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Fulltext Crystallographic analysis of ground and space thermostable T1 lipase crystal obtained via counter diffusion method approach

Mohamad Aris SN, Thean Chor AL, Mohamad Ali MS, Basri M, Salleh AB, Raja Abd Rahman RN

Biomed Res Int, 2014;2014:904381.
PMID: 24516857 DOI: 10.1155/2014/904381

Three-dimensional structure of thermostable lipase is much sought after nowadays as it is important for industrial application mainly found in the food, detergent, and pharmaceutical sectors. Crystallization utilizing the counter diffusion method in space was performed with the aim to obtain high resolution diffracting crystals with better internal order to improve the accuracy of the structure. Thermostable T1 lipase enzyme has been crystallized in laboratory on earth and also under microgravity condition aboard Progress spacecraft to the ISS in collaboration with JAXA (Japanese Aerospace Exploration Agency). This study is conducted with the aims of improving crystal packing and structure resolution. The diffraction data set for ground grown crystal was collected to 1.3 Å resolution and belonged to monoclinic C2 space group with unit cell parameters a = 117.40 Å, b = 80.95 Å, and c = 99.81 Å, whereas the diffraction data set for space grown crystal was collected to 1.1 Å resolution and belonged to monoclinic C2 space group with unit cell parameters a = 117.31 Å, b = 80.85 Å, and c = 99.81 Å. The major difference between the two crystal growth systems is the lack of convection and sedimentation in microgravity environment resulted in the growth of much higher quality crystals of T1 lipase.
Fulltext Capillary-seeding crystallization and preliminary crystallographic analysis of a solvent-tolerant elastase from Pseudomonas aeruginosa strain K

Ali MS, Said ZS, Rahman RN, Chor AL, Basri M, Salleh AB

Int J Mol Sci, 2013 Aug 28;14(9):17608-17.
PMID: 23989606 DOI: 10.3390/ijms140917608

Seeding is a versatile method for optimizing crystal growth. Coupling this technique with capillary counter diffusion crystallization enhances the size and diffraction quality of the crystals. In this article, crystals for organic solvent-tolerant recombinant elastase strain K were successfully produced through microseeding with capillary counter-diffusion crystallization. This technique improved the nucleation success rate with a low protein concentration (3.00 mg/mL). The crystal was grown in 1 M ammonium phosphate monobasic and 0.1 M sodium citrate tribasic dihydrate pH 5.6. The optimized crystal size was 1 × 0.1 × 0.05 mm³. Elastase strain K successfully diffracted up to 1.39 Å at SPring-8, Japan, using synchrotron radiation for preliminary data diffraction analysis. The space group was determined to be monoclinic space group P12(1)1 with unit cell parameters of a = 38.99 Ǻ, b = 90.173 Å and c = 40.60 Å.
Fulltext Homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8

Garba L, Mohamad Yussoff MA, Abd Halim KB, Ishak SNH, Mohamad Ali MS, Oslan SN, et al.

