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Platelet-activating factor in liver injury: A relational scope

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World Journal of Gastroenterology 2006年第23期12卷 3695-3706页

作者： Nikolaos P Karidis Gregory Kouraklis stamatios E theocharis Department of Forensic Medicine and Toxicology University of Athens Medical SchoolAthensGreece Second Department of Propaedeutic SurgeryUniversity of Athens Medical SchoolAthensGreece Second Department of Propaedeutic Surgery University of Athens Medical SchoolAthensGreece Department of Forensic Medicine and Toxicology University of Athens Medical SchoolAthensGreece

The hepatocyte, the main cellular component of the liver, exhibits variable susceptibility to different types of injury induced by endogenous or exogenous factors. Hepatocellular dysfunction or death and regeneration are dependent upon the complicated interactions between numerous biologically active molecules. Platelet- activating factor （PAF） seems to play a pivotal role as the key mediator of liver injury in the clinical and experimental setting, as implied by the beneficial effects of its receptor antagonists. A comprehensive up-to-date overview of the specific functional and regulatory properties of PAF in conditions associated with liver injury is attempted in this review.

关键词： PAF PAF-R antagonists Liver Injury Regeneration

Angiogenesis in gastrointestinal stromal tumors:From bench to bedside

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1469-1477页

作者： Stavros P Papadakos Christos Tsagkaris Marios Papadakis Andreas S Papazoglou Dimitrios V Moysidis Constantinos G Zografos stamatios theocharis First Department of Pathology School of MedicineNational and Kapodistrian University of AthensAthens 10679Greece Faculty of Medicine University of CreteHeraklion 71003Greece University Hospital Witten-Herdecke University of Witten-HerdeckeWuppertal 42283Germany First Department of Cardiology AHEPA University HospitalAristotle University of ThessalonikiThessaloniki 54636Greece First Department of Surgery Athens Medical SchoolNational and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece First Department of Pathology Medical SchoolUniversity of AthensAthens 11527Greece

Gastrointestinal stromal tumors(GISTs)are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per *** most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach,but also the small intestine,the omentum,mesentery and *** available treatments for GIST are associated with a significant rate of recurrent disease and adverse *** understanding of GIST’s pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this *** present review summarizes the existing evidence about the role of angiogenesis in GIST’s development and progression and discusses its clinical underpinnings.

关键词： Gastrointestinal stromal tumor Cancer Oncology Angiogenesis Gastrointestinal oncology Stromal tumors

Histone deacetylase inhibitors and pancreatic cancer:Are there any promising clinical trials?

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World Journal of Gastroenterology 2013年第8期19卷 1173-1181页

作者： Ioannis Koutsounas Constantinos Giaginis stamatios theocharis Department of Forensic Medicine and Toxicology Medical SchoolUniversity of AthensGR-11527 AthensGreece Department of Food Science and Nutrition University of the AegeanGR-81400 LemnosGreece

Pancreatic cancer,although not very frequent,has an exceptionally high mortality rate,making it one of the most common causes of cancer mortality in developed *** cancer is difficult to diagnose,allowing few patients to have the necessary treatment at a relatively early *** a marginal benefit in survival,the overall response of pancreatic cancer to current systemic therapy continues to be poor,and new therapies are desperately *** deacetylase(HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors(HDACIs) have been shown to induce differentiation and cell cycle arrest,activate the extrinsic or intrinsic pathways of apoptosis,and inhibit invasion,migration and angiogenesis in different cancer cell *** a result of promising preclinical data,various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological *** was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell *** use of HDACIs in clinical trials,in pretreated and relapsed patients suffering from advanced pancreatic cancer is ***,clinical data for HDACIs in patients with pancreatic cancer are inadequate,because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase Ⅱ/Ⅲ trials,among others with advanced solid tumors,is very *** studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.

关键词： Pancreatic cancer Histone deacetylases Histone deacetylase inhibitors Clinical trials

Circadian variation in expression of G_1 phase cyclins D_1 and E and cyclin-dependent kinase inhibitors p16 and p21 in human bowel mucosa

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World Journal of Gastroenterology 2006年第13期12卷 2109-2114页

作者： John Griniatsos Othon P Michail stamatios theocharis Antonios Arvelakis Ioannis Papaconstantinou Evangelos Felekouras Emmanouel Pikoulis Ioannis Karavokyros Chris Bakoyiannis George Marinos John Bramis Panayiotis O Michail 1st Department of Surgery Medical School University of AthensGreece Department of Forensic Medicine and Toxicology Medical School University of AthensGreece

AIM： To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS： Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalinfixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours （00：00, 06：00, 12：00, 18：00 and 24：00）, we studied the expression of G1 phase cyclins （D1 and E） as well as the expression of the G1 phase cyclin-dependent kinase （CDK） inhibitors p16 and p21 as indicators of cell cycle progres- sion in colonic epithelial cells using immunohistochemical methods. RESULTS： The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00：00 and 18：00, respectively （P〈 0.001）. A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12：00 and 18：00 （P〈0.001）, respectively. When the complexes cyclins D1-p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D1-p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00：00, 06：00 and 24：00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18：00. CONCLUSION： Colonic epithelial cells seem to enter the G1 phase of the cell cycle during afternoon （between 12：00 and 18：00） with the highest rates obtained at 18：00. From a clinical point of view, the present results suggest that G1-phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.

关键词： G1 phase proteins CDK inhibitors Cell proliferation Circadian rhythm

Current evidence for histone deacetylase inhibitors in pancreatic cancer

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World Journal of Gastroenterology 2013年第6期19卷 813-828页

作者： Ioannis Koutsounas Constantinos Giaginis Efstratios Patsouris stamatios theocharis First Department of Pathology Medical SchoolNational and Kapodistrian University of AthensGR-11527 AthensGreece Department of Food Science and Nutrition University of the AegeanGR-81400 LemnosGreece

Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every *** recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient *** effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of *** new agents,histone deacetylase inhibitors (HDACIs) are now being *** have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and *** induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell *** the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are *** constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses.

