Displaying publications 981 - 1000 of 9211 in total

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  1. pink1, atp13a2 and uchl1 expressions are affected by inflammation in the brain
    Moriya S, Tan VP, Yee AK, Parhar IS
    Neurosci Lett, 2019 08 24;708:134330.
    PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330
    In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.
    Matched MeSH terms: Brain/metabolism*; Encephalitis/metabolism*; Proton-Translocating ATPases/metabolism*; Protein-Serine-Threonine Kinases/metabolism*; Zebrafish Proteins/metabolism*; Ubiquitin Thiolesterase/metabolism*
  2. High PHA density fed-batch cultivation strategies for 4HB-rich P(3HB-co-4HB) copolymer production by transformant Cupriavidus malaysiensis USMAA1020
    Norhafini H, Huong KH, Amirul AA
    Int J Biol Macromol, 2019 Mar 15;125:1024-1032.
    PMID: 30557643 DOI: 10.1016/j.ijbiomac.2018.12.121
    P(3HB-co-4HB) with a high 4HB monomer composition was previously successfully produced using the transformant Cupriavidus malaysiensis USMAA1020 containing an additional copy of the PHA synthase gene. In this study, high PHA density fed-batch cultivation strategies were developed for such 4HB-rich P(3HB-co-4HB). The pulse, constant and mixed feeding strategies resulted in high PHA accumulation, with a PHA content of 74-92 wt% and 4HB monomer composition of 92-99 mol%. The pulse-feed of carbon and nitrogen resulted in higher PHA concentration (30.7 g/L) than carbon alone (22.3 g/L), suggesting that a trace amount of nitrogen is essential to support cell density for PHA accumulation. Constant feeding was found to be a more feasible strategy than mixed feeding, since the latter caused a drastic fluctuation in the C/N ratio, as evidenced by higher biomass formation indicating more carbon flux towards the competitive TCA pathway. A two-times carbon and nitrogen pulse feeding was the most optimal strategy achieving 92 wt% accommodation of the total biomass, with the highest PHA concentration (46 g/L) and yield (Yp/x) of 11.5 g/g. The strategy has kept the C/N at optimal ratio during the active PHA-producing phase. This is the first report of the production of high PHA density for 4HB-rich P(3HB-co-4HB).
    Matched MeSH terms: Acyltransferases/metabolism*; Bacterial Proteins/metabolism*; Carbon/metabolism; Hydroxybutyrates/metabolism*; Nitrogen/metabolism; Polyesters/metabolism*
  3. Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture model
    Elendran S, Muniyandy S, Lee WW, Palanisamy UD
    Food Funct, 2019 Feb 20;10(2):602-615.
    PMID: 30566155 DOI: 10.1039/c8fo01927d
    Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.
    Matched MeSH terms: Adenocarcinoma/metabolism*; Colonic Neoplasms/metabolism*; Ellagic Acid/metabolism; Gallic Acid/metabolism; Glucosides/metabolism*; Hydrolyzable Tannins/metabolism*
  4. Fulltext Organ-Specific Analysis of Morus alba Using a Gel-Free/Label-Free Proteomic Technique
    Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654535 DOI: 10.3390/ijms20020365
    Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.
    Matched MeSH terms: Antioxidants/metabolism; Flavonoids/metabolism; Plant Proteins/metabolism; Plant Leaves/metabolism; Morus/metabolism*; Secondary Metabolism
  5. Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study
    Mohamad Pakarul Razy NH, Wan Abdul Rahman WF, Win TT
    Asian Pac J Cancer Prev, 2019 Jan 25;20(1):277-282.
    PMID: 30678450
    Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in
    thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR).
    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of
    PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management
    of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF
    and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on
    paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in
    the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and
    VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of
    PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference
    of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no
    significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1
    was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF
    and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid
    extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2
    showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more
    significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a
    promising prospect for tumour management in thyroid carcinoma.
    Matched MeSH terms: Carcinoma, Papillary/metabolism*; Hyperplasia/metabolism*; Thyroid Gland/metabolism; Vascular Endothelial Growth Factor Receptor-1/metabolism; Vascular Endothelial Growth Factor Receptor-2/metabolism; Vascular Endothelial Growth Factor A/metabolism*
  6. Fulltext Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
    Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.
    Molecules, 2020 Jul 28;25(15).
    PMID: 32731323 DOI: 10.3390/molecules25153403
    Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
    Matched MeSH terms: Melanoma, Experimental/metabolism*; Neoplasm Proteins/metabolism; Monophenol Monooxygenase/metabolism; Zebrafish/metabolism*; Zebrafish Proteins/metabolism; Microphthalmia-Associated Transcription Factor/metabolism
  7. Development of microbial spoilage and lipid and protein oxidation in rabbit meat
    Nakyinsige K, Sazili AQ, Aghwan ZA, Zulkifli I, Goh YM, Abu Bakar F, et al.
