Displaying publications 701 - 720 of 1059 in total

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  1. Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 assimilate cholesterol and modulate ABCA1, CD36, NPC1L1 and SCARB1 in vitro
    Lim FT, Lim SM, Ramasamy K
    Benef Microbes, 2017 Feb 07;8(1):97-109.
    PMID: 27903090 DOI: 10.3920/BM2016.0048
    There is growing interest in the use of probiotic lactic acid bacteria (LAB) for prevention of hypercholesterolaemia. This study assessed the cholesterol lowering ability of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 in growth media. Both LAB yielded >98% (39.2 μg/ml) cholesterol lowering in growth media. Nile Red staining indicated direct assimilation of cholesterol by the LAB. The LAB were then explored for their prophylactic (pre-treatment of HT29 cells with LAB prior to cholesterol exposure) and biotherapeutic (treatment of HT29 cells with LAB after exposure to cholesterol) use against short and prolonged exposure of HT29 cells to cholesterol, respectively. For HT29 cells pre-treated with LAB, cholesterol lowering was accompanied by down-regulation of ATP-binding cassette family transporter-type A1 (ABCA1), cluster of differentiation 36 (CD36) and scavenger receptor class B member 1 (SCARB1). HT29 cells treated with LAB after prolonged exposure to cholesterol source, on the other hand, was associated with up-regulation of ABCA1, restoration of CD36 to basal level and down-regulation of Neimann-Pick C1-Like 1 (NPC1L1). The present findings implied the potential use of LAB4 and LAB12 as part of the strategies in prevention and management of hypercholesterolaemia.
    Matched MeSH terms: Antigens, CD36/metabolism
  2. Fulltext Identification, production and assessment of two Toxoplasma gondii recombinant proteins for use in a Toxoplasma IgG avidity assay
    Teh AY, Amerizadeh A, Osman S, Yunus MH, Noordin R
    Pathog Glob Health, 2016 Oct-Dec;110(7-8):277-286.
    PMID: 27697019
    The IgG avidity assay is an important tool in the management of suspected toxoplasmosis in pregnant women. This study aimed to produce new Toxoplasma gondii recombinant proteins and to assess their usefulness in an IgG avidity assay. Toxoplasma positive and negative serum samples were used, the former were categorized into low (LGA) and high (HGA) IgG avidity samples. Immunoblots were performed on 30 T. gondii cDNA clones to determine the reactivity and IgG avidity to the expressed proteins. Two of the clones were found to have diagnostic potential and were analyzed further; AG12b encoded T. gondii apical complex lysine methyltransferase (AKMT) protein and AG18 encoded T. gondii forkhead-associated (FHA) domain-containing protein. The His-tagged recombinant proteins, rAG12b and rAG18, were expressed and tested with LGA and HGA samples using an IgG avidity western blot and ELISA. With the IgG avidity western blot, rAG12b identified 86.4% of LGA and 90.9% of HGA samples, whereas rAG18 identified 81.8% of both LGA and HGA samples. With the IgG avidity ELISA, rAG12b identified 86.4% of both LGA and HGA samples, whereas rAG18 identified 77.3% of LGA and 86.4% of HGA serum samples. This study showed that the recombinant antigens were able to differentiate low avidity and high avidity serum samples, suggesting that they are potential candidates for use in the Toxoplasma IgG avidity assay.
    Matched MeSH terms: Antigens, Protozoan/immunology*
  3. Pegylated granulocyte-colony stimulating factor versus non-pegylated granulocyte-colony stimulating factor for peripheral blood stem cell mobilization: A systematic review and meta-analysis
    Kuan JW, Su AT, Leong CF
    J Clin Apher, 2017 Dec;32(6):517-542.
    PMID: 28485020 DOI: 10.1002/jca.21550
    Granulocyte-colony stimulating factor (G-CSF) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood, enabling its harvest by few apheresis procedures. The pegylated G-CSF has longer half-life and is given once only, which is more comfortable for patients, whereas the non-pegylated requires multiple daily injection because of its short half-life. We summarized results of randomized trials comparing the efficacy and safety of pegylated and non-pegylated G-CSF for peripheral blood stem cell mobilization. We searched the Cochrane CENTRAL, MEDLINE, EMBASE, and two conference proceedings. Two authors made the selection, extracted data and evaluated methodological quality using GRADE independently. We used random-effects model for meta-analysis. We found 3956 records and retrieved 47 full texts. We included eight randomized trials with a total number of 554 randomized and 532 analyzed subjects. The meta-analysis included five trials because not all trials reported the same outcomes. Pooling data from two studies shows no evidence for a difference in the successful mobilization rate (CD34+ cell ≥ 2 × 106 /kg collected) between pegfilgrastim 6 mg (early administration) and filgrastim 5 µg/kg/day (147 participants; risk ratio (RR) 0.87, 95% confidence interval (95%CI) 0.67-1.11; P = .26). Pooling data from three studies shows no difference in the incidence of adverse events between pegylated and non-pegylated G-CSF (170 participants; RR 0.86, 95%CI 0.34-2.17; P = .75). No difference found on the quantity of CD34+ cells collected, number of apheresis procedure in successful mobilization, level of peak PB CD34+ cells achieved, and day of neutrophil and platelet engraftment.
