Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

The intricate interplay of one-carbon metabolism (OCM) with various cellular processes has garnered substantial attention due to its fundamental implications in several biological processes. OCM serves as a pivotal hub for methyl group donation in vital biochemical reactions, influencing DNA methylation, protein synthesis, and redox balance. In the context of aging, OCM dysregulation can contribute to epigenetic modifications and aberrant redox states, accentuating cellular senescence and age-associated pathologies. Furthermore, OCM\u27s intricate involvement in cancer progression is evident through its capacity to provide essential one-carbon units crucial for nucleotide synthesis and DNA methylation, thereby fueling uncontrolled cell proliferation and tumor development. In neurodegenerative disorders like Alzheimer\u27s and Parkinson\u27s, perturbations in OCM pathways are implicated in the dysregulation of neurotransmitter synthesis and mitochondrial dysfunction, contributing to disease pathophysiology. This review underscores the profound impact of OCM in diverse disease contexts, reinforcing the need for a comprehensive understanding of its molecular complexities to pave the way for targeted therapeutic interventions across inflammation, aging and neurodegenerative disorders

Comparing HLA Shared Epitopes in French Caucasian Patients with Scleroderma

Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, 67FLEDR71, shared by HLA-DRB susceptibility alleles, or 71TRAELDT77, shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient’s clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ2 = 28.4, p<10−6) and with anti-topoisomerase antibody (ATA) production (χ2 = 43.9, p<10−9) whereas TRAELDT association is weaker in both subgroups (χ2 = 7.2, p = 0.027 and χ2 = 14.6, p = 0.0007 respectively). Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes

X-linked genetic factors behind gender bias in rheumatoid arthritis

Comme dans la plupart des maladies auto-immunes une prédominance féminine est observée dans la polyarthrite rhumatoïde (PR). Le chromosome X, présent en 2 exemplaires chez la femme, est intéressant puisque beaucoup de gènes à fonctions immunitaires y sont localisés. Dans ce travail, nous montrons que certains de ces gènes peuvent augmenter leur nombre de copies quand l'individu vieillit. En outre, cette variation est spécifique au sexe avec une augmentation chez les hommes et l'inverse chez les femmes. D’autre part, alors que généralement les femmes inactivent aléatoirement (50:50) le chromosome X d’origine maternel ou X d’origine paternel, nous montrons un biais d’inactivation (≥ 80:20) chez les femmes atteintes de PR. De plus ce biais est préférentiellement associé à celles qui portent les gènes de susceptibilité à la maladie. Ces résultats soulignent l’importance du chromosome X dans le développement de l’auto-immunité et aident à la compréhension du biais féminin dans ces maladies.As in many autoimmune diseases, a female predominance is observed in rheumatoid arthritis (RA). The X chromosome, present in 2 copies in females, is of particular interest as it contains many genes with immune functions. In this work, we show an increase with age in copy number of some X-linked genes in peripheral blood cells of men, healthy or with RA. Importantly, this increase is not observed in women. On the other hand, when in fact females generally randomly inactivate (50:50) either the paternally-derived or the maternally-derived X chromosome, we show a skewed inactivation (≥ 80:20) in women with RA. Moreover this skewing correlates preferentially with women carrying disease susceptibility genes. Altogether, our findings highlight the importance of this fascinating chromosome in the development of autoimmunity in a step forward to better understand female predilection to autoimmune diseases

Investigating the asymmetric impact of oil prices on GCC stock markets

International audienc

Analyzing HLA-G polymorphisms in children from women with scleroderma.

International audienceEmbryos during pregnancy and organs during transplantation, express high levels of soluble HLA-G (sHLA-G) molecules for successful implantation and protection against maternal immune cells or recipient's cells. We and others have shown that women with scleroderma (SSc) carry cells/DNA arising from pregnancy, so-called fetal microchimerism (Mc) more often and in higher quantities than healthy women decades after delivery. We hypothesized that high levels of fetal Mc were the consequence of a fetus with a high sHLA-G profile, therefore that children from women with SSc would have this profile more often than children from healthy women. High sHLA-G secretor profile is influenced by at least two variations in the HLA-G 3' untranslated region (UTR): a 14 bp deletion in exon 8 and the presence of cysteine (C) in position +3142 and by one variation in the 5' Upstream Regulatory Region (URR) at position -725. By a previously developed three-step multiplex PCR SNaPshot method, we evaluated 16 HLA-G polymorphisms in DNA samples from the first-born children of 39 women with SSc and 32 healthy women. Contrary to expectations, children from women with SSc did not have a high sHLA-G profile, but rather the opposite. We discuss possible reasons for this result and future orientations for HLA-G studies in SSc

Antimycobacterial Activity of <i>Rosmarinus officinalis</i> (Rosemary) Extracted by Deep Eutectic Solvents

