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Naif A Al-Gabri,1,2 Sultan AM Saghir,3 Sallah A Al-Hashedi,4 Ali H El-Far,5 Asmaa F Khafaga,6 Ayman A Swelum,7 Abdullah S Al-wajeeh,8 Shaker A Mousa,9 Mohamed E Abd El-Hack,10 Mohammed AE Naiel,11 Khaled A El-Tarabily12,13 1Department of Pathology, Faculty of Veterinary Medicine, Thamar University, Dhamar, Yemen; 2Laboratory of Regional Djibouti Livestock Quarantine, Abu Yasar international Est. 1999, Arta, Djibouti; 3Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Medical Sciences, AlHussein Bin Talal University, Ma’an, 71111, Jordan; 4Central Labs, King Faisal University, Al-Ahsa, Saudi Arabia; 5Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt; 6Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina, 22758, Egypt; 7Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt; 8Anti-Doping Lab Qatar, Doha, Qatar; 9Department of Pharmaceutical Sciences, the Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, 12144, USA; 10Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig, 44519, Egypt; 11Animal Production Department, Faculty of Agriculture, Zagazig University, Zagazig, 44519, Egypt; 12Department of Biology, College of Science, United Arab Emirates University, Al-Ain, 15551, United Arab Emirates; 13Biosecurity and One Health Research Centre, Harry Butler Institute, Murdoch University, Murdoch, Western Australia, 6150, AustraliaCorrespondence: Khaled A El-Tarabily Email ktarabily@uaeu.ac.aeAbstract: As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.Keywords: anticancer activity, antimicrobial activity, bioavailability, drug delivery, molecular potential, lung disease, nanoparticle, thymoquinone

Samah A Loutfy,1,2 Mostafa H Elberry,1 Khaled Yehia Farroh,3 Hossam Taha Mohamed,4,5 Aya A Mohamed,4 ElChaimaa B Mohamed,1 Ahmed Hassan Ibrahim Faraag,6 Shaker A Mousa7 1Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Nanotechnology Research Center, British University, Cairo, Egypt; 3Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt; 4Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th October, Giza, Egypt; 5Department of Zoology, Faculty of Science,Cairo University, Giza, Egypt; 6Botany and Microbiology Department, Bioinformatics Center, Faculty of Science, Helwan University, Cairo, Egypt; 7The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USACorrespondence: Samah A LoutfyVirology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr El Eini, Fom El-Khalig, Cairo 11796, EgyptTel +20 1222840964Email Samah.loutfy@gmail.comPurpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7.Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot.Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29– 39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 μg/mL for curcumin and 25 μg/mL for the nanocomposite on Huh7 but was 25.8 μg/mL and 34 μg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression.Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.Keywords: caspase-dependent pathway, chitosan curcumin nanocomposite, hepatitis C virusgenotype 4a, Huh7, docking

Purpose Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29–39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.

Deena S Mousa,1 Ali H El-Far,2 Amna A Saddiq,3 Thangirala Sudha,4 Shaker A Mousa4 1Yale University, New Haven, CT, USA; 2Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt; 3Faculty of Science, Department of Biology, University of Jeddah, Jeddah 21589, Saudi Arabia; 4Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USACorrespondence: Shaker A MousaProfessor of Pharmacology, Albany College of Pharmacy and Health Sciences, Chairman and Executive Vice President, The Pharmaceutical Research Institute, One Discovery Drive, Rensselaer, New York 12144, USAEmail shaker.mousa@acphs.eduPurpose: This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer.Background: Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3′-diindolylmethane (DIM) and ellagicacid (EA) demonstrated anticancer efficacy against various cancer types. However, DIMis insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells.Methods: Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model.Results: Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24hrs (P < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight (P < 0.01), tumor cell viability, and tumor angiogenesis (P < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone.Conclusion: Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.Keywords: pancreatic cancer, 3, 3′-diindolylmethane, ellagic acid, PLGA-PEG nanoparticles, anti-angiogenesis, chick chorioallantoic membrane model

Taher A Salaheldin,1,2 Samah A Loutfy,3 Marwa A Ramadan,4 Tareq Youssef,4 Shaker A Mousa11Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; 2Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt; 3Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 4Department of Photochemistry Photobiology, National Institute for Laser Enhanced Science (NILES) Cairo University, Cairo, EgyptBackground: Graphene magnetite nanocomposites (G/Fe3O4) exhibit light photothermal conversion upon enhancement by 808 nm IR laser excitation. We evaluated the cytotoxic and photothermal effects of G/Fe3O4 on a HepG2 human liver cancer cell model.Methods: Graphene nanosheets (rGO), magnetite nanoparticles (Fe3O4), and G/Fe3O4 were prepared by chemical methods and characterized using transmission electron microscopy, Raman spectroscopy, zeta analysis, and vibrating sample magnemeter. Dark and light cytotoxicity were screened with colorimetric Sulforhodamine B cell viability assay after 24 and 48 hours. DNA fragmentation and some apoptotic genes on a transcriptional RNA level expression were performed. All prepared nanomaterials were evaluated for their photothermal effect at concentrations of 10 and 50 μg/mL. The power density incident on the cells by 300 mW 808 IR diode laser was 0.597 W/cm2,.Results: Treatment of HepG2 with 400 μg/mL of rGO, Fe3O4, and G/Fe3O4 showed alteration in cell morphology after 24 hours of cell treatment and revealed toxic effects on cellular DNA. Evaluation of the cytotoxic effects showed messenger RNA (mRNA) in β-actin and Bax apoptotic genes, but no expression of mRNA of caspase-3 after 24 hours of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway. A photothermal effect was observed for G/Fe3O4 after irradiation of the HepG2 cells. A marked decrease was found in cell viability when treated with 10 and 50 μg/mL G/Fe3O4 from 40% to 5% after 48 hours of cell treatment.Conclusion: Results indicate that G/Fe3O4 nanocomposite was effective at transformation of light into heat and is a promising candidate for cancer therapy.Keywords: graphene magnetite nanocomposite, HepG2 human liver cancer, cytotoxicity, photothermal effect, PCR

Dhruba J Bharali, Marianne Khalil, Mujgan Gurbuz, Tessa M Simone, Shaker A MousaPharmaceutical Research Institute at Albany College of Pharmacy, Rensselaer, NY, USAAbstract: The emergence of nanotechnology has had a profound effect on many areas of healthcare and scientific research. Having grown exponentially, the focus of nanotechnology has been on engineering diversified novel applications that even go beyond therapeutic activity; nanotechnology also offers the ability to detect diseases, such as cancer, much earlier than ever imaginable. Often, patients diagnosed with breast, lung, colon, prostate, and ovarian cancer have hidden or overt metastatic colonies. With the advent of diagnostic nanotechnology, these numbers are expected to greatly diminish. This review provides a brief description of nanoparticle (liposome, quantum dot, and dendrimer)-mediated cancer therapy in the last decade with an emphasis on the development and use of dendrimers in cancer therapeutics.Keywords: nanoparticles, dendrimer, quantum dots, liposome