    Matched MeSH terms: Antigens, CD34/analysis
  4. Clinico-pathology and hemato-biochemistry responses in buffaloes infected with Pasteurella multocida type B:2 immunogen outer membrane protein
    Chung ELT, Abdullah FFJ, Marza AD, Saleh WMM, Ibrahim HH, Abba Y, et al.
    Microb Pathog, 2017 Jan;102:89-101.
    PMID: 27894962 DOI: 10.1016/j.micpath.2016.11.015
    The aim of this study was to investigate the clinico-pathology and haemato-biochemistry alterations in buffaloes inoculated with Pasteurella multocida type B:2 immunogen outer membrane protein via subcutaneous and oral routes. Nine buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 mL of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 mL of outer membrane protein broth subcutaneously and orally respectively. Group 2 buffaloes showed typical haemorrhagic septicaemia clinical signs and were only able to survive for 72 h of the experiment. However, Group 3 buffaloes were able to survive throughout the stipulated time of 21 days of experiment. There were significant differences (p  0.05) in edema between groups except for the lung. This study was a proof that oral route infection of Pasteurella multocida type B:2 immunogen outer membrane protein can be used to stimulate host cell.
    Matched MeSH terms: Antigens, Bacterial/immunology*
  5. Fulltext SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression
    Ten LC, Chin YM, Tai MC, Chin EF, Lim YY, Suthandiram S, et al.
    Sci Rep, 2017 01 31;7:41400.
    PMID: 28139690 DOI: 10.1038/srep41400
    Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
    Matched MeSH terms: Histocompatibility Antigens Class II/genetics*
  6. [The biological and hemagglutinating properties of Ghetah arbovirus]
    Leont'eva NA, Fadeeva LL
    Vopr. Virusol., 1969 Jul-Aug;14(4):464-8.
    PMID: 4982330
    Matched MeSH terms: Antigens/analysis*
  7. Fulltext Evaluation of a Commercial Immuno-Chromatographic Assay Kit for Rapid Detection of IgM Antibodies against Leptospira Antigen in Human Serum
    Amran F, Liow YL, Halim NAN
    J Korean Med Sci, 2018 Apr 23;33(17):e131.
    PMID: 29686599 DOI: 10.3346/jkms.2018.33.e131
    Leptospirosis is a febrile zoonotic disease. Routine diagnosis of leptospirosis is based on the detection of specific antibodies with serological tests. The aim of our study was to determine the usefulness of immunochromatographic assay (ICA), ImmuneMed Leptospira IgM Duo Rapid test kit from Korea, in rapid screening of acute leptospirosis in emergency cases with limited expertise. A total of 197 serum samples (93 positive, 104 negative) were selected randomly. The test has good diagnostic sensitivity 73% and specificity 90%. With positive predictive value of 87% and negative predictive value of 79%, this reassures patients have higher chance of correct diagnosis. This ICA is acceptable for screening of leptospirosis but confirmation with microscopic agglutination test should follow.
    Matched MeSH terms: Antigens, Bacterial/immunology
  8. Fulltext Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
    Kared H, Martelli S, Tan SW, Simoni Y, Chong ML, Yap SH, et al.
    Front Immunol, 2018;9:686.
    PMID: 29731749 DOI: 10.3389/fimmu.2018.00686
    Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
    Matched MeSH terms: Antigens, CD57/immunology
  9. Parallel ELISAs using crude soluble antigen and excretory-secretory antigen for improved serodiagnosis of amoebic liver abscess
    Wong WK, Foo PC, Olivos-Garcia A, Noordin R, Mohamed Z, Othman N, et al.
    Acta Trop, 2017 Aug;172:208-212.
