sergio ammendola - Academia.edu (original) (raw)

Papers by sergio ammendola

Bioengineering

Nanomedicine can represent a new strategy to treat several types of diseases such as those with i... more Nanomedicine can represent a new strategy to treat several types of diseases such as those with inflammatory aetiology. Through this strategy, it is possible to obtain nanoparticles with controlled shape, size, and eventually surface charge. Moreover, the use of molecules in nanoform may allow more effective delivery into the diseased cells and tissues, reducing toxicity and side effects of the used compounds. The aim of the present manuscript was the evaluation of the effects of N-acetylglucosamine in nanoform (GlcNAc NP) in an in vitro model of osteoarthritis (OA). Human primary chondrocytes were treated with Tumor Necrosis Factor (TNF)-α to simulate a low-grade inflammation and then treated with both GlcNAc and GlcNAc NP, in order to find the lowest concentrations able to counteract the inflammatory state of the cells and ensure a chondroprotective action. The findings showed that GlcNAc NP was able to decrease the pro-inflammatory mediators, IL-6 and IL-8, which are among the ma...

Pharmaceuticals

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a l... more The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of Harpagophytum procumbens root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to clarify the effects of the pure single components, the bioactive constituent, harpagoside, and the main volatile compounds were studied alone or in a reconstituted mixture. Human fibroblast-like synoviocytes, extracted by joints of patients, who underwent a total knee replacement, were treated with an H. procumbens root extract dissolved in DMSO (HPEDMSO). The effectiveness of HPEDMSO to affect CB2 pathways was studied by analyzing the modulation of cAMP, the activation of PKA and ERK MAP kinase, and ...

Nutrients

Obesity is considered an increasingly widespread disease in the world population, regardless of a... more Obesity is considered an increasingly widespread disease in the world population, regardless of age and gender. Genetic but also lifestyle-dependent causes have been identified. Nutrition and physical exercise play an important role, especially in non-genetic obesity. In a three-compartment model, the body is divided into fat mass, fat-free mass and water, and obesity can be considered a condition in which the percentage of total fat mass is in excess. People with a high BMI index or overweight use self-medications, such as food supplements or teas, with the aim to prevent or treat their problem. Unfortunately, there are several obesity modulators that act both on the pathways that promote adipogenesis and those that inhibit lipolysis. Moreover, these pathways involve different tissues and organs, so it is very difficult to identify anti-obesity substances. A network of factors and cells contributes to the accumulation of fat in completely different body districts. The identificatio...

Predicting virus mutations through statistical relational learning

Unità Operativa Geriatria Oncologica, INRCA (W.G.), Rome, Italy; Departments of Biochemical Scien... more Unità Operativa Geriatria Oncologica, INRCA (W.G.), Rome, Italy; Departments of Biochemical Sciences (A.R., M.B., S.A., R.S.), Experimental Medicine (P.G., F.P., A.M.A.), Geriatrics (M.P., V.M.), Medical Physiopathology (S.M., G.S.), University of “La Sapienza,” 00161 Rome, Italy; Hospital San Carlo-IDI Sanità (S.V.), 00100 Rome, Italy; and University of Siena, Siena, Italy, and Eli Lilly & Co. (D.A.), 50019 Florence, Italy

ABSTRACT Export Date: 23 March 2014, Source: Scopus

Osteoarthritis (OA) is a joint disorder characterized by a progressive degradation of joint carti... more Osteoarthritis (OA) is a joint disorder characterized by a progressive degradation of joint cartilage. Cartilage is a connective tissue consisting of an extracellular matrix (ECM) of collagen fibers and elastic fibers embedded in a rubberlike substance. The ECM is produced by chondrocytes, which remain embedded in the same matrix they produced. The ECM is made up of type II collagen (COL2), negatively charged proteoglycans, water, and some other minor components including some glycoproteins and noncollagenous proteins. Cartilage degeneration is a consequence of chondrocyte hypertrophy, characterized by wrong synthesis of ECM and by high expression of proteolytic enzymes. OA can be induced by several cause, among them mechanical joint injury, aging, diet, and metabolism. Foods contain antioxidant and pro-oxidant compounds, which affect cell signaling by stimulating inflammation and senescence of articular cells. In this chapter, we describe the effects of pro-oxidant agents on chondr...

