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  1. Fulltext Experimental exposure of Burkholderia pseudomallei crude culture filtrate upregulates PD-1 on T lymphocytes
    Menon N, Mariappan V, Vellasamy KM, Samudi C, See JX, Ganesh PS, et al.
    Access Microbiol, 2020;2(5):acmi000110.
    PMID: 32974575 DOI: 10.1099/acmi.0.000110
    Burkholderia pseudomallei is the causative agent for melioidosis. Because of its intracellular nature, the bacterium is capable of replicating within a plethora of eukaryotic cell lines. B. pseudomallei can remain dormant within host cells without symptoms for years, causing recrudescent infections. Here, we investigated the pathogenesis mechanism behind the suppression of T cell responses by B. pseudomallei . Peripheral blood mononuclear cells (1×106 cells/well) isolated by Ficoll Paque (Sigma-Aldrich) density gradient centrifugation were incubated with optimized concentrations of bacterial crude culture filtrate antigens (CFAs) (10 ug ml-1) and heat-killed bacteria [1 : 10 multiplicity of infection (m.o.i.)]. Following incubation, cells were investigated for surface expression of coinhibitory molecules by flow cytometry. We found that B. pseudomallei induced the upregulation of programmed death 1 (PD-1), a molecule responsible for T cell exhaustion, on T cells in vitro following exposure to crude CFAs of B. pseudomallei . This upregulation of PD-1 probably contributes to poor immune surveillance and disease pathogenesis.
    Matched MeSH terms: Leukocytes, Mononuclear
  2. Fulltext Effects of annexin A1 on apoptosis and cell cycle arrest in human leukemic cell lines
    Sabran A, Kumolosasi E, Jantan I
    Acta Pharm, 2019 Mar 01;69(1):75-86.
    PMID: 31259717 DOI: 10.2478/acph-2019-0005
    Recent studies suggest that annexin A1 (ANXA1) promotes apoptosis in cancerous cells. This study aims to investigate the effects of ANXA1 on apoptosis and cell cycle arrest in K562, Jurkat and U937 cells and peripheral blood mononu-clear cells (PBMC). Cells were treated with ANXA1 and cyclophosphamide prior to flow cytometry analysis for apoptosis and cell cycle arrest induction. At 2.5µM, ANXA1 induced significant apoptosis in K562 (p ≤ 0.001) and U937 (p ≤ 0.05) cells, with EC50 values of 3.6 and 3.8 µM, respectively. In Jurkat cells, induction was not significant (EC50, 17.0 µM). No significant apoptosis induction was observed in PBMC. ANXA1 caused cycle arrest in the G0/G1 phase in K562 and U937 cells with p ≤ 0.001 for both, and (p ≤ 0.01) for Jurkat cells. ANXA1 induced apoptosis and cycle arrest in the G0/G1 phase in K562 and U937 cells, causing only cell cycle arrest in Jurkat cells.
    Matched MeSH terms: Leukocytes, Mononuclear/metabolism*; Leukocytes, Mononuclear/physiology*
  3. Fulltext Newcastle disease virus strain AF2240 as an oncolytic virus: A review
    Kalyanasundram J, Hamid A, Yusoff K, Chia SL
    Acta Trop, 2018 Jul;183:126-133.
