Displaying publications 2601 - 2620 of 9219 in total

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  1. Malik R, Paudel KR, Manandhar B, De Rubis G, Shen J, Mujwar S, et al.
    Pathol Res Pract, 2023 Nov;251:154895.
    PMID: 37879146 DOI: 10.1016/j.prp.2023.154895
    PURPOSE: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE'RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro.

    METHODS: The antioxidant and anti-inflammatory activity of DE'RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE'RAAQSIN were investigated via qPCR.

    RESULTS: LPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-α, IL-1β, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE'RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-α, IL-1β, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components.

    CONCLUSIONS: We propose DE'RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE'RAAQSIN.

    Matched MeSH terms: Inflammation/metabolism; Nitric Oxide/metabolism; Tumor Necrosis Factor-alpha/metabolism; Interleukin-6/metabolism; NF-kappa B/metabolism; Reactive Oxygen Species/metabolism
  2. Kuah MK, Jaya-Ram A, Shu-Chien AC
    PMID: 27421235 DOI: 10.1016/j.cbpa.2016.07.007
    There is a lack of understanding on how the environment and trophic niche affect the capability of long-chain polyunsaturated fatty acids (LC-PUFA) in freshwater carnivorous teleost. In this present study, we isolated and functionally characterised a fatty acyl desaturase (Fads) from the striped snakehead Channa striata. Sequence comparison and phylogenetic analysis suggested a Fads2 protein that is closely related to previously characterised Fads2 proteins from freshwater carnivorous and marine herbivorous fish species. We further demonstrated the capacity of Δ6 and Δ5 desaturation activities for this particular desaturase, with highest activities towards the conversion of omega-3 (n-3) polyunsaturated fatty acids (PUFA). Low Δ4 desaturation activity was also detected, although the significance of this at a physiological level remains to be studied. The expression of this striped snakehead Δ6/Δ5 fads2 gene was highest in brain, followed by liver and intestine. In liver, diet fortified with high LC-PUFA concentration impeded the expression of Δ6/Δ5 fads2 gene compared to vegetable oil (VO) based diets. The discovery of Δ6/Δ5 Fads2 desaturase here complements the previous discovery of a Δ4 Fads2 desaturase and an Elovl5 elongase, lending proof to the existence of all the required enzymatic machinery to biosynthesise LC-PUFA from C18 PUFA in a freshwater carnivorous species.
    Matched MeSH terms: Dietary Fats, Unsaturated/metabolism; Fatty Acids, Unsaturated/metabolism; Perciformes/metabolism*; Fish Proteins/metabolism*; Fatty Acid Desaturases/metabolism*; Linoleoyl-CoA Desaturase/metabolism
  3. Mohamad M, Loy SL, Lim PY, Wang Y, Soo KL, Mohamed HJJ
    PMID: 29895806 DOI: 10.3390/ijerph15061250
    The prevalence of childhood obesity is increasing at an alarming rate in Malaysia. Metabolic changes during pregnancy are critical to the development of infant adiposity, due to imbalanced adipokines production. Hence, we aimed to investigate the association of maternal serum and breast milk adipokines with infant adiposity development. The study was conducted from April 2010 until December 2012. A total of 155 healthy pregnant mothers aged 19 to 40 years were recruited during the first and second trimester in Kelantan, Malaysia. Data consisted of maternal sociodemographic details, anthropometry and clinical biochemistry analysis; and the infant’s anthropometry and feeding patterns. Maternal fasting serum and breast milk samples were analysed for adiponectin and leptin levels. Data collection was performed in the second and third trimester of pregnancy, and continued with follow-up visits at birth, two, six, and 12 months postpartum. Multiple linear regression (MLR) analyses were performed to examine the associations between maternal serum and breast milk adiponectin and leptin and infant adiposity development. MLR models showed that, in the first year, as maternal serum and breast milk adiponectin increased, infant weight, BMI-for-age Z scores and abdominal circumference significantly decreased (p < 0.05). Maternal serum and/or breast milk adiponectin was associated with first-year infant adiposity development.
    Matched MeSH terms: Milk, Human/metabolism*; Pregnancy Trimester, Second/metabolism*; Pregnancy Trimester, Third/metabolism*; Biomarkers/metabolism; Leptin/metabolism; Adiponectin/metabolism*
  4. Kadir FA, Kassim NM, Abdulla MA, Yehye WA
    BMC Complement Altern Med, 2013 Oct 30;13:294.
    PMID: 24499255 DOI: 10.1186/1472-6882-13-294
    BACKGROUND: Oxidative stress due to abnormal induction of reactive oxygen species (ROS) molecules is believed to be involved in the etiology of many diseases. Evidences suggest that ROS is involved in nephrotoxicity through frequent exposure to industrial toxic agents such as thioacetamide (TAA). The current investigation was designed to explore the possible protective effects of the leaves of Vitex negundo(VN) extract against TAA-induced nephrotoxicity in rats.

