课程文献中心 更多>>

关键词： Sepsis   cognitive impairment   S100B   GFAP   IL-6  

摘要： Objective The main purpose of this study was to comprehensively investigate the combined utility of S100B, GFAP, and IL-6 as predictors of long-term cognitive impairment in sepsis survivors. Specifically, we aimed to determine whether these biomarkers, either individually or in combination, could effectively predict the occurrence of long-term cognitive impairment in this patient population, and to explore their potential as valuable clinical tools for early detection and intervention. Methods This retrospective study enrolled 114 sepsis patients. Patients were divided into non-cognitive impairment and cognitive impairment groups. Serum biomarker levels were compared, and correlations between biomarkers and cognitive impairment were explored. ROC analysis evaluated the predictive value of S100B, GFAP, and IL-6 levels, and the combined diagnosis of the three biomarkers was studied. Results The non-cognitive impairment group had a younger age, higher education level, employment rate, married rate, and presence of family members (p < 0.05). Correlation analysis showed positive correlations between cognitive impairment and CRP, IL-10, S100B, GFAP, and IL-6 (p < 0.05). AUC values of S100B, GFAP, and IL-6 were 0.792, 0.752, and 0.732, respectively, indicating significant predictive value for cognitive impairment. Combined prediction using the three biomarkers had an AUC value of 0.887, with a specificity of 88% and sensitivity of 89%. Conclusion Long-term cognitive impairment in sepsis survivors is influenced by various cytokines. Significant differences were found in biomarker levels between non-cognitive impairment and cognitive impairment groups. The combined utility of S100B, GFAP, and IL-6 showed significant predictive value for cognitive impairment in survivors of sepsis.

关键词： Lymphocyte cytosolic protein 1 (LCP1)   Oral cavity squamous cell carcinoma (OSCC)   Interleukin-1 beta (IL-1 beta)   EGFR signaling pathway   Cancer progression   Proteomics  

摘要： Oral cancer is the sixth leading cause of cancer-related mortality in Taiwan, with over 90% of cases being oral cavity squamous cell carcinomas (OSCCs). The high mortality rate of OSCC is largely attributed to metastasis and locoregional relapse, underscoring the need to identify key drivers of tumor progression. To uncover proteins involved in OSCC relapse, we conducted an iTRAQ-based proteomic profiling of OSCC tissues from 6 patients with primary tumors and 4 patients with relapsed tumors. Lymphocyte cytosolic protein 1 (LCP1) emerged as a candidate associated with OSCC progression, further supported by transcriptomic analysis from The Cancer Genome Atlas (TCGA). LCP1 showed a 2.4-fold upregulation in relapsed tumors and correlated with poor patient survival. Functional assays revealed that LCP1 expression promoted tumor growth in vivo and enhances proliferation, migration, invasion, and cisplatin resistance in vitro across four OSCC cell lines. Mechanistically, LCP1 expression and phosphorylation were induced by EGF via the EGFR/PI3K/AKT and EGFR/ERK signaling pathways. Additionally, LCP1 activated the JAK2/STAT3 axis to upregulate pro-interleukin-1 beta (IL-1 beta) expression and IL-1 beta secretion, thereby amplifying OSCC cell aggressiveness. In summary, this study provides novel insights into the oncogenic role of LCP1 in OSCC, linking EGFR-mediated signals and IL-1 beta production, and identifies LCP1 as a promising target for therapeutic intervention.