    Meat Sci, 2015 Oct;108:125-31.
    PMID: 26115345 DOI: 10.1016/j.meatsci.2015.05.029
    This experiment aimed to determine microbial spoilage and lipid and protein oxidation during aerobic refrigerated (4°C) storage of rabbit meat. Forty male New Zealand white rabbits were slaughtered according to the Halal slaughter procedure. The hind limbs were used for microbial analysis while the Longissimus lumborum m. was used for determination of lipid and protein oxidation. Bacterial counts generally increased with aging time and the limit for fresh meat (10(8)cfu/g) was reached at d 7 postmortem. Significant differences in malondialdehyde content were observed after 3d of storage. The thiol concentration significantly decreased with increase in aging time. The band intensities of myosin heavy chain and troponin T significantly reduced with increased refrigerated storage while actin remained relatively stable. This study thus proposes protein oxidation as a potential deteriorative change in refrigerated rabbit meat along with microbial spoilage and lipid oxidation.
    Matched MeSH terms: Actins/metabolism; Sulfhydryl Compounds/metabolism; Myosin Heavy Chains/metabolism; Troponin T/metabolism; Lipid Metabolism*
  8. The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes
    Chew BL, Fisk ID, Fray R, Tucker GA, Bodi Z, Ferguson A, et al.
    Plant Cell Rep, 2017 Jan;36(1):81-87.
    PMID: 27662835 DOI: 10.1007/s00299-016-2058-z
    KEY MESSAGE: This study highlights the changes in umami-related nucleotide and glutamate levels when the AMP deaminase gene was elevated in transgenic tomato. Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway.
    Matched MeSH terms: Adenosine Monophosphate/metabolism; AMP Deaminase/metabolism*; Fruit/metabolism; Guanosine Monophosphate/metabolism; Lycopersicon esculentum/metabolism; Glutamic Acid/metabolism
  9. The kinetic properties of the glutamate dehydrogenase of Teladorsagia circumcincta and their significance for the lifestyle of the parasite
    Muhamad N, Simcock DC, Pedley KC, Simpson HV, Brown S
    Comp Biochem Physiol B Biochem Mol Biol, 2011 Jun;159(2):71-7.
    PMID: 21296180 DOI: 10.1016/j.cbpb.2011.01.008
    Like other nematodes, both L(3) and adult Teladosagia circumcincta secrete or excrete NH(3)/NH(4)(+), but the reactions involved in the production are unclear. Glutamate dehydrogenase is a significant source NH(3)/NH(4)(+) in some species, but previous reports indicate that the enzyme is absent from L(3)Haemonchus contortus. We show that glutamate dehydrogenase was active in both L(3) and adult T. circumcincta. The apparent K(m)s of the L(3) enzyme differed from those of the adult enzyme, the most significant of these being the increase in the K(m) for NH(4)(+) from 18mM in L(3) to 49mM in adults. The apparent V(max) of the oxidative deamination reaction was greater than that of the reductive reaction in L(3), but this was reversed in adults. The activity of the oxidative reaction of the L(3) enzyme was not affected by adenine nucleotides, but that of the reductive reaction was stimulated significantly by either ADP or ATP. The L(3) enzyme was more active with NAD(+) than it was with NADP(+), although the activities supported by NADH and NADPH were similar at saturating concentrations. While the activity of the oxidative reaction was sufficient to account for the NH(3)/NH(4)(+) efflux we have previously reported, the reductive amination reaction was likely to be more active.
    Matched MeSH terms: Adenosine Diphosphate/metabolism; Adenosine Triphosphate/metabolism; Ammonia/metabolism*; Glutamate Dehydrogenase/metabolism*; NAD/metabolism; NADP/metabolism
  10. Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities
    Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
    Matched MeSH terms: Eosinophils/metabolism; Lung/metabolism; Respiration Disorders/metabolism; Respiratory Tract Diseases/metabolism; Cytokines/metabolism; Th2 Cells/metabolism
  11. Fulltext New Recombinant Cold-Adapted and Organic Solvent Tolerant Lipase from Psychrophilic Pseudomonas sp. LSK25, Isolated from Signy Island Antarctica
    Salwoom L, Raja Abd Rahman RNZ, Salleh AB, Mohd Shariff F, Convey P, Mohamad Ali MS
    Int J Mol Sci, 2019 Mar 13;20(6).
