Antonio Ponzetto - Academia.edu (original) (raw)

Papers by Antonio Ponzetto

Gastroenterology, 2000

The prevalence of Helicobacter pylori in patients with alcoholic and nonalcoholic cirrhosis is un... more The prevalence of Helicobacter pylori in patients with alcoholic and nonalcoholic cirrhosis is uncertain. The present study was aimed at determining the prevalence of H. pylori infection among cirrhotic patients and to explore its relationship to demography, etiology of cirrhosis, and liver function. Thirty-three cirrhotic patients were included. H. pylori infection was determined by the 14C urea breath test (n = 30) and endoscopy with antral biopsy (n = 4). Etiology of cirrhosis was classified as alcoholic or nonalcoholic. The rate of H. pylori infection was related to age, gender, etiology, Child-Pugh grading, portal hypertension, and portal-systemic encephalopathy (PSE). None of the patients received antibiotics for at least the last 3 months. Twelve alcoholic and 21 nonalcoholic cirrhotics, with a median age of 57 years and a male:female ratio of 1:1.4 were studied. Overall H. pylori prevalence was 45.5%. This prevalence varied from 47.1% to 43.8% in those younger and older than the median age, and from 35.7% to 52.6% in men and women, respectively. Fifty percent of alcoholic and 42.9% of nonalcoholic cirrhotics were H. pylori-positive. According to Child-Pugh grading, 69% of grade A, 40% of grade B, and 0% of grade C were infected (p = .03). Among patients with PSE, 25% were H. pylori-positive compared to 52% of those without PSE (p = .24). The prevalence of H. pylori infection in cirrhotics is 45.5%. Prevalence was unrelated to age, gender, and etiology of cirrhosis. An inverse relation to the Child-Pugh grading and a tendency to a lower prevalence in PSE was found.

…, 1996

MARIA TORRANI CERENZIA,1 LUIGI FIUME,2 WILMA DE BERNARDI VENON,1 BRUNA LAVEZZO,1 MAURIZIA ROSSANA... more MARIA TORRANI CERENZIA,1 LUIGI FIUME,2 WILMA DE BERNARDI VENON,1 BRUNA LAVEZZO,1 MAURIZIA ROSSANA BRUNETTO,1 ANTONIO PONZETTO,1 GIUSEPPINA DI STEFANO,2 CORRADO BUSI,2 ALESSANDRO MATTIOLI,2 GIOVANNI BATTISTA ...

Cell, Nov 1, 1996

homozygous mutant embryos, the liver is reduced in and Carola Ponzetto † size and shows extensive... more homozygous mutant embryos, the liver is reduced in and Carola Ponzetto † size and shows extensive loss of parenchymal cells *European Molecular Biology Laboratory (Schmidt et al., 1995). Furthermore, consistent with the Meyerhofstrasse 1 scattering activity of HGF, Met-deficient embryos lack 69117 Heidelberg muscles of the limbs, diaphragm, and tip of the tongue, Federal Republic of Germany all deriving from migratory precursors (Bladt et al., 1995). † Department of Biomedical Sciences and Oncology Considerable progress has been made in understand-University of Torino ing the mechanism of Met signaling in cultured cells. 10126 Torino We have previously shown that the biological activity of Italy the receptor depends on the presence of two phospho-‡ International Institute of Genetics and Biophysics tyrosines (Y1349VHVNATY1356VNV) in the carboxy-terminal via G. Marconi 12 tail, which act as multifunctional docking sites for SH2-80125 Napoli containing effectors and activate an array of transduc-Italy tional pathways (Ponzetto et al., 1994). The Y 1356 VNV § Institute for Cancer Research motif, in particular, binds Grb2 (Songyang et al., 1993) 10060 Candiolo (Torino) and links the receptor with Ras. Mutation of Y 1356 alone Italy interferes heavily with all Met-mediated events, whereas mutation of Y 1349 has only a limited effect on transformation and no effect on motility. Mutation of both tyrosines Summary completely abrogates Met function (

