Displaying publications 1 - 20 of 29 in total

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  1. Observation of WWγ Production and Search for Hγ Production in Proton-Proton Collisions at sqrt[s]=13  TeV
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Mar 22;132(12):121901.
    PMID: 38579207 DOI: 10.1103/PhysRevLett.132.121901
    The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138  fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling)  fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
  2. Fulltext Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
    Vimali J, Yong YK, Murugesan A, Tan HY, Zhang Y, Ashwin R, et al.
    Front Biosci (Landmark Ed), 2024 Mar 22;29(3):128.
    PMID: 38538288 DOI: 10.31083/j.fbl2903128
    BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells.

    METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression.

    RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL.

    CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

  3. New Structures in the J/ψJ/ψ Mass Spectrum in Proton-Proton Collisions at sqrt[s]=13  TeV
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Mar 15;132(11):111901.
    PMID: 38563916 DOI: 10.1103/PhysRevLett.132.111901
    A search is reported for near-threshold structures in the J/ψJ/ψ invariant mass spectrum produced in proton-proton collisions at sqrt[s]=13  TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135  fb^{-1}. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638_{-38}^{+43}(stat)_{-31}^{+16}(syst)  MeV. Another structure with even higher significance is found at a mass of 6847_{-28}^{+44}(stat)_{-20}^{+48}(syst)  MeV, which is consistent with the X(6900) resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134_{-25}^{+48}(stat)_{-15}^{+41}(syst)  MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference.
  4. Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pp Collisions at sqrt[s]=13  TeV
    Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Feb 09;132(6):061801.
    PMID: 38394587 DOI: 10.1103/PhysRevLett.132.061801
    The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
  5. Genomic surveillance of omicron B.1.1.529 SARS-CoV-2 and its variants between December 2021 and March 2023 in Tamil Nadu, India-A state-wide prospective longitudinal study
    Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.
    J Med Virol, 2024 Feb;96(2):e29456.
    PMID: 38329187 DOI: 10.1002/jmv.29456
    A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
  6. Fulltext Predicting sustainable fashion consumption intentions and practices
    Hong Y, Al Mamun A, Yang Q, Masukujjaman M
    Sci Rep, 2024 Jan 19;14(1):1706.
    PMID: 38243057 DOI: 10.1038/s41598-024-52215-z
    The fashion industry has a significant impact on the environment, and sustainable fashion consumption (SFC) has become a pressing concern. This study aimed to investigate the factors influencing sustainable fashion consumption behavior (SCB) among Chinese adults, specifically the role of values, attitudes, and norms in shaping such behavior, using the value-belief-norm framework. The study used an online cross-sectional survey design to collect data from 350 participants recruited through a convenience sampling method using social media platforms and email invitations, and the obtained data were analyzed using partial least squares structural equation modelling. The results of the study showed that biospheric (BV), altruistic (AV), and egoistic (EV) values significantly influenced the New ecological paradigm (EP), which, in turn, positively affected awareness of consequences (AC). Personal norms (PN) were positively influenced by EP, AC, and ascription of responsibility (AR). Social norms (SN) and trust in recycling (TR) were also found to positively influence sustainable