1.Distribution of virulence genes in clinical isolates of hospital-associated and community-associated methicillin-susceptible Staphylococcus aureus from Terengganu, Malaysia
Che Hamzah, A.M. ; Yeo, C.C. ; Puah, S.M. ; Chua, K.H. ; A. Rahman, N.I. ; Ismail, S. ; Abdullah, F.H. ; Othman, N. ; Chew, C.H.
Tropical Biomedicine 2024;41(No.2):149-156
		                        		
		                        			
		                        			Staphylococcus aureus is a common bacterial pathogen known to cause various kinds of infections due to 
its repertoire of virulence factors. This study aimed to investigate the distribution of 19 types of virulence 
genes among clinical isolates of methicillin-susceptible S. aureus (MSSA) using the polymerase chain 
reaction. A total of 109 MSSA isolates, i.e., 63 hospital-associated (HA) and 46 community-associated (CA) 
were collected from Hospital Sultanah Nur Zahirah, the main tertiary hospital in Terengganu, Malaysia, 
from July 2016 to June 2017. The most frequent virulence genes detected were hla (78.9%, n=86) and 
hld (78.0%, n=85) encoding hemolysins, lukED (56.9%, n=62) encoding leukotoxin ED, followed by seb
(26.6%, n=29) and sea (24.8%, n=27) encoding enterotoxins. Among 34 (31.2%) isolates carrying six 
or more virulence genes, only five were multidrug resistant (MDR) while the remaining isolates were 
susceptible. Significant associations were discovered between the hld gene with CA-MSSA (p=0.016) and 
the seo gene with HA-MSSA (p=0.023). However, there is no significant association between virulence 
genes among the different types of infection. The clinical MSSA isolates in Terengganu showed high 
prevalence and high diversity of virulence gene carriage.
		                        		
		                        		
		                        		
		                        	
2.Efficacy and safety of endoscopic submucosal dissection for colorectal dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis
Talia F. MALIK ; Vaishnavi SABESAN ; Babu P. MOHAN ; Asad Ur RAHMAN ; Mohamed O. OTHMAN ; Peter V. DRAGANOV ; Gursimran S. KOCHHAR
Clinical Endoscopy 2024;57(3):317-328
		                        		
		                        			 Background/Aims:
		                        			In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD). 
		                        		
		                        			Methods:
		                        			Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity. 
		                        		
		                        			Results:
		                        			Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc resection, R0 resection, and curative resection rates were 92.5% (95% confidence interval [CI], 87.9%–95.4%; I2=0%), 81.5% (95% CI, 72.5%–88%; I2=43%), and 48.9% (95% CI, 32.1%–65.9%; I2=87%), respectively. The local recurrence rate was 3.9% (95% CI, 2%–7.5%; I2=0%). The pooled rates of bleeding and perforation were 7.7% (95% CI, 4.5%–13%; I2=10%) and 5.3% (95% CI, 3.1%–8.9%; I2=0%), respectively. The rates of metachronous recurrence and additional surgery following ESD were 10% (95% CI, 5.2%–18.2%; I2=55%) and 13% (95% CI, 8.5%–19.3%; I2=54%), respectively. 
		                        		
		                        			Conclusions
		                        			ESD is safe and effective for the resection of dysplastic lesions in IBD with an excellent pooled rate of en-bloc and R0 resection. 
		                        		
		                        		
		                        		
		                        	
3.The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease
Osama Nady MOHAMED ; Mahmoud Ragab Mohamed MOHAMED ; Israa Gamal HASSAN ; Atef Farouk ALAKKAD ; Ashraf OTHMAN ; Amr SETOUHI ; Ahmed S. ISSA
Journal of Lipid and Atherosclerosis 2024;13(2):194-211
		                        		
		                        			 Objective:
		                        			This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD). 
		                        		
		                        			Methods:
		                        			The study included 135 adult patients with CKD at stages 3–5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques. 
		                        		
		                        			Results:
		                        			CAC patients had considerably higher levels of TNF-α (p<0.001), IL-6 (p<0.001), hs-CRP (p=0.006), TC, TG, parathyroid hormone (PTH) (p<0.001) and phosphorus (p<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (p<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (p=0.046), age (p=0.009), TNF-α (p=0.027), IL-6 (p=0.005), TG (p=0.002), PTH (p=0.002), and phosphorus (p=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (p=0.045). 
		                        		
		                        			Conclusion
		                        			Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD. 
		                        		
		                        		
		                        		
		                        	
4.Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent.
Mohamed S OTHMAN ; Sofian T OBEIDAT ; Amal H AL-BAGAWI ; Mohamed A FAREID ; Alaa FEHAID ; Ahmed E ABDEL MONEIM
Journal of Integrative Medicine 2022;20(1):65-72
		                        		
		                        			OBJECTIVE:
		                        			The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).
		                        		
