Displaying publications 81 - 100 of 129 in total

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  1. Rosli R, Dali AF, Aziz NA, Ming LC, Manan MM
    Front Pharmacol, 2017;8:30.
    PMID: 28239351 DOI: 10.3389/fphar.2017.00030
    Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children.
  2. Alkhader E, Roberts CJ, Rosli R, Yuen KH, Seow EK, Lee YZ, et al.
    J Biomater Sci Polym Ed, 2018 12;29(18):2281-2298.
    PMID: 30376409 DOI: 10.1080/09205063.2018.1541500
    Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6 hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.
  3. Al-Fahdawi MQ, Rasedee A, Al-Doghachi FA, Rosli R, Taufiq-Yap YH, Al-Qubaisi MS
    Nanomedicine (Lond), 2020 03;15(6):547-561.
    PMID: 32063101 DOI: 10.2217/nnm-2019-0178
    Aim: To prepare, physicochemically characterize and determine the anticancer effects of palladium-doped magnesia (Pd/MgO) nanoparticles. Materials & methods: Pd/MgO nanoparticles were prepared by the co-precipitation method from the aqueous solution of Mg(NO3)2.6H2O using K2CO3 and the impregnation of MgO into palladium acetylacetonate. Results: Pd/MgO nanoparticles were between 47 and 70 nm in size, cuboid in shape, and tended to form aggregates. Nanoparticles were more antiproliferative toward cancer than the normal cells. In cancer cells, Pd/MgO nanoparticles induced apoptosis by increasing caspase activities and stimulating cytochrome C release. The anticancer effects of Pd/MgO nanoparticles were accentuated by the upregulation of Bax and p53 and downregulation of Bcl-2 protein expressions. Conclusion: Pd/MgO nanoparticles have potential to be developed as an anticancer compound.
  4. Md Yusof K, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1055-1061.
    PMID: 33906296 DOI: 10.31557/APJCP.2021.22.4.1055
    INTRODUCTION: The survival rate of female breast cancer survivors has been reported to be higher than other types of cancer in Malaysia. Nonetheless, breast cancer survivors face new challenges from unwanted side effects of treatment or management such as fatigue, psychological disturbance, or arm swelling, which can lead to the decline of quality of life (QOL). This study aims to adapt the Malay version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) to evaluate the QOL and to test its reliability and validity in Malaysian breast cancer survivors.

    METHODS: The Malay version of the FACT-B, with Disabilities of Arms, Shoulders and Hands (DASH), and Patient Health Questionnaire Anxiety-Depression Scale (PHQ-ADS) were distributed to female breast cancer survivors which were recruited on a voluntary basis, from cancer support groups based in selected states in Malaysia. Reliability was assessed based on internal consistency (Cronbach's α), whereas concurrent validity was examined by comparing domains in FACT-B with DASH and PHQ-ADS. Finally, total scores of each domain were analysed between lymphedema and without lymphedema groups for known-group validity.

    RESULTS: A total of 113 breast cancer survivors agreed to participate (response rate = 100%) in the study. Our results showed that the Cronbach's α value for Malay FACT-B is 0.88, and each domain ranged from 0.62 to 0.88. A strong correlation was found between the physical well-being domain of FACT-B with DASH. Meanwhile, the breast cancer scale (BCS) displayed significant correlation with the instrument, Patient Health Questionnaire- Anxiety Depression Scale (PHQ-ADS), indicating that multiple factors including psychological distress were measured in the BCS domain. Furthermore, the instrument was able to detect differences in physical, functional and QOL between participants from lymphedema and without lymphedema groups.

    CONCLUSION: The Malay version of the FACT-B demonstrated reliable properties and is effective in assessing QOL and can be applied in Malaysian breast cancer survivors.

  5. Haghshenas B, Nami Y, Almasi A, Abdullah N, Radiah D, Rosli R, et al.
    Iran J Microbiol, 2017 Aug;9(4):234-243.
    PMID: 29238459
    Background and Objectives: Probiotics are live microorganisms, which show beneficial health effects on hosts once consumed in sufficient amounts. LAB group can be isolated and characterized from traditional dairy sources. This study aimed at isolating, identifying, and in vitro characterizing (low pH/high bile salt tolerance, antibacterial activity, and antibiotic susceptibility) LAB strains from traditional Iranian dairy products.

