Displaying publications 1881 - 1900 of 9214 in total

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  1. Ahmad Hairi H, Jamal JA, Aladdin NA, Husain K, Mohd Sofi NS, Mohamed N, et al.
    Molecules, 2018 Jul 11;23(7).
    PMID: 29997309 DOI: 10.3390/molecules23071686
    Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17β-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κβ ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.
    Matched MeSH terms: Calcium/metabolism; Collagen/metabolism; Osteoblasts/metabolism*; Receptors, Estrogen/metabolism; Biomarkers/metabolism; Osteoprotegerin/metabolism; RANK Ligand/metabolism
  2. Nurfarahin AH, Mohamed MS, Phang LY
    Molecules, 2018 May 01;23(5).
    PMID: 29723959 DOI: 10.3390/molecules23051049
    Surfactants are compounds that can reduce the surface tension between two different phases or the interfacial tension of the liquid between water and oil, possessing both hydrophilic and hydrophobic moieties. Biosurfactants have traits that have proven to be advantageous over synthetic surfactants, but these compounds do not compete economically with synthetic surfactants. Different alternatives increase the yield of biosurfactants; development of an economical production process and the usage of cheaper substrates during process have been employed. One of the solutions relies on the suitable formulation of a production medium by including alternative raw materials sourced from agro-wastes, hydrocarbons, or by-products of a process might help in boosting the biosurfactant production. Since the nutritional factors required will be different among microorganisms, the establishment of a suitable formulation for biosurfactant production will be challenging. The present review describes various nutrients and elements considered in the formulation of a production medium with an approach focusing on the macronutrient (carbon, nitrogen source, and C/N ratio), minerals, vitamins, metabolic regulators, and salinity levels which may aid in the study of biosurfactant production in the future.
    Matched MeSH terms: Surface-Active Agents/metabolism*
  3. Mazlan SNHS, Ali MSM, Rahman RNZRA, Sabri S, Jonet MA, Leow TC
    Int J Biol Macromol, 2018 Nov;119:1188-1194.
    PMID: 30102982 DOI: 10.1016/j.ijbiomac.2018.08.022
    GDSL esterase J15 (EstJ15) is a member of Family II of lipolytic enzyme. The enzyme was further classified in subgroup SGNH hydrolase due to the presence of highly conserve motif, Ser-Gly-Asn-His in four conserved blocks I, II, III, and V, respectively. X-ray quality crystal of EstJ15 was obtained from optimized formulation containing 0.10 M ammonium sulphate, 0.15 M sodium cacodylate trihydrate pH 6.5, and 20% PEG 8000. The crystal structure of EstJ15 was solved at 1.38 Å with one molecule per asymmetric unit. The structure exhibits α/β hydrolase fold and shared low amino acid sequence identity of 23% with the passenger domain of the autotransporter EstA of Pseudomonas aeruginosa. The active site is located at the centre of the structure, formed a narrow tunnel that hinder long substrates to be catalysed which was proven by the protein-ligand docking analysis. This study facilitates the understanding of high substrate specificity of EstJ15 and provide insights on its catalytic mechanism.
    Matched MeSH terms: Esterases/metabolism
  4. Loganathan K, Moriya S, Parhar IS
    Zebrafish, 2018 10;15(5):473-483.
    PMID: 30102584 DOI: 10.1089/zeb.2018.1594
    Ambient light and temperature affect reproductive function by regulating kisspeptin and gonadotrophin-releasing hormone (GnRH) in vertebrates. Melatonin and melatonin receptors, as well as the two-pore domain K+ channel-related K+ (TREK) channels, are affected by light and/or temperature; therefore, these molecules could modulate kisspeptin and GnRH against ambient light and temperature. In this study, we investigated the effect of light and temperature, which affect melatonin levels in gene expression levels of TREK channels, kisspeptin, and GnRH. We first investigated the effects of different light and temperature conditions on brain melatonin concentrations by ELISA. Fish were exposed to either constant darkness, constant light, high temperature (35°C), or low temperature (20°C) for 72 h. Brain melatonin levels were significantly high under constant darkness and high temperature. We further investigated