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摘要： Background and Aims: Pro-inflammatory cytokines, such as IL-1β, play a crucial role in propagating atherogenesis. Pharmacological blockade of IL-1β is effective in reducing atherosclerosis-associated cardiac events, however, additional anti-IL-1β ...

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： Chronic rhinosinusitis   Nasal polyps   Regulatory T cell   Interleukin-17A  

摘要： During nasal polyp (NP) development, activated T cells differentiate into T helper (Th) 1, Th2, and Th17 cells. Additionally, regulatory T cells (Tregs) that have an immune suppressive function are involved in the pathophysiology of chronic rhinosinusitis (CRS) with NP (CRSwNP). Tregs can act as effector cells that produce inflammatory cytokines, such as interleukin (IL)-17A. We sought to identify the cellular expression of IL-17A and Treg markers in sinonasal tissue from CRSwNP patients and to investigate whether Tregs are involved in IL-17A secretion. The uncinate process (UP) and NP tissues were harvested from patients with CRSwNP, CRS without NP (CRSsNP), and normal controls. Expression of IL-17A and Foxp3 in each group was observed with immunohistochemistry and immunofluorescence. Expression of IL-17A in Treg was evaluated by flow cytometry of single cells isolated from sinonasal tissues. UP tissue from controls (n = 17), UP from CRSsNP (n = 24), and UP (n = 19) and NP (n = 29) from CRSwNP were obtained. The percentage of Foxp3+ cells was higher in CRS tissues compared with normal controls. IL-17A+ cells were most increased in NP tissues from CRSwNP patients. Expression of IL-17A in some Foxp3+ cells was observed in double immunofluorescence. Foxp3+ cells, IL-17A+ cells, and Foxp3+IL-17A+ cells were increased in the UP and NP tissues from CRSwNP patients. CD45RA-Foxp3+ cells were increased in CRSwNP, and IL-17A+ cells were observed most frequently in CD4+CD45RA-Foxp3+ cells from NP tissues. These findings show that CD4+CD45RA-Foxp3+ Tregs are involved in NP pathogenesis by producing IL-17A.

关键词： MHC-associated peptides   immunopeptidomics   phosphorylation   post-translational modification   cancer immunotherapy  

摘要： Over the past 3 decades, the Hunt laboratory has developed advancements in mass spectrometry-based technologies to enable the identification of peptides bound to major histocompatibility complex (MHC) molecules. The MHC class I processing pathway is responsible for presenting these peptides to circulating cytotoxic T cells, allowing them to recognize and eliminate malignant cells, many of which have aberrant signaling. Professor Hunt hypothesized that due to the dysregulation in phosphorylation in cancer that abnormal phosphopeptides could be presented by this pathway, and went on to demonstrate that this was, in fact, the case. Thereafter, the laboratory continued to sequence MHC-associated phosphopeptides and contributed several improved methods for their enrichment, detection, and sequencing. This article summarizes the most recent advancements in identification of modified MHC-associated peptides and includes the cumulative list of phosphopeptides sequenced by the Hunt lab. Further, many other post-translational modifications (PTMs) were found to modify MHC peptides, including O-GlcNAcylation, methylation, and kynurenine;in total, we present here a list of 2450 MHC-associated PTM peptides. Many of these were disease-specific and found across several patients, thus highlighting their potential as cancer immunotherapy targets. We are sharing this list with the field in hopes that it might be used in investigating this potential. Overall, the Hunt lab's contributions have significantly advanced our understanding of antigen presentation and dysregulation of PTMs, supporting modern immunotherapy and vaccine development efforts.

