معهد البحوث والاستشارات الطبية | Institute for Research and Medical Consultations
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Item Development of New Drug against Multidrug Resistance Candida auris by Mining Genome from Marine Bacteria(2023) Eman Saleh Alhasani; Noor B AlmandilThe most common multi-drug-resistant fungal infection in the Arabian Peninsula is Candida auris, which is responsible for high mortality. Identifying novel drugs is in high demand in this scenario. Microbes in marine environments are genetically adapted to survive in varying conditions like extreme temperatures, salinity, pH, and extra stress features by synthesizing different bioactive metabolites. These microbial bioactive novel secondary metabolites are highpotential compounds that can be utilized as anti-Candida molecules. Microorganisms in the marine environment can produce diverse ranges of secondary metabolites (SM), which are also known as natural products. Finding and identifying novel drugs from synthetic bacterial compounds or natural materials is a promising strategy due to the scarcity of antifungal medications and the evolution of drug resistance in C. auris. Natural compounds have many benefits over synthetic substances, including structural variety and comparatively low toxicity. Next-generation sequence-based studies on anti-Candida auris bacterial organisms for discovering novel drug candidates are scanty. Hence, this study is proposed to identify biosynthetic gene clusters from marine bacteria using next-generation sequencing for discovering novel drug compounds against MDR C. auris. More than 68 isolates have been isolated from various marine environments using standard techniques. All these isolates were tested against the multi-drug-resistant C. auris. Bacterial strain ESH58 isolated from a fish liver sample showed the highest and most constant activity against C. auris. Cell membrane disruption was observed in C. auris by the defused metabolites of ESH58 bacteria using SEM. An experimental in vitro assessment of the toxicity revealed no cell cytotoxicity of ESH58 against HFF-1 cells. The native bacterial strain ESH58 with a biosynthetic gene cluster of potential natural anti-C. auris compounds with no pathogenic protein-coding genes highlights the significance of marine bacteria in the fight against Candida auris. After the in vivo studies, drug targets will be taken for the pre-clinical studies in association with pharmaceutical companies in the future.Item Development of an SNP detection panel for the cost-effective diagnosis of thrombosis risk factors(2023) Reham Khalid Altwayan; Huseyin TombulogluThrombophilia is defined as the willingness of blood to clot easily in a situation of imbalances between fibrinolysis and coagulation. It is classified as inherited and acquired thrombophilia. Several studied revealed that the inherited thrombophilia is strongly associated with single nucleotide polymorphisms (SNP) or deletions on certain genes, such as FV Leiden, MTHFR1, MTHFR2, Serpine-1, and Factor II. The current genotyping techniques to identify these mutations are based on PCR and sequencing, which are time consuming and expensive methods. Therefore, a cost-effective, time- saving, and accurate technique is needed to screen symptomatic and asymptomatic suspicious people. This thesis aims to develop an SNP detection panel based on Kompetitive Allele Specific Primer-polymerase chain reaction (KASP-PCR) technique. Results revealed that 86.5% of susceptible patients (n = 111) contain at least one mutation. The results were validated through a novel colorimetric loop-amplified isothermal amplification (LAMP) and sanger sequencing techniques by selecting random samples. Rather than expensive and time-consuming approaches, the current assay enables the cost-effective advantage of the KASP-PCR, which reduces the diagnostic cost with a fast and convenient way. After clinical validation and approval, it can be used in hospitals, research centers, and diagnostic laboratories to determine the genetic susceptibility of individuals to thrombosis and also for research purposes.Item Study the toxicity and biocompatibility aspects of Zinc Phosphate [Zn3(PO4)2] nanoparticles in Mice and Rats and their effect on body functions.