Lemonica J. Koumbi - Academia.edu (original) (raw)

Papers by Lemonica J. Koumbi

Journal of Hepatology, 2013

Public Health and Toxicology, May 27, 2022

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

EC Gastroenterology and Digestive System, Jul 23, 2020

Since December 2019 a global epidemic of the novel coronavirus disease (Covid19) started, caused ... more Since December 2019 a global epidemic of the novel coronavirus disease (Covid19) started, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfolding the natural history of the disease proved that although the predominant site of infection is the lungs, about one third of Covid19 patients present extrapulmonary symptoms especially in the gastrointestinal (GI) system such as anorexia, diarrhea, vomiting, and abdominal pain. SARS-CoV-2 can actively infect and replicate in the GI tract through its entry receptor angiotensin converting enzyme 2 (ACE2) that is highly expressed in both alveolar and GI epithelial cells. These findings imply the possible involvement of the gut microbiota, which is known to influence the effectiveness of lung immunity. The aim of this rapid-review is to provide an update of the impact of Covid19 infection on the GI tract with a special focus on the microbiome. A better understanding of the relationship between Covid19 and the digestive system may explain why the virus results in severe complications in some patients and mild responses in others.

Frontiers in Immunology, Apr 7, 2021

Breastfeeding not only provides the optimum source of nutrients for the neonate and its first str... more Breastfeeding not only provides the optimum source of nutrients for the neonate and its first strong shield against infection but also lays the foundation for somatic and psychological bonding between the mother and child. During the current COVID-19 pandemic, although the guidelines of the relevant international and national agencies recommend breastfeeding by SARS-CoV-2-infected mothers, considerable insecurity persists in daily clinical practice regarding the safety of the infants and the perceived advantages and disadvantages of discontinuation of breastfeeding. This is a systematic review of the currently available information regarding the transmissibility of SARS-CoV-2 through or while breastfeeding and the protection against infection that breast milk might provide. The accumulated body of knowledge regarding the role of breast milk in the development of the neonatal immune system and protection against infection by other respiratory viruses is discussed, with a focus on the anti-inflammatory role of the antibodies, microbes, and viruses provided to the infant in breast milk and its relevance to the case of SARS-CoV-2.

Frontiers in Neurology

BackgroundThe MIND diet, a hybrid of the Mediterranean and DASH diets, has been shown to reduce c... more BackgroundThe MIND diet, a hybrid of the Mediterranean and DASH diets, has been shown to reduce cognitive decline and dementia occurrence.AimIn the current cross-sectional study the effect of the MIND diet in elderly Greek individuals, assessed for cognitive decline, was investigated. Confirmatory factor analysis (CFA) evaluated the MIND diet score's factor structure in relation to the ability to distinguish the Greek elderly population diagnosed with or without dementia.MethodsOne hundred fifteen participants recently diagnosed with dementia and 52 cognitively healthy controls, after proper neuropsychological testing by neurologists, were included. To ensure the variance-covariance of matrix for the CFA, a second reference group of 36 participants who self-reported as healthy in terms of cognitive status from the general Greek population, was included. Demographic, anthropometric characteristics, emotional status, cognitive function, and dementia diagnosis were recorded. A pred...

Public Health and Toxicology

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

Public Health and Toxicology, May 27, 2022

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

Livers, 2021

Hepatocellular carcinoma (HCC) occurs in patients with chronic liver damage, inflammation and cir... more Hepatocellular carcinoma (HCC) occurs in patients with chronic liver damage, inflammation and cirrhosis. The facilitators involved in increasing the HCC risk in the damaged liver are yet to be discovered. Diet and lifestyle have a profound effect on the liver inflammation and HCC. The term “gut liver axis” describes the bidirectional relationship between the liver and the gut, which are both anatomically and functionally related. Chronic liver damage is characterised by increased intestinal permeability that allows the translocation of various components and metabolites from the gut microbiota to the liver, resulting in liver inflammation and fibrosis. In this review, we discuss how diet-induced changes in gut microbiome composition, such as lipopolysaccharide and lipoteichoic acid, and its metabolites, such as bile acids, play a role in the pathogenesis of liver fibrosis and HCC.

