Displaying publications 1 - 20 of 209 in total

Abstract:
Sort:
  1. Neoh CH, Lam CY, Ghani SM, Ware I, Sarip SH, Ibrahim Z
    3 Biotech, 2016 Dec;6(2):143.
    PMID: 28330215 DOI: 10.1007/s13205-016-0455-1
    The biggest agricultural sector that contributes to the Malaysian economy is the oil palm industry. The effluent generated during the production of crude palm oil known as palm oil mill effluent (POME). POME undergoes anaerobic treatment that requires long retention time and produces large amount of methane that consequently contributes to global warming. In this study, an isolated bacteria was selected based on its ability to degrade kraft lignin (KL) and identified as Ochrobactrum sp. The bacteria were able to treat POME (from anaerobic pond) under the aerobic condition without addition of nutrient, resulting in a significant chemical oxygen demand (COD) removal of 71 %, removal rate of 1385 mg/l/day, and 12.3 times higher than that of the ponding system. It has also resulted in 60 % removal of ammoniacal nitrogen and 55 % of total polyphenolic after 6-day treatment period with the detection of lignocellulolytic enzymes.
  2. Lim CK, Seow TW, Neoh CH, Md Nor MH, Ibrahim Z, Ware I, et al.
    3 Biotech, 2016 Dec;6(2):195.
    PMID: 28330267 DOI: 10.1007/s13205-016-0513-8
    Sanitary landfilling is the most common way to dispose solid urban waste; however, improper landfill management may pose serious environmental threats through discharge of high strength polluted wastewater also known as leachate. The treatment of landfill leachate to fully reduce the negative impact on the environment, is nowadays a challenge. In this study, an aerobic sequencing batch reactor (ASBR) was proposed for the treatment of locally obtained real landfill leachate with initial ammoniacal nitrogen and chemical oxygen demand (COD) concentration of 1800 and 3200 mg/L, respectively. ASBR could remove 65 % of ammoniacal nitrogen and 30 % of COD during seven days of treatment time. Thereafter, an effective adsorbent, i.e., zeolite was used as a secondary treatment step for polishing the ammoniacal nitrogen and COD content that is present in leachate. The results obtained are promising where the adsorption of leachate by zeolite further enhanced the removal of ammoniacal nitrogen and COD up to 96 and 43 %, respectively. Furthermore, this combined biological-physical treatment system was able to remove heavy metals, i.e. aluminium, vanadium, chromium, magnesium, cuprum and plumbum significantly. These results demonstrate that combined ASBR and zeolite adsorption is a feasible technique for the treatment of landfill leachate, even considering this effluent's high resistance to treatment.
  3. Mohamad MS, Omatu S, Deris S, Yoshioka M, Abdullah A, Ibrahim Z
    Algorithms Mol Biol, 2013;8(1):15.
    PMID: 23617960 DOI: 10.1186/1748-7188-8-15
    Gene expression data could likely be a momentous help in the progress of proficient cancer diagnoses and classification platforms. Lately, many researchers analyze gene expression data using diverse computational intelligence methods, for selecting a small subset of informative genes from the data for cancer classification. Many computational methods face difficulties in selecting small subsets due to the small number of samples compared to the huge number of genes (high-dimension), irrelevant genes, and noisy genes.
  4. Mohd Bahari Z, Ali Hamood Altowayti W, Ibrahim Z, Jaafar J, Shahir S
    Appl Biochem Biotechnol, 2013 Dec;171(8):2247-61.
    PMID: 24037600 DOI: 10.1007/s12010-013-0490-x
    The ability of non-living biomass of an arsenic-hypertolerant Bacillus cereus strain SZ2 isolated from a gold mining environment to adsorb As (III) from aqueous solution in batch experiments was investigated as a function of contact time, initial As (III) concentration, pH, temperature and biomass dosage. Langmuir model fitted the equilibrium data better in comparison to Freundlich isotherm. The maximum biosorption capacity of the sorbent, as obtained from the Langmuir isotherm, was 153.41 mg/g. The sorption kinetic of As (III) biosorption followed well the pseudo-second-order rate equation. The Fourier transform infrared spectroscopy analysis indicated the involvement of hydroxyl, amide and amine groups in As (III) biosorption process. Field emission scanning electron microscopy-energy dispersive X-ray analysis of the non-living B. cereus SZ2 biomass demonstrated distinct cell morphological changes with significant amounts of As adsorbed onto the cells compared to non-treated cells. Desorption of 94 % As (III) was achieved at acidic pH 1 showing the capability of non-living biomass B. cereus SZ2 as potential biosorbent in removal of As (III) from arsenic-contaminated mining effluent.