    Materials and Methods: Isolated strains were identified by Gram staining, catalase assay, and 3 molecular identification methods; namely, (GTG) 5-PCR fingerprinting, ARDRA, and 16S rDNA gene sequencing.

    Results: A total of 19 LAB strains belonging to 4 genera (Lactococcus, Leuconostoc, Lactobacillus and Enterococcus) were identified.

    Conclusion: The experiments revealed that L. plantarum 15HN, L. lactis subsp. cremoris 44L and E. mundtii 50H strains, which were isolated from shiraz, cheese and shiraz, respectively, displayed a desirable tolerance to low pH and high bile salts, favorable anti-pathogen activity, and acceptable antibiotic susceptibility; hence, they could be considered as novel probiotic candidates and applied in the food industry.

  6. Nigjeh SE, Yeap SK, Nordin N, Kamalideghan B, Ky H, Rosli R
    BMC Complement Altern Med, 2018 Feb 13;18(1):56.
    PMID: 29433490 DOI: 10.1186/s12906-018-2115-y
    BACKGROUND: Breast cancer remains a leading cause of death in women worldwide. Although breast cancer therapies have greatly advanced in recent years, many patients still develop tumour recurrence and metastasis, and eventually succumb to the disease due to chemoresistance. Citral has been reported to show cytotoxic effect on various cancer cell lines. However, the potential of citral to specifically target the drug resistant breast cancer cells has not yet been tested, which was the focus of our current study.

    METHODS: The cytotoxic activity of citral was first tested on MDA-MB-231 cells in vitro by MTT assay. Subsequently, spheroids of MDA-MB-231 breast cancer cells were developed and treated with citral at different concentrations. Doxorubicin, cisplatin and tamoxifen were used as positive controls to evaluate the drug resistance phenotype of MDA-MB-231 spheroids. In addition, apoptosis study was performed using AnnexinV/7AAD flowcytometry. Aldefluor assay was also carried out to examine whether citral could inhibit the ALDH-positive population, while the potential mechanism of the effect of citral was carried out by using quantitative real time- PCR followed by western blotting analysis.

    RESULTS: Citral was able to inhibit the growth of the MDA-MB-231 spheroids when compared to a monolayer culture of MDA-MB-231 cells at a lower IC50 value. To confirm the inhibition of spheroid self-renewal capacity, the primary spheroids were then cultured to additional passages in the absence of citral. A significant reduction in the number of secondary spheroids were formed, suggesting the reduction of self-renewal capacity of these aldehyde dehydrogenase positive (ALDH+) drug resistant spheroids. Moreover, the AnnexinV/7AAD results demonstrated that citral induced both early and late apoptotic changes in a dose-dependent manner compared to the vehicle control. Furthermore, citral treated spheroids showed lower cell renewal capacity compared to the vehicle control spheroids in the mammosphere formation assay. Gene expression studies using quantitative real time PCR and Western blotting assays showed that citral was able to suppress the self-renewal capacity of spheroids and downregulate the Wnt/β-catenin pathway.

    CONCLUSION: The results suggest that citral could be a potential new agent which can eliminate drug-resistant breast cancer cells in a spheroid model via inducing apoptosis.

  7. Adamu HA, Imam MU, Ooi DJ, Esa NM, Rosli R, Ismail M
    BMC Complement Altern Med, 2017 Jan 21;17(1):67.
    PMID: 28109299 DOI: 10.1186/s12906-017-1571-0
    The development of insulin resistance is multifactorial, with maternal pre- and postnatal nutrition having significant influences. In this regard, high fat diet (HFD) feeding in pregnancy has been shown to increase risks of metabolic diseases. Thus, we investigated the effects of supplementation of HFD with germinated brown rice (GBR) and GBR-derived gamma oryzanol-rich extract (OE) on insulin resistance and its epigenetic implications in pregnant rats and their offsprings.
  8. Yusof KM, Groen K, Rosli R, Abdullah M, Mahmud R, Avery-Kiejda KA
    Int J Mol Sci, 2022 Sep 26;23(19).
    PMID: 36232660 DOI: 10.3390/ijms231911359
    Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.
  9. Maniam R, Subramanian P, Singh SK, Lim SK, Chinna K, Rosli R
    Singapore Med J, 2014 Sep;55(9):476-82.
    PMID: 25273932
    INTRODUCTION: Fatigue and quality of sleep are the main factors that contribute to a poor quality of life among patients on long-term haemodialysis. Studies have also emphasised the importance of exercise for improving the wellbeing of dialysis patients. This study aimed to determine the effectiveness of a predialysis low-to-moderate-intensity exercise programme for reducing fatigue and improving sleep disorders among long-term haemodialysis patients.

