Displaying publications 181 - 200 of 322 in total

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  1. Concentrations and profiles of urinary polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in several Asian countries
    Guo Y, Senthilkumar K, Alomirah H, Moon HB, Minh TB, Mohd MA, et al.
    Environ Sci Technol, 2013 Mar 19;47(6):2932-8.
    PMID: 23409981 DOI: 10.1021/es3052262
    Concentrations of 12 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were determined in 306 urine samples collected from seven Asian countries (China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The total concentrations of OH-PAHs found in the seven Asian countries were in the following increasing order: Malaysia (median: 2260 pg/mL) < Japan (4030 pg/mL) < China (5770 pg/mL) < India (6750 pg/mL) < Vietnam (8560 pg/mL) < Korea (9340 pg/mL) < Kuwait (10170 pg/mL). The measured urinary concentrations of 1-hydroxypyrene (1-PYR) in samples from Malaysia, Korea, and Japan (∼ 100 pg/mL) were similar to those reported for North America and Western Europe. The concentrations of 1-PYR in urine samples from China, India, and Vietnam were 4-10 times higher than those reported for other countries, thus far. Among the 12 OH-PAH compounds analyzed, hydroxynaphthalene (NAP: sum of 1-hydroxynaphthalene and 2-hydroxynaphthalene) was the dominant compound (accounting for 60-90% of total OH-PAHs), followed by hydroxyphenanthrene (PHEN: sum of 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, and 9-hydroxyphenanthrene [3-16%]), 2-hydroxyfluorene (3-20%), and 1-PYR (2-8%). The total daily intakes (DIs) of PAHs were estimated based on the urinary concentrations of their metabolites. The DIs of naphthalene were found to be higher for populations in Korea, Kuwait, and Vietnam (> 10 μg/day) than those of the other countries studied (∼ 5 μg/day). The DIs of phenanthrene and pyrene (> 10 μg/day) in the populations of China, India, and Vietnam were higher than those estimated for the populations in the other countries studied (∼ 5 μg/day).
    Matched MeSH terms: Tandem Mass Spectrometry
  2. Fulltext Temporal regulation of proteome profile in the fruit fly, Drosophila melanogaster
    Subramanian P, Jayapalan JJ, Abdul-Rahman PS, Arumugam M, Hashim OH
    PeerJ, 2016;4:e2080.
    PMID: 27257555 DOI: 10.7717/peerj.2080
    Background. Diurnal rhythms of protein synthesis controlled by the biological clock underlie the rhythmic physiology in the fruit fly, Drosophila melanogaster. In this study, we conducted a proteome-wide investigation of rhythmic protein accumulation in D. melanogaster. Materials and Methods. Total protein collected from fly samples harvested at 4 h intervals over the 24 h period were subjected to two-dimensional gel electrophoresis, trypsin digestion and MS/MS analysis. Protein spots/clusters were identified with MASCOT search engine and Swiss-Prot database. Expression of proteins was documented as percentage of volume contribution using the Image Master 2D Platinum software. Results. A total of 124 protein spots/clusters were identified using MS/MS analysis. Significant variation in the expression of 88 proteins over the 24-h period was observed. A relatively higher number of proteins was upregulated during the night compared to the daytime. The complexity of temporal regulation of the D. melanogaster proteome was further reflected from functional annotations of the differently expressed proteins, with those that were upregulated at night being restricted to the heat shock proteins and proteins involved in metabolism, muscle activity, protein synthesis/folding/degradation and apoptosis, whilst those that were overexpressed in the daytime were apparently involved in metabolism, muscle activity, ion-channel/cellular transport, protein synthesis/folding/degradation, redox homeostasis, development and transcription. Conclusion. Our data suggests that a wide range of proteins synthesized by the fruit fly, D. melanogaster, is under the regulation of the biological clock.
    Matched MeSH terms: Tandem Mass Spectrometry
  3. Enzyme-assisted extraction and identification of antioxidative and α-amylase inhibitory peptides from Pinto beans (Phaseolus vulgaris cv. Pinto)
    Ngoh YY, Gan CY
    Food Chem, 2016 Jan 1;190:331-7.
    PMID: 26212978 DOI: 10.1016/j.foodchem.2015.05.120
    Antioxidant and α-amylase inhibitor peptides were successfully extracted from Pinto bean protein isolate (PBPI) using Protamex. A factorial design experiment was conducted and the effects of extraction time, pH and temperature were studied. pH 7.5, extraction time of 1h, S/E ratio of 10 (w/w) and temperature of 50 °C gave the highest antioxidant activities (i.e., ABTS scavenging activity (53.3%) and FRAP value (3.71 mM)), whereas pH 6.5 with the same extraction time, S/E ratio and temperature, gave the highest α-amylase inhibitory activity (57.5%). It was then fractioned using membrane ultrafiltration with molecular weight cutoffs of 100, 50, 30, 10 and 3 kDa. Peptide fraction <3 kDa, which exhibited the highest antioxidant activities (i.e., ABTS (42.2%) and FRAP (0.81 mM)) and α-amylase inhibitory activity (62.1%), was then subjected to LCMS and MS/MS analyses. Six sequences were identified for antioxidant peptides, whereas seven peptides for α-amylase inhibitor.