fashion consumption intentions (SCI). Finally, the study found that SCI and TR were significant predictors of SCB, whereas the moderating effect of TR not statistically significant. The study's originality lies in its comprehensive investigation of the interplay between various factors (particularly using norms in two facets; PN and SN) in shaping SCB, using a structural equation modeling approach, and exploring the moderating effect of TR. The findings of this study suggest that interventions aimed at promoting SFC should focus on fostering values and beliefs that prioritize the environment, encouraging individuals to take responsibility for their actions, creating an environment in which SFC is normalized, and increasing TR.
  7. Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC
    Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  8. Fulltext Peripheral Follicular T Helper Cells and Mucosal-Associated Invariant T Cells Represent Activated Phenotypes During the Febrile Phase of Acute Dengue Virus Infection
    Preeyaa SU, Murugesan A, Sopnajothi S, Yong YK, Tan HY, Larsson M, et al.
    Viral Immunol, 2020 11;33(9):610-615.
    PMID: 32996843 DOI: 10.1089/vim.2020.0149
    Peripheral follicular helper T (pTfh) cells represent specialized CD4+ T cells that help B cells to secrete antibodies. Dengue infection appears to cause immune activation in a wide array of immune cells. Herein, we investigated the signatures of immune activation of circulating Tfh cells and mucosal-associated invariant T (MAIT) cells in adult subjects with confirmed acute clinical dengue virus (DENV) infection by multiparametric flow cytometry. The acute DENV infection induced a significant expansion of highly activated pTfh cells and circulating MAIT cells during acute febrile infection. We found a higher frequency of activated PD-1+ Tfh cells and CD38+ pTfh cells in clinical DENV infection. We also found similar activated and expanding phenotypes of MAIT cells in the patients tested. The total counts of activated pTfh cells and circulating MAIT cells were higher in dengue patients relative to healthy controls. We concluded that pTfh cells and circulating MAIT cells represent activated phenotypes in acute DENV infection.
  9. Fulltext Effect of different cloning strategies in pET-28a on solubility and functionality of a staphylococcal phage endolysin
    Tham HY, Song AA, Yusoff K, Tan GH
    Biotechniques, 2020 09;69(3):161-170.
    PMID: 32787565 DOI: 10.2144/btn-2020-0034
    Endolysins have been studied intensively as an alternative to antibiotics. In this study, endolysin derived from a phage which infects methicillin-resistant Staphylococcus aureus (MRSA) was cloned and expressed in Escherichia coli pET28a. Initially, the endolysin was cloned using BamHI/XhoI, resulting in expression of a recombinant endolysin which was expressed in inclusion bodies. While solubilization was successful, the protein remained nonfunctional. Recloning the endolysin using NcoI/XhoI resulted in expression of soluble and functional proteins at 18°C. The endolysin was able to form halo zones on MRSA plates and showed a reduction in turbidity of MRSA growth. Therefore, cloning strategies should be chosen carefully even in an established expression system as they could greatly affect the functionality of the expressed protein.
  10. Diminished Co-inhibitory Molecule 2B4 expression is Associated with Preserved iNKT cell Phenotype in HIV Long-term Non-progressors
    Ansari AW, Ahmad F, Shankar EM, Kong YY, Tan HY, Jacobs R, et al.
    J Acquir Immune Defic Syndr, 2020 May 07.
    PMID: 32398557 DOI: 10.1097/QAI.0000000000002399
    BACKGROUND: We have previously shown an association of elevated co-inhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term non-progressors (LTNPs) and progressors.