Research in Chronic Viral Hepatitis, 1993

Two woodchucks (Marmota monax) intrahepatically inoculated with hepatitis delta virus (HDV) compl... more Two woodchucks (Marmota monax) intrahepatically inoculated with hepatitis delta virus (HDV) complementary DNA clones pSVL-D3 and pSVL-Ag showed virological and pathological signs of acute and chronic HDV infection. HDV-RNA and hepatitis delta antigen (HDAg) were detected in serum by slot-blot hybridization and by western blot five weeks after inoculation. Liver biopsy specimens collected at 8th week post inoculum were positive for HDV-RNA. Anti-HDV antibodies were detected at the 11th and 9th weeks, respectively. Histological finding of hepatocarcinoma and persistence of circulating HDV-RNA and anti-HDV were observed up to the 10th month. Both woodchucks produced "small" and "large" HDAg antigen, although the inoculated cloned DNA bears the coding capability solely for the small antigen. A transient decrease of woodchuck hepatitis virus DNA (WHV-DNA) level was observed during the peak of HDV infection. Successive inoculation of acute-phase serum in three woodchucks resulted in a successful infection in one of the animals.

Hepatology, 1996

Differences have been found in the expression of c-met pro-Increased levels of expression of hepa... more Differences have been found in the expression of c-met pro-Increased levels of expression of hepatocyte growth tooncogene product (c-met pp) and HGF in liver tissue. In factor (HGF) and its specific receptor c-met have been normal human liver, HGF has been detected in bile duct shown in the liver of several benign and malignant paepithelia and in endothelial cells of both the central-lobular thologies, both in experimental models and humans. We vein and portal tracts vessels, 8-10,12 whereas c-met pp has been investigated by immunohistochemistry the presence of identified only in normal mature hepatocytes. 6 In rat liver, both HGF and c-met protooncogene product (c-met pp) HGF has also been found to be expressed in Kupffer cells in 20 hepatocellular carcinomas (HCCs), 5 focal nodular and Ito cells, 9-13 and c-met pp in the ''facultative stem cells'' hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), often referred to as oval cells (OCs). 13 The latter are considand 1 case of regenerated liver. The c-met protooncogene ered to be bipotential progenitor cells, because they can difproduct was expressed in all cases with marked overexferentiate either toward bile duct epithelial cells or hepatopression in the HCCs and in ductular metaplasia. HGF cytes. 14 Small single cells with an oval nucleus, scanty was detected in the Ito cells of all cases and in neoplastic cytoplasm, and ultrastructural and phenotypic features simihepatocytes of 9 of 20 HCCs (45%). The proliferative inlar to rat OCs have recently been identified in human regendex of each lesion was evaluated by means of the polyerating liver. 15 These cells react with the rat OC-specific clonal antibody anti-cyclin A. When the level of expresmonoclonal antibody (MoAb), OV-6. 16 sion of HGF and c-met protooncogene product with the Increases in c-met pp expression have been reported in percentage of cyclin A / nuclei were compared, the closhepatocytes of many benign and malignant human liver tisest relationship was between c-met protooncogene prodsues. 17-19 Furthermore, in experimental hepatic regeneration, uct and cyclin A. In 11 of 20 HCCs (55%), there was no the overexpression of c-met pp in OCs matches that of HGF correlation between HGF positivity and cyclin A. This in Ito cells. 13 To the best of our knowledge, however, the seems to suggest that, independently of the levels of naexpression of HGF and its specific c-met pp receptor has not tive liver HGF, c-met protooncogene product is the most yet been studied extensively in different pathological human active modulator of liver cell proliferation. (HEPATOLOGY liver conditions, although conflicting results have been re-1996;24:60-64.) ported in a small series of hepatomas. 20 Identification of the mechanism that modulates the proliferation of OCs could Hepatocyte growth factor (HGF) is believed to be the most benefit our understanding of liver regeneration and the early important mitogen for hepatocytes in vitro, and the humoral steps of liver carcinogenesis. mediator of liver regeneration. 1 Originally identified in the It has been shown that HCCs overexpress c-met pp in comserum of partially hepatectomized rats, 2 HGF has also been parison with normal liver. 17-19 We therefore decided to invesisolated from humans and its gene cloned. 3-5 HGF's receptor tigate the expression of HGF and c-met pp in a series of has been characterized as the product of the protooncogene benign and malignant liver lesions that involve mature pac-met, 6 which is overexpressed in solid tumors, such as colonic renchymal cells, malignant hepatocytes, and OCs. The postuand gastric cancers. 7 This suggests an involvement of HGF, lated mitogenic effect of HGF was evaluated by comparing which is present in many organs 8-12 in some developmental the expressions of HGF, c-met pp, and the cell-cycle-related steps of human carcinogenesis. 6 antigen, cyclin A.