    Matched MeSH terms: Tandem Mass Spectrometry
  4. Fulltext Antioxidative Effects and Inhibition of Human Low Density Lipoprotein Oxidation In Vitro of Polyphenolic Compounds in Flammulina velutipes (Golden Needle Mushroom)
    Rahman MA, Abdullah N, Aminudin N
    Oxid Med Cell Longev, 2015;2015:403023.
    PMID: 26180589 DOI: 10.1155/2015/403023
    Dietary polyphenolic compounds mediate polynomial actions in guarding against multiple diseases. Atherosclerosis is an oxidative stress driven pathophysiological complication where free radical induced oxidative modification of low density lipoprotein (LDL) plays the ground breaking role. Mushrooms have been highly regarded for possessing an antioxidant arsenal. Polyphenolic compounds present in dietary mushrooms seem pertinent in withstanding LDL oxidation en route to controlling atherosclerosis. In this study, the antioxidative effect of five solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ) of Flammulina velutipes was evaluated. M : DCM fraction showed the most potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect with IC50 of 0.86 mg/mL and total phenolic content of 56.36 gallic acid equivalent/g fraction. In LDL oxidation inhibitory tests, M : DCM fraction at 1 µg/mL concentration mostly lengthened the lag time (125 mins) of conjugated diene formation and inhibited the formation of thiobarbituric acid reactive substances (48.71%, at 1 mg/mL concentration). LC-MS/MS analyses of M : DCM fraction identified the presence of polyphenolic substances protocatechuic acid, p-coumaric, and ellagic acid. These chain-breaking polyphenolics might impart the antioxidative effects of F. velutipes. Thus, mushroom-based dietary polyphenolic compounds might be implicated in slowing down the progression of atherosclerosis.
    Matched MeSH terms: Tandem Mass Spectrometry
  5. Uncovering Tumor-Stroma Inter-relationships Using MALDI Mass Spectrometry Imaging
    Boyle ST, Mittal P, Kaur G, Hoffmann P, Samuel MS, Klingler-Hoffmann M
    J Proteome Res, 2020 10 02;19(10):4093-4103.
    PMID: 32870688 DOI: 10.1021/acs.jproteome.0c00511
    Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. We used peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify the proteomic changes occurring within tumors and their stroma in their regular spatial context. Peptides were ranked according to their ability to discriminate between the two groups, using a receiver operating characteristic tool. Peptides were identified by liquid chromatography tandem mass spectrometry, and protein expression was validated by quantitative immunofluorescence using an independent set of tumor samples. We have identified and validated four key proteins upregulated in ROCK-activated mammary tumors relative to those expressing kinase-dead ROCK, namely, collagen I, α-SMA, Rab14, and tubulin-β4. Rab14 and tubulin-β4 are expressed within tumor cells, whereas collagen I is localized within the stroma. α-SMA is predominantly localized within the stroma but is also expressed at higher levels in the epithelia of ROCK-activated tumors. High expression of COL1A, the gene encoding the pro-α 1 chain of collagen, correlates with cancer progression in two human breast cancer genomic data sets, and high expression of COL1A and ACTA2 (the gene encoding α-SMA) are associated with a low survival probability (COLIA, p = 0.00013; ACTA2, p = 0.0076) in estrogen receptor-negative breast cancer patients. To investigate whether ROCK-activated tumor cells cause stromal cancer-associated fibroblasts (CAFs) to upregulate expression of collagen I and α-SMA, we treated CAFs with medium conditioned by primary mammary tumor cells in which ROCK had been activated. This led to abundant production of both proteins in CAFs, clearly highlighting the inter-relationship between tumor cells and CAFs and identifying CAFs as the potential source of high levels of collagen 1 and α-SMA and associated enhancement of tissue stiffness. Our research emphasizes the capacity of MALDI-MSI to quantitatively assess tumor-stroma inter-relationships and to identify potential prognostic factors for cancer progression in human patients, using sophisticated mouse cancer models.
    Matched MeSH terms: Tandem Mass Spectrometry
  6. Fulltext Cytotoxicity of Snake Venoms and Cytotoxins From Two Southeast Asian Cobras (Naja sumatrana, Naja kaouthia): Exploration of Anticancer Potential, Selectivity, and Cell Death Mechanism
    Chong HP, Tan KY, Tan CH
    Front Mol Biosci, 2020;7:583587.
    PMID: 33263003 DOI: 10.3389/fmolb.2020.583587
