Institut Perubatan & Pergigian Termaju - Tesis

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Optimization Of Immunoillstochemistry: Testing For Mlhl And Msh2 Proteins In Colon Tissue
(2005-05)
Muhsain, Siti Nur Fadzilah
Microsatellite instability (MSI) accounts for the development of about 15% of all colorectal cancers. It is characterized by mutations in mismatch repair (MMR) genes that render cells unable to detect errors during DNA replication. Mutations in the MMR genes, MLHl and MSH2 are responsible for the majority of CRC with MSI. These MMR proteins can be detected by immunohistochemistry (lllC). IHC has proved sensitive and specific when compared to molecular analysis of MSI. Nevertheless, generally, there is no published literature as yet on studies of MSI in Malaysia, and specifically using lliC. Before any lliC staining procedure can be done, it has to be optimized. In this study, attempts were made to optimize rnc staining of MLHl and MSH2 proteins using polyclonal rabbit antibody by Biovision on formalin-fixed paraffm-embedded sections of normal colon, taken from resected margins of colectomy specimens. Either Vectastain Elite ABC Kit or DAKO En Vision Kit was used as secondary detection system. The staining procedure was done using different dilutions of the primary antibodies and incubated for different durations at different temperatures. Antigen retrieval procedures were introduced using citrate buffer pH 6 or Tris-EDTA buffer pH 9. The results showed that incubation of sections at room temperature using different dilutions of antibody failed to produce any nuclear staining. Staining with DAKO En Vision was still unsatisfactory, although background staining was reduced. Introduction of antigen retrieval procedure using microwave did not improve results. When incubated at 4°C, non-specific background staining was produced.
Determination Of Epstein-barr Virus In Gastrointestinal Lymphomas (With Special Reference To Non-hodgkin's Lymphoma Of Small Intestine): Study On Malaysian Patients.
(2005-05)
Yunos, Asmah Md
Non-Hodgkin's lymphoma (NHL) is ranked twelfth among all cancers world-wide, in which it is more prevalent in males compared to females. The aim of the present study was to determine the presence and distribution of Epstein-Barr virus (EBV) in non-Hodgkin's lymphomas (NHL) of the gastrointestinal tract (GIT) tissue samples obtained from 25 Malaysian patients diagnosed clinically and histopathologically. The gastrointestinal lymphomas analysed in the present study was divided into NHL of the ileocecal (9 cases), NHL of the small intestine (7 cases), NHL of the stomach (5 cases), NHL of the abdomen (1 case), NHL of the wedge ulcer (1 case), NHL of rectum fotic (1 case) and finally NHL of the hemicolon (1 case). The presence of EBV in all of the above mentioned tissue samples, after formalin fixation and paraffin embedding was carried out by using conventional in situ hybridization technology. Two out of 25 cases of NHL of the GIT analysed in the present study, demonstrated positive signals for EBV/EBER. In the first positive case, EBV/EBER signals were located in transformed lymphocytes in the serosa layer of the small intestine (14.3%). In the second EBV positive case, EBV/EBER signals were located in diffuse B-cell lymphomas of the ileocecal (11.1 %). In conclusion, these finding demonstrate a rare association between EBV and lower gastrointestinal lymphomas (excluding stomach).
Polymeric Nano-encapsulation Of Наемоglobin Isolated From Expired Human Redblood Cells For Use As Blood Substitute
(2018)
Mahmud, Khadijah
To date, blood scarcity in transfusion service demand vigorous scientific works looking for possible red blood cells alternatives. In this study, we aim to isolate and purify human haemoglobin (hb) from expired red cells by multiple washing, sonication, organic extraction and dialysis method. Analysis of the UV-Vis spectrum comparing hb and red blood cells (RBC) showed that the protein has been isolated successfully. Subsequently, the hb was encapsulated by polymeric micelle upon hydrophobic interaction (micellisation) of the methoxy poly (ethylene glycol)-b-poly (E-caprolactone) (PEG-PCL), a diblock copolymer in an aqueous buffer. The hb-micelle complex was then further analysed for half-life, oxygen reversibility, and cell-viability assay. Average encapsulation efficiency of the hb within the polymeric micelle achieved 45%. This is due to the high solubility of free hb in aqueous solution limiting the entry of hb into the polymer. However, the result indicated that the average of two units hb were successfully encapsulated by each polymer micelle. The hbmicelle recorded a higher half-life of 112,242 mins as compared to 30 mins of the free hb alone during oxygen stability study. The hb-micelle system also showed the ability to bind oxygen reversibly. Oxygenation and deoxygenation processes recorded average of six cycles before the sample was evaporated due to oxygenation, in contrast with only one cycle at average for free hb as a control. In cell viability study, the hb-micelle sample with concentrations of 1.89 x10³mg/mL in two preparations of micelles at 1.0 and 2.0 mg/mL while as a control, free hb sample from human and free bovine at 0.1 mg/mL and 0.2 mg/mL concentrations and also bovine hb-micelle (hb concentration at 2.21 ×105 mg/mL) have been tested on murine macrophage cells (RAW 264.7), incubated for 24 hours before treatments. Treated cells were then incubated further for 48 hours where the cell viability analysed at time points of 4, 8, 24 and 48 h. Generally, the free hb recorded reduction in cell growth approximately by 10% and 18% as early as 4h compared to hb-micelle which showed no toxic effects on the cells until 24 hours onwards. This result probably due to the free hb from human used in the test may have contained lipid debris from the membrane lysis during extraction process. However, it showed that hb-micelle system can safely interact with normal cells for potential future use compared to free hb without encapsulation by polymer. These findings indicated the potential of the hb 'harvested' from expired human red cells encapsulated by the diblock copolymer for development as red blood cells substitute.