Digestive and Liver Disease, Aug 1, 2008

ABSTRACT

Gastroenterology, Apr 1, 1995

International Journal of Molecular Sciences

We present a novel thermodynamic approach to the epigenomics of cancer metabolism. Here, any chan... more We present a novel thermodynamic approach to the epigenomics of cancer metabolism. Here, any change in a cancer cell’s membrane electric potential is completely irreversible, and as such, cells must consume metabolites to reverse the potential whenever required to maintain cell activity, a process driven by ion fluxes. Moreover, the link between cell proliferation and the membrane’s electric potential is for the first time analytically proven using a thermodynamic approach, highlighting how its control is related to inflow and outflow of ions; consequently, a close interaction between environment and cell activity emerges. Lastly, we illustrate the concept by evaluating the Fe2+-flux in the presence of carcinogenesis-promoting mutations of the TET1/2/3 gene family.

International Journal of Molecular Sciences

In our recent studies, we have developed a thermodynamic biochemical model able to select the res... more In our recent studies, we have developed a thermodynamic biochemical model able to select the resonant frequency of an extremely low frequency electromagnetic field (ELF-EMF) specifically affecting different types of cancer, and we have demonstrated its effects in vitro. In this work, we investigate the cellular response to the ELF electromagnetic wave in three-dimensional (3D) culture models, which mimic the features of tumors in vivo. Cell membrane was modelled as a resistor–capacitor circuit and the specific thermal resonant frequency was calculated and tested on two-dimensional (2D) and three-dimensional (3D) cell cultures of human pancreatic cancer, glioblastoma and breast cancer. Cell proliferation and the transcription of respiratory chain and adenosine triphosphate synthase subunits, as well as uncoupling proteins, were assessed. For the first time, we demonstrate that an ELF-EMF hampers growth and potentiates both the coupled and uncoupled respiration of all analyzed models...

Applied Sciences, 2021

Alternative treatment strategies are necessary to reduce the severity of glaucoma, a group of eye... more Alternative treatment strategies are necessary to reduce the severity of glaucoma, a group of eye conditions that progressively damage the optic nerve and impair vision. The aim of this review is to gain insight into potentially exploitable molecular mechanisms to slow down the death of retinal ganglion cells (RGCs), a fundamental element in the pathophysiology of all forms of glaucoma, and to stimulate adult optic nerve repair. For this purpose, we focus our analysis on both visible and far-red to near-infrared light photobiomodulation (PBM) as phototherapeutic agents, which were recently proposed in RGCs, and on the nerve lamina region neural progenitor cell (ONLR-NPC) niche. Both are suggested as potential strategies in glaucoma neuroprotection. We discuss the impact of beneficial molecular effects of PBM on both mitochondrial derangement and the alteration of ion fluxes that are considered important causes of RGC damage, as well as on the stimulation of progenitor cells. We sugg...

Applied Sciences, 2021

Recently, a non-equilibrium thermodynamic approach has been developed in order to model the funda... more Recently, a non-equilibrium thermodynamic approach has been developed in order to model the fundamental role of the membrane electric potential in the cell behaviour. A related new viewpoint is introduced, with a design of a photobiomodulation treatment in order to restore part of the visual field. Here, a first step in experimental evidence of the validity of the thermodynamic approach is developed. This result represents the starting point for future experimental improvements for light stimulation in order to improve the quality of life of the patients. The future possible therapy will be in addition to the pharmacological treatments.

