Displaying publications 2621 - 2640 of 9219 in total

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  1. The capacity for long-chain polyunsaturated fatty acid synthesis in a carnivorous vertebrate: Functional characterisation and nutritional regulation of a Fads2 fatty acyl desaturase with Δ4 activity and an Elovl5 elongase in striped snakehead (Channa striata)
    Kuah MK, Jaya-Ram A, Shu-Chien AC
    Biochim. Biophys. Acta, 2015 Mar;1851(3):248-60.
    PMID: 25542509 DOI: 10.1016/j.bbalip.2014.12.012
    The endogenous production of long-chain polyunsaturated fatty acids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh. We also functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the ∆4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores.
    Matched MeSH terms: Acetyltransferases/metabolism*; Brain/metabolism; Escherichia coli/metabolism; Liver/metabolism; Muscles/metabolism; Perciformes/metabolism*; Recombinant Proteins/metabolism; Fish Proteins/metabolism*; Fatty Acid Desaturases/metabolism*
  2. Fulltext Characterisation of Drosophila Ubx CPTI000601 and hth CPTI000378 protein trap lines
    Choo SW, Beh CY, Russell S, White R
    ScientificWorldJournal, 2014;2014:191535.
    PMID: 25389534 DOI: 10.1155/2014/191535
    In Drosophila, protein trap strategies provide powerful approaches for the generation of tagged proteins expressed under endogenous control. Here, we describe expression and functional analysis to evaluate new Ubx and hth protein trap lines generated by the Cambridge Protein Trap project. Both protein traps exhibit spatial and temporal expression patterns consistent with the reported endogenous pattern in the embryo. In imaginal discs, Ubx-YFP is expressed throughout the haltere and 3rd leg imaginal discs, while Hth-YFP is expressed in the proximal regions of haltere and wing discs but not in the pouch region. The Ubx (CPTI000601) line is semilethal as a homozygote. No T3/A1 to T2 transformations were observed in the embryonic cuticle or the developing midgut. The homozygous survivors, however, exhibit a weak haltere phenotype with a few wing-like marginal bristles on the haltere capitellum. Although hth (CPTI000378) is completely lethal as a homozygote, the hth (CPTI000378) /hth (C1) genotype is viable. Using a hth deletion (Df(3R)BSC479) we show that hth (CPTI000378) /Df(3R)BSC479 adults are phenotypically normal. No transformations were observed in hth (CPTI000378), hth (CPTI000378) /hth (C1), or hth (CPTI000378) /Df(3R)BSC479 embryonic cuticles. We have successfully characterised the Ubx-YFP and Hth-YFP protein trap lines demonstrating that the tagged proteins show appropriate expression patterns and produce at least partially functional proteins.
    Matched MeSH terms: Bacterial Proteins/metabolism; Drosophila melanogaster/metabolism; Intestinal Mucosa/metabolism; Luminescent Proteins/metabolism; Recombinant Fusion Proteins/metabolism; Transcription Factors/metabolism; Homeodomain Proteins/metabolism; Drosophila Proteins/metabolism; Imaginal Discs/metabolism
  3. Fulltext DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury
    Dongworth RK, Mukherjee UA, Hall AR, Astin R, Ong SB, Yao Z, et al.
    Cell Death Dis, 2014 Feb 27;5:e1082.
    PMID: 24577080 DOI: 10.1038/cddis.2014.41
    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
    Matched MeSH terms: Adenosine Triphosphate/metabolism; Calcium/metabolism; Mitochondria, Heart/metabolism; Myocardial Infarction/metabolism; Myocardium/metabolism*; Myocardial Reperfusion Injury/metabolism; Oncogene Proteins/metabolism*; Myocytes, Cardiac/metabolism; Mitochondrial Membrane Transport Proteins/metabolism
  4. Fulltext The phosphorylation of endogenous Nedd4-2 In Na(+)-absorbing human airway epithelial cells
    Ismail NA, Baines DL, Wilson SM
    Eur J Pharmacol, 2014 Jun 05;732:32-42.
    PMID: 24657276 DOI: 10.1016/j.ejphar.2014.03.005
