scholarly journals SEX-DIMORPHISM IN THE GENOMIC REGULATION OF AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S768-S769
Author(s):  
Bérénice A Benayoun ◽  
Ryan A Lu ◽  
Nirmal K Sampathkumar

Abstract The current cohort of human supercentenarians reveals a surprising predictor for achieving such an exceptional longevity: being female. Indeed, out of 34 living supercentenarians, 33 are women. We obtained samples from 4 and 20 months old female and male mice. Our data indicates that cytokine levels are differentially regulated with age in males vs. females, with pro-inflammatory cytokines specifically upregulated in the serum of old males, but not females. Because of the central role of macrophages in inflammation and their infiltration in tissues with age, we have generated RNA-seq from purified macrophages of aging animals. Female macrophages displayed ~7-20-fold more transcriptional remodeling with aging than males. Pathways specifically downregulated in females with aging included lysosome, inflammation and phagolysosome. Consistently, our data shows that aged female, but not male macrophages, display decreased phagocytic efficiency. Our results support the notion that there are differences in aging trajectories in female vs. male mice.

2020 ◽  
Author(s):  
Nikita Mikhailov ◽  
Kseniia Koroleva ◽  
Ali Abdollahzadeh ◽  
Raisa Giniatullina ◽  
Oleg Gafurov ◽  
...  

AbstractBackgroundA system of lymphatic vessels has been recently characterized in the meninges, with a postulated role in ‘cleaning’ the brain via cerebral fluid drainage. As meninges are the origin site of migraine pain, we hypothesized that malfunctioning of the lymphatic system should affect the local trigeminal nociception. To test this hypothesis, we studied nociceptive and inflammatory mechanisms in the meninges of K14-VEGFR3-Ig mice lacking the meningeal lymphatic system.MethodsWe recorded the spiking activity of meningeal afferents and estimated the local mast cells infiltration, calcitonin gene-related peptide (CGRP) and cytokine levels (basal and stimulated), as well as the dural trigeminal innervation in freshly-isolated hemiskull preparations from K14-VEGFR3-Ig (K14) or wild type C57BL/6 mice (WT).ResultsWe found that the meningeal level of CGRP and of the pro-inflammatory cytokines IL12-p70 and TNFα (implicated in migraine) were reduced in the meninges of K14 mice. On the contrary, in the meninges of K14 mice, we found an increased level of the mast cell activator MCP-1 and, consistently, a larger number of dural mast cells. The other migraine-related pro-inflammatory cytokines did not differ between the two genotypes. The patterns of trigeminal innervation in meninges remained unchanged and we did not observe alterations in basal or ATP-induced nociceptive firing in the meningeal afferents.ConclusionsIn summary, the lack of meningeal lymphatic system does not induce migraine-like nociceptive state per se, but leads to a new balance between pro- and antiinflammatory factors implicated in migraine mechanisms.


2021 ◽  
Author(s):  
Fanny Ponthieux ◽  
Nicolas Dauby ◽  
Evelyne Maillart ◽  
Jean-François Fils ◽  
Julie Smet ◽  
...  

Abstract Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 and may explain why TCZ has failed to improve survival in critically ill COVID-19 patients when given alone.


2016 ◽  
pp. 73-76
Author(s):  
B.M. Ventskivskiy ◽  
◽  
I.V. Poladych ◽  
S.O. Avramenko ◽  
◽  
...  

In recent years there has been an increase in the frequency of multiple pregnancies and the associated perinatal losses. It is a result of multiple pregnancy in ART refers to a high-risk gestation, at which premature births occur in 2 times more often than in singleton pregnancies. The objective: to determine the role of pro-inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy, as a result of assisted reproductive technology. Patients and methods. to determine the pro-inflammatory cytokines that all pregnant with bagtopliddyam held immunosorbent assay, defined concentrations of interleukin (IL) in serum and cervical mucus. Results. The analysis of the levels of pro-inflammatory cytokines (IL-1, IL-8) in the test environment, found high concentrations in the surveyed women with multiple pregnancy, due to the use of ART, compared with spontaneous multiple and singleton pregnancy. Increased concentration of proinflammatory cytokines in patients with multiple pregnancy by ART is associated with their synthesis at the system level, it stimulated foci of inflammation in the female genitals and extragenital localization. This correlates with the clinical data and statistical analysis, patients with multiple pregnancy as a result of ART had weighed infectious-inflammatory history. Conclusion. The study showed that elevated levels of proinflammatory cytokines in the systemic and local level in patients with multiple pregnancy due to ART, typical for women with miscarriage, because of the physiological course of pregnancy characterized by the predominance of anti-inflammatory cytokines that prevent rejection of the fetus as a foreign factor. Based on the data obtained proved the role of systemic inflammatory factors in the genesis of preterm labor in women with a multiple pregnancy, as a result of assisted reproductive technology. Key words: multiple pregnancy, assisted reproductive technology, premature birth, interleukine-1, interleukine-8.


Author(s):  
Basmah Eldakhakhny ◽  
Hadeel Al Sadoun ◽  
Nehal Bin Taleb ◽  
Dunya Ahmed Nori ◽  
Nawal Helmi ◽  
...  

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared


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