    PMID: 29626432 DOI: 10.1016/j.actatropica.2018.04.007
    The discovery of tumour selective virus-mediated apoptosis marked the birth of an alternative cancer treatment in the form of oncolytic viruses. Even though, its oncolytic efficiency was demonstrated more than 50 years ago, safety concerns which resulted from mild to lethal side effects hampered the progress of oncolytic virus research. Since the classical oncolytic virus studies rely heavily on its natural oncolytic ability, virus manipulation was limited, thereby, restricted efforts to improve its safety. In order to circumvent such restriction, experiments involving non-human viruses such as the avian Newcastle disease virus (NDV) was conducted using cultured cells, animal models and human subjects. The corresponding reports on its significant tumour cytotoxicity along with impressive safety profile initiated immense research interest in the field of oncolytic NDV. The varying degree of oncolytic efficiency and virulency among NDV strains encouraged researchers from all around the world to experiment with their respective local NDV isolates in order to develop an oncolytic virus with desirable characteristics. Such desirable features include high tumour-killing ability, selectivity and low systemic cytotoxicity. The Malaysian field outbreak isolate, NDV strain AF2240, also currently, receives significant research attention. Apart from its high cytotoxicity against tumour cells, this strain also provided fundamental insight into NDV-mediated apoptosis mechanism which involves Bax protein recruitment as well as death receptor engagement. Studies on its ability to selectively induce apoptosis in tumour cells also resulted in a proposed p38 MAPK/NF-κB/IκBα pathway. The immunogenicity of AF2240 was also investigated through PBMC stimulation and macrophage infection. In addition, the enhanced oncolytic ability of this strain under hypoxic condition signifies its dynamic tumour tropism. This review is aimed to introduce and discuss the aforementioned details of the oncolytic AF2240 strain along with its current challenges which outlines the future research direction of this virus.
    Matched MeSH terms: Leukocytes, Mononuclear
  4. Application of Ti3 C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine
    Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.
    Adv Healthc Mater, 2019 08;8(16):e1900569.
    PMID: 31265217 DOI: 10.1002/adhm.201900569
    Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.
    Matched MeSH terms: Leukocytes, Mononuclear/drug effects; Leukocytes, Mononuclear/metabolism
  5. Effect of exogenous nitric oxide on murine splenic immune response induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide
    Sosroseno W, Bird PS, Seymour GJ
    Anaerobe, 2009 Jun;15(3):95-8.
    PMID: 19402196 DOI: 10.1016/j.anaerobe.2009.01.002
    The aim of this study was to determine the effect of exogenous nitric oxide (NO) on the induction of murine splenic immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in vitro. BALB/c mice were immunized with A. actinomycetemcomitans LPS and a control group was sham-immunized. Spleen cells were obtained, cultured and stimulated with A. actinomycetemcomitans LPS with or without the presence of S-nitroso acetyl-penicillamine (SNAP), a NO donor, and carboxy-PTIO, an NO scavenger. Culture supernatants were assessed for inducible nitric oxide synthase (iNOS) activity, specific IgG subclass levels, and both IFN-gamma and IL-4 levels. The results showed that in A. actinomycetemcomitans LPS-stimulated cells, SNAP enhances iNOS activity but inhibits the levels of specific IgG2a and IFN-gamma suggesting a Th1 response. The effect of SNAP on these immune parameters was ablated by carboxy-PTIO. These results suggest that exogenous NO may suppress the Th1-like immune response of A. actinomycetemcomitans LPS-stimulated murine spleen cells.
    Matched MeSH terms: Leukocytes, Mononuclear/immunology
  6. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
    Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
    Matched MeSH terms: Leukocytes, Mononuclear/cytology*; Leukocytes, Mononuclear/metabolism
  7. Fulltext Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells
    Aziz J, Abu Kassim NL, Abu Kasim NH, Haque N, Rahman MT
    BMC Complement Altern Med, 2015;15:215.
    PMID: 26152209 DOI: 10.1186/s12906-015-0749-6
    Use of Carica papaya leaf extracts, reported to improve thrombocyte counts in dengue patients, demands further analysis on the underlying mechanism of its thrombopoietic cytokines induction
    Matched MeSH terms: Leukocytes, Mononuclear/cytology
  8. Fulltext Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus Schum. & Thonn. induces anti-tumor immune response
    Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM
    BMC Complement Altern Med, 2018 Aug 06;18(1):232.
    PMID: 30081891 DOI: 10.1186/s12906-018-2296-4
    BACKGROUND: Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release.

    METHODS: The effect of P. amarus-generated TLY on DCs maturation was evaluated by determination of MHC class I, II and CD 11c expression as well as the co-stimulatory molecules CD 83 and 86 by using flow cytometry. The phagocytic capacity of TLY-pulsed DCs was investigated through FITC-dextran uptake by using flow cytometry. The effect on the cytokines release including IL-12, IL-6 and IL-10 was elucidated by using ELISA. The migration capacity and T cell proliferation activity of pulsed DCs were measured. The relative gene expression levels of cytokines were determined by using qRT-PCR. The major constituents of P. amarus extract were qualitatively and quantitatively analyzed by using validated reversed-phase high performance liquid chromatography (HPLC) methods.

