Displaying publications 41 - 60 of 92 in total

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  1. Sood S, Winn T, Ibrahim S, Gobindram A, Arumugam AA, Razali NC, et al.
    Med J Malaysia, 2015 Dec;70(6):341-5.
    PMID: 26988206 MyJurnal
    OBJECTIVE: The natural history of asymptomatic (silent) gallstones has been inadequately studied. Existing information derives from studies based on oral cholecystography or relatively small sample sizes. We planned a retrospective cohort study in subjects with gallstones to determine conversion rates from asymptomatic to symptomatic.
    METHODS: We extracted data from computerised databases of one government hospital and two private clinics in Malaysia. Files were scrutinised to ensure that criteria for asymptomatic gallstones were fulfilled. Patients were called on telephone, further questioned to confirm that the gallstones at detection were truly asymptomatic, and asked about symptoms that were consistent with previously defined criteria for biliary colic. Appropriate ethical clearances were taken.
    RESULTS: 213 (112 males) patients fulfilled the criteria for asymptomatic gallstones and could be contacted. 23 (10.8%) developed pain after an average follow up interval of 4.02 years (range 0.1-11 years). Conversion rates from asymptomatic to symptomatic gallstones were high in the first two years of follow up, averaging 4.03±0.965 per year. Over time the conversion rates slowed, and by year 10 the annual conversion rate averaged only 1.38±0.29. Conversion rates were much higher for females compared to males (F:M hazard ratio 3.23, SE 1.54, p>z 0.014). The lifetime risks for conversion approached 6.15% for males, and 22.1% for females.
    CONCLUSION: In conclusion, asymptomatic gallstones are much more likely to convert to symptomatic in females than in males. Males in whom asymptomatic stones are discovered should be advised conservative treatment. Surgery may be preferable to conservative management if the subject is a young female.
    m radiology records of Hospital
    Study site: Computerised database, Hospital Selayang, Selangor; private clinics, Kuala Lumpur, Malaysia
  2. Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
  3. Kosai NR, Rajan R, Roslani EJ, Sutton PA, Mustafa M, Das S
    Clin Ter, 2015 Nov-Dec;166(6):248-52.
    PMID: 26794812 DOI: 10.7417/CT.2015.1896
    In the modern era of surgery, minimally invasive surgery is increasingly applied for excision of gastrointestinal stromal tumors. Site, size and tumor location are important factors that affect the surgical approach and excision. We performed a laparoendoscopic transgastric enucleation of a 4-cm pericardial endophytic gastrointestinal stromal tumor (GIST) using an energy device. The surgery was successful and post-operative recovery uneventful. No tumor recurrence was detected on surveillance gastroscopy. In the safe hands of a well-trained laparoscopic upper gastrointestinal surgeon, pericardial GIST can be enucleated safely by this method. The avoidance of surgical staplers is not only cost-effective, but also reduces the risk of associated complications.
  4. Jeong SJ, Italiano C, Chaiwarith R, Ng OT, Vanar S, Jiamsakul A, et al.
    AIDS Res Hum Retroviruses, 2016 Mar;32(3):255-61.
    PMID: 26414065 DOI: 10.1089/AID.2015.0058
    Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003-2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count <200 cells/μl or an AIDS-defining event within ±3 months of first positive HIV test) were analyzed in a random effects logistic regression model. Among 3,744 patients, 2,681 (72%) were late presenters. In the multivariable model, older patients were more likely to be late presenters than younger (≤30 years) patients [31-40, 41-50, and ≥51 years: odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.31-1.88; OR = 2.01, 95% CI 1.58-2.56; and OR = 1.69, 95% CI 1.23-2.31, respectively; all p ≤ 0.001]. Injecting drug users (IDU) were more likely (OR = 2.15, 95% CI 1.42-3.27, p < 0.001) and those with homosexual HIV exposure were less likely (OR = 0.45, 95% CI 0.35-0.58, p < 0.001) to be late presenters compared to those with heterosexual HIV exposure. Females were less likely to be late presenters (OR = 0.44, 95% CI 0.36-0.53, p < 0.001). The year of first positive HIV test was not associated with late presentation. Efforts to reduce the patients who first seek HIV care at the late stage are needed. The identified risk factors associated with late presentation should be utilized in formulating targeted public health intervention to improve earlier entry into HIV care.
  5. Jiamsakul A, Kerr SJ, Ng OT, Lee MP, Chaiwarith R, Yunihastuti E, et al.
    Trop Med Int Health, 2016 May;21(5):662-74.
    PMID: 26950901 DOI: 10.1111/tmi.12690
    OBJECTIVES: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.

    METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.

    RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).

    CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

  6. Ku NS, Jiamsakul A, Ng OT, Yunihastuti E, Cuong DD, Lee MP, et al.
    Medicine (Baltimore), 2016 Aug;95(32):e4570.
    PMID: 27512885 DOI: 10.1097/MD.0000000000004570
    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.
  7. Tijjani Salihu A, Muthuraju S, Aziz Mohamed Yusoff A, Ahmad F, Zulkifli Mustafa M, Jaafar H, et al.
    Behav Brain Res, 2016 10 01;312:374-84.
    PMID: 27327104 DOI: 10.1016/j.bbr.2016.06.034
    The present study aimed to investigate the behavior and neuronal morphological changes in the perihaemorrhagic tissue of the mouse intracerebellar haemorrhage experimental model. Adult male Swiss albino mice were stereotactically infused with collagenase type VII (0.4U/μl of saline) unilaterally in to the cerebellum, following anaesthesia. Motor deficits were assessed using open field and composite score for evaluating the mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase infusion. The animals were sacrificed at the same time interval for evaluation of perihaematomal neuronal degeneration using haematoxylin and eosin staining and Annexin V-FITC/Propidium iodide assay. At the end of the study, it was found that infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the mice especially within the first week post surgery, and that this gradually improved within three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7 days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in the perihaematomal area were phagocytosed and the remaining neuronal cells around the scar tissue appeared normal. Moreover, Annexin-V/propidium iodide-positive cells were observed at the perihaematomal area at 3 and 7 days implying that the neurons likely die via apoptosis. It was concluded that a population of potentially salvageable neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a wide time window that could be amenable to treatment.
  8. Ab Halim MH, Nor Anuar A, Abdul Jamal NS, Azmi SI, Ujang Z, Bob MM
    J Environ Manage, 2016 Dec 15;184(Pt 2):271-280.
    PMID: 27720606 DOI: 10.1016/j.jenvman.2016.09.079
    The effect of temperature on the efficiency of organics and nutrients removal during the cultivation of aerobic granular sludge (AGS) in biological treatment of synthetic wastewater was studied. With this aim, three 3 L sequencing batch reactors (SBRs) with influent loading rate of 1.6 COD g (L d)(-1) were operated at different high temperatures (30, 40 and 50 °C) for simultaneous COD, phosphate and ammonia removal at a complete cycle time of 3 h. The systems were successfully started up and progressed to steady state at different cultivation periods. The statistical comparison of COD, phosphate and ammonia for effluent from the three SBRs revealed that there was a significant difference between groups of all the working temperatures of the bioreactors. The AGS cultivated at different high temperatures also positively correlated with the accumulation of elements including carbon, oxygen, phosphorus, silicon, iron, aluminium, calcium and magnesium that played important roles in the granulation process.
  9. Abdul Manaf MR, Mustafa M, Abdul Rahman MR, Yusof KH, Abd Aziz NA
    PLoS One, 2016;11(6):e0156937.
    PMID: 27280529 DOI: 10.1371/journal.pone.0156937
    BACKGROUND AND PURPOSE: Mental health problems are common in old age, but frequently remain undetected and untreated. Mental health problems in the elderly are the result of a complex interaction of social, psychological and biological factors. The aim of this study is to determine the prevalence of mental health problems (depression, anxiety, and emotional stress) and their associated factors among the Malay elderly in a rural community of Perak, Malaysia.

