课程文献中心 更多>>

关键词： IFN-gamma   Cytokine   Malignancy   Anti-tumor   Immunotherapy  

摘要： Interferon-gamma (IFN-gamma) is recognized for its ability to inhibit cell growth, promote programmed cell death, and stimulate immune responses against tumor progression. However, cancerous cells exploit IFN-gamma by producing factors that suppress anti-tumor immune responses. Exploring the diverse functions of IFN-gamma can offer fresh perspectives for cancer research and the development of immune-based therapies. IFN-gamma plays a multifaceted role in the immune system, which includes aiding in boosting the effectiveness of cancer immunotherapy, particularly immune checkpoint inhibitor therapy, by triggering the expression of checkpoint molecules like PD-L1 on tumor cells. Conversely, it can also diminish the effectiveness of immunotherapy by contributing to tumor resistance. Moreover, the level of IFN-gamma present inside the microenvironment of the tumor appears to dictate whether IFN-gamma acts as a pro-tumor or anti-tumor response. Therefore, enhanced comprehension of IFN-gamma's multifaceted actions can revolutionize approaches to cancer biology and intervention strategies targeting the immune system. This review provides an overview of the regulatory roles of IFN-gamma in cancer and immunology.

关键词： Rheumatoid arthritis   TNF-alpha   IL-6R   Fenobody   GelMA microneedle  

摘要： Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by inflammatory imbalance. The cytokine-targeted therapy is a non-traditional form of RA treatment that is mighty effective but poses the challenge of pharmaceutical storage conditions, professional injection, frequent injection administrations and poor patient adherence, and due to individual differences in sensitivity to TNF-alpha and IL-6R, monotherapy with a single antibody is effective in fewer than 30 % of cases. Hence, to address these issues, we have developed a macromolecule polymer GelMA microneedle sustained-release platform for transdermal delivery of a dual-specific fenobody targeting TNF-alpha and IL-6R in an arthritic rat model. The results demonstrated that the IL-6R-TNF-alpha-fenobody exhibited enhanced specificity and affinity and an extended half-life. IL-6R-TNF-alpha-fenobody effectively neutralizes rhTNF-alpha-induced cytotoxicity in L929 cells, while inhibiting the phosphorylation of I kappa B alpha and p65 in the classical NF-kappa B signaling pathway, and significantly blocks JAK-dependent phosphorylation of STAT3, thereby exerting its anti-inflammatory effects via multiple signaling pathways. The GelMA hydrogel microneedle sustained-release platform facilitates controlled cargo delivery to alleviate the inflammatory environment and reduce over-activated synoviocyte activity, thus promoting bone and joint regeneration. In collagen-induced arthritis (CIA) rats, cross-linked gelatin microneedles demonstrated high mechanical strength, facilitating the effective delivery of fenobodies to the dermis for optimal microcirculation, reduced levels of inflammatory factors, this strategy significantly inhibited the progression of RA. Overall, the IL-6R-TNF-alpha-Fenobody therapy promoted bone and joint regeneration by synergistic inflammation-resolving, osteogenesis. Excitingly, the microneedle group showed comparable treatment outcomes to the injection group, providing a

摘要： Cocaine dysregulates tumor necrosis factor (TNF) signaling in mesolimbic substrates, suggesting a role for TNF in cocaine-induced hyperlocomotion, a signature preclinical effect of cocaine. Inhibition of TNF signaling by genetic deletion or with a brain-penetrable TNF antagonist enhances cocaine-induced hyperlocomotion in male mice, but roles for sex and peripheral TNF are unclear. Also unknown is how peripherally restricted etanercept, the world's most widely prescribed TNF inhibitor, affects cocaine-induced locomotor responses. We determined effects of etanercept on a triad of cocaine-induced locomotor responses (e.g., ambulation, stereotypy, distance traveled) in male and female rats and impacts of etanercept-cocaine exposure on tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA levels in the ventral tegmental area (VTA). Etanercept (20 mg/kg, IP) and a submaximal dose of cocaine (10 mg/kg, IP) were used initially, and etanercept was injected 48 h before cocaine to capture peak plasma concentrations. Etanercept itself did not affect spontaneous locomotor responses in male or female rats. In male rats, etanercept increased cocaine-induced ambulatory and stereotypical activities and enhanced cocaine-induced distance traveled. Etanercept modestly reduced TH mRNA levels in the VTA of cocaine-na & iuml;ve and cocaine treated male rats. Locomotor responses in male rats that were evoked by a higher dose of cocaine (20 mg/kg, IP) were not affected by etanercept. In female rats, etanercept did not affect any cocaine-induced locomotor responses. These results show that etanercept exerts effects on locomotor behaviors induced by cocaine that depend on both sex and cocaine dose and suggest that peripheral inhibition of TNF influences cocaine-induced behaviors. Key words: etanercept;TNF;cocaine;dopamine;tyrosine hydroxylase;DAT;locomotor.