  5. Alajerami YS, Hashim S, Ghoshal SK, Ramli AT, Saleh MA, Ibrahim Z, et al.
    Appl Radiat Isot, 2013 Dec;82:12-9.
    PMID: 23948307 DOI: 10.1016/j.apradiso.2013.07.005
    Understanding the influence of co-dopants in the luminescence enhancement of carbonate glasses is the key issue in dosimetry. A series of borate glasses modified by lithium and potassium carbonate were synthesized by the melt-quenching method. The glass mixture activated with various concentrations of TiO2 and MgO was subjected to various doses of gamma-rays ((60)Co). The amorphous nature of the samples was confirmed by x-ray diffraction (XRD) spectra. The simple glowing curve of the glass doped with TiO2 features a peak at 230°C, whose intensity is maximal at 0.5 mol% of the dopant. The intensity of the glowing curve increases with the concentration of MgO added as a co-dopant up to 0.25 mol%, where it is two times higher than for the material without MgO thermoluminescence properties, including dose response, reproducibility, and fading were studied. The effective atomic number of the material was also determined. Kinetic parameters, such as kinetics order, activation energy, and frequency factor are estimated. The photoluminescence spectra of the titanium-doped glass consist of a prominent peaks at 480 nm when laser excitation at 650 nm is used. A three-fold photoluminescence enhancement and a blue shift of the peak were observed when 0.1% MgO was introduced. In addition, various physical parameters, such as ion concentration, polaron radius and internuclear distances were calculated. The mechanism for the thermoluminescence and photoluminescence enhancements are discussed.
  6. Shahar S, Ibrahim Z, Fatah AR, Rahman SA, Yusoff NA, Arshad F, et al.
    Asia Pac J Clin Nutr, 2007;16(2):346-53.
    PMID: 17468093
    A multidimensional assessment of nutritional and health status comprised of subjective global assessment (SGA), anthropometry function, biochemistry, dietary intake, social and health aspects was carried out on 820 older people (52.8% men and 47.2% women) from four rural areas of Peninsular Malaysia. A proportion of the subjects had been classified as either overweight (25.7%) or chronic energy deficient (20.3%). Although 49% of subjects had normal body weight, 68.4% have been classified as having mild to moderate malnutrition according to the SGA. Only 1.1% and 2.3% had low serum albumin and ferritin, respectively. Almost 80% of subjects, especially men, were at high risk of cardiovascular diseases on the basis of the assessment of total cholesterol and LDL-cholesterol. The majority of the subjects (87.2%) were fully independent in performing daily tasks, with men having a significantly higher score compared to women (p<0.001). However, men were less likely to be able to perform a flexibility test (50.7%) than were women (27.0%) (p<0.05). The mean energy intake for men (1412 +/- 461 kcal/d) and women (1201 +/- 392 kcal/d) were below the Recommended Nutrient Intake (RNI) for Malaysia, although this is a difficult assertion to make in an age-group which generally experiences declining energy expenditure. Moreover, 52.5% of men and 47.5% of women might have underreported their food intake. Dietary micronutrients most likely to be deficient were thiamin, riboflavin and calcium. It is concluded that a substantial proportion of rural elderly Malays had problems related to both undernutrition and overnutrition. An appropriate nutrition intervention program is needed to improve the nutritional status of rural elderly Malays.
  7. Bahari Z, Ibrahim Z, Adznam SNA, Yusof BNM
    Asia Pac J Clin Nutr, 2017 8 15;26(5):781-787.
    PMID: 28802285 DOI: 10.6133/apjcn.102016.02
    BACKGROUND AND OBJECTIVES: Assessment of the nutrition care process (NCP) knowledge, attitudes, practices, and perceived barriers (KAPB) of dietetics practitioners is imperative before NCP is implemented completely in dietetics practice. No questionnaire assessing NCP KAPB has been developed and validated. Hence, we developed an NCP KAPB questionnaire called the KAPB-NCP and established its content validity.

