课程文献中心 更多>>

关键词： Interleukin-6   Circadian rhythms   Metabolic cycles   Energy balance   Sexual dimorphism  

摘要： Objective: Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation and energy metabolism. Its diurnal secretion influences core circadian components, emphasizing its critical role in circadian biology. Despite known sex differences in immune, circadian, and metabolic processes, how IL-6 integrates these processes remains poorly understood. Methods: IL6 knockout (KO) and control mice of both sexes were phenotyped for circadian and metabolic traits under standard (STD) and high-fat diet (HFD), fasting, and time-restricted feeding. Molecular analyses in muscle, liver, and hypothalamus assessed clock gene expression and IL-6 signaling pathway. Circulating sex steroid hormones were quantified to examine their contribution to the observed sex-specific phenotypes. Results: IL-6 deficiency disrupts circadian locomotor and metabolic rhythms in a sex-and diet-dependent manner. Males exhibit impaired light-driven circadian rhythms under STD conditions and metabolic misalignment under HFD, whereas females display greater circadian resilience under STD conditions but increased vulnerability to circadian disruption during HFD. Additionally, IL-6 emerges as a novel regulator of the foodentrainable oscillator (FEO), linking food anticipatory activity and metabolic cycles under both STD and HFD in a sex-dependent manner. Conclusions: These findings identify IL-6 as a critical mediator of circadian-metabolic plasticity, shaping sex-and diet-specific trade-offs between circadian stability and metabolic homeostasis. Our study highlights IL-6 as a potential therapeutic target for mitigating circadian misalignment-associated metabolic disorders, with implications for the timed modulation of IL-6 signaling. (c) 2025 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： cell contact   chemokines   mesenchymal stem/stromal cells   paracrine factor   type 1 diabetes mellitus  

摘要： Interferon-gamma (IFN gamma) plays a crucial role in the pathogenesis of type 1 diabetes (T1D) and is widely utilized to license mesenchymal stem/stromal cells (MSCs) to enhance their immunosuppressive properties through a process known as preconditioning or priming. This study investigates the interaction of MSCs preconditioned with (IFN gamma+) or without (IFN gamma-) IFN gamma, with peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and T1D patients. We assessed the effects of these interactions on anti-inflammatory gene expression, chemokine and receptor profiles, and the induction of regulatory T (Treg) cells. Our findings reveal contrasting responses in HC and T1D PBMCs when exposed to IFN gamma+ and IFN gamma- MSCs, particularly in the expression of key genes such as CXCR3 and its ligands (CXCL9, CXCL10), CXCR6, CCR5, and its ligands (CCL3 and CCL4). Pathway enrichment analysis further showed that IFN gamma preconditioning tailors MSC responses to specific immune microenvironments. These differential gene expression patterns were also reflected in the proportions of Treg cells, which varied depending on whether paracrine signaling or direct cell contact was involved. Collectively, our results demonstrate that IFN gamma+ and IFN gamma- MSCs create distinct immunomodulatory microenvironments in T1D PBMCs compared to HC PBMCs, emphasizing the potential for tailored MSC-based therapies in T1D treatment.

关键词： Host resistance   Haemonchus contortus   Cytokine   Gene expression   Garole sheep  

摘要： Role of IFN-gamma and IL-10 cytokines and associated genes (IFN-gamma and IL-10) on Haemonchus contortus resistance was studied in experimentally infected resistant and susceptible Garole sheep. Nine resistant and nine susceptible Garole sheep were selected based on faecal egg counts (FEC) and divided into 3 groups;uninfected control (n = 6), infected resistant (n = 6) and infected susceptible (n = 6). Sheep of infected groups were orally challenged with 500 H. contortus infective larvae per kg body weight of experimental sheep. Faecal egg counts were measured from 18 days post infection (DPI) at 3 days intervals for nine occasions, and plasma cytokines (IFN-gamma and IL-10) concentration and expressions of cytokine genes (IFN-gamma and IL-10) expressions were measured from 0 DPI to 40 DPI at 10 days intervals. Resistant sheep had significantly (P < 0.001) lower FEC from 27 DPI onwards compared to susceptible sheep and subsequently no eggs were found in resistant sheep from 33 DPI onwards. In resistant sheep, significantly higher concentration of IFN-gamma cytokine and expression of IFN-gamma gene were observed at early stage (10-20 DPI), and IL-10 cytokine production and IL-10 gene expression upregulated at later stage of infection (20-30 DPI) after which there was significant reduction of egg output in faeces of resistant group of sheep. Hence in Garole sheep both the IFN-gamma and IL-10 cytokines and their associated genes might be linked with H. contortus resistance with IL-10 cytokine gene playing comparatively more active role in development of resistance to H. contortus.