Nutrients, 2020

Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controvers... more Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controversial. The objective of this pilot crossover, randomized, two-period study was to examine the effect of dietary histamine intake on asthma symptoms in twenty-one children with mild intermittent asthma. Children were randomly assigned to either a high- or low-histamine diet, based on the Mediterranean pattern, for 4 weeks. After a 2-week washout period, patients crossed to the alternative diet for 4 additional weeks. Asthma symptoms were assessed at baseline and after the completion of each diet period by a clinician. Daily symptoms and peak flow were recorded throughout the intervention. Adherence to the dietary intervention was assessed via analysis of four random 24-h recalls, for each intervention period. Eighteen children completed the study. Significantly higher mean air flow obstruction was recorded and a trend for prolonged and more severe symptoms was observed during the high-hista...

Current Developments in Nutrition, 2020

During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mai... more During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mainly due to the ambiguous notion that gluten avoidance promotes health. Gluten intolerance has been implicated in non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS), 2 disorders with overlapping symptoms and increasing trend. Together with gluten, other wheat components; fermentable oligo-, di-, monosaccharide, and polyols (FODMAPs); and amylase trypsin inhibitors (ATIs), are implicated in the pathogenesis of both disorders. Gut microflora alterations in IBS and NCGS have been described, while microbiota manipulations have been shown to be promising in some IBS cases. This literature review summarizes our current knowledge on the impact of wheat ingredients (gluten, FODMAPs, and ATIs) in IBS and NCGS. In both disorders, FODMAPs and ATIs trigger gut dysbiosis, suggesting that gluten may not be the culprit, and microbiota manipulations can be applied in diagnostic and i...

World Journal of Hepatology, 2017

Liver cancer is the third leading cause of cancer mortality worldwide with hepatocellular carcino... more Liver cancer is the third leading cause of cancer mortality worldwide with hepatocellular carcinoma (HCC) representing more than 90% of primary liver cancers. Most HCC patients are also suffering from chronic liver disease (CLD). Evidence is emerging that the composition of diet plays an important role in HCC and CLD development and may also have a chemoprotective role. In contrast to other types of cancer, there are few studies investigating the role of diet in hepatocarcinogenesis. From the available data it is evident that high intakes of red meat and dietary sugar positively correlate with HCC occurrence. On the contrary, high consumption of white meat, fish, vegetables, fruits and cereals are inversely associated with HCC risk. This letter discusses the potential role of dietary interventions in the prevention of hepatocarcinogenesis. The increasing HCC incidence and its high fatality are making HCC prevention an urgent matter. Dietary modifications are found to offer protection against HCC, however, new studies from well-designed and large prospective trials are required to confirm these results.

Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology

Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated... more Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. In general, high HBV replication i...

Frontiers in Microbiology, 2016

Epigenetic modifications are stable alterations in gene expression that do not involve mutations ... more Epigenetic modifications are stable alterations in gene expression that do not involve mutations of the genetic sequence itself. It has become increasingly clear that epigenetic factors contribute to the outcome of chronic hepatitis B virus (HBV) infection by affecting cellular and virion gene expression, viral replication and the development of hepatocellular carcinoma. HBV persists in the nucleus of infected hepatocytes as a stable non-integrated covalently closed circular DNA (cccDNA) which functions as a minichromosome. There are two major forms of HBV epigenetic regulation: posttranslational modification of histone proteins associated with the cccDNA minichromosome and DNA methylation of viral and host genomes. This review explores how HBV can interphase with host epigenetic regulation in order to evade host defences and to promote its own survival and persistence. We focus on the effect of cccDNA bound-histone modifications and the methylation status of HBV DNA in regulating viral replication. Investigation of HBV epigenetic control has important clinical correlates with regards to the development of potential therapeutic regimens that will successfully eradicate HBV infection and deal with HBV reactivation in those undergoing treatment with demethylating agents.

World Journal of Hepatology, 2015

Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a... more Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Nutrition and Cancer, 2008

Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used bro... more Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.

Cellular & molecular immunology, 2010

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined a... more Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon...