the effects of high brain melatonin levels by constant darkness and high temperature on gene expression levels of melatonin receptors (mt1, mt2, and mel1c), TREK channels (trek1b, trek2a, and trek2b), gnrh3, and kiss2 in the adult zebrafish brain by real-time polymerase chain reaction. Fish were exposed to constant darkness or elevated temperatures (35°C) for 72 h. trek2a, kiss2, and gnrh3 levels were increased under constant darkness. High temperature decreased gene expression levels of mt1, mt2, mel1c, and gnrh3 in the preoptic area, whereas other genes remained unchanged. Melatonin receptors, TREK channels, gnrh3, and kiss2 responded differently under high melatonin conditions. The melatonin receptors and the TREK channels could play roles in the regulation of reproduction by environmental cues, especially ambient light and temperature.
    Matched MeSH terms: Brain/metabolism*; Gonadotropin-Releasing Hormone/metabolism; Zebrafish/metabolism*; Potassium Channels/metabolism*; Zebrafish Proteins/metabolism*; Receptor, Melatonin, MT1/metabolism*; Kisspeptins/metabolism
  5. Dzaki N, Wahab W, Azlan A, Azzam G
    Biochem Biophys Res Commun, 2018 10 20;505(1):106-112.
    PMID: 30241946 DOI: 10.1016/j.bbrc.2018.09.074
    CTP Synthase (CTPS) is a metabolic enzyme that is recognized as a catalyst for nucleotide, phospholipid and sialoglycoprotein production. Though the structural characteristics and regulatory mechanisms of CTPS are well-understood, little is known regarding the extent of its involvement during the early developmental stages of vertebrates. Zebrafish carries two CTPS genes, annotated as ctps1a and ctps1b. Phylogenetic analyses show that both genes had diverged from homologues in the ancestral Actinopterygii, Oreochromis niloticus. Conservation of common CTPS-catalytic regions further establishes that both proteins are likely to be functionally similar to hsaCTPS. Here, we show that ctps1a is more critical throughout the initial period of embryonic development than ctps1b. The effects of concurrent partial knockdown are dependent on ctps1a vs ctps1b dosage ratios. When these are equally attenuated, abnormal phenotypes acquired prior to the pharyngula period disappear in hatchlings (48hpf); however, if either gene is more attenuated than the other, these only become more pronounced in advanced stages. Generally, disruption to normal ctps1a or ctps1b expression levels by morpholinos culminates in the distortion of the early spinal column as well as multiple-tissue oedema. Other effects include slower growth rates, increased mortality rates and impaired structural formation of the young fish's extremities. Embryos grown in DON, a glutamine-analogue drug and CTPS antagonist, also exhibit similar characteristics, thus strengthening the validity of the morpholino-induced phenotypes observed. Together, our results demonstrate the importance of CTPS for the development of zebrafish embryos, as well as a disparity in activity and overall importance amongst isozymes.
    Matched MeSH terms: Body Fluids/metabolism*; Embryo, Nonmammalian/metabolism; Isoenzymes/metabolism; Spine/metabolism*; Zebrafish/metabolism; Carbon-Nitrogen Ligases/metabolism; Zebrafish Proteins/metabolism
  6. Salleh MSM, Ibrahim MF, Roslan AM, Abd-Aziz S
    Sci Rep, 2019 05 15;9(1):7443.
    PMID: 31092836 DOI: 10.1038/s41598-019-43718-1
    Simultaneous saccharification and fermentation (SSF) with delayed yeast extract feeding (DYEF) was conducted in a 2-L bioreactor equipped with in-situ recovery using a gas stripping in order to enhance biobutanol production from lignocellulosic biomass of oil palm empty fruit bunch (OPEFB). This study showed that 2.88 g/L of biobutanol has been produced from SSF with a similar yield of 0.23 g/g as compared to separate hydrolysis and fermentation (SHF). An increase of 42% of biobutanol concentration was observed when DYEF was introduced in the SSF at 39 h of fermentation operation. Biobutanol production was further enhanced up to 11% with a total improvement of 72% when in-situ recovery using a gas stripping was implemented to reduce the solvents inhibition in the bioreactor. In overall, DYEF and in-situ recovery were able to enhance biobutanol production in SSF.
    Matched MeSH terms: Ethanol/metabolism*
  7. Tang ACI, Stoy PC, Hirata R, Musin KK, Aeries EB, Wenceslaus J, et al.
    Sci Total Environ, 2019 Sep 15;683:166-174.