Journal of Endocrinological Investigation, 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2019

The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth... more The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift.

Mayo Clinic Proceedings, 2019

European Journal of Gastroenterology & Hepatology, 2019

A frequent, often life-threatening, complication of cirrhosis is portal vein thrombosis; for its ... more A frequent, often life-threatening, complication of cirrhosis is portal vein thrombosis; for its treatment, Valentin et al. [1] reviewed transjugular intrahepatic portosystemic shunt; however, its cost compared with anticoagulation is staggering. Moreover, a five times increase in deaths due to acute myocardial infarction and ischemic stroke among patients with liver cirrhosis has been reported [2,3]. These events highlight the existence of other, often neglected causes, of thrombosis in cirrhotic patients. One such possible cause that could be easily and cost-effectively detected and cured, if searched for, is the infection by pathogenic strains of Helicobacter pylori particularly those strains expressing the cytotoxin-associated antigen A protein that has been found with high prevalence in patients with cirrhosis [4], myocardial infarction [5], and ischemic stroke [6]. This bacterium is known to mimic human antigens and induce autoimmunity against endothelial cells [7], cause the antiphospholipid syndrome [8] and autoimmune thrombotic thrombocythemia that are ameliorated after the infection is eradicated [8,9]. Furthermore, a neutrophilic-activating protein is secreted by H.pylori, which causes neutrophilic infiltration of the vascular wall and activates neutrophils stimulating the production of reactive oxygen species, and inflammation. Neutrophilic-activating protein also stimulates the production of tissue factor and plasminogen activator inhibitor-2 by mononuclear cells [10]. These latter effects are procoagulant and antifibrinolytic thus affecting the coagulation-fibrinolysis balance toward fibrin deposition and coagulation [10]. Patients infected by H. pylori circulate aggregates of platelets and neutrophils [11]: neutrophilic infiltration of vascular walls may lead to venous thrombosis [12]. We suggest that all patients with cirrhosis ought to be tested for the presence of pathogenic strains of H. pylori and to cure those who are positive. This simple action will decrease the risk of gastric and duodenal ulcer, and possibly also portal vein thrombosis and other ischemic illnesses in cirrhosis patients.

Chinese Medical Journal, 2018

This is an open access journal, and articles are distributed under the terms of the Creative Comm... more This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Annals of Hepatology, 2018

Cruz-Ramon, et al. report on portal vein thrombosis (PVT) in patients with liver cirrhosis. 1 We ... more Cruz-Ramon, et al. report on portal vein thrombosis (PVT) in patients with liver cirrhosis. 1 We feel the necessity to avert and cure such underestimated and undertreated complication: PVT often proceeds to severe portal hypertension and bleeding, and correlates with lower life expectancy. A major problem is the wide disparity of treatments. We believe that a comment is warranted, as other possible mechanisms leading to PVT are often overlooked.. These mechanisms include neutrophilic infiltration, a cause of neutrophilic extracellular traps or NETosis, 2 and anti-phospholipid syndrome (APS). Both conditions can be elicited by Helicobacter pylori (H. pylori) infection. 3 APS is characterized by anti-cardiolipin antibodies which are also increased in cirrhotics. H. pylori infection is a frequent finding in cirrhosis patients, 4 and a well-established cause of autoimmunity, including that one against endothelial cells, as bacterial proteins cross reacts with human endothelial antigens via antigenic mimicry. 5 Moreover, the bacterium secretes a neutrophilicactivating protein (NAP); neutrophilic infiltration of vascular walls may lead to venous thrombosis, that has been recognized involved in atherosclerosis as well, as reviewed by Mozzini. 2 Cirrhotic patients very frequently are also infected by pathogenic strains of H. Pylori, 6 which are also known to correlate with acute ischemic stroke and autoimmune thrombotic thrombocytemia. Hence, PVT might benefit by the simple cure of H.pylori, which in turn will lower serum levels of anti-phospholipid antibodies, 7 rescind endothelial activation, 8 and decrease circulating levels of pro-inflammatory cytokines.