(2023) Noha Mubarak Bin Mahfooz; Abdelgadir Musa HomeidaNanomaterials (NMs), substances that have internal or surface structure dimension that is at the nanoscale (less than 100 nm) have been employed throughout biomedical research studies The objective of this study was to synthesize Zinc Phosphate Nanoparticles (ZnP NPs) Zn3(PO4)2, analyse the chemical characteristic, structure and morphology, study the cytotoxicity and haemolytic effect in-vitro and to investigate the acute toxic potential in adult male rats and mice. In this study, a formulation of phosphate-based zinc nanoparticles was synthetized and tested. The formulation of zinc nanoparticles based on phosphates with irregular morphology were prepared. Transmission electron microscopy (TEM) was used to examine the morphology and size of Zn3(PO4)2The size average was about 43 nm as calculated by TEM image. It also shows that nanoparticle is asymmetrical in shape, semispherical and includes heterojunctions in-between. Scanning electron microscopy (SEM), demonstrates the surface of ZnP NPs which looks like fine flakes. The NPs produced in-vitro 20% haemolysis of rat red blood cells a concentration of 1mg/mL. The MTT assay (cell viability) was performed in normal cell line of Human embryonic kidney (HEK 293). Zinc phosphate nanoparticles showed a non-toxic effect on HEK 293 cells when the concentration of NPs was lower than 1mg/ mL. However, the concentration of the nanoparticles is directly proportional with cell toxicity, higher the concentration, more the toxicity. The highest in-vitro inhibitory effect of our NPs was observed against viability of cells. After the successful in-vitro testing, the in vivo LD50 was determined in rats and mice. Values of LD50 acute toxicity of zinc phosphate nanomaterials were determined. According to Hodge and Sterner toxicity scale, the obtained value of LD 50 of zinc phosphate nanoparticles in rats is 2512 mg/Kg body weight which is of slightly toxic category. In mice the LD50 is 5000 mg/Kg body weight which is practically non-toxic. The clinical blood chemistry analyses showed no significant differences in serum metabolites or enzyme activities between the control group and the exposed rats dosed with 300mg/Kg body weight. However, enzyme activities, and concentration of blood urea nitrogen and uric acid were significantly increased in rats dosed with 2000 mg/Kg body weight. The results indicated that ZPNMs are nontoxic at a dose of 1mg/mL in-vitro and at a dose of 300mg/Kg body weight in-vivo in rats.Item Enhancement of superconducting performances of YBa2Cu3O7-δ compound with co-addition of nanoparticles of ternary and binary perovskite oxides(2022) Alotaibi, Sarah Awaadh Fares; Yassine Slimani; Munirah Abdullah AlmessiereThe discovery of high-temperature superconducting materials (HTS) is a new leap in materials science for their unique properties that differentiate them from other conductive materials, which give them preference in the field of practical and technical applications. Interesting generation of high-temperature superconducting was discovered for the called Yttrium Barium Copper Oxide (YBa2Cu3Oy, noted as YBCO for abbreviation) material with high critical current density (Jc), elevated critical temperature (Tc) above the liquid nitrogen boiling point (77 K), and high critical magnetic fields (Hc). These unique features open the way for YBCO superconductors for various applications. The main issue in YBCO performance was the rapid decrease in Jc value at high applied fields. This is due to the existence of weak links within the polycrystalline YBCO materials and the motion of vortices under an applied magnetic field. Improving the intergranular properties of polycrystalline YBCO materials and generating artificial pinning centers (APCs) within YBCO matrix were the most efficient solutions. These can be achieved by using chemical doping/substitution or additives. In this work, we aimed to enhance the performance of YBCO superconductor by introducing appropriate and efficient pinning centers. Accordingly, we have studied the influence of co-adding a ternary dielectric perovskite oxide and a binary perovskite oxide like transition metal oxide on the superconducting properties of YBCO material. For doing so, high purity of BaTiO3 and WO3 nanoparticles were firstly prepared via sol-gel auto-combustion route and hydrothermal method, respectively. Then, pure YBCO (x = 0.00 wt.%) and YBCO co-added with different amounts of nanoparticles of BaTiO3 and WO3 (x = 0.05, 0.10, and 0.20 wt.