关键词： Exosome   Anti-inflammation   Osteoarthritis   MicroRNA (miRNA)  

摘要： Background:This study investigated anti-inflammatory effects of exosomes derived from human fetal cartilage progenitor cells (hFCPC-Exo) and their microRNAs (miRNAs) on the osteoarthritis (OA) phenotype in vitro in comparison with exosomes from bone marrow mesenchymal stem cells (MSC-Exo).Methods:SW982 cells (synoviocytes) or hFCPCs (chondrocytes) were stimulated with 10 ng/mL IL-1 beta to mimic OA phenotypes. The effects of hFCPC-Exo and MSC-Exo were compared by measuring the expression of inflammatory cytokines and an anti-inflammatory protein. miRNA profiles of hFCPC-Exo and MSC-Exo were analyzed using a 2588 human miRNA dataset, and miRNAs potentially involved in the anti-inflammatory effect of hFCPC-Exo were selected. miRNA mimics and antisense inhibitors were used to investigate the role of selected miRNAs in the IL-1 beta signaling ***:Both hFCPC-Exo and MSC-Exo significantly decreased the expression of inflammatory cytokines (IL-1 beta, IL-6, and MCP-1), while slightly increased an anti-inflammatory protein (SOCS1) in IL-1 beta-treated SW982 cells. miRNA sequencing revealed anti-inflammatory miRNAs present in large amounts in both hFCPC-Exo and MSC-Exo. Among them, miR-125b-5p mimic significantly suppressed the expression of inflammatory cytokines induced by IL-1 beta, while anti-sense inhibitor of miR-125b-5p efficiently blocked anti-inflammatory effects of hFCPC-Exo. Both hFCPC-Exo and miR-125b-5p inhibited I kappa B alpha down-regulation and -NF-kappa B stabilization in IL-1 beta-treated SW982 cells. Additionally, hFCPC-Exo and miR-125b-5p showed similar effects on IL-1 beta-treated hFCPCs as an OA model in chondrocytes by down-regulating the expression of IL-1 beta, MMP13, and ADAMTS-5 and up-regulating the expression of aggrecan (ACAN) and type II collagen (COL2A1).Conclusion:This study demonstrated that hFCPC-Exo exhibits anti-inflammatory effects on IL-1 beta-treated synoviocytes and chondrocytes in vitro possibly by down-regulating the I

关键词： pelvic pain   endometriosis   infertility   sNCAM   sIL-2R alpha   VAS score  

摘要： Introduction Pelvic pain, often associated with endometriosis, significantly affects women's quality of life. This study explored the soluble neural cell adhesion molecules (sNCAM), soluble interleukin 2 receptor alpha (sIL-2R alpha), and IL-2 levels in the serum and peritoneal fluid of infertile women with pelvic *** We enrolled 86 infertile women aged 24 to 41 years undergoing diagnostic laparoscopy: 44 women with endometriosis and 42 women who acted as controls. Pain intensity was assessed using the visual analog scale. The soluble molecules were measured using enzyme-linked immunosorbent *** Serum and peritoneal sNCAM, sIL-2R alpha, and IL-2 levels were statistically significantly higher in women with pelvic pain. Both serum and peritoneal sNCAM levels correlated with visual analog scale scores, indicating a relationship between these markers and pain severity. Elevated peritoneal sIL-2R alpha levels were also associated with pelvic pain. Receiver operating characteristic curve analysis showed the potential of serum sNCAM in distinguishing between mild and moderate to severe *** Elevated levels of sNCAM, sIL-2R alpha, and IL-2 in serum and peritoneal fluid correlate with pelvic pain severity in infertile women, suggesting their involvement in disease pathogenesis and potential as objective biomarkers for pain assessment in endometriosis. Further research is needed to validate these findings for clinical use.

摘要： HLA-G*01:62 differs from HLA-G*01:04:01 by one nonsynonymous nucleotide substitution in codon 269 in exon 4.