Gastroenterology, 2000

The prevalence of Helicobacter pylori in patients with alcoholic and nonalcoholic cirrhosis is un... more The prevalence of Helicobacter pylori in patients with alcoholic and nonalcoholic cirrhosis is uncertain. The present study was aimed at determining the prevalence of H. pylori infection among cirrhotic patients and to explore its relationship to demography, etiology of cirrhosis, and liver function. Thirty-three cirrhotic patients were included. H. pylori infection was determined by the 14C urea breath test (n = 30) and endoscopy with antral biopsy (n = 4). Etiology of cirrhosis was classified as alcoholic or nonalcoholic. The rate of H. pylori infection was related to age, gender, etiology, Child-Pugh grading, portal hypertension, and portal-systemic encephalopathy (PSE). None of the patients received antibiotics for at least the last 3 months. Twelve alcoholic and 21 nonalcoholic cirrhotics, with a median age of 57 years and a male:female ratio of 1:1.4 were studied. Overall H. pylori prevalence was 45.5%. This prevalence varied from 47.1% to 43.8% in those younger and older than the median age, and from 35.7% to 52.6% in men and women, respectively. Fifty percent of alcoholic and 42.9% of nonalcoholic cirrhotics were H. pylori-positive. According to Child-Pugh grading, 69% of grade A, 40% of grade B, and 0% of grade C were infected (p = .03). Among patients with PSE, 25% were H. pylori-positive compared to 52% of those without PSE (p = .24). The prevalence of H. pylori infection in cirrhotics is 45.5%. Prevalence was unrelated to age, gender, and etiology of cirrhosis. An inverse relation to the Child-Pugh grading and a tendency to a lower prevalence in PSE was found.

…, 1996

MARIA TORRANI CERENZIA,1 LUIGI FIUME,2 WILMA DE BERNARDI VENON,1 BRUNA LAVEZZO,1 MAURIZIA ROSSANA... more MARIA TORRANI CERENZIA,1 LUIGI FIUME,2 WILMA DE BERNARDI VENON,1 BRUNA LAVEZZO,1 MAURIZIA ROSSANA BRUNETTO,1 ANTONIO PONZETTO,1 GIUSEPPINA DI STEFANO,2 CORRADO BUSI,2 ALESSANDRO MATTIOLI,2 GIOVANNI BATTISTA ...

Cell, Nov 1, 1996

homozygous mutant embryos, the liver is reduced in and Carola Ponzetto † size and shows extensive... more homozygous mutant embryos, the liver is reduced in and Carola Ponzetto † size and shows extensive loss of parenchymal cells *European Molecular Biology Laboratory (Schmidt et al., 1995). Furthermore, consistent with the Meyerhofstrasse 1 scattering activity of HGF, Met-deficient embryos lack 69117 Heidelberg muscles of the limbs, diaphragm, and tip of the tongue, Federal Republic of Germany all deriving from migratory precursors (Bladt et al., 1995). † Department of Biomedical Sciences and Oncology Considerable progress has been made in understand-University of Torino ing the mechanism of Met signaling in cultured cells. 10126 Torino We have previously shown that the biological activity of Italy the receptor depends on the presence of two phospho-‡ International Institute of Genetics and Biophysics tyrosines (Y1349VHVNATY1356VNV) in the carboxy-terminal via G. Marconi 12 tail, which act as multifunctional docking sites for SH2-80125 Napoli containing effectors and activate an array of transduc-Italy tional pathways (Ponzetto et al., 1994). The Y 1356 VNV § Institute for Cancer Research motif, in particular, binds Grb2 (Songyang et al., 1993) 10060 Candiolo (Torino) and links the receptor with Ras. Mutation of Y 1356 alone Italy interferes heavily with all Met-mediated events, whereas mutation of Y 1349 has only a limited effect on transformation and no effect on motility. Mutation of both tyrosines Summary completely abrogates Met function (