%) were synthesized by using the solid-state reaction approach. The structure, morphology, electrical, and magnetic properties of different compositions were deeply investigated using X-ray powder diffraction (XRD), field-emission scanning electron microscope (FESEM), standard four-probe method, and physical property measurement system (PPMS), respectively. XRD analyses revealed that the orthorhombic structure is preserved for lower concentrations of co-added BTO/WO3 nanoparticles. FESEM observations showed the implantation of W-rich nanosized entities within the grains and dispersion of both BTO and WO3 nanoparticles at the grain boundaries to play the role of bridges connecting the superconducting grains. The electrical resistivity measurements revealed the manifestation of transition to the superconducting state for all prepared samples. Further analyses of the critical current density (Jc), flux pinning, as well as intergranular and intragranular properties, were explored by using the DC magnetization and AC magnetic susceptibility measurements. The magnetization critical current density (Jc) and intergranular critical current density J_cinter are significantly enhanced for the 0.05 wt.% BTO/WO3 nanoparticles co-added YBCO sample. The boosting factor for Jc in this composition reached up to 45 in the entire applied magnetic field compared to the pristine YBCO sample. All these results proved the important role of BaTiO3/WO3 nanoparticles co-addition on the flux pinning strengthening in the YBCO superconductor, indicating that these nanoparticles are promising artificial pinning centers to enhance the performance of YBCO material. Our obtained results can provide a reference for the demonstration of large-scale HTSc systems in different technologies and are very encouraging in view of the wide implementation of these YBCO/(BTO/WO3)x samples in several applications including power energy transmission, energy storage, superconducting MRI magnets, etc.Item Design and Structure of Nano Spinel Ferrite-Based Electrodes for High-Performance Supercapacitor Applications(2022) Alqarni, Ameerah Nasser Ali; إمري سيفيكItem The Impact of Biologically Synthesized Nanoparticles on Colon Cancer Cells: In Vitro Cellular and Morphological Investigation(2022) Rasdan, Alia Saeed Mohammed; فردوس علم خانAbstract: Colorectal cancer (CRC) attacks the colon or rectal region of the large intestine. CRC is the third globally prevalent cause of cancer mortality. Although current treatments are effective, they have several drawbacks such as systemic toxicity. Therefore, nanoparticles (NPs) are being investigated as delivery systems. Green synthesized NPs are eco-friendly, non-toxic, and safe to manufacture, making them a better option than chemically synthesized NPs. In this project, we tested green vs. chemically synthesized NPs with and without date extract to study their cytotoxic effects. The sol-gel approach was used to create CoFe2O4/(Ni0.4Cu0.2Zn0.4Fe1.8O4( NPs. Characterization was performed using XRD, SEM, TEM, and zeta potential to investigate the NP structure and morphology. These assays confirmed the chemical composition with size ranging from 24 to 41 nm. Furthermore, we performed MTT, DAPI, and cell migration on HCT116 (colorectal cancer) and HEK293 (human embryonic kidney) cell lines. Treatment groups included: (BS1, BS2, BS3, BS4, BS5, BS6, BS7, BS8, and S9) at varying concentrations for 48h. For HCT116, MTT results revealed that the lowest viability was 20.1% after treatment with BS8 and the highest was 23.76% in BS1. Whereas for HEK293, the lowest viability was 21.72% in S9 and the highest was 25.84% in BS6. The results obtained from DAPI assay suggest that all NPs inhibit the growth of both cell lines with significantly shrunken and fragmented nuclei. In cell migration, treatment with BS1, BS2, BS3, BS7, BS8, and S9 showed very few cells migrated across the empty areas in HCT116. Cell migration was observed in HEK293 following treatment with BS1, BS2, BS3, BS4, BS6, BS7, BS8, and S9 NPs. Thus, these results suggest that BS1, BS2, BS3, BS7, BS8, and S9 can be good candidates for CRC therapy. This research will help find a new therapy for CRC treatment.Item Development of a Colorimetric SARS-CoV-2 Detection Technology Using Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay(2022) Alhamid, Galyah Mohammed Abdullah; حسين كومبول اوغلوThe ongoing COVID-19 remains to spread worldwide, causing new cases and deaths daily since its declaration as a pandemic over two years ago. Diagnostic tests are the first line of defense against the transmission of this disease, with the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) being the approved gold standard. However, due to the global demand for