scholarly journals Bioinformatic Analysis Identified Hub Genes Associated with Heterocyclic Amines Induced Cytotoxicity of Peripheral Blood Mononuclear Cells

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1888
Author(s):  
Xinyang Li ◽  
Lu Dong ◽  
Huaning Yu ◽  
Yan Zhang ◽  
Shuo Wang

Heterocyclic amines (HCAs) are a set of food contaminants that may exert a cytotoxic effect on human peripheral blood mononuclear cells (PBMC). However, the genetic mechanism underlying the cytotoxicity of HCAs on PBMC has not been investigated. In the study, bioinformatic analysis on gene dataset GSE19078 was performed. The results of weighted correlation network analysis and linear models for microarray and RNA-seq data analysis showed that four gene modules were relevant to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exposure while one gene module was correlated with 2-amino-3-methyl-3H-imidazo[4,5f]quinoline (IQ) exposure. Gene functional analysis showed that the five modules were annotated mainly with mRNA transcriptional regulation, mitochondrial function, RNA catabolic process, protein targeting, and immune function. Five genes, MIER1, NDUFA4, MLL3, CD53 and CSF3 were recognized as the feature genes for each hub gene network of the corresponding gene module, and the expression of feature genes was observed with a significant difference between the PhIP/IQ samples and the other samples. Our results provide novel genes and promising mechanisms for exploration on the genetic mechanism of HCAs on PBMC.

2014 ◽  
Vol 40 (04) ◽  
pp. 181-190
Author(s):  
Shiow-Chen Lin ◽  
Tien-Fu Chuang ◽  
Chen-Shi Lin ◽  
Dah-Sheng Lin ◽  
Albert Taiching Liao

Canine transmissible venereal tumor (CTVT) is a tumor which can be transmitted naturally through mucosa contact between dogs. When CTVT cells are experimentally inoculated on dogs, they will grow rapidly (Progressive/P phase) and then regress (Regressive/R phase) spontaneously. Therefore, it is a good model to investigate the interactions between tumor cells and host immune system. Previous studies have shown that CTVT cells cannot grow in the dogs restored from CTVT inoculation. To investigate the possible mechanism, this study characterized the CTVT-specific immune response of the peripheral blood mononuclear cells (PBMCs) which isolated from the blood of "naïve" or "CTVT-restored" dogs. The phenotypes (CD3, CD4, CD8, or CD21) of PBMCs were examined by flowcytometry. In response to CTVT stimulation, proliferation, IFN-γ secretion, and cytotoxicity of PBMCs were analyzed. Expression level of proinflammatory cytokines (TNF-α, IL-1β, IL-6, TGF-β), Th1 (IL-2, IFN-γ), and Th2 cytokines (IL-4, IL-10) and cytotoxic proteins (Granzyme B, Perforin) in PBMCs was also evaluated by real-time RT-PCR. The results indicated that there is no significant difference between two groups on lymphocyte phenotypes. Proliferation, IFN-γ secretion, and cytotoxicity of PBMCs between two groups showed no significant difference, except naïve PBMCs present higher proliferation after Con-A stimulation. Production of IL-1β and IL-6 in naïve PBMCs was higher than that in CTVT-restored PBMCs (p < 0.05). The production difference of IL-1β and IL-6 between two groups might be the reason why CTVT cannot be reinoculated on CTVT-restored dog. However, further investigations are necessary to explore the exact role of these cytokines in CTVT growth.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 490-490
Author(s):  
Rachel Cole ◽  
Austin Angelotti ◽  
Genevieve Sparagna ◽  
Ai Ni ◽  
Martha Belury

Abstract Objectives Linoleic acid (LA) is the major fatty acid in cardiolipin (CL), a phospholipid important for mitochondria function. Increasing dietary LA elevates tetralinoleoyl CL (LA4 CL) in cardiac muscle of animals; however, it is not clear if dietary LA increases LA4 CL in humans. The aim of this study was to determine if daily consumption of a cookie made with a LA-rich oil for two weeks could alter LA4 CL in peripheral blood mononuclear cells (PBMC) in healthy adults. Methods In a double-masked placebo-controlled study, 84 healthy adults were randomly assigned to consume one cookie made with LA-rich grapeseed oil (LA-cookie) or one cookie made with oleic acid-rich (OA) safflower oil (OA-cookie), every day for two weeks.  Fasting blood samples were collected for analysis of PBMC cardiolipin species. Results Daily consumption of the LA-cookie for 2 weeks increased LA4 CL in PBMC, while consuming the OA-cookie did not alter LA4 CL (group x week interaction p &lt; 0.01).  LA3OA1 CL decreased in the LA-cookie group but was unchanged in the OA-cookie group (group x week interaction p &lt; 0.01).  There was no significant difference in the change of LA2OA2 CL or LA1OA3 CL between the groups. Conclusions Increasing LA intake through daily cookie consumption increased LA4 CL and altered other CL species in the PBMC of healthy adults.  Future studies are needed to assess if PBMC CL species may be a biomarker for CL species in other tissues and to determine if changes in CL species through increased dietary LA intake are associated with altered mitochondria function. Funding Sources Funding was provided by the Carol S. Kennedy Professorship and the Ohio Agriculture Research and Development Center.