Rh D Negative Blood Donors: Strategies To Improve Blood Donation
(2018)
Abas, Anis Salwa
Background: Only 2.2% of Malaysians are blood donors and less than 2.5% of them are Rh D negative blood donors. An effective blood donor retention strategy to sustain the responsive and reliable Rh D negative blood donor pool is paramount. However at National Blood Centre, Kuala Lumpur (NBCKL) only 7% of early career blood donors responded to the standard blood donation invitation. This study compared a new blood donation invitation strategy against the standard method. This study also aims to identify any association between the blood donors socio-demographic and donation characteristics with responses towards the blood donation invitation. Methods: An interventional with historical control study was conducted. The interventional group was selected from the blood donors who had donated within 1st January 2016 to 31st December 2016. The interventional group received a personalised blood donation invitation letter with an educational brochure followed by a phone call. The historical control group was the blood donors who previously invited through a general short message service (SMS) and a phone call within 1st July 2013 to 31st December 2014. The blood donors' response was measured within 6 weeks period after the invitations. The blood donors' socio-demographic and donation characteristics were analysed. Results: The new blood donation invitation strategy had resulted in a significantly more attendance among the early career Rh D negative blood donors as compared to the standard blood donation invitation. About 24.7% of participants in the interventional group had responded compared to 5.6% of participants in the historical control group.The odd for the interventional group to respond was 5.6 (p<0.001).The Rh D negative blood donors who had a shorter interval of previous blood donation of 3 to 12 months had 5.9 time the odd to respond (p=0.009). No significant association of blood donors age, gender and race but the blood donors who were non-professional were 78% less likely to respond (p=0.045). Conclusions: A personalised blood donation invitation with an educational brochure on Rh D negative phenotype had resulted in more attendance among early career Rh D negative blood donors. The blood donors' previous blood donation interval and occupation were associated with responses towards blood donation invitation.
Multifunctional Gold-Silica Composite Platform Towards Comprehensive Cancer Therapy
(2018)
Tew, Lih Shin
Incomplete cancer cells eradication with sole treatment of chemotherapy or radiation therapy was commonly reported. Therefore, gold nanoshells-based nanodevices have gained interests owing to the tuneablity of the localised surface plasmon resonance (LSPR) from visible to near infrared (NIR) wavelength, which is favourable for biomedical applications. In this work, gold nanoshell (GNS), of which has mesoporous silica nanoparticle core (MSN) filled doxorubicin (DOX) as well as polyethylene glycol (PEG) and AS1141 aptamer (Apt) at the outer layer (DOX-GNS-PEG-Apt), was designed for two photon laser-triggered chemo- and photothermal therapy. The results show 30.00 2.91 % of doxorubicin (DOX) was loaded into MSNs. The synthesised GNS was thenanalysed by UV-Vis spectroscopy and TEM, of which 4:1 ratio of K-gold to MSN-NH2 seed produced ideal gold thickness. The nanoparticles with a complete gold coverage on mesoporous silica core were observed. Based on the TEM and Energy Dispersive X-Ray spectroscopy (EDX) data, the gold film synthesised via grow-mediated process was approximately 10 – 15 nm thickness. Then, two photon excitation (TPE) was introduced to evaluate the efficacy of photothermal therapy (PTT) alone and the synergistic chemo-photothermal therapy. Deformation of GNS was evidenced by the blue shift of plasmon resonance peak from 800 to 570 nm and the morphology of the GNS after TPE was further confirmed with TEM. According to the in vitro study, DOX-GNS-PEG-Apt positive selectively bound to MDA-MB-231 cells (cancerous) but not MCF-10A cells (non-cancerous).