    METHODS: Twenty four Sprague Dawleyrats were divided into four groups: (A) Normal control, (B) TAA (0.03% w/v in drinking water), (C) VN100 (VN 100 mg/kg + TAA) and (D) VN300 (VN 300 mg/kg + TAA). Blood urea and serum creatinine levels were measured,supraoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels of renal tissue were assayed. Histopathological analysis together with the oxidative stress nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in kidney sections were examined in all experimental groups.

    RESULTS: Blood urea and serum creatinine levels were increased in TAA group as a result of the nephrotoxicity compared to the VN100 and VN300 groups where, the levels were significantly decreased (p 

    Matched MeSH terms: Catalase/metabolism; Kidney/metabolism; Kidney Diseases/metabolism; Malondialdehyde/metabolism; Superoxide Dismutase/metabolism; Reactive Oxygen Species/metabolism
  5. Hamid AA, Idrus RB, Saim AB, Sathappan S, Chua KH
    Clinics (Sao Paulo), 2012;67(2):99-106.
    PMID: 22358233
    OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction.

    MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction.

    RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN) was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction.

    CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adipose-derived stem cells was most prominent after one week of chondrogenic induction.

    Matched MeSH terms: Collagen/metabolism*; Elastin/metabolism; Biomarkers/metabolism; Chondrocytes/metabolism*; SOX9 Transcription Factor/metabolism; Mesenchymal Stromal Cells/metabolism*
  6. Teh HF, Neoh BK, Hong MP, Low JY, Ng TL, Ithnin N, et al.
    PLoS One, 2013;8(4):e61344.
    PMID: 23593468 DOI: 10.1371/journal.pone.0061344
    To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes.
    Matched MeSH terms: Amino Acids/metabolism; Fruit/metabolism*; Malates/metabolism; Biomarkers/metabolism; Citric Acid/metabolism; Arecaceae/metabolism*
  7. Iezhitsa I, Agarwal R, Saad SD, Zakaria FK, Agarwal P, Krasilnikova A, et al.
    Mol Vis, 2016;22:734-47.
    PMID: 27440992
    PURPOSE: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.

    METHODS: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging. At the end of the experimental period, the lenses were removed and subjected to analysis for oxidative and nitrosative stress, Ca and Mg levels, ATP content, Ca(2+)-ATPase, Na(+),K(+)-ATPase, and calpain II activities.

    RESULTS: The LTau and LMgT groups showed significantly lower opacity index values at all time points compared to the corresponding vehicle groups (p<0.001). However, the opacity index in the LMgT group was lower than that in the LTau group (p<0.05). Significantly reduced oxidative and nitrosative stress was observed in the LTau and LMgT groups. The lens Ca/Mg ratio in LMgT group was decreased by 1.15 times compared to that in the LVh group. Calpain II activity in the LMgT group was decreased by 13% compared to the LVh group. The ATP level and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly increased in the LMgT group compared to the LVh group (p<0.05).

    CONCLUSIONS: Topical liposomal MgT delays cataractogenesis in galactose-fed rats by maintaining the lens mineral homeostasis and reducing lenticular oxidative and nitrosative stress.

