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关键词： Osteoporosis   Bone metabolism   Epimedii Folium decoction   Gut microbiota   Butyric acid  

摘要： Aim of the study: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". Material and methods: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. Results: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1 beta signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, , Coriobacteriaceae, , bacteria of family S24-7, , Clostridiales, , and Prevotella, , and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. Conclusions: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.

摘要： 抗髓鞘少突胶质细胞糖蛋白免疫球蛋白G抗体相关疾病(myelin oligodendrocyte glycoprotein immu-noglobulin G-associated disorders,MOGAD)是一种区别于多发性硬化(multiple sclerosis,MS)和视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder,NMOSD)的自身免疫相关中枢神经系统炎性脱髓鞘性疾病[1-2].

关键词： NAFLD   MAFLD   ELOVL1   PPAR alpha   lipid   metabolism   sexual dimorphism  

摘要： Males are at higher risk for developing metabolic dysfunction-associated steatohepatitis (MASH) than females;however, mechanisms mediating sexual dimorphism in MASH development are not completely understood. Nutrition-based mouse models suggest that dysregulated fatty acid biosynthesis promotes MASH. Drugs recapitulate MASH without diet variabilities. This brief report investigates associations of sexual dimorphism with male susceptibility to MASH utilizing a drug-induced MASH model and focuses on very-long-chain fatty acid biosynthesis pathways. We assessed male and female mouse livers at 5 and 15 weeks following MASH induction by immunizations and age-matched un-immunized controls utilizing Western blot. Our results suggest that PPAR alpha and CYP4a12a protect females, while CYP4v2 does not protect males from MASH development. Our results have important implications for understanding sexual dimorphism in the pathogenesis of MASH.

关键词： bovine turbinate primary epithelial cells   bovine type III interferon   bovine viral diarrhea virus   IFN-lambda 3   IL-28R alpha   IL-10R beta   Madin-Darby bovine kidney cells  

摘要： Introduction The antiviral activity of recombinant bovine interferon lambda 3 (bovIFN-lambda 3) against bovine viral diarrhea virus (BVDV) has been demonstrated in vitro in Madin-Darby bovine kidney cells (MDBK) and in vivo in cattle. However, anti-BVDV activity of bovIFN-lambda 3 has not been studied in bovine respiratory tract epithelial cells, supposedly a primary target of BVDV infection when entering the host by the oronasal *** Here we investigated the anti-BVDV activity of bovIFN-lambda 3 in bovine turbinate-derived primary epithelial cells (BTu) using BVDV infection and immunoperoxidase staining, TCID50, RT-qPCR, DNA and transcriptome sequencing, and transfection with plasmids containing the two subunits, IL-28R alpha and IL-10R beta that constitute the bovIFN-lambda 3 *** Our immunoperoxidase staining, RT-qPCR, and TCID50 results show that while BVDV was successfully cleared in MDBK cells treated with bovIFN-lambda 3 and bovIFN-alpha, only the latter, bovIFN-alpha, cleared BVDV in BTu cells. Preincubation of MDBK cells with bovIFN-lambda 3 before BVDV infection was needed to induce optimal antiviral state. Both cell types displayed intact type I and III IFN signaling pathways and expressed similar levels of IL-10R beta subunit of the type III IFN receptor. Sequencing of PCR amplicon of the IL-28R alpha subunit revealed intact transmembrane domain and lack of single nucleotide polymorphisms (SNPs) in BTu cells. However, RT-qPCR and transcriptomic analyses showed a lower expression of IL-28R alpha transcripts in BTu cells as compared to MDBK cells. Interestingly, transfection of BTu cells with a plasmid encoding IL-28R alpha subunit, but not IL-10R beta subunit, established the bovIFN-lambda 3 sensitivity showing similar anti-BVDV activity to the response in MDBK *** Our results demonstrate that the sensitivity of cells to bovIFN-lambda 3 depends not only on the quality but also of the quantity of the IL-28R alpha subunit o

关键词： IL-15/IL-15Ra   IL-12   cytotoxic cells   SHIV infection.  

摘要： Cytokines are key mediators of immune regulation, orchestrate communication between immune cells, and play a pivotal role in shaping the immune landscape during chronic infection and cancer. The therapeutic potential of IL-15/IL-15R alpha and IL-12 has been explored individually in various immunotherapeutic strategies, though not as a combination. Therefore, we investigated whether the combination of IL-15/IL-15R alpha and IL-12 treatment would enhance the potency and quality of either NK cells, SIV-specific CD8 T cells, or both, compared with single cytokine treatment. Our findings reveal that in vitro IL-15/IL-15R alpha and IL-15/IL-15R alpha plus IL-12 treatment results in an expansion of functional CD8 T cells and NK cells from uninfected and chronically infected macaques with simian/human immunodeficiency virus. Additionally, the cytokine combination significantly reduced CCR5 expression on total CD4 T cells, limiting the number of viral targets. This study supports the potential utilization of combined IL-15/IL-15R alpha plus IL-12 treatment for chronic viral infections and cancer.

