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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： Ras homolog family member J (RhoJ)   clear cell renal cell carcinoma (ccRCC)   drugs   tumor necrosis factor (TNF)   nuclear factor kappa B (NF-kappa B)  

摘要： Background: Clear cell renal cell carcinoma (ccRCC) represents the predominant form of kidney cancer. The Ras homology (Rho) GTPases family plays essential roles in several tumors. However, few studies have reported the function and clinical value of the Rho GTPases family in ccRCC. Our study aimed to systematically investigate the expression profiles, functional roles, and clinical significance of Rho GTPases in ccRCC, with the goal of identifying potential biomarkers and novel therapeutic targets to improve the treatment outcomes and survival rates of this aggressive kidney cancer. Methods: The expression level of Ras homolog family member J (RhoJ) was detected in ccRCC cells and tissues using quantitative polymerase chain reaction (qPCR), western blotting, and immunohistochemistry (IHC). The biological functions of RhoJ were evaluated via in vitro and in vivo assays. RNA sequencing was used to investigate the underlying mechanisms. Potential RhoJ inhibitors were identified using virtual screening in a Food and Drug Administration (FDA)-approved drugs repository. Results: Our study identified RhoJ as the only Ras-homologous guanosine triphosphate (GTP)-binding protein (Rho GTPase) associated with poor prognosis in ccRCC patients. Using ccRCC cells and tumor tissues, we found that RhoJ was significantly highly expressed in ccRCC. Moreover, RhoJ apparently enhanced ccRCC cell proliferation, migration, and invasion. Further, upregulated RhoJ could accelerate cell cycle progression, inhibit apoptosis, and enhance epithelial-mesenchymal transition (EMT). Through orthotopic tumor models, we found that knocking down RhoJ inhibited tumor growth. Mechanically, RhoJ influenced ccRCC progression through the tumor necrosis factor-alpha/nuclear factor kappa B (TNF-alpha/NF-kappa B) axis. Blocking this axis could partially rescue malignant phenotypes caused by RhoJ. Finally, since there are no available drugs targeting RhoJ, the virtual screening was used to identify potential

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： 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.

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： NLRC3   RIP2   TRAF6   STING   TBK1   Large yellow croaker  

摘要： As a member of the NLRs family, NLRC3 has been determined to function in the NF-kappa B, MAPK, and type I IFN signaling, which are crucial for the host innate immunity and inflammatory response. In this study, an NLRC3 ortholog, named as Lc-NLRC3, was cloned and identified in large yellow croaker (Larimichthys crocea). The gene characteristics analysis revealed that Lc-NLRC3 consists of 18 exons and 17 introns, with a full-length open reading frame (ORF) of 3405 bp, encoding a protein of 1134 amino acids (aa), that containing a N-terminal CARD domain, a central NACHT domain, and a C-terminal LRRs domain. It was shown that Lc-NLRC3 is predominantly found in the cytosol, and was widely distributed across various tissues/organs, with the highest expression detected in the intestine, and could be induced by poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulation. Importantly, Lc-NLRC3 overexpression significantly activate NF-kappa B, TNF alpha, IL-1 beta, IRF3, IRF7, and IFN1 promoters, whereas when co-expressed with RIP2, STING, or TBK1, it down-regulated those promoter activation compared to their individual overexpression alone, thereby suppressing downstream antiviral and inflammatory gene expression. Interestingly, Lc-NLRC3 associated with TRAF6 in IRF3/IRF7 promoter activation, and enhanced the expression of IRF7, Mx, ISG15, and TNF-alpha. Co-immunoprecipitation assays also confirmed interactions of Lc-NLRC3 with RIP2, STING, TBK1, and TRAF6. The above results imply that Lc-NLRC3 is an important regulator in RIP2, STING, TBK1, and TRAF6 mediated type I IFN signaling and inflammatory response.

关键词： BaEV lentivirus   CAR-NK   CD80   CD80-41BBL-mbIL21 K562 cells   umbilical cord blood-derived NK cells  

摘要： Natural Killer (NK) cells are an important population of the immune system, and NK cell-based therapy has shown great potential in the treatment of cancers. However, to apply NK cells clinically, producing a large number of cells with high cytotoxicity remains a challenge. Current strategies focus on employing different irradiated feeder cells to stimulate NK expansion, maturation, and cytotoxicity. While co-stimulatory signals play critical roles in promoting NK cell proliferation and activating their functions, the exploitation of these signals for expanding NK cells has not been fully explored. To identify the optimal engineered feeder cells for expanding umbilical cord blood-derived NK cells, we generated different feeder cells expressing the co-stimulatory molecules CD80, 4-1BBL, or membrane-bound IL-21 (mbIL21). We then evaluated the transduction efficacy of a chimeric antigen receptor (CAR) construct into expanded NK cells using various lentiviral vectors. Our results showed that CD80, in combination with 4-1BBL and mbIL21, induced the highest expansion of NK cells from cord blood. The expanded NK cells displayed higher cytotoxicity toward target cells compared to T cells following CAR transduction using BaEV lentivirus.