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Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

World Journal of Gastroenterology 2017年第5期23卷 743-750页

作者： youssef Alhmada Denis Selimovic Fadi Murad Sarah-Lilly Hassan youssef haikel Mossaad Megahed Matthias Hannig Mohamed Hassan Department of Pathology University of Mississippi Medical Center Graduate School of Dental Medicine Depart-ment of Restorative DentistryDivision of Oral Health ScienceHokkaido University Clinic of Operative Dentistry Periodontology and Preventive DentistrySaarland University Department of Surgery Tulane University School of Medicine Clinic of Dermatology University Hospital of Aachen Institut National de la Santéet de la RecherchéMédicale Department of Operative Dentistry and Endodontics Dental FacultyUniversity of Strasbourg

In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients’ sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.

关键词： Hepatitis C virus Pruritus Cholestasis Autotoxin Lysophosphatidic acid PI3 kinase

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Hepatitis C virus-related hepatocellular carcinoma:An insight into molecular mechanisms and therapeutic strategies

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World Journal of Hepatology 2012年第12期4卷 342-355页

作者： Denis Selimovic Abdelouahid El-Khattouti Hanan Ghozlan youssef haikel Ola Abdelkader Mohamed Hassan Institut National de la Santé et de la Recherche Médicale U 97767000 StrasbourgFrance Department of Operative Dentistry and Endodontics Dental FacultyUniversity of Strasbourg67000 StrasbourgFrance Cancer Institute University of Mississippi Medical CenterJacksonMS 39216United States Deparment of Microbiology Faculty of ScienceUniversity of AlexandriaAlexandria 4285455Egypt Department of Microbiology Medical Research InstituteUniversity of AlexandriaAlexandria 4285455Egypt

Hepatitis C virus(HCV) infects more than 170 million people worldwide,and thereby becomes a series global health *** infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular *** the multiple functions of the HCV proteins and their impacts on the modulation of the intracellular signaling transduction processes,the drive of carcinogenesis during the infection with HCV,is thought to result from the interactions of viral proteins with host cell ***,the induction of mutator phenotype,in liver,by the expression of HCV proteins provides a key mechanism for the development of HCV-associated hepatocellular carcinoma(HCC).HCC is considered one of the most common malignancies worldwide with increasing incidence during the past *** many countries,the trend of HCC is attributed to several liver diseases including HCV ***,the development of HCC is very complicated and results mainly from the imbalance between tumor suppressor genes and oncogenes,as well as from the alteration of cellular factors leading to a genomic *** the poor prognosis of HCC patients,this type of tumor is quite resistance to the available ***,understanding the molecular mechanisms,which are implicated in the development of HCC during the course of HCV infection,may help to design a general therapeutic protocol for the treatment and/or the prevention of this *** review summarizes the current knowledge of the molecular mechanisms,which are involved in the development of HCV-associated HCC and the possible therapeutic strategies.

关键词： Hepatitis C virus Hepatocellular carcinoma Cirrhosis Fibrosis Inflammation Carcinogenesis

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Hepatitis C virus-mediated angiogenesis:Molecular mechanisms and therapeutic strategies

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World Journal of Gastroenterology 2014年第42期20卷 15467-15475页

作者： Mohamed Hassan Denis Selimovic Abdelouahid El-Khattouti Martine Soell Hanan Ghozlan youssef haikel Ola Abdelkader Mosaad Megahed Cancer Institute University of Mississippi Medical Center Institut National de la Santé et de la Recherché Médicale S 1121 Hospitals of Hautepierre Dental Faculty University of Strasbourg Department of Operative Dentistry and Endodontics Hospitals of Hautepierre Dental Faculty University of Strasbourg Department of Periodontology Hospitals of Hautepierre Dental Faculty University of Strasbourg Department of Microbiology Faculty of Science Medical research Institute University of Alexandria Department of Microbiology Medical research Institute University of Alexandria Clinic of Dermatology University Hospital of Aachen

Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus(HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.

关键词： Hepatitis C virus Hepatocellular carcinoma Angiogenesis Signaling pathway Therapy

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Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment

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World Journal of Experimental Medicine 2015年第4期5卷 206-217页

作者： Mohamed Hassan Denis Selimovic Matthias Hannig youssef haikel Robert T Brodell Mossaad Megahed Clinic of Operative Dentistry Periodontology and Preventive DentistryUniversity Hospital Saarland University Cancer Institute University of Mississippi Medical Center Department of Pathology University of Mississippi Medical Center Institut National de la Santé et de la Recherché Medical U1121 University of Strasbourg Department of Operative Dentistry and Endodontics Dental Faculty University of Strasbourg Department of Dermatology University of Mississippi Medical Center Clinic of Dermatology University Hospital of Aachen

Melanoma is the most aggressive form of skin *** intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation,there is increasing evidence that endoplasmic reticulum(ER) stress-associated pathways play a role in the potentiation,initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment.