PeerJ, 2018;6:e4347.
PMID: 29576935 DOI: 10.7717/peerj.4347

Membrane-bound fatty acid desaturases perform oxygenated desaturation reactions to insert double bonds within fatty acyl chains in regioselective and stereoselective manners. The Δ9-fatty acid desaturase strictly creates the first double bond between C9 and 10 positions of most saturated substrates. As the three-dimensional structures of the bacterial membrane fatty acid desaturases are not available, relevant information about the enzymes are derived from their amino acid sequences, site-directed mutagenesis and domain swapping in similar membrane-bound desaturases. The cold-tolerantPseudomonassp. AMS8 was found to produce high amount of monounsaturated fatty acids at low temperature. Subsequently, an active Δ9-fatty acid desaturase was isolated and functionally expressed inEscherichia coli. In this paper we report homology modeling and docking studies of a Δ9-fatty acid desaturase from a Cold-tolerantPseudomonassp. AMS8 for the first time to the best of our knowledge. Three dimensional structure of the enzyme was built using MODELLER version 9.18 using a suitable template. The protein model contained the three conserved-histidine residues typical for all membrane-bound desaturase catalytic activity. The structure was subjected to energy minimization and checked for correctness using Ramachandran plots and ERRAT, which showed a good quality model of 91.6 and 65.0%, respectively. The protein model was used to preform MD simulation and docking of palmitic acid using CHARMM36 force field in GROMACS Version 5 and Autodock tool Version 4.2, respectively. The docking simulation with the lowest binding energy, -6.8 kcal/mol had a number of residues in close contact with the docked palmitic acid namely, Ile26, Tyr95, Val179, Gly180, Pro64, Glu203, His34, His206, His71, Arg182, Thr85, Lys98 and His177. Interestingly, among the binding residues are His34, His71 and His206 from the first, second, and third conserved histidine motif, respectively, which constitute the active site of the enzyme. The results obtained are in compliance with thein vivoactivity of the Δ9-fatty acid desaturase on the membrane phospholipids.
Fulltext Isolation, Characterisation, and Lipase Production of a Cold-Adapted Bacterial Strain Pseudomonas sp. LSK25 Isolated from Signy Island, Antarctica

Salwoom L, Raja Abd Rahman RNZ, Salleh AB, Mohd Shariff F, Convey P, Pearce D, et al.

Molecules, 2019 Feb 16;24(4).
PMID: 30781467 DOI: 10.3390/molecules24040715

In recent years, studies on psychrophilic lipases have been an emerging area of research in the field of enzymology. This study focuses on bacterial strains isolated from anthropogenically-influenced soil samples collected around Signy Island Research Station (South Orkney Islands, maritime Antarctic). Limited information on lipase activities from bacteria isolated from Signy station is currently available. The presence of lipase genes was determined using real time quantification PCR (qPCR) in samples obtained from three different locations on Signy Island. Twenty strains from the location with highest lipase gene detection were screened for lipolytic activities at a temperature of 4 °C, and from this one strain was selected for further examination based on the highest enzymatic activities obtained. Analysis of 16S rRNA sequence data of this strain showed the highest level of sequence similarity (98%) to a Pseudomonas sp. strain also isolated from Antarctica. In order to increase lipase production of this psychrophilic strain, optimisation of different parameters of physical and nutritional factors were investigated. Optimal production was obtained at 10 °C and pH 7.0, at 150 rev/min shaking rate over 36 h incubation.
Enhancing the stability of Geobacillus zalihae T1 lipase in organic solvents and insights into the structural stability of its variants

Maiangwa J, Hamdan SH, Mohamad Ali MS, Salleh AB, Zaliha Raja Abd Rahman RN, Shariff FM, et al.

J Mol Graph Model, 2021 06;105:107897.
PMID: 33770705 DOI: 10.1016/j.jmgm.2021.107897

Critical to the applications of proteins in non-aqueous enzymatic processes is their structural dynamics in relation to solvent polarity. A pool of mutants derived from Geobacillus zalihae T1 lipase was screened in organic solvents (methanol, ethanol, propanol, butanol and pentanol) resulting in the selection of six mutants at initial screening (A83D/K251E, R21C, G35D/S195 N, K84R/R103C/M121I/T272 M and R106H/G327S). Site-directed mutagenesis further yielded quadruple mutants A83D/M121I/K251E/G327S and A83D/M121I/S195 N/T272 M, both of which had improved activity after incubation in methanol. The km and kcat values of these mutants vary marginally with the wild-type enzyme in the methanol/substrate mixture. Thermally induced unfolding of mutants was accompanied with some loss of secondary structure content. The root mean square deviations (RMSD) and B-factors revealed that changes in the structural organization are intertwined with an interplay of the protein backbone with organic solvents. Spatially exposed charged residues showed correlations between the solvation dynamics of the methanol solvent and the hydrophobicity of the residues. The short distances of the radial distribution function provided the required distances for hydrogen bond formation and hydrophobic interactions. These dynamic changes demonstrate newly formed structural interactions could be targeted and incorporated experimentally on the basis of solvent mobility and mutant residues.
Cold-adapted organic solvent tolerant alkalophilic family I.3 lipase from an Antarctic Pseudomonas

Ganasen M, Yaacob N, Rahman RN, Leow AT, Basri M, Salleh AB, et al.