    Matched MeSH terms: Sodium-Potassium-Exchanging ATPase/metabolism; Calcium/metabolism; Calpain/metabolism; Cataract/metabolism; Lens, Crystalline/metabolism; Magnesium/metabolism
  8. Lau YY, How KY, Yin WF, Chan KG
    Microbiologyopen, 2018 Dec;7(6):e00610.
    PMID: 29982994 DOI: 10.1002/mbo3.610
    In gram-negative bacteria, bacterial communication or quorum sensing (QS) is achieved using common signaling molecules known as N-acyl homoserine lactones (AHL). We have previously reported the genome of AHL-producing bacterium, Enterobacter asburiae strain L1. In silico analysis of the strain L1 genome revealed the presence of a pair of luxI/R genes responsible for AHL-type QS, designated as easIR. In this work, the 639 bp luxI homolog, encoding 212 amino acids, have been cloned and overexpressed in Escherichia coli BL21 (DE3)pLysS. The purified protein (~25 kDa) shares high similarity to several members of the LuxI family among different E asburiae strains. Our findings showed that the heterologously expressed EasI protein has activated violacein production by AHL biosensor Chromobacterium violaceum CV026 as the wild-type E. asburiae. The mass spectrometry analysis showed the production of N-butanoyl homoserine lactone and N-hexanoyl homoserine lactone from induced E. coli harboring the recombinant EasI, suggesting that EasI is a functional AHL synthase. E. asburiae strain L1 was also shown to possess biofilm-forming characteristic activity using crystal violet binding assay. This is the first report on cloning and characterization of the luxI homolog from E. asburiae.
    Matched MeSH terms: Bacterial Proteins/metabolism; Enterobacter/metabolism; Repressor Proteins/metabolism; Transcription Factors/metabolism; Trans-Activators/metabolism; Acyl-Butyrolactones/metabolism*
  9. Kumar MR, Yeap SK, Mohamad NE, Abdullah JO, Masarudin MJ, Khalid M, et al.
    BMC Complement Med Ther, 2021 Jul 01;21(1):183.
    PMID: 34210310 DOI: 10.1186/s12906-021-03358-3
    BACKGROUND: In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.

    METHODS: This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.

    RESULTS: The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.

    CONCLUSIONS: This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.

