, EPA and AA on LXR transcription factor, while no interaction was found with saturated SA, indicating that these effects are specific. We conclude that analyzed PUFA selectively down-regulate lipogenic pathways through LXR inhibition and consequent SREBP-1c and SCD1 expression down-regulation
International Conference Bio & Food Electrotechnologies BFE 2012, 2012
European Journal of Medicinal Chemistry, 2022
The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression an... more The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression and exacerbation of different aggressive tumors such as glioblastoma, hepatocarcinoma, pancreas, bone, and triple-negative breast cancer. Few chemotypes are currently available as selective GLS-1 inhibitors, and still, fewer of them are at the clinical stage. In the present paper, starting from a naturally-inspired antitumor compound library, metabolomics has been used to putatively identify the molecular mechanism underlying biological activity. GLS-1 was identified as a potential target. Biochemical analysis confirmed the hypothesis leading to the identification of a new hit compound acting as a GLS-1 selective inhibitor (IC50 = 3.96 ± 1.05 μM), compared to the GLS-2 isoform (IC50 = 12.90 ± 0.87 μM), with remarkable antitumor potency over different aggressive tumor cell lines. Molecular modelling studies revealed new insight into the drug-target interaction providing robust SAR clues for the rational hit-to-lead development. The approach undertaken underlines the wide potential of metabolomics applied to drug discovery, particularly in target identification and hit discovery following phenotype screening.
There are many evidence in scientific literature that relate to causal nutrition and risk of dise... more There are many evidence in scientific literature that relate to causal nutrition and risk of disease. The concept that proper nutrition can be a significant protective factor that can significantly affect the risk of cardiovascular and neoplastic diseases is widely demonstrated by scientific literature. Evidence has been shown at an epidemiological level first: it has been shown that a certain qualitative and quantitative composition of nutritional support can be both a protective factor that can reduce the incidence of pathologies and, in other dietary formulations, a a causal factor that can increase its etiopathogenetic effect. It is well known, for example, how the incidence of cardiovascular disease is closely related to the lifestyle of the person, and in particular the excess energy and / or lipids, particularly saturated. Likewise, the characteristics of the diet also significantly affect the incidence of neoplastic diseases. It is believed that on the combination of neoplastic and cardiovascular diseases, which then represent the first two causes of death in the most developed countries, at least one-third of case histories recognize diet as the main causal factor. While the first evidence of nutrition and health relationship has come from epidemiological data on populations, subsequent research is progressively identifying the molecular pathophysiological mechanisms at the basis of the observed effects. The evidence that they are showing shows significant mechanisms involved in nutrition. Nutrients, ie molecules absorbed within the body by the digestive tract, are classically divided into energetic and structural, wanting to indicate with what food-derived molecules can or give the energy needed for various metabolic processes or become part of the cellular and tissue structures of the body. The study of the relationship between nutrition and health has recently added to those categories that of chemiopreventive or bioactive nutrients. With this term we want to point out those molecules made by the diet, for which, regardless of their role as nutritional energy or structural, it is noticed how the magnitude of their representation in the diet is associated with a reduction in the risk of pathologies, sometimes being also known explanations of the molecular mechanism with which this occurs. For example, polyunsaturated omega-3fatty acids derived from diet seem to be the basis of the mechanism for which epidemiology has shown that a diet with various weekly fish portions significantly reduces cardiovascular risk. Many other substances, often with protective power against the mechanisms of oxidative cell damage, are increasingly placed under careful attention to explain the relationship between nutrition and health at the molecular level.
European Journal of Medicinal Chemistry, 2021
Acta Diabetologica, 2020
Aims Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key f... more Aims Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key features of diabetes mellitus, being both diagnostic parameters and pathogenetic mechanisms. Vascular endothelial growth factor (VEGF) is importantly implicated in the physiology and pathology of blood vessels, including diabetic vascular damage. Methods These factors certainly affect endothelial cells, and to evaluate mechanisms involved, we took advantage of telomerase-immortalized human microvascular endothelial (TIME) cells. TIME cells were exposed to different glucose concentrations and to VEGF treatments. Culture conditions also included the use of basement membrane extract, as an in vitro differentiation model. Cell morphology was then evaluated in the different conditions, and cellular proteins were extracted to analyze specific protein products by Western blot. Results High glucose concentrations and VEGF did substantially affect neither morphology nor growth of cultured TIME cells, while both considerably increased differentiation into "capillary-like" structures when cells were cultured on basement membrane extract. Conclusions Under these conditions, high glucose concentration and VEGF also produced a short-term increase in pERK1/2 and p85 proteins, while total and phosphorylated AKT were not affected. These data suggest a direct angiogenetic effect of glucose, affecting intracellular transduction mechanisms with an action similar to that of VEGF. This effect on endothelial cell proliferation and differentiation could be part of pathogenetic mechanisms producing diabetic microvascular alterations.
PLOS ONE, 2020
Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease.... more Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutarylcoenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.