    METHODS: It was a cross-sectional study. The Malay elderly aged 60 years and above were selected through convenient sampling to give a total of 230 respondents. The Depression, Anxiety, and Stress Scale (DASS-21) was used to assess the symptoms of depression, anxiety, and stress. Bivariate analyses were performed using chi-square tests and multiple logistic regression analyses were conducted to determine the association between the factors and each of the mental health statuses assessed.

    RESULTS: The results showed that the prevalence of depression, anxiety, and stress among the elderly respondents was 27.8%, 22.6%, and 8.7%, respectively. The significant factors for depression were single elderly (Adjusted OR = 3.27, 95%CI 1.66, 6.44), living with family (Adjusted OR = 4.98, 95%CI 2.05, 12.10), and poor general health status (Adjusted OR = 2.28, 95%CI 1.20, 4.36). Living with family was the only significant factor for anxiety (Adjusted OR = 2.68, 95%CI 1.09, 6.57). There was no significant factor for stress.

    CONCLUSIONS: Depression and anxiety among the Malay elderly in the rural community were very worrying. More equity in health should be created or strengthened in order to intensify the opportunity to identify, diagnose, and treat those with mental health problems. Living arrangement in the rural community was an important factor that had influenced depression and anxiety. Therefore, further research is recommended for more comprehensive information, as a result of which appropriate intervention can be made.

  10. Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al.
    PLoS One, 2016;11(3):e0150512.
    PMID: 26933963 DOI: 10.1371/journal.pone.0150512
    BACKGROUND: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

    METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

    RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

    CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

  11. Jagwani AV, Reynu R, Affirul CA, Mustafa MT, Kosai NR
    Clin Ter, 2016;167(4):99-100.
    PMID: 27598021 DOI: 10.7417/CT.2016.1937
    We discuss a 48-year old, who presented with upper epigastrium pain associated with early satiety and significant weight loss. Physical examination revealed a thickening and darkening of skins around the skin folds, scalp, back and front of abdomen. A diagnosis of gastro-esophageal junction adenocarcinoma was confirmed by oesophagogastroduodenoscopy (OGDS) and biopsy. The biopsy of the skin lesion revealed a diagnosis of acanthosis nigricans, He underwent a total gastrectomy followed by adjuvant chemo-radiotherapy. Recovery is unremarkable. Interestingly, the skin lesions disappear following our therapy. We believe this may be attributed to the treatment of the malignancy. We highlight the interesting association, pathophysiology and therapy.
  12. Tanuma J, Jiamsakul A, Makane A, Avihingsanon A, Ng OT, Kiertiburanakul S, et al.
    PLoS One, 2016;11(8):e0161562.
    PMID: 27560968 DOI: 10.1371/journal.pone.0161562
    BACKGROUND: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.

    METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.

    RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).

    CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.

