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A simplified multiplex PCR assay for fast and easy discrimination of globally distributed staphylococcal cassette chromosome mec types in meticillin-resistant Staphylococcus aureus

Ghaznavi-Rad E, Nor Shamsudin M, Sekawi Z, van Belkum A, Neela V

J Med Microbiol, 2010 Oct;59(Pt 10):1135-1139.
PMID: 20616192 DOI: 10.1099/jmm.0.021956-0

A multiplex PCR assay was developed for the identification of major types and subtypes of staphylococcal cassette chromosome mec (SCCmec) in meticillin-resistant Staphylococcus aureus (MRSA) strains. The method uses a novel 9 valent multiplex PCR plus two primer pairs for S. aureus identification and detection of meticillin resistance. All 389 clinical MRSA isolates from Malaysia and 18 European isolates from the Harmony collection harbouring different SCCmec types that we tested were correctly characterized by our PCR assay. SCCmec type III and V were by far the most common types among both hospital- and community-acquired Malaysian MRSA isolates, with an apparent emergence of MRSA harbouring the IVh type.
Fulltext Detection and characterization of viruses causing hand, foot and mouth disease from children in Seri Kembangan, Malaysia

Ling BP, Jalilian FA, Harmal NS, Yubbu P, Sekawi Z

Trop Biomed, 2014 Dec;31(4):654-62.
PMID: 25776590 MyJurnal

Hand, foot and mouth disease (HFMD) is a common viral infection among infants and children. The major causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were reported in neighboring countries. Infected infants and children may present with fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71 infections might cause fatal neurological complications. Since 1997, EV71 caused fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to identify and classify the viruses which detected from the patients who presenting clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December 2012 until July 2013, a total of 28 specimens were collected from patients with clinical case definitions of HFMD. The HFMD viruses were detected by using semi-nested reverse transcription polymerase chain reaction (snRT-PCR). The positive snRT-PCR products were sequenced and phylogenetic analyses of the viruses were performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6 (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis studies, EV71 strains were identified as sub-genotype B5; CVA16 strains classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by different types of Enterovirus, which were EV71, CVA6 and CVA16.
Human leukocyte antigen (HLA) class II association in chronic hepatitis B patients with hepatocellular carcinoma in a Malay population: A pilot study

Krishnan PB, Abdullah M, Hudu SA, Sekawi Z, Tan SS, Amin-Nordin S

Trop Biomed, 2019 Sep 01;36(3):703-708.
PMID: 33597492

Asian countries account for almost three quarter of hepatocellular carcinoma (HCC) reported globally and chronic hepatitis B infection is one of the main contributors. Clinical observations show that Malay patients with chronic hepatitis B and HCC tend to have a worse outcome, when compared to other two major races in Malaysia. The objectives of this study was to determine the frequency of human leukocyte antigen (HLA) class II alleles in chronic hepatitis B patients with HCC among Malays compared to the general population to identify potential associations of HLA alleles with this disease. HLA class II typing was performed in chronic hepatitis B patients with hepatocellular carcinoma (n=12) by -polymerase chain reaction, sequence specific primer (PCR-SSP) method. There were higher allelic frequencies of certain HLA-DQB1 and HLA-DRB1 alleles; HLA-DQB1*03 (07) (41.7%), and HLA-DRB1*12 (41.7% vs 28.6%) and compared to controls (41.7% vs 29.7%). However, there was no significant statistical correlation found when compared with the normal healthy general population. This study provides an insight into the HLA Class II association with chronic hepatitis B and hepatocellular carcinoma in Malays. However, findings from this study should be validated with a larger number of samples using a high resolution HLA typing.
Quantitative Hepatitis B e Antigen: A Better Predictor of Hepatitis B Virus DNA than Quantitative Hepatitis B Surface Antigen

Hudu SA, Niazlin MT, Nordin SA, Saeed MI, Tan SS, Omar H, et al.