    Neural precursor cell expressed, developmentally down-regulated protein 4-2 (Nedd4-2) mediates the internalisation / degradation of epithelial Na(+) channel subunits (α-, β- and γ-ENaC). Serum / glucocorticoid inducible kinase 1 (SGK1) and protein kinase A (PKA) both appear to inhibit this process by phosphorylating Nedd4-2-Ser(221), -Ser(327) and -Thr(246). This Nedd4-2 inactivation process is thought to be central to the hormonal control of Na(+) absorption. The present study of H441 human airway epithelial cells therefore explores the effects of SGK1 and / or PKA upon the phosphorylation / abundance of endogenous Nedd4-2; the surface expression of ENaC subunits, and electrogenic Na(+) transport. Effects on Nedd4-2 phosphorylation/abundance and the surface expression of ENaC were monitored by western analysis, whilst Na(+) absorption was quantified electrometrically. Acutely (20min) activating PKA in glucocorticoid-deprived (24h) cells increased the abundance of Ser(221)-phosphorylated, Ser(327)-phosphorylated and total Nedd4-2 without altering the abundance of Thr(246)-phosphorylated Nedd4-2. Activating PKA under these conditions did not cause a co-ordinated increase in the surface abundance of α-, β- and γ-ENaC and had only a very small effect upon electrogenic Na(+) absorption. Activating PKA (20min) in glucocorticoid-treated (0.2µM dexamethasone, 24h) cells, on the other hand, increased the abundance of Ser(221)-, Ser(327)- and Thr(246)-phosphorylated and total Nedd4-2; increased the surface abundance of α-, β- and γ-ENaC and evoked a clear stimulation of Na(+) transport. Chronic glucocorticoid stimulation therefore appears to allow cAMP-dependent control of Na(+) absorption by facilitating the effects of PKA upon the Nedd4-2 and ENaC subunits.
    Matched MeSH terms: Epithelial Cells/metabolism*; Sodium/metabolism; Protein-Serine-Threonine Kinases/metabolism; Cyclic AMP-Dependent Protein Kinases/metabolism; Immediate-Early Proteins/metabolism; Respiratory Mucosa/metabolism*; Ubiquitin-Protein Ligases/metabolism*; Epithelial Sodium Channels/metabolism; Endosomal Sorting Complexes Required for Transport/metabolism*
  5. Fulltext Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa
    Tor YS, Yazan LS, Foo JB, Armania N, Cheah YK, Abdullah R, et al.
    BMC Complement Altern Med, 2014;14:55.
    PMID: 24524627 DOI: 10.1186/1472-6882-14-55
    Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.
    Matched MeSH terms: Adenocarcinoma/metabolism; Breast Neoplasms/metabolism; Catalase/metabolism; RNA, Messenger/metabolism; Superoxide Dismutase/metabolism; NF-kappa B/metabolism; p38 Mitogen-Activated Protein Kinases/metabolism; Apoptosis Regulatory Proteins/metabolism; Proto-Oncogene Proteins c-akt/metabolism
  6. Fulltext Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways
    Looi CY, Moharram B, Paydar M, Wong YL, Leong KH, Mohamad K, et al.
    BMC Complement Altern Med, 2013;13:166.
    PMID: 23837445 DOI: 10.1186/1472-6882-13-166
    Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called "Kayakalp", commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.
    Matched MeSH terms: Melanoma/metabolism*; Mitochondria/metabolism*; Skin Neoplasms/metabolism; Tumor Suppressor Protein p53/metabolism*; NF-kappa B/metabolism*; Reactive Oxygen Species/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism*; Caspases/metabolism; Cytochromes c/metabolism
  7. Fulltext In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell
    Chong HZ, Rahmat A, Yeap SK, Md Akim A, Alitheen NB, Othman F, et al.
    BMC Complement Altern Med, 2012;12:35.
    PMID: 22471785 DOI: 10.1186/1472-6882-12-35
    Strobilanthes crispus has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of S. crispus is still unclear.
    Matched MeSH terms: Adenocarcinoma/metabolism; Breast Neoplasms/metabolism; Hormones/metabolism; Mitochondria/metabolism; Tumor Suppressor Protein p53/metabolism; Cytochromes c/metabolism; X-Linked Inhibitor of Apoptosis Protein/metabolism; Caspase 3/metabolism; Caspase 7/metabolism
  8. Growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of Lactobacillus upon ultraviolet radiation
    Yeo SK, Liong MT
    Int J Food Sci Nutr, 2012 Nov;63(7):821-31.
    PMID: 22264088 DOI: 10.3109/09637486.2011.652942