Anti-angiogenic Properties Of Nanoparticles: A Systematic Review
(2018)
Salem Brhaish, Ali Saeed
Introduction: Angiogenesis develops new blood vessels from the old ones, and this process is controlled by balancing the angiogenic and anti-angiogenic factors. The domination of angiogenic leads to pathological angiogenesis that causes diseases, such as diabetic retinopathy and cancer. Anti-angiogenesis therapy targets angiogenesis to treat these diseases. Hence, nanoparticles appear to be one of the most promising agents that offer efficacy in therapy. The objective of this research is to review systematically studies that have probed into the effect of nanoparticles on angiogenesis. Methodology: The literature was searched electronically (PubMed, Science Direct, Google Scholar, Medline, Scopus, and Springer) to identify as many relevant articles as possible for the topic at hand, which is the effect of nanoparticles on angiogenic. The inclusion criteria, such as articles published in the English language during the period from January 2008 until January 2018, were strictly adhered to. The Medical Subject Heading (MeSH) (nanoparticles) and anti-angiogenesis or angiogenesis were used to extract articles from PubMed and Medline, while search terms or keywords of the title had been applied to retrieve more journals and articles from other databases. Additionally, references that were cited in the initial search were sought to identify more potential articles. Next, articles that did not meet the inclusion criteria and those duplicate were discarded. Results: Out of the 218 articles obtained from the literature search, only 22 seemed to conform to the inclusion criteria. The spherical shape is the most common shape employed to investigate the role of nanoparticles in angiogenesis therapy. The size of nanoparticles appears to play a crucial role for efficacy on angiogenesis, in which 20 nm emerged as the preferred size. Gold nanoparticle exhibit the most promising type as an anti-angiogenesis agent. The nanoparticles were active for both in vitro and in vivo models. The biosynthesis of nanoparticles is safer than chemical synthesis. The toxicity was adjustable based on the dosages applied. Conclusion: Nanoparticles are a promising treatment for angiogenesis-related diseases. Nanoparticles inhibit angiogenesis in different pathways. Size and shape play a role in the anti-angiogenesis effects of nanoparticles. Gold nanoparticle exhibit higher anti-angiogenesis properties.
Seroprevalence Of Hepatitis B In First- Time Blood Donors Of National Blood Centre After Implementation Of National Vaccination Programmе
(2018)
SOW, EMMY
Background: Malaysia's prevalence of hepatitis B is about 5% with the related mortality rate of 0.04 in 2013. Transmission preventive measures were implemented via national vaccination programme since 1989 with vaccine coverage of 99.3%. In Malaysia, universal blood donor screening for hepatitis B virus (HBV) using serology method was implemented since 1974 while nucleic acid testing (NAT) began since 2007 in National Blood Centre. Objective: To determine the seroprevalence of hepatitis B among first-time blood donors after implementation of national hepatitis B vaccination programme. Methods: A cross sectional study involving review of 215 Malaysian first time donors records that was screened positive for HBV and donated between 1st January 2010 to 31st December 2015 at National Blood Centre. Results: The overall prevalence of hepatitis B among the first-time blood donors of NBC from 1st January 2010 to 31st December 2015 was 0.15%. The prevalence of hepatitis B was higher at 0.23% among donors born before year 1989 (pre-vaccination era) compared to 0.05% among donors born in and after year 1989 (post-vaccination era). More donors born pre-vaccination era have known risk factors compared to the other group of donors. The stages of infection were highest for non-replicating followed by replicating and convalescence regardless year of birth. Among donors born pre-vaccination era, majority (97.2%) were HBsAg+, all were anti-HBc+, 30.3% were HBeAg+ and 71% were antiHBe+. For donors born post-vaccination era, 98.6% were HBsAg+ and anti-HBc+, 50% were HBeAg+ and 48.6% were antiHBe+. All donors were NAT+ irrespective of year of birth. There was significant association of the seroprevalence for HBeAg and anti-HBe with year of birth (p < 0.05). There was no association between stages of infection with risk factors and demographic characteristics of donors (p > 0.05). Conclusions: The prevalence of HBV among donors who received birth vaccination was lower than those who did not. Occult infection (anti-HBc+, NAT+ with HBsAg-) was also reduced in donors who received birth vaccination. Implementation of national vaccination programme for HBV infection has contributed to the reduction of HBV infection and in minimizing the risk of transfusion-related transmission.