Integrative Food, Nutrition and Metabolism, 2017
Nutrigenomics will therefore be an individual genomic analysis aimed at examining the genome and ... more Nutrigenomics will therefore be an individual genomic analysis aimed at examining the genome and its expression in relation to the effects of nutrients derived from the diet. The different individual susceptibility to the effect of nutrients can however result in the fact that the effect of diet on gene expression is partly subject to variability [16-22]. Figure 1 wants to schematically represent how the relationship between exposure to bioactive nutrients in relation to the state of nutrition, which however concerns the development of nutritional situations in the long term and not individual moments, comes to affect the health of an individual, acting on the magnitude of the risk of disease. This effect, however, is carried out through a series of mechanisms that can greatly affect the characteristics. The bioactive nutrient can be variable absorbed as well as subsequently variably activated or inactivated. His biological activity will thus expose on specific molecular "targets" which may also be variable or modulable in relation to the genomic characteristics of the individual affecting its quality and quantity [22-25].
Journal of Cellular Physiology, May 26, 2015
Serum composition is linked to metabolic diseases not only to understand their pathogenesis but a... more Serum composition is linked to metabolic diseases not only to understand their pathogenesis but also for diagnostic purposes. Quality and quantity of nutritional intake can affect disease risk and serum composition. It is then possible that diet derived serum components directly affect pathogenetic mechanisms. To identify involved factors, we evaluated the effect on gene expression of direct addition of dyslipidemic human serum samples to cultured human hepatoma cells (HepG2). Sera were selected on the basis of cholesterol level, considering this parameter as mostly linked to dietary intake. Cells were treated with 32 sera from hypercholesterolemic and normocholesterolemic subjects to identify differentially regulated mRNAs using DNA microarray analysis. We identified several mRNAs with the highest modulations in cells treated with dyslipidemic sera versus cells treated with normal sera. Since the two serum groups had variable polyunsaturated fatty acids (PUFAs) contents, selected mRNAs were further assessed for their regulation by docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA). Four genes resulted both affected by serum composition and PUFAs: 3‐hydroxy‐3‐methylglutaryl‐CoenzymeA synthase 2 (HMGCS2), glutathione S‐transferase alpha 1 (GSTA1), liver expressed antimicrobial peptide 2 (LEAP2) and apolipoprotein M (ApoM). HMGCS2 expression appears the most relevant and was also found modulated via transcription factors peroxysome proliferator activated receptor α (PPARα) and forkhead box O1 (FoxO1). Our data indicate that expression levels of the selected mRNAs, primarily of HMGCS2, could represent a reference of nutritional intake, PUFAs effects and dyslipidemic diseases pathogenesis. J. Cell. Physiol. 230: 2059–2066, 2015. © 2015 Wiley Periodicals, Inc.
Central nervous system agents in medicinal chemistry, Jun 1, 2010
Bioelectromagnetics, Nov 23, 2010
Low-frequency (LF) electric fields (EFs) are currently used in clinical therapies of several bone... more Low-frequency (LF) electric fields (EFs) are currently used in clinical therapies of several bone diseases to increase bone regenerative processes. To identify possible molecular mechanisms involved in these processes, we evaluated the effects on cell cultures of 1 h exposures to the signal generated by an apparatus of current clinical use (frequency 60 kHz, frequency of the modulating signal 12.5 Hz, 50% duty cycle, peak-to-peak voltage 24.5 V). Two different human cell lines, bone SaOS-2 and liver HepG2, were used. Exposures significantly increased alkaline phosphatase (ALP) enzymatic activity in both cell lines. The increase was about 35% in SaOS-2 cells and about 80% in HepG2 cells and occurred in the first 4 h after exposure and decreased to almost no change by 24 h. Since ALP represents a typical marker of bone regeneration, these results represent a first molecular evidence of biological effects from 60 kHz EF exposures. The finding of similar effects in cells derived from two different tissues more likely indicates the effective operation of the mechanism in living organisms.
BENTHAM SCIENCE PUBLISHERS eBooks, Aug 18, 2010
Diseases and disorders, 2017
Histone acetyltransferase inhibitors are able to induce neuroprotection because of their antioxid... more Histone acetyltransferase inhibitors are able to induce neuroprotection because of their antioxidant properties, so, their therapeutic use in limiting neurological damage is strongly supported. Histone acetyltransferase inhibitors treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression and to repair the damaged structures. The acetylation and deacetylation of histones are involved in the regulation of gene expression and the regular function of histone acetyltransferases (HATs) and deacetylases (HDACs) provide regulatory steps for gene expression and cell cycle. Functional defects of these enzymes may lead to several diseases, including neurodegenerative disorders. The studies reported in the present review support the view that the histone acetyltransferase inhibitors may be a key modulatory element in the control of neurodegenerative disorders. This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data. Furthermore, these studies support the idea of developing novel pharmacotherapies with histone acetyltransferase inhibitors that selectively target specific area of CNS.
This book was written assuming that car driving, likely also racing car driving, will became obso... more This book was written assuming that car driving, likely also racing car driving, will became obsolete while autonomous vehicles will be developed with technology progresses. However, the good legacy of these activities will stay forever and driving among life choices will certainly continue to be a fundamental feature of human nature. Actually, driving between good and bad is what an “Auriga Virtutum", a Charioteer of the Virtues, is expected to do using his free will. The book reports the feelings of a Formula One follower about drivers and championship seasons of the last fifty years. Following these competitions and all involved people may be not only pleasant and interesting, but it can also become a way to generally think over the goal of life and the sense of living, certainly this being just one possible way to do that among many others. While this effort is not specifically targeted to people interested to Formula One, hopefully it will be worth to read it also for them. Likely, it was possibly opportune to write a book about these subjects, but that it would also be much more important if anybody will find it useful to read.