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关键词： cancer progression   cytokines   inflammation  

摘要： The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization-an essential factor in the immune landscape of tumors-thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies.

关键词： Diabetic foot ulcer   C-X-C ligand 1   TNF-alpha signaling pathway   Oxidative stress levels   Inflammation  

摘要： Diabetic foot ulcer (DFU) is an immune disease associated with diabetes. C-X-C ligand 1 (CXCL1) is a pro-inflammatory factor. Both of them have been reported to associated with the activation of oxidative stress and inflammation. This study aimed to explore the relationship between CXCL1 action mechanism and DFU occurrence through studying inflammation and oxidative stress. Firstly, used bioinformatics analysis to investigate highly expressed genes/pathways in DFU based on GEO database. After that, CXCL1-specific shRNA (sh-CXCL1) was transfected in to human umbilical vein epithelial cells (HUVEC) in high glucose (HG) condition to establish sh-CXCL1 cells, then CXCL1 expression, cell viability, inflammatory levels and oxidative stress were verified. Moreover, TNF-alpha overexpression plasmids (oe-TNF-alpha) were transfected to the HG + sh-CXCL1 group cells, and TNF-alpha expression, cell viability, inflammatory levels and oxidative stress were also assessed. Bioinformatics analysis indicated that CXCL1 and TNF-alpha were highly expressed in DFU, and there was a positive correlation between them. After transfection with sh-CXCL1, in HG conditions, the expression levels of CXCL1 and TNF-alpha in human umbilical vein endothelial cells (HUVEC) were significantly decreased, and oxidative stress and inflammatory responses were inhibited, while cell viability was significantly increased. However, after transfection of oe-TNF-alpha in sh-CXCL1 cells, all these effects were reversed. CXCL1 activates the TNF-alpha signaling pathway, increase oxidative stress and inflammatory response, thereby inducing DFU occurrence.

关键词： Mesenchymal stem cells   Cellular senescence   Inflammation mediators   Olink proteomics   Apoptosis  

摘要： Mesenchymal stem cells (MSCs) are frequently employed in transplantation therapies for chronic inflammatory diseases. However, the impact of the inflammatory microenvironment on the functionality of MSCs remains poorly understood. Tumor necrosis factor-alpha (TNF-alpha) is a prevalent inflammatory mediator at transplantation sites, and prior research has indicated that the role of TNF-alpha in MSCs transplantation is ambiguous. The mechanisms by which TNF-alpha modulates the function of MSCs require further elucidation. To investigate this, we conducted comprehensive OLINK proteomic and transcriptomic analyses. The results showed After TNF stimulation, MSCs underwent apoptosis and aging, and their immune regulation, cell migration, and differentiation function were reduced. The signaling pathways involved include NF-KB, MAPK, stem cell pluripotency, etc. In conclusion, TNF activates the immune response of MSCs and impairs their stemness, thereby significantly affecting their capacity for cartilage differentiation.

关键词： ICP0   ICP35 (γ34.5)   ICP4   LAT   gB   survival   type-1 IFN  

摘要： Type-I Interferon (IFN) is essential for antiviral immunity in both mice and humans; thus, we investigated whether LAT affects HSV-1 infectivity in the absence of IFN by infecting IFNαβR and wild-type control mice with HSV-1 McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. IFNαβR mice survived ocular infection with the LAT-plus virus, while no infected mice survived infection with the LAT-minus virus. Increased death in infected mice correlated with a higher expression in the neurovirulence γ34.5 gene but not with gB expression. To determine the region of LAT that contributed to higher mortality, IFNαβR mice were infected with recombinant viruses expressing the first 1.5 kb or the first 811bp region of 1.5 kb LAT. Similar to LAT-plus infected mice, IFNαβR mice infected with LAT1.5kb were protected from death, while infection with the LAT811bp virus was similar to that of LAT-minus, suggesting that increased pathogenicity in the absence of LAT depends on the second half of 1.5 kb LAT. To confirm the in vivo upregulation of γ34.5 expression in the absence of LAT, rabbit skin and Neuro2A cells were infected with LAT-plus, LAT-minus, LAT1.5kb, or LAT811bp viruses. γ34.5 expression was significantly higher in LAT-minus- and LAT811bp-infected rabbit skin cells and Neuro2A cells than in LAT-plus- and LAT1.5kb-infected cells, suggesting that sequences after the 811bp of LAT contribute to γ34.5 upregulation. However, except for γ34.5 expression, ICP0, ICP4, and gB expression were not affected by the absence of LAT or truncated forms of LAT. To confirm that higher γ34.5 expression contributes to higher mortality in the absence of LAT, we infected IFNαβR mice with a recombinant virus lacking LAT and γ34.5 expression, and, in contrast to LAT-minus, all infected mice survived. Our results suggest that LAT controls γ34.5 expression and that higher γ34.5 expression and mortality in infected mice are associated with the second half of 1.5 kb LAT.

