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Micelles as potential drug delivery systems for colorectal cancer treatment

World Journal of Gastroenterology 2022年第25期28卷 2867-2880页

作者： Zaynab Fatfat Maamoun Fatfat hala gali-muhtasib Department of Biology American University of BeirutBeirut 11072020Lebanon Center for Drug Discovery American University of BeirutBeirut 11072020Lebanon

Despite the significant progress in cancer therapy,colorectal cancer(CRC)remains one of the most fatal malignancies *** is currently the mainstay therapeutic modality adopted for CRC ***,the long-term effectiveness of chemotherapeutic drugs has been hampered by their low bioavailability,non-selective tumor targeting mechanisms,non-specific biodistribution associated with low drug concentrations at the tumor site and undesirable side *** the last decade,there has been increasing interest in using nanotechnology-based drug delivery systems to circumvent these *** nanoparticles have been developed for delivering chemotherapeutic drugs among which polymeric micelles are attractive *** micelles are biocompatible nanocarriers that can bypass the biological barriers and preferentially accumulate in tumors via the enhanced permeability and retention *** can be easily engineered with stimuli-responsive and tumor targeting moieties to further ensure their selective uptake by cancer cells and controlled drug release at the desirable tumor *** have been shown to effectively improve the pharmacokinetic properties of chemotherapeutic drugs and enhance their safety profile and anticancer efficacy in different types of *** that combination therapy is the new strategy implemented in cancer therapy,polymeric micelles are suitable for multidrug delivery and allow drugs to act concurrently at the action site to achieve synergistic therapeutic *** also allow the delivery of anticancer genetic material along with chemotherapy drugs offering a novel approach for CRC ***,we highlight the properties of polymeric micelles that make them promising drug delivery systems for CRC *** also review their application in CRC chemotherapy and gene therapy as well as in combination cancer chemotherapy.

关键词： Polymeric micelles Drug delivery Colorectal cancer Chemotherapy Gene therapy Combination cancer therapy

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Antioxidative, cytotoxic, and anti-metastatic potentials of Laurencia obtusa and Ulva lactuca seaweeds

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Asian Pacific Journal of Tropical Biomedicine 2021年第7期11卷 308-316页

作者： Reem Al Monla Yahya Salma Achraf Kouzayha hala gali-muhtasib Zeina Dassouki Hiba Mawlawi Laboratory of Applied Biotechnology(LBA3B) AZM Center for Research in Biotechnology and its ApplicationsDoctoral School for Sciences and TechnologyLebanese UniversityTripoliLebanon Department of Biology American University of BeirutLebanon Center for Drug Discovery American University of BeirutRiad El Solh 11072020BeirutLebanon

Objective:To investigate the antioxidant and cytotoxic properties of the most active extracts from Ulva lactuca and Laurencia obtusa against colon and cervical cancer cell ***:The antioxidant radical scavenging activity of the algal extracts was estimated using the 2,2-diphenyl-1-picrylhydrazyl colorimetric ***,the cytotoxic potential of these bioactive extracts was studied against HCT-116 and HeLa cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide *** healing analysis was adopted to evaluate the antimetastatic effects of protein extracts from both *** cycle analysis was performed by flow cytometry,and apoptotic bodies were detected using 4′,6-diamidino-2-phenylindole fluorescent *** acids of hydrolyzed protein extract were separated and identified chromatographically by high performance liquid ***:The green algae Ulva lactuca had higher lipid content than Laurencia obtusa,whereas the latter had higher protein content with high antioxidant *** extracts had significant dose-and time-dependent cytotoxicity and anti-metastatic activity against HCT-116 *** b extracts of both algae obtained from the chloroform:hexane solvent lipid-free residue caused morphological changes and induced apoptosis of HCT-116 *** analysis revealed that apoptosis induced upon Laurencia obtusa protein b treatment was triggered via the ROS pathway,causing a significant increase in the sub-G_(1) *** and arginine(5.94 and 5.47μM,respectively)were the most common amino acids in Laurencia obtusa protein b ***:Proteins of Laurencia obtusa and Ulva lactuca could be considered as an adjuvant nutraceutical source of pro-apoptotic and anti-metastatic biomolecules against colon cancer.