关键词： Polycythemia vera   IFN-alpha2   Transcriptional profiles   Co-expression analysis   Modules  

摘要： Polycythemia vera (PV) is the most common chronic myeloproliferative neoplasm (MPN) in adults. Pegylated interferon-alpha 2 (IFN-alpha 2) is an effective and safe drug for the treatment of PV. However, the mechanisms of its action in PV are still not fully understood. Using the WGCNA and Limma algorithm, we found a subset of IFN-alpha 2 sensitive genes and four gene co-expression modules. Meanwhile, we also found 820 genes were differentially expressed in PV compared with healthy controls. By integrating the above results, several differentially expressed genes (DEGs) that were up- or down-regulated in PV but showed opposite alterations in the IFN-alpha 2-treated group were found. These genes were mainly related to three types of biological processes (metal ion homeostasis, metabolic/catabolic process, and Jak-STAT signaling pathway), the dysfunctions of which were prevalent in PV. Moreover, we applied another threshold-free analysis method to compare global gene expression between IFN-alpha 2 treated PV, PV, and control groups. Results showed the transcriptome changes of PV versus controls were negatively correlated with that of IFN-alpha 2 treated versus untreated PV, indicating IFN-alpha 2 treatment could partially reverse the dysregulated gene expression profile due to PV pathology. In summary, interferon may alleviate the progression of PV through multiple pathways. The findings may be of assistance in understanding the molecular basis underlying this treatment.

关键词： β-cell   inflammation   BET bromodomains   Bromodomain-containing protein 4 (BRD4   NF-κB transcription factor   diabetes   epigenetics   transcription   small molecule   gene regulation  

摘要： Cytokine-stimulated transcription of NF-kB target genes is linked to the development of multiple inflammatory and autoimmune diseases. Inhibitors of bromodomain and extra-terminal domain (BET) epigenetic reader proteins attenuate inflammatory gene transcription and delay the onset of several inflammatory diseases, including autoimmune diabetes. Our previous studies showed that BET bromodomain inhibitors disrupt the interaction between BET family member BRD4 and NF-kB transcription factor p65 in (3-cells, thus attenuating cytokine-stimulated NF-kB-dependent gene and functional changes. However, the role of NF-kB in developing inflamma-tory disease is controversial, as NF-kB inhibition can promote disease progression in some contexts. NF-kB target genes play both physiological and pathophysiological roles in regulating the cellular response to cytokines. Here, using cytokinestimulated pancreatic (3-cells as an inflammatory disease model, we show that NF-kB-dependent gene products that participate in inflammation are sensitive to BET bromodomain inhibition. In contrast, gene products that maintain cellular homeostasis or protect (3-cells from stressors are largely insensitive to BET bromodomain inhibition. These studies define a novel and selective role for BET bromodomaincontaining proteins in regulating inflammatory gene activation.

关键词： Psoriasis   Arthritis   Gut microbiota   Interleukin 17   Carbohydrate-Active enZymes  

摘要： Objectives: To explore the evolution of gut microbiota in taxonomy and function in PsA patients during IL-17i treatment. Methods: Twenty PsA patients treated with secukizumab were included. Fecal samples were collected before treatment (0 mo.), first month (1 mo.) and third month (3 mo.) after treatment, and a total of 60 samples were collected. Shotgun metagenomic sequencing was used to detect all fecal samples. Results: In the 1 mo. and 3 mo. after IL-17i treatment, the disease activity in PsA patients decreased significantly. Compared with 0 mo., alpha-diversity calculated by Shannon index and Pielou index increased significantly at 1 mo. and 3 mo. after treatment. Microbial genes encoding Carbohydrate-Active enZymes (CAZymes) tended to be upregulated after treatment. After treatment, Bacteroidota phylum expanded, especially the abundance of Phocaeicola genus increased gradually with the treatment time (P < 0.05). The abundance of Phocaeicola genus was positively correlated with the alpha-diversity. The Polysaccharide Lyases and Carbohydrate Esterases in CAZymes were significantly positively correlated with most of species in Phocaeicola genus. Conclusions: Treatment with IL-17i induces gut microbiota evolution in PsA patients. The key features of this evolution include increased alpha-diversity, expansion of the Phocaeicola genus, and upregulation of CAZymes. Species within the Phocaeicola genus may be the critical bacteria driving this evolution. (c) 2025 Socioto Franoaise de Rhumatologie. Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.