    PMID: 28506795 DOI: 10.1016/j.actatropica.2017.05.017
    Crude soluble antigen (CSA) produced from Entamoeba histolytica trophozoite is conventionally used for serodiagnosis of invasive amoebiasis. However, high background seropositivities by CSA-assay in endemic areas complicate the interpretation of positive result in clinical settings. Instead, incorporating a second assay which indicates active or recent infection into the routine amoebic serology could possibly complement the limitations of CSA-assay. Hence, the present study aimed to evaluate the diagnostic efficacies of indirect ELISAs using CSA and excretory-secretory antigen (ESA) for serodiagnosis of amoebic liver abscess (ALA). Reference standard for diagnosis of ALA at Hospital Universiti Sains Malaysia is based on clinical presentation, radiological imaging and positive indirect haemagglutination assay (titer ≥256). Five groups of human serum samples collected from the hospital included Group I - ALA diagnosed by the reference standard and pus aspirate analysis using real-time PCR (n=10), Group II - ALA diagnosed by the reference standard only (n=41), Group III - healthy control (n=45), Group IV - other diseases control (n=51) and Group V - other infectious diseases control (n=31). For serodiagnosis of ALA serum samples (Group I and II), CSA-ELISA showed sensitivities of 100% for both groups, while ESA-ELISA showed sensitivities of 100% and 88%, respectively. For serodiagnosis of non-ALA serum samples (Group III, IV and V), CSA-ELISA showed specificities of 91%, 75% and 100%, respectively; while ESA-ELISA showed specificities of 96%, 98% and 100%, respectively. Indirect ELISAs using CSA and ESA have shown distinct strength for serodiagnosis of ALA, in terms of sensitivity and specificity, respectively. In conclusion, parallel analysis by both assays improved the overall efficacies of amoebic serology as compared to either single assay.
    Matched MeSH terms: Antigens, Protozoan/immunology*
  10. Indirect hemagglutination with extracts of various helminths in eosinophilic lung (tropical eosinophilia)
    Pacheco G, Danaraj TJ
    Am J Trop Med Hyg, 1966 May;15(3):355-8.
    PMID: 5938434
    Saline extracts of ether-treated Dirofilaria immitis, Ascaris suum, and Ancylostoma spp. were used in indirect hemagglutination tests of serum from 164 patients with a diagnosis of eosinophilic lung and 114 persons with other diseases or no disease (blood donors). In the first group, positive reactions with one, two or all three antigens were obtained in 89 percent of cases and the titers, at medium or high levels in 77 percent, decreased after treatment with diethylcarbamazine. In the other group, antibodies were demonstrable in the serum of only 22 percent of cases and titers usually were low. These observations indicate the presence of several antigen-antibody systems, some of which appear to be specific. With extracts of Dirofilaria the indirect hemagglutination and the complement-fixation tests were similar in sensitivity and specificity, but the results from neither test appeared to indicate infection with a specific worm.
    Matched MeSH terms: Antigen-Antibody Reactions*; Antigens*
  11. Fulltext AIM2 Inflammasome-Mediated Pyroptosis in Enterovirus A71-Infected Neuronal Cells Restricts Viral Replication
    Yogarajah T, Ong KC, Perera D, Wong KT
    Sci Rep, 2017 07 19;7(1):5845.
    PMID: 28724943 DOI: 10.1038/s41598-017-05589-2
    Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells. Downstream AIM2-induced genes, CARD16, caspase-1 and IL-1β were also up-regulated and caspase-1 was activated to form cleaved caspase-1 p20 subunits. As evidenced by 7-AAD positivity, pyroptosis was confirmed in infected cells. Overall, these findings have a strong correlation with decreases in viral titers, copy numbers and proteins, and reduced proportions of infected cells. AIM2 and viral antigens were detected by immunohistochemistry in infected neurons in inflamed areas of the CNS in EV-A71 encephalomyelitis. In infected AIM2-knockdown cells, AIM2 and related downstream gene expressions, and pyroptosis were suppressed, resulting in significantly increased virus infection. These results support the notion that AIM2 inflammasome-mediated pyroptosis is an important mechanism of neuronal cell death and it could play an important role in limiting EV-A71 replication.
    Matched MeSH terms: Antigens/metabolism
  12. Fulltext Hepatitis B and C virus infection and diabetes mellitus: A cohort study
    Hong YS, Chang Y, Ryu S, Cainzos-Achirica M, Kwon MJ, Zhang Y, et al.
    Sci Rep, 2017 07 04;7(1):4606.