关键词： Macroalgae Laurencia obtusa Ulva lactuca Reactive oxygen species Apoptosis

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Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

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World Journal of Clinical Oncology 2021年第7期12卷 522-543页

The long-term success of standard anticancer monotherapeutic strategies has been hampered by intolerable side effects,resistance to treatment and cancer *** monotherapeutic strategies shrink the tumor bulk but do not effectively eliminate the population of self-renewing cancer stem cells(CSCs)that are normally present within the *** surviving CSCs develop mechanisms of resistance to treatment and refuel the tumor,thus causing cancer *** ensure durable tumor control,research has moved away from adopting the monotreatment paradigm towards developing and using combination *** different therapeutic modalities has demonstrated significant therapeutic outcomes by strengthening the anti-tumor potential of monotreatment against cancer and cancer stem cells,mitigating their toxic adverse effects,and ultimately overcoming ***,there has been growing interest in combining natural products from different sources or with clinically used chemotherapeutics to further improve treatment efficacy and ***(TQ),the main bioactive constituent of Nigella sativa,has gained great attention in combination therapy research after demonstrating its low toxicity to normal cells and remarkable anticancer efficacy in extensive preclinical studies in addition to its ability to target chemoresistant ***,we provide an overview of the therapeutic responses resulting from combining TQ with conventional therapeutic agents such as alkylating agents,antimetabolites and antimicrotubules as well as with topoisomerase inhibitors and non-coding *** also review data on anticancer effects of TQ when combined with ionizing radiation and several natural products such as vitamin D3,melatonin and other compounds derived from Chinese medicinal *** focus of this review is on two outcomes of TQ combination therapy,namely eradicating CSCs and treating various types of *** conclusion,the ability of TQ to potentiate the ant

关键词： Thymoquinone Combination therapy Cancer cells Cancer stem cells Conventional cancer therapy Natural products

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Thymoquinone anticancer activity is enhanced when combined with royal jelly in human breast cancer

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World Journal of Clinical Oncology 2021年第5期12卷 342-354页

作者： Maya M Moubarak Nour Chanouha Najwa Abou Ibrahim hala Khalife hala gali-muhtasib Department of Biology American University of BeirutBeirut 1107-2020Lebanon Rammal Rammal Laboratory(ATAC group) Faculty of Sciences IHadath 1003Lebanon Department of Biology and Center for Drug Discovery American University of BeirutBeirut 1107-2020Lebanon

BACKGROUND Breast cancer is the most common cause of the majority of cancer-related deaths in women,among which triple-negative breast cancer is the most aggressive type of breast cancer diagnosed with limited treatment ***(TQ),the main bioactive constituent of Nigella sativa,has been extensively studied as a potent anticancer molecule against various types of *** products such as the royal jelly(RJ),the nutritive secretion fed to honeybee queens,exhibit a variety of biological activities besides its anticancer ***,the anticancer activity of the combination of TQ and RJ against breast cancer is still *** To investigate cytotoxicity of RJ in FHs 74 Int cells and the anticancer effects of TQ,RJ,and their combinations in the MDA-MB-231 cell *** Cells were treated with TQ,RJ,and their combinations for 24 *** 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,we determined the half-maximal inhibitory concentration of *** blue and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were then performed to assess the cell viability in response to different treatment *** death and cycle regulation were investigated using propidium iodide deoxyribonucleic acid staining followed by flow cytometry in response to a single dose of TQ,RJ,and their *** for cleaved caspase 3 and Ki67 expression was used to determine apoptosis induction and changes in cell *** TQ alone inhibited cell viability in a dose-dependent manner at concentrations below and above the half-maximal inhibitory *** exhibited relatively nontoxic effects against MDA-MB-231 cells and FHs 74 Int small intestinal cells at concentrations below 5μg/*** doses of RJ(200μg/mL)had greater toxicity against MDA-MB-231 ***,the inhibition of cell viability was most pronounced in response to 15μmol/L TQ and 5μg/mL RJ.A dose of 15μmol/L TQ caused a