Knowledge Of Clinical Transfusion Among Postgraduate Residents In Hospital Universiti Sains Malaysia
(2018)
WAN Alkamar Shah, WAN Nurul Husna
Background: Blood transfusion is one of common therapy prescribed by clinicians. Despite that, injudicious and unsafe transfusion contributes to leading causes of morbidity and mortality globally, as it jeopardizes quality of care and cause wastage of blood product resource. Therefore, it is vital that clinicians, mainly postgraduate residents to possess knowledge of clinical transfusion. The current level of knowledge among postgraduate residents in Hospital Universiti Sains Malaysia (HUSM) is not yet known. Objectives: To study the clinical transfusion knowledge level among postgraduate residents within the Departments of Anaesthesiology and Intensive Care, Accident and Emergency, Obstetrics and Gynaecology, General Surgery, and General Medicine in HUSM in 2017. Study design and method: This is a cross-sectional study using a validated selfadministered questions involving 210 participants between Year 1 to Year 4 postgraduate residents within five departments in HUSM. The validated assessment tool consists of six demographics survey (department, age, gender, working experience, postgraduate year, formal training in clinical transfusion) and 20 questions on clinical transfusion knowledge (total score of 20). Score of 0 - 9 are categorised as 'poor' knowledge and score of 10- 20 are categorised as 'good' knowledge. Results: Majority of participants (27.6%) are from Department of Accident and Emergency. Based on postgraduate year, Year 1 accounts for majority of participants (31.9%). Mean (SD) age is 32.9 (1.45). Number of male and female participants are nearly balanced which are 104 (49.5%) and 106 (50.5%) respectively. Formal training was attended by 111 (52.9%) of participants. Mean (SD) working experience is 7.46 (1.07) years. A total of 125 (59.5%) participants have poor knowledge level. Mean (SD) score is 8.77 (1.77). No majority of participants in each variable tested reported to have good knowledge status. No significant association found between the demographic factors (department, gender, age, postgraduate year, working experience, formal training) with the knowledge status in this study. Conclusion: In general, more than half of the participants had poor knowledge status in clinical transfusion. However, no significant associations found between demographic factors and knowledge status. This study reflects the lack of knowledge among clinicians in some aspects of clinical transfusion. Thus, Blood Transfusion Service in HUSM should focus on collaboration with the respective clinical departments to conduct continuous medical educational (CME) sessions and speciality based training for the improvement of knowledge of clinical transfusion among postgraduate residents.
A Systematic Review Of Targeted Titanium Dioxide Nanoparticles For Cancer Theraрy
(2018)
Mohd Azlan, Nur Hazirah
Titanium dioxide nanoparticles (nano-TiO2) provides promising application as targeted cancer therapeutics. Further understanding on the toxicity guidelines and ideal physiochemical properties are crucial for efficient clinical application. This study provides an updated review on nano-TiO2 as nanotherapeutics focusing on the modification of physiochemical properties, potential routes of administration, biodistribution, clearance and toxicity profile. The review conducted is based on PRISMA-P protocol. It began with literature searching from selected databases; PubMed, Springer Link, Science Direct and general search engine Google Scholar based on the pre-determined keywords (titanium dioxide nanoparticles, targeted drug delivery, targeted cancer therapy, surface modification, delivery route, route of administration).The search generated 873 manuscripts. We included all pre-clinical and clinical studies, original and in-press articles published within the past 6 years (2013 till 2018). Studies involving usage of organic nanoparticles, and those in predatory or blacklisted journals were excluded. Selected studies underwent thorough appraisal yielded 61 articles that answered the research questions and met the inclusion and exclusion criteria. Results suggested that nano-TiO2 can be considered an ideal candidate for cancer nanotherapuetics. Surface modification of nano-TiO2 with different ligands enhanced the treatment efficacy and minimize the adverse effects that current cancer treatment might cause. Delivery of nanoTiO2 in human as targeted cancer therapy through different routes seems promising and require further exploration and research on this issue. Review summarized that,biodistribution, cleranace and toxicity risk of nano-TiO2 can be tackeld by modulating their physio-chemical properties. Future studies should be directed towards discovering actual potential of nano-TiO2 for cancer therapeutics which may indeed encourage its clinical application in near future.