facilities, reagents, and healthcare workers needed for rapid population-based testing, alternative tests need to be invested. The most common limitation in using RT-qPCR is giving false diagnoses, which puts others at risk of infection. Efficient fighting against this pandemic correlates with easy and large-scale accessibility of detection tools. Therefore, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to diagnose COVID-19 by targeting and amplifying the SARS-CoV-2 E gene. The reaction takes place isothermally in a water bath set at 65 °C, and the positive results are read out with the naked eye via a color change from red to yellow, without requiring expensive and bulky instruments. In addition, a fluorometric RT-LAMP assay was developed to validate the results. Both colorimetric and fluorometric assays performed superbly when testing 150 clinical specimens, yielding 89.5% and 100% sensitivities, respectively. Optimizing the originally designed primer set (E-ID1) successfully detected SARS-CoV-2 in 20 minutes with a limit of detection of 500 copies/reaction, corresponding to 20 copies/µL, with no cross-reactivity observed among other respiratory viruses. No misamplification was evident after prolonged reaction times, which eliminates the most common limitation of potential false-positive diagnoses. Furthermore, we used a color sensor to demonstrate that the RGB codes gradually increase with the color change in positive RT-LAMP reactions, providing a simple alternative monitoring technique. Lyophilization of the colorimetric RT-LAMP reagents showed promising results to develop in-home and easy-to-store testing kit. These findings are essential to support the use of this technique in healthcare systems in fighting the COVID-19 pandemic, especially in resource-limited areas.Item Identifying Pathogenic Variations on Early Stage of Pregnancy Using Invasive and Non-Invasive Prenatal Samples(2022) Sonbol, Bayan Sameer Mohammed; Francis Borgio; Sayed AbdulAzeezVarious factors can increase the risk of fetal genetic abnormalities during pregnancy, such as maternal age and family history. Prenatal diagnosis is a critical clinical practice for couples at risk of genetic disorders in the fetus. The study aims to identify pathogenic gene variations in the early stage of fetal development using invasive and non-invasive prenatal samples by developing fetal cell isolation, gender determination, and gene variation screening. Different samples were collected from various sources, maternal blood (n=10), serum (n=8), paternal blood (n=7), maternal buccal swab (n=8), maternal urine (n=9), and amniotic fluid (n=6). Coelomic fluid (n=1) was also collected for the first time in the history of Saudi Arabia. Different methods were used for fetal cell isolation: morphology based using a designed manual micromanipulator from invasive samples; Cluster of differentiation 71 (CD71) microbeads mediated magnetic cell sorting and percoll based subfractionation for fetal nucleated red blood cells (fNRBCs) from invasive and non-invasive samples. In-house multiplex gender PCR was used for the fetus gender determination. Nested and Amplification refractory mutation system (ARMS) PCR with newly designed primers carried out for detecting sickle cell disease (SCD) mutation (HBB:c.20A>T) in the isolated fetal cells. Our study has successfully identified a heterozygous sickle mutation in HBB gene from amniotic fluid cells and fetal DNA sample (n=3) using ARMS PCR. The study has also determined the fetal gender in single cell and fetal DNA using the gender PCR multiplex. All fetal DNA of fetal cells had a high accuracy than cell free fetal DNA (cffDNA). This study highlights that single-cell isolation from amniotic fluid and coelomic fluid could be used for accurate genetic screening for early diagnosis upon largescale validation.Item The Cellular and Molecular Impacts of Doxorubicin on Breast and Ovarian Cancer Cells(2022) ALKhalifah, Zahra Abdul Jaleel; حسن ثابت; سارة المفتيCancer is the most serious disease caused by gene mutation, these mutations can disturb three types of genes, DNA repair genes, proto-oncogenes, and tumor suppressor genes, which affect the cell cycle, proliferation, differentiation, and programmed cell death. Breast and ovarian cancer are the further most commonly occurring cancer in women globally. As of 2021, an estimated 281,550 females will be diagnosed with breast cancer, and about 43,600 of these females will pass away from this disease. Breast cancer (BC) may begin in various parts of the breast, such as the ducts, the lobules, or the tissues in between that contain many genetic and epigenetic abnormalities. Ovarian cancer (OC) has a high death rate worldwide and it is considered the seventh most fatal cancer among women globally. Cancer therapy has different approaches, chemotherapy is one of the best approaches, which is used worldwide. Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs in cancer therapy. In the present study, we evaluated the role of DOX in cell cycle regulation, proliferation, differentiation, and apoptosis on BC, OC, and control healthy cells of human foreskin fibroblast cells. DOX was used in different doses (1 µM, 2 µM, 4 µM) and 0.1% DMSO for the control treatment, DOX incubation time was 24 h and 48 h. We performed a cell viability assay, wound healing assay, and quantitative real-time PCR. Finally, we evaluated the gene expression and alterations of different cancer-related genes. Results obtained indicated that there was suppression in some cancer-related genes (NOTCH1, PDGFA, TMEM45A, KRAS, NRAS, LAMA4, PTEN, ALK, and BRAF) in the MCF-7 and SKOV-3 cells, which indicate that the DOX has a major effect on inhibiting cancer cells proliferation.Item Synthesis, characterization, and application of redox active electrolytes for high performance flexible supercapacitors(2021) Almofleh, Atheel Awad; ايهان بوزكورت; ايميري سيفيكOver the recent years, there has been a significant advancement in the energy storage systems with improved energy storage capacity and cyclic stability. Amongst these systems, supercapacitors have outstanding characteristics that include fast charge/ discharge, long cycle life, environmental compatibility and high-power density. Many techniques for enhancing the performance of supercapacitors have been reliant on the materials to manage the storage mechanism exploits. They include pseudocapacitance and the EDL (Electrical Double Layer Capacitance). In these instances, an electrolyte is expected to be electrochemically inert to allow for the achievement of full potential capacity. The EDL capacitance is as a result of ionic and electronic separation at the interface of the electrolyte. Contrastingly, pseudocapacitance charges have been widely linked to the faradaic procedures (redox processes), which occurs at the surface of electrodes. According to Frackowiak [135] an electrolyte's surface total charge is correspondent to the surface area electrochemically available on the electrode. Consequently, only well-developed properties of materials, can offer effective performance as electrolyte on the devices. The production of novel electrolytes with high ionic conductivity and improved chemical and electrochemical stability for assembling supercapacitors is a challenge but it has both practical and scientific significance. It has been confirmed that application of redox electrolytes improves the capacity of charge storage within supercapacitors. However, this performance is noted by the consideration of redox electrolyte contribution, which can the increase in the charge capacity. The specific capacitance is enhanced by rise quick faradaic reactions of electrodes using redox mediator electrolytes. The combination of the capacitance of the SC with that provided by the redox reaction of the electrolyte will lead to an increase in overall capacitance. This concept is demonstrated by showing the effects of adding an electrochemically active compound, Co, to polymer-gel electrolyte (GlyP5) This work includes the construction of flexible supercapacitors using a new electrolyte comprising a biobased host material and H3PO4/Co as guest additives. The gel electrolytes were produced in various contents of H3PO4 and Co in the host materials to get a series of electrolytes to evaluate both EDL and redox contributions in assembled devices. The performances of the devices were examined by galvanostatic charge-discharge (GCD), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). The specific capacitance (Cs) of the supercapacitor device comprising active carbon (AC) composite electrode and gel electrolytes were measured. The energy density, power density and cyclic robustness of the device were evaluated. Flexible supercapacitors were assembled by using carbon composite electrodes and the bio-electrolytes; GlyPCoX (X: 1, 3, 5, 10). The electrolyte, GlyP5Co5 was proposed as the optimum composition which contributes for both EDL formation as well as redox reaction at the interface during GCD processes. The specific