Nutrients

Harpagophytum procumbens (Burch.) DC. ex Meisn. is a traditional remedy for osteoarticular diseas... more Harpagophytum procumbens (Burch.) DC. ex Meisn. is a traditional remedy for osteoarticular diseases, including osteoarthritis (OA), although the bioactive constituents and mechanisms involved are yet to be clarified. In the present study, an aqueous H. procumbens root extract (HPE; containing 1.2% harpagoside) was characterized for its effects on synoviocytes from OA patients and phytochemical composition in polyphenols, and volatile compounds were detected. HPE powder was dissolved in different solvents, including deionized water (HPEH2O), DMSO (HPEDMSO), 100% v/v ethanol (HPEEtOH100), and 50% v/v ethanol (HPEEtOH50). The highest polyphenol levels were found in HPEDMSO and HPEEtOH50, whereas different volatile compounds, mainly β-caryophyllene and eugenol, were detected in all the extracts except for HPEH2O. HPEH2O and HPEDMSO were able to enhance CB2 receptor expression and to downregulate PI-PLC β2 in synovial membranes; moreover, all the extracts inhibited FAAH activity. The pre...

International Journal of Clinical Nutrition & Dietetics

During the last decade the interest for the mesenchymal cells is growing due to their possible us... more During the last decade the interest for the mesenchymal cells is growing due to their possible uses in therapies to treat certain degenerative pathologies. Mesenchymal stem cells have been found in the bone marrow and they have been shown to be responsible for bone repair and fat cells production. Mesenchymal stromal cells can be obtained from a wide variety of tissues in addition to bone marrow and can differentiate into many other cell types. The study of cell differentiation and programming provides new models for drug discovery and cell therapy that now overcomes gene therapy. Senescence, cancer development and degenerative diseases depend on mesenchymal cells contribution to tissue homeostasis. On the other hand, diet and life style are included among risk factors, which can contribute to the success of pharmacological treatments. This review focuses on nutrients from Mediterranean diet and supplements, which have been shown to influence mesenchymal stem cells and cells derived from them. Dietary intake of nutrients impairs both in vitro and in vivo observations, this review aims to gather the results about the effects of food compounds on mesenchymal cells from which adipocytes and osteoblasts derive. Amino acids and proteins, carbohydrates, lipids, fatty acids and vegetable secondary metabolites, differently act on mesenchymal cells bearing on modulation of gene expression and controlling the fate of cell lineages. Remarkable, the analysis of literature shows that the main effect of nutrients on mesenchymal cells is the stimulation of transcription factors which address the cells toward proliferation or differentiation. For instance, carbohydrates, simple or complex, and lipids appear to stimulate the PPAR receptors, whereas proteins and amino acids result to act on the mTOR system and they can also stimulate the MyoD-1 transcription factor and cooperating proteins. In conclusion, nutrients can promote cell growth and differentiation of mesenchymal cells.

Journal of the American College of Nutrition, Jan 13, 2018

The aim of the present study was to investigate how different extravirgin olive oils (EVOOs), obt... more The aim of the present study was to investigate how different extravirgin olive oils (EVOOs), obtained by blending Olea europea cultivars, could influence the cell growth, the response to inflammatory stimuli, and oxidative stress in a culture of the osteosarcoma cell line Saos-2. Three different extravirgin olive oils were physicochemically characterized, determining the free acidity, the oxidation status, the polyphenols content, and the antioxidative activity. Moreover, the effects on Saos-2 cell culture were determined, studying the mRNA expression level by real-time polymerase chain reaction (PCR) assays and the antioxidative activity using fluorescent probes. The cultivars used in the south of Italy, yield extravirgin oils with different amount of fatty acids and polyphenols, which counteract induction of proinflammatory cytokines and regulate free radical production in hydrogen peroxide-stimulated cells. In vitro analysis using the human osteoblast cell line Saos-2 showed tha...