    RESULTS: P. amarus-generated TLY significantly up-regulated the expression levels of MHC class I, CD 11 c, CD 83 and 86 in pulsed DCs. The release of interleukin IL-12 and IL-6 was enhanced by TLY-DCs at a ratio of 1 DC: 3 tumor apoptotic bodies (APO), however, the release of IL-10 was suppressed. The migration ability as well as allogeneic T-cell proliferation activities of loaded DCs were significantly enhanced, but their phagocytic capacity was highly attenuated. The gene expression profiles for IL-12 and IL-6 of DCs showed increase in their mRNA gene expression in TLY pulsed DCs versus unloaded and LPS-treated only DCs.

    CONCLUSION: The effect of P. amarus-generated TLY on the immune effector mechanisms of DCs verified its potential to induce an in vitro anti-tumor immune response against the recognized tumor antigen.

    Matched MeSH terms: Leukocytes, Mononuclear/drug effects; Leukocytes, Mononuclear/immunology
  9. In-vitro antimalarial activity of methanolic leaf- and stem-derived extracts from four Annonaceae plants
    Lithanatudom P, Chawansuntati K, Saenjum C, Chaowasku T, Rattanathammethee K, Wungsintaweekul B, et al.
    BMC Res Notes, 2023 Dec 22;16(1):381.
    PMID: 38135870 DOI: 10.1186/s13104-023-06664-w
    OBJECTIVE: Plants in the Annonaceae family are known for having abundant biologically active secondary metabolites. They have been used in alternative drugs for various diseases in several countries, for instance, the bark of Cananga odorata (Lam.) Hook and Thomson is used for Ophthalmic inflammation and wound healing in Malaysia. Extracts from the leaves and stems of four Annonaceae plants, namely Uvaria longipes (Craib) L.L.Zhou, Y.C.F.Su & R.M.K.Saunders, Dasymaschalon sp., Artabotrys burmanicus A.DC, and Marsypopetalum modestum (Pierre) B.Xue & R.M.K.Saunders were investigated for growth inhibitory activity against blood-stage Plasmodium falciparum growth in vitro and for non-specific cytotoxicity against normal peripheral blood mononuclear cells (PBMCs). Antimalarial activity was assessed by invasion inhibition assay and the percentage of infected red blood cells on blood smears were determined. Cytotoxicity was tested by culturing PBMCs with the extracts, and viabilities were determined by Annexin V/propidium iodide staining.

    RESULTS: A. burmanicus stem extract and M. modestum leaf extract were capable of inhibiting growth of P. falciparum when used at 200 µg/mL compared to chloroquine. The extracts at effective concentrations, did not affect the viability of PBMCs. These results support further need for characterization of active compounds from specific Annonaceae plants in order to exploit their components for potential malaria treatment.

    Matched MeSH terms: Leukocytes, Mononuclear
  10. Effect of orally administered soy milk fermented with Lactobacillus plantarum LAB12 and physical exercise on murine immune responses
    Appukutty M, Ramasamy K, Rajan S, Vellasamy S, Ramasamy R, Radhakrishnan AK
    Benef Microbes, 2015;6(4):491-6.