Tuberculosis (TB) is a massive problem for public health and is the leading cause of illness and death worldwide. Rosemary (Rosmarinus officinalis) is used traditionally to treat many diseases, such as infections of the lungs including pulmonary TB. R. officinalis was collected from Al Anbar Governorate, Iraq, and was extracted with deep eutectic solvents (DESs) of many different kinds and with conventional water solvent. The antimycobacterial activities of the R. officinalis extracts were tested against multidrug-resistant (MDR) Mycobacterium tuberculosis by agar disc diffusion assay. Minimum inhibitory concentrations were measured spectrophotometrically at 570 nm. Then, a time-kill assay and cell membrane integrity analysis were conducted to investigate the effects of the most active extracts on cell growth. The in vitro cytotoxicity of the most active extracts was evaluated against Rat Embryonic Fibroblasts (REF) cell line by MTT assay. Liquid chromatography-mass spectrometry (LC-MS) was conducted to analyze the chemical components of the most active extracts. At 200 mg/mL concentration, a significant inhibition activity was seen in DES2: Tailor (DIZ = 17.33 ± 1.15 mm), followed by DES3: ChGl, DES1: LGH and DES4: ChXl. The best result was DES2: Tailor, which had a MIC of 3.12 mg/mL and an MBC of 12.5 mg/mL. The DES2 extract exhibited a high drop in the number of colonies over time, killing more than 80 colonies. The main phytochemical compounds of the R. officinalis extract were camphene, camphenilol, α-pinene, limonene, apigenin, camphor, carnosol, linalool and myrcene. R. officinalis extracts obtained by DESs have shown evident power in treating tuberculosis, and extraction by DES is a greener procedure than the methods involving conventional extraction solvents. As a result, additional research into the application of DES should be considered

Antimycobacterial Activity of Rosmarinus officinalis (Rosemary) Extracted by Deep Eutectic Solvents

Tuberculosis (TB) is a massive problem for public health and is the leading cause of illness and death worldwide. Rosemary (Rosmarinus officinalis) is used traditionally to treat many diseases, such as infections of the lungs including pulmonary TB. R. officinalis was collected from Al Anbar Governorate, Iraq, and was extracted with deep eutectic solvents (DESs) of many different kinds and with conventional water solvent. The antimycobacterial activities of the R. officinalis extracts were tested against multidrug-resistant (MDR) Mycobacterium tuberculosis by agar disc diffusion assay. Minimum inhibitory concentrations were measured spectrophotometrically at 570 nm. Then, a time-kill assay and cell membrane integrity analysis were conducted to investigate the effects of the most active extracts on cell growth. The in vitro cytotoxicity of the most active extracts was evaluated against Rat Embryonic Fibroblasts (REF) cell line by MTT assay. Liquid chromatography-mass spectrometry (LC-MS) was conducted to analyze the chemical components of the most active extracts. At 200 mg/mL concentration, a significant inhibition activity was seen in DES2: Tailor (DIZ = 17.33 &plusmn; 1.15 mm), followed by DES3: ChGl, DES1: LGH and DES4: ChXl. The best result was DES2: Tailor, which had a MIC of 3.12 mg/mL and an MBC of 12.5 mg/mL. The DES2 extract exhibited a high drop in the number of colonies over time, killing more than 80 colonies. The main phytochemical compounds of the R. officinalis extract were camphene, camphenilol, &alpha;-pinene, limonene, apigenin, camphor, carnosol, linalool and myrcene. R. officinalis extracts obtained by DESs have shown evident power in treating tuberculosis, and extraction by DES is a greener procedure than the methods involving conventional extraction solvents. As a result, additional research into the application of DES should be considered

1.65 Copy number variation of TLR7 and TLR8 genes is age and sex biased: which role in autoimmunity?

International audienceBACKGROUND AND OBJECTIVES: Women, having two X chromosomes, are more predisposed than men to autoimmune diseases. The X chromosome contains many genes linked to immunity which may contribute to this gender bias. In a mouse model, a duplication of the innate immunity X-linked toll like receptor 7 (Tlr7) gene has been shown to potentiate autoimmunity in males. We then proposed to investigate whether TLR7 gene and its neighboring paralog TLR8 could have variations in their copy numbers, contributing to the pathogenesis of rheumatoid arthritis (RA) in men. METHODS: A real-time quantitative PCR protocol was developed to assess copy number variation (CNV) of TLR7 and TLR8 gene, using sensitive and optimised ΔΔCt and standard curve methods, in DNA from peripheral blood mononuclear cells of 60 patients with RA (including 49 men) and 64 healthy controls (including 42 men). Among them, 31 men with RA and 18 healthy men were further screened for TLR7/8 CNV in 4 subpopulations: B cells, T cells, granulocytes and the depleted fraction of the former 3. RESULTS: TLR7/8 copy numbers significantly increased with age in PBMCs from all men (P < 0.0001, Spearman's rank correlation test), whether they had RA or not. The increase had mean amplitude of 20%, spanning from the age of 20 until 80, according to the linear-regression-curve's best fit. This age-dependent and disease-independent CNV increase was also observed in all cell subsets. Interestingly, such increase was not observed in women, healthy or with RA, but rather an opposite trend. CONCLUSION AND PERSPECTIVES: For the first time we showed an increased CNV in TLR7 and TLR8 genes which is age and sex-mediated. Several hypotheses could explain such phenomenon. For example, somatically acquired duplications can affect some cells over time and result in an increase with age in men. In parallel, X chromosome monosomy, previously described in aging women could account for the opposite trend in those. Another explanation for men can be due to the presence of feminine microchimerism, arising from feto-maternal or twin sister exchange during in utero life, as previously described. Such cells would carry 2 X chromosomes and contribute to the increased pool of X-linked genes among XY host cells. Investigating these hypotheses would provide better understanding of age-associated X-linked genetic modifications and the role of the X chromosome in gender differences in health and disease. Abstract topicOther