Journal of the American College of Nutrition

ABSTRACT Objective: Herbal extract compositions are largely used to manage vein diseases. We prep... more ABSTRACT Objective: Herbal extract compositions are largely used to manage vein diseases. We prepared a new composition of herbs, named FLEBO OK™, that, when administered as a nutraceutical to patients affected by peripheral vascular diseases, was able to improve their health conditions. We analyzed the effects of this nutraceutical composition on in vitro cultured cells with the aim to obtain information about its mechanisms of action. Methods: A culture of human osteoblast cell line Saos-2 was stimulated with tumor necrosis factor (TNF)-α or interleukin (IL)-1β to induce the expression of some chemokines and matrix metalloproteases (MMPs). This cell culture was then exposed to the prepared composition and the amount of expression of the genes coding for the monocyte chemotactic protein (MCP)-1, IL-8, IL-1β, MMP-2, MMP-3, MMP-9 proteins was measured by real-time polymerase chain reaction (RT-PCR). The experiments were repeated exposing the cells to the same amount of the well-known micronized purified flavonoid fraction. Moreover, we describe the effects of the administration of nutraceutical composition to 20 patients affected by peripheral vascular diseases and 20 healthy individuals. Results: The RT-PCR analyses showed that the new composition induces the expression of MMP-3 and MMP-9 and downregulates MMP-2 in cell cultures stimulated with IL-1β, whereas it induces the expression of IL-8 and represses the expression of IL-1β and MCP-1 in cell cultures stimulated with TNF-α. The induction of the expression of MMP-3 and the downregulation of MCP-1 might result in an antiplatelet activity that was not observed for the micronized purified flavonoid fraction. Interviewed patients reported an improvement in their conditions after 1 month of FLEBO OK treatment. Conclusion: These findings could provide a hypothesis for the high efficiency of the identified nutraceutical composition to management of peripheral vascular diseases.

Journal of the American College of Nutrition, 2016

Objectives: This study aimed to investigate the effects of a nutraceutical composition on the exp... more Objectives: This study aimed to investigate the effects of a nutraceutical composition on the expression of some genes involved in muscle cells and functioning in osteoblast cells. The effects of nutraceutical composition have been compared to the effects of atorvastatin, which induces muscle pain and elevated creatine phosphokinase (CPK) serum level when administered to patients. In particular, we analyzed the MyoD-1 gene, which is responsible for modulation of the CPK gene, which is a marker of muscle pain and damage. Methods: The effects of nutraceutical composition on Saos-2 cells were compared with the effects of atorvastatin. The mRNAs were extracted and the expression levels of mitochondrial and cytoplasmic CPK genes and MyoD-1 were analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, the effects on lactate dehydrogenase (LDH) activity and adenosine triphosphate (ATP) synthesis were measured in the osteoblast cell line. Furthermore, 11 patients with muscle pain or elevated CPK serum levels received a supplementation of the nutraceutical composition to test whether CPK levels could be downregulated. Results: The analysis in Saos-2 cells showed that the nutraceutical composition upregulates the gene expression of MyoD-1 and downregulates the expression of the cytoplasmic isoform of CPK gene expression (p ≤ 0.05); moreover, it slightly increases ATP amount and decreases LDH activity. Conversely, atorvastatin represses the expression of MyoD-1 gene without significant changing into the expression levels of both cytoplasmic and mitochondrial CPK genes. Moreover, atorvastatin does not increase the ATP amount or increase LDH activity. Remarkable, the nutraceutical composition is able to decrease CPK levels in serum of patients and in some cases improve myalgia symptoms. Conclusion: The nutraceutical composition decreases CPK levels both in vitro and in vivo, suggesting that it might be useful to management of nonneurological myalgia symptoms.

ABSTRACT Export Date: 23 March 2014, Source: Scopus

BMC Bioinformatics, 2014

Background Viruses are typically characterized by high mutation rates, which allow them to quickl... more Background Viruses are typically characterized by high mutation rates, which allow them to quickly develop drug-resistant mutations. Mining relevant rules from mutation data can be extremely useful to understand the virus adaptation mechanism and to design drugs that effectively counter potentially resistant mutants. Results We propose a simple statistical relational learning approach for mutant prediction where the input consists of mutation data with drug-resistance information, either as sets of mutations conferring resistance to a certain drug, or as sets of mutants with information on their susceptibility to the drug. The algorithm learns a set of relational rules characterizing drug-resistance and uses them to generate a set of potentially resistant mutants. Learning a weighted combination of rules allows to attach generated mutants with a resistance score as predicted by the statistical relational model and select only the highest scoring ones. Conclusions Promising results w...

