Displaying publications 41 - 60 of 71 in total

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  1. Fulltext Analysis of expression of vitamin E-binding proteins in H2O2 induced SK-N-SH neuronal cells supplemented with α-tocopherol and tocotrienol-rich fraction
    Chiroma AA, Khaza'ai H, Abd Hamid R, Chang SK, Zakaria ZA, Zainal Z
    PLoS One, 2020;15(11):e0241112.
    PMID: 33232330 DOI: 10.1371/journal.pone.0241112
    Natural α-tocopherol (α-TCP), but not tocotrienol, is preferentially retained in the human body. α-Tocopherol transfer protein (α-TTP) is responsible for binding α-TCP for cellular uptake and has high affinity and specificity for α-TCP but not α-tocotrienol. The purpose of this study was to examine the modification of α-TTP together with other related vitamin E-binding genes (i.e., TTPA, SEC14L2, and PI-TPNA) in regulating vitamin E uptake in neuronal cells at rest and under oxidative stress. Oxidative stress was induced with H2O2 for an hour which was followed by supplementation with different ratios of α-TCP and tocotrienol-rich fraction (TRF) for four hours. The cellular levels of vitamin E were quantified to determine bioavailability at cellular levels. The expression levels of TTPA, SEC14L2, and PI-TPNA genes in 0% α-TCP were found to be positively correlated with the levels of vitamin E in resting neuronal cells. In addition, the regulation of all the above-mentioned genes affect the distribution of vitamin E in the neuronal cells. It was observed that, increased levels of α-TCP secretion occur under oxidative stress. Thus, our results showed that in conclusion vitamin E-binding proteins may be modified in the absence of α-TCP to produce tocotrienols (TCT), as a source of vitamin E. The current study suggests that the expression levels of vitamin E transport proteins may influence the cellular concentrations of vitamin E levels in the neuronal cells.
    Matched MeSH terms: Carrier Proteins/metabolism
  2. Proteomics, oxidative stress and male infertility
    Agarwal A, Durairajanayagam D, Halabi J, Peng J, Vazquez-Levin M
    Reprod Biomed Online, 2014 Jul;29(1):32-58.
    PMID: 24813754 DOI: 10.1016/j.rbmo.2014.02.013
    Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.
    Matched MeSH terms: Carrier Proteins/metabolism
  3. Adenine derivatives invert high glucose-induced thioredoxin-interacting protein overexpression
    Zhong L, Liu Q, Ting YS, Thien VY, Binti Kalong NS, Yang D, et al.
    Chem Biol Drug Des, 2018 12;92(6):1998-2008.
    PMID: 30043441 DOI: 10.1111/cbdd.13371
    Overexpression of thioredoxin-interacting protein (TXNIP) is associated with reduced insulin sensitivity and β-cell apoptosis. We have previously shown that W2476 inhibited high glucose-induced TXNIP expression at both mRNA and protein levels in INS-1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS-1E cells, increasing insulin production, and reducing high glucose-induced apoptosis in INS-1E cells.
    Matched MeSH terms: Carrier Proteins/metabolism*
  4. Fulltext TranCEP: Predicting the substrate class of transmembrane transport proteins using compositional, evolutionary, and positional information
    Alballa M, Aplop F, Butler G
    PLoS One, 2020;15(1):e0227683.
    PMID: 31935244 DOI: 10.1371/journal.pone.0227683
    Transporters mediate the movement of compounds across the membranes that separate the cell from its environment and across the inner membranes surrounding cellular compartments. It is estimated that one third of a proteome consists of membrane proteins, and many of these are transport proteins. Given the increase in the number of genomes being sequenced, there is a need for computational tools that predict the substrates that are transported by the transmembrane transport proteins. In this paper, we present TranCEP, a predictor of the type of substrate transported by a transmembrane transport protein. TranCEP combines the traditional use of the amino acid composition of the protein, with evolutionary information captured in a multiple sequence alignment (MSA), and restriction to important positions of the alignment that play a role in determining the specificity of the protein. Our experimental results show that TranCEP significantly outperforms the state-of-the-art predictors. The results quantify the contribution made by each type of information used.
    Matched MeSH terms: Carrier Proteins/chemistry
  5. Fulltext Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma
    Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.
    Nat Genet, 2012 Oct;44(10):1142-1146.
    PMID: 22922875 DOI: 10.1038/ng.2390
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
    Matched MeSH terms: Carrier Proteins/genetics*
  6. Fulltext New emm (M protein gene) sequences of group A streptococci isolated from Malaysian patients
    Jamal F, Pit S, Facklam R, Beall B
    Emerg Infect Dis, 1999 Jan-Feb;5(1):182-3.
    PMID: 10081694
    Matched MeSH terms: Carrier Proteins/genetics*
  7. Mechanisms of action of 17βH-neriifolin on its anticancer effect in SKOV-3 ovarian cancer cell line
    Mutalip SS, Yunos NM, Abdul-Rahman PS, Jauri MH, Osman A, Adenan MI
    Anticancer Res, 2014 Aug;34(8):4141-51.
    PMID: 25075041
    AIM: Abnormalities in apoptotic signalling pathways often occur in cancer cells and limit the successful chemotherapy outcomes in cancers. Therefore, there is an urgent need to discover new anticancer agents with novel mechanisms of action to overcome the resistance effect in chemotherapy.