The Effects Of 940 Nm Diode Laser On Morphology And Temperature Of Human Extracted Teeth
(2018-06)
Ahmed Ghazal, Rehab Mahmoud
Tooth sensitivity is a totally common dental condition that could cause a huge obstacle for dentist and patient, due to the short, sharp pain arising as a response to stimulation applied on uncovered dentine. The aim of this investigation is to evaluate the effectiveness of 940 nm diode laser as a treatment modality for dentine hypersensitivity. The laser is expected to cause ultrastructural changes of dentine such as narrowing and plugging the wide dentinal tubules. The safest parameters to be used on the dental tissues to provoke the melting of dentine layer without damaging the pulp tissue by heat will be defined. Seven sound, caries free upper premolar teeth with two roots were collected. The teeth were extracted for orthodontic purpose or periodontal disease. Dentine surface were irradiated with a 940 nm diode laser at different output power settings: 1.5 W, 2.0 W and 2.5 W, continuously for 10 seconds. Each tooth had been divided into 4 groups: Group A (control), Group B (1.5 W), Group C (2.0 W) and Group D (2.5 W). Diode laser irradiations at 2.0 W and 2.5 W led to effectively narrowing or sealing of dentinal tubules without provoking carbonisation or any destruction on the dentine surface. Samples that had been irradiated with 1.5 W showed partially narrowing of the dentinal tubules. The pulp temperature increased during irradiation, within a range of 2.6°C to 7.3°C. The temperature increment for all samples was statistically significant (p-value < 0.001). From this study, it is observed that irradiation of 940 nm diode laser at 2.0 W and 2.5 W settings, for 10 seconds in a continuous mode, is able to seal the dentinal tubules. Additionally, these parameters are within the safe range as assessed by the morphology and changes in temperature of the samples, which will not cause a harmful effect to the pulp tissues, and could be effective in the treatment of dentinal hypersensitivity.
Anion Exchanger 1 Gene (AE1) Single Nucleotide Polymorphism (SNP) Analysis Among Malays With Distal Renal Tubular Acidosis (DRTA) And Southeast Asian Ovalocytosis (SAO)
(2018-08)
Anion Exchanger 1 (AE1) encoding the erythroid and kidney isoforms of AE1 protein is located on chromosome 17. Distal renal tubular acidosis (dRTA) is characterized as its inability to acidify urine pH caused by AE1 polymorphisms. Southeast Asian Ovalocytosis (SAO) is a hereditary red blood cell abnormality caused by 27bp deletions in AE1. dRTA and SAO is highly prevalent in Southeast Asian countries. Polymorphism in AE1 is known to cause both SAO and dRTA associated with 27bp deletions which is still unclear.
The Imраст Оf Malocclusion On Selfesteem And Oral Health Related Quality Of Life
(2018-08)
Elyaskhil, Marghana
Background: By further understanding the impact of malocclusion on self-esteem and different domains of Oral Health Related Quality of Life (OHRQoL) such as functional, physical, social and psychological in school children, it will aid in planning a realistic treatment, as expected by patients. Aim: To determine the impact of the severity of malocclusion on self-esteem and OHRQoL among Malay ethnic students. This study also evaluated the relationship of malocclusion severity with self-esteem and OHRQoL. Method: This prospective cross-sectional study was conducted on 252 Malay students aged 13 to 16 years old. Rosenberg self-esteem Scale (RSE scale) and Oral Health Impact Profile14 questionnaires (OHIP-14) were used for assessing the children's self-esteem and OHRQoL respectively. Oral examination was performed by the use of Index of Orthodontic Treatment Need (IOTN) ruler to examine the severity of malocclusion. Pearson correlation coefficient was used to evaluate the relationship between severity of malocclusion, selfesteem, and OHRQoL. Regression analysis was done to determine the effects of the severity of malocclusion on self-esteem and OHRQOL. Result: 139 (55.2%) of participants were male and 113 (44.8%) were female. 133 (52.8%) aged 13 to 14 and 119 (47.2) were 15 to 16 years old. Mean scores and standard deviation of the RSES and OHIP-14 were 33.64 (±3.40) and 9.72 (±8.39) respectively. There was no statistically significant difference in malocclusion severity between male/female and students age group (p>0.05). A weak positive relationship was observed between OHIP-14 and IOTN DHC (r = 0.186; p < 0.01). OHIP-14 was significantly and positively associated with sex, females have higher impact scores than males (B =2.413;p <0.05), indicating the significant association between sex and OHIP-14 score. This association became stronger in multivariate model [B = 2.673; 95% confidence interval (CI) = 0.639-4.707; р < 0.05]. There was а significant association between (IOTN-DHC) and OHIP-14. (B=1.235 p <0.05). Conclusion: Female exhibited more negative impact of malocclusion on their OHRQoL. A weak positive correlation was found between malocclusion and OHRQoL. In the present study the OHRQoL of the students was affected by malocclusion severity. This study provided information that low quality of life was associated with severity of malocclusion.