    Venoms of cobras (Naja spp.) contain high abundances of cytotoxins, which contribute to tissue necrosis in cobra envenomation. The tissue-necrotizing activity of cobra cytotoxins, nevertheless, indicates anticancer potentials. This study set to explore the anticancer properties of the venoms and cytotoxins from Naja sumatrana (equatorial spitting cobra) and Naja kaouthia (monocled cobra), two highly venomous species in Southeast Asia. The cytotoxicity, selectivity, and cell death mechanisms of their venoms and cytotoxins (NS-CTX from N. sumatrana: NS-CTX; N. kaouthia: NK-CTX) were elucidated in human lung (A549), prostate (PC-3), and breast (MCF-7) cancer cell lines. Cytotoxins were purified through a sequential fractionation approach using cation-exchange chromatography, followed by C18 reverse-phase high-performance liquid chromatography (HPLC) to homogeneity validated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and identified by liquid chromatography-tandem mass spectrometry (LCMS/MS). The cobra venoms and their respective cytotoxins exhibited concentration-dependent growth inhibitory effects in all cell lines tested, with the cytotoxins being more potent compared to the corresponding whole venoms. NS-CTX and NK-CTX are, respectively, P-type and S-type isoforms of cytotoxin, based on the amino acid sequences as per LCMS/MS analysis. Both cytotoxins exhibited differential cytotoxic effects in the cell lines tested, with NS-CTX (P-type cytotoxin) being significantly more potent in inhibiting the growth of the cancer cells. Both cytotoxins demonstrated promising selectivity only for the A549 lung cancer cell line (selectivity index = 2.17 and 2.26, respectively) but not in prostate (PC-3) and breast (MCF-7) cancer cell lines (selectivity index < 1). Flow cytometry revealed that the A549 lung cancer cells treated with NS-CTX and NK-CTX underwent necrosis predominantly. Meanwhile, the cytotoxins induced mainly caspase-independent late apoptosis in the prostate (PC-3) and breast (MCF-7) cancer cells lines but lacked selectivity. The findings revealed the limitations and challenges that could be faced during the development of new cancer therapy from cobra cytotoxins, notwithstanding their potent anticancer effects. Further studies should aim to overcome these impediments to unleash the anticancer potentials of the cytotoxins.
    Matched MeSH terms: Tandem Mass Spectrometry
  7. Fulltext Microalgal metabolites as anti-cancer/anti-oxidant agents reduce cytotoxicity of elevated silver nanoparticle levels against non-cancerous vero cells
    Hussein HA, Maulidiani M, Abdullah MA
    Heliyon, 2020 Oct;6(10):e05263.
    PMID: 33102866 DOI: 10.1016/j.heliyon.2020.e05263
    Heavy metal pollution has become a major concern globally as it contaminates eco-system, water networks and as finely suspended particles in air. In this study, the effects of elevated silver nanoparticle (AgNPs) levels as a model system of heavy metals, in the presence of microalgal crude extracts (MCEs) at different ratios, were evaluated against the non-cancerous Vero cells, and the cancerous MCF-7 and 4T1 cells. The MCEs were developed from water (W) and ethanol (ETH) as green solvents. The AgNPs-MCEs-W at the 4:1 and 5:1 ratios (v/v) after 48 and 72 h treatment, respectively, showed the IC50 values of 83.17-95.49 and 70.79-91.20 μg/ml on Vero cells, 13.18-28.18 and 12.58-25.7 μg/ml on MCF-7; and 16.21-33.88 and 14.79-26.91 μg/ml on 4T1 cells. In comparison, the AgNPs-MCEs-ETH formulation achieved the IC50 values of 56.23-89.12 and 63.09-91.2 μg/ml on Vero cells, 10.47-19.95 and 13.48-26.61 μg/ml on MCF-7; 14.12-50.11 and 15.13-58.88 μg/ml on 4T1 cells, respectively. After 48 and 72 h treatment, the AgNPs-MCE-CHL at the 4:1 and 5:1 ratios exhibited the IC50 of 51.28-75.85 and 48.97-69.18 μg/ml on Vero cells, and higher cytotoxicity at 10.47-16.98 and 6.19-14.45 μg/ml against MCF-7 cells, and 15.84-31.62 and 12.58-24.54 μg/ml on 4T1 cells, respectively. The AgNPs-MCEs-W and ETH resulted in low apoptotic events in the Vero cells after 24 h, but very high early and late apoptotic events in the cancerous cells. The Liquid Chromatography-Mass Spectrometry-Electrospray Ionization (LC-MS-ESI) metabolite profiling of the MCEs exhibited 64 metabolites in negative ion and 56 metabolites in positive ion mode, belonging to different classes. The microalgal metabolites, principally the anti-oxidative components, could have reduced the toxicity of the AgNPs against Vero cells, whilst retaining the cytotoxicity against the cancerous cells.
    Matched MeSH terms: Tandem Mass Spectrometry
  8. Fulltext Antioxidants and α-glucosidase inhibitors from Neptunia oleracea fractions using 1H NMR-based metabolomics approach and UHPLC-MS/MS analysis
    Lee SY, Mediani A, Ismail IS, Maulidiani, Abas F
    BMC Complement Altern Med, 2019 Jan 07;19(1):7.
    PMID: 30616569 DOI: 10.1186/s12906-018-2413-4
    BACKGROUND: Neptunia oleracea is a plant cultivated as vegetable in Southeast Asia. Previous works have revealed the potential of this plant as a source of natural antioxidants and α-glucosidase inhibitors. Continuing our interest on this plant, the present work is focused in identification of the bioactive compounds from different polarity fractions of N. oleracea, namely hexane (HF), chloroform (CF), ethyl acetate (EF) and methanol (MF).