capacitance of the as-assembled system is 349 Fg-1 after inserting Co which is more than two-fold enhancement compared to GlyP5. The supercapacitor has excellent cyclic stability with excellent capacitance retention of 15.000 cycles. Furthermore, a single supercapacitor has superior flexibility under bent and twist conditions without performance alteration. This novel system can deliver a high specific energy of 47 Wh kg-1 at the corresponding specific power of 420 W kg-1. This system may pave to environmental benign, low-cost and long-term application of supercapacitors in flexible electronics.Item The Impact of Gold Nanoparticles on Colon Cancer: An In Vitro Cellular and Molecular Analysis(2021) Aldahhan, Razan Abdulhameed; دانة عبد الرحمن المهيزعيItem Study of antibiotic resistance genes of Candida auris and nanoparticles as a potential therapeutic(2022) Al-Dossary, Hanan Abdulrahman Nasser; فرانسيس بيرجيوIn recent years, Candida auris (C. auris), a nosocomial infection, has emerged as a challenge, due to the limited therapeutic options and multidrug-resistance leading to a higher mortality rate. C. auris is reported to have developed resistance to various antifungal drugs such as fluconazole, amphotericin B, 5-fluorocytosine, caspofungin, etc., Hence, it becomes imperative to study and detect different resistant genes occurring among different strains isolated from the nosocomial infections. On the other hand, nanomaterials are known to have an exclusive characteristic in antimicrobial therapy through their controlled size and targeted drug delivery. Therefore, this study was conducted with the aim of identifying nineteen C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam then identified by 18S rRNA gene and ITS region sequencing technique and detecting the drug resistance-associated mutations in ERG11, TAC1B and FUR1 genes to get an insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug resistance associated missense variants identified in ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains. Additionally, the current study offers the prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial against the nineteen clinical strains of C. auris, TiZSM-5, 4wt%Ag/TiZSM-5 were prepared using impregnation technique, Ag-silicalite-1 (25) and Ag-silicalite-1 (100) nanoformulations were characterized using different phases determination (XRD), surface area analysis (BET), diffuse reflectance UV-Visible spectroscopy (DRS-UV-Vis), thermogravimetric analysis and differential thermal analysis (TGA-DTA), morphological studies [(scanning electron microscopy/energy dispersive X-Rays spectroscopy (SEM/EDX) and transmission electron microscope (TEM)]. All the collected C. auris strains were subjected to antifungal efficacy by colony forming unit (CFU) technique and antibiofilm activity by employing cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the nineteen C. auris strains, 4wt% Ag/TiZSM-5 and Ag-silicalite-1 significantly inhibited the growth of the majority of C. auris strains and a significant inhibitory effect on biofilm’s survival rate, the lowest inhibition value was (10 %) with Ag-silicalite-1 at 24 and 48h incubation. A profound change in morphogenesis and in addition to the reduction in the number of C. auris cells was shown by SEM and light microscopy. The presence of high surface area and uniform dispersion of nanosized Ag species displays an enhanced anti-Candida activity and therefore it has a great potential against the emerging multidrug-resistant C. auris.Item Synthesis of Novel Magnetoelectric Nanocomposites as Advanced anti-cancer drug in vitro(2021) Al-Fareed, Tahani Mohammed Ahmad; منيرة بنت عبدالله المصيرعيMagnetoelectric nanocomposites are a new generation of multiferroics materials that have great potential in enormous fields owing to their unique properties. The conjunction between ferroelectric and ferromagnetic phases provides a direct and indirect exchange between magnetic, and electric properties. The core-shell diphasic systems are the most attractive structure for different applications due to presence of strong magnetoelectric coupling at room temperature. In the present thesis, we have synthesized several spinel ferrites’ groups MFe1.8O4 , Co0.5A0.5Fe1.8O4, Co0.8Mn0.2R0.02Fe1.8O4 , Ni0.5Zn0.5R0.02Fe1.8O4 , Zn1-2xCaxMgxFe1.8O4 (M= Co, Ni , Zn , Cu, Mg , or Mn ; A=Ni, Cu, Mg, Zn, or Mn ; R = Ce , Eu , Tb ,Tm, or Gd ; x = 0.05 , 0.1 , 0.15 , 0.2 , 0.25 , 0.3) as a magnetic core part by sonochemical method. Then, each spinel