课程文献中心 更多>>

关键词： Primary central nervous system lymphoma   TNF-alpha   IFN-gamma   NF-kappa B   PD-L1  

摘要： AIDS-related primary central nervous system lymphoma (AR-PCNSL) differs from immunocompetent PCNSL (ICPCNSL) due to its immune function and higher mortality rates, emphasizing the urgent need for new treatment targets. This study aimed to investigate the role of the NF-kappa B p65/PD-L1 signaling pathway in AR-PCNSL. A total of 56 PCNSL tissue samples, including 32 AR-PCNSL cases and 24 IC-PCNSL cases, were analyzed for clinicopathological and imaging features. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, PD-L1 immunohistochemistry and Epstein-Barr encoding region (EBER) in situ hybridization. Differentially expressed molecules (DEMs) were identified via bulk RNA-Seq analysis, while functional pathways were explored through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. MYD88 L265P and CD79B mutations were detected using sanger sequencing. Additionally, RT-PCR was used to measure the mRNA expression levels of TNF-alpha and IFN-gamma in frozen tissues, while western blotting assessed the protein expression levels of p-NF-kappa B p65, NF-kappa B p65, and PD-L1 in cell lines. Compared with IC-PCNSL tissues, AR-PCNSL tissues demonstrated significantly more necrosis (p = 0.001). Imaging analysis showed that AR-PCNSLs had lower ADC (Apparent Diffusion Coefficient, ADC) values (p = 0.000) and more frequent annular enhancement signals (p = 0.007) on DWI (diffusion weighted imaging, DWI). The PD-L1 and EBER positivity rates were higher in ARPCNSL patients. Co-occurring mutations in MYD88 L265P and CD79B were rare in AR-PCNSL, and were found in only 6.7 % (1/15) of samples, while these mutations appeared in 60.0 % (9/15) of the IC-PCNSL patients (p = 0.005). The RNA levels of TNF-alpha and IFN-gamma were significantly higher in AR-PCNSL patients than in IC-PCNSL patients (p = 0.001). Western blot analysis after TNF-alpha and IFN-gamma treatment revealed increased expression of pP65 protein and PD-L1. This study provides new

关键词： Trained immunity   Neutrophils   Bactericidal activity   Turbot  

摘要： Trained immunity refers to the immune memory of innate immune cells, which is driven by metabolic rewiring and epigenetic reprogramming after initial stimulation. Several endogenous inducers of trained immunity have been reported, such as oxidized low-density lipoprotein (oxLDL), interleukin, and interferon. However, the negative regulatory molecules of trained immunity remain largely elusive. In this study, we identify a member of IL-1 family receptors, interleukin-1 receptor 2 (IL-1R2), as a potential inhibitory regulator of trained immunity in turbot. Pre-incubating recombinant IL-1R2 protein (rIL-1R2) with turbot neutrophils could inhibit (3-glucaninduced training phenotypes. Specifically, rIL-1R2 incubation significantly decreases the expression of genes involved in the TLR/IL-1R and downstream MAPK/NF-kappa B signaling pathway in trained neutrophils, and further reversing the elevated expression of pro-inflammatory cytokines such as IL-6 and TNF-alpha in response to bacterial reinfection. Moreover, rIL-1R2 inhibits the increasing production of intracellular reactive oxygen (ROS), myeloperoxidase (MPO) activity and neutrophil extracellular traps (NETs) in trained neutrophils, ultimately impairing the bacterial killing ability. Taken together, our work demonstrates that the decoy receptor IL-1R2 could negatively regulate trained immunity activation in turbot neutrophils. These findings enrich the theory of trained immunity in teleost fish and provide a potential target for disease prevention and treatment in aquaculture.

关键词： Cyprinid herpesvirus 2 (CyHV-2)   ORF67   IFN   Phosphorylation   Immune escape  

摘要： Cyprinid herpesvirus 2 (CyHV-2) caused hematopoietic necrosis in crucian carp (Carassius auratus) has resulted in huge economic losses to the carp aquaculture. Interferon (IFN) response serves as a crucial line of defense for fish against CyHV-2 infection;however, CyHV-2 frequently overcomes this defense, resulting in damage and even substantial mortality. The mechanism by which CyHV-2 evades the fish IFN antiviral response remains unclear. In this study, we chose the open reading frame 67 (ORF67) of CyHV-2 as the target of our research. Firstly, the results of Co-immunoprecipitation (Co-IP) assay and in vitro phosphorylation showed that the ORF67 inhibited the expression of IFN by binding to TBK1-A/B and competitively blocking STING-A/B phosphorylation. Then, we elaborated on the effect of ORF67 on the cell's antiviral function by cytopathic effect (CPE) and immunoblot analysis. In summary, this study has clarified the molecular mechanism of immune evasion by ORF67 through the inhibition of host IFN expression. This research enhances our understanding of the pathogenesis of CyHV-2 and provides theoretical references for the prevention and treatment of hematopoietic necrosis.