European Journal of Cancer Prevention, 2009

In recent years, natural dietary agents have drawn a great deal of attention owing to their demon... more In recent years, natural dietary agents have drawn a great deal of attention owing to their demonstrated ability to suppress cancer. We aimed to investigate the in-vitro gastric cancer preventive activity of a methanol extract obtained from table olives of Greek origin. Tested were AGS cell proliferation, induction of apoptosis and inhibition of inflammation. AGS stomach cancer cells were cultured at a density of 10 5 cells/ml. Methanol extract of olive was added to cultures at concentrations of 2.0, 1.6, 1.0, and 0.4 lg phenols/ml. Effect on cellular viability was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and percentages of early and late apoptotic cells were assayed by annexin V-FITC staining on a FACS scan. Interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM)-1 mRNA and protein production were measured by applying reverse transcriptase-PCR and enzyme-linked immunosorbent assay. Olive extract significantly suppressed cell proliferation at 2.0, 1.6, and 1.0 lg phenols/ml. Flow cytometric analysis of Annexin-V labeled cells indicated that 2.0 lg phenols/ml significantly induced apoptosis. Similarly, at 2.0, 1.6, and 1.0 lg phenols/ ml a significant decrease of ICAM-1 and IL-8 protein levels was observed. ICAM-1, as well as IL-8, mRNA expression were decreased in the presence of 2.0 lg phenols/ml. Results indicate that the methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death and suppressing inflammation in AGS cells.

Clinical and Vaccine Immunology, 2010

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses ... more Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-α) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. H...

World journal of hepatology, Jan 28, 2015

Hepatitis B virus (HBV) infection is the leading cause of liver disease and hepatocellular carcin... more Hepatitis B virus (HBV) infection is the leading cause of liver disease and hepatocellular carcinoma (HCC) worldwide, in spite of prophylactic vaccination and antiviral treatment modalities. The immunopathogenesis of HBV infection has been intensively studied and is propelled by complex interactions between the virus and the host immune system. Natural killer group 2D (NKG2D) is a well-characterized activating receptor, expressed on natural killer (NK) cells, NK T cells and CD8(+) cytotoxic T cells. This receptor is present in both humans and mice and binds to a diverge family of ligands that resemble the MHC-class I molecules. Increasing evidence shows that NKG2D-ligand interactions are critical in the establishment of HBV persistence and the development of liver injury and HCC. The expression of NKG2D ligands depends on the presence of several polymorphisms and is also modulated post-transcriptionally by HBV. While it is known that HBV circumvents host's innate immunity via th...

Journal of Hepatology, 2013

Public Health and Toxicology, May 27, 2022

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

EC Gastroenterology and Digestive System, Jul 23, 2020

Since December 2019 a global epidemic of the novel coronavirus disease (Covid19) started, caused ... more Since December 2019 a global epidemic of the novel coronavirus disease (Covid19) started, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfolding the natural history of the disease proved that although the predominant site of infection is the lungs, about one third of Covid19 patients present extrapulmonary symptoms especially in the gastrointestinal (GI) system such as anorexia, diarrhea, vomiting, and abdominal pain. SARS-CoV-2 can actively infect and replicate in the GI tract through its entry receptor angiotensin converting enzyme 2 (ACE2) that is highly expressed in both alveolar and GI epithelial cells. These findings imply the possible involvement of the gut microbiota, which is known to influence the effectiveness of lung immunity. The aim of this rapid-review is to provide an update of the impact of Covid19 infection on the GI tract with a special focus on the microbiome. A better understanding of the relationship between Covid19 and the digestive system may explain why the virus results in severe complications in some patients and mild responses in others.

Frontiers in Immunology, Apr 7, 2021

Breastfeeding not only provides the optimum source of nutrients for the neonate and its first str... more Breastfeeding not only provides the optimum source of nutrients for the neonate and its first strong shield against infection but also lays the foundation for somatic and psychological bonding between the mother and child. During the current COVID-19 pandemic, although the guidelines of the relevant international and national agencies recommend breastfeeding by SARS-CoV-2-infected mothers, considerable insecurity persists in daily clinical practice regarding the safety of the infants and the perceived advantages and disadvantages of discontinuation of breastfeeding. This is a systematic review of the currently available information regarding the transmissibility of SARS-CoV-2 through or while breastfeeding and the protection against infection that breast milk might provide. The accumulated body of knowledge regarding the role of breast milk in the development of the neonatal immune system and protection against infection by other respiratory viruses is discussed, with a focus on the anti-inflammatory role of the antibodies, microbes, and viruses provided to the infant in breast milk and its relevance to the case of SARS-CoV-2.

