Displaying publications 1 - 20 of 26 in total

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  1. Hamad F, Elnour AA, Elamin A, Mohamed S, Yousif I, Don J, et al.
    Curr Diabetes Rev, 2021;17(3):280-292.
    PMID: 32867644 DOI: 10.2174/1573399816999200821164129
    BACKGROUND: The major cardiovascular outcome trials on glucagon-like peptide one-receptor agonists have examined its effect on hospitalization of subjects with heart failure; however, very limited trials have been conducted on subjects with reduced left ventricular ejection fraction (r- LVEF) as a primary outcome.

    OBJECTIVE: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure.

    METHODS: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks.

    RESULTS: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28).

    CONCLUSION: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.

  2. Mehmood R, Sadiq A, Alsantali RI, Mughal EU, Alsharif MA, Naeem N, et al.
    ACS Omega, 2022 Feb 01;7(4):3775-3795.
    PMID: 35128286 DOI: 10.1021/acsomega.1c06694
    In the present work, a concise library of 1,3,5-triaryl-2-pyrazolines (2a-2q) was designed and synthesized by employing a multistep strategy, and the newly synthesized compounds were screened for their urease and α-glucosidase inhibitory activities. The compounds (2a-2q) were characterized using a combination of several spectroscopic techniques including FT-IR, 1H NMR, 13C NMR, and EI-MS. All the synthesized compounds, except compound 2i, were potent against urease as compared to the standard inhibitor thiourea (IC50 = 21.37 ± 0.26 μM). These analogs disclosed varying degrees of urease inhibitory activities ranging from 9.13 ± 0.25 to 18.42 ± 0.42 μM. Compounds 2b, 2g, 2m, and 2q having IC50 values of 9.36 ± 0.27, 9.13 ± 0.25, 9.18 ± 0.35, and 9.35 ± 0.35 μM, respectively, showed excellent inhibitory activity as compared to standard thiourea (IC50 = 21.37 ± 0.26 μM). A kinetic study of compound 2g revealed that compound 2g inhibited urease in a competitive mode. Among the synthesized pyrazolines, the compounds 2c, 2k, 2m, and 2o exhibited excellent α-glucosidase inhibitory activity with the lowest IC50 values of 212.52 ± 1.31, 237.26 ± 1.28, 138.35 ± 1.32, and 114.57 ± 1.35 μM, respectively, as compared to the standard acarbose (IC50 = 375.82 ± 1.76 μM). The compounds (2a-2q) showed α-glucosidase IC50 values in the range of 114.57 ± 1.35 to 462.94 ± 1.23 μM. Structure-activity relationship revealed that the size and electron-donating or -withdrawing effects of substituents influenced the activities, which led to the urease and α-glucosidase inhibiting properties. Compound 2m was a dual potent inhibitor against urease and α-glucosidase due to the presence of 2-CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of urease and α-glucosidase with minimum IC50 values. The cytotoxicity of the compounds (2a-2q) was also investigated against human cell lines MCF-7 and HeLa. Compound 2l showed moderate cytotoxic activity against MCF-7 and HeLa cell lines. Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease and α-glucosidase enzymes. Some compounds exhibited drug-like characteristics due to their lower cytotoxic and good ADME profiles.
  3. Nithya R, Ahmed SA, Hoe CH, Gopinath SC, Citartan M, Chinni SV, et al.
    PLoS One, 2015;10(3):e0118668.
    PMID: 25774907 DOI: 10.1371/journal.pone.0118668
    Salmonellosis, a communicable disease caused by members of the Salmonella species, transmitted to humans through contaminated food or water. It is of paramount importance, to generate accurate detection methods for discriminating the various Salmonella species that cause severe infection in humans, including S. Typhi and S. Paratyphi A. Here, we formulated a strategy of detection and differentiation of salmonellosis by a multiplex polymerase chain reaction assay using S. Typhi non-protein coding RNA (sRNA) genes. With the designed sequences that specifically detect sRNA genes from S. Typhi and S. Paratyphi A, a detection limit of up to 10 pg was achieved. Moreover, in a stool-seeding experiment with S. Typhi and S. Paratyphi A, we have attained a respective detection limit of 15 and 1.5 CFU/mL. The designed strategy using sRNA genes shown here is comparatively sensitive and specific, suitable for clinical diagnosis and disease surveillance, and sRNAs represent an excellent molecular target for infectious disease.
  4. Quan Y, Ahmed SA, Menezes da Silva N, Al-Hatmi AMS, Mayer VE, Deng S, et al.
    Fungal Biol, 2021 04;125(4):276-284.
    PMID: 33766306 DOI: 10.1016/j.funbio.2020.11.006