Toxicology and Applied Pharmacology, 2009

Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of spe... more Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (<1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

Bioengineering

Nanomedicine can represent a new strategy to treat several types of diseases such as those with i... more Nanomedicine can represent a new strategy to treat several types of diseases such as those with inflammatory aetiology. Through this strategy, it is possible to obtain nanoparticles with controlled shape, size, and eventually surface charge. Moreover, the use of molecules in nanoform may allow more effective delivery into the diseased cells and tissues, reducing toxicity and side effects of the used compounds. The aim of the present manuscript was the evaluation of the effects of N-acetylglucosamine in nanoform (GlcNAc NP) in an in vitro model of osteoarthritis (OA). Human primary chondrocytes were treated with Tumor Necrosis Factor (TNF)-α to simulate a low-grade inflammation and then treated with both GlcNAc and GlcNAc NP, in order to find the lowest concentrations able to counteract the inflammatory state of the cells and ensure a chondroprotective action. The findings showed that GlcNAc NP was able to decrease the pro-inflammatory mediators, IL-6 and IL-8, which are among the ma...

Pharmaceuticals

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a l... more The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of Harpagophytum procumbens root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to clarify the effects of the pure single components, the bioactive constituent, harpagoside, and the main volatile compounds were studied alone or in a reconstituted mixture. Human fibroblast-like synoviocytes, extracted by joints of patients, who underwent a total knee replacement, were treated with an H. procumbens root extract dissolved in DMSO (HPEDMSO). The effectiveness of HPEDMSO to affect CB2 pathways was studied by analyzing the modulation of cAMP, the activation of PKA and ERK MAP kinase, and ...

Nutrients

Obesity is considered an increasingly widespread disease in the world population, regardless of a... more Obesity is considered an increasingly widespread disease in the world population, regardless of age and gender. Genetic but also lifestyle-dependent causes have been identified. Nutrition and physical exercise play an important role, especially in non-genetic obesity. In a three-compartment model, the body is divided into fat mass, fat-free mass and water, and obesity can be considered a condition in which the percentage of total fat mass is in excess. People with a high BMI index or overweight use self-medications, such as food supplements or teas, with the aim to prevent or treat their problem. Unfortunately, there are several obesity modulators that act both on the pathways that promote adipogenesis and those that inhibit lipolysis. Moreover, these pathways involve different tissues and organs, so it is very difficult to identify anti-obesity substances. A network of factors and cells contributes to the accumulation of fat in completely different body districts. The identificatio...

Predicting virus mutations through statistical relational learning

Unità Operativa Geriatria Oncologica, INRCA (W.G.), Rome, Italy; Departments of Biochemical Scien... more Unità Operativa Geriatria Oncologica, INRCA (W.G.), Rome, Italy; Departments of Biochemical Sciences (A.R., M.B., S.A., R.S.), Experimental Medicine (P.G., F.P., A.M.A.), Geriatrics (M.P., V.M.), Medical Physiopathology (S.M., G.S.), University of “La Sapienza,” 00161 Rome, Italy; Hospital San Carlo-IDI Sanità (S.V.), 00100 Rome, Italy; and University of Siena, Siena, Italy, and Eli Lilly & Co. (D.A.), 50019 Florence, Italy

ABSTRACT Export Date: 23 March 2014, Source: Scopus

Osteoarthritis (OA) is a joint disorder characterized by a progressive degradation of joint carti... more Osteoarthritis (OA) is a joint disorder characterized by a progressive degradation of joint cartilage. Cartilage is a connective tissue consisting of an extracellular matrix (ECM) of collagen fibers and elastic fibers embedded in a rubberlike substance. The ECM is produced by chondrocytes, which remain embedded in the same matrix they produced. The ECM is made up of type II collagen (COL2), negatively charged proteoglycans, water, and some other minor components including some glycoproteins and noncollagenous proteins. Cartilage degeneration is a consequence of chondrocyte hypertrophy, characterized by wrong synthesis of ECM and by high expression of proteolytic enzymes. OA can be induced by several cause, among them mechanical joint injury, aging, diet, and metabolism. Foods contain antioxidant and pro-oxidant compounds, which affect cell signaling by stimulating inflammation and senescence of articular cells. In this chapter, we describe the effects of pro-oxidant agents on chondr...