    METHODS: Anti-retroviral therapy (ART) naïve HIV-seropositive individuals (progressors, n=16) and long-term non-progressors (LTNPs, n=10) were recruited for this study. We employed multi-color flow cytometry on frozen peripheral blood mononuclear cells (PBMCs) to determine iNKT subset frequencies, the levels of co-inhibitory 2B4 expression, and intracellular IFN-γ production. CD1d tetramer was used to characterize iNKT cells.

    RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells as well as on their CD4 subsets compared to HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T cell count, HIV viral load and IFNγ production by iNKT cells.

    CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated co-inhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.

  11. WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Seoul, Republic of Korea, 25-26 June 2019
    Wadhwa M, Kang HN, Jivapaisarnpong T, WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Andalucia LR, Blades CDRZ, et al.
    Biologicals, 2020 May;65:50-59.
    PMID: 31959504 DOI: 10.1016/j.biologicals.2019.12.008
    The first global workshop on implementation of the WHO guidelines on procedures and data requirements for changes to approved biotherapeutic products adopted by the WHO Expert Committee in 2018 was held in June 2019. The workshop participants recognized that the principles based on sound science and the potential for risk, as described in the WHO Guidelines on post-approval changes, which constitute the global standard for product life-cycle management are providing clarity and helping national regulatory authorities in establishing guidance while improving time-lines for an efficient regulation of products. Consequently, the regulatory situation for post-approval changes and guideline implementation is changing but there is a disparity between different countries. While the guidelines are gradually being implemented in some countries and also being considered in other countries, the need for regional workshops and further training on post-approval changes was a common theme reiterated by many participants. Given the complexities relating to post-approval changes in different regions/countries, there was a clear understanding among all participants that an efficient approach for product life-cycle management at a national level is needed to ensure faster availability of high standard, safe and efficacious medicines to patients as per the World Health Assembly Resolution 67.21.
  12. Fulltext Modulation of Crustacean Innate Immune Response by Amino Acids and Their Metabolites: Inferences From Other Species
    Huang Z, Aweya JJ, Zhu C, Tran NT, Hong Y, Li S, et al.
    Front Immunol, 2020;11:574721.
    PMID: 33224140 DOI: 10.3389/fimmu.2020.574721
    Aquaculture production of crustaceans (mainly shrimp and crabs) has expanded globally, but disease outbreaks and pathogenic infections have hampered production in the last two decades. As invertebrates, crustaceans lack an adaptive immune system and mainly defend and protect themselves using their innate immune system. The immune system derives energy and metabolites from nutrients, with amino acids constituting one such source. A growing number of studies have shown that amino acids and their metabolites are involved in the activation, synthesis, proliferation, and differentiation of immune cells, as well as in the activation of immune related signaling pathways, reduction of inflammatory response and regulation of oxidative stress. Key enzymes in amino acid metabolism have also been implicated in the regulation of the immune system. Here, we reviewed the role played by amino acids and their metabolites in immune-modulation in crustaceans. Information is inferred from mammals and fish where none exists for crustaceans. Research themes are identified and the relevant research gaps highlighted for further studies.
  13. Fulltext Coordination of Nanoconjugation with an Antigen/Antibody for Efficient Detection of Gynecological Tumors
    Liu X, Yang X, Shao J, Hong Y, Gopinath SCB, Chen Y, et al.
    J Anal Methods Chem, 2020;2020:6528572.
    PMID: 32309010 DOI: 10.1155/2020/6528572
    Cervical, ovarian, and endometrial cancers are common in the female reproductive system. Cervical cancer starts from the cervix, while ovarian cancer develops when abnormal cells grow in the ovary. Endometrial or uterine cancer starts from the lining of the womb in the endometrium. Approximately 12,000 women are affected every year by cervical cancer in the United States. Squamous cell carcinoma antigen (SCC-Ag) is a well-established biomarker in serum for diagnosing gynecological cancers, and its levels were observed to be elevated in cervical, ovarian, and endometrial cancer patients. Moreover, SCC-Ag was used to identify the tumor size and progression stages. Various biosensing systems have been proposed to identify SCC-Ag; herein, enhanced interdigitated electrode sensing is presented with the use of gold nanoparticles (GNPs) to conjugate an antigen/antibody. It was proved that the limit of detection is 62.5 fM in the case of antibody-GNP, which is 2-fold higher than that by SCC-Ag-GNP. Furthermore, the antibody-GNP-modified surface displays greater current increases with concomitant dose-dependent SCC-Ag levels. High analytical performance was shown by the discrimination against α-fetoprotein and CYFRA 21-1 at 1 pM. An enhanced sensing system is established for gynecological tumors, representing an advance from the earlier detection methods.
  14. Factors influencing patients' hypertension self-management and sustainable self-care practices: a qualitative study
    M Yatim H, Wong YY, Neoh CF, Lim SH, Hassali MA, Hong YH
    Public Health, 2019 Aug;173:5-8.
    PMID: 31207425 DOI: 10.1016/j.puhe.2019.04.020
    OBJECTIVE: The objective of this study was to explore factors influencing patients with hypertension to participating in a hypertension self-management education (HSME) programme and challenges of sustaining the learnt self-care practices.

    STUDY DESIGN: This was a qualitative study with focus group discussions.

    METHODS: Focus group discussions using a semistructured moderator guide were conducted among participants who had attended the HSME programme. Data were audio recorded, transcribed verbatim and analysed using a thematic analysis approach.

    RESULTS: Three focus groups involving 19 participants were conducted. Four major themes emerged from the data collected. Most participants enjoyed the group-based HSME sessions because sharing experiences with those having similar health problems can reduce their sense of isolation. However, the participants highlighted the difficulty in sustaining self-care practices in the presence of friends and family influences.

