Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investi... more Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in ...
Background: High-grade gliomas (HGG) are malignant brain tumors associated with frequent recurren... more Background: High-grade gliomas (HGG) are malignant brain tumors associated with frequent recurrent disease. Clinical management of HGG patients is currently devoid of blood biomarkers for early diagnosis, monitoring therapeutic effects and predicting recurrence. Different circulating miRNAs, both free and associated with exosomes, are described in patients with HGG. We previously identified miR-21, miR-222 and miR-124-3p purified from serum exosomes as molecular signature to help pre-operative clinical diagnosis and grading of gliomas. The aim of the present study was to verify this signature as a tool to assess the effect of treatment and for the early identification of progression in newly diagnosed HGG patients. Material and Methods: Major inclusion criteria were newly diagnosed, histologically confirmed HGG patients, no prior chemotherapy, ECOG PS 0-2 and patients scheduled for radiochemotherapy with temozolomide as first-line treatment after surgery. RANO criteria were used for...
As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be... more As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5.To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Coll...
Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte s... more Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte size and its relation with insulin resistance and adipokines. Biopsies were collected from subcutaneous, epicardial-, and peritoneal fat from 21 males undergoing elective cardiac surgery either for coronary artery bypass grafting (n=11) or for valve replacement (n=10). We assessed epicardial adipocyte size, comparing it with that from subcutaneous fat and peritoneal fat. The adipocyte size was determined by using collagenase digestion of adipose tissue, separation of adipocytes by centrifugation, methylene blue staining of the nuclei, and measurement of the cell diameter. Patient's weight, height, body mass index, waist, as well as glucose, insulin, homeostatic model assessment index, adiponectin, and leptin serum levels were determined. Adiponectin mRNA levels were determined by real-time polymerase chain reaction on subcutaneous fat and epicardial fat biopsies. Adipocytes in epicardial fat were significantly smaller than those in subcutaneous and peritoneal fat. The adipocyte size in epicardial fat correlated positively with insulin resistance and serum leptin, and correlated negatively with serum and mRNA expression of adiponectin. Adiponectin mRNA expression in epicardial fat was significantly lower than in subcutaneous fat. Adipocyte size in epicardial fat was significantly smaller in valve-replacement patients than in coronary artery bypass graft patients. Adiponectin gene expression was lower in the latter than in the former, although not significantly. Adipocytes in epicardial fat are smaller than those in peritoneal and subcutaneous fat. Adipocyte size, both in epicardial and in subcutaneous fat, is positively related with insulin resistance, shows negative association with local adiponectin gene expression, and is decreased in subjects with coronary artery disease. Adiponectin gene expression is significantly lower in epicardial- than in subcutaneous fat.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical pla... more Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM...
International Journal of High Dilution Research - ISSN 1982-6206
Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area,... more Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area, are highly reactive forms of their source material with biological, chemical, optical, electromagnetic, and thermal properties different from larger bulk forms of the same material. It has been speculated that NPs can occur in homeopathic products as a function of trituration and shaking into glass containers. Moreover, the presence of sugars additives like lactose and of silicates leaked from the glassware are reported to stabilize the nanoparticles.1 Up to now some authors observed nanoparticles in highly diluted samples2, 3, but further studies are needed to know the nature of the NPs. Actually, nanostructures in the solutions may derive from the source materials but also from stuff contaminations and also may be constituted by nano-bubbles.4, 5 Moreover, the mechanism by which the nanostructures can be formed and the effect of serial dilution/succussions of the NPs suspension should...
Background: Arnica montana is a popular traditional remedy widely used in complementary medicine,... more Background: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. Methods: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. Results: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited th...
International Journal of Molecular Medicine, Dec 1, 2009
It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an impor... more It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an important role in controlling the inflammation and metabolic alterations associated with obesity. In endothelial and monocytic cells, adiponectin acts as a modulator of the inflammatory response, suppressing NF-kappaB activation. The aim of this study was to assess the ability of different forms of adiponectin to modulate the inflammatory response in adipocytes. 3T3-L1 preadipocytes were cultured according to standard conditions. Fully differentiated adipocytes were stimulated with 1 microg/ml lipopolysaccharides (LPS) for 16 h, with or without pre-treatment with 10 microg/ml of globular (AdG) or full-length (AdFl) adiponectin. Both AdG and AdFl significantly suppressed LPS-induced expression of IL-6 mRNA in adipocytes and reduced the concentration of IL-6 in culture media. Adiponectin pre-treatment significantly reduced the increase in MCP-1 mRNA in adipocytes exposed to LPS. In culture media, the increase in MCP-1 detected after LPS stimulation was significantly attenuated after pre-treatment with AdG. In 3T3-L1, AdG and AdFl reduced NF-kappaB activity by 50 and 40%, respectively compared to the NF-kappaB activation induced by LPS alone. Moreover, both forms of adiponectin significantly attenuated IkappaB-alpha as well as IKK gene expression. Pre-treatment of adipocytes with AdG or AdFl significantly increased PPARgamma mRNA levels, taking its expression back to the basal level. Both AdG and AdFl exert anti-inflammatory activity suppressing IL-6 and MCP-1 production from inflamed adipocytes. This anti-inflammatory action may be mediated through inhibition of NF-kappaB activity as well as through increased PPARgamma expression.
