143 research outputs found
Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease
No full textCopyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients.
Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ.
Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score.
Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London
Clinic
The Effect of Aerobic Training on Parathyroid Hormone and Alkaline Phosphatase as Bone Markers in Men with Mild to Moderate Asthma: The Effect of Aerobic Training on Parathyroid Hormone …
No full textBackground and Aim: Inhalation of corticosteroids in patients with asthma is associated with an increased risk of osteoporosis. This study aimed to assess the effect of aerobic training on alkaline phosphatase (ALP), parathyroid hormone (PTH) as bone biomarkers in men with mild to moderate asthma.
Methods: Twenty four sedentary middle-aged men with asthma aged 40±5 years were randomly assigned to two groups as exercise (aerobic training, n=12) and control (no training, n =12). Aerobic training was performed 3 days a week for 12 weeks in the form of running on a flat surface at 60-75% of HRmax. Fasting blood samples were taken before and after the training program for measuring serum ALP and PTH.
Results: There were no statistically significant differences between groups with regard to anthropometrical and bone markers at baseline (p>0.05). Aerobic training resulted in significant increase in ALP (p = 0.023) and PTH (p = 0.016) in exercise individuals. All variables remained unchanged in the control group (p>0.05).
Conclusion: With an emphasis on the increase in ALP and PTH, it is concluded that relatively long-term aerobic exercise is associated with improved bone formation markers in patients with asthma treated with inhaled corticosteroids.
*Corresponding Author: Mojtaba Eizadi; Email: [email protected]
Please cite this article as: Eizadi M, Behboudi L, Afsharmand Z. The Effect of Aerobic Training on Parathyroid Hormone and Alkaline Phosphatase as Bone Markers in Men with Mild to Moderate Asthma. Arch Med Lab Sci. 2020;6:1-9 (e20). https://doi.org/10.22037/amls.v6. 3353
Association of COX-2-induced TGF-β+ suppressor T-cells in the immunosuppression induced by Marek’s disease virus
No full textThis thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonMarek's disease virus (MDV) is an avian alphaherpesvirus that transforms CD4+ T
cells, causes a deadly lymphoma, and induces immunosuppression in the infected
chickens. However, the underlying mechanisms of MDV-induced immunosuppression
have not yet been established. The hypothesis for this project is that MDV infection
induces the expansion of regulatory T (Treg)-cells in chickens via the activation of
Cyclooxygenase-2 (COX-2)/ prostaglandin E2 (PGE2) and through the expression of
the inhibitory molecule-transforming growth factor-β (TGF-β) at membrane-bound and
intercellular levels. The hypothesis is that the TGF-β activation is dependent on the
induction of pathways which are exclusive to the virulent virus but not the nonpathogenic
strains. This PhD project aims to identify the mechanism involved in the
induction of putative Treg cells in the MDV-infected chickens.
As the orthologue for FoxP3 (Forkhead Box P3), a classical marker, for the
identification of human and murine Tregs, had not been found in chickens, we used
membrane bound TGF-β on CD4 and CD4+CD25+ T cells as a marker for identification
of chicken Treg cells. An in vitro CFSE-based T cell inhibition assay was used to
demonstrate the inhibitory properties of chicken TGF-β+CD4+ T cells. Similarly, data
from RT-qPCR showed a high expression of immunosuppressive genes such as
CTLA-4. IL-10, PD-1 and PDL-1 by chicken TGF-β+ CD4+ T cells. Using flow
cytometry, the frequencies of TGF-β+ Treg-like cells, were found to be expressed at
higher frequencies in higher in genetically MD-susceptible compared to that in
genetically MD-resistant chicken lines. Interestingly, infection of chickens with virulent,
but not the vaccine strain, induced expansion of TGF-β+ Treg-like cells at 4 days post
infection in the lungs and 21 days post infection in splenocytes of the infected
chickens. The results suggest that expansion of these cells is associated with MDVinduced
immunosuppression.
In the last chapter of this thesis, the mechanisms involved in the expansion of TGF-
β+ Treg cells during MDV infection were explored. The RT-PCR, western blot and/or
PGE2 ELISA assays were utilized to demonstrate the activation of COX-2/PGE2
pathway by the virulent, but not the vaccine strains of MDV. In the absence of the
chemical inhibitors of the COX-2/PGE2 pathway, MDV infection upregulated ITGB8 gene, encoding integrin avb8 receptor, on chicken macrophages as determined
using RT-PCR. Using gene silencing approach and the chemical inhibitors, the
results showed that the macrophages, exposed to soluble factors released from
MDV-infected cells, obtained the ability to induce TGF-β in an COX2/PGE2/ITGB8
dependent manner. TGF-β maturation was determined using an adopted the
luciferase assay to determine the bioactivity of TGF-β. Using gene silencing
techniques, the results confirmed that ITGB8-induced TGF-β maturation by the
macrophages is required for induction of TGF-β+ Treg-like cells with the ability to
suppress T cell proliferation in vitro and express immunosuppressive genes including
CTLA4, PD1, PDL1 and IL-10.