Int J Biol Macromol, 2016 Nov;92:1266-1276.
PMID: 27506122 DOI: 10.1016/j.ijbiomac.2016.06.095

Lipolytic enzymes with cold adaptation are gaining increasing interest due to their biotechnological prospective. Previously, a cold adapted family I.3 lipase (AMS8 lipase) was isolated from an Antarctic Pseudomonas. AMS8 lipase was largely expressed in insoluble form. The refolded His-tagged recombinant AMS8 lipase was purified with 23.0% total recovery and purification factor of 9.7. The purified AMS8 lipase migrated as a single band with a molecular weight approximately 65kDa via electrophoresis. AMS8 lipase was highly active at 30°C at pH 10. The half-life of AMS8 lipase was reported at 4 and 2h under the incubation of 30 and 40°C, respectively. The lipase was stable over a broad range of pH. It showed enhancement effect in its relative activity under the presence of Li(+), Na(+), K(+), Rb(+) and Cs(+) after 30min treatment. Heavy metal ions such as Cu(2+), Fe(3+) and Zn(2+) inhibited AMS8 activity. This cold adapted alkalophilic AMS lipase was also active in various organic solvent of different polarity. These unique properties of this biological macromolecule will provide considerable potential for many biotechnological applications and organic synthesis at low temperature.
Fulltext Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

Maiangwa J, Mohamad Ali MS, Salleh AB, Rahman RNZRA, Normi YM, Mohd Shariff F, et al.

PeerJ, 2017;5:e3341.
PMID: 28533982 DOI: 10.7717/peerj.3341

The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA) for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent systems, which could lead to weaknesses in the catalytic H-bond network and most likely a drop in catalytic activity. The conformational variation of the lid domain caused by the solvent molecules influenced its gradual opening. Formation of additional hydrogen bonds and hydrophobic interactions indicates that the contribution of the cooperative network of interactions could retain the stability of the protein in some solvent systems. Time-correlated atomic motions were used to characterize the correlations between the motions of the atoms from atomic coordinates. The resulting cross-correlation map revealed that the organic solvent mixtures performed functional, concerted, correlated motions in regions of residues of the lid domain to other residues. These observations suggest that varying lengths of polar organic solvents play a significant role in introducing dynamic conformational diversity in proteins in a decreasing order of polarity.
Fulltext The Effect of N-Terminal Domain Removal towards the Biochemical and Structural Features of a Thermotolerant Lipase from an Antarctic Pseudomonas sp. Strain AMS3

Latip W, Raja Abd Rahman RNZ, Leow ATC, Mohd Shariff F, Kamarudin NHA, Mohamad Ali MS

Int J Mol Sci, 2018 Feb 13;19(2).
PMID: 29438291 DOI: 10.3390/ijms19020560

Lipase plays an important role in industrial and biotechnological applications. Lipases have been subject to modification at the N and C terminals, allowing better understanding of lipase stability and the discovery of novel properties. A thermotolerant lipase has been isolated from Antarctic Pseudomonas sp. The purified Antarctic AMS3 lipase (native) was found to be stable across a broad range of temperatures and pH levels. The lipase has a partial Glutathione-S-transferase type C (GST-C) domain at the N-terminal not found in other lipases. To understand the influence of N-terminal GST-C domain on the biochemical and structural features of the native lipase, the deletion of the GST-C domain was carried out. The truncated protein was successfully expressed in E. coli BL21(DE3). The molecular weight of truncated AMS3 lipase was approximately ~45 kDa. The number of truncated AMS3 lipase purification folds was higher than native lipase. Various mono and divalent metal ions increased the activity of the AMS3 lipase. The truncated AMS3 lipase demonstrated a similarly broad temperature range, with the pH profile exhibiting higher activity under alkaline conditions. The purified lipase showed a substrate preference for a long carbon chain substrate. In addition, the enzyme activity in organic solvents was enhanced, especially for toluene, Dimethylsulfoxide (DMSO), chloroform and xylene. Molecular simulation revealed that the truncated lipase had increased structural compactness and rigidity as compared to native lipase. Removal of the N terminal GST-C generally improved the lipase biochemical characteristics. This enzyme may be utilized for industrial purposes.
Fulltext Short-term Gini coefficient estimation using nonlinear autoregressive multilayer perceptron model

