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Naif Khalaf Alharbi,1,2 Jaffar A Al-Tawfiq,3– 5 Amal Alwehaibe,1 Mohamed W Alenazi,1 Abdulrahman Almasoud,1 Abdullah Algaisi,6 Fahad A Alhumaydhi,7 Anwar M Hashem,8,9 Mohammed Bosaeed,1,2,10 Suliman A Alsagaby11 1Vaccine Development Unit, King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 2College of Medicine, King Saud bin Abdulaziz University for Health Science (KSAU-HS), Riyadh, Saudi Arabia; 3Specialty Internal Medicine and Quality Department, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia; 4Infectious Diseases Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 5Infectious Diseases Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 6Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 8Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 9Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 10King Abdulaziz Medical City (KAMC), Ministry of National Guard – Health Affairs (MNG-HA), Riyadh, Saudi Arabia; 11Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi ArabiaCorrespondence: Naif Khalaf Alharbi, Email naifkhalaf2014@gmail.comPurpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia.Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples.Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01).Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.Keywords: COVID-19, vaccines, BNT162b2, AZD1222, Immune responses, antibody, IgG

Suliman A Alsagaby Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, AL-Majmaah, 11932, Saudi ArabiaCorrespondence: Suliman A Alsagaby, Email s.alsaqaby@mu.edu.saIntroduction: Zinc oxide nanoparticles (ZnO NPs) show anti-cancer activity. Diffuse Large B-cell Lymphoma (DLBCL) is a type of B-cell malignancies with unsatisfying treatment outcomes. This study was set to assess the potential of ZnO NPs to selectively induce apoptosis in human DLBCL cells (OCI-LY3), and to describe possible molecular mechanisms of action.Methods: The impact of ZnO NPs on DLBCL cells and normal peripheral blood mononuclear cells (PBMCs) was studied using cytotoxicity assay and flow-cytometry. Transcriptomics analysis was conducted to identify ZnO NPs-dependent changes in the transcriptomic profiles of DLBCL cells.Results: ZnO NPs selectively induced apoptosis in DLBCL cells, and caused changes in their transcriptomes. Deferential gene expression (DGE) with fold change (FC) ≥ 3 and p ≤ 0.008 with corrected p ≤ 0.05 was identified for 528 genes; 125 genes were over-expressed and 403 genes were under-expressed in ZnO NPs-treated DLBCL cells. The over-expressed genes involved in biological processes and pathways like stress response to metal ion, cellular response to zinc ion, metallothioneins bind metals, oxidative stress, and negative regulation of growth. In contrast, the under-expressed genes were implicated in DNA packaging complex, signaling by NOTCH, negative regulation of gene expression by epigenetic, signaling by WNT, M phase of cell cycle, and telomere maintenance. Setting the FC to ≥ 1.5 with p ≤ 0.05 and corrected p ≤ 0.1 showed ZnO NPs to induce over-expression of anti-oxidant genes and under-expression of oncogenes; target B-cell receptor (BCR) signaling pathway and NF-κB pathway; and promote apoptosis by intrinsic and extrinsic pathways.Discussion: Overall, ZnO NPs selectively induced apoptosis in DLBCL cells, and possible molecular mechanisms of action were described.Keywords: transcriptomics, ZnO NPs, DLBCL, apoptosis, mechanism of action

Suliman A Alsagaby,1 Mafawez T Alharbi2 1Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia; 2Department of Natural and Applied Sciences, Community College, Qassim University, Buraydah, Saudi ArabiaCorrespondence: Mafawez T Alharbi; Suliman A Alsagaby Email maft.alharbi@qu.edu.sa; s.alsaqaby@mu.edu.saBackground: Information technology (IT) has emerged as a promising enabler to address the issue of big data in health care. Despite the urgent need for an IT-based tool to tackle this issue, one is not available to specifically study the massive data related to cancer among Saudis.Objective: To develop a web-based application, which we named “Cancer in Saudi Arabia (CSA)” to provide an interactive, quick, and easy method to reach, extract, compare, and visualize cancer data from Saudi Cancer Incidence Reports (SCIRs).Methods: We used waterfall model to develop CSA. Next, we used CSA to study the data of non-Hodgkin lymphoma (NHL) in Saudis reported in the SCIRs (1999– 2015).Results: CSA-based analysis showed that NHL incidence rate increased with age and the disease was more common among males compared with females. In addition, NHL was most predominant in the regions of Riyadh and Eastern, while it was the least prevalent in Jazan Region. Interestingly, the largest proportion of NHL patients was diagnosed in the late stage, and malignant lymphoma, large B-cell diffuse, OS (DLBCL) were the most frequent subtypes of NHL.Conclusion: As a user-friendly application, we believe that CSA will be a useful tool for studying cancer data in Saudis and will make the data published in SCIRs more reachable and usable. Our findings of NHL provided an almost comprehensive view of the epidemiology of the disease in Saudis for 17 years.Keywords: information technology, cancer in Saudis, epidemiology, big data, waterfall model

Suliman A Alsagaby,1 Rajendran Vijayakumar,2 Mariappan Premanathan,2 Suresh Mickymaray,2 Wael Alturaiki,1 Raid S Al-Baradie,1 Saleh AlGhamdi,3,4 Mohammad A Aziz,4,5 Fahad A Alhumaydhi,6 Faisal A Alzahrani,7 Ameen S Alwashmi,6 Waleed Al Abdulmonem,8 Naif Khalaf Alharbi,4,9 Chris Pepper10 1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11932, Saudi Arabia; 2Department of Biology, College of Sciences, Majmaah University, Majmaah 11932, Saudi Arabia; 3Clinical Research Department, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia; 4King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia; 5Colorectal Cancer Research Program, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 6Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia; 7Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 8Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia; 9Department of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 10Brighton and Sussex Medical School, University of Sussex, Brighton, UKCorrespondence: Suliman A AlsagabyDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, PO Box 1712, Majmaah 11932, Saudi ArabiaTel +966 542552749Email s.alsaqaby@mu.edu.saIntroduction: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach.Objective: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action.Methods: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells.Results: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤ 0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥ 4 and p≤ 0.008 with corrected p≤ 0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in “response to zinc”, “response to toxic substance” and “negative regulation of growth” (corrected p≤ 0.05). In contrast, the repressed genes positively regulated “cell proliferation”, “cell migration”, “cell adhesion”, “receptor signaling pathway via JAK-STAT” and “phosphatidylinositol 3-kinase signaling” (corrected p≤ 0.05). Lowering the FC to ≥ 1.5 with p≤ 0.05 and corrected p≤ 0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway.Conclusion: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.Keywords: transcriptomics, ZnO NPs, CML, apoptosis