    Among ancestral fungi in Chaetothyriales, several groups have a life style in association with tropical ants, either in domatia or in carton-nests. In the present study, two strains collected from ant carton in Thailand and Malaysia were found to represent hitherto undescribed species. Morphological, physiological, phylogenetic data and basic genome information are provided for their classification. Because of the relatively large phylogenetic distances with known species confirmed by overall genome data, large subunit (LSU) and Internal Transcribed Spacer (ITS) ribosomal DNA sequences were sufficient for taxonomic circumscription of the species. The analyzed strains clustered with high statistical support as a clade in the family Trichomeriaceae. Morphologically they were rather similar, lacking sporulation in vitro. In conclusion, Incumbomyces delicatus and Incumbomyces lentus were described as new species based on morphological, physiological and phylogenetic analysis.
  5. Kanniappan P, Ahmed SA, Rajasekaram G, Marimuthu C, Ch'ng ES, Lee LP, et al.
    J Cell Mol Med, 2017 10;21(10):2276-2283.
    PMID: 28756649 DOI: 10.1111/jcmm.13148
    Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples. For proof of principle, we developed a multiplex PCR assay and report its validation with 500 clinical cultures, positive for Mycobacteria. The analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative predictive values of 98.6% and 96.8%, respectively. These results underscore the diagnostic value of the sRNA gene as diagnostic marker for the specific detection of MTB in clinical samples. Its successful application and the general ease of PCR-based detection compared to standard bacterial culture techniques might be the first step towards 'point-of-care' diagnostics of Mycobacteria. To the best of our knowledge, this is the first time for the design of diagnostic applications based on sRNA genes, in Mycobacteria.
  6. Ab Rahman WS, Abdullah WZ, Mustaffa R, Ahmed SA, Hassan MN, Husin A
    PMID: 24093001 DOI: 10.4137/CCRep.S12122
    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria.
  7. Musa RH, Ahmed SA, Hashim H, Ayob Y, Asidin NH, Choo PY, et al.
    Asian J Transfus Sci, 2012 Jan;6(1):3-9.
    PMID: 22623834 DOI: 10.4103/0973-6247.95042
    Human blood groups are polymorphic and inherited integral structures of the red cell membrane. More than 300 red cell antigens have been identified and further categorized into 30 major discrete systems. Their distribution varies in different communities and ethnic groups.
  8. Roshan TM, Rosline H, Ahmed SA, Rapiaah M, Wan Zaidah A, Khattak MN
    Int J Lab Hematol, 2009 Oct;31(5):505-12.
    PMID: 18498389 DOI: 10.1111/j.1751-553X.2008.01068.x
    Health and disease can only be distinguished by accurate and reliable reference values of a particular laboratory test. It is now a proven fact that there is considerable variation in hematology reference intervals depending on the demographic and preanalytical variables. There are evidences that values provided by manufacturers do not have appropriate application for all populations. Moreover, reference ranges provided by different laboratory manuals and books also do not solve this problem. We are presenting here normal reference ranges of Malaysian population. These values were determined by using Sysmex XE-2100 and ACL 9000 hematology and coagulation analyzers. Results from this study showed that there were considerable differences in the reference values from manufacturers, western population or laboratory manuals compared with those from the local population.
  9. Ahmed SA, Al-Joudi FS, Zaidah AW, Roshan TM, Rapiaah M, Abdullah YM, et al.
    PMID: 17124989
    Human cytomegalovirus (HCMV) is a species-specific DNA virus of the Herpetoviridae family. After a primary infection, HCMV persists in a latent form most probably in bone marrow progenitor cells or in peripheral blood monocytes. The virus can reactivate to result in shedding of the virus leading to virus dissemination and new infections. Immunocompromized patients are the ones most vulnerable to serious diseases occasionally acquired in blood transfusions. In a human population, HCMV seropositivity increases steadily with age to become approximately 100% in adults. This study was performed to detect seropositivity among regular blood donors in The Hospital of the Universiti Sains Malaysia, in the state of Kelantan. Using an enzyme immunoassay, it was found that 97.6% of blood donors were HCMV-positive. HCMV is highly prevalent and may be endemic in Kelantan. Hence, long-term strategies are required for the reduction of disease dissemination, and to prevent the exposure of immunocompromized patients to the virus.
  10. Rosline H, Ahmed SA, Al-Joudi FS, Rapiaah M, Naing NN, Adam NA
    PMID: 17120978
    The aim of this study was to screen and identify the types of thalassemia among blood donors at the Hospital Universiti Sains Malaysia (HUSM). Thalassemia screening was performed by hemoglobin electrophoresis. A total number of 80 blood samples were obtained from donors at the Transfusion Medicine Unit, HUSM. The ethnic origins of the donors were Malays (n=73, 91.3%) and non-Malays (n=7, 8.75%). Males comprised 88.1% of the donors. Thalassemia was detected in 16.25% (n=13) of the blood donors. Of those with thalassemia, 46.2% (6/13) were anemic. Microcytosis and hypochromia were detected in 84.6% (n=l1) and 84.6% (n=l1) of these donors, respectively. The types of thalassemias detected were Hb E, 11.25% (n=9/80) and beta thalassemia trait, 5% (n=4/80). Among the thalassemias detected, the Hb E hemoglobinopathy was comprised of Hb E/ alpha-thalassemia (38.5%: n=5), Hb E /beta-thalassemia (23.1%: n=3), Hb E trait (7.6%: n=1) and beta-thalassemia (30.8%: n=4). In conclusion, screening for thalassemia trait should be included as part of a standard blood testing before blood donation. Further studies are required to look at the effects of donated thalassemic blood.