关键词： Pancreatic cancer Histone deacetylases Histone deacetylase inhibitors Experimental studies

Slope stability of reclaimed coal mines through a new water filling index

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第3期16卷 828-839页

作者： Antonios Mikroutsikos Alexandros I.theocharis Nikolaos C.Koukouzas Ioannis E.Zevgolis Chemical Process&Energy Resources Institute Centre for Research&Technology HellasAthensGreece School of Mining and Metallurgical Engineering National Technical University of AthensAthensGreece

A common reclamation practice for closed coal surface mines is filling them with water to form pit *** creation and sustainability of these lakes are significantly affected by the stability of the corresponding *** present study provides a general framework for analyzing the water filling’s effect on slope stability based on a new water filling index,which can indirectly consider the factors affecting the process and efficiently quantify the filling speed’s *** assumptions of the proposed approach are thoroughly discussed,and the range of the water filling index is ***,the safety factor is calculated using the finite element method with the shear strength reduction technique during the filling process for various conditions(soil properties,slope geometry,hydraulic conditions,and water filling speed).Results are presented as normalized stability charts for practical *** the water filling,the stability gradually decreases until the reservoir reaches a critical level of 10%e40%of the total height;it then increases to even more stable conditions than the initial ***,the present analysis allows for the preliminary stability evaluation of a coal mine during the formation of a pit lake and the appropriate quantification of the water filling’s effect.

关键词： Post-coal era Open-pit flooding Stability charts Critical level

Drawing lines in the sand: The growing threat of obesity in type 1 diabetes

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World Journal of Diabetes 2024年第5期15卷 823-827页

作者： theocharis Koufakis Dimitrios Patoulias Ioanna Zografou Nikolaos Papanas Djordje S Popovic Second Propedeutic Department of Internal Medicine Aristotle University of ThessalonikiThessaloniki 54642Greece Diabetes Centre Second Department of Internal MedicineDemocritus University of ThraceAlexandroupolis 68100Greece Clinic for Endocrinology Diabetes and Metabolic DisordersClinical Center of VojvodinaMedical FacultyUniversity of Novi SadNovi Sad 21000Serbia

In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in *** focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this *** exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in *** our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of *** regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes *** this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

关键词： Obesity Overweight Type 1 diabetes Metabolic syndrome

Remission of type 2 diabetes depends on prompt comprehensive lifestyle changes upon diagnosis: How can this“Road to Damascus” experience be supported?

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Journal of Integrative Medicine 2022年第4期20卷 288-291页

作者： theocharis Koufakis Kalliopi Kotsa Nikolaos Papanas Division of Endocrinology and Metabolism and Diabetes Centre First Department of Internal MedicineMedical SchoolAristotle University of ThessalonikiAHEPA University Hospital54636 ThessalonikiGreece Diabetes Centre Second Department of Internal MedicineDemocritus University of Thrace68100 AlexandroupolisGreece

Theoretically, a new diagnosis of type 2 diabetes mellitus(T2DM) requires a dramatic change in an individual’s way of life. Weight loss and physical activity can lead to remission of diabetes, which has been associated with a lower risk of developing complications. Today, the importance of a healthy lifestyle is further highlighted by data showing that obesity and diabetes increase the risk of severe complications from coronavirus disease 2019. However, remission rarely occurs in reality, probably due to the inability of people with T2DM to adhere to the intensive lifestyle interventions that are necessary. The complexity of contributing factors may explain why making these changes is so challenging and underscore the fact that there is no magical solution for T2DM. Instead, hard work from both patients and health care providers is needed for the conversion to be achieved. This article calls for more research on the underlying reasons why adhering to a healthy way of life is so difficult for people with diabetes and obesity. Clearly defining these barriers would facilitate the planning of effective policies to promote the adoption of appropriate lifestyle changes early in the course of the disease.

关键词： Type 2 diabetes Remission Exercise Diet Lifestyle change

A real-world data collection framework for a fused dataset creation for joint human and remotely operated vehicle monitoring and anomalous command detection

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CAAI Transactions on Intelligence Technology 2022年第3期7卷 432-445页

作者： Rafaella Elia George Plastiras Eva Pettemeridou Antonis Savva theocharis Theocharides Department of Electrical and Computer Engineering University of CyprusNicosiaCyprus KIOS Research and Innovation Center of Excellence University of CyprusNicosiaCyprus Center for Applied Neuroscience(CAN) University of CyprusNicosiaCyprus

Unmanned Remotely Operated Vehicles(ROVs)are widely used in safety-critical missions,spanning across monitoring,surveillance,and search and rescue *** most cases,the human operator controls the ROV under stressful conditions and in harsh *** physical and mental states of the operator are vital as they may cause involuntary movements,issuing unintentional commands due to fatigue or ***,a joint monitoring mechanism that will assess the operator's commands can be beneficial in preventing potentially catastrophic events,such as *** this end,in this study,we propose a data collection framework for creating a fused dataset,consisting of data obtained from both the human operator and the ROV,and we integrate stress induction to stimulate stress and fatigue that may affect operators during *** optimise the dataset,which includes the operator's physiological signals and inertial measurement unit(IMU)sensor data from the ROV,using data fusion approaches and feature *** evaluate the dataset through the statistical analysis,illustrating a statistical difference between data characterising normal and involuntary ***,we evaluate the optimised and original datasets over a variety of classifiers,demonstrating an accuracy of 94%and 95%,respectively.

关键词： operator fused operators