Current MDV vaccines do not provide sterilizing immunity and the vaccinated birds
can shed the virus after infection. Such imperfect vaccines put the MDV viruses under
high selection pressure which can drive the evolution of more virulent pathogen strains
of MDV. A comprehensive understanding of host-pathogen interaction and an
identification of novel targets and immune mechanisms involved in the pathogenesis
of MD could prove useful in providing new insights essential for the development of
more effective vaccines. Collectively, the results from this PhD project extend our
understanding of the immune mechanisms involved in MDV-induced
immunosuppression and could potentially be exploited for the future development of
novel immune approaches against MDV.BBSR
Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2
No full textCopyright © 2021 Kamble, Gurung, Kaufer, Pathan and Behboudi. Marek’s disease virus (MDV), an avian alphaherpesvirus, infects chickens, transforms CD4+ T cells, and induces immunosuppression early during infection. However, the exact mechanisms involved in MDV-induced immunosuppression are yet to be identified. Here, our results demonstrate that MDV infection in vitro and in vivo induces activation of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). This exerts its inhibitory effects on T cell proliferation at day 21 post infection via PGE2 receptor 2 (EP2) and receptor 4 (EP4). Impairment of the MDV-induced T cell proliferation was associated with downregulation of IL-2 and transferrin uptake in a COX-2/PGE2 dependent manner in vitro. Interestingly, oral administration of a COX-2 inhibitor, meloxicam, during MDV infection inhibited COX-2 activation and rescued T cell proliferation at day 21 post infection. Taken together, our results reveal a novel mechanism that contributes to immunosuppression in the MDV-infected chickens.U.K. Research and Innovation Biotechnology and Biological Sciences Research Council Grants BBS/E/I/00001825, BBS/E/I/00007030, BBS/E/I/00007031, BB/S01506X/1, BBS/E/I/00002529, BBS/E/I/00007039, BBS/E/I/00007032, BB/N002598/1 and BB/V019031/1
Direct Growth Inhibitory Effect of Platelet Activating Factor C-16 and Its Structural Analogs on Mycobacteria
No full textCopyright © 2018 Riaz, Kaur, Shwayat, Behboudi, Kishore and Pathan. Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is one of the leading causes of human deaths due to a single infectious agent. M.tb infection of the host initiates a local inflammatory response, resulting in the production of a range of inflammatory factors at the site of infection. These inflammatory factors may come in direct contact with M.tb and immune cells to activate different signalling pathways. One such factor produced in excess during inflammation is a phospholipid compound, Platelet Activating Factor C-16 (PAF C-16). In this study, PAF C-16 was shown to have a direct inhibitory effect on the growth of
Mycobacterium bovis BCG (M.bovis BCG) and Mycobacterium smegmatis (M.smegmatis) in a dose and time-dependent manner. Use of a range of PAF C-16 structural analogues, including the precursor form Lyso-PAF, revealed that small modifications in the structure of
PAF C-16 did not alter its mycobacterial growth inhibitory properties. Subsequent experiments suggested that the attachment of aliphatic carbon tail via ether bond to the glycerol backbone of PAF C-16 was likely to play a vital role in its growth inhibition ability against mycobacteria. Fluorescence microscopy and flow cytometry using Propidium iodide (PI) indicated that PAF C-16 treatment had a damaging effect on the cell membrane of M.bovis BCG and M.smegmatis. Furthermore, the growth inhibitory effect of PAF C-16 was partially mitigated by treatment with membrane-stabilizing agents, α-tocopherol and Tween-80, which further suggests that the growth inhibitory effect of PAF C-16 was mediated through bacterial cell membrane damage
Preeclampsia and the ten-year risk of incident chronic kidney disease
No full textThis is an Accepted Manuscript of an article published by S. Karger AG in CardioRenal Medicine in May 2020. Available online: https://www.karger.com/Article/FullText/506469This is an Accepted Manuscript of an article published by S. Karger AG in CardioRenal Medicine in May 2020.Available online: https://www.karger.com/Article/FullText/506469acceptedVersio
Skin: Clear cell hidradenoma of the skin (CCH)
No full textReview on Skin: Clear cell hidradenoma of the skin (CCH), with data on clinics, and the genes involved
Trends of women's authorship in an Iranian medical journal from 1999 to 2019
No full textAuthor's gender is a potential factor in scientific publications. We evaluated the trends of authorship gender by focusing on women in an Iranian medical journal and followed two aims: A) Mapping gender trends in authorship positions; B) Drawing the patterns among authors. Our results showed that between 1999 and 2019, the role of women as first author was 26.7 and 54.9 (p < 0.05); as last authors 33.3 and 37.3 and as corresponding author 23.3 and 36.7, respectively. Despite progresses made by women, they were not significantly successful as corresponding and last authors. Further researchers around the world can have similar focus and be useful in making decisions for equality issues
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