    PMID: 30871178 DOI: 10.3390/ijms20061264
    In recent years, studies on psychrophilic lipases have become an emerging area of research in the field of enzymology. The study described here focuses on the cold-adapted organic solvent tolerant lipase strain Pseudomonas sp. LSK25 isolated from Signy Station, South Orkney Islands, maritime Antarctic. Strain LSK25 lipase was successfully cloned, sequenced, and over-expressed in an Escherichia coli system. Sequence analysis revealed that the lipase gene of Pseudomonas sp. LSK25 consists of 1432 bp, lacks an N-terminal signal peptide and encodes a mature protein consisting of 476 amino acids. The recombinant LSK25 lipase was purified by single-step purification using Ni-Sepharose affinity chromatography and had a molecular mass of approximately 65 kDa. The final recovery and purification fold were 44% and 1.3, respectively. The LSK25 lipase was optimally active at 30 °C and at pH 6. Stable lipolytic activity was reported between temperatures of 5⁻30 °C and at pH 6⁻8. A significant enhancement of lipolytic activity was observed in the presence of Ca2+ ions, the organic lipids of rice bran oil and coconut oil, a synthetic C12 ester and a wide range of water immiscible organic solvents. Overall, lipase strain LSK25 is a potentially desirable candidate for biotechnological application, due to its stability at low temperatures, across a range of pH and in organic solvents.
    Matched MeSH terms: Bacterial Proteins/metabolism; Escherichia coli/metabolism; Lipase/metabolism*; Pseudomonas/metabolism*; Recombinant Proteins/metabolism*; Solvents/metabolism*
  12. Genetically-modified human mesenchymal stem cells to express erythropoietin enhances differentiation into retinal photoreceptors: An in-vitro study
    Ding SLS, Koh AE, Kumar S, Ali Khan MS, Alzahrani B, Mok PL
    J. Photochem. Photobiol. B, Biol., 2019 Jun;195:33-38.
    PMID: 31060031 DOI: 10.1016/j.jphotobiol.2019.04.008
    Dysfunctional or death of retinal photoreceptors is an irreversible phenomenon that is closely associated with a broad range of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), resulting in successive loss of visual function and blindness. In search for viable treatment for retinal degenerative diseases, mesenchymal stem cells (MSCs) has demonstrated promising therapeutic capabilities to repair and replace damaged photoreceptor cells in both in vitro and in vivo conditions. Nevertheless, the dearth of MSC differentiation capacity into photoreceptors has limited its use in cell replacement therapy. Erythropoietin (EPO) has vital role in early neural retinal cell differentiation and demonstrated rescue potential on dying photoreceptor cells. Hence, we aimed to evaluate the differentiation capacity of MSCs into photoreceptor cells in the presence of human EPO protein. We derived the MSC from human Wharton's jelly of umbilical cord and transduced the cells with lentivirus particles encoding EPO and green fluorescent protein (GFP) as reporter gene. The transduced cells were selectively cultured and induced to differentiate into photoreceptors by exposing to photoreceptor differentiation cocktail. Our preliminary results showed that transduced cells exposed to induction medium had an enhanced differentiation capacity when compared to non-transduced cells. Our results demonstrated a novel strategy to increase the yield of in vitro photoreceptor differentiation and may be potentially useful in improving the efficiency of stem cell transplantation for ocular disorders.
    Matched MeSH terms: Erythropoietin/metabolism*; Rhodopsin/metabolism; Trans-Activators/metabolism; Homeodomain Proteins/metabolism; Photoreceptor Cells, Vertebrate/metabolism*; Mesenchymal Stromal Cells/metabolism*
  13. ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors
    Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM
    Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
    PMID: 31030477
    Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
    common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
    degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
    therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
    factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
    Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
    obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
    ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
    using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
    ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
    positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
    the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
    with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
    [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
    type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
    The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
    prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).
    Matched MeSH terms: Adenocarcinoma/metabolism; Carcinoma, Squamous Cell/metabolism; Uterine Cervical Neoplasms/metabolism; Membrane Proteins/metabolism*; Biomarkers, Tumor/metabolism*; ADAM Proteins/metabolism*
  14. A century old renin-angiotensin system still grows with endless possibilities: AT1 receptor signaling cascades in cardiovascular physiopathology
    Balakumar P, Jagadeesh G
    Cell Signal, 2014 Oct;26(10):2147-60.