    METHODS AND STUDY DESIGN: A total of 116 items associated with sociodemographic characteristics (7 items), professional development (3 items), organisational culture's support for the NCP (2 items), knowledge (27 items), attitudes (39 items), practices (20 items), and perceived barriers to implementing the NCP (14 items) were generated for potential inclusion in the KAPB-NCP questionnaire. The questionnaire was reviewed online by an expert panel for its content validity. An in-depth review was conducted by the research team for evaluating the overall comprehensiveness of the questionnaire.

    RESULTS: In total, 87 of 100 items of the KAPB sections showed an excellent content validity index (CVI; k* >0.74), whereas 10 showed a satisfactory CVI (k*=0.60-0.74). Only 3 items had a low CVI (k* <0.40). According to the expert panel revisions and the in-depth review, 72 items were incorporated into the questionnaire.

    CONCLUSIONS: The KAPB-NCP questionnaire is a content-valid instrument that can assess NCP KAPB.

  8. Riyahi N, Tohit ERM, Thambiah SC, Ibrahim Z
    Asia Pac J Clin Nutr, 2017 12 10;27(1):182-188.
    PMID: 29222897 DOI: 10.6133/apjcn.032017.01
    BACKGROUND AND OBJECTIVES: Recent studies have reported that obesity is associated with platelet activation and systemic inflammation. Malaysia has the highest prevalence of obesity, hence, this research is performed to evaluate the development of low-grade inflammation and platelet activation, measured using soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel), and to determine their association with obesity. In addition, we assessed the mean platelet volume (MPV) and platelet count (PLT), which are novel parameters consistently associated with obesity.

    METHODS AND STUDY DESIGN: A cross-sectional study was conducted on 112 healthy men and women from 3 main ethnic group (Malay, Chinese, and Indian) who were aged 18-60 years. The participants were categorized into normal body mass index (BMI), overweight and obese groups according to WHO criteria for BMI in Asian populations (18.5 kg/m2

  9. Latiff LA, Ibrahim Z, Pei CP, Rahman SA, Akhtari-Zavare M
    Asian Pac J Cancer Prev, 2015;16(18):8495-501.
    PMID: 26745108
    PURPOSE: This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection.

    MATERIALS AND METHODS: Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test.

    RESULTS: For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p= 0.014).

    CONCLUSION: The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia.

  10. Chua NYC, Chong PF, Najme Khir R, Lim CW, Ismail JR, Mohd Arshad MK, et al.
    Atherosclerosis, 2017 Aug;263:e184.
    PMID: 29365712 DOI: 10.1016/j.atherosclerosis.2017.06.591
  11. Abdul-Razak S, Rahmat R, Mohd Kasim A, Rahman TA, Muid S, Nasir NM, et al.
    BMC Cardiovasc Disord, 2017 Oct 16;17(1):264.
    PMID: 29037163 DOI: 10.1186/s12872-017-0694-z
    BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC.

    METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.

    RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p 

  12. Ismail AM, Mohamad MS, Abdul Majid H, Abas KH, Deris S, Zaki N, et al.
    Biosystems, 2017 Dec;162:81-89.
    PMID: 28951204 DOI: 10.1016/j.biosystems.2017.09.013
    Mathematical modelling is fundamental to understand the dynamic behavior and regulation of the biochemical metabolisms and pathways that are found in biological systems. Pathways are used to describe complex processes that involve many parameters. It is important to have an accurate and complete set of parameters that describe the characteristics of a given model. However, measuring these parameters is typically difficult and even impossible in some cases. Furthermore, the experimental data are often incomplete and also suffer from experimental noise. These shortcomings make it challenging to identify the best-fit parameters that can represent the actual biological processes involved in biological systems. Computational approaches are required to estimate these parameters. The estimation is converted into multimodal optimization problems that require a global optimization algorithm that can avoid local solutions. These local solutions can lead to a bad fit when calibrating with a model. Although the model itself can potentially match a set of experimental data, a high-performance estimation algorithm is required to improve the quality of the solutions. This paper describes an improved hybrid of particle swarm optimization and the gravitational search algorithm (IPSOGSA) to improve the efficiency of a global optimum (the best set of kinetic parameter values) search. The findings suggest that the proposed algorithm is capable of narrowing down the search space by exploiting the feasible solution areas. Hence, the proposed algorithm is able to achieve a near-optimal set of parameters at a fast convergence speed. The proposed algorithm was tested and evaluated based on two aspartate pathways that were obtained from the BioModels Database. The results show that the proposed algorithm outperformed other standard optimization algorithms in terms of accuracy and near-optimal kinetic parameter estimation. Nevertheless, the proposed algorithm is only expected to work well in small scale systems. In addition, the results of this study can be used to estimate kinetic parameter values in the stage of model selection for different experimental conditions.
  13. Parvaneh K, Ebrahimi M, Sabran MR, Karimi G, Hwei AN, Abdul-Majeed S, et al.
    Biomed Res Int, 2015;2015:897639.
    PMID: 26366421 DOI: 10.1155/2015/897639
    Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 10(8)-10(9) colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.
  14. Nor FHM, Abdullah S, Ibrahim Z, Nor MHM, Osman MI, Al Farraj DA, et al.
    Bioprocess Biosyst Eng, 2023 Mar;46(3):381-391.
    PMID: 35779113 DOI: 10.1007/s00449-022-02749-1
    An effective biosurfactant producer and extremophiles bacteria, Bacillus cereus KH1, was isolated from textile effluent and the biosurfactant was produced using molasses as the sole carbon source. Growth parameters such as pH, temperature, salinity and concentration of molasses were optimised for decolourising the textile effluent with 24-h incubation. The biosurfactant property of B. cereus KH1 was evaluated based on haemolytic activity, oil displacement technique, drop-collapsing test and emulsification index. The results of the produced biosurfactant showed a positive reaction in haemolytic activity, oil displacement technique, drop-collapsing test and exhibiting a 67% emulsification index. The cell-free broth was stable in 40 °C pH 7, 7% salinity and 7% molasses. Thin-Layer Chromatography and Fourier Transform Infrared Spectroscopy analysis revealed that the biosurfactant was a lipopeptide with a yield 2.98 g L-1. These findings proved the synergistic action of B. cereus KH1 with lipopeptide biosurfactant may accelerated the decolourisation efficiency to 87%.
  15. Nor MH, Mubarak MF, Elmi HSh, Ibrahim N, Wahab MF, Ibrahim Z
    Bioresour Technol, 2015 Aug;190:458-65.
    PMID: 25799955 DOI: 10.1016/j.biortech.2015.02.103
    A double-chambered membrane microbial fuel cell (MFC) was constructed to investigate the potential use of natural microflora anaerobic palm oil mill effluent (POME) sludge and pure culture bacteria isolated from anaerobic POME sludge as inoculum for electricity generation. Sterilized final discharge POME was used as the substrate with no addition of nutrients. MFC operation using natural microflora anaerobic POME sludge showed a maximum power density and current density of 85.11mW/m(2) and 91.12mA/m(2) respectively. Bacterial identification using 16S rRNA analysis of the pure culture isolated from the biofilm on the anode MFC was identified as Pseudomonas aeruginosa strain ZH1. The electricity generated in MFC using P. aeruginosa strain ZH1 showed maximum power density and current density of 451.26mW/m(2) and 654.90mA/m(2) respectively which were five times higher in power density and seven times higher in current density compared to that of MFC using anaerobic POME sludge.
  16. Najib MZM, Salmiati, Ujang Z, Salim MR, Ibrahim Z, Muda K
    Bioresour Technol, 2016 Dec;221:157-164.
    PMID: 27639234 DOI: 10.1016/j.biortech.2016.08.119
    The developed microbial granules containing photosynthetic pigments had successfully achieved approximately 18-21% of carbon dioxide (CO2) removal in POME for one complete SBR cycle. Also, the granules had reached CO2 removal at 15-29% within 24h and removal of 25% after 5 days. Both results were inconsistent possibly due to the slow mass transfer rate of CO2 from gas to liquid as well as the simultaneous effect of CO2 production and respiration among the microbes. Furthermore, results showed the removal of CO2 from air increases proportionally with the CO2 removed in liquid. The CO2 biofixation of granules attained was approximately 0.23g/L/day for a week. Using the regression model, the removal of CO2 between liquid and gas, CO2 biofixation rate were highly correlated with the treatment time. A statistically significant relationship was obtained between CO2 concentration in liquid, biomass productivity and treatment time for the CO2 biofixation rate of the granules.
  17. Yousefi S, Bayat S, Rahman MB, Ibrahim Z, Abdulmalek E
    Chem Biodivers, 2017 Apr;14(4).
    PMID: 28036129 DOI: 10.1002/cbdv.201600362
    Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-Aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug.
  18. Gan HM, Shahir S, Ibrahim Z, Yahya A
    Chemosphere, 2011 Jan;82(4):507-13.
    PMID: 21094980 DOI: 10.1016/j.chemosphere.2010.10.094
    A co-culture consisting of Hydrogenophaga sp. PBC and Ralstonia sp. PBA, isolated from textile wastewater treatment plant could tolerate up to 100 mM 4-aminobenzenesulfonate (4-ABS) and utilize it as sole carbon, nitrogen and sulfur source under aerobic condition. The biodegradation of 4-ABS resulted in the release of nitrogen and sulfur in the form of ammonium and sulfate respectively. Ninety-eight percent removal of chemical oxygen demand attributed to 20 mM of 4-ABS in cell-free supernatant could be achieved after 118 h. Effective biodegradation of 4-ABS occurred at pH ranging from 6 to 8. During batch culture with 4-ABS as sole carbon and nitrogen source, the ratio of strain PBA to PBC was dynamic and a critical concentration of strain PBA has to be reached in order to enable effective biodegradation of 4-ABS. Haldane inhibition model was used to fit the degradation rate at different initial concentrations and the parameters μ(max), K(s) and K(i) were determined to be 0.13 h⁻¹, 1.3 mM and 42 mM respectively. HPLC analyses revealed traced accumulation of 4-sulfocatechol and at least four unidentified metabolites during biodegradation. This is the first study to report on the characterization of 4-ABS-degrading bacterial consortium that was isolated from textile wastewater treatment plant.
  19. Ho CY, Ibrahim Z, Abu Zaid Z, Mat Daud Z', Md Yusop NB
    Clin Nutr, 2021 06;40(6):4373-4379.
    PMID: 33485706 DOI: 10.1016/j.clnu.2021.01.008
    BACKGROUND: Malnutrition is common among cancer patients regardless of stage of cancer. Given the strong association between malnutrition with prolonged hospitalization, delayed recovery and even higher post-operative complications among gynaecologic cancer (GC) patients, it is important to understand its predictive factors. The current study aimed to determine malnutrition predictors among GC patients before elective operation.