    PMID: 25691103 DOI: 10.3920/BM2014.0129
    Probiotics are live microorganisms that confer health benefits through the gastrointestinal microbiota. This nutritional supplement may benefit athletes who undergo rigorous training by maintaining their gastrointestinal functions and overall health. In this study the influence of moderate physical exercise using a graded treadmill exercise, alone or in combination with the consumption of a soy product fermented with Lactobacillus plantarum LAB12 (LAB12), on tumour necrosis factor alpha (TNF-α) responses was investigated in a murine model. Male BALB/c mice were randomly divided into four groups of six mice each (control, exercise alone, LAB12 and LAB12 + exercise). Mice treated with the potential probiotic LAB12 were orally gavaged for 42 days. At autopsy, blood and spleen from the animals were collected. The splenocytes were cultured in the presence of a mitogen, concanavalin A (Con A). The amount of TNF-α produced by the Con A-stimulated splenocytes was quantified using ELISA, while their proliferation was determined using the [(3)H]-thymidine incorporation method. This study shows that LAB12-supplemented and exercise-induced mice showed marked increase (P<0.05) in cell proliferation compared to the control animals. TNF-α production was suppressed (P<0.05) in the LAB12 group compared to the untreated mice. These results demonstrate that supplementation with LAB12 has immunomodulatory effects, under conditions of moderate physical exercise, which may have implications for human athletes. Further investigation in human trials is warranted to confirm and extrapolate these findings.
    Matched MeSH terms: Leukocytes, Mononuclear/drug effects; Leukocytes, Mononuclear/immunology
  11. Fulltext Single nucleotide polymorphism in the promoter of the human interleukin-13 gene is associated with asthma in Malaysian adults
    Radhakrishnan AK, Raj VL, Tan LK, Liam CK
    Biomed Res Int, 2013;2013:981012.
    PMID: 23865080 DOI: 10.1155/2013/981012
    Asthma susceptibility genes are mapped to a region on human chromosome 5q31-q33, which contains a cluster of proinflammatory cytokine genes such as interleukin-13 (IL-13), which is associated with asthma. This study investigated the allele frequencies of two single nucleotide polymorphisms (SNPs) (-1111C>T and 4257C>A) in the IL-13 gene between asthmatics and healthy volunteers as well as the relationship between these SNPs and IL-13 production. DNA extracted from buffy coat of asthmatic and control subjects was genotyped using the PCR-RFLP method. Amount of IL-13 produced by mitogen-stimulated peripheral blood leucocytes PBLs (PBLs) was determined by ELISA. The frequencies of the -1111C and 4257G wild-type alleles were 0.52 and 0.55 in asthmatics and were 0.67 and 0.56 in controls. A significant (P < 0.05) association was found between genotype and allele frequencies of SNP at position -1111C>T between asthmatic and control groups (OR, 1.810; 95% CI = 1.184 to 2.767; P < 0.05). The mitogen-stimulated PBLs from asthmatics produced higher amounts of IL-13 production (P < 0.001). The 4257GA heterozygous and 4257AA homozygous mutant alleles were associated with higher IL-13 production in asthmatics (P < 0.05). Our results show that the -1111T mutant allele are associated with asthma and the 4257A mutant alleles are associated with elevated IL-13 production.
    Matched MeSH terms: Leukocytes, Mononuclear/metabolism
  12. Lectin extracts of champedak seeds demonstrate selective stimulation of T lymphocyte proliferation
    Hashim OH, Gendeh GS, Jaafar MI
    Biochem. Int., 1992 Jun;27(1):139-43.
    PMID: 1627170
    The effect of extracts of champedak (Artocarpus integer) seed lectin on the proliferation of normal human lymphocyte was investigated. The IgA1 binding lectin was demonstrated to stimulate the proliferation of human peripheral blood mononuclear cells. Action of the lectin on enriched T and B cell populations demonstrated T lymphocyte specificity. The lectin was not mitogenic to B lymphocytes. Optimal stimulation of proliferative response was achieved when cells were subjected to 5 days exposure to the crude lectin at 20 micrograms/ml.
    Matched MeSH terms: Leukocytes, Mononuclear/drug effects
  13. Antioxidant enzyme activities of human peripheral blood mononuclear cells exposed to trace elements
    Kuppusamy UR, Dharmani M, Kanthimathi MS, Indran M
    Biol Trace Elem Res, 2005 Jul;106(1):29-40.