Research in Chronic Viral Hepatitis, 1993

Two woodchucks (Marmota monax) intrahepatically inoculated with hepatitis delta virus (HDV) compl... more Two woodchucks (Marmota monax) intrahepatically inoculated with hepatitis delta virus (HDV) complementary DNA clones pSVL-D3 and pSVL-Ag showed virological and pathological signs of acute and chronic HDV infection. HDV-RNA and hepatitis delta antigen (HDAg) were detected in serum by slot-blot hybridization and by western blot five weeks after inoculation. Liver biopsy specimens collected at 8th week post inoculum were positive for HDV-RNA. Anti-HDV antibodies were detected at the 11th and 9th weeks, respectively. Histological finding of hepatocarcinoma and persistence of circulating HDV-RNA and anti-HDV were observed up to the 10th month. Both woodchucks produced "small" and "large" HDAg antigen, although the inoculated cloned DNA bears the coding capability solely for the small antigen. A transient decrease of woodchuck hepatitis virus DNA (WHV-DNA) level was observed during the peak of HDV infection. Successive inoculation of acute-phase serum in three woodchucks resulted in a successful infection in one of the animals.

Hepatology, 1996

Differences have been found in the expression of c-met pro-Increased levels of expression of hepa... more Differences have been found in the expression of c-met pro-Increased levels of expression of hepatocyte growth tooncogene product (c-met pp) and HGF in liver tissue. In factor (HGF) and its specific receptor c-met have been normal human liver, HGF has been detected in bile duct shown in the liver of several benign and malignant paepithelia and in endothelial cells of both the central-lobular thologies, both in experimental models and humans. We vein and portal tracts vessels, 8-10,12 whereas c-met pp has been investigated by immunohistochemistry the presence of identified only in normal mature hepatocytes. 6 In rat liver, both HGF and c-met protooncogene product (c-met pp) HGF has also been found to be expressed in Kupffer cells in 20 hepatocellular carcinomas (HCCs), 5 focal nodular and Ito cells, 9-13 and c-met pp in the ''facultative stem cells'' hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), often referred to as oval cells (OCs). 13 The latter are considand 1 case of regenerated liver. The c-met protooncogene ered to be bipotential progenitor cells, because they can difproduct was expressed in all cases with marked overexferentiate either toward bile duct epithelial cells or hepatopression in the HCCs and in ductular metaplasia. HGF cytes. 14 Small single cells with an oval nucleus, scanty was detected in the Ito cells of all cases and in neoplastic cytoplasm, and ultrastructural and phenotypic features simihepatocytes of 9 of 20 HCCs (45%). The proliferative inlar to rat OCs have recently been identified in human regendex of each lesion was evaluated by means of the polyerating liver. 15 These cells react with the rat OC-specific clonal antibody anti-cyclin A. When the level of expresmonoclonal antibody (MoAb), OV-6. 16 sion of HGF and c-met protooncogene product with the Increases in c-met pp expression have been reported in percentage of cyclin A / nuclei were compared, the closhepatocytes of many benign and malignant human liver tisest relationship was between c-met protooncogene prodsues. 17-19 Furthermore, in experimental hepatic regeneration, uct and cyclin A. In 11 of 20 HCCs (55%), there was no the overexpression of c-met pp in OCs matches that of HGF correlation between HGF positivity and cyclin A. This in Ito cells. 13 To the best of our knowledge, however, the seems to suggest that, independently of the levels of naexpression of HGF and its specific c-met pp receptor has not tive liver HGF, c-met protooncogene product is the most yet been studied extensively in different pathological human active modulator of liver cell proliferation. (HEPATOLOGY liver conditions, although conflicting results have been re-1996;24:60-64.) ported in a small series of hepatomas. 20 Identification of the mechanism that modulates the proliferation of OCs could Hepatocyte growth factor (HGF) is believed to be the most benefit our understanding of liver regeneration and the early important mitogen for hepatocytes in vitro, and the humoral steps of liver carcinogenesis. mediator of liver regeneration. 1 Originally identified in the It has been shown that HCCs overexpress c-met pp in comserum of partially hepatectomized rats, 2 HGF has also been parison with normal liver. 17-19 We therefore decided to invesisolated from humans and its gene cloned. 3-5 HGF's receptor tigate the expression of HGF and c-met pp in a series of has been characterized as the product of the protooncogene benign and malignant liver lesions that involve mature pac-met, 6 which is overexpressed in solid tumors, such as colonic renchymal cells, malignant hepatocytes, and OCs. The postuand gastric cancers. 7 This suggests an involvement of HGF, lated mitogenic effect of HGF was evaluated by comparing which is present in many organs 8-12 in some developmental the expressions of HGF, c-met pp, and the cell-cycle-related steps of human carcinogenesis. 6 antigen, cyclin A.