Amin Megat Ali MS, Zabidi A, Md Tahir N, Mohd Yassin I, Eskandari F, Saadon A, et al.

Heliyon, 2024 Feb 29;10(4):e26438.
PMID: 38420485 DOI: 10.1016/j.heliyon.2024.e26438

Poverty, an intricate global challenge influenced by economic, political, and social elements, is characterized by a deficiency in crucial resources, necessitating collective efforts towards its mitigation as embodied in the United Nations' Sustainable Development Goals. The Gini coefficient is a statistical instrument used by nations to measure income inequality, economic status, and social disparity, as escalated income inequality often parallels high poverty rates. Despite its standard annual computation, impeded by logistical hurdles and the gradual transformation of income inequality, we suggest that short-term forecasting of the Gini coefficient could offer instantaneous comprehension of shifts in income inequality during swift transitions, such as variances due to seasonal employment patterns in the expanding gig economy. System Identification (SI), a methodology utilized in domains like engineering and mathematical modeling to construct or refine dynamic system models from captured data, relies significantly on the Nonlinear Auto-Regressive (NAR) model due to its reliability and capability of integrating nonlinear functions, complemented by contemporary machine learning strategies and computational algorithms to approximate complex system dynamics to address these limitations. In this study, we introduce a NAR Multi-Layer Perceptron (MLP) approach for brief term estimation of the Gini coefficient. Several parameters were tested to discover the optimal model for Malaysia's Gini coefficient within 1987-2015, namely the output lag space, hidden units, and initial random seeds. The One-Step-Ahead (OSA), residual correlation, and residual histograms were used to test the validity of the model. The results demonstrate the model's efficacy over a 28-year period with superior model fit (MSE: 1.14 × 10-7) and uncorrelated residuals, thereby substantiating the model's validity and usefulness for predicting short-term variations in much smaller time steps compared to traditional manual approaches.
Fulltext The Role of Solvent-Accessible Leu-208 of Cold-Active Pseudomonas fluorescens Strain AMS8 Lipase in Interfacial Activation, Substrate Accessibility and Low-Molecular Weight Esterification in the Presence of Toluene

Yaacob N, Ahmad Kamarudin NH, Leow ATC, Salleh AB, Raja Abd Rahman RNZ, Mohamad Ali MS

Molecules, 2017 Aug 12;22(8).
PMID: 28805665 DOI: 10.3390/molecules22081312

The alkaline cold-active lipase from Pseudomonas fluorescens AMS8 undergoes major structural changes when reacted with hydrophobic organic solvents. In toluene, the AMS8 lipase catalytic region is exposed by the moving hydrophobic lid 2 (Glu-148 to Gly-167). Solvent-accessible surface area analysis revealed that Leu-208, which is located next to the nucleophilic Ser-207 has a focal function in influencing substrate accessibility and flexibility of the catalytic pocket. Based on molecular dynamic simulations, it was found that Leu-208 strongly facilitates the lid 2 opening via its side-chain. The KM and Kcat/KM of L208A mutant were substrate dependent as it preferred a smaller-chain ester (pNP-caprylate) as compared to medium (pNP-laurate) or long-chain (pNP-palmitate) esters. In esterification of ethyl hexanoate, L208A promotes a higher ester conversion rate at 20 °C but not at 30 °C, as a 27% decline was observed. Interestingly, the wild-type (WT) lipase's conversion rate was found to increase with a higher temperature. WT lipase AMS8 esterification was higher in toluene as compared to L208A. Hence, the results showed that Leu-208 of AMS8 lipase plays an important role in steering a broad range of substrates into its active site region by regulating the flexibility of this region. Leu-208 is therefore predicted to be crucial for its role in interfacial activation and catalysis in toluene.
Effect of cysteine mutation at Ca2+ coordinating residues to the autolysis, folding and hydrophobicity of full length and mature Rand protease: molecular dynamics simulation and essential dynamics