关键词： Long-COVID   T cells   Cytokines   IL-3  

摘要： Following SARS-CoV-2 infection, some individuals develop Long-COVID-syndrome lasting for more than 3 months. We analyzed blood samples from patients with Long-COVID, controls without persistent symptoms following SARS-CoV-2-infection and non-infected donors without a history of infection. Long-COVID patients showed clear signs of T cell hyper-activation predominantly in the CD8+ T cell subset with a 4-fold higher expression of CD25 and 2-fold more effector-memory T cells. Following polyclonal T cell stimulation, we found a 2-fold stronger upregulation of CD25 and a 7-fold higher release of IL-3 in Long-COVID. Intracellular staining revealed 5-fold more IL-3-expressing CD8+ T cells in Long-COVID, while GM-CSF, IFN-gamma and IL-2 were much less upregulated. These changes correlated with the severity of Long-COVID and persisted for up to 18 months after infection. Our data reveal a pronounced and long-lasting CD8+ T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.

关键词： IL-8 gene   Rs4073   Polymorphism   Oral mucositis  

摘要： Objectives The aim of this study was to investigate the association between Interleukin-8 (IL-8) rs4073 polymorphism and oral mucositis (OM). Design A prospective randomized controlled design was employed in this study. The investigation encompassed 107 patients diagnosed with OM following radiotherapy and 153 patients who did not develop OM post-radiotherapy. The study period spanned from the initiation of radiotherapy to six weeks post-treatment. All participants were diagnosed with head and neck cancer and were undergoing radiation therapy. Patient ages ranged from 33 to 75 years. This single-center study was conducted at Southern Hospital. The Visual Analogue Scale (VAS) and the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) were utilized to evaluate OM. Additionally, genotyped using Sanger sequencing, and serum IL-8 expression levels were quantified by ELISA. Results Individuals carrying the A allele (OR=1.470, 95 %CI= (1.028-2.101)) and AA genotype (OR=2.165, 95 %CI=(1.044-4.489)) may face a significantly higher risk of OM (P < 0.05). Notably, the concentration of IL-8 in serum samples from patients with OM was markedly elevated compared to that observed in the control group (P < 0.001). The A allele and AA genotype of the polymorphic site rs4073 of IL-8 were significantly correlated with the severity (A vs. T: OR=1.983, 95 %CI= (1.136-3.460);AA vs. TT: OR= 3.545, 95 %CI= (1.135-11.075)) and intensity of pain (A vs. T: OR=1.889, 95 %CI=(1.095-3.260);AA vs. TT: OR= 3.438, 95 %CI= (1.133-10.425)) in OM (P < 0.05). Conclusion The IL-8 rs4073 polymorphism may exert a significant influence on the susceptibility to OM after radiation therapy.

关键词： Chicken interleukin-17   Infectious bursal disease virus   DNA vaccine   Adjuvant  

摘要： Infectious bursal disease virus (IBDV) is an important immunosuppressive virus in chickens, which caused an acute and highly contagious infectious disease and resulted in considerable economic losses in the world poultry industry. Although IBDV VP2 DNA vaccine has been extensively proved only partial protection, the efficacy of DNA vaccines against IBDV can be augmented by choosing potential molecular adjuvants. To investigate whether chicken IL-17 (chIL-17) is qualified for the molecular adjuvant, we constructed chIL-17 gene vector, coimmunized chickens with chIL-17 gene vector and IBDV VP2 DNA vector, and analyzed the effect of IL-17 gene on the immunogenicity of VP2 DNA vaccine. Results showed that co-administrated chIL-17 gene and VP2 DNA vaccine significantly increased IBDV-specific serum antibody titer, and promoted lymphocyte proliferation and interference-gamma (IFN-gamma) production. Mechanically, chIL-17 reduced virus titer in bursa of fabricius tissue and mortality of IBDV-infected chicken. More importantly, chIL-17 gene significantly enhanced the protection induced by the VP2 gene against virulent IBDV *** data show that chIL-17 is a promising immunoadjuvant to facilitate humoral as well as cellular immunity in a vaccine setting against IBDV, and suggest that it should be evaluated as a new DNA vaccine adjuvant in strategies for other poultry diseases.