    PMID: 28676706 DOI: 10.1038/s41598-017-04206-6
    The role of hepatitis virus infection in glucose homeostasis is uncertain. We examined the associations between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the development of diabetes in a cohort (N = 439,708) of asymptomatic participants in health screening examinations. In cross-sectional analyses, the multivariable-adjusted odds ratio for prevalent diabetes comparing hepatitis B surface antigen (HBsAg) (+) to HBsAg (-) participants was 1.17 (95% CI 1.06-1.31; P = 0.003). The corresponding odds ratio comparing hepatitis C antibodies (HCV Ab) (+) to HCV Ab (-) participants was 1.43 (95% CI 1.01-2.02, P = 0.043). In prospective analyses, the multivariable-adjusted hazard ratio for incident diabetes comparing HBsAg (+) to HbsAg (-) participants was 1.23 (95% CI 1.08-1.41; P = 0.007). The number of incident cases of diabetes among HCV Ab (+) participants (10 cases) was too small to reliably estimate the prospective association between HCV infection and diabetes. In this large population at low risk of diabetes, HBV and HCV infections were associated with diabetes prevalence and HBV infection with the risk of incident diabetes. Our studies add evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.
    Matched MeSH terms: Hepatitis B Surface Antigens/metabolism*
  13. Differences in humoral immune response between patients with or without nasal carriage of Staphylococcus aureus
    Ghasemzadeh-Moghaddam H, van Wamel W, van Belkum A, Hamat RA, Neela VK
    Eur J Clin Microbiol Infect Dis, 2017 Mar;36(3):451-458.
    PMID: 27815779 DOI: 10.1007/s10096-016-2817-3
    The humoral immune response against 43 staphylococcal antigens was compared among hospitalized patients where none of them had any staphylococcal infection on the day of admission with or without nasal Staphylococcus aureus carriage. Fifty-nine carriers and 59 matched non-carriers were studied. The carriers harbored S. aureus of 35 different spa types, including three t037/ST239 methicillin-resistant S. aureus (MRSA) (5.1%). Among the 118 patients, 31 acquired S. aureus during hospitalization. In colonized and non-colonized patients, unique patterns of S. aureus-specific immune responses were observed. The mean fluorescence indices (MFIs) of antibodies against 36/43 (83.7%) antigens were seen to be elevated among carriers. The MFI among carriers with acquisition was significantly higher for staphylococcal superantigen-like protein 5 (SSL5, p = 0.028) when compared to carriers without acquisition. High antibody levels against staphylococcal enterotoxin A (SEA) among carriers illustrate its role as a superantigen in both infection and colonization. We also report a dynamic immune response in S. aureus-carrying patients against the recently reported formyl peptide receptor-like inhibitory (FLIPr)-like protein. In the current study, the dynamics of antibodies against staphylococcal antigens among carrier patients seem quite similar to non-carrier patients. To better understand the dynamic immunogenicity during S. aureus infection and colonization, artificial colonization studies and investigation of the changes in the levels of antibodies against other staphylococcal antigens are recommended.
    Matched MeSH terms: Antigens, Bacterial/immunology
  14. Immune Stimulation of RAP domain binding protein (rTgRA15) from Toxoplasma gondii
    Lew MH, Noordin R, Monsur Alam Khan M, Tye GJ
    Pathog Glob Health, 2018 10;112(7):387-394.
    PMID: 30332344 DOI: 10.1080/20477724.2018.1536854
    Toxoplasmosis, a parasitic disease in human and animals, is caused by Toxoplasma gondii. Our previous study has led to the discovery of a novel RAP domain binding protein antigen (TgRA15), an apparent in-vivo induced antigen recognised by antibodies in acutely infected individuals. This study is aimed to evaluate the humoral response and cytokine release elicited by recombinant TgRA15 protein in C57BL/6 mice, demonstrating its potential as a candidate vaccine for Toxoplasma gondii infection. In this study, the recombinant TgRA15 protein was expressed in Escherichia coli, purified and refolded into soluble form. C57BL/6 mice were immunised intradermally with the antigen and CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity). Antigen-specific humoral and cell-mediated responses were evaluated using Western blot and ELISA. The total IgG, IgG1 and IgG2a antibodies specific to the antigen were significantly increased in treatment group compare to control group. A higher level of interferon gamma (IFN-γ) secretion was demonstrated in the mice group receiving booster doses of rTgRA15 protein, suggesting a potential Th1-mediated response. In conclusion, the rTgRA15 protein has the potential to generate specific antibody response and elicit cellular response, thus potentially serve as a vaccine candidate against T. gondii infection.
    Matched MeSH terms: Antigens, Protozoan/immunology
  15. Fulltext Laboratory Evaluation of a Rapid IgG4 Antibody Test (BLF Rapid™) for Bancroftian Filariasis
    Noordin R, Yunus MH, Robinson K, Won KY, Babu S, Fischer PU, et al.