Mohd Azrin NA, Mohamad Ali MS, Raja Abd Rahman RNZ, Mohd Shariff F, Ahmad Kamarudin NH, Muhd Noor ND

J Biomol Struct Dyn, 2023 Aug 22.
PMID: 37608543 DOI: 10.1080/07391102.2023.2249105

Rand protease is a serine protease that shared common characteristics with members of the MEROPS S8 subtilisin family. It is thermostable, highly stable in organic solvent and broad in specificity. Many structures of homologous protein solved by X-ray crystallography and NMR have been deposited to Protein Data Bank (PDB) which allowed this study to rely on structure prediction by deep learning to build three-dimensional (3D) structure of full length and mature Rand protease (flRP and mRP). In silico cysteine mutation to 7 predicted high affinity Ca2+ coordinating residues were introduced, and the mutants were subjected to molecular dynamics simulation to study its effect on flRP and mRP. MD simulation showed a marked increase in flexibility of the pro-peptide segment indicating the impact of single cysteine substitution at high affinity Ca2+ coordinating residues to autolysis of flRP. MD simulation for mRP reaffirmed the role of Ca2+ coordinating sites in providing stability to Rand protease. In addition, these residues also affect the autolysis, folding and hydrophobicity of RP. Essential dynamics observed large contribution of the first few eigenvectors of flRP, mRP and their high affinity Ca2+ coordinating residues mutants to the TMSF values which indicates that these values account for a large portion of the overall atomic fluctuations. These results have given a more comprehensive understanding on the role of cysteine substituted Ca2+ coordinating surface loop to the structure of flRP and mRP which are important in contributing to the structural stability of subtilisin.Communicated by Ramaswamy H. Sarma.
Investigating Physical and Nutritional Changes During Prolonged Intermittent Fasting in Hemodialysis Patients: A Prospective Cohort Study

Adanan NIH, Md Ali MS, Lim JH, Zakaria NF, Lim CTS, Yahya R, et al.

J Ren Nutr, 2020 03;30(2):e15-e26.
PMID: 31420234 DOI: 10.1053/j.jrn.2019.06.003

OBJECTIVE: Studies investigating the health effects of prolonged intermittent fasting during Ramadan among Muslim patients on hemodialysis (HD) are limited and reported heterogeneous findings. This study aimed to evaluate the effects of intermittent fasting during Ramadan on nutritional and functional status of patients on maintenance HD.
DESIGN AND METHODS: This was a 12-week, multicenter, prospective observational study. The study setting included three HD centers. Adult Muslim patients, who were undergoing HD session thrice weekly and planned to fast during Ramadan, were screened for eligibility and recruited. Nutritional and functional status assessments were carried out 2 weeks before (V0), at the fourth week of Ramadan (V1), and 4 weeks after Ramadan (V2). Nutritional status parameters included anthropometry (body mass index, interdialytic weight gain, waist circumference), body composition (mid-arm circumference, triceps skinfold, body fat percentage), blood biochemistry (albumin, renal profile, lipid profile, and inflammatory markers), blood pressure, dietary intake, and handgrip strength. Changes in nutritional and functional status parameters across study timepoints were analyzed using repeated-measures analysis of variance.
RESULTS: A total of 87 patients completed the study, with 68 patients (78.2%) reporting fasting ≥20 days. Ramadan fasting led to significant reductions (all P .05). Significant improvement was observed in serum phosphate levels, but serum albumin, urea, and creatinine were also reduced significantly during Ramadan (P
Engine performance and emission characteristics of palm biodiesel blends with graphene oxide nanoplatelets and dimethyl carbonate additives

Razzaq L, Mujtaba MA, Soudagar MEM, Ahmed W, Fayaz H, Bashir S, et al.