关键词： hepatic macrophages   IL-25   macrophage polarisation   MAFLD   notch signalling  

摘要： Background and Aims: Hepatic steatosis is characterised by hepatic lipid accumulation, inflammation and fibrosis, with macrophage polarisation playing a central role in disease progression. This study investigates the role of interleukin-25 (IL-25) in modulating macrophage polarisation and Notch signalling in a methionine-choline-deficient (MCD) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) model. Methods: C57BL/6 mice were fed a MCD diet to induce MAFLD. Human hepatocytes and primary hepatic macrophages were treated with palmitic acid and/or IL-25. Methods included RT-qPCR, ELISA, Western blot and immunofluorescence for gene/protein expression. ChIP and luciferase assays were used to analyse STAT3/Notch-1 signalling. Results: We found that IL-25 expression was significantly downregulated in the livers of MCD-fed mice and in palmitic acid-treated hepatocytes. IL-25 treatment promoted M2 macrophage polarisation, evidenced by increased expression of Arg1, Chi3l3 and anti-inflammatory cytokines (IL-10, TGF-beta), while suppressing pro-inflammatory cytokines (TNF-alpha, IL-6). Mechanistically, IL-25 inhibited the STAT3/Notch-1 pathway and induced IL-33, which negatively regulated the NF-kappa B/Jagged-1 axis, preventing M1 macrophage polarisation. Adoptive transfer of IL-25-induced M2a macrophages ameliorated hepatic steatosis and reduced ductular reaction in MCD-fed mice. Conclusions: These findings suggest a role for IL-25 in modulating macrophage polarisation and inflammation in metabolic dysfunction-associated fatty liver disease, supporting its further exploration as a potential therapeutic strategy for inflammatory liver diseases.

摘要：

关键词： Infliximab   Cyclophosphamide   Myelosuppression   Splenotoxicity   Rats  

摘要： PurposeCyclophosphamide is a widely used anticancer agent, though its clinical application is often constrained by myelotoxicity. Infliximab, a monoclonal antibody targeting TNF-alpha, may alleviate this toxicity by mitigating oxidative stress. This study aimed to assess the protective effects of infliximab against cyclophosphamide-induced myelotoxicity, focusing on bone marrow and spleen-related *** Wistar rats (260 +/- 20 g) were randomly divided into four groups (n = 5 each): Control (normal saline), Infliximab (7 mg/kg, IP), Cyclophosphamide (200 mg/kg, IP), and Infliximab + Cyclophosphamide (same respective doses with a four-day interval between administrations). Nine days after the initiation of the experiment, bone marrow and spleen histopathology, bone marrow cellularity, spleen index, and levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in bone marrow tissue, along with serum TNF-alpha and G-CSF concentrations, were *** prevented myelofibrosis in bone marrow tissue;however, it did not mitigate cellularity depletion. It failed to counteract the effects of cyclophosphamide on spleen histology and the spleen index. Additionally, infliximab enhanced antioxidant activity in the bone marrow. Moreover, inhibition of TNF-alpha was associated with an increase in G-CSF *** infliximab improved molecular pathways associated with cyclophosphamide-induced bone marrow and hematologic toxicity in the rat model, it did not lead to significant improvements in clinical manifestations.

关键词： Anterior uveitis   Cytomegalovirus   Human leukocyte antigen-B27   Retinal microvasculature   Choriocapillaris  

摘要： PurposeThis study assessed posterior segment microvascular changes in patients with cytomegalovirus (CMV) anterior uveitis (AU) during acute episodes by comparing retinal and choroidal changes to those in patients with HLA-B27 AU and healthy controls, aiming to evaluate their impact on visual *** this retrospective study, 85 patients with CMV AU, 93 with HLA-B27 AU, and 80 healthy controls underwent comprehensive ocular evaluations, including optical coherence tomography (SS-OCT) and OCT angiography (OCTA). Retinal thickness, vascular density (VD), and choroidal parameters were evaluated, and statistical comparisons were made among *** microvascular changes were observed in both uveitis groups. In CMV AU, parafoveal superficial vascular plexus (SVP) VD, deep capillary plexus (DCP) VD, and choriocapillaris flow deficit (CCFD) areas were significantly associated with visual acuity. CMV AU patients showed lower parafoveal SVP and DCP VD and larger CCFD areas than healthy controls. Compared to HLA-B27 AU, CMV AU exhibited a lower DCP VD and higher CCFD area, indicating distinct retinal and choroidal *** microvascular changes occur in acute AU, affecting visual acuity, even without evident retinal or vitreous involvement. The effects of CMV AU on the retinal and choroidal microvasculature highlight the need for posterior segment evaluation to manage AU. What is known:CMV anterior uveitis is typically seen as an anterior segment disease with little focus on posterior *** is new:CMV AU shows distinct choroidal and retinal microvascular changes compared to HLA-B27 AU and healthy *** segment changes in CMV AU correlate with visual acuity, highlighting their clinical importance.