Clin. Lab., 2018 Apr 01;64(4):443-449.
PMID: 29739076 DOI: 10.7754/Clin.Lab.2017.170916

BACKGROUND: Hepatitis B surface antigen is usually secreted by infected hepatocytes in the form of subviral particles rather than infectious virions, while the hepatitis B e antigen originates from the core gene and is modified and secreted by hepatocytes into the circulation and functions as a marker of active viral replication. This study aimed to study the relationship between HBV DNA and quantitative hepatitis B surface and e antigen in Malaysian patients.
METHODS: A total of 82 chronic hepatitis B patients were recruited for this study from the Hepatology Department of Selayang Hospital. Quantitative hepatitis surface and e antigen was performed retrospectively on frozen plasma using enzyme linked immunosorbent assay according to the manufacturer's instructions. Hepatitis B viral DNA was extracted from all plasma samples and quantified using real-time PCR.
RESULTS: Quantitative hepatitis B surface and e antigens were found be high in 54.9% and 52.4% of the patients, respectively, while hepatitis B virus DNA level was high in 70.7%. The median of the viral load of HBV was 8,934.89 IU/mL and both hepatitis B surface and e antigens were also found to be high on average for qHBsAg (M = 5.19 IU/mL, SD ± 4. 33) and qHBeAg (M = 4.74IU/mL, SD ± 4.20), with qHBeAg being more strongly correlated to HBV DNA than qHBsAg (r = 0.893; p < 0.01).
CONCLUSIONS: This study revealed HBeAg to be the most appropriate marker that correlates well with HBV DNA, thus not completely novel but confirmative, and related to the Malaysian situation.
Fulltext Genetic diversity of hepatitis B co-infection with hepatitis C, D and E viruses among Malaysian chronic hepatitis B patients

Hudu SA, Niazlin MT, Nordin SA, Tan SS, Omar H, Shahar H, et al.

Afr Health Sci, 2018 Dec;18(4):1117-1133.
PMID: 30766578 DOI: 10.4314/ahs.v18i4.33

Background: Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.
Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.
Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.
Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).
Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.
Fulltext Predictors of severe leptospirosis: a multicentre observational study from Central Malaysia

Philip N, Lung Than LT, Shah AM, Yuhana MY, Sekawi Z, Neela VK

BMC Infect Dis, 2021 Oct 19;21(1):1081.
PMID: 34666707 DOI: 10.1186/s12879-021-06766-5

BACKGROUND: Leptospirosis is a re-emerging disease with vast clinical presentations, that ranges from subclinical or mild to severe and fatal outcomes. Leptospirosis can be managed well if diagnosed earlier, however, similar clinical presentations by several other febrile illnesses or co-infections, and laboratory diagnostic challenges due to the biphasic nature of the illness, often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study.
METHODS: A prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity.
RESULTS: Among the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet 50 IU and platelet
An Overview of Hepatitis B Virus Surface Antigen Mutant in the Asia Pacific

Hudu SA, Malik YA, Niazlin MT, Harmal NS, Sekawi Z

Curr Issues Mol Biol, 2014;16:69-78.
PMID: 24014801

Hepatitis B virus infection is a serious health problem worldwide, and more than 350 million people are chronic carriers, constituting a major global threat. Southeast Asia and the Western Pacific have the highest levels of endemicity in the world, with an estimated seroprevalence ranging between 2% and 31%. Mutations in the hepatitis B surface antigen (HBsAg) have been reported in many parts of the world but are most common in Asian infants; such mutants have several clinical effects, such as the development of hepatocellular carcinoma. Diagnostic failures by commercial assays have reduced the diagnostic effectiveness of HBsAg detection. For example the substitution of an amino acid in the major hydrophilic region of the S gene reduces the binding of hepatitis B surface antibodies leading to immune escape. The safety of blood transfusion may be compromised by current screening tests due to escape from being neutralised by antibodies induced by HBsAg mutants, and undetectable levels of viral surface protein. Data on the epidemiology of HBsAg mutation in Asia Pacific are scant; however, this manuscript has reviewed the available information on the epidemiology of HBsAg mutation in Asia Pacific.
Fulltext Epstein-Barr virus infection is associated with the nuclear factor-kappa B p65 signaling pathway in renal cell carcinoma

Farhadi A, Namdari S, Chong PP, Geramizadeh B, Behzad-Behbahani A, Sekawi Z, et al.