ferrite nanoparticles SFNPs was coated with barium titanate BaTiO3 (noted as BTO) by sol-gel method to form various core-shell of MFe1.8O4@BTO , Co0.5A0.5Fe1.8O4@BTO, Co0.8Mn0.2R0.02Fe1.8O4@BTO , Ni0.5Zn0.5R0.02Fe1.8O4@BTO , Zn1-2xCaxMgxFe1.8O4@BTO (M= Co, Ni , Zn , Cu, Mg , or Mn ; A=Ni, Cu, Mg, Zn, or Mn ; R = Ce , Eu , Tb ,Tm, or Gd ; x = 0.05 , 0.1 , 0.15 , 0.2 , 0.25 , 0.3) magnetoelectric nanocomposites (MENs). The microstructure and morphology of core-shell MENs were evaluated through XRD, SEM, TEM and EDS as well as the magnetoelectric measurements. The different characterization techniques confirmed the purity and the successful formation of core-shell MENs. The average crystallite size was calculated via Sherrer’s equation and are estimated to be in the range of 24 to 29 nm. The biological impact of SFNPs and core-shell MENs were examined by MTT assay and nuclear DAPI staining on (human colorectal carcinoma cells) HCT-116 and (human embryonic kidney cells) HEK-293. We have found that the magnetic core treatment exhibited a significant reduction in cancer cell viability as well as they induced nuclear condensation, cell membrane disintegration, and cell death as revealed by DAPI staining. However, there was a negligible or no toxicity for core-shell MENs treatment at 141.75 µg/0.1ml, suggesting that the BTO coating improve the biocompatibility of SFNPs. Hence, the MENs seem to be ideal as they are non-toxic, and they can be a promise candidate for anticancer drug delivery and magnetoelectric voltage generator.Item Comparing the Effect of Two Pyrimidine Analogues on Colorectal Cancer Cells(2021) Alshammari, Thamer Marhoun Bin Jarbou; حسين حسن ثابت; سارة أمين المفتيNowadays, people are living in an era with high standards of healthcare accessibility, which can remarkably improve the diagnostic tools and the treatment plans of different diseases. These standards contribute to the determination of the general life expectancy in many parts of the world. With cancer, however, the mortality rate has globally increased by almost 40% over the past four decades, and it is expected that the mortality will further increase to reach 60% in the current decade with an estimated death of 13 million cancer patients by the year 2030. Colorectal cancer (CRC) is considered the third most frequent type of cancer and the second leading cause of cancer-related deaths, for both sexes, in the world. The explanation of the increased mortality of colorectal cancer might be due to some environmental factors, such as; smoking, bad diet, obesity, and very low physical activity, in addition to genetic background. The major pathways of either environmental (epigenetic) or genetic causes of CRC include CpG hypermethylation and microsatellite instability (MSI) due to the mismatch repair (MMR) gene deficiency. Considering that CRC accounts for 10% of the most commonly diagnosed types of cancer, there is an urgent need for developing effective treatment plans for CRC patients. 5-Azacytidine (5-AZA), a cytidine pyrimidine nucleoside analogue, is an epigenetic drug that incorporates into DNA and blocks the activity of the DNMT enzyme and thereby inhibits DNA methylation that might cause CRC. In addition to 5-AZA, another chemotherapeutic drug named 5-fluorouracil (5-FU) was applied either synergistically with 5-AZA, or alone, in this study. Both drugs were applied to the human colorectal carcinoma cell line, HCT116, by performing several methods, such as MTT assay, wound healing assay, and colony formation assay to assess the cells viability and migration property before and after treatment to analyse their effect on CRC. In addition, whole exome sequencing (WES) was performed to assess the genetic changes after treatment with 5-FU. HEK293, which is the human embryonic kidney cell line, was used in the study as the control cell line receiving the same treatment regime as the HCT116 cells. The main result of this study shows that both drugs have a noticeable effect on the viability of HCT116 cells. 5-AZA alone possesses the highest efficacy on HCT116 cells, followed by the drugs combination and 5-FU alone, respectively. In addition, WES results show that 5-FU diminished the number of mutations in HCT116 cells. In a conclusion, 5-AZA alone as a treatment plan for CRC has more efficacy than either 5-FU alone or the drugs combination which leads to the recommendation of using it alone as an anticancer drug. Also, WES results suggest that the 5-FU mechanism of action as a DNA damage drug is proven.