关键词： nanoparticles   T regulatory cells (Tregs)   NK cells   autoimmunity   immune tolerance   IL-2   TGF-beta  

摘要： T regulatory cells (Tregs) generated in the periphery (pTregs) are initially unstable, but some of them stabilize with time. The stabilization signals, however, are poorly understood. We have previously reported that the treatment of mice with poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) decorated with anti-CD2 antibodies and encapsulating IL-2 and TGF-beta induced tolerogenic CD4+ and CD8+ pTregs that protected mice from fatal graft-versus-host disease (GvHD). These NPs also induced TGF-beta-producing NK cells. Here we show that initially unstable Tregs are stabilized and maintained by NK-cell derived TGF-beta. Blockade of TGF-beta signaling or NK cell depletion hindered the induction of Tregs and converted tolerogenic responses into immunogenic responses, leading to an accelerated demise of the mice. IL-2 from the NPs and TGF-beta from NP-induced NK cells were sufficient for the maintenance of the Tregs, making the encapsulated TGF-beta unnecessary. These results identify a new non-redundant cellular source of TGF-beta required for the support of newly induced Tregs. NPs inducing cross-communicating innate and adaptive tolerogenic cells can represent a new cell-targeted approach to induce and maintain long-term immune tolerance in immune-mediated diseases.

关键词： MAPK/JNK pathway   TNF-α   apoptosis   breast cancer   c-Jun  

摘要： Breast cancer is the second most common cancer in the United States and consists of 30% of all new female cancer each year. PKC iota (PKC-ι) is a bonafide human oncogene and is overexpressed in many types of cancer, including breast cancer. This study explores the role of PKC-ι in regulating the transcription factor Jun proto-oncogene (c-Jun), pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α), and the Mitogen-Activated Protein Kinase/Jun N-terminal kinase (MAPK/JNK) pathway, which also exhibits an oncogenic role in breast cancer. ICA-1S, a PKC-ι specific inhibitor, was used to inhibit PKC-ι to observe the subsequent effect on the levels of c-Jun, TNF-α, and the MAPK/JNK signaling pathway. To obtain the results, cell proliferation assay, Western blotting, co-immunoprecipitation, small interfering RNA (siRNA), immunofluorescence, flow cytometry, cycloheximide (CHX) chase assay, and reverse transcription quantitative PCR (RT-qPCR) techniques were implemented. ICA-1S significantly inhibited cell proliferation and induced apoptosis in both breast cancer cell lines. Treatment with ICA-1S and siRNA also reduced the expression levels of the MAPK/JNK pathway protein, c-Jun, and TNF-α in both cell lines. PKC-ι was also found to be strongly associated with c-Jun, via which it regulated the MAPK/JNK pathway. Additionally, ICA-1S was found to promote the degradation of c-Jun and decrease the mRNA levels of c-Jun. We concluded that PKC-ι plays a crucial role in regulating breast cancer, and the inhibition of PKC-ι by ICA-1S reduces breast cancer cell proliferation and induces apoptosis. Therefore, targeting PKC-ι as a potential therapeutic target in breast cancer could be a significant approach in breast cancer research.