    CONCLUSION: A number of patient-, family- and community-level motivators and barriers to patients' hypertension self-management have been identified. Efforts to tailor behavioural interventions to sustain daily self-care activities during social and cultural events are imperative.
  15. Fulltext Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects
    Yong YK, Tan HY, Saeidi A, Wong WF, Vignesh R, Velu V, et al.
    Front Microbiol, 2019;10:2789.
    PMID: 31921004 DOI: 10.3389/fmicb.2019.02789
    Tuberculosis (TB) treatment monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. Although GeneXpert detects total DNA present in the sample regardless live or dead bacilli present in clinical samples, all the commercial tests available thus far have low sensitivity. Humoral responses against Mycobacterium tuberculosis (Mtb) antigens are generally low, which precludes the use of serological tests for TB diagnosis, prognosis, and treatment monitoring. Mtb-specific CD4+ T cells correlate with Mtb antigen/bacilli burden and hence might serve as good biomarkers for monitoring treatment progress. Omics-based techniques are capable of providing a more holistic picture for disease mechanisms and are more accurate in predicting TB disease outcomes. The current review aims to discuss some of the recent advances on TB biomarkers, particularly host biomarkers that have the potential to diagnose and differentiate active TB and LTBI as well as their use in disease prognosis and treatment monitoring.
  16. Fulltext Water-based alkyl ketene dimer ink for user-friendly patterning in paper microfluidics
    Hamidon NN, Hong Y, Salentijn GI, Verpoorte E
    Anal Chim Acta, 2018 Feb 13;1000:180-190.
    PMID: 29289307 DOI: 10.1016/j.aca.2017.10.040
    We propose the use of water-based alkyl ketene dimer (AKD) ink for fast and user-friendly patterning of paper microfluidic devices either manually or using an inexpensive XY-plotter. The ink was produced by dissolving hydrophobic AKD in chloroform and emulsifying the solution in water. The emulsification was performed in a warm water bath, which led to an increased rate of the evaporation of chloroform. Subsequent cooling led to the final product, an aqueous suspension of fine AKD particles. The effects of surfactant and AKD concentrations, emulsification procedure, and cooling approach on final ink properties are presented, along with an optimized protocol for its formulation. This hydrophobic agent was applied onto paper using a plotter pen, after which the paper was heated to allow spreading of AKD molecules and chemical bonding with cellulose. A paper surface patterned with the ink (10 g L-1 AKD) yielded a contact angle of 135.6° for water. Unlike organic solvent-based solutions of AKD, this AKD ink does not require a fume hood for its use. Moreover, it is compatible with plastic patterning tools, due to the effective removal of chloroform in the production process to less than 2% of the total volume. Furthermore, this water-based ink is easy to prepare and use. Finally, the AKD ink can also be used for the fabrication of so-called selectively permeable barriers for use in paper microfluidic networks. These are barriers that stop the flow of water through paper, but are permeable to solvents with lower surface energies. We applied the AKD ink to confine and preconcentrate sample on paper, and demonstrated the use of this approach to achieve higher detection sensitivities in paper spray ionization-mass spectrometry (PSI-MS). Our patterning approach can be employed outside of the analytical lab or machine workshop for fast prototyping and small-scale production of paper-based analytical tools, for use in limited-resource labs or in the field.
  17. Fulltext Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
    Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.
    Front Immunol, 2018;9:472.
    PMID: 29616020 DOI: 10.3389/fimmu.2018.00472
    Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
  18. Decrease of CD69 levels on TCR Vα7.2+CD4+ innate-like lymphocytes is associated with impaired cytotoxic functions in chronic hepatitis B virus-infected patients
    Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.
    Innate Immun, 2017 07;23(5):459-467.
    PMID: 28606013 DOI: 10.1177/1753425917714854
    Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
  19. 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 

  20. Fulltext Negative Checkpoint Regulatory Molecule 2B4 (CD244) Upregulation Is Associated with Invariant Natural Killer T Cell Alterations and Human Immunodeficiency Virus Disease Progression
    Ahmad F, Shankar EM, Yong YK, Tan HY, Ahrenstorf G, Jacobs R, et al.
    Front Immunol, 2017;8:338.
    PMID: 28396665 DOI: 10.3389/fimmu.2017.00338
    The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4(-)iNKT cells, 2B4 expression was significantly higher on CD4(+) iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
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