Efficacy And Safety Of Annona Muricata L. As A Pharmaceutical Agent In Diabetes: A Systematic Review
(2018-08)
Alwan Alogaili, Iqdam Abdulmaged
Diabetes is a metabolic disorder characterized by chronic hyperglycemia due to the absence or insufficient production of insulin. The use of medicinal plants in the management of diabetes is globally spread. Annona muricata L. is a plant of Annonaceae family and known to have antihyperglycemic effect. During the past few decades, numerous scientific investigations have been conducted on the antidiabetic effects of A. muricata and its safety effects. However, no comprehensive evidence-based systematic review regarding these topics is available. Hence, this review was aimed to summarize up-to-date and comprehensive studies on the antidiabetic activity, the possible mechanism of antidiabetic action and the possible toxic effects of A. muricata.Six online databases which were PubMed, Web of Science, Scopus, ScienceDirect, Google scholar, SpringerLink were used to systematically search for the related articles over the period of 2002 till April 2018. The search terms used were A. muricatal soursop/ graviola/ guanabana and diabetes, antihyperglycemia, glucose and toxicity/ safety. The final articles included in this review were twenty-four. Different parts of the plant extracts, particularly leaves showed significant effect on the antidiabetic parameters which include reduction of blood glucose, stimulation of insulin secretion and restoration of body weight and lipid profile. Further studies have elucidated the possible mechanisms of antidiabetic effect which includes improvement in antioxidant enzymes, reduction of lipid peroxidation, pancreas protective and hepatoprotective effects, as well as inhibition of carbohydrate metabolizing enzymes. On the hand, safety studies of A. muricata reported mixed findings. In vivo studies showed no toxic effect upon ingestion of pulp and seed extracts in rat models. On contrary, several in vitro studies have reported neurotoxicity and neurodegenerative effects of A. muricata and its isolated acetogenins and alkaloids. As a conclusion, A. muricata has a promising therapeutic effect against diabetes. However, further investigations are required to identify the active principles responsible for the antidiabetic effect and to determine the threshold value of these compounds at which this effect is caused before any clinical trial could be conducted. In vivo toxicity study on the effect of neurotoxins of A. muricata is also needed to verify their toxic effects on human.
Identifying The Effect Of Biosynthesized Agnp From Garcinia Atroviridis Aqueous Extract On Induced T-regulatory Cells From Non-obese Resistance (Nor) Mouse Model
(2018-08)
MD Yusof, Nur Azirah
CD4+CD25+ Foxp3+ T regulatory cells (Tregs) are important for maintenance of immune homeostasis. Thus, harnessing their function as immune modulator may be coupled with the rapid advancement of nanotechnology development. In the current study, biosynthesized silver nanoparticle (AgNP) from aqueous extract of Garcinia Atroviridis (GA) was used to identify its synergistic effect on modulatory properties of induced Treg (iTreg) cells from Non-Obese Resistance (NOR) Mice Model. Conventional CD4+ T cells were isolated using magnetic separation from NOR mice spleen and then cultured. Next, 1x105cells/mL were stimulated with anti CD3/CD28, TGF-B and IL-2 to induce CD4+Foxp3+ cells (iTreg). The cells were treated with or without GA-AgNP and were cultured for 120 hours. Expression of extracellular and intracellular markers were evaluated by using fluorochrome dye to detect CD4+, Foxp3,IL-17R, ICOS, TIGIT, P38, STAT5 and ERK1/2. Cells were analysed using BD FACS DIVA Cell analysis system. Control group was set as CD4+IL17Rhigh and stimulated with anti-CD3/CD28 and IL-2 only. Treated groups were designated as following: Group 1. anti-CD3/CD28, IL-2, TGF- ẞ Group 2. anti-CD3/CD28, IL-2, TGF- ẞ, GAAgNP and 3. anti-CD3/CD28, IL-2, GA-AgNP. Current results showed that GA-AgNP modulated the expressions of several molecules on isolated CD4+IL17Rhigh T cell population. Levels of CD4+ expression were significantly reduced in Group and Group 3 which were treated with GA-AgNPs as compared to control group. Similarly, Group 1 expressed almost similar patterns of molecular expression with control group. In contrast, transcription factor Foxp3 was not significantly induced in all groups as compared to control group. The expression of ICOS and TIGIT markers in CD4+IL17Rhigh cells in all groups remained unchanged as compared to control group.In contrast, transcription factor Foxp3 in all groups was not significantly induced compared to control group. The phosphorylation of p38 protein and ERK1/2 of MAPК pathways did not significantly detected in all groups of cells as compared to control group. None of the cell groups showed significant STAT5 phosphorylation level compared to control group. These findings may suggest GA-AgNP in modulating CD4+IL-17Rhigh cell population and did not significantly induce the formation of CD4+Foxp3+ cells. Thus, the addition of GA-AgNP in TGF-B/IL2 environment may trigger the plasticity of CD4+ cells into different population. Further studies are necessary to identify the molecular mechanisms involved. Current findings may serve as a basis for immunotoxicity study of nanomaterial used in therapeutic bio-products.