    PMID: 25007996 DOI: 10.1016/j.cellsig.2014.06.011
    Ang II, the primary effector pleiotropic hormone of the renin-angiotensin system (RAS) cascade, mediates physiological control of blood pressure and electrolyte balance through its action on vascular tone, aldosterone secretion, renal sodium absorption, water intake, sympathetic activity and vasopressin release. It affects the function of most of the organs far beyond blood pressure control including heart, blood vessels, kidney and brain, thus, causing both beneficial and deleterious effects. However, the protective axis of the RAS composed of ACE2, Ang (1-7), alamandine, and Mas and MargD receptors might oppose some harmful effects of Ang II and might promote beneficial cardiovascular effects. Newly identified RAS family peptides, Ang A and angioprotectin, further extend the complexities in understanding the cardiovascular physiopathology of RAS. Most of the diverse actions of Ang II are mediated by AT1 receptors, which couple to classical Gq/11 protein and activate multiple downstream signals, including PKC, ERK1/2, Raf, tyrosine kinases, receptor tyrosine kinases (EGFR, PDGF, insulin receptor), nuclear factor κB and reactive oxygen species (ROS). Receptor activation via G12/13 stimulates Rho-kinase, which causes vascular contraction and hypertrophy. The AT1 receptor activation also stimulates G protein-independent signaling pathways such as β-arrestin-mediated MAPK activation and Src-JAK/STAT. AT1 receptor-mediated activation of NADPH oxidase releases ROS, resulting in the activation of pro-inflammatory transcription factors and stimulation of small G proteins such as Ras, Rac and RhoA. The components of the RAS and the major Ang II-induced signaling cascades of AT1 receptors are reviewed.
    Matched MeSH terms: Angiotensin II/metabolism; Arrestins/metabolism; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism; Receptor, Angiotensin, Type 2/metabolism; Receptor, Angiotensin, Type 1/metabolism*; STAT Transcription Factors/metabolism
  15. Epithelial membrane antigen (EMA) or MUC1 expression in monocytes and monoblasts
    Leong CF, Raudhawati O, Cheong SK, Sivagengei K, Noor Hamidah H
    Pathology, 2003 Oct;35(5):422-7.
    PMID: 14555387
    AIMS: Epithelial membrane antigen (EMA) or MUC1 belongs to a heterogeneous group of heavily glycosylated proteins and is expressed in most normal and epithelial neoplastic cells. EMA is also expressed in plasma cells, anaplastic large cell lymphoma (Ki-1 antigen), malignant histiocytosis and erythroleukaemia. In 1996, Cheong et al. (Hematology 1996; 1: 223) demonstrated the positive expression of EMA in monoblasts. Since there were very few useful markers for differentiating subtypes of acute myeloid leukaemia with a monocytic component from the those without, a study was conducted to evaluate the prevalence of EMA expression and its relationship with known markers for monocytic-macrophage lineage (CD11c, CD14 and intracellular CD68) in monocytes and monoblasts.

    METHODS: EMA detection was performed by flow cytometry in monocytes and monoblasts. EMA expression was compared with other known markers of monocytic-macrophage lineage (CD11c, CD14 and intracellular CD68). Samples of purified monocytes were obtained from 20 healthy volunteers. Twenty-two cases of monocytic AML (M4 and M5) were studied and controls were selected from 20 cases of acute lymphoblastic leukaemia (ALL) and 18 cases of non-monocytic AML (M0, M1, M2, M3, and M7).

    RESULTS: EMA was shown to be expressed strongly on the surface of all purified monocytes. EMA expression was observed on blast cells in 18/22 (81.8%) cases of AML M4 and M5, but not in that of non-monocytic AML or ALL. In this study EMA monoclonal antibody has demonstrated a strong association (P<0.001) with all the other known markers of monocytic-macrophage lineage in acute leukaemia subtypes. EMA had also shown 100% specificity and 81.8% sensitivity in the diagnosis of AML M4 and M5.

    CONCLUSIONS: The monoclonal antibody EMA (clone E29) is a useful marker in the classification of acute myeloid leukaemia and can be used as a supplementary analysis for the diagnosis of acute leukemia with monocytic involvement.

    Matched MeSH terms: Bone Marrow Cells/metabolism; Leukemia, Monocytic, Acute/metabolism; Monocytes/metabolism*; Stem Cells/metabolism*; Antigens, CD/metabolism; Mucin-1/metabolism*
  16. Fulltext The Role of Inflammation in the Pathogenesis of Osteoarthritis
    Chow YY, Chin KY
    Mediators Inflamm, 2020;2020:8293921.
