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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

World Journal of Stem Cells 2024年第5期16卷 551-559页

作者： Amani Yehya Joseph Azar Mohamad Al-Fares Helene Boeuf wassim abou-kheir Dana Zeineddine Ola Hadadeh Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal Lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,*** mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac *** hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of *** size of the generated EBs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and ***,troponin T protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of Bcl-

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation B-cell lymphoma 2 PIM-2 Metallothionein-1

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Colorectal cancer:Recent advances in management and treatment

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World Journal of Clinical Oncology 2024年第9期15卷 1136-1156页

作者： Hiba Fadlallah Jad El Masri Hiam Fakhereddine Joe Youssef Chrystelle Chemaly Samer Doughan wassim abou-kheir Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Department of Surgery American University of Beirut Medical CenterBeirut 1107-2020Lebanon

Colorectal cancer(CRC)is the third most common cancer worldwide,and the second most common cause of cancer-related *** 2020,the estimated number of deaths due to CRC was approximately 930000,accounting for 10%of all cancer deaths ***,there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and *** management strategies for CRC include surgical procedures for resectable cases,and radiotherapy,chemotherapy,and immunotherapy,in addition to their combination,for non-resectable *** these options,CRC remains incurable in 50%of ***,significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated,leading to the availability of new drugs and therapeutic *** review summarizes the most recent therapeutic approaches for CRC,with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC.

关键词： Colorectal cancer Treatment Surgery Chemotherapy Targeted therapy Immunotherapy

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Tissue-specific cancer stem/progenitor cells:Therapeutic implications

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World Journal of Stem Cells 2023年第5期15卷 323-341页

作者： Amani Yehya Joe Youssef Sana Hachem Jana Ismael wassim abou-kheir Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon

Surgical resection,chemotherapy,and radiation are the standard therapeutic modalities for treating *** approaches are intended to target the more mature and rapidly dividing cancer ***,they spare the relatively quiescent and intrinsically resistant cancer stem cells(CSCs)subpopulation residing within the tumor ***,a temporary eradication is achieved and the tumor bulk tends to revert supported by CSCs'resistant *** on their unique expression profile,the identification,isolation,and selective targeting of CSCs hold great promise for challenging treatment failure and reducing the risk of cancer ***,targeting CSCs is limited mainly by the irrelevance of the utilized cancer models.A new era of targeted and personalized anti-cancer therapies has been developed with cancer patient-derived organoids(PDOs)as a tool for establishing pre-clinical tumor ***,we discuss the updated and presently available tissue-specific CSC markers in five highly occurring solid ***,we highlight the advantage and relevance of the threedimensional PDOs culture model as a platform for modeling cancer,evaluating the efficacy of CSC-based therapeutics,and predicting drug response in cancer patients.

关键词： Cancer stem cells Therapy resistance Tissue-specific cancer stem cell markers Patient-derived organoids Pre-clinical cancer models

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Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer:Updates and beyond

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World Journal of Gastroenterology 2023年第9期29卷 1395-1426页

作者： Samar Al Bitar Marwan El-Sabban Samer Doughan wassim abou-kheir Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Department of Surgery American University of Beirut Medical CenterBeirut 1107-2020Lebanon

Colorectal cancer(CRC)is the third most diagnosed malignancy and a major leading cause of cancer-related deaths *** advances in therapeutic regimens,the number of patients presenting with metastatic CRC(mCRC)is increasing due to resistance to therapy,conferred by a small population of cancer cells,known as cancer stem *** therapies have been highly successful in prolonging the overall survival of patients with *** are being developed to target key molecules involved in drug-resistance and metastasis of CRC,and these include vascular endothelial growth factor,epidermal growth factor receptor,human epidermal growth factor receptor-2,mitogen-activated extracellular signal-regulated kinase,in addition to immune ***,there are several ongoing clinical trials of newly developed targeted agents,which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional *** this review,we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and ***,we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies,in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection.

关键词： Colorectal cancer Metastatic colorectal cancer Targeted therapy Drugresistance Personalized medicine

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Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling

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World Journal of Stem Cells 2021年第8期13卷 1112-1126页

作者： Zaki abou-Mrad Jolie Bou Gharios Maya M Moubarak Ahmad Chalhoub Charbel Moussalem Hisham F Bahmad wassim abou-kheir Department of Anatomy Cell Biology and Physiological SciencesFaculty of MedicineAmerican University of BeirutBeirut 1107-2020Lebanon Division of Neurosurgery Department of SurgeryAmerican University of Beirut Medical CenterBeirut 1107-2020Lebanon Arkadi M.Rywlin M.D.Department of Pathology and Laboratory Medicine Mount Sinai Medical CenterMiami BeachFL 33140United States

Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and ***,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable *** tumors are highly heterogenous and complex in their *** to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in ***-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to ***,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo ***,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic *** this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current *** will also elaborate on the future implications of these models and their benefit in the clinical setting.