Association Analysis Of Single Nucleotide Polymorphism Of Opioid Dependence Genes Among Malay Males In Malaysia
(2018-09)
Nagaya, Devaki
Drug addiction is a chronic and relapsing disorder is associated with genetics. There are many studies have been reported the roles of single nucleotide polymorphisms (SNPs) with drug dependence and among those, twelve (12) candidate genes that were associated with drug dependence will be. investigated in this study. The candidate genes are OPRD1 (Delta Opioid Receptor), OPR.K1 (Kappa Opioid Receptor), COMT (Catechol — O-Methyltransferase gene), PDYN (Prodynorphin), DRD4 (Dopamine receptor D4), ABCB1(P glycoprotein), DUSP (Dual Specificity Phosphatase 27) and rs 10494334. The goal of this study was to determine the frequencies of these SNPs rsl042114, rs702764, rs 199774, rs 1022563, rs910080, rs737866, rs 10494334, rsl800955, rsl 128503, rsl045642, and rs2032582 and to study their association with opioid dependence in Malay males in Malaysian population.
Nanoencapsulation Of Thiolated Sodium Alginate: Synthesis, Drug Release And Cellular Uptake Studies
(2018-11)
Oral drug delivery has becoming the most preferred route of administration for chemotherapeutic drugs, however its application is limited due to lack of drug targeting specificity to the localised cancerous cells but not to the normal cells. Polymeric nanoparticulate drug delivery is a potential solution to deliver hydrophobic drugs specifically to colon, thus causing less side effects.
Gene And Protein Analyses Of Selected Drug-resistan Breast Cancer Cell Lines Treated With Thymoquinone-nanoparticle
(2018-12)
Ahmad, Rozaina
Chemotherapy is an important option for the treatment of breast cancer. Nevertheless, drug resistance is one of the major obstacles. There is a need to address this challenge with a new drug using nanotechnology. Nanomedicine is used for drug delivery in the current cancer therapy. Free thymoquinone (TQ) is a potential active compound of Nigella sativa seed extract that exhibits medicinal value. Therefore, present study aimed to synthesise and characterise the TQ encapsulated poly (d 1- lactide-co-glycolide) polyethylene glycol (PLGA-PEG) nanoparticles to conserve its bioavailability and also to develop MCF-7 cell line resistance to tamoxifen (TAМ). Subsequently, the resistance breast cancer cell line were treated with TQ-nanoparticle to determine the modulation of targeted protein, and gene expression. TQnanoparticles were prepared by solvent displacement technique.It was then characterised with different techniques which involved Transmission Electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-VIS), dynamic light scattering (DLS), attenuated total reflectance infrared (ATR-IR), entrapment efficiency and drug release analysis. In this study, two type of breast cancer cell lines are used which were MCF-7 and UACC 732 to study effectiveness of TQnanoparticle. The MCF-7 is estrogen receptor positive (ER +) cell line from the luminal A subtype. Development of Tamoxifen (TAM) resistance MCF-7 was done using pulse method. Resistance index was determined after treatment with TAM using MTS assay. The UACC-732 cell line is human epidermal growth factor receptor 2 (HER2) overexpress and resistance to trastuzumab and lapatinib. Genetic and proteomic modulation caused by TQ-nanoparticles in drug-resistant cancer subtypes were investigated. TQ-nanoparticle structure characterisation by DLS and TEM revealed particle diameter between 50-100 nm. Zeta potential estimation revealed that the TQ-nanoparticle formulations were negatively charged (-25 mV). This would confer facilitated cellular uptake. The success of drug encapsulation within polymer was confirmed with ATR-IR technique. Encapsulation efficiency of TQ was 79.9% and drug release showed a maximum release of TQ at 50.3 %. Development of drug resistant MCF-7 cells showed that the 8 µM TamR MCF-7 cells achieved the highest resistance index compared to parental MCF-7 and cells exposed to other concentrations. It was further supportted by proteomic analysis, in which MDR1 expression was significantly upregulated (p<0.05).Findings indicated TQnanoparticle significantly reduced expression of MDR1, HER2 and MRP4 protein in UACC 732 cell (p<0.05). Similarly, resistant TamR MCF-7 cells showed reduction in expression, however they were not significant (p>0.05). Gene expression analysis was done to compare effect of TQ-nanoparticles with doxorubicin. Study showed significant decrease in expression of two drug resistant genes (ABCC5 and HER2/ERBB2) and cancer proliferation gene (BCL2). In conclusion, this study show that TQ-nanoparticle based on PLGA-PEG can reduce the expression of drug resistant gene and protein. Application of TQ-nanoparticle potentially can be used as new treatment to HER2 breast cancer.