关键词： stroke   interleukin-27   inflammation   oxidative stress   T-cell  

摘要： Stroke is a life-threatening cerebrovascular disorder categorized into two major subtypes: Ischemic and hemorrhagic. Characterized by high morbidity and mortality rates, its clinical management remains challenging due to limited therapeutic options. Interleukin (IL)-27, a pleiotropic cytokine with demonstrated neuroprotective potential, has emerged as a promising candidate for stroke intervention. IL-27 exerts immunomodulatory effects within the central nervous system, including suppression of proinflammatory T-cell proliferation and induction of regulatory T-cell differentiation. These mechanisms collectively attenuate neuroinflammation, mitigate neuronal apoptosis and prevent neurodegenerative processes. The efficacy of IL-27 in reducing cerebral damage in both ischemic and hemorrhagic stroke models has been validated, although clinical translation remains to be achieved. The present review summarizes: i) The epidemiology of stroke;ii) the immunoregulatory functions of IL-27 and its neuroprotective mechanisms across stroke subtypes;iii) innovative brain-targeted delivery approaches;iv) IL-27 clinical applicability with supporting evidence;and v) possible risks and solutions in clinical applications. By collating the current knowledge, the present study provides a translational framework for advancing IL-27-based therapies in stroke management.

关键词： chronic nonbacterial osteomyelitis   CNO   autoinflammatory   autoinflammatory bone disorder   chronic recurrent multifocal osteomyelitis   CRMO   DMARD   disease-modifying anti-rheumatic drug   CARRA   Childhood Arthritis and Rheumatology Research Alliance   CNO   Chronic nonbacterial osteomyelitis   CRMO   Chronic recurrent multifocal osteomyelitis   IBD   Inflammatory bowel disease   IL   Interleukin   MRI   Magnetic resonance imaging   NSAID   Non-steroidal anti-inflammatory drug   PPP   Palmoplantar pustulosis   SAPHO   Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis   TNFi   Tumor necrosis factor-inhibitor   WB-MRI   Whole-body MRI  

关键词： TNF‑receptor associated factor 3   bone fracture healing   fracture callus   otubain 2   ubiquitin  

摘要： Increased incidence of traumatic fracture markedly effects the quality of life of patients. Using a rat model of femur fracture, the present study aimed to investigate the effects of otubain 2 (OTUB2), a deubiquitinating enzyme, on bone fracture healing. Bone marrow mesenchymal stem cells (BMSCs) were harvested from the marrow cavity of rat femurs and tibiae and subsequently subjected to osteogenic differentiation . Results of the present study revealed that lentivirus‑mediated OTUB2 overexpression accelerated rat bone fracture healing, potentiated fracture callus formation and cartilaginous ossification and regulated the expression of proteins associated with bone remodeling. In addition, OTUB2 overexpression facilitated the osteogenic differentiation and mineralization of BMSCs and promoted the expression of TNF‑receptor associated factor 3 (TRAF3) both and . Co‑immunoprecipitation analysis was used to verify the physical interaction between OTUB2 and TRAF3 and further results demonstrated that OTUB2 reduced the ubiquitination of TRAF3. The results of the present study also demonstrated that TRAF3 knockdown repressed the OTUB2‑induced osteogenic differentiation and mineralization of BMSCs. Collectively, these results demonstrated that OTUB2 may stabilize TRAF3 to accelerate bone fracture healing.

关键词： human epidermal growth factor receptor 2-positive breast cancer   pyrotinib   cytokine   interferon-gamma   clinical efficacy   adverse events  

摘要： Pyrotinib has been extensively utilized in the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), yet few reliable markers for predicting pyrotinib efficacy in these patients have been identified. Therefore, the present study aimed to explore the predictive clinical factors for treating patients with HER2-positive ABC with pyrotinib. To this aim, a prospective observational study was conducted on the prognostic potential of serum cytokines in a cohort of 58 patients with HER2-positive cancer receiving pyrotinib treatment, enrolled from January 2020 to December 2022. Patients were treated with oral pyrotinib (400 mg/day, 30 min after eating) combined with capecitabine (1,000 mg/m2 twice daily on days 1-14 of a 21-day cycle) or vinorelbine soft capsules (40 mg/day, 3 times weekly). Peripheral blood was collected from these patients before and 4 weeks after the initial administration of pyrotinib. Plasma cytokine levels (IL-6, IL-8, IL-10, IL-17 and IFN-gamma) were measured via multiple microsphere flow cytometry luminescence. Univariate analysis revealed that patients who received pyrotinib as second-line therapy had an improved progression-free survival (PFS) time compared with those who received it as third- or later-line therapy [median PFS (mPFS), 17.0 vs. 9.5 months;P=0.016]. Furthermore, patients with increased plasma IL-8 levels had a poorer PFS time than those with decreased levels (mPFS, 9.4 vs, 14.0 months;P=0.021). Patients with increased plasma IFN-gamma levels had a longer PFS time than those with decreased levels (mPFS, 13.0 vs. 11.0 months;P=0.010). Multivariate Cox regression analysis revealed that pyrotinib application beyond third-line therapy and decreased plasma IFN-gamma levels were independent risk factors for PFS (P=0.025 and P=0.033, respectively). In conclusion, early application of pyrotinib may improve the PFS time of patients with HER2-positive ABC who are resistant to trastuzum