J Environ Manage, 2021 Mar 15;282:111917.
PMID: 33453625 DOI: 10.1016/j.jenvman.2020.111917

This study investigated the engine performance and emission characteristics of biodiesel blends with combined Graphene oxide nanoplatelets (GNPs) and 10% v/v dimethyl carbonate (DMC) as fuel additives as well as analysed the tribological characteristics of those blends. 10% by volume DMC was mixed with 30% palm oil biodiesel blends with diesel. Three different concentrations (40, 80 and 120 ppm) of GNPs were added to these blends via the ultrasonication process to prepare the nanofuels. Sodium dodecyl sulphate (SDS) surfactant was added to improve the stability of these blends. GNPs were characterised using Scanning Electron Microscope (SEM) and Fourier Transform Infrared (FTIR), while the viscosity of nanofuels was investigated by rheometer. UV-spectrometry was used to determine the stability of these nanoplatelets. A ratio of 1:4 GNP: SDS was found to produce maximum stability in biodiesel. Performance and emissions characteristics of these nanofuels have been investigated in a four-stroke compression ignition engine. The maximum reduction in BSFC of 5.05% and the maximum BTE of 22.80% was for B30GNP40DMC10 compared to all other tested blends. A reduction in HC (25%) and CO (4.41%) were observed for B30DMC10, while a reduction in NOx of 3.65% was observed for B30GNP40DMC10. The diesel-biodiesel fuel blends with the addition of GNP exhibited a promising reduction in the average coefficient of friction 15.05%, 8.68% and 3.61% for 120, 80 and 40 ppm concentrations compared to B30. Thus, combined GNP and DMC showed excellent potential for utilisation in diesel engine operation.
Fulltext Effect of Berberis vulgaris L. root extract on ifosfamide-induced in vivo toxicity and in vitro cytotoxicity

Ilyas S, Tabasum R, Iftikhar A, Nazir M, Hussain A, Hussain A, et al.

Sci Rep, 2021 01 18;11(1):1708.
PMID: 33462261 DOI: 10.1038/s41598-020-80579-5

Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.
Fulltext Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats

Quah Y, Park NH, Lee EB, Lee KJ, Yi-Le JC, Ali MS, et al.

BMC Complement Med Ther, 2022 Jan 04;22(1):5.
PMID: 34983484 DOI: 10.1186/s12906-021-03486-w

BACKGROUND: Trifolium pratense (red clover) ethanolic extract (TPEE) has been used as a popular over-the-counter remedy for the management of menopausal symptoms. Prolonged consumption of herbal extract has been shown to regulate the composition of gut microbiota. This study was designed to elucidate the influence of TPEE on the gut microbiota composition in the ovariectomized (OVX) rats.
METHODS: OVX rats were treated with TPEE at 125, 250, 500 mg/kg/day, or controls (pomegranate extract, 500 mg/kg/day; estradiol, 25 μg/kg/day) for 12 weeks. Gut microbiota analysis was conducted by extracting the microbial DNA from fecal samples and microbiome taxonomic profiling was carried out by using next-generation sequencing. The levels of serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The prediction of functional biomarker of microbiota was performed using PICRUSt to investigate the potential pathways associated with gut health and serum lipid profile regulation. To study the correlation between gut microbiota composition and serum lipid levels, Spearman's correlation coefficients were defined and analyzed. Additionally, gas chromatography-mass spectrometry analysis was conducted to uncover additional physiologically active ingredients.
RESULTS: TPEE-treated OVX rats showed significant reduction in serum triglycerides (TG), total cholesterols (TCHOL), and LDL/VLDL levels but increase in HDL level. The alteration in the pathways involve in metabolism was the most common among the other KEGG categories. Particularly, TPEE also significantly reduced the relative abundance of sequences read associated with inflammatory bowel disease (IBD) and the peroxisome proliferator-activated receptor (PPAR) signalling pathway. TPEE intervention was seen to reduce the Firmicutes to Bacteroidetes (F/B) ratio in the OVX rats, denoting a reduction in microbial dysbiosis in the OVX rats. Correlation analysis at the phylum level revealed that Bacteriodetes and Proteobacteria were strongly correlated with serum TG, TCHOL and HDL levels. At the species level, Bifidobacterium pseudolongum group was seen to positively correlate with serum HDL level and negatively correlated with serum AST, ALT, LDL/VLDL, TCHOL, and TG levels.
CONCLUSIONS: TPEE treatment showed therapeutic benefits by improving the intestinal microbiota composition which strongly correlated with the serum lipid and cholesterol levels in the OVX rats.
Fulltext Bioassay Directed Isolation, Biological Evaluation and in Silico Studies of New Isolates from Pteris cretica L