Anti-cancer And Anti-angiogenic Activities Of Natural Compound Zerumbone From Zingiber Zerumbet - A Systematic Review
(2019)
Elfagie, Rehab M. H.
Significant number ofliterature has demonstrated the anti proliferative effect of Zerumbone and its role as anti-angiogenesis. The aims of this systematic review were to evaluate the anti-cancer effects of Zerumbone and the role of its antiangiogenic properties in treating cancer. Relevant articles were selected based on specific inclusion criteria. Articles chosen for this systematic review were between January 2008 and December 2018. Relevant articles were identified through an extensive search in Science Direct, PubMed, Google Scholar and Scopus. The literature searches of the electronic databases combined the following key words: anti-angiogenic, anticancer, Zerumbone and Zingiber zerumbet. Studies chosen for this review includes the following designs in vitro, in vivo and ex vivo. The initial literature search obtained a total of 352 related records and the final number of studies that met the inclusion criteria in the current review was 43 studies. In vitro studies was the commonest study design. Evidently, Zerumbone demonstrate a potential antiproliferative and antiangiogenic. The anti proliferative activities of Zerumbone was shown to induce by different signalling pathway.Zerumbone through its antiangiogenic effect play a great role in reducing invasion and metastasis. Some selected studies on Zerumbone were found to plague with limitation such as lack of toxic threshold value which may be needed for the clinical trials on this compound.
Association Between Tumor-infiltrating Lymphocytes And Pd-ll Expression In Human Invasive Breast Ductal Carcinoma, Nst
(2019)
Yusuf, Nur Fatihah
Introduction: Breast cancer is the second common cancer diagnosed after lung cancer. It is the commonest cause of cancer-related mortality among women. Several lines of evidence link the roles of tumor infiltrating lymphocytes and PD-Ll expression with host antitumor immunity. This study aims to investigate the association among tumorinfiltrating lymphocytes, PD-Ll and clinicopathological parameters in invasive breast ductal carcinoma. Methods: A total of 80 cases of breast cancer from year 2016 to 2018 were utilized to investigate the presence of tumor-infiltrating lymphocytes. Relevant clinicopathological information was extracted. lmmunohistochemistry methods were used to investigate the expression of PD-Ll in 67 breast cancer tissue section. The association between tumor infiltrating lymphocytes, PD-Ll expression and clinicopathological parameters were analysed. Results: Over half of the patients were over 40 years of age. Majority of the patients were Malays. In addition, 42.5% of cases were classified as lymphocyte predominant breast cancer (score 2'.:50 %). Tumor-infiltrating lymphocytes had a significant association with tumor grades, ER receptor status, PR receptor status and Ki-67 index. The expression of PD-LI in tumor area was shown in 22of67 cases and 28of67 cases in stromal area. PD-L 1 was significantly associated with higher tumor grades and higher levels of tumor infiltrating-lymphocytes. Conclusion: Tumor infiltrating lymphocytes and PD-Ll expression is an important indicator of immunological imbalance and they are associated with unfavourable characteristic of breast cancer.
Factors That Contribute To Red Blood Cells Transfusion Among Obstetrics Patients In Hospital Serdang, Selangor
(2019)
Ismail, Amrah
Background: Transfusion of blood and blood components among obstetrics patients is a common practice. However, it is associated with significant clinical risks. There is usually high request for blood transfusion among obstetrics patients but only some is used for transfusion. This study aimed to determine the crossmatch to transfusion ratio (C: T ratio) and the factors that contribute to red blood cells transfusion among obstetrics patients. Methods: Retrospective cohort study with data collected from crossmatch requests forms of 350 obstetrics patients who were admitted to Hospital Serdang. Results: The mean C:T ratio is 3.08. Majority of the patients transfused were those who had intrapartum fever (60%), haemoglobinopathy (75.9%), those who consumed anti-thrombotic medications (100%), those who had history of post-partum haemorrhage (63.6%) and those who underwent laparotomy (100.0%). In addition, most of the patients who had haemoglobin level <7g/dL (90.5%) and patients with estimated blood loss >2 litre were also transfused. Caesarean section, haemoglobin level and estimated blood loss were the factors that significantly associated with red blood cells transfusion (p<0.05) among obstetrics patients. Conclusions: Identification of the factors contributing to red blood cells transfusion among obstetrics patients, results in minimising the unnecessary blood ordering.

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