We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene ... more We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene expression and protein secretion profiles of adipocytes. 3T3-L1 mouse preadipocytes were cultured according to standard conditions and analyzed at different time points both at the basal state and after an acute stimulation with LPS. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP)alpha, peroxisome proliferator-activated receptor (PPAR)gamma and S100A1 were maximal during adipocyte differentiation and then significantly decreased. The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells. The mRNA levels and secretion of adiponectin, quickly rose as adipocytes matured and then declined. The mRNA levels of IL6, as well as its secretion, increased as preadipocytes matured and became old cells; a similar trend was also found for MCP-1. LPS decreased the mRNA levels of C/EBPalpha and PPARgamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin. LPS significantly increased the mRNA levels of IL-6, as well as its secretion, with a similar trend also observed for MCP-1. These data suggest that aging adipocytes in vitro show a decline in pro-adipogenic signals, in genes involved in glucose metabolism and cytoskeleton maintenance and in adiponectin. These changes are paralleled by an increase in inflammatory cytokines; inflammation seems to mimic and amplify the effects of cellular aging on adipocytes.
Here we survey the homeopathic basic principles (Similia and dilution/dynamization) with the aim ... more Here we survey the homeopathic basic principles (Similia and dilution/dynamization) with the aim of examining their consistency with modern scientific knowledge. Recognition of the function of enzymes, receptors and signal transduction and their dynamic interaction with drugs, makes it possible to look at homeopathy in a rational light. The cornerstone of homeopathy - that the whole clinical picture of the individual patient be taken into consideration - is not in dispute, but laboratory models also allow the mechanism(s) of action of drugs to be investigated in animals, cells, tissues, and even at the molecular level. The cell is the elementary particle of life and its sensitivity to external perturbations is the basis of both pathologic changes and therapeutic interventions. The effects of homeopathic remedies in cellular models are well documented for a wide range of dilutions/dynamizations, albeit not all homeopathic effects can be reduced to the cellular level. Many of these ef...
Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investi... more Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in ...
Background: High-grade gliomas (HGG) are malignant brain tumors associated with frequent recurren... more Background: High-grade gliomas (HGG) are malignant brain tumors associated with frequent recurrent disease. Clinical management of HGG patients is currently devoid of blood biomarkers for early diagnosis, monitoring therapeutic effects and predicting recurrence. Different circulating miRNAs, both free and associated with exosomes, are described in patients with HGG. We previously identified miR-21, miR-222 and miR-124-3p purified from serum exosomes as molecular signature to help pre-operative clinical diagnosis and grading of gliomas. The aim of the present study was to verify this signature as a tool to assess the effect of treatment and for the early identification of progression in newly diagnosed HGG patients. Material and Methods: Major inclusion criteria were newly diagnosed, histologically confirmed HGG patients, no prior chemotherapy, ECOG PS 0-2 and patients scheduled for radiochemotherapy with temozolomide as first-line treatment after surgery. RANO criteria were used for...
As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be... more As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5.To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Coll...
Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte s... more Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte size and its relation with insulin resistance and adipokines. Biopsies were collected from subcutaneous, epicardial-, and peritoneal fat from 21 males undergoing elective cardiac surgery either for coronary artery bypass grafting (n=11) or for valve replacement (n=10). We assessed epicardial adipocyte size, comparing it with that from subcutaneous fat and peritoneal fat. The adipocyte size was determined by using collagenase digestion of adipose tissue, separation of adipocytes by centrifugation, methylene blue staining of the nuclei, and measurement of the cell diameter. Patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s weight, height, body mass index, waist, as well as glucose, insulin, homeostatic model assessment index, adiponectin, and leptin serum levels were determined. Adiponectin mRNA levels were determined by real-time polymerase chain reaction on subcutaneous fat and epicardial fat biopsies. Adipocytes in epicardial fat were significantly smaller than those in subcutaneous and peritoneal fat. The adipocyte size in epicardial fat correlated positively with insulin resistance and serum leptin, and correlated negatively with serum and mRNA expression of adiponectin. Adiponectin mRNA expression in epicardial fat was significantly lower than in subcutaneous fat. Adipocyte size in epicardial fat was significantly smaller in valve-replacement patients than in coronary artery bypass graft patients. Adiponectin gene expression was lower in the latter than in the former, although not significantly. Adipocytes in epicardial fat are smaller than those in peritoneal and subcutaneous fat. Adipocyte size, both in epicardial and in subcutaneous fat, is positively related with insulin resistance, shows negative association with local adiponectin gene expression, and is decreased in subjects with coronary artery disease. Adiponectin gene expression is significantly lower in epicardial- than in subcutaneous fat.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical pla... more Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM...