  11. Ahmed SA, Raabe CA, Cheah HL, Hoe CH, Rozhdestvensky TS, Tang TH
    Am J Trop Med Hyg, 2019 06;100(6):1328-1334.
    PMID: 30963989 DOI: 10.4269/ajtmh.18-0525
    The diarrheal disease "cholera" is caused by Vibrio cholerae, and is primarily confined to endemic regions, mostly in Africa and Asia. It is punctuated by outbreaks and creates severe challenges to public health. The disease-causing strains are most-often members of serogroups O1 and O139. PCR-based methods allow rapid diagnosis of these pathogens, including the identification of their biotypes. However, this necessitates the selection of specific target sequences to differentiate even the closely related biotypes of V. cholerae. Oligonucleotides for selective amplification of small RNA (sRNA) genes that are specific to these V. cholerae subtypes were designed. The resulting multiplex PCR assay was validated using V. cholerae cultures (i.e., 19 V. cholerae and 22 non-V. cholerae isolates) and spiked stool samples. The validation using V. cholerae cultures and spiked stool suspensions revealed detection limits of 10-100 pg DNA per reaction and 1.5 cells/mL suspension, respectively. The multiplex PCR assay that targets sRNA genes for amplification enables the sensitive and specific detection, as well as the differentiation of V. cholerae-O1 classical, O1 El Tor, and O139 biotypes. Most importantly, the assay enables fast and cheaper diagnosis compared with classic culture-based methods.
  12. Cheah HL, Raabe CA, Lee LP, Rozhdestvensky TS, Citartan M, Ahmed SA, et al.
    Crit Rev Biochem Mol Biol, 2018 08;53(4):335-355.
    PMID: 29793351 DOI: 10.1080/10409238.2018.1473330
    Over the past decade, RNA-deep sequencing has uncovered copious non-protein coding RNAs (npcRNAs) in bacteria. Many of them are key players in the regulation of gene expression, taking part in various regulatory circuits, such as metabolic responses to different environmental stresses, virulence, antibiotic resistance, and host-pathogen interactions. This has contributed to the high adaptability of bacteria to changing or even hostile environments. Their mechanisms include the regulation of transcriptional termination, modulation of translation, and alteration of messenger RNA (mRNA) stability, as well as protein sequestration. Here, the mechanisms of gene expression by regulatory bacterial npcRNAs are comprehensively reviewed and supplemented with well-characterized examples. This class of molecules and their mechanisms of action might be useful targets for the development of novel antibiotics.
  13. Tan LL, Ahmed SA, Ng SK, Citartan M, Raabe CA, Rozhdestvensky TS, et al.
    Food Chem, 2020 Mar 30;309:125654.
    PMID: 31678669 DOI: 10.1016/j.foodchem.2019.125654
    A specialized DNA extraction method and a SYBR Green quantitative polymerase chain reaction (SyG-qPCR) assay were combined to generate a ready-to-use kit for rapid detection of porcine admixtures in processed meat products. Our qPCR assay utilized repetitive LINE-1 elements specific to the genome of Sus scrofa domesticus (pig) as a target and incorporated internal controls. We improved the genomic DNA extraction method, and reduced extraction times to the minimum. The method was validated for specificity, sensitivity (0.001% w/w) and robustness, and values were compared with those of a commercially available kit. We also tested our method using 121 processed food products and consistently detected amplification only in samples containing pork. Due to its efficiency and cost-effectiveness, our method represents a valuable new method for detecting food adulteration with pork that is superior to existing quality control approaches.
  14. Ahmed SA, Al-Shanon AF, Al-Saffar AZ, Tawang A, Al-Obaidi JR
    J Genet Eng Biotechnol, 2023 Jul 02;21(1):75.
    PMID: 37393563 DOI: 10.1186/s43141-023-00529-2
    INTRODUCTION: Cancer is a major issue in medical science with increasing death cases every year worldwide. Therefore, searching for alternatives and nonorthodox methods of treatments with high efficiency, selectivity and less toxicity is the main goal in fighting cancer. Acetyl-11-keto-β-boswellic acid (AKBA), is a derivative pentacyclic triterpenoid that exhibited various biological activities with potential anti-tumoral agents. In this research, AKBA was utilized to examine the potential cytotoxic activity against MCF-7 cells in vitro and monitor the cellular and morphological changes with a prospective impact on apoptosis induction.