    Matched MeSH terms: Brain/metabolism; Kidney/metabolism; Liver/metabolism; Nitric Oxide/metabolism; Spleen/metabolism; Superoxide Dismutase/metabolism
  10. Sayyed AH, Raymond B, Ibiza-Palacios MS, Escriche B, Wright DJ
    Appl Environ Microbiol, 2004 Dec;70(12):7010-7.
    PMID: 15574894
    The long-term usefulness of Bacillus thuringiensis Cry toxins, either in sprays or in transgenic crops, may be compromised by the evolution of resistance in target insects. Managing the evolution of resistance to B. thuringiensis toxins requires extensive knowledge about the mechanisms, genetics, and ecology of resistance genes. To date, laboratory-selected populations have provided information on the diverse genetics and mechanisms of resistance to B. thuringiensis, highly resistant field populations being rare. However, the selection pressures on field and laboratory populations are very different and may produce resistance genes with distinct characteristics. In order to better understand the genetics, biochemical mechanisms, and ecology of field-evolved resistance, a diamondback moth (Plutella xylostella) field population (Karak) which had been exposed to intensive spraying with B. thuringiensis subsp. kurstaki was collected from Malaysia. We detected a very high level of resistance to Cry1Ac; high levels of resistance to B. thuringiensis subsp. kurstaki Cry1Aa, Cry1Ab, and Cry1Fa; and a moderate level of resistance to Cry1Ca. The toxicity of Cry1Ja to the Karak population was not significantly different from that to a standard laboratory population (LAB-UK). Notable features of the Karak population were that field-selected resistance to B. thuringiensis subsp. kurstaki did not decline at all in unselected populations over 11 generations in laboratory microcosm experiments and that resistance to Cry1Ac declined only threefold over the same period. This finding may be due to a lack of fitness costs expressed by resistance strains, since such costs can be environmentally dependent and may not occur under ordinary laboratory culture conditions. Alternatively, resistance in the Karak population may have been near fixation, leading to a very slow increase in heterozygosity. Reciprocal genetic crosses between Karak and LAB-UK populations indicated that resistance was autosomal and recessive. At the highest dose of Cry1Ac tested, resistance was completely recessive, while at the lowest dose, it was incompletely dominant. A direct test of monogenic inheritance based on a backcross of F1 progeny with the Karak population suggested that resistance to Cry1Ac was controlled by a single locus. Binding studies with 125I-labeled Cry1Ab and Cry1Ac revealed greatly reduced binding to brush border membrane vesicles prepared from this field population.
    Matched MeSH terms: Bacillus thuringiensis/metabolism; Bacterial Proteins/metabolism*; Bacterial Toxins/metabolism*; Endotoxins/metabolism*; Microvilli/metabolism; Moths/metabolism
  11. Kim Y, Griffin JM, Nor MNM, Zhang J, Freestone PS, Danesh-Meyer HV, et al.
    Neurotherapeutics, 2017 Oct;14(4):1148-1165.
    PMID: 28560708 DOI: 10.1007/s13311-017-0536-9
    The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
    Matched MeSH terms: Adenosine Triphosphate/metabolism; Encephalitis/metabolism; Lysosomes/metabolism; Nerve Tissue Proteins/metabolism; Connexins/metabolism; Connexin 43/metabolism*
  12. Mohd Zahari MA, Ariffin H, Mokhtar MN, Salihon J, Shirai Y, Hassan MA
    J Biomed Biotechnol, 2012;2012:125865.
    PMID: 23133311 DOI: 10.1155/2012/125865
    Factors influencing poly(3-hydroxybutyrate) P(3HB) production by Cupriavidus necator CCUG52238(T) utilizing oil palm frond (OPF) juice were clarified in this study. Effects of initial medium pH, agitation speed, and ammonium sulfate (NH(4))(2)SO(4) concentration on the production of P(3HB) were investigated in shake flasks experiments using OPF juice as the sole carbon source. The highest P(3HB) content was recorded at pH 7.0, agitation speed of 220 rpm, and (NH(4))(2)SO(4) concentration at 0.5 g/L. By culturing the wild-type strain of C. necator under the aforementioned conditions, the cell dry weight (CDW) and P(3HB) content obtained were 9.31 ± 0.13 g/L and 45 ± 1.5 wt.%, respectively. This accounted for 40% increment of P(3HB) content compared to the nonoptimized condition. In the meanwhile, the effect of dissolved oxygen tension (DOT) on P(3HB) production was investigated in a 2-L bioreactor. Highest CDW (11.37 g/L) and P(3HB) content (44 wt.%) were achieved when DOT level was set at 30%. P(3HB) produced from OPF juice had a tensile strength of 40 MPa and elongation at break of 8% demonstrated that P(3HB) produced from renewable and cheap carbon source is comparable to those produced from commercial substrate.
    Matched MeSH terms: Hydroxybutyrates/metabolism*; Plant Extracts/metabolism*; Plant Oils/metabolism*; Polyesters/metabolism*; Plant Leaves/metabolism*; Cupriavidus necator/metabolism*
  13. Ling AP, Tan KP, Hussein S
    J Zhejiang Univ Sci B, 2013 Jul;14(7):621-31.
    PMID: 23825148 DOI: 10.1631/jzus.B1200135
    OBJECTIVE: Labisia pumila var. alata, commonly known as 'Kacip Fatimah' or 'Selusuh Fatimah' in Southeast Asia, is traditionally used by members of the Malay community because of its post-partum medicinal properties. Its various pharmaceutical applications cause an excessive harvesting and lead to serious shortage in natural habitat. Thus, this in vitro propagation study investigated the effects of different plant growth regulators (PGRs) on in vitro leaf and stem explants of L. pumila.