BMC Urol, 2022 Feb 07;22(1):17.
PMID: 35130882 DOI: 10.1186/s12894-022-00964-2

BACKGROUND: There have been few studies regarding viral involvement in the pathogenesis of renal cell carcinoma (RCC). The aim of this study was to examine the possible association of Epstein-Barr virus (EBV) infection with clinicopathological features and cellular biomarkers including p53, p16INK4a, Ki-67 and nuclear factor-kappa B (NF-κB) in RCC tumors.
METHODS: In this prospective study, 122 histologically confirmed Formalin-fixed Paraffin-embedded RCC tissue specimens along with 96 specimens of their corresponding peritumoral tissues and 23 samples of blunt renal injuries were subjected to nested polymerase chain reaction (nPCR) in order to amplify EBV DNA sequences. The expression of p53, p16INK4a, Ki-67 and NF-κB was investigated by immunohistochemistry (IHC) assay. Statistical analysis was employed to demonstrate the possible associations.
RESULTS: Infection with EBV was found to be significantly associated with RCC. Our results indicate that p65 NF-κB signaling pathway is probably involved in EBV-mediated RCC pathogenesis. Moreover, we found p53, Ki-67 and cytoplasmic NF-κB expression to be associated with tumor nuclear grade in RCC patients. The expression of p53 and Ki-67 was associated with primary tumor category as well. In addition, p53 overexpression was significantly more frequent among nonconventional RCC tumors than the conventional histologic type.
CONCLUSIONS: Infection with EBV is likely to play an important role in the development of RCC through the constitutive and permanent activation of NF-κB p65 signaling pathway. However, more experiments and supporting data are required to reach a decisive conclusion.
Distribution of pathogenic Leptospira in environmental water and soils of selected recreational forests in Perak, Malaysia

Yap ML, Chew LJ, Pritpal Singh SS, Sekawi Z, Chee HY, Ong HKO, et al.

Trop Biomed, 2021 Jun 01;38(2):122-128.
PMID: 34172700 DOI: 10.47665/tb.38.2.047

Leptospirosis is an emerging zoonotic disease endemic in tropical regions. Aiming at assessing the potential infection risks via recreational exposure, the molecular prevalence of pathogenic Leptospira in 14 amenity forests in five selected districts of the state of Perak was determined. Water and soil samples along streams and waterfalls were subjected to culture of leptospires and the pathogenic Leptospira spp. was detected by lipL32-based polymerase chain reaction (PCR). Twenty out of 154 samples (13%) that tested positive for leptospires were mostly soils and still water recorded with tolerable temperatures (22.2- 26.5°C) and pHs (5.73-6.70). The localised prevalence was highly varied among eight positive forests (6.7-41.7%), particularly higher in Kampar and Kinta districts which are the more populated urban areas. The importance of public health surveillance should not be underrated given the high prevalence of Leptospira spp. in forests in close proximity to indigenous settlements, even where the places are clean. Overall, this study discovered a wide distribution of pathogenic Leptospira spp. in recreational areas.
Fulltext Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells

Reza Etemadi M, Ling KH, Zainal Abidin S, Chee HY, Sekawi Z

PLoS One, 2017;12(5):e0176947.
PMID: 28558071 DOI: 10.1371/journal.pone.0176947

Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
Fulltext Expression of Human Cytokine Genes Associated with Chronic Hepatitis B Disease Progression

Hudu SA, Niazlin MT, Nordin SA, Saeed MI, Tan SS, Sekawi Z

Iran J Immunol, 2017 Dec;14(4):281-292.
PMID: 29276181 DOI: IJIv14i4A3

BACKGROUND: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated events.
OBJECTIVE: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection.
METHODS: We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on a master cycler ep realplex and the data were analyzed using an online data analysis software.
RESULTS: Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression.
CONCLUSION: Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a role in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.
The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma multiforme cancer stem cells

Vazifehmand R, Ali DS, Othman Z, Chau DM, Stanslas J, Shafa M, et al.