    METHODS: The N. oleracea fractions were obtained using solid phase extraction (SPE). A metabolomics approach that coupled the use of proton nuclear magnetic resonance (1H NMR) with multivariate data analysis (MVDA) was applied to distinguish the metabolite variations among the N. oleracea fractions, as well as to assess the correlation between metabolite variation and the studied bioactivities (DPPH free radical scavenging and α-glucosidase inhibitory activities). The bioactive fractions were then subjected to ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis to profile and identify the potential bioactive constituents.

    RESULTS: The principal component analysis (PCA) discriminated EF and MF from the other fractions with the higher distributions of phenolics. Partial least squares (PLS) analysis revealed a strong correlation between the phenolics and the studied bioactivities in the EF and the MF. The UHPLC-MS/MS profiling of EF and MF had tentatively identified the phenolics present. Together with some non-phenolic metabolites, a total of 37 metabolites were tentatively assigned.

    CONCLUSIONS: The findings of this work supported that N. oleracea is a rich source of phenolics that can be potential antioxidants and α-glucosidase inhibitors for the management of diabetes. To our knowledge, this study is the first report on the metabolite-bioactivity correlation and UHPLC-MS/MS analysis of N. oleracea fractions.

    Matched MeSH terms: Tandem Mass Spectrometry
  9. The effect of mesenchymal stem cell-secreted factors on airway epithelial repair
    Halim NS, Aizat WM, Yahaya BH
    Regen Med, 2019 01;14(1):15-31.
    PMID: 30566028 DOI: 10.2217/rme-2018-0020
    AIM: This study was aimed to investigate the effect of mesenchymal stem cell (MSC)-secreted factors on airway repair.