    PMID: 31132697 DOI: 10.1016/j.scitotenv.2019.05.217
    Tropical rainforests control the exchange of water and energy between the land surface and the atmosphere near the equator and thus play an important role in the global climate system. Measurements of latent (LE) and sensible heat exchange (H) have not been synthesized across global tropical rainforests to date, which can help place observations from individual tropical forests in a global context. We measured LE and H for four years in a tropical peat forest ecosystem in Sarawak, Malaysian Borneo using eddy covariance, and hypothesize that the study ecosystem will exhibit less seasonal variability in turbulent fluxes than other tropical ecosystems as soil water is not expected to be limiting in a tropical forested wetland. LE and H show little variability across seasons in the study ecosystem, with LE values on the order of 11 MJ m-2 day and H on the order of 3 MJ m-2 day-1. Annual evapotranspiration (ET) did not differ among years and averaged 1579 ± 47 mm year-1. LE exceeded characteristic values from other tropical rainforest ecosystems in the FLUXNET2015 database with the exception of GF-Guy near coastal French Guyana, which averaged 8-11 MJ m-2 day-1. The Bowen ratio (Bo) in tropical rainforests in the FLUXNET2015 database either exhibited little seasonal trend, one seasonal peak, or two peaks. Volumetric water content (VWC) and VPD explained a trivial amount of the variability of LE and Bo in some of the tropical rainforests including the study ecosystem, but were strong controls in others, suggesting differences in stomatal regulation and/or the partitioning between evaporation and transpiration. Results demonstrate important differences in the seasonal patterns in water and energy exchange across different tropical rainforest ecosystems that need to be understood to quantify how ongoing changes in tropical rainforest extent will impact the global climate system.
    Matched MeSH terms: Energy Metabolism*
  8. Wang H, Lakshmipriya T, Chen Y, Gopinath SCB
    Biomed Res Int, 2019;2019:2807123.
    PMID: 31080815 DOI: 10.1155/2019/2807123
    Cervical cancer is a life-threatening complication, appearing as the uncontrolled growth of abnormal cells in the lining of the cervix. Every year, increasing numbers of cervical cancer cases are reported worldwide. Different identification strategies were proposed to detect cervical cancer at the earlier stages using various biomarkers. Squamous cell carcinoma antigen (SCC-Ag) is one of the potential biomarkers for this diagnosis. Nanomaterial-based detection systems were shown to be efficient with different clinical biomarkers. In this study, we have demonstrated strontium oxide-modified interdigitated electrode (IDE) fabrication by the sol-gel method and characterized by scanning electron microscopy and high-power microscopy. Analysis of the bare devices indicated the reproducibility with the fabrication, and further pH scouting on the device revealed that the reliability of the working pH ranges from 3 to 9. The sensing surface was tested to detect SCC-Ag against its specific antibody; the detection limit was found to be 10 pM, and the sensitivity was in the range between 1 and 10 pM as calculated by 3σ. The specificity experiment was carried out using major proteins from human serum, such as albumin and globulin. SCC-Ag was shown to be selectively detected on the strontium oxide-modified IDE surface.
    Matched MeSH terms: Antigens, Neoplasm/metabolism; Carcinoma, Squamous Cell/metabolism; Uterine Cervical Neoplasms/metabolism; Cervix Uteri/metabolism; Neoplasm Recurrence, Local/metabolism; Biomarkers, Tumor/metabolism*; Serpins/metabolism
  9. Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al.
    Cell Rep, 2019 01 29;26(5):1112-1127.e9.
    PMID: 30699343 DOI: 10.1016/j.celrep.2019.01.023
    The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.
    Matched MeSH terms: Apolipoproteins E/metabolism; Neurons/metabolism*; Repressor Proteins/metabolism*; Amyloid beta-Peptides/metabolism; Nuclear Lamina/metabolism; Induced Pluripotent Stem Cells/metabolism*; Neural Stem Cells/metabolism
  10. Wong SK, Chin KY, Ima-Nirwana S
    Phytomedicine, 2020 Jul 15;73:152892.
    PMID: 30902523 DOI: 10.1016/j.phymed.2019.152892
    BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders.

    PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders.

    METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed.

    RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/β-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties.

    CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

    Matched MeSH terms: Musculoskeletal Diseases/metabolism; NF-kappa B/metabolism; Phosphatidylinositol 3-Kinases/metabolism; p38 Mitogen-Activated Protein Kinases/metabolism; beta Catenin/metabolism; Transcription Factor RelA/metabolism; RANK Ligand/metabolism
  11. Mahamad Maifiah MH, Velkov T, Creek DJ, Li J
    Methods Mol Biol, 2019;1946:321-328.
    PMID: 30798566 DOI: 10.1007/978-1-4939-9118-1_28
    Acinetobacter baumannii is rapidly emerging as a multidrug-resistant pathogen responsible for nosocomial infections including pneumonia, bacteremia, wound infections, urinary tract infections, and meningitis. Metabolomics provides a powerful tool to gain a system-wide snapshot of cellular biochemical networks under defined conditions and has been increasingly applied to bacterial physiology and drug discovery. Here we describe an optimized sample preparation method for untargeted metabolomics studies in A. baumannii. Our method provides a significant recovery of intracellular metabolites to demonstrate substantial differences in global metabolic profiles among A. baumannii strains.
    Matched MeSH terms: Acinetobacter baumannii/metabolism*
  12. Fong MJB, Loy ACM, Chin BLF, Lam MK, Yusup S, Jawad ZA
    Bioresour Technol, 2019 Oct;289:121689.
    PMID: 31252316 DOI: 10.1016/j.biortech.2019.121689
    In the present study, catalytic pyrolysis of Chlorella vulgaris biomass was conducted to analyse the kinetic and thermodynamic performances through thermogravimetric approach. HZSM-5 zeolite, limestone (LS), bifunctional HZSM-5/LS were used as catalysts and the experiments were heated from 50 to 900 °C at heating rates of 10-100 °C/min. Iso-conversional model-free methods such as Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), Starink's, and Vyazovkin (V) were employed to evaluate the kinetic parameters meanwhile the thermodynamic parameters were determined by using FWO and KAS methods. The calculated EA values of non-catalytic and catalytic pyrolysis of HZSM-5 zeolite, LS, and bifunctional HZSM-5/LS were determined to be in the range of 156.16-158.10 kJ/mol, 145.26-147.84 kJ/mol, 138.81-142.06 kJ/mol, and 133.26 kJ/mol respectively. The results have shown that catalytic pyrolysis with the presence of bifunctional HZSM-5/LS resulted to a lower average EA and ΔH compared to HZSM-5, and LS which indicated less energy requirement in the process.
    Matched MeSH terms: Chlorella vulgaris/metabolism*
  13. Shrivastava G, Bakshi HA, Aljabali AA, Mishra V, Hakkim FL, Charbe NB, et al.
    Curr Drug Deliv, 2020;17(2):101-111.
    PMID: 31906837 DOI: 10.2174/1567201817666200106104332
    BACKGROUND: Nucleus targeted drug delivery provides several opportunities for the treatment of fatal diseases such as cancer. However, the complex nucleocytoplasmic barriers pose significant challenges for delivering a drug directly and efficiently into the nucleus. Aptamers representing singlestranded DNA and RNA qualify as next-generation highly advanced and personalized medicinal agents that successfully inhibit the expression of certain proteins; possess extraordinary gene-expression for manoeuvring the diseased cell's fate with negligible toxicity. In addition, the precisely directed aptamers to the site of action present a tremendous potential to reach the nucleus by escaping the ensuing barriers to exhibit a better drug activity and gene expression.