关键词： Melanoma Endoplasmic reticulum Apoptosis Autophagy Signaling pathways Chemotherapy

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Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies

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World Journal of Experimental Medicine 2012年第2期2卷 7-25页

作者： Mohamed Hassan Denis Selimovic Abdelouahid El-Khattouti Hanan Ghozlan youssef haikel Ola Abdelkader National Institute of Health and Medical Research U 977Faculty of Medicineand Dental Faculty Department of Operative Dentistry and Endodontics Dental FacultyUniversity of Strasbourg Laboratory for Molecular Tumor Therapy niversity Hospital of Duesseldorf Institute of Haemostasis and Transfusion Medicine University Hospital of Duesseldorf Deparment of Microbiology Faculty of ScienceUniversity of Alexandria Department of Microbiology Medical Research InstituteUniversity of Alexandria

Hepatitis C virus(HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon basedtherapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection(HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.

关键词： Hepatitis C virus Hepatocellular carcinoma Extrahepatic Signalling Therapy

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Isolation and Identification of Two Antibacterial Agents from <i>Chromolaena odorata</i>L. Active against Four Diarrheal Strains

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Advances in Microbiology 2013年第1期3卷 115-121页

作者： Ménonvè Atindehou Latifou Lagnika Bernard Guérold Jean Marc Strub Minjie Zhao Alain Van Dorsselaer Eric Marchioni Gilles Prévost youssef haikel Corinne Taddéi Ambaliou Sanni Marie-Hélène Metz-Boutigue CNRS UMR7178 University of Strasbourg Strasbourg France EA 7290 University of Strasbourg Strasbourg France Faculté de Chirurgie Dentaire Université de Strasbourg Strasbourg France Inserm UMR 1121 University of Strasbourg Strasbourg France IPHC-DSA CNRS University of Strasbourg Strasbourg France Université d’Abomey-Calavi Laboratoire de Biochimie et Biologie Moléculaire (LBBM) Cotonou Bénin

Chromolaena odorata L (Asteraceae) is a bad invasive plant, found in the humid tropics and sub-tropics worldwide. It is used against dysentery, diarrhea, malaria, wound healing, headache and toothache in traditional medicine. In the present study, we investigated the antibacterial activities of different leaves extracts of Chromolaena odorata L. (cyclohexane, dichloromethane, ethyl acetate and butanol) against four clinical diarrheal strains (Klebsiella oxytoca, Salmonella enterica, Shigella sonnei and Vibrio cholera). We demonstrated that C. odorata leaves extracts show an antibacterial activity between 0.156 and 1.25 mg/mL. Bioassay-guided chromatography by bioautography with iodonitrotetrazolium-based colorimetric assay allowed the isolation and identification of two active compounds. After the combination of RP-HPLC, mass spectrometry analysis, 1D and 2D-NMR spectroscopy, we isolated and characterized two active molecules corresponding to 3’,4’,5,6,7-Pentamethoxyflavone (Sinensetin) and4’,5,6,7-Tetramethoxyflavone (Scutellareintetramethyl ether).

关键词： Chromolaena odorata 3’ 4’ 5 6 7-Pentamethoxyflavone (Sinensetin) 7-Tetramethoxyflavone (Scutellareintetramethyl ether) Antibacterial Activity Diarrheal Strains

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CNN Ensemble Approach to Detect COVID-19 from Computed Tomography Chest Images

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Computers, Materials & Continua 2021年第6期67卷 3581-3599页

作者： haikel Alhichri Department Computer Engineering Advanced Lab for Intelligent SystemsCollege of Computer and Information SciencesKing Saud ArabiaRiyadh11543Saudi Arabia

In January 2020,the World Health Organization declared a global health emergency concerning the spread of a new coronavirus disease,which was later named *** and fast diagnosis and isolation of COVID-19 patients have proven to be instrumental in limiting the spread of the *** tomography(CT)is a promising imaging method for fast diagnosis of *** this study,we develop a unique preprocessing step to resize CT chest images to a fixed size(256×256 pixels)that preserves the aspect ratio and reduces image ***,we present a deep learning(DL)method to classify CT chest images based on the light-weight pre-trained EfficientNet-B3 CNN model and ensemble *** proposed method,which we refer to as EfficientNet-B3-GAP-Ensemble,comprises an ensemble of a modified version of the *** build the ensemble using multiple runs and multiple training *** test the EfficientNet-B3-GAPEnsemble on two common benchmark datasets,i.e.,the COVID19-CT and SARS-CoV-2-CT *** proposed method has outperformed state-ofthe-art methods for both *** the COVID19-CT dataset,it achieved 88.18%sensitivity,88.29%precision,88.18%accuracy,an F1-score of 88.15%,and AUC of 92.10%.With the SARS-CoV-2-CT dataset,we tested the proposed method under different train-test splits,i.e.,20%–80%,50%–50%,and 80%–20%.For the latter split,the proposed method achieved 99.72%accuracy,99.80%sensitivity,precision,and F1-scores,and an AUC score of 99.99%.