关键词： IL-23   IL-17   Imiquimod   Psoriasis   Yinxie I Formula  

摘要： Psoriasis is considered a chronic inflammatory skin disorder characterized by keratinocytes hyperproliferation. The IL-23/IL-17 immune pathway has been substantiated in numerous studies to be closely associated with psoriasis progression. Yinxie I Formula is a traditional Chinese medicine made from 9 herbal medicines, which has excellent clinical efficacy in psoriasis. However, to date, the mechanism of action of Yinxie I Formula against psoriasis remains unknown. In this perspective, we discuss the efficacy of Yinxie I Formula in mice with imiquimod (IMQ) induced psoriasis. Yinxie I Formula significantly reduced the area of skin lesions and the inflammatory response in mice with psoriasis. Furthermore, Yinxie I Formula alleviated the expression levels of inflammation-related genes IL-6, IL-17 A, IL-22, IL-23, TNF-alpha and IL-23, IL-18, IL-6 and IL-1 beta-related proteins and alleviated the abnormal surge of dendritic cells, macrophages and T cells in the skin and spleen. Meanwhile we found that Yinxie I Formula reduced the release of NO, TNF-alpha, IL-1 beta and IL-23 in lipopolysaccharide-induced mouse macrophage RAW264.7 cell line. The results suggest that the therapeutic mechanism of Yinxie I Formula may also be correlated with the STAT signaling pathway. We further analyzed the active ingredient of Yinxie I Formula, Buddleoside, which may be the main substance that exerts the therapeutic effect. In conclusion, we have investigated that Yinxie I Formula attenuates the IMQ-induced inflammatory response in psoriasis by inhibiting the IL-23/IL-17 axis, which lays the foundation for the antipsoriasis mechanism and provides a theoretical basis for the clinical promotion of Yinxie I Formula.

关键词： Autoimmune diseases   Clinical trials   Inflammatory bowel disease  

摘要： Risankizumab outperformed ustekinumab for the treatment of moderate to severe Crohn’s disease in patients refractory to anti-TNF therapy.

关键词： NKG2D   IL-15/IL-15R alpha   CAR-T cells   EBV infection   Post-transplantation  

摘要： Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15R alpha-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15R alpha-NKG2D CAR-T cells, respectively. B-lymphoblastoid cell lines (B-LCLs) and the xenografted mouse models were established to evaluate the efficacy of these CAR-T cells. IL-15/IL-15R alpha-NKG2D CAR-T cells exhibited superior proliferation and antigen-specific cytotoxic effect compared to NKG2D CAR-T, as IL-15/IL-15R alpha signaling promoted the expansion of less differentiated central memory T cells (TCM) and increased expression of CD107a and IFN-gamma. Moreover, EBV DNA load was dramatically reduced, and 80% B-LCL cells were eliminated by IL-15/IL-15R alpha-NKG2D CAR-T cells after co-culturing. In-vivo study confirmed that IL-15/IL-15R alpha-NKG2D CAR-T cell therapy significantly enhanced antiviral efficacy in mice, as the serum load of EBV after IL-15/IL-15R alpha-NKG2D CAR-T cell infusion was 1500 times lower than the untreated control (P < 0.001). The enhanced efficacy of IL-15/IL-15R alpha-NKG2D CAR T cells was probably due to the IL-15/IL-15R alpha signaling improved homing and persistence of NKG2D CAR-T cells in vivo, and increased the production of IFN-gamma, Perforin, and Granulysin. In conclusion, NKG2D CAR-T cells co-expressing IL-15/IL-15R alpha promoted the central memory CAR T cell proliferation and improved the homing and persistence of CAR T cells in vivo, resul

摘要： Retraction: Natural killer cell-derived exosomal miR-3607-3p inhibits pancreatic cancer progression by targeting IL-26 Sun H, Shi K, Qi K, Kong H, Zhang J, Dai S, Ye W, Deng T, He Q and Zhou M (2019) Natural Killer Cell-Derived Exosomal miR-3607-3p Inhibits Pancreatic Cancer Progression by Targeting IL-26. Front. Immunol. 10:2819. doi: 10.3389/fimmu.2019.02819 Following publication, concerns were raised regarding the integrity of the images in the published figures. The authors failed to provide a satisfactory explanation during the investigation, which was conducted in accordance with Frontiers' policies. This retraction was approved by the Chief Editors of Frontiers in Immunology and the Chief Executive Editor of Frontiers. The authors agree to this retraction.