关键词： Lycium barbarum glycopeptide   Alkali burn   Inflammation   miR-21a-5p   Fibrosis  

摘要： Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties;however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGF(3-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (aSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-xB/NLRP3/IL-1(3 signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGF(3-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGF(3/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.

关键词： antibody mediated rejection   daratumumab   desensitization   pediatric heart transplant   ventricular assist device  

摘要： BackgroundPediatric heart transplant recipients have high rates of alloantibody development and antibody-mediated rejection (AMR). Daratumumab is a novel therapy that targets plasma cells and has been utilized in transplant populations, but data in pediatric populations are limited. Here, we describe the utilization of daratumumab in pediatric heart transplant *** patients at a single institution were treated with daratumumab for AMR (n = 9) or anti-HLA antibody desensitization (n = 3). Three doses of daratumumab were administered with additional doses based on clinical response. For AMR, response to daratumumab was evaluated based on hemodynamics, histopathology, biopsy mRNA expression profiling, ejection fraction, donor-specific antibody titers, and donor-derived cell-free DNA fraction. For desensitization, cPRA pre- and post-daratumumab were ***-five daratumumab infusions were administered to 12 patients (age 0.5-24 years;weight 8-90 kg). Infusion reactions occurred in 12% of infusions;however, none required discontinuation. Nine patients (75%) experienced infection;most were common childhood infections and did not require hospitalization. All 9 AMR patients showed improvement in AMR, and those with chronic AMR benefitted from repeat daratumumab administration. All desensitization patients had dramatic declines in cPRA, and two underwent successful transplantation without rejection 9 months *** report that daratumumab is safe and effective in a small series of pediatric heart transplant patients, including patients as young as 6 months old. Daratumumab could prove to be a valuable tool for desensitization and AMR treatment;however, additional studies are needed to corroborate these findings and determine long-term outcomes.

关键词： SARS-CoV-2   Severe acute respiratory syndrome coronavirus   CAA   Cerebral amyloid angiopathy   LATE-NC   limbic predominant age-related   TDP-43   encephalopathy-neuropathologic changes   AD   Alzheimer’s Disease   IgG   Immunoglobulin G   ANNA-1   type-1 antineuronal nuclear antibody   IFN   Interferon   IL   Interleukin   IL-1RA   Interleukin-1 Receptor Antagonist   IP-10   Interferon gamma-induced protein 10   MCP-1   Monocyte Chemoattractant Protein-1   MIP-1α   Macrophage Inflammatory Protein-1 alpha   TNFα   Tumor Necrosis Factor alpha   VEGF   Vascular Endothelial Growth Factor   RANTES   Regulated upon Activation, Normal T cell Expressed and Secreted  

摘要： Background and Objectives: A spectrum of neurologic complications associated with COVID-19 are well documented. While neuroinflammation in the brain of COVID19 patients likely contributes to these complications, the mechanisms of neuroinflammation and correlates of neurologic complications remain elusive, especially since the etiologic pathogen of COVID-19, SARS-CoV-2, minimally invades the CNS. This study aimed to evaluate markers of neuroinflammation, IgG glycosylation patterns indicative of pro-or anti-inflammatory state, and prevalence of brain auto-reactive antibodies in the CSF of COVID-19 patients and their relationship to brain neuropathology. Methods: We evaluated the CSF of 11 deceased unvaccinated COVID-19 donors and 13 matched non-COVID-19 controls. Markers of neuroinflammation, IgG glycosylation patterns, and brain auto-reactive antibodies were assessed, along with their correlation to brain neuropathology. Statistical analyses were performed to compare groups and assess relationships between variables, using non-parametric tests and bootstrap analysis. Results: COVID-19 CSF showed higher levels of neopterin and ANNA-1, markers of neuroinflammation and autoimmunity, respectively, and lower IFN response compared to non-COVID-19 donors. In brain regions of high microglial activation, IL4 and RANTES were significantly increased. SARS-CoV-2 was undetectable in the CSF and brain of COVID-19 donors, yet anti-SARS-CoV-2 CSF antibodies were detected. Fucosylated IgG were associated with Spike IgG, CSF protein, and soluble CD14, whereas afucosylated bisecting IgG were inversely correlated with Spike IgG. Sialic acid containing IgG were positively correlated with IL1 beta and TNF alpha. These associations were not found in non-COVID-19 donors. Inflammatory agalactosylated fucosylated IgG (G0F) were associated with infiltrating CD4 + T cells in the brains of COVID-19 donors. COVID-19 donor CSF displayed higher levels of auto-reactive antibodies to human brain anti