فهرست مطالب

  • Volume:17 Issue: 1, 2020
  • تاریخ انتشار: 1399/01/27
  • تعداد عناوین: 10
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  • Hongyan Xu, Yueqing Yang, Qianhong Wu, Yan Zhang * Pages 1-13
    Background
    Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB).
    Objective
    To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB.
    Methods
    We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence.
    Results
    The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71. Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous.
    Conclusion
    Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence.
    Keywords: Drug Resistant, PD-L1, Th1, Th2, Tuberculosis
  • John Gordon Page 2
  • Meiling Hou, Xiaodong Wang, Jike Lu, Xun Guo, Cong Ding, Taotao Liang, Zhenyu Ji, Peng Xie, Xin Liu *, Qiaozhen Kang Pages 14-25
    Background
    Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination.
    Objective
    To improve the efficacy of dendritic cell-based vaccines by the adjuvant activity of Helicobacter pylori neutrophil activating protein (HP-NAP), which is a virulence factor of Helicobacter pylori, has been proved as a TLR agonist with effective immunomodulatory activity.
    Methods
    The recombinant HP-NAP (rHP-NAP) was expressed by using prokaryotic expression system. Dendritic cells (DCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After treating with rHP-NAP, the maturation of DCs and dendritic cell-based vaccine were assayed by using flow cytometry and qRT-PCR. The activation and proliferation of T cells were measured by FCM, ELISA and MTT methods. The tumor specific cytotoxic response to resistant B16F10 was detected by using lactate dehydrogenase-release assay and qRT-PCR.
    Results
    The recombinant HP-NAP (rHP-NAP), prepared from E. coli prokaryotic expression system, was able to significantly promote the maturation of dendritic cell-based vaccine loaded with tumor cell lysate (TCL) of B16F10 (DC-B16F10-TCL). Furthermore, it effectively induced the activation and proliferation of T cells and tumor specific cytotoxic response to resistant B16F10 melanoma tumor cells.
    Conclusion
    These results suggested that rHP-NAP possesses the potential for use as an adjuvant of dendritic cell-based vaccine in anti-melanoma treatment.
    Keywords: Cytotoxic Response, Dendritic Cell-Based Vaccine, Melanoma, rHP-NAP
  • Yousef Nikmanesh, Shohreh Shahmahmoodi, Ramin Yaghobi, SayedMahdi Marashi, Mahmood Mahmoudi, Mahdokht Hossein Aghdaie, Maryam Khosravi, MohammadHossein Karimi * Pages 26-40
    Background

    Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated.

    Objective

    To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs).

    Methods

    Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized. Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs.

    Results

    A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α.

    Conclusion

    Despite improvements in maturity status, pp150-stimulated DCs does not seem to be able to induce Th1 or Th2 immunity. In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's action mechanism. However, it is necessary to conduct further investigations to corroborate these observations.

    Keywords: Dendritic Cell Maturation, Cytomegalovirus, pp150
  • Khadijeh Ramezani Ali Akbari, Anwar Fathollahi, SeyedMahmoud Hashemi, Ramin Pouriran, Farshid Yeganeh * Pages 41-51
    Background

    Emerging evidence suggests that secretome of mesenchymal stem cells has many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of autoimmune and degenerative diseases. Dipeptidyl Peptidase-IV (DPP-IV)/CD26 and Aminopeptidase N (APN)/CD13 are ubiquitous ecto-enzymes which can digest various substrates including some chemokines and neuropeptides that are involved in inflammatory conditions.

    Objective

    To evaluate the enzymatic activity of DPP-IV/CD26 and APN/CD13 in MSC conditioned media (MSC-CM).

    Methods

    The MSCs were isolated from the mouse’s abdominal adipose tissues and were cultured without or with preconditioning by adding 2 µg/mL phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). The levels of interleukin-10 (IL-10), nitric oxide (NO), as well as the enzymatic activities of DPP-IV/CD26 and APN/CD13 were measured in MSC-CM.

    Results

    The level of IL-10 and the enzyme activity of APN/CD13 did not show any changes in the MSC-CM of stimulated and non-stimulated cells. However, NO production was increased after treatment by LPS or PMA; nevertheless, the DPP-IV/CD26 activity was decreased in MSC-CM merely following the stimulation of cells with LPS.

    Conclusion

    Our results indicated that MSC‐secretome had DPP-IV/CD26 and APN/CD13 activity. The DPP-IV/CD26 activity was decreased following stimulation of MSCs by toll-like receptor 4 agonist. Further studies are needed to reveal the possible contribution of DPP-IV/CD26 and APN/CD13 in the anti-inflammatory functions of MSC-CM.