    MATERIALS & METHODS: An indirect in vitro coculture model of injured airway epithelium explant with MSCs was developed. LC-MS/MS analysis was performed to determine factors secreted by MSCs and their involvement in epithelium repair was evaluated by histopathological assessment.

    RESULTS: The identification of 54 of MSC proteins of which 44 of them were secretory/extracellular proteins. 43 of the secreted proteins were found to be involved in accelerating airway epithelium repair by stimulating the migratory, proliferative and differentiation abilities of the endogenous repair mechanisms. MSC-secreted proteins also initiated epithelial-mesenchymal transition process during early repair.

    CONCLUSION: MSC-secreted factors accelerated airway epithelial repair by stimulating the endogenous reparative and regenerative ability of lung cells.

    Matched MeSH terms: Tandem Mass Spectrometry
  10. Daunorubicin oral bioavailability enhancement by surface coated natural biodegradable macromolecule chitosan based polymeric nanoparticles
    Ahmad N, Ahmad R, Alam MA, Ahmad FJ, Amir M, Pottoo FH, et al.
    Int J Biol Macromol, 2019 May 01;128:825-838.
    PMID: 30690115 DOI: 10.1016/j.ijbiomac.2019.01.142
    BACKGROUND: Daunorubicin hydrochloride (DAUN·HCl), due to low oral bioavailability poses the hindrance to be marketed as an oral formulation.

    AIM OF THE STUDY: To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN.

    RESULTS: A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p 

    Matched MeSH terms: Tandem Mass Spectrometry
  11. Fulltext Evaluation of female Aedes aegypti proteome via LC-ESI-MS/MS using two protein extraction methods
    Shettima A, Ishak IH, Abdul Rais SH, Abu Hasan H, Othman N
    PeerJ, 2021;9:e10863.
    PMID: 33717682 DOI: 10.7717/peerj.10863
    Background: Proteomic analyses have broadened the horizons of vector control measures by identifying proteins associated with different biological and physiological processes and give further insight into the mosquitoes' biology, mechanism of insecticide resistance and pathogens-mosquitoes interaction. Female Ae. aegypti ingests human blood to acquire the requisite nutrients to make eggs. During blood ingestion, female mosquitoes transmit different pathogens. Therefore, this study aimed to determine the best protein extraction method for mass spectrometry analysis which will allow a better proteome profiling for female mosquitoes.

    Methods: In this present study, two protein extractions methods were performed to analyze female Ae. aegyti proteome, via TCA acetone precipitation extraction method and a commercial protein extraction reagent CytoBusterTM. Then, protein identification was performed by LC-ESI-MS/MS and followed by functional protein annotation analysis.

    Results: The CytoBusterTM reagent gave the highest protein yield with a mean of 475.90 µg compared to TCA acetone precipitation extraction showed 283.15 µg mean of protein. LC-ESI-MS/MS identified 1,290 and 890 proteins from the CytoBusterTM reagent and TCA acetone precipitation, respectively. When comparing the protein class categories in both methods, there were three additional categories for proteins identified using CytoBusterTM reagent. The proteins were related to scaffold/adaptor protein (PC00226), protein binding activity modulator (PC00095) and intercellular signal molecule (PC00207). In conclusion, the CytoBusterTM protein extraction reagent showed a better performance for the extraction of proteins in term of the protein yield, proteome coverage and extraction speed.