关键词： 过敏性紫癜   祛风消癜方   免疫球蛋白A   半乳糖缺陷型IgA1   大鼠模型   24 h尿蛋白定量   尿红细胞计数  

摘要： 目的：观察祛风消癜方对过敏性紫癜模型大鼠免疫球蛋白A（IgA）的影响。方法：将45只无特定病原体(SPF)级斯泼累格·多雷(SD)雄性大鼠按照随机数字表法随机分为对照组9只和造模组36只，造模6周后，造模组按照随机数字表法随机分为模型组、复方甘草酸苷组、祛风消癜方低剂量组、祛风消癜方中剂量组和祛风消癜方高剂量组，每组6只。对照组和模型组大鼠灌服0.9%氯化钠溶液，复方甘草酸苷组灌服1.34 mg/mL的复方甘草酸苷混悬液，祛风消癜方低剂量组、祛风消癜方中剂量组、祛风消癜方高剂量组分别灌服0.74 g/ mL、1.48 g/ mL、2.96 g/ mL祛风消癜方混悬液，1次/d，持续4周。结果：造模组大鼠皮肤出现不规则出血斑点；皮肤苏木精-伊红（HE）染色结果显示大量粒细胞呈弥漫性浸润；24 h尿蛋白定量、尿红细胞计数显著高于对照组；肾小球系膜区IgA的表达强度较对照组显著增高。模型组大鼠肾小球系膜区IgA的表达强度、血清与肾脏IgA及半乳糖缺陷型IgA1(Gd-IgA1)水平较对照组显著升高（P<0.05），用药后，各用药组大鼠肾小球系膜区IgA的表达强度、IgA及Gd-IgA1水平较模型组显著降低（P<0.05）。结论：祛风消癜方可以降低过敏性紫癜大鼠IgA、Gd-IgA1水平。

关键词： biologic agents   psoriasis   treatment interruption  

摘要： Background and objectivesContinuous biologic treatment is recommended for patients with psoriasis;however, treatment interruption in daily practice is inevitable. The impact of treatment interruption is difficult to study in a real-world setting. In Taiwan, biologics are reimbursed by the National Health Insurance for moderate-to-severe psoriasis for a 2-year course, followed by regulatory discontinuation. Thus, our study provides pragmatic data on the impact of the interruption of biologics treatment for non-medical reasons on therapy *** and methodsThis single-center retrospective cohort study recruited patients who underwent two consecutive 2-year courses of biologics between 2012 to *** total of 192 treatment courses from 61 patients were analyzed, with secukinumab and ustekinumab being the most frequently administered biologics. Among patients who continued with the same biologic across two consecutive courses, the time to achieve PASI 75 was shorter during the first course compared to the second, while overall maintenance effects remained similar. Switching to a different biologic usually produced superior results in the second course of *** the overall effectiveness after interruption and resumption of treatment with secukinumab or ustekinumab was comparable, the time to achieve PASI 75 was longer following an interruption. Continuous, uninterrupted treatment with a given biologic is therefore recommended whenever possible.

摘要： Fatty acid metabolism mediates macrophage function; however, the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin(IL)-1β production remains to be uncovered. Here, we used genome-wide association studies(GWAS) to identify several porcine serum IL-1β-related genes, such as the fatty acid metabolizing enzyme acyl-CoA thioesterase 11(ACOT11). We then demonstrated that inflammatory macrophages have low expression of ACOT11, and ACOT11 overexpression inhibits IL-1β maturation from inflammatory macrophages. Mechanistically, ACOT11 promotes intracellular fatty acids accumulation, including eicosatetraenoic acid(EA) and stearic acid(SA), which inhibit activation of the Janus kinase(JAK)—signal transducer and activator of transcription(STAT) signaling through palmitoylation of interferon(IFN)-γ receptor(IFNGR) 2 at C261site. Furthermore, we also found that EA attenuates lipopolysaccharide(LPS)-induced sepsis in mice. Collectively, our findings reveal a mechanism involving ACOT11-mediated post-translational modification that regulates macrophage function and provide a promising therapeutic target for the treatment of inflammatory diseases associated with macrophages.