Digestive and Liver Disease, Aug 1, 2008

ABSTRACT

Gastroenterology, Apr 1, 1995

International Journal of Molecular Sciences

We present a novel thermodynamic approach to the epigenomics of cancer metabolism. Here, any chan... more We present a novel thermodynamic approach to the epigenomics of cancer metabolism. Here, any change in a cancer cell’s membrane electric potential is completely irreversible, and as such, cells must consume metabolites to reverse the potential whenever required to maintain cell activity, a process driven by ion fluxes. Moreover, the link between cell proliferation and the membrane’s electric potential is for the first time analytically proven using a thermodynamic approach, highlighting how its control is related to inflow and outflow of ions; consequently, a close interaction between environment and cell activity emerges. Lastly, we illustrate the concept by evaluating the Fe2+-flux in the presence of carcinogenesis-promoting mutations of the TET1/2/3 gene family.

International Journal of Molecular Sciences

In our recent studies, we have developed a thermodynamic biochemical model able to select the res... more In our recent studies, we have developed a thermodynamic biochemical model able to select the resonant frequency of an extremely low frequency electromagnetic field (ELF-EMF) specifically affecting different types of cancer, and we have demonstrated its effects in vitro. In this work, we investigate the cellular response to the ELF electromagnetic wave in three-dimensional (3D) culture models, which mimic the features of tumors in vivo. Cell membrane was modelled as a resistor–capacitor circuit and the specific thermal resonant frequency was calculated and tested on two-dimensional (2D) and three-dimensional (3D) cell cultures of human pancreatic cancer, glioblastoma and breast cancer. Cell proliferation and the transcription of respiratory chain and adenosine triphosphate synthase subunits, as well as uncoupling proteins, were assessed. For the first time, we demonstrate that an ELF-EMF hampers growth and potentiates both the coupled and uncoupled respiration of all analyzed models...

Applied Sciences, 2021

Alternative treatment strategies are necessary to reduce the severity of glaucoma, a group of eye... more Alternative treatment strategies are necessary to reduce the severity of glaucoma, a group of eye conditions that progressively damage the optic nerve and impair vision. The aim of this review is to gain insight into potentially exploitable molecular mechanisms to slow down the death of retinal ganglion cells (RGCs), a fundamental element in the pathophysiology of all forms of glaucoma, and to stimulate adult optic nerve repair. For this purpose, we focus our analysis on both visible and far-red to near-infrared light photobiomodulation (PBM) as phototherapeutic agents, which were recently proposed in RGCs, and on the nerve lamina region neural progenitor cell (ONLR-NPC) niche. Both are suggested as potential strategies in glaucoma neuroprotection. We discuss the impact of beneficial molecular effects of PBM on both mitochondrial derangement and the alteration of ion fluxes that are considered important causes of RGC damage, as well as on the stimulation of progenitor cells. We sugg...

Applied Sciences, 2021

Recently, a non-equilibrium thermodynamic approach has been developed in order to model the funda... more Recently, a non-equilibrium thermodynamic approach has been developed in order to model the fundamental role of the membrane electric potential in the cell behaviour. A related new viewpoint is introduced, with a design of a photobiomodulation treatment in order to restore part of the visual field. Here, a first step in experimental evidence of the validity of the thermodynamic approach is developed. This result represents the starting point for future experimental improvements for light stimulation in order to improve the quality of life of the patients. The future possible therapy will be in addition to the pharmacological treatments.