  13. Umar ZD, Aziz NA, Zulkifli SZ, Mustafa M
    MethodsX, 2017;4:104-117.
    PMID: 28280689 DOI: 10.1016/j.mex.2017.02.003
    Polycyclic Aromatic Hydrocarbons (PAHs) are complex and widely distributed environmental pollutants that can affect living ecosystems. This study was conducted to rapidly degrade phenanthrene and pyrene representing low and high molecular weight of PAHs, respectively. Cronobacter sakazakii MM045 (KT933253) was identified from used engine oil of contaminated soil. PAHs biodegradation was carried out using 2,6-dichlorophenol indophenol (DCPIP) assay. Biodegradation influencing factors including agitation, temperature, pH, inoculums volume and salinity were enhanced using Response Surface Methodology (RSM) by Central Composite Design (CCD). Phenanthrene and pyrene biodegrading metabolites were identified using gas chromatography mass spectrophotometer (GCMS). •Initial biodegradation indicated 75.2% and 54.3% phenanthrene and pyrene degraded by C. sakazakii MM045 within 24 h. After CCD optimisation, 100% degradation was achieved for each of the phenanthrene and pyrene, resulting in the formation of intermediate metabolites.•The identified phenanthrene metabolites were 3,4-dihydroxyphenathrene, phthalic acid, pyruvic acid, acetic acid and oxalic acid. Pyrene intermediates comprised pyrene cis-4,5-dihydrodiol, 3,4-dihydroxyphenanthrene, phthalic acid, pyruvic acid, acetic acid and lactic acid.•Cronbacter sakazakii MM045 was proven to be rapid and effective in degrading PAHs within 24 h despite the unavailability of existing literatures on PAHs biodegradation.
  14. Hanapiah M, Zulkifli SZ, Mustafa M, Mohamat-Yusuff F, Ismail A
    Mar Pollut Bull, 2018 Feb;127:453-457.
    PMID: 29475685 DOI: 10.1016/j.marpolbul.2017.12.015
    Diuron is an alternative biocide suggested to replace organotin in formulating antifouling paints to be applied on water-going vessels hull. However, it is potentially harmful to various non-targeted marine organisms due to its toxic properties. Present study aimed to isolate, screen and identify the potential of Diuron-degrading bacteria collected from the marine sediments of Port Klang, Malaysia. Preliminary screening was conducted by exposing isolated bacteria to 430ng/L (background level), followed by 600ng/L and 1000ng/L of Diuron concentrations. Nine bacteria colonies survived the exposure of the above concentrations. However, only two strains can tolerate to survive up to 1000μg/L, which were then characterised and identified using phenotypic tests and the standard 16S rRNA molecular identification. The strains were identified as Comamonas jiangduensis SZZ 10 and Bacillus aerius SZZ 19 (GenBank accession numbers: KU942479 and KU942480, respectively). Both strains have the potential of Diuron biodegradation for future use.
  15. Nirwati H, Hakim MS, Darma S, Mustafa M, Nuryastuti T
    Med J Malaysia, 2018 10;73(5):291-296.
    PMID: 30350807
    INTRODUCTION: Acinetobacter baumannii (A. baumannii) is commonly found as an agent of nosocomial infections and demonstrates a high antibiotic resistance due to its carbapenemase production. The objectives of this study were to explore the antibiotic resistance pattern, the presence of OXAs genes and the biofilm-producing capacity of A. baumannii isolated from clinical specimens.

    METHODS: Antibiotics susceptibility testing, detection of OXAs genes and the biofilm-producing capacity were performed using the Kirby Bauer method, polymerase chain reaction (PCR) and adherence quantitative assays, respectively.

    RESULTS: A total of 80 A. baumannii isolates were mainly obtained from sputum and most of them were resistant to antibiotics. All A. baumannii carried blaOXA-51 gene, yet no blaOXA-24 and blaOXA-58 genes were detected. Fourteen (82.4%) of the 17 meropenem resistant isolates carried blaOXA-23 gene, but it was not found in meropenem sensitive isolates. In addition, sixty (75.0%) of 80 isolates were biofilm producers with 2 (2.5%), 16 (20.0%), and 42 (52.5%) isolates were identified as strong, moderate and weak biofilm producers, respectively.

    CONCLUSION: Most of A. baumannii isolates had a high level of antibiotic resistance and had a capacity to produce biofilm.

  16. Hasanpourghadi M, Abdul Majid N, Rais Mustafa M
    PeerJ, 2018;6:e5577.
    PMID: 30245930 DOI: 10.7717/peerj.5577
    Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.
  17. Mohamad N, Amal MNA, Saad MZ, Yasin ISM, Zulkiply NA, Mustafa M, et al.
    BMC Vet Res, 2019 May 28;15(1):176.
    PMID: 31138199 DOI: 10.1186/s12917-019-1907-8
    BACKGROUND: Vibriosis is an important bacterial disease of cultured marine fishes worldwide. However, information on the virulence and antibiotic resistance of Vibrio spp. isolated from fish are scarce. This study investigates the distribution of virulence associated genes and antibiotic resistance patterns of Vibrio spp. isolated from cage-cultured marine fishes in Malaysia.