Saleem F, Mehmood R, Mehar S, Khan MTJ, Khan ZU, Ashraf M, et al.

Antioxidants (Basel), 2019 Jul 19;8(7).
PMID: 31331076 DOI: 10.3390/antiox8070231

Members of genus Pteris have their established role in the traditional herbal medicine system. In the pursuit to identify its biologically active constituents, the specie Pteris cretica L. (P. cretica) was selected for the bioassay-guided isolation. Two new maleates (F9 and CB18) were identified from the chloroform extract and the structures of the isolates were elucidated through their spectroscopic data. The putative targets, that potentially interact with both of these isolates, were identified through reverse docking by using in silico tools PharmMapper and ReverseScreen3D. On the basis of reverse docking results, both isolates were screened for their antioxidant, acetylcholinesterase (AChE) inhibition, α-glucosidase (GluE) inhibition and antibacterial activities. Both isolates depicted moderate potential for the selected activities. Furthermore, docking studies of both isolates were also studied to investigate the binding mode with respective targets followed by molecular dynamics simulations and binding free energies. Thereby, the current study embodies the poly-pharmacological potential of P. cretica.
Fulltext A Food Frequency Questionnaire for Hemodialysis Patients in Bangladesh (BDHD-FFQ): Development and Validation

Ahmed S, Rahman T, Ripon MSH, Rashid HU, Kashem T, Md Ali MS, et al.

Nutrients, 2021 Dec 17;13(12).
PMID: 34960076 DOI: 10.3390/nu13124521

Diet is a recognized risk factor and cornerstone for chronic kidney disease (CKD) management; however, a tool to assess dietary intake among Bangladeshi dialysis patients is scarce. This study aims to validate a prototype Bangladeshi Hemodialysis Food Frequency Questionnaire (BDHD-FFQ) against 3-day dietary recall (3DDR) and corresponding serum biomarkers. Nutrients of interest were energy, macronutrients, potassium, phosphate, iron, sodium and calcium. The BDHD-FFQ, comprising 132 food items, was developed from 606 24-h recalls and had undergone face and content validation. Comprehensive facets of relative validity were ascertained using six statistical tests (correlation coefficient, percent difference, paired t-test, cross-quartiles classification, weighted kappa, and Bland-Altman analysis). Overall, the BDHD-FFQ showed acceptable to good correlations (p < 0.05) with 3DDR for the concerned nutrients in unadjusted and energy-adjusted models, but this correlation was diminished when adjusted for other covariates (age, gender, and BMI). Phosphate and potassium intake, estimated by the BDHD-FFQ, also correlated well with the corresponding serum biomarkers (p < 0.01) when compared to 3DDR (p > 0.05). Cross-quartile classification indicated that <10% of patients were incorrectly classified. Weighted kappa statistics showed agreement with all but iron. Bland-Altman analysis showed positive mean differences were observed for all nutrients when compared to 3DDR, whilst energy, carbohydrates, fat, iron, sodium, and potassium had percentage data points within the limit of agreement (mean ± 1.96 SD), above 95%. In summary, the BDHD-FFQ demonstrated an acceptable relative validity for most of the nutrients as four out of the six statistical tests fulfilled the cut-off standard in assessing dietary intake of CKD patients in Bangladesh.
QbD Assisted Systematic Review for Optimizing the Selection of PVP as a Ternary Substance in Enhancing the Complexation Efficiency of Cyclodextrins: a Pilot Study

Mulenga G, Alahmed TAA, Sami F, Majeed S, Ali MS, Le JLJ, et al.