    METHODS: The cytotoxic activity of AKBA was measured by 3(4,5dimethylthiazole- 2-yl)-2,5 diphyneltetrazolium bromide (MTT) assay. A dose-dependent inhibition in MCF-7 cell viability was detected. The clonogenicity of MCF-7 cells was significantly suppressed by AKBA increment in comparison with untreated cells.

    RESULT: Morphologically, exposure of MCF-7 cells to high AKBA concentrations caused changes in cell nuclear morphology which was indicated by increasing in nuclear size and cell permeability intensity. The mitochondrial membrane potential (ΔΨm) was reduced by increasing AKBA concentration with a significant release of cytochrome c. Acridine orange/ethidium bromide dual staining experiment confirmed that MCF-7 cells treated with AKBA (IC50 concentration) displayed a late stage of apoptosis indicated by intense and bright reddish colour.

    CONCLUSION: A significant increase in reactive oxygen species formation was observed. Caspase 8 and caspase 9 activities were estimated and AKBA activated the production of caspase 8 and caspase 9 in a dose-dependent pattern. Finally, the cell phase distribution analysis was conducted, and flow cytometric analysis showed that AKBA at 200 μg mL-1 significantly arrest MCF-7 cells at the G1 phase and triggered apoptosis.

  15. Tan XY, Citartan M, Chinni SV, Ahmed SA, Tang TH
    Indian J Microbiol, 2023 Mar;63(1):33-41.
    PMID: 37188232 DOI: 10.1007/s12088-022-01050-9
    Regulatory small RNAs (sRNA) are RNA transcripts that are not translated into proteins but act as functional RNAs. Pathogenic Leptospira cause an epidemic spirochaetal zoonosis, Leptospirosis. It is speculated that Leptospiral sRNAs are involved in orchestrating their pathogenicity. In this study, biocomputational approach was adopted to identify Leptospiral sRNAs. In this study, two sRNA prediction programs, i.e., RNAz and nocoRNAc, were employed to screen the reference genome of Leptospira interrogans serovar Lai. Out of 126 predicted sRNAs, there are 96 cis-antisense sRNAs, 28 trans-encoded sRNAs and 2 sRNAs that partially overlap with protein-coding genes in a sense orientation. To determine whether these candidates are expressed in the pathogen, they were compared with the coverage files generated from our RNA-seq datasets. It was found out that 7 predicted sRNAs are expressed in mid-log phase, stationary phase, serum stress, temperature stress and iron stress while 2 sRNAs are expressed in mid-log phase, stationary phase, serum stress, and temperature stress. Besides, their expressions were also confirmed experimentally via RT-PCR. These experimentally validated candidates were also subjected to mRNA target prediction using TargetRNA2. Taken together, our study demonstrated that biocomputational strategy can serve as an alternative or as a complementary strategy to the laborious and expensive deep sequencing methods not only to uncover putative sRNAs but also to predict their targets in bacteria. In fact, this is the first study that integrates computational approach to predict putative sRNAs in L. interrogans serovar Lai.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-022-01050-9.

  16. Ahmed SA, Sandai DA, Musa S, Hoe CH, Riadzi M, Lau KL, et al.
    Malays J Med Sci, 2012 Jul;19(3):9-16.
    PMID: 23610544 MyJurnal