    Matched MeSH terms: Tandem Mass Spectrometry
  12. The identification of active compounds in Ganoderma lucidum var. antler extract inhibiting dengue virus serine protease and its computational studies
    Lim WZ, Cheng PG, Abdulrahman AY, Teoh TC
    J Biomol Struct Dyn, 2020 Sep;38(14):4273-4288.
    PMID: 31595837 DOI: 10.1080/07391102.2019.1678523
    The number of global dengue incidences is alarmingly high in recent years. The global distribution of four dengue serotypes has also added economic burden in the dengue-endemic countries. To discover the potent dengue virus inhibitors in the antler form of Ganoderma lucidum (Lingzhi or Reishi), the water extraction of normal G. lucidum and its antler form were conducted and the chemical compounds were identified by LC-MS. Six distinct chemical compounds identified in high abundance were hesperetin, thymidine, lucidenic acid, 11-aminoundecanoic acid, 5-carboxyvanillic acid and ganocin B. The water extracts of G. lucidum in its antler form inhibited the DENV2 NS2B-NS3 protease activity at 84.6 ± 0.7%, higher than the normal G. lucidum. Then, molecular docking was performed on the homology model built from an in-house sequence. Docking simulation results showed that hesperetin and ganocin B were the best leads to bind at the catalytic triad of DENV2 NS2B-NS3pro via hydrogen bonding, van der Waals and pi-pi interactions. Extensive overlapping of HOMO-LUMO orbitals at the ringed regions of hesperetin helped to facilitate the entry of ligand to the catalytic triad cleft. LC-MS, molecular docking and density functional theory analyses confirmed that hesperetin was the strongest inhibitor against NS2B-NS3 protease. Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Tandem Mass Spectrometry
  13. Shotgun Proteomics and Mass Spectrometry as a Tool for Protein Identification and Profiling of Bio-Carrier-Based Therapeutics on Human Cancer Cells
    Abidin SAZ, Othman I, Naidu R
    Methods Mol Biol, 2021;2211:233-240.
    PMID: 33336281 DOI: 10.1007/978-1-0716-0943-9_16
    Shotgun proteomics has been widely applied to study proteins in complex biological samples. Combination of high-performance liquid chromatography with mass spectrometry has allowed for comprehensive protein analysis with high resolution, sensitivity, and mass accuracy. Prior to mass spectrometry analysis, proteins are extracted from biological samples and subjected to in-solution trypsin digestion. The digested proteins are subjected for clean-up and injected into the liquid chromatography-mass spectrometry system for peptide mass identification. Protein identification is performed by analyzing the mass spectrometry data on a protein search engine software such as PEAKS studio loaded with protein database for the species of interest. Results such as protein score, protein coverage, number of peptides, and unique peptides identified will be obtained and can be used to determine proteins identified with high confidence. This method can be applied to understand the proteomic changes or profile brought by bio-carrier-based therapeutics in vitro. In this chapter, we describe methods in which proteins can be extracted for proteomic analysis using a shotgun approach. The chapter outlines important in vitro techniques and data analysis that can be applied to investigate the proteome dynamics.
    Matched MeSH terms: Tandem Mass Spectrometry
  14. Fulltext Biodiscovery of Potential Antibacterial Diagnostic Metabolites from the Endolichenic Fungus Xylaria venustula Using LC-MS-Based Metabolomics
    Santiago KAA, Edrada-Ebel R, Dela Cruz TEE, Cheow YL, Ting ASY
    Biology (Basel), 2021 Mar 04;10(3).
    PMID: 33806264 DOI: 10.3390/biology10030191
    Three species of the lichen Usnea (U. baileyi (Stirt.) Zahlbr., U. bismolliuscula Zahlbr. and U. pectinata Stirt.) and nine associated endolichenic fungi (ELF) were evaluated using a metabolomics approach. All investigated lichen crude extracts afforded antibacterial activity against Staphylococcus aureus (minimum inhibitory concentration (MIC): 0.0625 mg/mL), but none was observed against Escherichia coli, while the ELF extract Xylaria venustula was found to be the most active against S. aureus (MIC: 2.5 mg/mL) and E. coli (MIC: 5 mg/mL). X. venustula was fractionated and tested for to determine its antibacterial activity. Fractions XvFr1 to 5 displayed bioactivities against both test bacteria. Selected crude extracts and fractions were subjected to metabolomics analyses using high-resolution LC-MS. Multivariate analyses showed the presence of five secondary metabolites unique to bioactive fractions XvFr1 to 3, which were identified as responsible for the antibacterial activity of X. venustula. The p-values of these metabolites were at the margin of significance level, with methyl xylariate C (P_60) being the most significant. However, their high variable importance of projection (VIP) scores (>5) suggest these metabolites are potential diagnostic metabolites for X. venustula for "dual" bioactivity against S. aureus and E. coli. The statistical models also showed the distinctiveness of metabolites produced by lichens and ELF, thus supporting our hypotheses of ELF functionality similar to plant endophytes.
    Matched MeSH terms: Tandem Mass Spectrometry
  15. Fulltext Enhancement of phenolics and antioxidant activity via heat assisted extraction from Moringa oleifera using response surface methodology and its potential bioactive constituents
    Ammar Akram Kamarudin, Norazalina Saad, Nor Hafiza Sayuti, Nor Asma Ab. Razak, Norhaizan Mohd. Esa
    Malaysian Journal of Medicine and Health Sciences, 2020;16(2):83-90.
    MyJurnal
    Introduction: Moringa oleifera Lam. is a miracle tree that has been widely utilised in folklore medicine due to its immense amount of phenolic constituents that could treat various ailments. Different techniques have been imple- mented to extract the phenolic but the parameters may not be optimised to further enhance the amount of phenolic extracted. Thus, the work aimed to enhance phenolic content and antioxidant activity of M. oleifera through RSM methodology, which is rapid and convenience. Methods: At first, antioxidant activity of different parts of M. oleifera (leaves, stem, pod and seed) were investigated. The plant part with the highest antioxidant activity was selected for the optimisation of extraction condition using RSM. In RSM, temperature (XA), extraction time (XB) and solid-liquid ratio (XC) were employed to study the effects on yield, total phenolics, flavonoids and antioxidant activity. Then, the optimum extraction condition obtained via RSM was utilised in LC-MS and HPLC analysis to determine the poten- tial bioactive constituents. Results: The leaves of M. oleifera displayed the highest antioxidant activity as compared to other plant parts. The optimum extraction condition obtained for the leaves extract was: temperature (XA): 82°C, extraction time (XB): 48 min and solid-liquid ratio (XC): 1:30 g/mL (w/v). Meanwhile, LC-MS revealed the presence of gallic acid, chlorogenic acid, quercetin, kaempferol and 3-O-glucoside kaempferol. HPLC analysis detected six compounds; gallic acid, epicatechin gallate, chlorogenic acid, myricetin, quercetin and kaempferol. Conclusion: The optimisation are promising to improve yield and antioxidant activity in M. oleifera as compared to non-conven- tional extractions.