		                        			METHODS:
		                        			SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na
		                        		
		                        			RESULTS:
		                        			Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group.
		                        		
		                        			CONCLUSION
		                        			Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Antineoplastic Agents
		                        			;
		                        		
		                        			Antioxidants
		                        			;
		                        		
		                        			Berberine
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Nanoparticles
		                        			;
		                        		
		                        			Selenium
		                        			
		                        		
		                        	
5.High incidence of Plasmodium knowlesi malaria compared to other human malaria species in several hospitals in Malaysia
Lai, M.Y. ; Rafieqin, N. ; Lee, P.Y.@Lee, Z. ; Amir Rawa, M.S. ; Dzul, S. ; Yahaya, N. ; Abdullah, F.H. ; Othman, N. ; Jelip, J. ; Ooi, C.H. ; Ibrahim, J. ; Aung, M. ; Abdullah, A.H. ; Laili, Z. ; Lau, Y.L.
Tropical Biomedicine 2021;38(No.3):248-253
		                        		
		                        			
		                        			 Through the regional control programme, Malaysia has been successfully reducing the incidence of Plasmodium falciparum and Plasmodium vivax infections. However, the incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia especially Malaysian Borneo. The emergence of knowlesi infection has threatened the malaria elimination programme which the government aims to reduce the overall malaria infections by 2020. Unlike other benign human Plasmodium spp., P. knowlesi can cause fatal infections. The aim of this study was to determine the incidence and distribution of five human malaria parasites including P. knowlesi in Peninsular Malaysia and Malaysian Borneo. A total of 112 blood samples were collected from seven states and district hospitals in Peninsular Malaysia and Malaysian Borneo from year 2015 to 2016. The samples were examined by microscopy and further confirmed by nested PCR assay targeting 18S rRNA gene of Plasmodium spp. Following the nested PCR assays, a total of 54 (48.2%) samples were positive for P. knowlesi infections, 12 (10.7%) cases were positive for P. vivax infections, followed by 7 (6.3%) cases of P. falciparum and 4 (3.5%) cases of P. malariae. There were 3 cases (2.7%) of mixed infections (P. knowlesi/P. vivax). However, no cases were identified as P. ovale. A total of 32 (28.6%) cases were found as negative infections. LoopMediated Isothermal Amplification Assay (LAMP) was performed to confirm inconclusive results produced by microscopy and nested PCR. P. knowlesi showed the highest prevalence in Sarawak (n= 30), Sabah (n=13), Pulau Pinang (n=5) and Pahang (n=6). PCR and LAMP was not able to detect a large number of microscopy positive samples due to DNA degradation during storage and shipping. Among all the states involved in this study, the highest prevalence of P. knowlesi infection was found in Sabah and Sarawak.
		                        		
		                        		
		                        		
		                        	
6.Dengue protease inhibition activity of selected Malaysian medicinal herbs
Salleh, H.M. ; Chong, S.-L. ; Othman, R. ; Hazni, H. ; Ahmad, K. ; Mohd Yusof, M.Y.Z. ; Fauzi, N.W. ; Wahab, H.A. ; Liew, S.Y. ; Awang, K.
Tropical Biomedicine 2019;36(2):357-366
		                        		
		                        			
		                        			Dengue fever is one of major health problem around the world including Malaysia.
It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes
aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes
(DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various
Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops
aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited
potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of
Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with
IC50 value of 0.30 ± 0.16 μg/mL.
		                        		
		                        		
		                        		
		                        	
7.Lower Levels of Serum Adiponectin and the T Allele of rs1501299 of the ADIPOQ Gene Are Protective against Polycystic Ovarian Syndrome in Jordan.
Mahmoud A ALFAQIH ; Yousef S KHADER ; Ahmed N AL-DWAIRI ; Abdallah ALZOUBI ; Othman AL-SHBOUL ; Amanie HATIM
Korean Journal of Family Medicine 2018;39(2):108-113
		                        		