    METHODS: In this quasi-experimental study, an exercise programme was conducted three times a week for 12 weeks before long-term haemodialysis patients underwent dialysis at two centres. The patients were categorised into either the exercise group (n = 28) or control group (n = 27). The latter was asked to maintain their current lifestyles. Assessments of fatigue and sleep disorder levels were performed for both groups using self-reported questionnaires at baseline and after intervention. The patients' perception of the exercise programme was also determined using self-reported questionnaires.

    RESULTS: Paired sample t-test indicated improvements in fatigue level in the exercise group (mean fatigue score: post-treatment 40.5 ± 7.9 vs. pre-treatment 30.0 ± 10.9). Improvements in sleep disorders were also observed in the exercise group (mean score: post-treatment 7.6 ± 3.3 vs. pre-treatment 10.1 ± 3.8). However, sleep quality deteriorated in the control group (mean score: post-treatment 10.7 ± 2.9 vs. pre-treatment 9.3 ± 2.9).

    CONCLUSION: Simple low-to-moderate-intensity exercise is effective for improving fatigue, sleep disorders and the overall quality of life among haemodialysis patients.
  10. Yusof KM, Mohd Sidik S, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Breast Cancer, 2023 Sep;30(5):810-819.
    PMID: 37306933 DOI: 10.1007/s12282-023-01475-0
    BACKGROUND: Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition.

    METHODS: A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia. Psychological distress status was assessed based on depression and anxiety scores by applying the Malay version of Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7). Both instruments were self-administered along with a set of questionnaires comprising demographic, medical history, quality of life, and upper extremity function assessment. Outcomes from the PHQ-9 and GAD-7 were analyzed for severity level of psychological distress, and its association with relevant variables, arm morbidity symptoms, as well as the duration of cancer survivorship.

    RESULTS: The univariate analysis showed that breast cancer survivors with arm morbidities after breast surgery had a higher score of depression (5.0 vs 4.0, p = 0.011) and anxiety (3.0 vs 1.0, p = 0.026) than those who did not. Besides that, receiving fewer post-rehabilitation treatments (p = 0.049) and having a family history of cancer (p = 0.022) were correlated with higher anxiety level. The level of depression and anxiety was inversely proportionate with quality of life and positively correlated with greater disability of the arm function (p 

  11. Haghshenas B, Haghshenas M, Nami Y, Yari Khosroushahi A, Abdullah N, Barzegari A, et al.
    Adv Pharm Bull, 2016 Mar;6(1):37-47.
    PMID: 27123416 DOI: 10.15171/apb.2016.07
    PURPOSE: Probiotics are microorganisms, which show beneficial health effects on hosts once consumed in sufficient amounts. Among probiotic bacteria, the bioactive compounds from lactic acid bacteria (LAB) group can be utilized as preservative agents. LAB group can be isolated and characterized from traditional dairy sources. This study aimed to isolate, identify, and biologically characterize probiotic LAB strains from Iranian traditional dairy products.

    METHODS: A total of 19 LAB strains were identified by sequencing of their 16S rRNA genes. They were examined for adherence to human intestinal Caco-2 cells and tolerance to low pH/high bile salts and simulated in vitro digestion conditions. Moreover, they were evaluated further to assess their ability to prevent the adhesion of Escherichia coli 026 to the intestinal mucosa, inhibitory functions against pathogens, and sensitivity to conventional antibiotics.

    RESULTS: L. plantarum 15HN and E. mundtii 50H strains displayed ≥ 71% survival rates at low pH/high bile salts and ≥ 40% survival rates in digestive conditions. Their adherences to Caco-2 cells were 3.2×105 and 2.6×105 CFU mL-1 respectively and high values of anti-adhesion capability were observed (≥36%). They inhibited the growth of 13 and 11 indicator pathogens respectively. Moreover, they were sensitive or semi-sensitive to seven and three out of eight antibiotics respectively.

    CONCLUSION: L. plantarum 15HN and E. mundtii 50H, which were isolated from shiraz product, displayed above-average results for all of the criteria. Therefore, they can be introduced as novel candidate probiotics that could be used in the food industry.