    Am J Trop Med Hyg, 2018 12;99(6):1587-1590.
    PMID: 30350768 DOI: 10.4269/ajtmh.18-0566
    At the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis-endemic areas. This study evaluated the diagnostic performance of BLF Rapid™, a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84-100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make "Transmission Assessment Survey"-stopping decisions and conduct post-elimination surveillance.
    Matched MeSH terms: Antigens, Helminth/blood
  16. Amniotic Membrane Enhance the Effect of Vascular Endothelial Growth Factor on the Angiogenic Marker Expression of Stem Cells from Human Exfoliated Deciduous Teeth
    Yusof MFH, Hashim SNM, Zahari W, Chandra H, Noordin KBAA, Kannan TP, et al.
    Appl Biochem Biotechnol, 2020 May;191(1):177-190.
    PMID: 32096060 DOI: 10.1007/s12010-020-03266-1
    Previously, it was reported that human amniotic membrane (AM) induced stem cells from human deciduous exfoliated teeth (SHED) endothelial-like-cell differentiation. This interesting effect of AM matrix on SHED demands further elucidation. Objective of this in vitro work was to study the effect of 24-h VEGF induced on SHED endothelial differentiation when seeded on acellular stromal side (SS) of AM matrix. Stemness of SHED was identified by flow cytometry. Cell attachment and morphological changes towards the matrix was observed by scanning electron microscopy. Protein expression of endothelial marker was examined by Western blot. The expression of stem cells and endothelial-specific gene markers of VEGF-induced SHED cultured on human AM was inspected via reverse transcriptase-polymerase chain reaction. Results showed SHED at both passages retain stemness property. Ang-1 protein was expressed in SHED. Cells treated with VEGF and cultured on AM transformed attached well to AM. VEGF-induced SHED expressed both stem cell and endothelial-specific markers throughout the treatments and timeline. Interestingly, prolonged VEGF treatment increased the expression of Cox-2 and VE-Cadherin genes in all treated groups when compared to SHED. It was concluded that the VEGF-induced SHED showed better expression of endothelial-specific markers when cultured on SS of AM, with prolonged VEGF treatment.
    Matched MeSH terms: Antigens, Differentiation/biosynthesis*
  17. Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni
    Leow CY, Willis C, Chuah C, Leow CH, Jones M
    Parasite Immunol., 2020 03;42(3):e12693.
    PMID: 31880816 DOI: 10.1111/pim.12693
    AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model.

    METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected.

    CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.

    Matched MeSH terms: Antigens, Helminth/immunology*
  18. Fulltext Emergence of Undetectable Malaria Parasites: A Threat under the Radar amid the COVID-19 Pandemic?
    Beshir KB, Grignard L, Hajissa K, Mohammed A, Nurhussein AM, Ishengoma DS, et al.
    Am J Trop Med Hyg, 2020 08;103(2):558-560.
    PMID: 32553046 DOI: 10.4269/ajtmh.20-0467
    Rapid diagnostic tests (RDTs) play a critical role in malaria diagnosis and control. The emergence of Plasmodium falciparum parasites that can evade detection by RDTs threatens control and elimination efforts. These parasites lack or have altered genes encoding histidine-rich proteins (HRPs) 2 and 3, the antigens recognized by HRP2-based RDTs. Surveillance of such parasites is dependent on identifying false-negative RDT results among suspected malaria cases, a task made more challenging during the current pandemic because of the overlap of symptoms between malaria and COVID-19, particularly in areas of low malaria transmission. Here, we share our perspective on the emergence of P. falciparum parasites lacking HRP2 and HRP3, and the surveillance needed to identify them amid the COVID-19 pandemic.
    Matched MeSH terms: Antigens, Protozoan/analysis
  19. Fulltext CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients
    Mohd Shukri ND, Farah Izati A, Wan Ghazali WS, Che Hussin CM, Wong KK
    Front Immunol, 2021;12:675250.
    PMID: 34149710 DOI: 10.3389/fimmu.2021.675250
    The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.
    Matched MeSH terms: Antigens, CD4; Antigens, CD3
  20. Fulltext Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa
    Mohamed M, Gardeitchik T, Balasubramaniam S, Guerrero-Castillo S, Dalloyaux D, van Kraaij S, et al.
    J Inherit Metab Dis, 2020 11;43(6):1382-1391.
    PMID: 32418222 DOI: 10.1002/jimd.12255
    Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P2 were decreased. Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4-kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3 . Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature ageing and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics.
    Matched MeSH terms: Minor Histocompatibility Antigens/genetics*
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