    METHOD: A cross-sectional study was conducted among surgical GC patients who were admitted for elective surgery. Data on socio-demographic characteristics, clinical status (diagnosis, the staging of cancer, comorbidities and family history on cancer), anthropometric measures [ Body Mass Index (BMI), weight changes, the percentage of weight loss past one month, muscle mass, fat mass, fat-free mass and mid-upper arm circumference (MUAC)], biochemical profiles [C-reactive protein, albumin and C-reactive protein (CRP) to albumin ratio (CAR)], handgrip strength, total daily energy and protein intake, and malnutrition status [scored Patient Generated-Subjective Global Assessment (PG-SGA)] were assessed during admission.

    RESULTS: Study recruited 124 participants and 57.2% (n = 71) were malnourished. Mean for age, weight changes past one month, handgrip strength, total daily energy and protein intake, PG-SGA score and CAR of participants were 49.9 ± 12.5 years, -4.9 ± 7.2%, 15.6 ± 6.2 kg, 25±7 kcal/kg/day, 1.0 ± 0.3 g/kg/day, 6.5 ± 5.4 and 0.7 ± 1.9, respectively. Multiple linear regression test revealed that the percentage of weight loss past one month, haemoglobin, CRP and handgrip strength were the significant predictors of malnutrition.

    CONCLUSION: Malnutrition is common among GC patient even before elective operation. The early malnutrition screening following with proper nutritional intervention is crucial to optimize nutritional status among GC patients before elective operation.

  20. Zainal Fithri HH, Ibrahim Z, Ali EZ
    Comput Biol Chem, 2023 Dec;107:107962.
    PMID: 37847978 DOI: 10.1016/j.compbiolchem.2023.107962
    Protein arginine deiminase IV (PAD4) is a potential target for diseases including rheumatoid arthritis and cancers. Currently, GSK199 is a potent, selective yet reversible PAD4 inhibitor. Its derivative, GSK106, on the other hand, was reported as an inactive compound when tested against PAD4 assay. Although they had similar skeleton, their impact towards PAD4 structural and flexibility is unknown. In order to fill the research gap, the impact of GSK199 and GSK106 binding towards PAD4 stability and flexibility is investigated via a combination of computational methods. Molecular docking indicates that GSK199 and GSK106 are capable to bind at PAD4 pocket by using its back door with -10.6 kcal/mol and -9.6 kcal/mol, respectively. The simulations of both complexes were stable throughout 100 ns. The structure of PAD4 exhibited a tighter packing in the presence of GSK106 compared to GSK199. The RMSF analysis demonstrates significant changes between the PAD4-GSK199 and PAD4-GSK106 simulations in the regions containing residues 136, 160, 220, 438, and 606. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis shows a marked difference in binding free energies, with -11.339 kcal/mol for the PAD4-GSK199 complex and 1.063 kcal/mol for the PAD4-GSK106 complex. The hydrogen bond analysis revealed that the GSK199 and GSK106 binding to PAD4 are assisted by six hydrogen bonds and three hydrogen bonds, respectively. The visualisation of the MD simulations revealed that GSK199 remained in the PAD4 pocket, whereas GSK106 shifted away from the catalytic site. Meanwhile, molecular dockings of benzoyl arginine amide (BAEE) substrate have shown that BAEE is able to bind to PAD4 catalytic site when GSK106 was present but not when GSK199 occupied the site. Overall, combination of computational approaches successfully described the behaviour of binding pocket of PAD4 structure in the presence of the active and inactive compounds.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links