Journal of Endocrinological Investigation, 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2019

The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth... more The extremely low frequency electromagnetic stimulation selective for cancer cells elicits growth arrest through a metabolic shift.

Mayo Clinic Proceedings, 2019

European Journal of Gastroenterology & Hepatology, 2019

A frequent, often life-threatening, complication of cirrhosis is portal vein thrombosis; for its ... more A frequent, often life-threatening, complication of cirrhosis is portal vein thrombosis; for its treatment, Valentin et al. [1] reviewed transjugular intrahepatic portosystemic shunt; however, its cost compared with anticoagulation is staggering. Moreover, a five times increase in deaths due to acute myocardial infarction and ischemic stroke among patients with liver cirrhosis has been reported [2,3]. These events highlight the existence of other, often neglected causes, of thrombosis in cirrhotic patients. One such possible cause that could be easily and cost-effectively detected and cured, if searched for, is the infection by pathogenic strains of Helicobacter pylori particularly those strains expressing the cytotoxin-associated antigen A protein that has been found with high prevalence in patients with cirrhosis [4], myocardial infarction [5], and ischemic stroke [6]. This bacterium is known to mimic human antigens and induce autoimmunity against endothelial cells [7], cause the antiphospholipid syndrome [8] and autoimmune thrombotic thrombocythemia that are ameliorated after the infection is eradicated [8,9]. Furthermore, a neutrophilic-activating protein is secreted by H.pylori, which causes neutrophilic infiltration of the vascular wall and activates neutrophils stimulating the production of reactive oxygen species, and inflammation. Neutrophilic-activating protein also stimulates the production of tissue factor and plasminogen activator inhibitor-2 by mononuclear cells [10]. These latter effects are procoagulant and antifibrinolytic thus affecting the coagulation-fibrinolysis balance toward fibrin deposition and coagulation [10]. Patients infected by H. pylori circulate aggregates of platelets and neutrophils [11]: neutrophilic infiltration of vascular walls may lead to venous thrombosis [12]. We suggest that all patients with cirrhosis ought to be tested for the presence of pathogenic strains of H. pylori and to cure those who are positive. This simple action will decrease the risk of gastric and duodenal ulcer, and possibly also portal vein thrombosis and other ischemic illnesses in cirrhosis patients.

Chinese Medical Journal, 2018

This is an open access journal, and articles are distributed under the terms of the Creative Comm... more This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Annals of Hepatology, 2018

Cruz-Ramon, et al. report on portal vein thrombosis (PVT) in patients with liver cirrhosis. 1 We ... more Cruz-Ramon, et al. report on portal vein thrombosis (PVT) in patients with liver cirrhosis. 1 We feel the necessity to avert and cure such underestimated and undertreated complication: PVT often proceeds to severe portal hypertension and bleeding, and correlates with lower life expectancy. A major problem is the wide disparity of treatments. We believe that a comment is warranted, as other possible mechanisms leading to PVT are often overlooked.. These mechanisms include neutrophilic infiltration, a cause of neutrophilic extracellular traps or NETosis, 2 and anti-phospholipid syndrome (APS). Both conditions can be elicited by Helicobacter pylori (H. pylori) infection. 3 APS is characterized by anti-cardiolipin antibodies which are also increased in cirrhotics. H. pylori infection is a frequent finding in cirrhosis patients, 4 and a well-established cause of autoimmunity, including that one against endothelial cells, as bacterial proteins cross reacts with human endothelial antigens via antigenic mimicry. 5 Moreover, the bacterium secretes a neutrophilicactivating protein (NAP); neutrophilic infiltration of vascular walls may lead to venous thrombosis, that has been recognized involved in atherosclerosis as well, as reviewed by Mozzini. 2 Cirrhotic patients very frequently are also infected by pathogenic strains of H. Pylori, 6 which are also known to correlate with acute ischemic stroke and autoimmune thrombotic thrombocytemia. Hence, PVT might benefit by the simple cure of H.pylori, which in turn will lower serum levels of anti-phospholipid antibodies, 7 rescind endothelial activation, 8 and decrease circulating levels of pro-inflammatory cytokines.