    OBJECTIVE: This review epigrammatically highlights the significance of targeted drug delivery and presents a comprehensive description of the principal barriers faced by the nucleus targeted drug delivery paradigm and ensuing complexities thereof. Eventually, the progress of nucleus targeting with nucleic acid aptamers and success achieved so far have also been reviewed.

    METHODS: Systematic literature search was conducted of research published to date in the field of nucleic acid aptamers.

    CONCLUSION: The review specifically points out the contribution of individual aptamers as the nucleustargeting agent rather than aptamers in conjugated form.

    Matched MeSH terms: Cell Nucleus/metabolism*
  14. Albitar O, Harun SN, Zainal H, Ibrahim B, Sheikh Ghadzi SM
    Biomed Res Int, 2020;2020:9872936.
    PMID: 31998804 DOI: 10.1155/2020/9872936
    Background and Objective: Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models.

    Methods: A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded.

    Results: Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models.

    Conclusions: Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.

    Matched MeSH terms: Cytochrome P-450 CYP1A2/metabolism*
  15. Mohd Yusof H, Mohamad R, Zaidan UH, Rahman NA
    Microb Cell Fact, 2020 Jan 15;19(1):10.
    PMID: 31941498 DOI: 10.1186/s12934-020-1279-6
    BACKGROUND: The use of microorganisms in the biosynthesis of zinc oxide nanoparticles (ZnO NPs) has recently emerged as an alternative to chemical and physical methods due to its low-cost and eco-friendly method. Several lactic acid bacteria (LAB) have developed mechanisms in tolerating Zn2+ through prevention against their toxicity and the production of ZnO NPs. The LAB's main resistance mechanism to Zn2+ is highly depended on the microorganisms' ability to interact with Zn2+ either through biosorption or bioaccumulation processes. Besides the inadequate studies conducted on biosynthesis with the use of zinc-tolerant probiotics, the understanding regarding the mechanism involved in this process is not clear. Therefore, this study determines the features of probiotic LAB strain TA4 related to its resistance to Zn2+. It also attempts to illustrate its potential in creating a sustainable microbial cell nanofactory of ZnO NPs.

    RESULTS: A zinc-tolerant probiotic strain TA4, which was isolated from local fermented food, was selected based on the principal component analysis (PCA) with the highest score of probiotic attributes. Based on the 16S rRNA gene analysis, this strain was identified as Lactobacillus plantarum strain TA4, indicating its high resistance to Zn2+ at a maximum tolerable concentration (MTC) value of 500 mM and its capability of producing ZnO NPs. The UV-visible spectroscopy analysis proved the formations of ZnO NPs through the notable absorption peak at 380 nm. It was also found from the dynamic light scattering (DLS) analysis that the Z-average particle size amounted to 124.2 nm with monodisperse ZnO NPs. Studies on scanning electron microscope (SEM), energy-dispersive X-ray (EDX) spectroscopy, and Fourier-transform infrared spectroscopy (FT-IR) revealed that the main mechanisms in ZnO NPs biosynthesis were facilitated by the Zn2+ biosorption ability through the functional groups present on the cell surface of strain TA4.

    CONCLUSIONS: The strong ability of zinc-tolerant probiotic of L. plantarum strain TA4 to tolerate high Zn2+ concentration and to produce ZnO NPs highlights the unique properties of these bacteria as a natural microbial cell nanofactory for a more sustainable and eco-friendly practice of ZnO NPs biosynthesis.

    Matched MeSH terms: Lactobacillus plantarum/metabolism*
  16. Lim PS, Loke CF, Ho YW, Tan HY
    J Appl Microbiol, 2020 Nov;129(5):1374-1388.
    PMID: 32356362 DOI: 10.1111/jam.14678
    AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai).

    METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lactobacillus plantarum TAR4 showed the highest cholesterol reduction ability (48·01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration. Rats fed with high-cholesterol diet supplemented with Lact. plantarum TAR4 showed significant reduction in serum total cholesterol (29·55%), serum triglyceride (45·31%) and liver triglyceride (23·44%) as compared to high-cholesterol diet (HCD) group. There was a significant increment in faecal triglyceride (45·83%) and faecal total bile acid (384·95%) as compared to HCD group.