Nutrients

Harpagophytum procumbens (Burch.) DC. ex Meisn. is a traditional remedy for osteoarticular diseas... more Harpagophytum procumbens (Burch.) DC. ex Meisn. is a traditional remedy for osteoarticular diseases, including osteoarthritis (OA), although the bioactive constituents and mechanisms involved are yet to be clarified. In the present study, an aqueous H. procumbens root extract (HPE; containing 1.2% harpagoside) was characterized for its effects on synoviocytes from OA patients and phytochemical composition in polyphenols, and volatile compounds were detected. HPE powder was dissolved in different solvents, including deionized water (HPEH2O), DMSO (HPEDMSO), 100% v/v ethanol (HPEEtOH100), and 50% v/v ethanol (HPEEtOH50). The highest polyphenol levels were found in HPEDMSO and HPEEtOH50, whereas different volatile compounds, mainly β-caryophyllene and eugenol, were detected in all the extracts except for HPEH2O. HPEH2O and HPEDMSO were able to enhance CB2 receptor expression and to downregulate PI-PLC β2 in synovial membranes; moreover, all the extracts inhibited FAAH activity. The pre...

International Journal of Clinical Nutrition & Dietetics

During the last decade the interest for the mesenchymal cells is growing due to their possible us... more During the last decade the interest for the mesenchymal cells is growing due to their possible uses in therapies to treat certain degenerative pathologies. Mesenchymal stem cells have been found in the bone marrow and they have been shown to be responsible for bone repair and fat cells production. Mesenchymal stromal cells can be obtained from a wide variety of tissues in addition to bone marrow and can differentiate into many other cell types. The study of cell differentiation and programming provides new models for drug discovery and cell therapy that now overcomes gene therapy. Senescence, cancer development and degenerative diseases depend on mesenchymal cells contribution to tissue homeostasis. On the other hand, diet and life style are included among risk factors, which can contribute to the success of pharmacological treatments. This review focuses on nutrients from Mediterranean diet and supplements, which have been shown to influence mesenchymal stem cells and cells derived from them. Dietary intake of nutrients impairs both in vitro and in vivo observations, this review aims to gather the results about the effects of food compounds on mesenchymal cells from which adipocytes and osteoblasts derive. Amino acids and proteins, carbohydrates, lipids, fatty acids and vegetable secondary metabolites, differently act on mesenchymal cells bearing on modulation of gene expression and controlling the fate of cell lineages. Remarkable, the analysis of literature shows that the main effect of nutrients on mesenchymal cells is the stimulation of transcription factors which address the cells toward proliferation or differentiation. For instance, carbohydrates, simple or complex, and lipids appear to stimulate the PPAR receptors, whereas proteins and amino acids result to act on the mTOR system and they can also stimulate the MyoD-1 transcription factor and cooperating proteins. In conclusion, nutrients can promote cell growth and differentiation of mesenchymal cells.

Journal of the American College of Nutrition, Jan 13, 2018

The aim of the present study was to investigate how different extravirgin olive oils (EVOOs), obt... more The aim of the present study was to investigate how different extravirgin olive oils (EVOOs), obtained by blending Olea europea cultivars, could influence the cell growth, the response to inflammatory stimuli, and oxidative stress in a culture of the osteosarcoma cell line Saos-2. Three different extravirgin olive oils were physicochemically characterized, determining the free acidity, the oxidation status, the polyphenols content, and the antioxidative activity. Moreover, the effects on Saos-2 cell culture were determined, studying the mRNA expression level by real-time polymerase chain reaction (PCR) assays and the antioxidative activity using fluorescent probes. The cultivars used in the south of Italy, yield extravirgin oils with different amount of fatty acids and polyphenols, which counteract induction of proinflammatory cytokines and regulate free radical production in hydrogen peroxide-stimulated cells. In vitro analysis using the human osteoblast cell line Saos-2 showed tha...