    PMID: 16037608
    The trace elements copper, zinc, and selenium are important immune modulators and essential cofactors of the antioxidant enzymes. In the present study, the proliferative effect of human peripheral mononuclear cells (PBMCs) that have been exposed to copper, zinc, and selenium and the corresponding activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, were determined. Zinc and copper stimulated the PBMC proliferation in a dose-dependent manner within the dose range 25-200 micromol/L. SOD and GPx activities in PBMCs exposed to zinc were inhibited, whereas catalase activity was unaffected. All the three antioxidant enzymes in the cells exposed to copper were inhibited. Selenium exerted more potent inhibition of the cell proliferation while causing stimulation of the antioxidant enzymes at the lowest dose (25 micromol/L) than at the highest dose (200 micromol/L) tested. A significant negative correlation was observed between proliferation and antioxidant enzyme (SOD and GPx) activities in trace-element-exposed PBMC. The present findings substantiate the importance of trace elements as immune modulators and the involvement of enzymatic antioxidant system in the immune cell regulation.
    Matched MeSH terms: Leukocytes, Mononuclear/cytology*; Leukocytes, Mononuclear/drug effects*
  14. Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients
    Subramani B, Pullai CR, Krishnan K, Sugadan SD, Deng X, Hiroshi T, et al.
    Biomed Rep, 2014 Jul;2(4):505-508.
    PMID: 24944796
    Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the ex vivo activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8×107 initial PBMCs and 2.7×109 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large-scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.
    Matched MeSH terms: Leukocytes, Mononuclear
  15. Bioassay-guided identification of an anti-inflammatory prenylated acylphloroglucinol from Melicope ptelefolia and molecular insights into its interaction with 5-lipoxygenase
    Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, et al.
    Bioorg Med Chem, 2011 Nov 1;19(21):6340-7.
    PMID: 21958738 DOI: 10.1016/j.bmc.2011.09.001
    A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae) resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3-geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX. The anti-inflammatory action was also demonstrated on human leukocytes, where the compound showed prominent inhibitory activity against human PBML 5-LOX, with an IC(50) value of 0.42 μM, very close to the effect produced by the commonly used standard, NDGA. The compound concentration-dependently inhibited 5-LOX product synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50) value of 1.80 μM, and showed no cell toxicity effects. The anti-inflammatory action does not seem to proceed via redox or metal chelating mechanism since the compound tested negative for these bioactivities. Further tests on cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40 μM). The molecular features that govern the 5-LOX inhibitory activity was thus explored using in silico docking experiments. The residues Ile 553 and Hie 252 were the most important residues in the interaction, each contributing significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol (electrostatic and Van der Waals), respectively. The hydroxyl group of the phloroglucinol core of the compound forms a 2.56Å hydrogen bond with the side chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial amino acid residues which chelate with the metal ion in the active site. Distorting the geometry of these ligands could be the reason for the inhibition activity shown by tHGA. The molecular simulation studies supported the bioassay results and served as a good model for understanding the way tHGA binds in the active site of human 5-LOX enzyme.
    Matched MeSH terms: Leukocytes, Mononuclear/enzymology
  16. How the immune mousetrap works: Structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein
    Zabrodskaya Y, Tsvetkov V, Shurygina AP, Vasyliev K, Shaldzhyan A, Gorshkov A, et al.
    Biophys Chem, 2024 Apr;307:107176.
    PMID: 38219420 DOI: 10.1016/j.bpc.2024.107176
    One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization. It has also been suggested that this mechanism is used by influenza A virus in NS1-mediated immunosuppression. We have shown that the peptide corresponding to the primary structure of the potential immunosuppressive domain of NS1 protein (G51) can reduce concanavalin A-induced proliferation of PBMC cells, as well as in vitro, G51 can affect the oligomerization of the core peptide corresponding to the intramembrane domain of TCR, using AFM and small-angle neutron scattering. The results obtained using in cellulo and in vitro model systems suggest the presence of functional interaction between the NS1 fragment and the intramembrane domain of the TCR alpha subunit. We have proposed a possible scheme for such interaction obtained by computer modeling. This suggests the existence of another NS1-mediated mechanism of immunosuppression in influenza.