关键词： Central nervous system tumors Glioblastoma Three-dimensional modelling Spheroids Organoids

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Drug resistance in metastatic castration-resistant prostate cancer:an update on the status quo

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Cancer Drug Resistance 2022年第3期5卷 667-690页

作者： Amani Yehya Fatima Ghamlouche Amin Zahwe Yousef Zeid Kevork Wakimian Deborah Mukherji wassim abou-kheir Department of Anatomy Cell Biology and Physiological SciencesFaculty of MedicineAmerican University of BeirutBeirut 1107-2020Lebanon Division of Hematology/Oncology Faculty of MedicineAmerican University of Beirut Medical CenterBeirut 1107-2020Lebanon

Prostate cancer(PCa)is a leading cause of cancer-related morbidity and mortality in men *** improvements in the diagnosis and treatment of PCa,a significant proportion of patients with high-risk localized disease and all patients with advanced disease at diagnosis will experience progression to metastatic castration-resistant prostate cancer(mCRPC).Multiple drugs are now approved as the standard of care treatments for patients with mCRPC that have been shown to prolong *** the majority of patients will respond initially,primary and secondary resistance to these therapies make mCRPC an incurable *** molecular mechanisms underlie the development of mCRPC,with the androgen receptor(AR)axis being the main driver as well as the key drug *** resistance mechanisms is crucial for discovering novel therapeutic strategies to delay or reverse the progression of the *** this review,we address the diverse mechanisms of drug resistance in *** addition,we shed light on emerging targeted therapies currently being tested in clinical trials with promising potential to overcome mCRPC-drug resistance.

关键词： Prostate cancer mCRPC androgen receptor drug resistance novel targeted therapeutics

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Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and threedimensional in vitro models

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World Journal of Gastroenterology 2022年第33期28卷 4787-4811页

作者： Alissar Monzer Kevork Wakimian Farah Ballout Samar Al Bitar Amani Yehya Mariam Kanso Nour Saheb Ayman Tawil Samer Doughan Maher Hussein Deborah Mukherji Walid Faraj Hala Gali-Muhtasib wassim abou-kheir Department of Biology American University of BeirutBeirut 1107-2020Lebanon Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Department of Surgery American University of Beirut Medical CenterBeirut 1107-2020Lebanon Department of Pathology and Laboratory Medicine American University of Beirut Medical CenterBeirut 1107-2020Lebanon Department of Internal Medicine American University of Beirut Medical CenterBeirut 1107-2020Lebanon Department of Biology and Center for Drug Discovery American University of BeirutBeirut 1107-2020Lebanon

BACKGROUND Colorectal cancer(CRC) is the second leading cause of cancer-related *** stem cells(CSCs) in CRC, which are spared by many chemotherapeutics,have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone(DIQ) has shown promising effects on targeting colon ***, there is limited research on the effects of DIQ on eradicating CSCs in *** To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional(2D) and three-dimensional(3D) models using colonospheres and patient-derived *** Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays,immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid *** Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116and HT29 stem/progenitor cells at sub-toxic doses of 1 μmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related-catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil *** This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

关键词： Diiminoquinone Anticancer activity Colorectal cancer Cancer stem cells Patient-derived organoids Colonospheres

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A New Kind of Atomic Force Microscopy Scan Control Enabled by Artificial Intelligence:Concept for Achieving Tip and Sample Safety Through Asymmetric Control

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Nanomanufacturing and Metrology 2024年第2期7卷 50-59页

作者： Johannes Degenhardt Mohammed wassim Bounaim Nan Deng Rainer Tutsch Gaoliang Dai Physikalisch-Technische Bundesanstalt Bundesallee 10038116 BrunswickGermany Institut Für Prozessmess-und Sensortechnik Technische Universität Ilmenau EhrenbergstraBe 2998693 IlmenauGermany Institute of Production Metrology TU Braunschweig SchleinitzstraBe 2038106 BrunswickGermany

This paper introduces a paradigm shift in atomic force microscope(AFM)scan control,leveraging an artificial intelligence(AI)-based *** contrast to conventional control methods,which either show a limited performance,such as proportional integral differential(PID)control,or which purely focus on mathematical optimality as classical optimal control approaches,our proposed AI approach redefines the objective of control for achieving practical *** presented AI controller minimizes the root-mean-square control deviations in routine scans by a factor of about 4 compared to PID control in the presented setup and also showcases a distinctive asymmetric response in complex situations,prioritizing the safety of the AFM tip and sample instead of the lowest possible control *** development and testing of the AI control concept are performed on simulated AFM scans,demonstrating its huge potential.