    Keywords: Aminopeptidase N, CD13, CD26, Dipeptidyl Peptidase-IV, Mesenchymal Stem Cells
  • Min Lin, Jin Huang, Wei Chang Chen, Zhi Ning Fan, Xihu Qin * Pages 52-63
    Background

    Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well.

    Objective

    To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice.

    Methods

    Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA kits. Quantitative RT-PCR was performed to detect the transcript amounts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis.

    Results

    The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway.

    Conclusion

    Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

    Keywords: Acute Pancreatitis, Peritoneal Macrophage, Tim-3
  • Elahe Amirinezhad Fard, Zahra Fereydouni, Kamran Mansouri, Ali Mostafaie * Pages 64-74
    Background
    Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol.
    Objective
    To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L. (TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cell (HBMEC) lines.
    Methods
    Two cell lines were cultured and induced with lipopolysaccharide (LPS). The primed cells were then treated with aqueous extract and saponin fraction of TT. The protein profile of the endothelial cells was assessed under normal and LPS-induced conditions using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 2D gel electrophoresis (2-DE). The levels of VCAM-1, ICAM-1, and E-selectin were estimated by use of western blotting.
    Results
    LPS-induced HUVECs and HBMECs were shown to significantly increase the expression of ICAM-1, VCAM-1, and E-selectin in comparison to control groups. Our findings revealed that TT extract resulted in significantly more reduced levels of proteom (80 spots) as well as all the three mentioned proteins compared with the effect of saponin fraction alone.
    Conclusion
    TT extract and its saponin fraction exerted anti-inflammatory effects on HUVEC and HBMEC lines and reduced the expression of ICAM-1, VCAM-1, and E-selectin. However, the anti-inflammatory effect of aqueous extract was greater than that of saponin fraction. Therefore, TT could be considered as a potential candidate for the treatment or prevention of atherosclerosis.
    Keywords: ICAM-1, VCAM-1, Endothelial cells, Proteome, Tribulus Terrestris
  • Leila Safari Zanjani, Reza Shapoury *, Mehrouz Dezfulian, Mehdi Mahdavi, Mehdi Shafieeardestani Pages 75-86
    Background
    Pseudomonas aeruginosa has an important role in nosocomial infections.
    Objective
    To evaluate biological activity of the detoxified LPS (D-LPS) entrapped into Poly lactic-co-glycolic acid (PLGA) nanoparticles. Materials: LPS was extracted and detoxified from the P. aeruginosa strain PAO1. The D-LPS, conjugated to the PLGA nanoparticles with 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDAC) and N-hydroxy-succinimide (NHS). The connection was evaluated by FTIR (Fourier transform infrared), Zetasizer, and Atomic Force Microscope (AFM). The BALB/c mice injected intramuscularly with the D-LPS-PLGA with two-week intervals and then challenged two weeks after the last immunization. The bioactivity of the induced specific antisera  and cytokines responses against D-LPS-PLGA antigen was assessed by ELISA.
    Results
    D-LPS-PLGA conjugation was confirmed by FTIR, Zetasizer, and AFM. The ELISA results showed that D-LPS was successful in the stimulation of the humoral immune response. The immune responses raised against the D-LPS-PLGA, significantly decreased bacterial titer in the spleen of the immunized mice after challenge with PAO1 strain in comparison with the control groups.
    Conclusion
    The conjugation of the bacterial LPS to the PLGA nanoparticle increased their functional activity by decrease in bacterial dissemination and increase the killing of opsonized bacteria.
    Keywords: LPS, nanovaccine, PLGA, Pseudomonas Aeruginosa
  • Marina Nayeli Medina Rosales, Susana Godina Gonzalez, Mariana Haydee Garcia Hernandez * Pages 87-93
    Background

    Drugs used in cancer treatment specifically kill T regulatory cells.

    Objective

    To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) in plasma was evaluated by ELISA assay.

    Results

    Increased percentages of CD4+CD25+ T cells, CD4+CD39+ T cells, CD4+Foxp3+ T cells, and CD4+CD25High T cells were observed in children with ALL in comparison to healthy controls. In addition, the ALL patients with >12 months of therapy showed increased CD4+CD39+ T cells compared to the ALL patients with ≤12 months and healthy controls. Similarly, the CD4+CD25+ T cells and CD4+Foxp3+ T cells increased according to maintenance therapy time.

    Conclusion

    Our results showed increased percentages of regulatory T cells in pediatric ALL patients despite chemotherapy, which might be compromising the anti-leukemic cellular immune response.

    Keywords: Acute Lymphoblastic Leukemia, ALL, Chemoterapy, Pedriatic, T Regulatory Cells
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