J Neurovirol, 2022 Dec;28(4-6):566-582.
PMID: 35951174 DOI: 10.1007/s13365-022-01089-w

Glioblastoma multiforme is the most aggressive astrocytes brain tumor. Glioblastoma cancer stem cells and hypoxia conditions are well-known major obstacles in treatment. Studies have revealed that non-coding RNAs serve a critical role in glioblastoma progression, invasion, and resistance to chemo-radiotherapy. The present study examined the expression levels of microRNAs (in normoxic condition) and long non-coding RNAs (in normoxic and hypoxic conditions) in glioblastoma stem cells treated with the HSV-G47∆. The expression levels of 43 miRNAs and 8 lncRNAs isolated from U251-GBM-CSCs were analyzed using a miRCURY LNA custom PCR array and a quantitative PCR assay, respectively. The data revealed that out of 43 miRNAs that only were checked in normoxic condition, the only 8 miRNAs, including miR-7-1, miR-let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, and miR-874, were markedly upregulated. The expression levels of lncRNAs, including LEF1 antisense RNA 1 (LEF1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein coding RNA 470 (LINC00470), tumor suppressor candidate 7 (TUSC7), HOX transcript antisense RNA (HOTAIR), nuclear paraspeckle assembly transcript 1 (NEAT1), and X inactive specific transcript (XIST), were markedly downregulated in the hypoxic microenvironment, and H19-imprinted maternally expressed transcript (H19) was not observed to be dysregulated in this environment. Under normoxic conditions, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated and TUSC7 was not targeted by HSV-G47∆. Overall, the present data shows HSVG47Δ treatment deregulates non-coding RNA expression in GBM-CSC tumor microenvironments.
The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

Ghafourian S, Good L, Sekawi Z, Hamat RA, Soheili S, Sadeghifard N, et al.

Mem Inst Oswaldo Cruz, 2014 Jul;109(4):502-5.
PMID: 25004148

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems' locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.
Fulltext Isolated hepatitis B core antibody positive among vaccinated cohort in Malaysia

Hudu SA, Malik YA, Niazlin MT, Harmal NS, Alshrari AS, Sekawi Z

Ann Saudi Med, 2013;33(6):591-4.
PMID: 24413864 DOI: 10.5144/0256-4947.2013.591

BACKGROUND AND OBJECTIVES: Hepatitis B core antibodies (anti-HBc) are detected in almost every patient with previous exposure to hepatitis B virus (HBV). However, with this marker alone, one cannot understand the activity of the disease; therefore, this study aimed to identify the implication of isolated hepatitis B core antibody and evaluate the effect of hepatitis B vaccine booster in isolated anti-HBc among adults who received the HBV vaccine as infants.
DESIGN AND SETTINGS: A prospective cohort study of vaccinated undergraduate students of University Putra Malaysia.
PATIENTS AND METHODS: A total of 408 undergraduate students who received infant hepatitis B vaccination volunteered for this study; 5 mL of venous blood was taken from the volunteers. Hepatitis B surface antigen (HBsAg) and core antibodies were tested using a commercially available enzyme-linked immunosorbent assay kit according to the manufacturer's instructions (DRG international Inc., USA). Molecular detection of hepatitis B viral DNA was performed using nested polymerase chain reaction.
RESULTS: The prevalence of isolated anti-HBc among the vaccinated cohort was found to be 5.0%, out of which 80% had a hepatitis B surface antibodies (anti-HBs) titer higher than 10 IU/L, while 20% had less than 10 IU/L anti-HBs titer. All the anti-HBc positivesubjects had detectable hepatitis B viral DNA in their serum. Anamnestic response was found to be 100% among isolated anti-HBc with negative antibody.
CONCLUSION: Isolated anti-HBc developed protective levels of anti-HBs after a single dose of recombinant hepatitis B vaccination. HBV DNA was detected in all isolated anti-HBc indicating occult chronic HBV infection with undetectable HBsAg.
Fulltext Comparative characterisation of genotypically different clones of MRSA in the production of biofilms