    RESULTS: A total of 63 Vibrio spp. isolated from 62 cultured marine fishes in various geographical regions in Peninsular Malaysia were analysed. Forty-two of the isolates (66.7%) were positive for all chiA, luxR and vhpA, the virulence genes produced by pathogenic V. harveyi. A total of 62 Vibrio isolates (98%) had tlh gene of V. parahaemolyticus, while flaC gene of V. anguillarum was detected in 43 of isolates (68%). Other virulence genes, including tdh, trh, hlyA and toxRvc were absent from any of the isolates. Multiple antibiotic resistance (MAR) was exhibited in all strains of Harveyi clade, particularly against ampicillin, penicillin, polypeptides, cephems and streptomycin. The MAR index ranged between 0.06 and 0.56, and 75% of the isolates have MAR index of higher than 0.20. Host species and geographical origin showed no correlation with the presence of virulence genes and the antibiotic resistance patterns of Vibrio spp.

    CONCLUSIONS: The study indicates that majority of Vibrio spp. isolated from cultured marine fishes possess virulence genes, but were not associated with human pathogen. However, the antibiotics resistance is a real concern and warrants ongoing surveillance. These findings represent an updated knowledge on the risk of Vibrio spp. to human health, and also provides valuable insight on alternative approaches to combat vibriosis in cultured fish.

  18. Mohamad N, Mustafa M, Amal MNA, Saad MZ, Md Yasin IS, Al-Saari N
    J Aquat Anim Health, 2019 06;31(2):154-167.
    PMID: 30653742 DOI: 10.1002/aah.10062
    This study investigated the environmental factors associated with the presence of Vibrionaceae in economically important cage-cultured tropical marine fishes: the Asian Seabass Lates calcarifer, snapper Lutjanus sp., and hybrid grouper Epinephelus sp. Fish sampling was conducted at monthly intervals between December 2016 and August 2017. The body weight and length of individual fish were measured, and the skin, eye, liver, and kidney were sampled for bacterial isolation and identification. Water physicochemical parameters during the sampling activities were determined, and the enumeration of total Vibrionaceae count was also conducted from water and sediment samples. Nine species of Vibrio were identified, including V. alginolyticus, V. diabolicus, V. harveyi, V. campbellii, V. parahaemolyticus, V. rotiferianus, V. furnissii, V. fluvialis, and V. vulnificus. Photobacterium damselae subsp. damselae was also identified. A total of 73% of the isolated Vibrio belonged to the Harveyi clade, followed by the Vulnificus clade (5.5%) and Cholera clade (0.6%). Highest occurrence of Vibrio spp. and P. damselae subsp. damselae was found in hybrid grouper (72%), followed by Asian Seabass (48%) and snapper (36%). The associations of Vibrio spp. and P. damselae subsp. damselae with the host fish were not species specific. However, fish mortality and fish size showed strong associations with the presence of some Vibrio spp. On average, 60% of the infected cultured fish exhibited at least one clinical sign. Nevertheless, inconsistent associations were observed between the pathogens and water quality. The yearlong occurrence and abundance of Vibrionaceae in the environmental components indicate that they might serve as reservoirs of these pathogens.
  19. Shahruzaman SH, Mustafa MF, Ramli S, Maniam S, Fakurazi S, Maniam S
    BMC Complement Altern Med, 2019 Aug 19;19(1):220.
    PMID: 31426778 DOI: 10.1186/s12906-019-2628-z
    BACKGROUND: Baeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells.

    METHOD: B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC50 value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols.

    RESULTS: B. frutescens leaves extracts showed IC50 value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC50 value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC50 value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC50 value and subsequently cell death.

    CONCLUSION: This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism.

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