关键词： Anticancer activity Breast cancer cells Drug combination Natural products Royal jelly Thymoquinone

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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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Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis

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World Journal of Clinical Oncology 2023年第5期14卷 203-214页

作者： Sima AlDreini Zaynab Fatfat Najwa Abou Ibrahim Maamoun Fatfat hala gali-muhtasib hala Khalife Rammal Rammal Laboratory(ATAC Group) Faculty of Sciences IHadath 1003Lebanon Department of Biology American University of BeirutBeirut 1107-2020Lebanon Applied Biochemistry Laboratory School of PharmacyCamerino UniversityCamerino 62032Italy

BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous *** recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including ***,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of *** To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential *** Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu *** antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human *** anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer *** The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,*** natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced *** also dose-dependently decreased the viability of both cancer cell *** IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,***

关键词： Lebanese propolis Thymoquinone Combination Antioxidant activity Anticancer activity Phenolic compounds

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Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies

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World Journal of Gastrointestinal Pathophysiology 2021年第4期12卷 59-83页

作者： Samar Al Bitar Tala Ballouz Samer Doughan hala gali-muhtasib Nesrine Rizk Department of Biology American University of BeirutBeirut 11072020Lebanon Department of Internal Medicine American University of Beirut Medical CenterBeirut 11072020Lebanon Department of Surgery American University of Beirut Medical CenterBeirut 11072020Lebanon Department of Biology and Center for Drug Discovery American University of BeirutBeirut 11072020Lebanon

Despite advances in antiretroviral treatment(ART),human immunodeficiency virus(HIV)continues to be a major global public health issue owing to the increased mortality rates related to the prevalent oncogenic viruses among people living with HIV(PLWH).Human papillomavirus(HPV)is the most common sexually transmitted viral disease in both men and women ***-risk or oncogenic HPV types are associated with the development of HPV-related malignancies,including cervical,penile,and anal cancer,in addition to oral *** incidence of anal squamous cell cancers is increasing among PLWH,necessitating the need for reliable screening methods in this population at *** fact,the currently used screening methods,including the Pap smear,are invasive and are neither sensitive nor *** are interested in circulatory and tissue micro ribonucleic acids(miRNAs),as these small non-coding RNAs are ideal biomarkers for early detection and prognosis of *** miRNAs are deregulated during HIV and HPV infection and their deregulation contributes to the pathogenesis of ***,we will review the molecular basis of HIV and HPV co-infections and focus on the pathogenesis and epidemiology of anal cancer in *** limitations of screening for anal cancer and the need for a reliable screening program that involves specific miRNAs with diagnostic and therapeutic values is also discussed.

关键词： Human papillomavirus Human immunodeficiency virus Anal cancer Micro ribonucleic acids Biomarkers Cancer screening

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Enhancing Cancer Classification through a Hybrid Bio-Inspired Evolutionary Algorithm for Biomarker Gene Selection

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Computers, Materials & Continua 2024年第4期79卷 675-694页

作者： hala AlShamlan halah AlMazrua Department of Information Technology College of Computer and Information SciencesKing Saud UniversityP.O.Box 145111Riyadh4545Saudi Arabia

In this study,our aim is to address the problem of gene selection by proposing a hybrid bio-inspired evolutionary algorithm that combines Grey Wolf Optimization(GWO)with Harris Hawks Optimization(HHO)for feature *** for utilizingGWOandHHOstems fromtheir bio-inspired nature and their demonstrated success in optimization *** aimto leverage the strengths of these algorithms to enhance the effectiveness of feature selection in microarray-based cancer *** selected leave-one-out cross-validation(LOOCV)to evaluate the performance of both two widely used classifiers,k-nearest neighbors(KNN)and support vector machine(SVM),on high-dimensional cancer microarray *** proposed method is extensively tested on six publicly available cancer microarray datasets,and a comprehensive comparison with recently published methods is *** hybrid algorithm demonstrates its effectiveness in improving classification performance,Surpassing alternative approaches in terms of *** outcomes confirm the capability of our method to substantially improve both the precision and efficiency of cancer classification,thereby advancing the development ofmore efficient treatment *** proposed hybridmethod offers a promising solution to the gene selection problem in microarray-based cancer *** improves the accuracy and efficiency of cancer diagnosis and treatment,and its superior performance compared to other methods highlights its potential applicability in realworld cancer classification *** harnessing the complementary search mechanisms of GWO and HHO,we leverage their bio-inspired behavior to identify informative genes relevant to cancer diagnosis and treatment.