Atshan SS, Shamsudin MN, Lung LT, Sekawi Z, Ghaznavi-Rad E, Pei CP

J Biomed Biotechnol, 2012;2012:417247.
PMID: 22529705 DOI: 10.1155/2012/417247

The ability to adhere and produce biofilms is characteristic of enhanced virulence among isolates of methicillin-resistant Staphylococcus aureus (MRSA). The aim of the study is to find out whether these characteristics are consistently similar among isolates variations of MRSA. The study used 30 various isolates of MRSA belong to 13 spa types and 5 MLST types and determined the aggregation, the adherence, and the production of biofilms and slime for each isolate. The methods used to evaluate these characteristics were a modified Congo red agar assay (MCRA), a microtiter plate assay (MPA), high-magnification light microscopy, scanning electron microscopy (SEM), and PCR. The study found that isolates belonging to similar Spa, SCCmec, and ST types have similar abilities to produce biofilms; however, their ability to produce slime on CRA was found to be different. Moreover, isolates that have different Spa types showed high variation in their ability to produce biofilms. The results of light microscope revealed the isolates that produced strong and weak biofilms and formed similar aggregation on the glass surfaces. SEM results showed that all 30 MRSA isolates that were tested were 100% positive for biofilm formation, although to varying degrees. Further testing using PCR confirmed that 100% of the 30 isolates tested were positive for the presence of the icaADBC, fnbA, eno, ebps, clfA, and clfB genes. The prevalence of fib, cna, fnbB, and bbp in MRSA clones was 90, 93.33, 53.33, and 10%, respectively. This study indicate that differences in biofilm production capacities are caused by the differences in surface protein A (Spa) type and are not due to differences in MLST and SCCmec types.
Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions

Vazifehmand R, Ali DS, Homaie FM, Jalalvand FM, Othman Z, Deming C, et al.

Curr Cancer Drug Targets, 2024;24(12):1262-1274.
PMID: 38357955 DOI: 10.2174/0115680096274769240115165344

BACKGROUND: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion.
OBJECTIVE: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions.
METHODS: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways.
RESULTS: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments.
CONCLUSION: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.
Fulltext Diversity of respiratory viruses detected among hospitalized children with acute lower respiratory tract infections at Hospital Serdang, Malaysia

Etemadi MR, Jalilian FA, Othman N, Lye MS, Ansari S, Yubbu P, et al.

J Virol Methods, 2019 07;269:1-6.
PMID: 30910688 DOI: 10.1016/j.jviromet.2019.03.013

BACKGROUND: The role of respiratory viruses as the major cause of acute lower respiratory tract infections (ALRTIs) in children is becoming increasingly evident due to the use of sensitive molecular detection methods. The aim of this study was to use conventional and molecular detection methods to assess the epidemiology of respiratory viral infections in children less than five years of age that were hospitalized with ALRTIs.
METHODS: The cross-sectional study was designed to investigate the occurrence of respiratory viruses including respiratory syncytisl virus (RSV), human metapneumovirus (HMPV), influenza virus A and B (IFV-A and B), parainfluenzavirus 1, 2, 3 and 4 (PIV 1, 2, 3 and 4), human rhinoviruses (HRV), human enterovirus (HEV), human coronaviruses (HCoV) 229E and OC43, human bocavirus (HBoV) and human adenovirus (HAdV) in hospitalized children with ALRTIs, at Hospital Serdang, Malaysia, from June 16 to December 21, 2009. The study was also designed in part to assess the performance of the conventional methods against molecular methods.
RESULTS: Viral pathogens were detected in 158 (95.8%) of the patients. Single virus infections were detected in 114 (67.9%) patients; 46 (27.9%) were co-infected with different viruses including double-virus infections in 37 (22.4%) and triple-virus infections in 9 (5.5%) cases. Approximately 70% of samples were found to be positive using conventional methods compared with 96% using molecular methods. A wide range of respiratory viruses were detected in the study. There was a high prevalence of RSV (50.3%) infections, particularly group B viruses. Other etiological agents including HAdV, HMPV, IFV-A, PIV 1-3, HBoV, HCoV-OC43 and HEV were detected in 14.5, 9.6, 9.1, 4.8, 3.6, 2.4 and 1.8 percent of the samples, respectively.
CONCLUSION: Our results demonstrated the increased sensitivity of molecular detection methods compared with conventional methods for the diagnosis of ARTIs in hospitalized children. This is the first report of HMPV infections in Malaysia.
High-risk human papillomavirus infection in different histological subtypes of renal cell carcinoma

