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Background: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-β (TGF-β) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD., Methods: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed., Results: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores., Conclusions: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-β. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction Multiple sclerosis (MS) is an autoimmune condition marked by inflammation and the loss of myelin in the central nervous system (CNS). The aim of this research was to understand how Thymoquinone regulate the molecular and cellular processes involved in controlling experimental autoimmune encephalomyelitis (EAE), which is an animal model often used to study MS. Methods Female C57BL/6 mice were split into different groups receiving different doses (low, medium, and high) of Thymoquinone simultaneously with EAE induction. Clinical scores and other measurements were observed daily throughout the 25-day post immunization. We assessed lymphocyte infiltration and demyelination in the spinal cord through histological staining, analyzed T-cell profiles using ELISA, and quantified the expression levels of transcription factors in the CNS using Real-time PCR. Results Thymoquinone prevented the development of EAE. Histological experiments revealed only a small degree of leukocyte infiltration into the CNS. Thymoquinone resulted in a notable reduction in the generation of IFN-γ, IL-17, and IL-6, while simultaneously increasing the production of IL-4, IL-10, and TGF-β in Th2 and Treg cells. Results from Real-time PCR suggested Treatment with Thymoquinone decreased the expression of T-bet and ROR-γt while increasing the expression of Foxp3 and GATA3. Conclusion These findings showed that Thymoquinone could decrease both disease incidence and severity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Multiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder indicated by demyelination, chronic inflammation, and neuronal destruction. Regional demyelination, inflammation responses, scar development, and various axonal damage are pathological characteristics of MS. Curcumin is a hydrophobic polyphenol extracted from the rhizome of the turmeric plant. In addition to anti-inflammatory effects, beneficial therapeutic effects such as antioxidant, anti-cancer and nerve protection have also been seen from this compound. The purpose of the current investigation was to provide light on the potential benefits of Curcumin in treating experimental autoimmune encephalomyelitis (EAE), the animal model of MS., Methods and Results: in Female C57BL/6 mice were used to induce EAE through myelin oligodendroglial glycoprotein (MOG). Curcumin doses of 100 and 200 mg/kg were administered orally in the treatment groups starting on the first day of EAE induction. Brains and splenocytes were extracted from euthanized animals on day 25 following EAE induction. Demyelination and leukocyte infiltration, proliferation, cytokine, and gene expression profiles were assessed. Our findings demonstrate that both low and high doses of Curcumin decreased the progression of EAE. Histological analyses revealed low infiltration of leukocytes into the CNS. Curcumin therapy enhanced Th2 and Treg cell secretion of IL-4, IL-10, and TGF-β although considerably decreasing IFN-γ and TNF-α. Curcumin-induced Th2 and Treg cell cytokine production and transcription factor gene expression (IL-13, GATA3, STAT6 and IL-35, CTLA4, Foxp3) and anti-inflammatory cytokines (IL-27, IL-33)., Conclusion: Overall, these findings provide additional evidence that Curcumin can slow disease development and alleviate symptoms in EAE through stimulating Treg and Th2 cell polarization. They support Curcumin's potential therapeutic role in MS., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

There is a significant fluctuation in clinical symptoms of asthmatic females during their life course, suggesting that the reproductive status and the level of sex hormones may affect the development of asthma and its exacerbation. In this study, we aimed to assess the biological effects of 17β-estradiol (E2) and progesterone (P4), alone or in combination form, on the transcription factors and production of cytokines in peripheral blood mononuclear cells (PBMCs). PBMCs of the mild-to-moderate asthmatic patients and healthy controls (HCs) were treated with equivalent serum levels of E2 or P4 maintained during hormone replacement therapy (HRT). The expression levels of T-bet, GATA-3, RORγt, PU.1, and Foxp3 were assessed by quantitative PCR. We also measured the concentration of IL-4, IL-9, IL-10, IFN-γ, and TGF-β in cell culture supernatants using ELISA. IL-4 production and GATA-3 expression levels slightly increased when asthmatic PBMCs were treated with E2 (p < 0.01), P4 (p < 0.01), or E2 + P4 (p < 0.001) compared to the untreated cells. IL-9 secretion (p < 0.001) and PU.1 gene expression levels (p < 0.05) were slightly higher in asthmatic patients' PBMCs before treatment but hormone therapy did not affect the level of them. Although the untreated asthmatic PBMCs produced a lower amount of IFN-γ compared to HCs (p < 0.01), hormone treatment did not affect the levels of IFN-γ secretion in patient groups. Moreover, we did not observe any significant changes in IL-10 and TGF-β secretion in the supernatant of hormone treated cells. We found that the common applied HRT may faintly increase GATA-3 expression and IL-4 production levels in PBMCs of asthmatic patients and can slightly increase asthma severity.