关键词： Bio-inspired algorithms bioinformatics cancer classification evolutionary algorithm feature selection gene expression grey wolf optimizer harris hawks optimization k-nearest neighbor support vector machine

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Enhancing IoT Data Security with Lightweight Blockchain and Okamoto Uchiyama Homomorphic Encryption

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Computer Modeling in Engineering & Sciences 2024年第2期138卷 1731-1748页

作者： Mohanad A.Mohammed hala B.Abdul Wahab Computer Science Department The University of TechnologyBaghdadIraq

Blockchain technology has garnered significant attention from global organizations and researchers due to its potential as a solution for centralized system ***,the Internet of Things(IoT)has revolutionized the Fourth Industrial Revolution by enabling interconnected devices to offer innovative services,ultimately enhancing human *** paper presents a new approach utilizing lightweight blockchain technology,effectively reducing the computational burden typically associated with conventional blockchain *** integrating this lightweight blockchain with IoT systems,substantial reductions in implementation time and computational complexity can be ***,the paper proposes the utilization of the Okamoto Uchiyama encryption algorithm,renowned for its homomorphic characteristics,to reinforce the privacy and security of IoT-generated *** integration of homomorphic encryption and blockchain technology establishes a secure and decentralized platformfor storing and analyzing sensitive data of the supply chain *** platformfacilitates the development of some business models and empowers decentralized applications to perform computations on encrypted data while maintaining data *** results validate the robust security of the proposed system,comparable to standard blockchain implementations,leveraging the distinctive homomorphic attributes of the Okamoto Uchiyama algorithm and the lightweight blockchain paradigm.

关键词： Blockchain IoT integration of IoT and blockchain consensus algorithm Okamoto Uchiyama homomorphic encryption lightweight blockchain

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Progression of e-ticketing implementation for state transportation agencies for asphalt materials

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Journal of Road Engineering 2024年第1期4卷 80-92页

作者： Joshua Withrow Gabriel B.Dadi hala Nassereddine Department of Civil Engineering University of KentuckyLexingtonKY 40506USA Kentucky Transportation Cabinet FrankfortKY 40622USA

E-ticketing,which has been promoted by the Federal Highway Administration(FHWA)“every day counts”(EDC)initiative,utilizes software applications to digitally track and store information regarding highway construction materials paid by state transportation agencies(STAs)by weight in unit bid contract *** often face implementation barriers such as institutional inertia,or the resistance by stakeholders to adopt changes from the status quo,including new *** purpose of this paper is to determine the progression of STA e-ticketing policy adoption,specifically with a focus on asphalt paving operations,due to the COVID-19 *** accomplish this research effort,previous FHWA data,National Cooperative Highway Research Program(NCHRP)data,and other literatures are reviewed to determine an implementation *** data is collected from the American Association of State Highway and Transportation Officials Committee on Con-struction to gain current feedback from STAs and their highway contractor partners after the COVID-19 ***,a case study featuring the Kentucky Transportation Cabinet(KYTC),the Kentucky Association of Highway Contractors(KAHC),and the Plantmix Asphalt Industry of Kentucky(PAIKY)is performed to provide more in-depth *** major finding includes a statistically significant result indicating increased imple-mentation of e-ticketing for asphalt operations within the last two years,along with noting benefits including employee safety,task loading,and project documentation along with concerns regarding cellular connectivity and procurement *** findings indicate the importance of STAs investing in partnership with con-tractors to improve stakeholder buy-in before proceeding towards e-ticketing adoption.

关键词： Asphalt paving Construction inspection E-ticketing COVID-19

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