Farhadi A, Behzad-Behbahani A, Geramizadeh B, Sekawi Z, Rahsaz M, Sharifzadeh S

J Med Virol, 2014 Jul;86(7):1134-44.
PMID: 24700118 DOI: 10.1002/jmv.23945

Limited data exist regarding whether a high-risk human papillomavirus (HR-HPV) infection increases the risk of developing renal cell carcinoma. The aim of this study was to investigate whether HPV infection has a role in the pathogenesis or development of a certain histological subtype of renal cell carcinoma. Formalin-fixed paraffin-embedded (FFPE) specimens of 122 patients with histopathologically proven renal cell carcinoma and their respective peritumoral tissues were examined. The presence of HPV-DNA was determined by a combination of MY/GP+ consensus primers and HPV-16/18 type specific nested PCRs followed by direct sequencing. Catalyzed signal-amplified colorimetric in situ hybridization (CSAC-ISH) technique was applied to determine the physical status of viral genome. The expression of p16INK4a and HPV L1 capsid proteins was evaluated using immunohistochemistry. HPV genome was detected in 37 (30.3%) tumor specimens and their four (4.1%) corresponding peritumoral tissues. HPV-18 was the most common viral type identified followed by HPV-16 and 58. Immunoexpression of p16INK4a was detected in 24 (20.3%) cases. Data analysis showed a significant correlation between p16INK4a expression and the presence of HR-HPV DNA (P
Fulltext The Prevalence of ESBLs Producing Klebsiella pneumoniae Isolates in Some Major Hospitals, Iran

Ghafourian S, Bin Sekawi Z, Sadeghifard N, Mohebi R, Kumari Neela V, Maleki A, et al.

Open Microbiol J, 2011;5:91-5.
PMID: 21915229 DOI: 10.2174/1874285801105010091

Aims of this study were to investigate on antibiotic resistance and molecular epidemiology of K.pneumoniae producing ESBLs isolates of respiratory tract infections in some major hospitals in Iran. K.pneumonaie were obtained of patients with RTI. K. pneumoniae producing ESBLs detected by screening, confirming and PCR methods. During the 12-month period, a total of one hundred and thirteen of K.pneumoniae were found from RTI in three cities in different region of Iran which Sixty seven strains (59.2%) were ESBLs producer. In Ilam hospitals, seventeen strains (43.6%), in Milad hospital, thirty-seven strains (74%) and in Emam Reza hospital, thirteen strains (54.2%) were ESBLs producer. The findings showed that among sixty-seven K.pneumoniae producing ESBLs, Sixty-three strains (94%) were positive for blaSHV, eleven strains (16.4%) contained blaTEM and sixteen strains (23.9%) harbored blaCTX-M. Imipenem was found as an effectiveness antibiotic. In the current study, Majority of the ESBLs production had occurred in Milad hospital in Tehran (74%). In conclusion, spreading ESBL-producing strains is a concern, as it causes limitations to the antimicrobial agents for optimal treatment of patients.
Fulltext Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model

Khodavandi A, Alizadeh F, Harmal NS, Sidik SM, Othman F, Sekawi Z, et al.

FEMS Microbiol Lett, 2011 Feb;315(2):87-93.
PMID: 21204918 DOI: 10.1111/j.1574-6968.2010.02170.x

The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.

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