    CONCLUSIONS: The findings showed that probiotic Lact. plantarum TAR4 supplementation reduced the absorption of bile acids for enterohepatic recycling and increased the catabolism of cholesterol to bile acids and not by suppressing the rate of cholesterol synthesis.

    SIGNIFICANCE AND IMPACT OF STUDY: Probiotic supplements could provide a new nonpharmacological alternative to reduce cardiovascular risk factors.

    Matched MeSH terms: Bile Acids and Salts/metabolism; Cholesterol/metabolism*; Triglycerides/metabolism; Lactobacillus plantarum/metabolism; Lipid Metabolism/drug effects; Lactobacillales/metabolism
  17. Nguyen DDN, Zain SM, Kamarulzaman MH, Low TY, Chilian WM, Pan Y, et al.
    Am J Physiol Heart Circ Physiol, 2021 10 01;321(4):H770-H783.
    PMID: 34506226 DOI: 10.1152/ajpheart.00058.2021
    Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
    Matched MeSH terms: DNA-Binding Proteins/metabolism; Muscle, Smooth, Vascular/metabolism*; Transcription Factors/metabolism; Myocytes, Smooth Muscle/metabolism*; MicroRNAs/metabolism*; Exosomes/metabolism*; Endosomal Sorting Complexes Required for Transport/metabolism
  18. Tahir Ul Qamar M, Ahmad S, Khan A, Mirza MU, Ahmad S, Abro A, et al.
    Comput Biol Med, 2021 11;138:104929.
    PMID: 34655900 DOI: 10.1016/j.compbiomed.2021.104929
    Cholera is a severe small intestine bacterial disease caused by consumption of water and food contaminated with Vibrio cholera. The disease causes watery diarrhea leading to severe dehydration and even death if left untreated. In the past few decades, V. cholerae has emerged as multidrug-resistant enteric pathogen due to its rapid ability to adapt in detrimental environmental conditions. This research study aimed to design inhibitors of a master virulence gene expression regulator, HapR. HapR is critical in regulating the expression of several set of V. cholera virulence genes, quorum-sensing circuits and biofilm formation. A blind docking strategy was employed to infer the natural binding tendency of diverse phytochemicals extracted from medicinal plants by exposing the whole HapR structure to the screening library. Scoring function criteria was applied to prioritize molecules with strong binding affinity (binding energy 
    Matched MeSH terms: Bacterial Proteins/metabolism
  19. Thuy DTB, Nguyen A, Khoo KS, Chew KW, Cnockaert M, Vandamme P, et al.
    Bioengineered, 2021 12;12(1):54-62.
    PMID: 33350336 DOI: 10.1080/21655979.2020.1857626
    This study was aimed to identify and optimize the culture conditions for gamma-aminobutyric acid (GABA) production by a lactic acid bacterium strain isolated from mam nem, a fermented fish sauce. Among the six isolates obtained from mam nem, the MN12 had the most potent GABA-producing capability. The strain was then identified to be Pedioccocus pentosaceus by employing MALDI-TOF-MS and phenylalanyl-tRNA synthase sequencing methods. The initial cell density of 5.106 CFU/mL, monosodium glutamate concentration of 60 mM, initial pH of 7, temperature of 45°C and cultivation time of 72 h were found to be the optimal culture conditions for highest production of GABA, reaching 27.9 ± 0.42 mM, by this strain. The cultivation conditions for GABA production by P. pentosaceus MN12 have been successfully optimized, providing a foundation for the development of fermented foods enriched with GABA.
    Matched MeSH terms: Pediococcus pentosaceus/metabolism*
  20. Chai TT, Koh JA, Wong CC, Sabri MZ, Wong FC
    Molecules, 2021 Dec 06;26(23).
    PMID: 34885982 DOI: 10.3390/molecules26237396
    Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.
    Matched MeSH terms: Antineoplastic Agents/metabolism*; Antioxidants/metabolism*; Peroxidase/metabolism; Peptides/metabolism*; Plant Extracts/metabolism*; Xanthine Oxidase/metabolism; Kelch-Like ECH-Associated Protein 1/metabolism
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