  12. Mansor NI, Ling KH, Rosli R, Hassan Z, Adenan MI, Nordin N
    J Alzheimers Dis, 2023;94(s1):S21-S44.
    PMID: 37334592 DOI: 10.3233/JAD-221233
    BACKGROUND: Centella asiatica (L.) (C. asiatica) is commonly known in South East and South East Asia communities for its nutritional and medicinal benefits. Besides being traditionally used to enhance memory and accelerate wound healing, its phytochemicals have been extensively documented for their neuroprotective, neuroregenerative, and antioxidant properties.

    OBJECTIVE: The present study aims to investigate the effects of a standardized raw extract of C. asiatica (RECA) on hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in neural-like cells derived from mouse embryonic stem (ES) cell line.

    METHODS: A transgenic mouse ES cell (46C) was differentiated into neural-like cells using 4-/4+ protocol with addition of all-trans retinoic acid. These cells were then exposed to H2O2 for 24 h. The effects of RECA on H2O2-induced neural-like cells were assessed through cell viability, apoptosis, and reactive oxygen species (ROS) assays, as well as neurite length measurement. The gene expression levels of neuronal-specific and antioxidant markers were assessed by RT-qPCR analysis.

    RESULTS: Pre-treatment with H2O2 for 24 hours, in a dose-dependent manner, damaged neural-like cells as marked by a decrease in cell viability, substantial increase in intracellular ROS accumulation, and increase in apoptotic rate compared to untreated cells. These cells were used to treat with RECA. Treatment with RECA for 48 h remarkably restored cell survival and promoted neurite outgrowth in the H2O2- damaged neurons by increasing cell viability and decreasing ROS activity. RT-qPCR analysis revealed that RECA upregulated the level of antioxidant genes such as thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1) of treated cells, as well as the expression level of neuronal-specific markers such as Tuj1 and MAP2 genes, suggesting their contribution in neuritogenic effect.

    CONCLUSION: Our findings indicate that RECA promotes neuroregenerative effects and exhibits antioxidant properties, suggesting a valuable synergistic activity of its phytochemical constituents, thus, making the extract a promising candidate in preventing or treating oxidative stress-associated Alzheimer's disease.

  13. Zamanian M, Qader Hamadneh LA, Veerakumarasivam A, Abdul Rahman S, Shohaimi S, Rosli R
    Cancer Cell Int, 2016;16:56.
    PMID: 27418879 DOI: 10.1186/s12935-016-0329-y
    The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion.
  14. Chan KL, Rosli R, Tatarinova TV, Hogan M, Firdaus-Raih M, Low EL
    BMC Bioinformatics, 2017 Jan 27;18(Suppl 1):1426.
    PMID: 28466793 DOI: 10.1186/s12859-016-1426-6
    BACKGROUND: Gene prediction is one of the most important steps in the genome annotation process. A large number of software tools and pipelines developed by various computing techniques are available for gene prediction. However, these systems have yet to accurately predict all or even most of the protein-coding regions. Furthermore, none of the currently available gene-finders has a universal Hidden Markov Model (HMM) that can perform gene prediction for all organisms equally well in an automatic fashion.

    RESULTS: We present an automated gene prediction pipeline, Seqping that uses self-training HMM models and transcriptomic data. The pipeline processes the genome and transcriptome sequences of the target species using GlimmerHMM, SNAP, and AUGUSTUS pipelines, followed by MAKER2 program to combine predictions from the three tools in association with the transcriptomic evidence. Seqping generates species-specific HMMs that are able to offer unbiased gene predictions. The pipeline was evaluated using the Oryza sativa and Arabidopsis thaliana genomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis showed that the pipeline was able to identify at least 95% of BUSCO's plantae dataset. Our evaluation shows that Seqping was able to generate better gene predictions compared to three HMM-based programs (MAKER2, GlimmerHMM and AUGUSTUS) using their respective available HMMs. Seqping had the highest accuracy in rice (0.5648 for CDS, 0.4468 for exon, and 0.6695 nucleotide structure) and A. thaliana (0.5808 for CDS, 0.5955 for exon, and 0.8839 nucleotide structure).

    CONCLUSIONS: Seqping provides researchers a seamless pipeline to train species-specific HMMs and predict genes in newly sequenced or less-studied genomes. We conclude that the Seqping pipeline predictions are more accurate than gene predictions using the other three approaches with the default or available HMMs.