    Traditionally, the most common diagnostic approach used for diagnosing leptospirosis was the demonstration of immune-seroconversion in acute and convalescent patient serum samples. Recently, a variety of molecular techniques, including conventional and real-time polymerase chain reaction (PCR), have been developed for the specific detection of pathogenic bacteria from the genus Leptospira. PCR is a sensitive, specific, and rapid technique that has been successfully used to detect several microorganisms; including those of clinical significance.
  17. Yaseen SG, Ahmed SA, Johan MF, Kiron R, Daher AM
    Transfus Apher Sci, 2013 Dec;49(3):647-51.
    PMID: 23890575 DOI: 10.1016/j.transci.2013.07.003
    Transmission of infectious diseases is a recognized complication of blood transfusion and blood products. Nucleic acid testing (NAT) may contribute to improved efficiency of blood screening and thereby increase the safety margin for transfused blood.
  18. Tang TH, Ahmed SA, Musa M, Zainuddin ZF
    World J Microbiol Biotechnol, 2013 Dec;29(12):2389-95.
    PMID: 23807412 DOI: 10.1007/s11274-013-1407-0
    Although the multi-copy and specific element IS6110 provides a good target for the detection of Mycobacterium tuberculosis complex by PCR techniques, the emergence of IS6110-negative strains suggested that false negative may occur if IS6110 alone is used as the target for detection. In this report, a multiplex polymerase chain reaction (mPCR) system was developed using primers derived from the insertion sequence IS6110 and an IS-like elements designated as B9 (GenBank accession no. U78639.1) to overcome the problem of detecting negative or low copy IS6110 containing strains of M. tuberculosis. The mPCR was evaluated using 346 clinical samples which included 283 sputum, 19 bronchial wash, 18 pleural fluid, 9 urine, 7 CSF, 6 pus, and 4 gastric lavage samples. Our results showed that the sensitivity (93.1 %) and specificity (89.6 %) of the mPCR system exceeds that of the conventional method of microscopy and culture. The mPCR assay provides an efficient strategy to detect and identify M. tuberculosis from clinical samples and enables prompt diagnosis when rapid identification of infecting mycobacteria is necessary.
  19. Roshan TM, Rosline H, Ahmed SA, Rapiaah M, Khattak MN
    PMID: 20578467
    Blood donors with reactive screening test results are requested to come in for counseling by letter and telephone call. It has been noticed many donors responded to neither the letters nor the telephone calls. We evaluated 589 cases with reactive screening test results (208 positive for hepatitis C, 209 for hepatitis B, 85 for VDRL and 87 for HIV). In the hepatitis C positive group 61 donors (29.3%) did not respond and 4.7% missed their follow-up appointment. Similarly low response rates were noted with the HBV (58.9%) and VDRL (67.1%) positive groups. Among HIV positive donors 46.0% failed to respond to multiple calls. We conclude that blood donors in Malaysia have a poor response to calls from the blood transfusion unit. A review of the effectiveness of the current deferral system and an increased public knowledge of transmissible infectious diseases may encourage blood donors to have a better response rate.
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