关键词： Atomic force microscopy Artificial intelligence Deep reinforcement learning Optimal control

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Solute transport and geochemical modeling of the coastal quaternary aquifer, Delta Dahab Basin, South Sinai, Egypt

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Acta Geochimica 2024年第1期43卷 16-39页

作者： Amira Samy Mustafa Eissa Seham Shahen Moustafa M.Said Rabab M.abou-shahaba Division of Water Resources and Arid Land Department of HydrogeochemistryDesert Research CenterCairoEgypt Egypt Desalination Research Center of Excellence Desert Research CenterCairoEgypt Center for Water Supply Studies S&E-Physical&Environmental SciencesTexas A&M University Corpus ChristiCorpus ChristiUSA Department of Chemistry Faculty of Science(Girls)Al-Azhar UniversityYousef Abbas StrNasr CityP.O.Box:11754CairoEgypt

The wadi dahab delta is in a dry, arid coastal zone within Egypt’s south Sinai Peninsula’s eastern portion. The primary water source is the Quaternary coastal alluvial aquifer. The groundwater salinity varies from 890to 8213 mg/L, with a mean value of 3417 mg/L. The dissolved major ions have been used to calculate the seawater mixing index(SWMI) using a linear equation that discriminates the groundwater mostly affected by water–rock interaction(SWMI 1>) and other samples mixed with Seawater(SWMI < 1). The isotopic composition of groundwater for specifically chosen groundwater samples ranges from-0.645‰ to +5.212‰ for δ^(18)O and from-9.582‰ to + 22.778‰ for δ^(2)H, where the seawater represented by a Red Sea water sample(δ^(18)O + 1.64‰-δ^(2)H + 9.80‰) and reject brine water are considerably enriched the isotopic groundwater values. The geochemical NETPATH model constrained by the dissolved significant ions, isotopes, and the rock aquifer forming minerals as phases indicate the mixing percent with the seawater ranges from 9% to 97% of seawater from 91% to 3% of original recharge water. According to the SEAWAT 3-D flow models, seawater has penetrated the Northeastern Dahab delta aquifer, with the intrusion zone extending1500 m inland. The salt dissolution, upwelling of saline water, recharge from the upstream mountain block, and seawater encroachment are the primary aspects contributing to the deterioration of groundwater quality. These findings may have significance for effective groundwater withdrawal management in arid locations worldwide with similar hydrogeological systems.

关键词： Groundwater geochemistry Seawater intrusion Solute transport SEAWAT

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An Application of Machine Learning Methods to Detect Mango Varieties

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Open Journal of Applied Sciences 2024年第7期14卷 1666-1690页

作者： abou Bakary Ballo Moustapha Diaby Adama Coulibaly Department of Mathematics and Computer Science University FLIX HOUPHOUT-BOIGNY Abidjan Cte dIvoire African College of Information and Communication Technologies Abidjan Cte dIvoire

The mango, a fruit of immense economic and dietary significance in numerous tropical and subtropical regions, plays a pivotal role in our agricultural landscape. Accurate identification is not just a necessity, but a crucial step for effective classification, sorting, and marketing. This study delves into the potential of machine learning for this task, comparing the performance of four models: MobileNetV2, Xception, VGG16, and ResNet50V2. These models were trained on a dataset of annotated mango images, and their performance was evaluated using precision, accuracy, F1 score, and recall, which are standard metrics for image classification. The Xception model, with its exceptional performance, outshone the other models on all performance indicators. It achieved a staggering accuracy of 99.47%, an F1 score of 99.43%, and a recall of 99.43%, showcasing its remarkable ability to accurately identify mango varieties. MobileNetV2 followed closely with performances of 98.95% accuracy, 98.85% F1 score, and 98.86% recall. ResNet50V2 also delivered satisfactory results with 97.39% accuracy, 97.08% F1 score, and 97.17% recall. VGG16, however, was the least effective, with a precision rate of 83.25%, an F1 score of 83.25%, and a recall of 85.47%. These results confirm the superiority of the Xception model in detecting mango varieties. Its advanced architecture allows it to capture more distinguishing features of mango images, leading to greater precision and reliability. Xception’s robustness in identifying true positives is another advantage, minimizing false positives and contributing to more accurate classification. This study highlights the promising potential of machine learning, particularly the Xception model, for accurately identifying mango varieties.

关键词： Machine Learning Recognition Mango Varieties Algorithms Feature Extraction Convolution Training Classification

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