    MATERIALS AND METHODS: In the present study, the anticancer effects and the mechanisms of action of 17βH-neriifolin (cardiac glycoside) were evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and a proteomic approach in treated and non-treated SKOV-3 ovarian cancer cells.

    RESULTS: 17βH-neriifolin was found to be active with IC50 values of 0.01 ± 0.001 in SKOV-3 ovarian cancer cell line, as evaluated by the sulforhodamine B (SRB) assay. RESULTS from TUNEL assay indicated that 17βH-neriifolin caused apoptosis in SKOV-3 cells in a dose-dependent manner. Based on differential analysis of treated and non-treated SKOV-3 two-dimensional electrophoresis (2-DE) profiles, four proteins, namely vimentin (VIM), pyruvate kinase, muscle (PKM), heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and transgelin (TAGLN1) were identified to be involved in apoptosis. Other proteins including piggybac transposable element derived 5 (PGBD5), DENN/MADD domain containing 2D (DENND2D) and formin-like 1(FMNL) have also been identified to be associated in SKOV-3 cell death induced by 17βH-neriifolin.

    CONCLUSION: These findings may provide new insights on the potential of 17βH-neriifolin's mechanism of action in killing ovarian cancer cells.

    Matched MeSH terms: Carrier Proteins/physiology
  8. Fulltext A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia
    Lim FS, Koh MT, Tan KK, Chan PC, Chong CY, Shung Yehudi YW, et al.
    BMC Infect Dis, 2014;14:530.
    PMID: 25278086 DOI: 10.1186/1471-2334-14-530
    BACKGROUND: The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed.
    METHODS: In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA.
    RESULTS: Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study.
    CONCLUSIONS: PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile.This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625.
    Matched MeSH terms: Carrier Proteins/administration & dosage
  9. Penicillin susceptibility and molecular characteristics of clinical isolates of Streptococcus pneumoniae at the University of Malaya Medical Center, Kuala Lumpur, Malaysia
    Desa MN, Lin TK, Yasin RM, Parasakthi N
    Int J Infect Dis, 2003 Sep;7(3):190-7.
    PMID: 14563222
    To determine the prevalence of penicillin resistance and molecular characteristics of pneumococcal isolates at the University of Malaya Medical Center.
    Matched MeSH terms: Carrier Proteins/genetics
  10. Characterization of group A streptococci isolated in Kuala Lumpur, Malaysia
    Jamal F, Pit S, Johnson DR, Kaplan EL
    J Trop Med Hyg, 1995 Oct;98(5):343-6.
    PMID: 7563264
    T-agglutination patterns of 190 strains of group A streptococci isolated between January 1989 and December 1993 from body fluids (10), throat culture (56), pus (51) and skin lesions (73) were determined. Mucoid colonial morphology was exhibited by 6.3% (12/190) of the strains on initial isolation. Type T-5,11,27,44 comprised 23.7%, followed by T-1,3,13,B3264 (11.1%), T-4,6 (8.4%) and T-8,25, Imp 19 (7.9%). About 42% (80/190) strains could not be characterized by T agglutination pattern. T-typing of 71 selected strains at WHO Collaborating Center, Minneapolis yielded similar results. Nineteen selected strains were further characterized by M-typing; only three strains were M-typeable. These strains were isolated from throat (M1), sputum (M5) and pus (M12). About 68% (48/71) isolates produced serum opacity factor. These data support the existence of as yet uncharacterized group A streptococcal serotypes in this region.
    Matched MeSH terms: Carrier Proteins*
  11. Blood-based dynamic genomic signature for obsessive-compulsive disorder
    Wang Y, Cheng C, Zhang Z, Wang J, Wang Y, Li X, et al.
    Am J Med Genet B Neuropsychiatr Genet, 2018 12;177(8):709-716.
    PMID: 30350918 DOI: 10.1002/ajmg.b.32675
    No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.
    Matched MeSH terms: Carrier Proteins/genetics
  12. Fulltext Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease
    Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.
    J Transl Med, 2017 05 31;15(1):121.
    PMID: 28569153 DOI: 10.1186/s12967-017-1226-4
    BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.

    METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).

    RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P 

    Matched MeSH terms: Carrier Proteins/blood
  13. Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice
    Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.
    Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
    PMID: 27495788 DOI: 10.1007/s00280-016-3120-9
    PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.

    METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.

    RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p 

    Matched MeSH terms: Carrier Proteins/metabolism
  14. Fulltext Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using In Vitro and In Vivo Models
    Pramanik A, Xu Z, Shamsuddin SH, Khaled YS, Ingram N, Maisey T, et al.
    ACS Appl Mater Interfaces, 2022 Mar 09;14(9):11078-11091.
    PMID: 35196008 DOI: 10.1021/acsami.1c21655
    Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
    Matched MeSH terms: Carrier Proteins/metabolism*
  15. Fulltext An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression
    Wyszynski A, Hong CC, Lam K, Michailidou K, Lytle C, Yao S, et al.
    Hum Mol Genet, 2016 Sep 01;25(17):3863-3876.
    PMID: 27402876 DOI: 10.1093/hmg/ddw223
    Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 × 10-19) and identify 13 additional linked variants (r2 > 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 × 10-15 - 5.6 × 10-17). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.
    Matched MeSH terms: Carrier Proteins/genetics*
  16. The Potential of Eight Plasma Proteins as Biomarkers in Redefining Leptospirosis Diagnosis
    Fish-Low CY, Than LTL, Ling KH, Sekawi Z
    J Proteome Res, 2024 Sep 06;23(9):4027-4042.
    PMID: 39150348 DOI: 10.1021/acs.jproteome.4c00376
    Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.
    Matched MeSH terms: Carrier Proteins/blood
  17. Enterovirus-Specific Anti-peptide Antibodies
    Poh CL, Kirk K, Chua HN, Grollo L
    Methods Mol Biol, 2015;1348:341-50.
    PMID: 26424285 DOI: 10.1007/978-1-4939-2999-3_29
    Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.
    Matched MeSH terms: Carrier Proteins
  18. Fulltext Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1
    Greenwood MP, Greenwood M, Gillard BT, Chitra Devi R, Murphy D
    Front Mol Neurosci, 2017;10:413.
    PMID: 29311806 DOI: 10.3389/fnmol.2017.00413
    Cyclic AMP (cAMP) inducible transcription factor cAMP responsive element binding protein 3 like 1 (Creb3l1) is strongly activated in the hypothalamus in response to hyperosmotic cues such as dehydration (DH). We have recently shown that Creb3l1 expression is upregulated by cAMP pathways in vitro, however the exact mechanisms are not known. Here we show that increasing Creb3l1 transcription by raising cAMP levels in mouse pituitary AtT20 cells automatically initiates cleavage of Creb3l1, leading to a greater abundance of the transcriptionally active N-terminal portion. Inhibiting protein synthesis indicated that de novo protein synthesis of an intermediary transcription factor was required for Creb3l1 induction. Strategic mining of our microarray data from dehydrated rodent hypothalamus revealed four candidates, reduced to two by analysis of acute hyperosmotic-induced transcriptional activation profiles in the hypothalamus, and one, orphan nuclear receptor Nr4a1, by direct shRNA mediated silencing in AtT20 cells. We show that activation of Creb3l1 transcription by Nr4a1 involves interaction with a single NBRE site in the promoter region. The ability to activate Creb3l1 transcription by this pathway in vitro is dictated by the level of methylation of a CpG island within the proximal promoter/5'UTR of this gene. We thus identify a novel cAMP-Nr4a1-Creb3l1 transcriptional pathway in AtT20 cells and also, our evidence would suggest, in the hypothalamus.