关键词： Curcumin   HPSE   Colorectal cancer   IL-6-STAT5 axis   Non-coding RNAs  

摘要： Our previous research demonstrated that curcumin suppresses mouse colorectal cancer (CRC) cell CT26 migration and invasion by inhibiting heparanase (HPSE) mRNA expression. To further elucidate the mechanism of curcumin in human CRC treatment, we hypothesized that HPSE plays a pivotal role in human CRC metastasis and that curcumin inhibits this process by downregulating HPSE expression through epigenetic regulation mediated by non-coding RNAs. For further research, human CRC cells were infected with lentivirus to establish overexpression of HPSE cell lines and corresponding negative control cell lines. In vitro and in vivo experiments showed that curcumin inhibited the proliferation, migration, and metastasis of CRC cancer by inhibiting HPSE expression. In the tumor microenvironment, HPSE played an important role in activating the IL-6/STAT5 axis signaling pathway by destructing the extracellular matrix and releasing large number of cytokines, while changing the tumor microenvironment and EMT process, thus promoting tumor metastasis. RNA-seq analysis combined with qRT-PCR results showed that curcumin's inhibition of HPSE expression involved the regulation of non-coding RNAs. Taken together, our results suggested that HPSE promotes CRC metastasis by activating the IL-6/STAT5 signaling axis, disrupting the ECM, releasing cytokines, and altering the tumor microenvironment to facilitate EMT. Curcumin significantly inhibits CRC cell proliferation, migration, and metastasis by downregulating HPSE expression via non-coding RNAs, which related to IL-6/STAT5 axis signal pathways. This research provides a comprehensive understanding of the molecular mechanisms underlying curcumin's anti-CRC effects, emphasizing the role of HPSE and non-coding RNAs in tumor metastasis. These findings pave the way for the development of novel therapeutic strategies targeting HPSE and its regulatory pathways in CRC.

关键词： IL-10   aTCMR   NFATc1 signaling pathway   T cell   Kidney transplantation  

摘要： The cause of acute T cell-mediated rejection (aTCMR) is believed to be immune hyperfunction of T cells after kidney transplantation. Nowadays, calcineurin inhibitors are widely used to inhibit the proliferation of T cells when aTCMR occurs. However, the therapeutic dose window of these drugs is relatively narrow and long time use of these drugs may lead to serious side effects. Besides, whether IL-10, a new immune tolerance mediator, playing a therapeutic role on aTCMR remains unclear. The level of IL-10 decreased in patients with aTCMR, suggesting that IL-10 may be involved in the progression of aTCMR. IL-10 could inhibit the proliferation and metabolism of T cells in vitro and in vivo, accompanied by reducing the levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, we confirmed that IL-10 exerts immunosuppressive effects by inhibiting the NFATc1 signaling pathway of T cells. This viewpoint may provide a new therapeutic idea for clinical application.

关键词： Peritoneal dialysis   Peritoneal equilibration test   Peritoneal solute transport rate   Cytokine   IL-8  

摘要： Background: Several cytokine levels in dialysate, particularly interleukin-6 (IL-6), have been investigated as potential biomarkers for peritoneal solute transport rate (PSTR). However, studies examining the relationship between systemic cytokine levels and PSTR have yielded contradictory results. In this study, we aimed to assess 12 kinds of cytokines in serum and explore their potential relationship with peritoneal transport function. Methods: Patients undergoing peritoneal dialysis (PD) from September 2022 to September 2024 were retrospectively analyzed at our PD center. The patients were categorized into fast and non-fast PSTR groups based on the 4-h dialysate creatinine /plasma creatinine ratio (D/P Cr). The systemic levels of 12 cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17 A, TNF-alpha, IFN-alpha, and IFN-gamma) in both groups were measured using flow cytometry and compared. The relationship between serum cytokine levels and baseline peritoneal transport status was analyzed by univariate and multivariate logistic regression analyses. Results: A total of 284 patients were enrolled in this study. According to the D/P Cr, 171 patients (60.2 %) were classified as non-fast PSTR group, while 113 patients (39.8 %) were classified as fast PSTR group. Among the 12 cytokines analyzed, serum IL-8 exhibited a significant difference between the two groups (P = 0.01). IL-8/IL-10 and IL-12p70/IL-10 ratios were also significantly higher in fast PSTR group. In the subgroup of incident PD patients, multivariate analysis revealed that total cholesterol (OR 0.559, 95 % CI 0.323-0.966, P = 0.037) and serum IL-8 (OR 1.040, 95 % CI 1.006-1.075, P = 0.021) were significantly and independently associated with baseline fast PSTR. Conclusion: The systemic IL-8 level is positively correlated with PSTR in patients undergoing PD, which may serve as an indicator of baseline peritoneal transport function.