Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

T Lymphocyte Characteristic Changes Under Serum Cytokine Deviations and Prognostic Factors of COVID-19 in Pregnant Women.

Physiological changes during pregnancy make the individuals more susceptible to severe respiratory diseases. Hence, pregnant women with coronavirus disease 2019 (COVID-19) are likely at a higher risk. We investigated the effects of COVID-19 on T cell response and serum cytokine profile in pregnant patients. Peripheral blood mononuclear cells (PBMCs) of women with COVID-19 were collected during the first trimester of pregnancy, and the percentage of total lymphocytes, as well as CD4 + and CD8 + T cells, was assessed using flow cytometry. The expression of the programmed death-1 (PD-1) marker for exhausted T cells was evaluated. Additionally, the serum samples were provided to evaluate the levels of antiviral and proinflammatory cytokines, as well as laboratory serological tests. Pregnant women with COVID-19 presented lymphopenia with diminished CD4 + and CD8 + T cells. Besides, high expression levels of the PD-1 gene and protein were observed on PBMCs and T cells, respectively, when compared with normal pregnant individuals. Moreover, serum levels of TNF-α, IL-6, IL-1ß, and IL-2 receptor were notably enhanced, while IFN-I α/ß values were significantly decreased in the patients when compared with controls. Furthermore, hyperlipidemia, hyperglycemia, and hypertension were directly correlated with the disease although serum albumin and vitamin D3 levels adversely affected the viral infection. Our study showed extreme lymphopenia and poor T cell response while elevated values of serum inflammatory cytokines in infected pregnant women. Moreover, a hypertension background or metabolic changes, including hyperlipidemia, hyperglycemia, and vitamin D3 or albumin deficiency, might be promising prognostic factors in pregnant women with COVID-19.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

Prospects for the application of mesenchymal stem cells in Alzheimer's disease treatment.

Alzheimer's disease (AD) as a dementia and neurodegenerative disease, is mostly prevalent among people more than 65 years. AD is mostly manifested in the form of degraded mental function, such as losing memory and impaired cognitive function. Due to inefficiency of traditional pharmacological therapeutic approaches with no long-term cure, cell therapy can be considered as a capable approach in AD management. Therapies based on mesenchymal stem cells (MSCs) have provided hopeful results in experimental models regarding several disorders. MSCs enhance the levels of functional recoveries in pathologic experimental models of central nervous system (CNS) and are being investigated in clinical trials in neurological disorders. However, there is limited knowledge on the protective capabilities of MSCs in AD management. Almost, several experiments have suggested positive effects of MSCs and helped to better understand of AD-related dementia mechanism. MSCs have the potential to be used in AD treatment through amyloid-ß peptide (AB), Tau protein and cholinergic system. This review aimed to clarify the promising perspective of MSCs in the context of AD.