    Matched MeSH terms: Carrier Proteins
  19. Expression of cytosolic and thiolated proteome of Musca domestica larvae under oxidative challenge
    Tan YH, Alias Z
    Trop Biomed, 2020 Sep 01;37(3):744-755.
    PMID: 33612787 DOI: 10.47665/tb.37.3.744
    The study was aimed to investigate the expression of cytosolic and thiolated proteins of Musca domestica larvae under oxidative stress. Proteins from acute treatment of hydrogen peroxide (LC50 = 21.52% (v/v)) on 3rd stage larvae of housefly were extracted and purified using an activated Thiol Sepharose® for thiolated protein purification. Two dimensional gel electrophoresis was used for visualizing and analyzing expression of cytosolic and thiolated proteins. Protein spots with more than 5 fold of expression change were identified using liquid chromatography- tandem mass spectrometry (LC-MS/MS). The cytosolic proteins were actin, tropomyosin, ubiquitin, arginine kinase, pheromone binding protein/general odorant binding protein, and ATP: guanidino phosphotransferase. The thiolated proteins with more than 5 fold change in expression as an effect to the acute treatment were fructose bisphosphate aldolase, short chain dehydrogenase and lactate/malate dehydrogenase. The proteins identified in the study should provide vital information for future reference in oxidative stress defence and response occurring in houseflies.
    Matched MeSH terms: Carrier Proteins
  20. Sequence diversity and positive selection at the Duffy-binding protein genes of Plasmodium knowlesi and P. cynomolgi: Analysis of the complete coding sequences of Thai isolates
    Putaporntip C, Kuamsab N, Jongwutiwes S
    Infect Genet Evol, 2016 Oct;44:367-375.
    PMID: 27480919 DOI: 10.1016/j.meegid.2016.07.040
    Plasmodium knowlesi and P. cynomolgi are simian malaria parasites capable of causing symptomatic human infections. The interaction between the Duffy binding protein alpha on P. knowlesi merozoite and the Duffy-antigen receptor for chemokine (DARC) on human and macaque erythrocyte membrane is prerequisite for establishment of blood stage infection whereas DARC is not required for erythrocyte invasion by P. cynomolgi. To gain insights into the evolution of the PkDBP gene family comprising PkDBPα, PkDBPβ and PkDBPγ, and a member of the DBP gene family of P. cynomolgi (PcyDBP1), the complete coding sequences of these genes were analyzed from Thai field isolates and compared with the publicly available DBP sequences of P. vivax (PvDBP). The complete coding sequences of PkDBPα (n=11), PkDBPβ (n=11), PkDBPγ (n=10) and PcyDBP1 (n=11) were obtained from direct sequencing of the PCR products. Nucleotide diversity of DBP is highly variable across malaria species. PcyDBP1 displayed the greatest level of nucleotide diversity while all PkDBP gene members exhibited comparable levels of diversity. Positive selection occurred in domains I, II and IV of PvDBP and in domain V of PcyDBP1. Although deviation from neutrality was not detected in domain II of PkDBPα, a signature of positive selection was identified in the putative DARC binding site in this domain. The DBP gene families seem to have arisen following the model of concerted evolution because paralogs rather than orthologs are clustered in the phylogenetic tree. The presence of identical or closely related repeats exclusive for the PkDBP gene family suggests that duplication of gene members postdated their divergence from the ancestral PcyDBP and PvDBP lineages. Intragenic recombination was detected in all DBP genes of these malaria species. Despite the limited number of isolates, P. knowlesi from Thailand shared phylogenetically related domain II sequences of both PkDBPα and PkDBPγ with those from Peninsular Malaysia, consistent with their geographic proximity.
    Matched MeSH terms: Carrier Proteins
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