    The objective of this study was to evaluate the effects of ultraviolet (UV) radiation (UVB; 90 J/m²) on growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of L. casei FTDC 2113. UV radiation significantly enhanced (P < 0.05) the growth of parent cells in mannitol-soymilk fermented at 37°C for 24 h. This had led to an enhanced intracellular and extracellular β-glucosidase activity with a subsequent increase in bioconversion of isoflavones in mannitol-soymilk (P < 0.05). UV radiation also promoted (P < 0.05) the tolerance of parent cells towards acidic condition (pH 2 and 3) and intestinal bile salts (oxgall, taurocholic and cholic acid). In addition, parent treated cells also exhibited better (P < 0.05) adhesion ability to mucin and antimicrobial activity compared to that of the control. All these positive effects of UV radiation were only prevalent in the parent cells without inheritance by first, second and third passage of cells. Although temporary, our results suggested that UV radiation could enhance the bioactive and probiotic potentials of L. casei FTDC 2113, and thus could be applied for the production of probiotic products with enhanced bioactivity.
    Matched MeSH terms: Bacterial Proteins/metabolism; beta-Glucosidase/metabolism; Bile Acids and Salts/metabolism; Gastric Mucins/metabolism; Isoflavones/metabolism*; Lactobacillus casei/metabolism; Mannitol/metabolism; Probiotics/metabolism*; Soy Milk/metabolism
  9. The expression of Bcl-2 by proliferating cells varies in different categories of B-cell lymphoma
    Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.
    Histopathology, 2010 Apr;56(5):617-26.
    PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x
    To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.
    Matched MeSH terms: Lymphoma, Follicular/metabolism; Biomarkers, Tumor/metabolism*; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism; Lymphoma, B-Cell/metabolism*; Lymphoma, Large B-Cell, Diffuse/metabolism; Lymphoma, B-Cell, Marginal Zone/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism*; Ki-67 Antigen/metabolism; Lymphoma, Mantle-Cell/metabolism
  10. Citalopram (antidepressant) administration causes sexual dysfunction in male mice through RF-amide related peptide in the dorsomedial hypothalamus
    Soga T, Wong DW, Clarke IJ, Parhar IS
    Neuropharmacology, 2010 Jul-Aug;59(1-2):77-85.
    PMID: 20381503 DOI: 10.1016/j.neuropharm.2010.03.018
    Citalopram is the most potent selective serotonin reuptake inhibitor (SSRI) which is used as an antidepressant but causes sexual dysfunction. Whether citalopram induced sexual dysfunction is a result of gonadotropin-releasing hormone (GnRH), kisspeptin or RF-amide related peptide (RFRP) alteration is unknown. In this study, we tested mice for sexual behavior after vehicle (0.9% NaCl) and citalopram treatment (5 mg/kg) daily for 1 day (acute) and 21 or 28 days (chronic). Effects of acute and chronic treatments on neuronal numbers and mRNA expression of GnRH, kisspeptin and RFRP were measured. In addition, RFRP fiber projections to preoptic (POA)-GnRH neurons were analyzed using double-label immunohistochemistry. The expression of 14 different serotonin receptor types mRNA was examined in immunostained laser dissected single RFRP neurons in the dorsomedial hypothalamus (DMH), however only 11 receptors types were identified. Acute citalopram treatment did not affect sexual behavior, whereas, the total duration of intromission was reduced with chronic treatment. There was no effect in the expression of kisspeptin (neuronal numbers and mRNA) in the anteroventral periventricular nucleus and the arcuate nucleus and expression of GnRH (neuronal numbers and mRNA) in the POA after citalopram treatment. However, RFRP neuronal numbers in the DMH and fiber projections to the POA were significantly increased after chronic citalopram treatment, which suggests citalopram induced inhibition of sexual behavior involves the modulation of RFRP through serotonin receptors in the DMH.
    Matched MeSH terms: Brain/metabolism; Hypothalamus/metabolism; Gonadotropin-Releasing Hormone/metabolism; Neural Pathways/metabolism; Neurons/metabolism; Neuropeptides/metabolism*; RNA, Messenger/metabolism; Sexual Dysfunctions, Psychological/metabolism; Tumor Suppressor Proteins/metabolism
  11. Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients
    Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M
    Pathol Oncol Res, 2010 Jun;16(2):239-48.
    PMID: 19882362 DOI: 10.1007/s12253-009-9216-3
    Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.