关键词： Emulsification  

摘要： Emulsion wastewater contains insoluble oils and polycyclic aromatic hydrocarbons (PAHs), which poses significant environmental and health risks. Membrane separation technology, known for its simplicity, efficiency, energy-saving and environmental friendliness, has demonstrated substantial potential for treating emulsion wastewater. In this study, the ionic liquid (IL), 1-vinyl-3-butylimidazolium tetrafluoroborate ([VBIM][BF4]), was grafted onto the polyvinylidene fluoride (PVDF) membrane surface via electron beam-induced polymerization. Subsequently, a straightforward anion exchange process introduced sulfonated butyl-beta-cyclodextrin (SBE-beta-CD-) into the membranes, resulting in PVDF-g-IL-SBE-beta-CD membranes. The modified PVDF membranes exhibited exceptional oil rejection efficiencies (achieving 94.3-99.5%) and remarkable antifouling properties in emulsion wastewater treatment. These enhancements are primarily attributed to the integration of hydrophilic ionic liquids into the membrane matrix, which significantly improves surface hydrophilicity and flux recovery rate, thereby enhancing overall membrane performance. Furthermore, the modified PVDF membranes exhibited excellent removal performance for low molecular weight PAHs in emulsions, owing to pi-pi interactions between the imidazolium groups and PAHs, as well as the host-guest inclusion effect of the cyclodextrin cavities. The membrane achieved a naphthalene (NAP) removal efficiency of up to 98.9%, with a water flux of 750.9 L m(-)2 h(-)1 and an emulsion flux of 296.2 L m(-)2 h(-)1. The best-performing M15-SBE-beta-CD membrane demonstrated emulsion fluxes exceeding 200 L m(-)2 h(-)1 and achieved over 95% removal efficiency of other typical PAHs, including phenanthrene (PHE) and anthracene (ANT). This study offers valuable insights and optimization strategies for advancing membrane technology in the efficient treatment of emulsion wastewater, pioneering the simultaneous filtration of emulsions and PAHs in a

关键词： Diabetic nephropathy   IL-6   Polymorphisms  

摘要： Introduction: The pathogenesis of diabetes mellitus (DM) and its complications has been previously linked to elevated levels of interleukin-6 (IL-6);IL-6 triggers intracellular pathways through interaction with the IL-6 receptor (IL-6R). This study aimed to determine the association of single nucleotide polymorphisms (SNPs) IL-6 -597G/A (rs1800797), -572G/C (rs1800796), -174G/C (rs1800795), its receptor (IL-6R) Asp358Ala (+48892A/C, rs2228145) and DM or its complications in the Czech population. Materials and Methods: In total, 669 subjects participated in this case-control study, including 167 controls, 119 patients with type 1 DM (T1DM), and 383 patients with type 2 DM (T2DM). The subjects were monitored for glycemia, glycated hemoglobin, lipid profile, glomerular filtration rate (GFR), and common complications, such as diabetic nephropathy (DN), retinopathy (DR), (poly)neuropathy (DPN), and periodontitis (P). Results: Frequencies of the IL-6 and IL-6R alleles or genotypes, and IL-6 haplotypes were similar between the controls and the patients with T1DM or T2DM (P > 0.05). However, lower values of GFR were observed in diabetic patients with IL-6 -174CC homozygotes compared to other (CG and GG) genotypes (P <= 0.05). In addition, the IL-6R Asp358Ala variant was associated with DN (P = 0.031, OR = 1.74, 95% CI: 1.05-2.89). After subclassification according to the type of DM, the significant association of the IL-6R polymorphism with DN was only found in T1DM (P = 0.013, OR = 2.90, 95% CI: 1.25-6.71). Conclusions: This study implies a significant relationship between the IL-6R Asp358Ala polymorphism and DN in Czech T1DM patients.

关键词： CD8(+) T cells   CMV vectors   HIV vaccine   MHC-E  

摘要： Strain 68-1 rhesus CMV (RhCMV) vectors induce immune responses that mediate early, complete replication arrest of SIV infection in similar to 60% of vaccinated rhesus macaques (RMs). This unique efficacy depends on the ability of these vectors to elicit effector memory (EM)-biased CD8(+) T cells recognizing SIV peptides presented by MHC-E, rather than MHC-Ia. These efficacious responses still occurred when spread of the 68-1 vector was impaired by deletion of the viral anti-host intrinsic immunity factor phosphoprotein 71 (pp71), but efficacy was lost with a more stringent attenuation strategy based on destabilization of Rh108, the ortholog of the essential human CMV (HCMV) transcription factor UL79 that is required for late viral gene expression. Although unable to produce infectious progeny (ie single-cycle infection), Rh108-deficient vectors elicited durable, high frequency, EM-biased, SIV-specific CD8(+) T-cell responses in RMs, but these responses were MHC-Ia-restricted and therefore non-efficacious. Here, we tested a different single-cycle attenuation strategy based on deletion (Delta) of the glycoprotein L (gL) that is essential for viral entry but allows for late gene expression and viral assembly. Delta gL 68-1 RhCMV/SIV vectors, grown on gL-complementing fibroblasts, were robustly immunogenic at doses above 10(5) PFU, generating high frequency, EM-biased, SIV-specific CD8(+) T-cell responses that were also unconventionally restricted, including the MHC-E restriction associated with efficacy. Indeed, these single-cycle vectors manifested replication arrest efficacy in 70% of vaccinated RMs, further linking MHC-E restriction with efficacy, and demonstrating that 68-1 RhCMV/SIV efficacy does not require vector dissemination within the host.

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.