    Matched MeSH terms: Tandem Mass Spectrometry
  16. Lead exposure induces metabolic reprogramming in rat models
    Mani MS, Joshi MB, Shetty RR, DSouza VL, Swathi M, Kabekkodu SP, et al.
    Toxicol Lett, 2020 Dec 15;335:11-27.
    PMID: 32949623 DOI: 10.1016/j.toxlet.2020.09.010
    Lead is a toxin of great public health concern affecting the young and aging population. Several factors such as age, gender, lifestyle, dose, and genetic makeup result in interindividual variations to lead toxicity mainly due to variations in metabolic consequences. Hence, the present study aimed to examine dose-dependent lead-induced systemic changes in metabolism using rat model by administering specific doses of lead such as 10 (low lead; L-Pb), 50 (moderate lead; M-Pb), and 100 mg/kg (high lead; H-Pb) body weight for a period of one month. Biochemical and haematological analysis revealed that H-Pb was associated with low body weight and feed efficiency, low total protein levels (p ≤ 0.05), high blood lead (Pb-B) levels (p ≤ 0.001), low ALAD (δ-aminolevulinate dehydratase) activity (p ≤ 0.0001), high creatinine (p ≤ 0.0001) and blood urea nitrogen (BUN) (p ≤ 0.01) levels, elevated RBC and WBC counts, reduced haemoglobin and blood cell indices compared to control. Spatial learning and memory test revealed that H-Pb exposed animals presented high latency to the target quadrant and escape platform compared to other groups indicating H-Pb alters cognition function in rats. Histopathological changes were observed in liver and kidney as they are the main target organs of lead toxicity. LC-MS analysis further revealed that Butyryl-L-carnitine (p ≤ 0.01) and Ganglioside GD2 (d18:0/20:0) (p ≤ 0.05) levels were significantly reduced in H-Pb group compared to all groups. Further, pathway enrichment analysis revealed abundance and significantly modulated metabolites associated with oxidative stress pathways. The present study is the first in vivo model of dose-dependent lead exposure for serum metabolite profiling.
    Matched MeSH terms: Tandem Mass Spectrometry
  17. Fulltext Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (Trimeresurus purpureomaculatus) venom and its disintegrin (purpureomaculin)
    Tan CH, Liew JL, Navanesan S, Sim KS, Tan NH, Tan KY
    J Venom Anim Toxins Incl Trop Dis, 2020;26:e20200013.
    PMID: 32742279 DOI: 10.1590/1678-9199-JVATITD-2020-0013
    Background: The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs.

    Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.

    Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.

    Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.

    Matched MeSH terms: Tandem Mass Spectrometry
  18. Occurrence and risk assessment of multiclass endocrine disrupting compounds in an urban tropical river and a proposed risk management and monitoring framework
    Wee SY, Aris AZ, Yusoff FM, Praveena SM
    Sci Total Environ, 2019 Jun 25;671:431-442.
    PMID: 30933799 DOI: 10.1016/j.scitotenv.2019.03.243
    Endocrine disrupting compounds (EDCs) are an emerging environmental concern and commonly occur as a mixture of compounds. The EDC mixture can be more toxic than any single compound. The present study analyses EDCs in surface water in the case of an urban tropical river, the Langat River, using the multiresidue analytical method of solid phase extraction and liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). The Langat River is used as a drinking water source and is treated for Malaysian drinking water supply. A total of 14 EDCs i.e. five hormones, seven pharmaceuticals, one pesticide, and one plasticizer were detected. Caffeine was observed to be highest at 19.33 ng/L, followed by bisphenol A and diclofenac at 8.24 ng/L and 6.15 ng/L, respectively. Using a conservative risk quotient (RQ) method, EDCs were estimated for having negligible risks under acute and chronic exposure (RQ 
    Matched MeSH terms: Tandem Mass Spectrometry
  19. Fulltext Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model
    Kundap UP, Paudel YN, Kumari Y, Othman I, Shaikh MF
    Front Pharmacol, 2019;10:315.
    PMID: 31057394 DOI: 10.3389/fphar.2019.00315
    Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.
    Matched MeSH terms: Tandem Mass Spectrometry
  20. Fulltext Heterometrus Spinifer: An Untapped Source of Anti-Tumor Molecules
    Soopramanien M, Khan NA, Ghimire A, Sagathevan K, Siddiqui R
    Biology (Basel), 2020 Jul 02;9(7).
    PMID: 32630812 DOI: 10.3390/biology9070150
    Despite intensive research, cancer incidence and mortality continue to rise. Consequently, the necessity to develop effective anti-cancer therapy is apparent. We have recently shown that the gut bacteria of animals living in polluted environments, such as crocodiles, are a potential source of novel anti-tumor molecules. To extend this work to other resilient species, we investigated the anti-tumor effects of gut bacteria of Heterometrus spinifer (a scorpion). Bacteria from the feces and gut were isolated, identified and evaluated for their anti-tumor effects. Bacterial-conditioned media was prepared in Roswell Park Memorial Institute (RPMI) 1640 media, and cytotoxicity and growth inhibitory properties were examined against cervical (HeLa) cancer cells. Liquid chromatography-mass spectrometry (LC-MS) was conducted to establish the identity of the molecules. Eighteen bacteria species from the gut (HSG01-18) and ten bacteria species from feces (HSF01-10) were tested for anti-tumor effects. Bacterial-conditioned media from scorpion gut and feces exhibited significant growth inhibitory effects against HeLa cells of 66.9% and 83.8%, respectively. Microscopic analysis of cancer cells treated with conditioned media HSG12 and HSG16 revealed apoptosis-like effects. HSG12 was identified as Pseudomonas aeruginosa and HSG16 was identified as Bacillus subtilis. Both conditioned media exhibited 100% growth inhibitory effects versus a selection of cancer cells, comprising cervical, breast and prostate cancer cells. LC-MS indicated the presence of 72 and 38 compounds, detected from HSG12 and HSG16, respectively. Out of these compounds, 47 were successfully identified while the remainder were unidentified and are possibly novel. This study suggests that the fecal and gut microbiota of scorpions might possess molecules with anti-cancer properties, however, further intensive research is needed to assess these expectations.
    Matched MeSH terms: Tandem Mass Spectrometry
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