    METHODS: The capabilities of callus, shoot, and root formation were evaluated by culturing both explants on Murashige and Skoog (MS) medium supplemented with various PGRs at the concentrations of 0, 1, 3, 5, and 7 mg/L.

    RESULTS: Medium supplemented with 3 mg/L indole-3-butyric acid (IBA) showed the optimal callogenesis from both leaf and stem explants with (72.34 ± 19.55)% and (70.40 ± 14.14)% efficacy, respectively. IBA was also found to be the most efficient PGR for root induction. A total of (50.00 ± 7.07)% and (77.78 ± 16.47)% of root formation were obtained from the in vitro stem and leaf explants after being cultured for (26.5 ± 5.0) and (30.0 ± 8.5) d in the medium supplemented with 1 and 3 mg/L of IBA, respectively. Shoot formation was only observed in stem explant, with the maximum percentage of formation ((100.00 ± 0.00)%) that was obtained in 1 mg/L zeatin after (11.0 ± 2.8) d of culture.

    CONCLUSIONS: Callus, roots, and shoots can be induced from in vitro leaf and stem explants of L. pumila through the manipulation of types and concentrations of PGRs.

    Matched MeSH terms: Kinetin/metabolism; Naphthalenes/metabolism; Plant Growth Regulators/metabolism*; Plants, Medicinal/metabolism; Zeatin/metabolism; Acetic Acid/metabolism
  14. Haghani A, Mehrbod P, Safi N, Kadir FA, Omar AR, Ideris A
    BMC Complement Altern Med, 2017 Jan 05;17(1):22.
    PMID: 28056926 DOI: 10.1186/s12906-016-1498-x
    Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized.
    Matched MeSH terms: Antiviral Agents/metabolism; Biological Factors/metabolism; Influenza, Human/metabolism; Actin Cytoskeleton/metabolism; rab5 GTP-Binding Proteins/metabolism; rhoA GTP-Binding Protein/metabolism
  15. Ghoussaini M, Edwards SL, Michailidou K, Nord S, Cowper-Sal Lari R, Desai K, et al.
    Nat Commun, 2014 Sep 23;4:4999.
    PMID: 25248036 DOI: 10.1038/ncomms5999
    GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
    Matched MeSH terms: Breast Neoplasms/metabolism; Chromatin/metabolism; Chromosomes, Human, Pair 2/metabolism; RNA, Messenger/metabolism*; Insulin-Like Growth Factor Binding Protein 5/metabolism; Hepatocyte Nuclear Factor 3-alpha/metabolism
  16. Agarwal R, Agarwal P
    Exp Biol Med (Maywood), 2017 Feb;242(4):374-383.
    PMID: 27798117 DOI: 10.1177/1535370216675065
    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.
    Matched MeSH terms: Transcription Factors/metabolism; Matrix Metalloproteinase 9/metabolism; Mitogen-Activated Protein Kinases/metabolism*; Proto-Oncogene Proteins c-akt/metabolism*; Sirtuin 1/metabolism; Phosphatidylinositol 3-Kinase/metabolism*
  17. Sultan MT, Butt MS, Karim R, Ahmed W, Kaka U, Ahmad S, et al.
    PMID: 26385559 DOI: 10.1186/s12906-015-0853-7
    Nigella sativa is an important component of several traditional herbal preparations in various countries. It finds its applications in improving overall health and boosting immunity. The current study evaluated the role of fixed and essential oil of Nigella sativa against potassium bromate induced oxidative stress with special reference to modulation of glutathione redox enzymes and myeloperoxidase.
    Matched MeSH terms: Glutathione/metabolism; Glutathione Peroxidase/metabolism; Glutathione Reductase/metabolism; Glutathione Transferase/metabolism; Peroxidase/metabolism; Tocopherols/metabolism
  18. Sabri S, Rahman RN, Leow TC, Basri M, Salleh AB
    Protein Expr Purif, 2009 Dec;68(2):161-6.
    PMID: 19679187 DOI: 10.1016/j.pep.2009.08.002
    Thermostable lipases are important biocatalysts, showing many interesting properties with industrial applications. Previously, a thermophilic Bacillus sp. strain L2 that produces a thermostable lipase was isolated. In this study, the gene encoding for mature thermostable L2 lipase was cloned into a Pichia pastoris expression vector. Under the control of the methanol-inducible alcohol oxidase (AOX) promoter, the recombinant L2 lipase was secreted into the culture medium driven by the Saccharomyces cerevisiae alpha-factor signal sequence. After optimization the maximum recombinant lipase activity achieved in shake flasks was 125 U/ml. The recombinant 44.5 kDa L2 lipase was purified 1.8-fold using affinity chromatography with 63.2% yield and a specific activity of 458.1 U/mg. Its activity was maximal at 70 degrees C and pH 8.0. Lipase activity increased 5-fold in the presence of Ca2+. L2 lipase showed a preference for medium to long chain triacylglycerols (C(10)-C(16)), corn oil, olive oil, soybean oil, and palm oil. Stabilization at high temperature and alkaline pH as well as its broad substrate specificity offer great potential for application in various industries that require high temperature operations.
    Matched MeSH terms: Bacillus/metabolism; Calcium/metabolism*; Lipase/metabolism; Metals/metabolism; Plant Oils/metabolism; Recombinant Fusion Proteins/metabolism
  19. Al Batran R, Al-Bayaty F, Abdulla MA, Al-Obaidi MM, Hajrezaei M, Hassandarvish P, et al.
    J Gastroenterol Hepatol, 2013 Aug;28(8):1321-9.
    PMID: 23611708 DOI: 10.1111/jgh.12229
    BACKGROUND AND AIM: Corchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats.