    Matched MeSH terms: Leukocytes, Mononuclear/metabolism
  17. Cryopreservation of Human Mesenchymal Stem Cells for Clinical Applications: Current Methods and Challenges
    Yong KW, Wan Safwani WK, Xu F, Wan Abas WA, Choi JR, Pingguan-Murphy B
    Biopreserv Biobank, 2015 Aug;13(4):231-9.
    PMID: 26280501 DOI: 10.1089/bio.2014.0104
    Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.
    Matched MeSH terms: Leukocytes, Mononuclear/cytology
  18. Peroxiredoxin of Arthrospira platensis derived short molecule YT12 influences antioxidant and anticancer activity
    Sannasimuthu A, Ramani M, Pasupuleti M, Saraswathi NT, Arasu MV, Al-Dhabi NA, et al.
    Cell Biol Int, 2020 Nov;44(11):2231-2242.
    PMID: 32716104 DOI: 10.1002/cbin.11431
    This study demonstrates both the antioxidant and anticancer potential of the novel short molecule YT12 derived from peroxiredoxin (Prx) of spirulina, Arthrospira platensis (Ap). ApPrx showed significant reduction in reactive oxygen species (ROS) against hydrogen peroxide (H2 O2 ) stress. The complementary DNA sequence of ApPrx contained 706 nucleotides and its coding region possessed 546 nucleotides between position 115 and 660. Real-time quantitative reverse transcription polymerase chain reaction analysis confirmed the messenger RNA expression of ApPrx due to H2 O2 exposure in spirulina cells at regular intervals, in which the highest expression was noticed on Day 20. Cytotoxicity assay was performed using human peripheral blood mononuclear cells, and revealed that at 10 μM, the YT12 did not exhibit any notable toxicity. Furthermore, ROS scavenging activity of YT12 was performed using DCF-DA assay, in which YT12 scavenged a significant amount of ROS at 25 μM in H2 O2 -treated blood leukocytes. The intracellular ROS in human colon adenocarcinoma cells (HT-29) was regulated by oxidative stress, where the YT12 scavenges ROS in HT-29 cells at 12.5 μM. Findings show that YT12 peptide has anticancer activity, when treated against HT-29 cells. Through the MTT assay, YT12 showed vital cytotoxicity against HT-29 cells. These finding suggested that YT12 is a potent antioxidant molecule which defends ROS against oxidative stress and plays a role in redox balance.
    Matched MeSH terms: Leukocytes, Mononuclear/metabolism
  19. Fulltext Autologous serum supplement favours in vitro regenerative paracrine factors synthesis
    Haque N, Kasim NHA, Kassim NLA, Rahman MT
    Cell Prolif, 2017 Aug;50(4).
    PMID: 28682474 DOI: 10.1111/cpr.12354
    OBJECTIVES: Foetal bovine serum (FBS) is often the serum supplement of choice for in vitro human cell culture. This study compares the effect of FBS and autologous human serum (AuHS) supplement in human peripheral blood mononuclear cell (PBMC) culture to prepare secretome.

    MATERIALS AND METHODS: The PBMC (n = 7) were cultured either in RPMI-1640 containing L-glutamine and 50 units/ml Penicillin-Streptomycin (BM) or in BM with either AuHS or FBS. Viability, proliferation and differentiation of PBMC were evaluated. Paracrine factors present in the secretomes (n = 6) were analysed using ProcartaPlex Human Cytokine panel (17 plex). Ingenuity Pathway Analysis (IPA) was performed to predict activation or inhibition of biological functions related to tissue regeneration.

    RESULTS: The viability of PBMC that were cultured with FBS supplement was significantly reduced at 96 h compared to those at 0 and 24 h (P 

    Matched MeSH terms: Leukocytes, Mononuclear/cytology; Leukocytes, Mononuclear/metabolism
  20. Gender effect on in vitro lymphocyte subset levels of healthy individuals
    Abdullah M, Chai PS, Chong MY, Tohit ER, Ramasamy R, Pei CP, et al.
    Cell Immunol, 2012;272(2):214-9.
    PMID: 22078320 DOI: 10.1016/j.cellimm.2011.10.009
    Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome.
    Matched MeSH terms: Leukocytes, Mononuclear/immunology*
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