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Fulltext Thalassemia among blood donors at the Hospital Universiti Sains Malaysia

Rosline H, Ahmed SA, Al-Joudi FS, Rapiaah M, Naing NN, Adam NA

Southeast Asian J Trop Med Public Health, 2006 May;37(3):549-52.
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.
Fulltext Non-protein coding RNA genes as the novel diagnostic markers for the discrimination of Salmonella species using PCR

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.
RNomic identification and evaluation of npcTB_6715, a non-protein-coding RNA gene as a potential biomarker for the detection of Mycobacterium tuberculosis

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.
Novel black yeast-like species in chaetothyriales with ant-associated life styles

Quan Y, Ahmed SA, Menezes da Silva N, Al-Hatmi AMS, Mayer VE, Deng S, et al.

Fungal Biol, 2021 Apr;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.
Fulltext Synthesis and Evaluation of 1,3,5-Triaryl-2-Pyrazoline Derivatives as Potent Dual Inhibitors of Urease and α-Glucosidase Together with Their Cytotoxic, Molecular Modeling and Drug-Likeness Studies

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.
Systematic Review of Glucagon-Like Peptide One Receptor Agonist Liraglutide of Subjects with Heart Failure with Reduced Left Ventricular Ejection Fraction

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.