Journal of the American College of Nutrition

ABSTRACT Objective: Herbal extract compositions are largely used to manage vein diseases. We prep... more ABSTRACT Objective: Herbal extract compositions are largely used to manage vein diseases. We prepared a new composition of herbs, named FLEBO OK™, that, when administered as a nutraceutical to patients affected by peripheral vascular diseases, was able to improve their health conditions. We analyzed the effects of this nutraceutical composition on in vitro cultured cells with the aim to obtain information about its mechanisms of action. Methods: A culture of human osteoblast cell line Saos-2 was stimulated with tumor necrosis factor (TNF)-α or interleukin (IL)-1β to induce the expression of some chemokines and matrix metalloproteases (MMPs). This cell culture was then exposed to the prepared composition and the amount of expression of the genes coding for the monocyte chemotactic protein (MCP)-1, IL-8, IL-1β, MMP-2, MMP-3, MMP-9 proteins was measured by real-time polymerase chain reaction (RT-PCR). The experiments were repeated exposing the cells to the same amount of the well-known micronized purified flavonoid fraction. Moreover, we describe the effects of the administration of nutraceutical composition to 20 patients affected by peripheral vascular diseases and 20 healthy individuals. Results: The RT-PCR analyses showed that the new composition induces the expression of MMP-3 and MMP-9 and downregulates MMP-2 in cell cultures stimulated with IL-1β, whereas it induces the expression of IL-8 and represses the expression of IL-1β and MCP-1 in cell cultures stimulated with TNF-α. The induction of the expression of MMP-3 and the downregulation of MCP-1 might result in an antiplatelet activity that was not observed for the micronized purified flavonoid fraction. Interviewed patients reported an improvement in their conditions after 1 month of FLEBO OK treatment. Conclusion: These findings could provide a hypothesis for the high efficiency of the identified nutraceutical composition to management of peripheral vascular diseases.

Journal of the American College of Nutrition, 2016

Objectives: This study aimed to investigate the effects of a nutraceutical composition on the exp... more Objectives: This study aimed to investigate the effects of a nutraceutical composition on the expression of some genes involved in muscle cells and functioning in osteoblast cells. The effects of nutraceutical composition have been compared to the effects of atorvastatin, which induces muscle pain and elevated creatine phosphokinase (CPK) serum level when administered to patients. In particular, we analyzed the MyoD-1 gene, which is responsible for modulation of the CPK gene, which is a marker of muscle pain and damage. Methods: The effects of nutraceutical composition on Saos-2 cells were compared with the effects of atorvastatin. The mRNAs were extracted and the expression levels of mitochondrial and cytoplasmic CPK genes and MyoD-1 were analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, the effects on lactate dehydrogenase (LDH) activity and adenosine triphosphate (ATP) synthesis were measured in the osteoblast cell line. Furthermore, 11 patients with muscle pain or elevated CPK serum levels received a supplementation of the nutraceutical composition to test whether CPK levels could be downregulated. Results: The analysis in Saos-2 cells showed that the nutraceutical composition upregulates the gene expression of MyoD-1 and downregulates the expression of the cytoplasmic isoform of CPK gene expression (p ≤ 0.05); moreover, it slightly increases ATP amount and decreases LDH activity. Conversely, atorvastatin represses the expression of MyoD-1 gene without significant changing into the expression levels of both cytoplasmic and mitochondrial CPK genes. Moreover, atorvastatin does not increase the ATP amount or increase LDH activity. Remarkable, the nutraceutical composition is able to decrease CPK levels in serum of patients and in some cases improve myalgia symptoms. Conclusion: The nutraceutical composition decreases CPK levels both in vitro and in vivo, suggesting that it might be useful to management of nonneurological myalgia symptoms.

ABSTRACT Export Date: 23 March 2014, Source: Scopus

BMC Bioinformatics, 2014

Background Viruses are typically characterized by high mutation rates, which allow them to quickl... more Background Viruses are typically characterized by high mutation rates, which allow them to quickly develop drug-resistant mutations. Mining relevant rules from mutation data can be extremely useful to understand the virus adaptation mechanism and to design drugs that effectively counter potentially resistant mutants. Results We propose a simple statistical relational learning approach for mutant prediction where the input consists of mutation data with drug-resistance information, either as sets of mutations conferring resistance to a certain drug, or as sets of mutants with information on their susceptibility to the drug. The algorithm learns a set of relational rules characterizing drug-resistance and uses them to generate a set of potentially resistant mutants. Learning a weighted combination of rules allows to attach generated mutants with a resistance score as predicted by the statistical relational model and select only the highest scoring ones. Conclusions Promising results w...

Toxicology and Applied Pharmacology, 2009

Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of spe... more Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (<1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.