    PMID: 32189997 DOI: 10.1155/2020/8293921
    A joint is the point of connection between two bones in our body. Inflammation of the joint leads to several diseases, including osteoarthritis, which is the concern of this review. Osteoarthritis is a common chronic debilitating joint disease mainly affecting the elderly. Several studies showed that inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. This stimulates the release of early-stage inflammatory cytokines like interleukin-1 beta (IL-1β), which in turn induces the activation of signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinase (MAPK). These events, in turn, generate more inflammatory molecules. Subsequently, collagenase like matrix metalloproteinases-13 (MMP-13) will degrade the extracellular matrix. As a result, anatomical and physiological functions of the joint are altered. This review is aimed at summarizing the previous studies highlighting the involvement of inflammation in the pathogenesis of osteoarthritis.
    Matched MeSH terms: Inflammation/metabolism*; NF-kappa B/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Mitogen-Activated Protein Kinases/metabolism; Matrix Metalloproteinase 13/metabolism; Interleukin-1beta/metabolism
  17. Kinetic behaviour of free lipase and mica-based immobilized lipase catalyzing the synthesis of sugar esters
    Zaidan UH, Abdul Rahman MB, Othman SS, Basri M, Abdulmalek E, Rahman RN, et al.
    Biosci Biotechnol Biochem, 2011;75(8):1446-50.
    PMID: 21821960
    The utilization of natural mica as a biocatalyst support in kinetic investigations is first described in this study. The formation of lactose caprate from lactose sugar and capric acid, using free lipase (free-CRL) and lipase immobilized on nanoporous mica (NER-CRL) as a biocatalyst, was evaluated through a kinetic study. The apparent kinetic parameters, K(m) and V(max), were determined by means of the Michaelis-Menten kinetic model. The Ping-Pong Bi-Bi mechanism with single substrate inhibition was adopted as it best explains the experimental findings. The kinetic results show lower K(m) values with NER-CRL than with free-CRL, indicating the higher affinity of NER-CRL towards both substrates at the maximum reaction velocity (V(max,app)>V(max)). The kinetic parameters deduced from this model were used to simulate reaction rate data which were in close agreement with the experimental values.
    Matched MeSH terms: Bacterial Proteins/metabolism*; Decanoic Acids/metabolism; Enzymes, Immobilized/metabolism*; Esters/metabolism*; Lactose/metabolism*; Lipase/metabolism*
  18. Fulltext The possible potential therapeutic targets for drug induced gingival overgrowth
    Subramani T, Rathnavelu V, Alitheen NB
    Mediators Inflamm, 2013;2013:639468.
    PMID: 23690667 DOI: 10.1155/2013/639468
    Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth.
    Matched MeSH terms: Fibroblasts/metabolism; Platelet-Derived Growth Factor/metabolism; Transforming Growth Factor beta/metabolism; Gingival Overgrowth/metabolism*; Endothelin-1/metabolism; Connective Tissue Growth Factor/metabolism
  19. Role of the cell envelope in the antibacterial activities of polymyxin B and polymyxin B nonapeptide against Escherichia coli
    Sahalan AZ, Dixon RA
    Int J Antimicrob Agents, 2008 Mar;31(3):224-7.
    PMID: 18083010
    The role of membrane permeabilisation and disruption in the mechanism of action of some polymyxin analogues against Gram-negative organisms is contentious. The effects of polymyxin B (PMB) and its analogue polymyxin B nonapeptide (PMBN) on Escherichia coli envelopes should correlate, but previous work by other workers suggests that PMBN has a different mode of action. This study has reassessed the biochemical techniques used previously and has shown that, in contrast to previous studies, PMBN (a well-characterised antibacterial synergist) readily releases periplasmic proteins and lipopolysaccharide from treated E. coli at subinhibitory concentrations in normal physiological buffer conditions. We conclude that, when tested with appropriate methodology, PMBN closely correlates with the early effects of PMB on the cell envelope of E. coli and this study shows that it is now consistent with the accepted interactions of membrane-active agents against Gram-negative cells.
    Matched MeSH terms: Cephalosporins/metabolism; Lipopolysaccharides/metabolism; Nitrophenols/metabolism; Polysaccharides, Bacterial/metabolism; Escherichia coli Proteins/metabolism; Periplasmic Proteins/metabolism
  20. Resistance against tumour necrosis factor α apoptosis by the cellular prion protein is cell-specific for oral, colon and kidney cancer cell lines
    Yap YH, Say YH
    Cell Biol Int, 2012 Mar 1;36(3):273-7.
    PMID: 21980981 DOI: 10.1042/CBI20110088
    Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFα (tumour necrosis factor α) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFα apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells.
    Matched MeSH terms: Carcinoma, Renal Cell/metabolism*; Colonic Neoplasms/metabolism*; Kidney Neoplasms/metabolism*; Mouth Neoplasms/metabolism*; Tumor Necrosis Factor-alpha/metabolism*; PrPC Proteins/metabolism*
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