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关键词： non-HLA antibodies   HLA   ABMR   antibody-mediated rejection   MVI   microvascular inflammation   GSTT1  

摘要： Introduction Donor-specific human leukocyte antigens antibodies (HLA-DSA) contribute toantibody-mediated rejection (ABMR) after kidney transplantation (KT). Non-HLA antibodies may play a role in ABMR in the presence of HLA-DSA or the development of microvascular inflammation (MVI) in its absence. Considering both types of antibodies in potential recipients could enhance ABMR/MVI risk *** We present a case-control study of 121 KT recipients, 46 with ABMR/ MVI diagnosis, and 75 control cases with available sera before and after KT, follow-up HLA antibody monitoring, and biopsies. We determined 60 serum non-HLA antibodies using a multiplex test with an established cutoff. We evaluated their association with ABMR/MVI using a sample median fluorescence intensity (MFI) ratio *** Following commercial cutoffs, non-HLA antibodies were detected in 87% of the patients before KT. We found that a high non-HLA antibody MFI ratio sum before KT and at biopsy were associated with an increased risk of ABMR/MVI, independently of HLA sensitization or HLA-DSA (OR = 1.039, p = 0.014 and OR = 1.036, p = 0.024). Antibodies against extracellular non-HLA antigens were associated with ABMR/MVI before KT (OR = 1.053, p = 0.040), but at diagnosis, only antibodies against intracellular non-HLA antigens were associated (OR = 1.062, p = 0.018).Conclusion These findings suggest that non-HLA antibody assessment offers valuable complementary information, regardless of HLA sensitization, though appropriate cut-offs should be explored.

关键词： 银屑病关节炎   托法替布   IL-17/23  

摘要： 目的 探讨托法替布（JAK抑制剂）对银屑病关节炎的作用机制。方法在原代PSA滑膜成纤维细胞（PsAFLS）分别加入0.5μmol/L和1.0μmol/L托法替布进行培养，CCK-8实验和Transwell实验检测托法替布对PsAFLS存活和迁移的影响；Westernblot分析托法替布对PsAFLS细胞IL-1β、IL-6、IL-17、IL-10和IL-23炎症因子表达的影响，以及对迁移相关蛋白MMP2和MMP9表达的影响。在加入托法替布的情况下给予外源IL-17和IL-23，探索托法替布是否通过IL-17/IL-23信号通路调控PsAFLS的存活和迁移。结果托法替布明显抑制PsAFLS的存活和迁移，显著降低PsAFLS细胞迁移相关蛋白表达MMP2和MMP9水平，降低IL-1β、IL-6、IL-17和IL-23的表达，增加IL-10蛋白表达。给予外源IL-17和IL-23可抑制托法替布的作用。结论托法替布可通过IL-17/IL-23信号通路调控PsAFLS的侵袭和迁移。

关键词： acute phase proteins   cytokines   cytokines/cytokine receptors   immune deficiencies  

关键词： tendinopathy   mRNA therapy   SM102 lipid nanoparticles   interleukin-1 receptor antagonist   anti-inflammatory therapy  

摘要： Tendinopathy treatment is hindered by persistent inflammation and irreversible matrix degradation, with current therapies offering transient symptom relief without addressing disease progression. Here, we developed an mRNA-based anti-inflammatory strategy utilizing SM102 lipid nanoparticles (LNPs) to deliver interleukin-1 receptor antagonist (Il1rn) mRNA for tendon repair. SM102-LNPs demonstrated efficient transfection of primary tendon stem cells, sustaining IL-1RA protein expression for over 72 h and neutralizing IL-1 beta-induced inflammatory cascades. In vitro, IL-1RA suppressed pro-inflammatory cytokines (TNF-alpha, IL-6, iNOS), restored collagen I/III balance, and enhanced cell migration. In collagenase-induced tendinopathy mice, a single SM102-Il1rn mRNA injection attenuated inflammation, reduced MMP1/13 expression, and improved collagen alignment within 1 week. By 4 weeks, treated tendons exhibited functional recovery with normalized gait patterns. Transcriptomics revealed dual modulation of IL-1 signaling and extracellular matrix (ECM) remodeling pathways, alongside macrophage polarization and oxidative stress regulation. Systemic safety was confirmed by unaltered serum biomarkers and organ histology. This SM102-Il1rn mRNA therapy enables spatiotemporally controlled anti-inflammatory therapy, providing a promising non-surgical solution for refractory tendinopathies. Its adaptable design allows expansion to other regenerative targets, advancing precision treatment for musculoskeletal degeneration.