2021 ◽  
Vol 10 (2) ◽  
pp. 53-72
Author(s):  
Wasan Jassim ◽  
Manal Al-Obaidi ◽  
Haider Ghazi

In recent years increasing evidence proposed that local immune cells at implantation site have largely contributed to embryo implantation. The intrauterine infusion of activated peripheral blood mononuclear cells culture 2 days before embryo transfer can enhance the implantation. One of the methods used to evaluate the endometrial receptivity is by assessing the sub endometrial blood flow. A total of 67 infertile women (30) women receives intrauterine non-invasive insemination of peripheral blood mononuclear cells (PBMC) culture 2 days before embryo transfer representing the PBMC test group, and (37) women without receiving any cell as Non-PBMC group. The cultured PBMC are administered into the uterine cavity of the patients. 2 days later, embryos are transferred into the uterine cavity. Endometrial thickness and sub-endometrial blood flow measurements are taken for all cases on trigger and embryo transfer days. On embryo transfer day there was no significant difference (p = 0.770) in mean endometrial thickness between the PBMC group and Non-PBMC group. There was a significant difference (p< 0.001) in the mean resistive index; the level being lower in the PBMC group. Moreover, there was a significant difference (p< 0.001) in the mean pulsatility index. Regarding all enrolled women, the pregnancy rate of 25.4 %, the rate was higher in the PBMC group in comparison with the Non-PBMC group, 43.3 % versus 10.8 %, respectively and the difference was significant (p = 0.002). The use of PBMC culture can improve sub-endometrial.


1988 ◽  
Vol 69 (2) ◽  
pp. 234-238 ◽  
Author(s):  
Vidar Bosnes ◽  
Henry Hirschberg

✓ Peripheral blood mononuclear cells from 11 glioma patients and 11 healthy control subjects were cultured in medium containing recombinant interleukin-2 for a period of 5 days. The cytotoxicity of these lymphokine-activated killer (LAK) cells was tested on chromium-51-labeled freshly prepared allogeneic glioblastoma cells, and on the cell lines K562 (natural killer cell (NK)-sensitive) and Daudi (NK-resistant). Peripheral blood mononuclear cells from all subjects showed high levels of cytotoxicity against these targets. There was no significant difference between the patients and the control group when LAK cytotoxicity was compared. Thus, although glioma patients are known to have depressed immunological reactivity, the cytotoxic capacity of LAK cells derived from glioma patients is similar to that of LAK cells from healthy control subjects. However, the glioma patients had significantly reduced numbers of mononuclear cells in their peripheral blood, possibly due to steroid treatment. Therefore, the volume of blood required to generate the same number of LAK cells was approximately three times larger from the glioma patients than from control subjects.


2019 ◽  
Vol 11 (2) ◽  
pp. 200-4
Author(s):  
Meira Erawati ◽  
Nyoman Suci Widyastiti ◽  
Tri Indah Winarni ◽  
Edi Dharmana

BACKGROUND: In tuberculosis infections, the immune system is weakened and cannot produce enough cytokines to against the infection. b-glucan is a potent immunomodulator that induces cytokine production in various bacterial infections. This study aimed to determine the effects of b-glucan on the production of interferon (IFN)-γ and interleukin (IL)-12 in peripheral blood mononuclear cells (PBMCs) induced by Mycobacterium tuberculosis DNA.METHODS: PBMCs were isolated from 11 healthy subjects. PBMCs were treated with/without 5 μg/mL b-glucan and M. tuberculosis rpoB wild-type or mutant DNA. The production of IFN-γ and IL-12 in the supernatant was performed with enzyme-linked immune-sorbent assay (ELISA).RESULTS: b-glucan increased significantly (p<0.05) IFN-γ of M. tuberculosis mutant DNA-induced PBMCs, M. tuberculosis wild-type DNA-induced PBMCs, and non-induced PBMCs. b-glucan also increased significantly (p<0.05) IL-12 of M. tuberculosis mutant DNA-induced PBMCs, M. tuberculosis wild-type DNA-induced PBMCs, and non-induced PBMCs. There were not any significant difference between male and female groups for IL-12 and IFN-γ in all treatment groups (p>0.05, ANOVA test).CONCLUSION: This in vitro study indicates that b-glucan increases the performance of PBMCs to produce IFN-γ and IL-12, with/without induction of M. tuberculosis wild-type/ mutant DNA.KEYWORDS: b-glucan, IFN-γ, IL-12, M. tuberculosis, rpoB


2020 ◽  
pp. dmm.046995
Author(s):  
Henrika Jodeleit ◽  
Paula Winkelmann ◽  
Janina Caesar ◽  
Sebastian Sterz ◽  
Lesca M. Holdt ◽  
...  

The goal of this study was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) may lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134) and CD14+ monocytes expressing OX40L (CD252) by flow cytometric analysis. A significant difference was observed between both groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17; mean±sd, non-UC: n=5, 30.7±34.92; p=0.02), no significant difference was detected for CD4+ OX40+. CD14+ OX40L+ monocytes correlated significantly with TH1 and TH2 cells. Secondly, NOD/Scid IL2-Rgamma null mice were reconstituted with peripheral blood mononuclear cells from UC donors exhibiting elevated levels of OX40L, and the efficacy of oxelumab was compared to that of adalimumab. Read out were the clinical, colon, andhistological scores, and serum levels of IL-6, IL-1ß and glutamic acid. Treatment with oxelumab or adalimumab resulted in significantly reduced clinical, colon, and histological scores, reduced serum levels of IL-6 and reduced frequencies of splenic human effector memory T cells and switched B cells. Comparison of efficacy of adalimumab and oxelumab by orthogonal partial least square discrimination analysis revealed that oxelumab was slightly superior to adalimumab, however, elevated serum levels of glutamic acid suggested ongoing inflammation. These results suggest that oxelumab addresses the pro-inflammatory arm of inflammation while promoting the remodeling arm and that patients exhibiting elevated levels of OX40L may benefit from treatment with oxelumab. Keywords: Ulcerative colitis, NOD/Scid IL2-Rγnull, NSG, anti-CD252 antibodies, oxelumab, inflammatory bowel disease


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