		                        			
		                        			BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive disorder. Obesity, which is linked with lower adiponectin levels, increases a woman's risk of developing PCOS; however, the association between adiponectin and PCOS is controversial. Adiponectin levels could be affected by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. This study aimed to test the relationship between serum adiponectin and PCOS in Jordan and the association between the rs2241766, rs1501299, and rs266729 SNPs in the ADIPOQ gene and PCOS. METHODS: One hundred and fifty-four women with PCOS and 149 age- and body mass index–matched normally menstruating controls were recruited. Serum adiponectin levels were measured using enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. RESULTS: Serum adiponectin levels were significantly lower (P=0.0064) in PCOS women and rs1501299 (+276 G/T) genotype distributions were significantly different (P=0.01) between them and normally menstruating women. Multivariate analysis revealed that adiponectin levels remained significantly lower in PCOS women (P=0.001; odds ratio [OR], 0.9; 95% confidence interval [CI], 0.84–0.96). The GT genotype of rs1501299 increased the risk of PCOS (P < 0.001; OR, 5.46; 95% CI, 2.42–12.33) and increased the risk of PCOS by three-fold (P < 0.001; OR, 3.00; 95% CI, 1.36–6.60) relative to the TT genotype. The GG genotype increased the risk of PCOS as well (P < 0.001; OR, 3:00; 95% CI, 1.36–6.60). CONCLUSION: PCOS is associated with lower serum adiponectin levels independent of age and body mass index. The T allele of the rs1501299 (+276 G/T) SNP of the ADIPOQ gene protects against PCOS.
		                        		
		                        		
		                        		
		                        			Adiponectin*
		                        			;
		                        		
		                        			Alleles*
		                        			;
		                        		
		                        			Body Mass Index
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Insulin Resistance
		                        			;
		                        		
		                        			Jordan*
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Obesity
		                        			;
		                        		
		                        			Odds Ratio
		                        			;
		                        		
		                        			Polycystic Ovary Syndrome*
		                        			;
		                        		
		                        			Polymorphism, Single Nucleotide
		                        			
		                        		
		                        	
8.Correction: Lower Levels of Serum Adiponectin and the T Allele of rs1501299 of the ADIPOQ Gene Are Protective against Polycystic Ovarian Syndrome in Jordan.
Mahmoud A ALFAQIH ; Yousef S KHADER ; Ahmed N AL-DWAIRI ; Abdallah ALZOUBI ; Othman AL-SHBOUL ; Amanie HATIM
Korean Journal of Family Medicine 2018;39(3):207-207
		                        		
		                        		
		                        		
		                        	
9.Ultrastructural changes of cell morphology and viral morphogenesis of two ecotypes of dengue virus infection in human monocytic U-937 cell
Fish-Low, C.Y ; Abu Bakar, S. ; Othman, F. ; Chee, H.Y.
Tropical Biomedicine 2018;35(4):1154-1159
		                        		
		                        			
		                        			Dengue virus (DENV) is maintained and circulated in both sylvatic/enzootic and
endemic/human cycles and spill over infection of sylvatic DENV into human populations has
been reported. Extensive deforestation and increase human activities in forest may increase
the risk of human exposure to sylvatic dengue infection and this may become a threat to
human. Present study investigated the changes in cell morphology and viral morphogenesis
upon infection with sylvatic and endemic ecotypes in human monocytic U-937 cells using
transmission electron microscopy. Autophagy, a process that is either pro-viral or anti-viral,
was observed in U-937 cells of both infections, however only the replication of endemic
DENV was evidenced. An insight into the infection responses of sylvatic progenitors of DENV
in susceptible host cells may provide better understanding on dengue emergence in human
populations.
		                        		
		                        		
		                        		
		                        	
10.The synthetic molecules YK51 and YK73 attenuate replication of dengue virus serotype 2
Gan, C.S. ; Yusof, R. ; Othman, S.
Tropical Biomedicine 2017;34(2):270-283
		                        		
		                        			
		                        			Dengue virus infection has been posing alarming economic and social burden on
affected nations. It is estimated that 50-100 million dengue infections occur annually with
over 2.5 billion people at risk for endemic transmission. In the effort to develop effective
antiviral agents, we previously reported potential antiviral activities from selected array of
natural products and compounds against dengue virus serotype 2 (DV2). In this study, we
report the synthesis of two efficacious novel compounds, YK51 and YK73, and their activities
against DV2 replication. Both compounds were chemically synthesised from nicotinic acid
using a modified method for the synthesis of dihydropyridine. The products were tested with
cell-based assays against DV2 followed by a serine protease assay. As a result, both YK51 and
YK73 exhibited intriguing antiviral properties with EC50 of 3.2 and 2.4 µM, respectively. In
addition, YK51 and YK73 were found to attenuate the synthesis of intracellular viral RNA and
protect the switching of non-classic mechanism of protein translation. These compounds
demonstrated inhibitory properties toward the activity of DV2 serine protease in a dose
dependent manner. These findings demonstrate that both YK51 and YK73 serve as DV2 serine
protease inhibitors that abrogate viral RNA synthesis and translation. Further investigation
on these compounds to corroborate its therapeutic properties towards dengue is warranted.
		                        		
		                        		
		                        		
		                        	
            

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