关键词： APOE   microglia   cGAS   tauopathy   Christchurch   Alzheimer’s   interferon   neurodegeneration   single-nuclei RNA sequencing   local field potentials  

摘要： The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background. The R136S mutation decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in hippocampal theta and gamma power. Additionally, the R136S mutation reduced interferon responses to tau pathology in both mouse and human microglia, suppressing cGAS-STING pathway activation. Treating E3 tauopathy mice with a cGAS inhibitor protected against tau-induced synaptic loss and induced transcriptomic alterations similar to the R136S mutation across brain cell types. Thus, suppression of the microglial cGAS-STING-interferon (IFN) pathway plays a central role in mediating the protective effects of R136S against tauopathy.

关键词： 猪   猪伪狂犬   血清学   抗原  

摘要： 为了解云南普洱市某规模猪场猪PRV免疫状况及其流行情况,于2020年采集184份血液样品、24份种公猪精液,要检测伪狂犬病gE、gB抗体和抗原就要用到ELISA和PCR技术。检测发现gE抗体阳性7例,其阳性率为3.8%,gB抗体阳性163例,其阳性率为88.6%;公猪精液抗原检测发现均为阴性。该场猪伪狂犬免疫保护率较好,但仍然存在野毒感染状况,应该继续加强疫病监测和感染抗体检测,定期检测种公猪带毒状况,为该场的猪伪狂犬病预防及净化打下良好基础。

关键词： italic>Toxoplasma   SAG1   attachment   interferon gamma   surface antigen   sialic acid  

摘要： Toxoplasma gondii is an obligate intracellular protozoan parasite that can establish lifelong infections and cause severe disease in immunocompromised individuals. Interferon gamma (IFN gamma) is a key host defense cytokine that induces a variety of toxoplasmacidal mechanisms. Recent CRISPR/Cas9 loss-of-function screens identified multiple Toxoplasma genes important for fitness in IFN gamma-stimulated cells. One consistent hit in several screens was the parasite surface antigen, SAG1. Here, we used CRISPR/Cas9 to generate a SAG1 knockout strain and found that SAG1 is important for parasite fitness specifically in IFN gamma-stimulated cells. Mechanistic studies revealed that host surface sialic acids are important for parasite attachment, especially in IFN gamma-stimulated cells. SAG1-deficient parasites had reduced attachment efficiency, which was exacerbated in IFN gamma-treated cells. These findings highlight the role of SAG1 in mediating robust parasite attachment, especially in the context of immune pressure.

关键词： Type 2 diabetes mellitus   Cognitive function   Physical activity   Metabolic health   IL-6   sIL-6R   sgp130  

摘要： IntroductionType 2 diabetes mellitus (T2DM) is associated with cognitive impairment, with dysregulation of the interleukin-6 (IL-6) signaling pathway-particularly its soluble receptors-implicated in both T2DM pathogenesis and cognitive dysfunction. The potential role of sIL-6R (soluble interleukin-6 receptor) and sgp130 (soluble glycoprotein 130) as mediators in the relationship between physical activity (PA) and cognitive performance in women with T2DM remains underexplored. This study examined the associations between PA, sIL-6R, and sgp130 levels and their relationship with cognitive function in this *** cross-sectional observational analytical study was conducted on 44 women (aged 50-75 years) with T2DM. We evaluated PA levels;serum concentrations of sIL-6R, sgp130, and IL-6;domain-specific cognitive performance;physical fitness;and diabetes-related metabolic indicators. Correlations between PA, selected cytokines, and cognitive performance were analyzed using correlation analyses and adjusted *** women had lower sIL-6R (p = 0.01, eta(2) = 0.15) and sgp130 (p = 0.01, eta(2) = 0.17) levels compared to inactive peers, with no difference in IL-6 (p = 0.84). Lower sIL-6R and sgp130 correlated with better processing speed (r = 0.37, p = 0.01) and visuospatial function (r = 0.36, p = 0.01);these associations remained significant after adjustment (r = 0.35, p = 0.04). PA was also associated with lower cholesterol (r = -0.37, p = 0.01) and FBS (r = -0.30, p = 0.04) and higher cardiovascular fitness (r = 0.32, p = 0.03).ConclusionRegular PA in women with T2DM is associated with reduced sIL-6R and sgp130 levels, which may be linked to better cognitive performance across multiple domains. These findings highlight the potential role of sIL-6R and sgp130 in linking PA to cognitive health, underscoring the importance of PA as a supportive strategy for managing inflammation and mitigating cognitive decline in T2DM.