  15. Mirakhorli M, Shayanfar N, Rahman SA, Rosli R, Abdullah S, Khoshzaban A
    Oncol Lett, 2012 Nov;4(5):893-897.
    PMID: 23162618
    Recurrence following failure of chemotherapy limits the application of high doses of anticancer drugs currently used for eliminating cancerous cells. It has been identified that ATP-binding cassette (ABC) multidrug transporters are associated with chemoresistance, which is a major obstacle in cancer therapy. The present study aimed to investigate the association of pretherapeutic multidrug resistance-associated protein 2 (MRP2) expression with response to chemotherapy in stage II/III colorectal cancer (CRC). Protein expression was determined by immunohistochemical analysis of 50 archival samples from patients who had not received preoperative chemotherapy and radiotherapy. All patients were treated with 5-fluorouracil/leucovorin (FL) plus oxaliplatin (FOLFOX-4) regimen for 6 months following curative resection. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) cases, of which 5 occurred at the time of chemotherapy. MRP2 expression was observed in 24 (48%) and 7 (14%) cases in the tumor tissues and matched normal tissues, respectively. A significant difference was observed between the positive expression frequency in the tumor tissues compared to the surrounding normal mucosa (P=0.003). The incidence of recurrence and metastasis for patients in the MRP2-positive group was lower than that in the MRP2-negative group (P>0.05); however, all 5 cases who demonstrated recurrence during their treatment were MRP2-positive (P=0.022). MRP2 expression was not correlated with the clinicopathological markers in this group of patients. Kaplan-Meier analysis revealed that MRP2 expression was not associated with a shorter disease-free survival or overall survival of patients (P>0.05). The results of this study indicated that MRP2 is overexpressed in the course of CRC development and progression. However, expression of MRP2 was not associated with recurrence of patients treated with FL and oxaliplatin in the population studied.
  16. Lee PY, Yong VC, Rosli R, Gam LH, Chong PP
    Protein Expr Purif, 2014 Feb;94:15-21.
    PMID: 24184232 DOI: 10.1016/j.pep.2013.10.012
    Squalene synthase (SS) is the key precursor and first committed enzyme of the sterol biosynthesis pathway. In a previous work, SS has been identified as one of the immunogenic proteins that could be a potential diagnostic candidate for the pathogenic fungus Candida tropicalis. In this study, SS from C. tropicalis was cloned and expressed as recombinant protein in Pichia pastoris to investigate its reactivity with serum antibodies. ERG9 gene that encodes for SS was amplified by PCR and cloned in-frame into pPICZB expression vector. The recombinant construct was then transformed into P. pastoris GS115 host strain. Expression of the recombinant protein was confirmed by SDS-PAGE and Western blot analysis using anti-His tag probe. Optimal protein production was achieved by cultivating the culture with 1.0% methanol for 72h. The recombinant protein was purified to approximately 97% pure in a single step immobilized metal affinity chromatography with a yield of 70.3%. Besides, the purified protein exhibited specific reactivity with immune sera on Western blot. This is the first report on heterologous expression of antigenic SS from C. tropicalis in P. pastoris which can be exploited for large-scale production and further research. The results also suggested that the protein might be of great value as antigen candidate for serodiagnosis of Candida infection.
  17. Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Saad N, et al.
    Neurotoxicology, 2019 12;75:89-104.
    PMID: 31521693 DOI: 10.1016/j.neuro.2019.09.008
    Neurodegenerative diseases (NDDs) are pathological conditions characterised by progressive damage of neuronal cells leading to eventual loss of structure and function of the cells. Due to implication of multi-systemic complexities of signalling pathways in NDDs, the causes and preventive mechanisms are not clearly delineated. The study was designed to investigate the potential signalling pathways involved in neuroprotective activities of purely isolated glucomoringin isothiocyanate (GMG-ITC) against H2O2-induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. GMG-ITC was isolated from Moringa oleifera seeds, and confirmed with NMR and LC-MS based methods. Gene expression analysis of phase II detoxifying markers revealed significant increase in the expression of all the genes involved, due to GMG-ITC pre-treatment. GMG-ITC also caused significant decreased in the expression of NF-kB, BACE1, APP and increased the expressions of IkB and MAPT tau genes in the differentiated cells as confirmed by multiplex genetic system analysis. The effect was reflected on the expressed proteins in the differentiated cells, where GMG-ITC caused increased in expression level of Nrf2, SOD-1, NQO1, p52 and c-Rel of nuclear factor erythroid factor 2 (Nrf2) and nuclear factor kappa-B (NF-kB) pathways respectively. The findings revealed the potential of GMG-ITC to abrogate oxidative stress-induced neurodegeneration through Nrf2 and NF-kB signalling pathways.