International Journal of High Dilution Research - ISSN 1982-6206
Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area,... more Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area, are highly reactive forms of their source material with biological, chemical, optical, electromagnetic, and thermal properties different from larger bulk forms of the same material. It has been speculated that NPs can occur in homeopathic products as a function of trituration and shaking into glass containers. Moreover, the presence of sugars additives like lactose and of silicates leaked from the glassware are reported to stabilize the nanoparticles.1 Up to now some authors observed nanoparticles in highly diluted samples2, 3, but further studies are needed to know the nature of the NPs. Actually, nanostructures in the solutions may derive from the source materials but also from stuff contaminations and also may be constituted by nano-bubbles.4, 5 Moreover, the mechanism by which the nanostructures can be formed and the effect of serial dilution/succussions of the NPs suspension should...
Background: Arnica montana is a popular traditional remedy widely used in complementary medicine,... more Background: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. Methods: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. Results: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited th...
International Journal of Molecular Medicine, Dec 1, 2009
It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an impor... more It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an important role in controlling the inflammation and metabolic alterations associated with obesity. In endothelial and monocytic cells, adiponectin acts as a modulator of the inflammatory response, suppressing NF-kappaB activation. The aim of this study was to assess the ability of different forms of adiponectin to modulate the inflammatory response in adipocytes. 3T3-L1 preadipocytes were cultured according to standard conditions. Fully differentiated adipocytes were stimulated with 1 microg/ml lipopolysaccharides (LPS) for 16 h, with or without pre-treatment with 10 microg/ml of globular (AdG) or full-length (AdFl) adiponectin. Both AdG and AdFl significantly suppressed LPS-induced expression of IL-6 mRNA in adipocytes and reduced the concentration of IL-6 in culture media. Adiponectin pre-treatment significantly reduced the increase in MCP-1 mRNA in adipocytes exposed to LPS. In culture media, the increase in MCP-1 detected after LPS stimulation was significantly attenuated after pre-treatment with AdG. In 3T3-L1, AdG and AdFl reduced NF-kappaB activity by 50 and 40%, respectively compared to the NF-kappaB activation induced by LPS alone. Moreover, both forms of adiponectin significantly attenuated IkappaB-alpha as well as IKK gene expression. Pre-treatment of adipocytes with AdG or AdFl significantly increased PPARgamma mRNA levels, taking its expression back to the basal level. Both AdG and AdFl exert anti-inflammatory activity suppressing IL-6 and MCP-1 production from inflamed adipocytes. This anti-inflammatory action may be mediated through inhibition of NF-kappaB activity as well as through increased PPARgamma expression.
We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene ... more We used an in vitro model to evaluate the effects of cellular aging and inflammation on the gene expression and protein secretion profiles of adipocytes. 3T3-L1 mouse preadipocytes were cultured according to standard conditions and analyzed at different time points both at the basal state and after an acute stimulation with LPS. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP)alpha, peroxisome proliferator-activated receptor (PPAR)gamma and S100A1 were maximal during adipocyte differentiation and then significantly decreased. The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells. The mRNA levels and secretion of adiponectin, quickly rose as adipocytes matured and then declined. The mRNA levels of IL6, as well as its secretion, increased as preadipocytes matured and became old cells; a similar trend was also found for MCP-1. LPS decreased the mRNA levels of C/EBPalpha and PPARgamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin. LPS significantly increased the mRNA levels of IL-6, as well as its secretion, with a similar trend also observed for MCP-1. These data suggest that aging adipocytes in vitro show a decline in pro-adipogenic signals, in genes involved in glucose metabolism and cytoskeleton maintenance and in adiponectin. These changes are paralleled by an increase in inflammatory cytokines; inflammation seems to mimic and amplify the effects of cellular aging on adipocytes.
Here we survey the homeopathic basic principles (Similia and dilution/dynamization) with the aim ... more Here we survey the homeopathic basic principles (Similia and dilution/dynamization) with the aim of examining their consistency with modern scientific knowledge. Recognition of the function of enzymes, receptors and signal transduction and their dynamic interaction with drugs, makes it possible to look at homeopathy in a rational light. The cornerstone of homeopathy - that the whole clinical picture of the individual patient be taken into consideration - is not in dispute, but laboratory models also allow the mechanism(s) of action of drugs to be investigated in animals, cells, tissues, and even at the molecular level. The cell is the elementary particle of life and its sensitivity to external perturbations is the basis of both pathologic changes and therapeutic interventions. The effects of homeopathic remedies in cellular models are well documented for a wide range of dilutions/dynamizations, albeit not all homeopathic effects can be reduced to the cellular level. Many of these ef...
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Papers by Debora Olioso