    METHODS: The rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations.

    RESULTS: Compared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole.

    CONCLUSIONS: Our study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats.

    Matched MeSH terms: Gastric Mucosa/metabolism; Gastrointestinal Hemorrhage/metabolism; Malondialdehyde/metabolism; Superoxide Dismutase/metabolism; HSP70 Heat-Shock Proteins/metabolism; bcl-2-Associated X Protein/metabolism
  20. Salamah MF, Ravishankar D, Kodji X, Moraes LA, Williams HF, Vallance TM, et al.
    Blood Adv, 2018 Nov 13;2(21):2973-2985.
    PMID: 30413433 DOI: 10.1182/bloodadvances.2018021758
    Platelet-associated complications including thrombosis, thrombocytopenia, and hemorrhage are commonly observed during various inflammatory diseases such as sepsis, inflammatory bowel disease, and psoriasis. Despite the reported evidence on numerous mechanisms/molecules that may contribute to the dysfunction of platelets, the primary mechanisms that underpin platelet-associated complications during inflammatory diseases are not fully established. Here, we report the discovery of formyl peptide receptor 2, FPR2/ALX, in platelets and its primary role in the development of platelet-associated complications via ligation with its ligand, LL37. LL37 acts as a powerful endogenous antimicrobial peptide, but it also regulates innate immune responses. We demonstrate the impact of LL37 in the modulation of platelet reactivity, hemostasis, and thrombosis. LL37 activates a range of platelet functions, enhances thrombus formation, and shortens the tail bleeding time in mice. By utilizing a pharmacological inhibitor and Fpr2/3 (an ortholog of human FPR2/ALX)-deficient mice, the functional dependence of LL37 on FPR2/ALX was determined. Because the level of LL37 is increased in numerous inflammatory diseases, these results point toward a critical role for LL37 and FPR2/ALX in the development of platelet-related complications in such diseases. Hence, a better understanding of the clinical relevance of LL37 and FPR2/ALX in diverse pathophysiological settings will pave the way for the development of improved therapeutic strategies for a range of thromboinflammatory diseases.
    Matched MeSH terms: Cyclic AMP/metabolism; Blood Platelets/metabolism; Calcium/metabolism; Antimicrobial Cationic Peptides/metabolism; Receptors, Formyl Peptide/metabolism; Receptors, Lipoxin/metabolism
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