关键词： Triple-negative breast cancer   High-intensityfocusedultrasound   CD8+T cell   Januskinase/signal transducers and activators of transcription   Il-2rb   IL-2   Immunotherapy  

摘要： Triple-negative breast cancer (TNBC) is characterized by a lack of effective targeted therapies and a challenging immunosuppressive microenvironment that limits the efficacy of immunotherapy. This study explores the potential of high-intensity focused ultrasound (HIFU) in modulating the immune response. Using the 4T1 mouse tumor model, we assessed the effects of thermal (T-HIFU) and mechanical (M-HIFU) HIFU on CD8+ T cells. Proteomic analysis revealed that T-HIFU and M-HIFU increased Il-2rb expression on CD8+ T cells, activating the JAK-STAT pathway and enhancing the efficacy of IL-2, leading to improved tumor growth inhibition and survival rates. The combination of HIFU and IL-2 demonstrated synergistic antitumor effects, indicating a new strategy for enhancing immunotherapy in TNBC. This approach uniquely boosts antitumor immunity by upregulating Il-2rb on CD8+ T cells, offering a promising avenue for overcoming the immunosuppression in TNBC.

关键词： ADAMTS-8   TNF   Colorectal cancer   NF-kappa B   PI3K   And SAPK/JNK  

摘要： Tumor necrosis factor-alpha (TNF-alpha) is associated with the metastatic phenotype and regulates cellular communication in Colorectal Cancer (CRC). This study investigates the effects of TNF-alpha on the expression of the ADAMTS-8 gene in SW480 colorectal cancer cells, focusing on both mRNA and protein levels, as well as the underlying intracellular signaling pathways activated in response to TNF-alpha. SW480 cells were treated with TNF-alpha at varying concentrations (10, 20, and 40 ng/mL) for 24, 48, and 72 h. Utilizing the MTT assay, a significant reduction in cell viability was observed at 48 and 72 h across all doses, indicating a cytostatic effect of TNF-alpha. The transcriptional activity of ADAMTS-8 was assessed through transient transfection of full-length and truncated promoter constructs, revealing that TNF-alpha significantly upregulated ADAMTS-8 expression through specific promoter regions. Quantitative RT-PCR and Western blot analyses demonstrated a time- and dose-dependent increase in both mRNA and protein levels of ADAMTS-8 in cells treated with 10 and 20 ng/mL of TNF-alpha. TNF-alpha strongly increased the transcriptional activity of several truncated ADAMTS-8 promoter constructs. Further exploration of intracellular signaling pathways revealed the activation of NF-kappa B, PI3K, and SAPK/JNK pathways, with limited activation of p38/MAPK. Inhibition studies employing specific pathway inhibitors indicated that blockade of NF-kappa B, PI3K, p38/MAPK, and JNK signaling pathways significantly suppressed TNF-alpha-induced ADAMTS-8 expression at both mRNA and protein levels. Additionally, Chromatin Immunoprecipitation (ChIP) assays confirmed the binding of NF-kappa B, STAT-3, ELK-1, c-Jun, and ATF-1 to the ADAMTS-8 promoter in response to TNF-alpha treatment. These findings suggest a multifaceted regulatory mechanism wherein TNF-alpha promotes ADAMTS-8 expression by activating key transcription factors and associated signaling cascades-in silico analysis