Frontiers in Neurology

BackgroundThe MIND diet, a hybrid of the Mediterranean and DASH diets, has been shown to reduce c... more BackgroundThe MIND diet, a hybrid of the Mediterranean and DASH diets, has been shown to reduce cognitive decline and dementia occurrence.AimIn the current cross-sectional study the effect of the MIND diet in elderly Greek individuals, assessed for cognitive decline, was investigated. Confirmatory factor analysis (CFA) evaluated the MIND diet score's factor structure in relation to the ability to distinguish the Greek elderly population diagnosed with or without dementia.MethodsOne hundred fifteen participants recently diagnosed with dementia and 52 cognitively healthy controls, after proper neuropsychological testing by neurologists, were included. To ensure the variance-covariance of matrix for the CFA, a second reference group of 36 participants who self-reported as healthy in terms of cognitive status from the general Greek population, was included. Demographic, anthropometric characteristics, emotional status, cognitive function, and dementia diagnosis were recorded. A pred...

Public Health and Toxicology

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

Public Health and Toxicology, May 27, 2022

is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interacti... more is a double-blind peer-reviewed open access journal. Its primary focus is to assess the interaction between public health and toxicology, including how population data on disease incidence can suggest possible etiologies and how genetic and epigenetic factors can influence risk for adverse health effects. The journal also focuses on the application of how these concepts provide evidence relevant to the understanding and prevention of morbidity and mortality resulting from environmental exposures to toxic substances.

Livers, 2021

Hepatocellular carcinoma (HCC) occurs in patients with chronic liver damage, inflammation and cir... more Hepatocellular carcinoma (HCC) occurs in patients with chronic liver damage, inflammation and cirrhosis. The facilitators involved in increasing the HCC risk in the damaged liver are yet to be discovered. Diet and lifestyle have a profound effect on the liver inflammation and HCC. The term “gut liver axis” describes the bidirectional relationship between the liver and the gut, which are both anatomically and functionally related. Chronic liver damage is characterised by increased intestinal permeability that allows the translocation of various components and metabolites from the gut microbiota to the liver, resulting in liver inflammation and fibrosis. In this review, we discuss how diet-induced changes in gut microbiome composition, such as lipopolysaccharide and lipoteichoic acid, and its metabolites, such as bile acids, play a role in the pathogenesis of liver fibrosis and HCC.

Nutrients, 2020

Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controvers... more Asthma is a complex chronic inflammatory disorder. Diet’s impact on asthma symptoms is controversial. The objective of this pilot crossover, randomized, two-period study was to examine the effect of dietary histamine intake on asthma symptoms in twenty-one children with mild intermittent asthma. Children were randomly assigned to either a high- or low-histamine diet, based on the Mediterranean pattern, for 4 weeks. After a 2-week washout period, patients crossed to the alternative diet for 4 additional weeks. Asthma symptoms were assessed at baseline and after the completion of each diet period by a clinician. Daily symptoms and peak flow were recorded throughout the intervention. Adherence to the dietary intervention was assessed via analysis of four random 24-h recalls, for each intervention period. Eighteen children completed the study. Significantly higher mean air flow obstruction was recorded and a trend for prolonged and more severe symptoms was observed during the high-hista...

Current Developments in Nutrition, 2020

During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mai... more During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mainly due to the ambiguous notion that gluten avoidance promotes health. Gluten intolerance has been implicated in non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS), 2 disorders with overlapping symptoms and increasing trend. Together with gluten, other wheat components; fermentable oligo-, di-, monosaccharide, and polyols (FODMAPs); and amylase trypsin inhibitors (ATIs), are implicated in the pathogenesis of both disorders. Gut microflora alterations in IBS and NCGS have been described, while microbiota manipulations have been shown to be promising in some IBS cases. This literature review summarizes our current knowledge on the impact of wheat ingredients (gluten, FODMAPs, and ATIs) in IBS and NCGS. In both disorders, FODMAPs and ATIs trigger gut dysbiosis, suggesting that gluten may not be the culprit, and microbiota manipulations can be applied in diagnostic and i...

World Journal of Hepatology, 2017

Liver cancer is the third leading cause of cancer mortality worldwide with hepatocellular carcino... more Liver cancer is the third leading cause of cancer mortality worldwide with hepatocellular carcinoma (HCC) representing more than 90% of primary liver cancers. Most HCC patients are also suffering from chronic liver disease (CLD). Evidence is emerging that the composition of diet plays an important role in HCC and CLD development and may also have a chemoprotective role. In contrast to other types of cancer, there are few studies investigating the role of diet in hepatocarcinogenesis. From the available data it is evident that high intakes of red meat and dietary sugar positively correlate with HCC occurrence. On the contrary, high consumption of white meat, fish, vegetables, fruits and cereals are inversely associated with HCC risk. This letter discusses the potential role of dietary interventions in the prevention of hepatocarcinogenesis. The increasing HCC incidence and its high fatality are making HCC prevention an urgent matter. Dietary modifications are found to offer protection against HCC, however, new studies from well-designed and large prospective trials are required to confirm these results.

Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology

Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated... more Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. In general, high HBV replication i...

Frontiers in Microbiology, 2016

Epigenetic modifications are stable alterations in gene expression that do not involve mutations ... more Epigenetic modifications are stable alterations in gene expression that do not involve mutations of the genetic sequence itself. It has become increasingly clear that epigenetic factors contribute to the outcome of chronic hepatitis B virus (HBV) infection by affecting cellular and virion gene expression, viral replication and the development of hepatocellular carcinoma. HBV persists in the nucleus of infected hepatocytes as a stable non-integrated covalently closed circular DNA (cccDNA) which functions as a minichromosome. There are two major forms of HBV epigenetic regulation: posttranslational modification of histone proteins associated with the cccDNA minichromosome and DNA methylation of viral and host genomes. This review explores how HBV can interphase with host epigenetic regulation in order to evade host defences and to promote its own survival and persistence. We focus on the effect of cccDNA bound-histone modifications and the methylation status of HBV DNA in regulating viral replication. Investigation of HBV epigenetic control has important clinical correlates with regards to the development of potential therapeutic regimens that will successfully eradicate HBV infection and deal with HBV reactivation in those undergoing treatment with demethylating agents.

World Journal of Hepatology, 2015

Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a... more Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Nutrition and Cancer, 2008

Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used bro... more Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.

Cellular & molecular immunology, 2010

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined a... more Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon...

European Journal of Cancer Prevention, 2009

In recent years, natural dietary agents have drawn a great deal of attention owing to their demon... more In recent years, natural dietary agents have drawn a great deal of attention owing to their demonstrated ability to suppress cancer. We aimed to investigate the in-vitro gastric cancer preventive activity of a methanol extract obtained from table olives of Greek origin. Tested were AGS cell proliferation, induction of apoptosis and inhibition of inflammation. AGS stomach cancer cells were cultured at a density of 10 5 cells/ml. Methanol extract of olive was added to cultures at concentrations of 2.0, 1.6, 1.0, and 0.4 lg phenols/ml. Effect on cellular viability was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and percentages of early and late apoptotic cells were assayed by annexin V-FITC staining on a FACS scan. Interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM)-1 mRNA and protein production were measured by applying reverse transcriptase-PCR and enzyme-linked immunosorbent assay. Olive extract significantly suppressed cell proliferation at 2.0, 1.6, and 1.0 lg phenols/ml. Flow cytometric analysis of Annexin-V labeled cells indicated that 2.0 lg phenols/ml significantly induced apoptosis. Similarly, at 2.0, 1.6, and 1.0 lg phenols/ ml a significant decrease of ICAM-1 and IL-8 protein levels was observed. ICAM-1, as well as IL-8, mRNA expression were decreased in the presence of 2.0 lg phenols/ml. Results indicate that the methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death and suppressing inflammation in AGS cells.

Clinical and Vaccine Immunology, 2010

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses ... more Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-α) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. H...

World journal of hepatology, Jan 28, 2015

Hepatitis B virus (HBV) infection is the leading cause of liver disease and hepatocellular carcin... more Hepatitis B virus (HBV) infection is the leading cause of liver disease and hepatocellular carcinoma (HCC) worldwide, in spite of prophylactic vaccination and antiviral treatment modalities. The immunopathogenesis of HBV infection has been intensively studied and is propelled by complex interactions between the virus and the host immune system. Natural killer group 2D (NKG2D) is a well-characterized activating receptor, expressed on natural killer (NK) cells, NK T cells and CD8(+) cytotoxic T cells. This receptor is present in both humans and mice and binds to a diverge family of ligands that resemble the MHC-class I molecules. Increasing evidence shows that NKG2D-ligand interactions are critical in the establishment of HBV persistence and the development of liver injury and HCC. The expression of NKG2D ligands depends on the presence of several polymorphisms and is also modulated post-transcriptionally by HBV. While it is known that HBV circumvents host's innate immunity via th...