关键词： COVID-19 detection computed tomography deep learning convolutional neural network EffecientNet-B3 ensemble techniques

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Photogrammetry and deep learning for energy production prediction and building-integrated photovoltaics decarbonization

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Building Simulation 2024年第2期17卷 189-205页

作者： Ilyass Abouelaziz youssef Jouane CESI LINEACT 7 bis Av.Robert Schuman51100ReimsFrance CESI LINEACT Parc Club des Tanneries 2 all Foulons67380StrasbourgFrance

Building-Integrated photovoltaics(BIPV)have emerged as a promising sustainable energy solution,relying on accurate energy production predictions and effective decarbonization strategies for efficient *** paper presents a novel approach that combines photogrammetry and deep learning techniques to address the problem of BIPV *** method is called BIM-AITIZATION referring to the integration of BIM data,AI techniques,and automation *** integrates photogrammetric data into practical BIM *** addition,it enhances the precision and reliability of PV energy prediction by using artificial intelligence *** primary aim of this approach is to offer advanced,data-driven energy forecasts and BIPV decarbonization while fully automating the underlying *** achieve this,the first step is to capture point cloud data of the building through photogrammetric *** data undergoes preprocessing to identify and remove unwanted points,followed by plan segmentation to extract the plan *** that,a meteorological dataset is assembled,incorporating various attributes that influence energy production,including solar irradiance parameters as well as BIM ***,machine and deep learning techniques are used for accurate photovoltaic energy predictions and the automation of the entire *** experiments are conducted,including multiple tests aimed at assessing the performance of diverse machine learning *** objective is to identify the most suitable model for our specific ***,a comparative analysis is undertaken,comparing the performance of the proposed model against that of various established BIPV software *** outcomes reveal that the proposed approach surpasses existing software solutions in both accuracy and *** extend its applicability,the approach is evaluated using a building case study,demonstrating its ability to generalize effectively to new bui

关键词： building-integrated photovoltaic(BIPV) deep learning building information modeling photogrammetric building decarbonization

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DEPENDENCE OF MODULUS OF ELASTICITY AND THERMAL CONDUCTIVITY ON REFERENCE TEMPERATURE IN GENERALIZED THERMOELASTICITY FOR AN INFINITE MATERIAL WITH A SPHERICAL CAVITY

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Applied Mathematics and Mechanics(English Edition) 2005年第4期26卷 470-475页

作者： Hamdy M.youssef Mathematical Department Faculty of Engineering Umm Al_Qura UniversityMakkah Al_Mokaramah P.5555 Saudi Arabia

The equations of generalized thermoelasticity with one relaxation time with variable modulus of elasticity and the thermal conductivity were used to solve a problem of an infinite material with a spherical *** inner surface of the cavity was taken to be traction free and acted upon by a thermal shock to the surface. Laplace transforms techniques were used to obtain the solution by a direct *** inverse Laplace transforms was obtained *** temperature,displacement and stress distributions are represented graphically.

关键词： thermoelasticity generalized thermoelasticity modulus of elasticity thermal conductivity

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Interleukin-1 and estrogen protect against disseminating dentoalveolar infections

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International Journal of Oral Science 2017年第1期9卷 16-23页

作者： hesham youssef philip stashenko host-microbiome center department of applied oral sciencesthe forsyth instituteCambridgeUSA

Dentoalveolar bacterial infections cause localized tissue and bone destruction, but usually remain well-localized within teeth in immunocompetent hosts. However, in certain cases these infections may invade head and neck tissues, resulting in orofacial abscesses, cellulitis and sepsis, with resultant high morbidity and even mortality. In the present studies, we developed a novel model of spreading dentoalveolar infections in mice by treatment with neutralizing antibodies against both interleukin-la （IL-1a） and IL-1β. Surprisingly male but not female mice given anti-lL-1 antibodies developed orofacial abscesses, weight loss, splenomegaly and sepsis. Female mice developed abscesses and sepsis comparable to males following ovariectomy （OVX）, which was reversed by estrogen supplementation. Anti-lL-1 blockade inhibited IL-12, interferon y （IFNy） and IL-6 but not IL-IO expression in infrabony lesions, suggestive of a local anti-inflammatory response. There was greater infiltration of neutrophils and other inflammatory ceils into lesions in anti-lL-l-treated animals; however, blood leukocytes had reduced bacterial phagocytic and killing activity ex vivo. Estrogen directly stimulated IL-1 production by macrophages, suggesting that the resistance of females to disseminating dentoalveolar infections may be due to their heightened pro-inflammatory responses following bacterial challenge, leading to enhanced localization of these infections.

关键词： cytokines dentoalveolar disseminating infections estrogen neutrophils

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