    Matched MeSH terms: Breast Neoplasms/metabolism*; Transcription Factors/metabolism*; Receptor, ErbB-2/metabolism*; Ki-67 Antigen/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Estrogen Receptor alpha/metabolism*; Estrogen Receptor beta/metabolism*; bcl-Associated Death Protein/metabolism*; Oncogene Protein v-akt/metabolism*
  12. S5 Lipase: an organic solvent tolerant enzyme
    Rahman RN, Baharum SN, Salleh AB, Basri M
    J Microbiol, 2006 Dec;44(6):583-90.
    PMID: 17205035
    In this study, an organic solvent tolerant bacterial strain was isolated. This strain was identified as Pseudomonas sp. strain S5, and was shown to degrade BTEX (Benzene, Toluene, Ethyl-Benzene, and Xylene). Strain S5 generates an organic solvent-tolerant lipase in the late logarithmic phase of growth. Maximum lipase production was exhibited when peptone was utilized as the sole nitrogen source. Addition of any of the selected carbon sources to the medium resulted in a significant reduction of enzyme production. Lower lipase generation was noted when an inorganic nitrogen source was used as the sole nitrogen source. This bacterium hydrolyzed all tested triglycerides and the highest levels of production were observed when olive oil was used as a natural triglyceride. Basal medium containing Tween 60 enhanced lipase production to the most significant degree. The absence of magnesium ions (Mg2+) in the basal medium was also shown to stimulate lipase production. Meanwhile, an alkaline earth metal ion, Na+, was found to stimulate the production of S5 lipase.
    Matched MeSH terms: Benzene/metabolism; Benzene Derivatives/metabolism; Lipase/metabolism*; Peptones/metabolism; Plant Oils/metabolism; Polysorbates/metabolism; Solvents/metabolism*; Toluene/metabolism; Xylenes/metabolism
  13. Fulltext A clinical and immunohistochemical study of gastrointestinal stromal tumours
    Khoo JJ, Gunn A
    Malays J Pathol, 2005 Jun;27(1):9-16.
    PMID: 16676687
    AIM: To study the clinical features, histology and immunohistochemical properties of gastrointestinal stromal tumours (GISTs); and establish any parameters that can help prognosticate the malignant potential.
    METHODS: Twenty-six patients with GISTs who were seen in Sultanah Aminah Hospital Johor, Malaysia from 1999 to 2003 were selected for study. Patient, clinical characteristics and outcome based on surgical records were analysed. Tumour variables (tumour size, cellularity, mitotic count, necrosis and haemorrhage) were compared between very low to low risk groups and intermediate to high risk groups. The immunohistochemical properties of GISTs were also studied.
    RESULTS: Patients with GISTs presented mainly with pain, palpable mass or gastrointestinal tract bleeding. The tumours were seen in stomach (50%) followed by small intestine (38.5%) and rectum (11.5%). In the period of study, six patients had metastasis, mainly in the liver or peritoneum. Immunoreactivity for CD117, CD34, vimentin, S100, neuron specific enolase, alpha-smooth-muscle-actin and desmin were observed in 100%, 76.9%, 61.5%, 46.1%, 80.8%, 11.5% and 0% of tumours respectively. The behaviour of GISTs was largely dependent on tumour size and number of mitosis. Necrosis and haemorrhage were seen in tumours with high risk potential.
    Matched MeSH terms: Actins/metabolism; Desmin/metabolism; Muscle, Smooth/metabolism; S100 Proteins/metabolism; Phosphopyruvate Hydratase/metabolism; Vimentin/metabolism; Antigens, CD34/metabolism; Proto-Oncogene Proteins c-kit/metabolism; Gastrointestinal Stromal Tumors/metabolism*
  14. Fulltext Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma
    Chai SJ, Yap YY, Foo YC, Yap LF, Ponniah S, Teo SH, et al.
    PLoS One, 2015;10(11):e0130464.
    PMID: 26536470 DOI: 10.1371/journal.pone.0130464
    Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.
    Matched MeSH terms: Antigens, Neoplasm/metabolism; Dendritic Cells/metabolism; T-Lymphocytes, Helper-Inducer/metabolism; Interferon-gamma/metabolism; Membrane Proteins/metabolism*; Nasopharyngeal Neoplasms/metabolism; T-Lymphocytes, Cytotoxic/metabolism; HLA-A2 Antigen/metabolism; Cytokines/metabolism
  15. Prospective association of liver function biomarkers with development of hepatobiliary cancers
    Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.
    Cancer Epidemiol, 2016 Feb;40:179-87.
    PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002
    INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

    METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

    RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).

    CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

    Matched MeSH terms: Alanine Transaminase/metabolism; Alkaline Phosphatase/metabolism; Aspartate Aminotransferases/metabolism; Bile Duct Neoplasms/metabolism; Biliary Tract Neoplasms/metabolism; gamma-Glutamyltransferase/metabolism; Carcinoma, Hepatocellular/metabolism; Liver Neoplasms/metabolism; Biomarkers/metabolism*
  16. Fulltext Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice
    Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY
    Drug Des Devel Ther, 2015;9:3923-34.
    PMID: 26251571 DOI: 10.2147/DDDT.S86345
    Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.
    Matched MeSH terms: Antioxidants/metabolism; Colitis/metabolism; Colon/metabolism; Interleukins/metabolism; RNA, Messenger/metabolism; Glucuronosyltransferase/metabolism; NAD(P)H Dehydrogenase (Quinone)/metabolism; NF-E2-Related Factor 2/metabolism; Interleukin-23/metabolism
  17. Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening
    Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.
    Asian Pac J Cancer Prev, 2015;16(9):3767-71.
    PMID: 25987035
    BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.

    MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.

    RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.

    CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

    Matched MeSH terms: Adenosine Triphosphatases/metabolism; Colorectal Neoplasms, Hereditary Nonpolyposis/metabolism*; DNA-Binding Proteins/metabolism; Nuclear Proteins/metabolism; Biomarkers, Tumor/metabolism*; Colorectal Neoplasms/metabolism*; DNA Repair Enzymes/metabolism*; Adaptor Proteins, Signal Transducing/metabolism; MutS Homolog 2 Protein/metabolism
  18. Virulence, Host-Selective Toxin Production, and Development of Three Cochliobolus Phytopathogens Lacking the Sfp-Type 4'-Phosphopantetheinyl Transferase Ppt1
    Zainudin NA, Condon B, De Bruyne L, Van Poucke C, Bi Q, Li W, et al.
    Mol Plant Microbe Interact, 2015 Oct;28(10):1130-41.
    PMID: 26168137 DOI: 10.1094/MPMI-03-15-0068-R
    The Sfp-type 4'-phosphopantetheinyl transferase Ppt1 is required for activation of nonribosomal peptide synthetases, including α-aminoadipate reductase (AAR) for lysine biosynthesis and polyketide synthases, enzymes that biosynthesize peptide and polyketide secondary metabolites, respectively. Deletion of the PPT1 gene, from the maize pathogen Cochliobolus heterostrophus and the rice pathogen Cochliobolus miyabeanus, yielded strains that were significantly reduced in virulence to their hosts. In addition, ppt1 mutants of C. heterostrophus race T and Cochliobolus victoriae were unable to biosynthesize the host-selective toxins (HST) T-toxin and victorin, respectively, as judged by bioassays. Interestingly, ppt1 mutants of C. miyabeanus were shown to produce tenfold higher levels of the sesterterpene-type non-HST ophiobolin A, as compared with the wild-type strain. The ppt1 strains of all species were also reduced in tolerance to oxidative stress and iron depletion; both phenotypes are associated with inability to produce extracellular siderophores biosynthesized by the nonribosomal peptide synthetase Nps6. Colony surfaces were hydrophilic, a trait previously associated with absence of C. heterostrophus Nps4. Mutants were decreased in asexual sporulation and C. heterostrophus strains were female-sterile in sexual crosses; the latter phenotype was observed previously with mutants lacking Nps2, which produces an intracellular siderophore. As expected, mutants were albino, since they cannot produce the polyketide melanin and were auxotrophic for lysine because they lack an AAR.
    Matched MeSH terms: Bacterial Proteins/metabolism; Fungal Proteins/metabolism; Iron/metabolism; Mycotoxins/metabolism; Peptide Synthases/metabolism; Siderophores/metabolism*; Transferases (Other Substituted Phosphate Groups)/metabolism; Polyketide Synthases/metabolism; L-Aminoadipate-Semialdehyde Dehydrogenase/metabolism
  19. Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats
    Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X
    Drug Dev Res, 2019 09;80(6):837-845.
    PMID: 31301179 DOI: 10.1002/ddr.21567
    The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.
    Matched MeSH terms: Alzheimer Disease/metabolism; Brain/metabolism; Catalase/metabolism; Glutathione/metabolism; Heme Oxygenase (Decyclizing)/metabolism; Peptide Fragments/metabolism; Superoxide Dismutase/metabolism; Amyloid beta-Peptides/metabolism; NF-E2-Related Factor 2/metabolism
  20. Fulltext Clinical Aspects of Janus Kinase (JAK) Inhibitors in the Cardiovascular System in Patients with Rheumatoid Arthritis
    Kotyla PJ, Islam MA, Engelmann M
    Int J Mol Sci, 2020 Oct 07;21(19).
    PMID: 33036382 DOI: 10.3390/ijms21197390
    Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.
    Matched MeSH terms: Arthritis, Rheumatoid/metabolism; Cardiovascular Diseases/metabolism; Cardiovascular System/metabolism; Cytokines/metabolism; Inflammation Mediators/metabolism; Lipid Metabolism/drug effects; STAT Transcription Factors/metabolism; Janus Kinases/metabolism
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