  18. Ting NC, Zaki NM, Rosli R, Low ET, Ithnin M, Cheah SC, et al.
    J Genet, 2010 Aug;89(2):135-45.
    PMID: 20861564
    This study reports on the detection of additional expressed sequence tags (EST) derived simple sequence repeat (SSR) markers for the oil palm. A large collection of 19243 Elaeis guineensis ESTs were assembled to give 10258 unique sequences, of which 629 ESTs were found to contain 722 SSRs with a variety of motifs. Dinucleotide repeats formed the largest group (45.6%) consisting of 66.9% AG/CT, 21.9% AT/AT, 10.9% AC/GT and 0.3% CG/CG motifs. This was followed by trinucleotide repeats, which is the second most abundant repeat types (34.5%) consisting of AAG/CTT (23.3%), AGG/CCT (13.7%), CCG/CGG (11.2%), AAT/ATT (10.8%), AGC/GCT (10.0%), ACT/AGT (8.8%), ACG/CGT (7.6%), ACC/GGT (7.2%), AAC/GTT (3.6%) and AGT/ACT (3.6%) motifs. Primer pairs were designed for 405 unique EST-SSRs and 15 of these were used to genotype 105 E. guineensis and 30 E. oleifera accessions. Fourteen SSRs were polymorphic in at least one germplasm revealing a total of 101 alleles. The high percentage (78.0%) of alleles found to be specific for either E. guineensis or E. oleifera has increased the power for discriminating the two species. The estimates of genetic differentiation detected by EST-SSRs were compared to those reported previously. The transferability across palm taxa to two Cocos nucifera and six exotic palms is also presented. The polymerase chain reaction (PCR) products of three primer-pairs detected in E. guineensis, E. oleifera, C. nucifera and Jessinia bataua were cloned and sequenced. Sequence alignments showed mutations within the SSR site and the flanking regions. Phenetic analysis based on the sequence data revealed that C. nucifera is closer to oil palm compared to J. bataua; consistent with the taxanomic classification.
  19. Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R, Yeap SK, et al.
    PLoS One, 2017;12(1):e0170233.
    PMID: 28103302 DOI: 10.1371/journal.pone.0170233
    Uridine-cytidine kinase 2 is an enzyme that is overexpressed in abnormal cell growth and its implication is considered a hallmark of cancer. Due to the selective expression of UCK2 in cancer cells, a selective inhibition of this key enzyme necessitates the discovery of its potential inhibitors for cancer chemotherapy. The present study was carried out to demonstrate the potentials of natural phytochemicals from the rhizome of Alpinia mutica to inhibit UCK2 useful for colorectal cancer. Here, we employed the used of in vitro to investigate the effectiveness of natural UCK2 inhibitors to cause HT-29 cell death. Extracts, flavokawain B, and alpinetin compound from the rhizome of Alpinia mutica was used in the study. The study demonstrated that the expression of UCK2 mRNA were substantially reduced in treated HT-29 cells. In addition, downregulation in expression of 18S ribosomal RNA was also observed in all treated HT-29 cells. This was confirmed by fluorescence imaging to measure the level of expression of 18S ribosomal RNA in live cell images. The study suggests the possibility of MDM2 protein was downregulated and its suppression subsequently activates the expression of p53 during inhibition of UCK2 enzyme. The expression of p53 is directly linked to a blockage of cell cycle progression at G0/G1 phase and upregulates Bax, cytochrome c, and caspase 3 while Bcl2 was deregulated. In this respect, apoptosis induction and DNA fragmentation were observed in treated HT-29 cells. Initial results from in vitro studies have shown the ability of the bioactive compounds of flavokawain B and alpinetin to target UCK2 enzyme specifically, inducing cell cycle arrest and subsequently leading to cancer cell death, possibly through interfering the MDM2-p53 signalling pathway. These phenomena have proven that the bioactive compounds could be useful for future therapeutic use in colon cancer.
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