AAPS PharmSciTech, 2024 Jun 11;25(5):134.
PMID: 38862663 DOI: 10.1208/s12249-024-02845-3

Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.
Fulltext Genomic analysis of methicillin-resistant Staphylococcus aureus strain SO-1977 from Sudan

Ali MS, Isa NM, Abedelrhman FM, Alyas TB, Mohammed SE, Ahmed AE, et al.

BMC Microbiol, 2019 06 11;19(1):126.
PMID: 31185900 DOI: 10.1186/s12866-019-1470-2

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is known as a leading cause of morbidity and mortality. Investigation of the MRSA's virulence and resistance mechanisms is a continuing concern toward controlling such burdens through using high throughput whole Genome Sequencing (WGS) and molecular diagnostic assays. The objective of the present study is to perform whole-genome sequencing of MRSA isolated from Sudan using Illumina Next Generation Sequencing (NGS) platform.
RESULTS: The genome of MRSA strain SO-1977 consists of 2,827,644 bp with 32.8% G + C, 59 RNAs and 2629 predicted coding sequences (CDSs). The genome has 26 systems, one of which is the major class in the disease virulence and defence. A total of 83 genes were annotated to virulence disease and defence category some of these genes coding as functional proteins. Based on genome analysis, it is speculated that the SO-1977 strain has resistant genes to Teicoplanin, Fluoroquinolones, Quinolone, Cephamycins, Tetracycline, Acriflavin and Carbapenems. The results revealed that the SO-1977, strain isolated from Sudan has a wide range of antibiotic resistance compared to related strains.
CONCLUSION: The study reports for the first time the whole genome sequence of Sudan MRSA isolates. The release of the genome sequence of the strain SO-1977 will avail MRSA in public databases for further investigations on the evolution of resistant mechanism and dissemination of the -resistant genes of MRSA.
Fulltext Knowledge, attitude, and practice of university students towards monkeypox in Bangladesh

Islam MA, Sathi NJ, Setu SP, Nahar MT, Khan MNA, Hasan M, et al.

PLoS One, 2023;18(10):e0287407.
PMID: 37824512 DOI: 10.1371/journal.pone.0287407

The recent outbreak of viral zoonotic disease-monkeypox-caused by the monkeypox virus, has infected many people worldwide. This study aims to explore the knowledge, attitudes, and practices (KAP) concerning monkeypox among university students in Bangladesh. Data were collected using purposive snowball sampling from 887 university students through an online survey using Google Form. The participants were mostly in their twenties (M = 22.33 [SD 2.01] years), and they spent, on average, 2.59 [SD 1.91] hours/day on electronic and social media. The participants generally showed moderate knowledge (39.5%), low attitude (25.1%), and moderate practice (48.6%) toward monkeypox, with 47.6% having had a moderate KAP score. Findings further showed that personal attributes of university students, i.e., age, sex, year of schooling, residence, living status, geographical distribution, e.g., division, were statistically and significantly associated with knowledge, attitudes, and practices regarding monkeypox and overall KAP score. It is also apparent that health status, susceptibility to monkeypox, and exposure to social media were the most common factors significantly associated with knowledge, attitudes, and practices regarding monkeypox and overall KAP score. The current study's findings underscore the need for developing appropriate information, education, and communication (IEC) materials and their dissemination, which could play an important role in reducing the risk of monkeypox and similar other infectious diseases, particularly among students in Bangladesh.

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