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关键词： Dual-sensing electrochemical aptasensor   Inflammatory markers   Clinical biomarker analysis  

摘要： Sepsis, a life-threatening condition often resulting from bacterial infections, can lead to multi-organ failure. Early diagnosis is critically urgent due to rapid clinical patient deterioration, where treatment delays drastically worsen outcomes. Identifying sepsis within a crucial intervention window decisively impacts survival rates and reduces complications. Timely identification relies heavily on the early measurement of biomarkers such as Creactive protein (CRP) and interleukin-6 (IL-6). However, the wide disparity in concentration ranges between these biomarkers has posed a significant challenge for their simultaneous detection, often necessitating two separate detection methods that are both time-consuming and labor-intensive. This inefficiency can delay critical clinical decisions, underscoring the need for more streamlined and efficient detection strategies. To date, this challenge has not been fully addressed, highlighting the necessity of novel approaches for rapid and simultaneous biomarker detection. To achieve simultaneous biomarker analysis, a dual-sensing electrochemical system was developed for CRP and IL-6 detection. The working electrode surface was modified with Ti3C2Tx-PB/Chit/Au NPs to enhance the detection sensitivity and selectivity for CRP and IL-6. This modification also increased the electrode's surface area, electrical conductivity, and electroactivity, optimizing it for accurate and efficient biomarker detection. When operated under optimal parameters, the developed sensor yielded a linear detection range for CRP (0.1-15 mu g mL- 1) and IL-6 (0.01-100 ng mL-1), which aligns well with clinically relevant concentrations. In simulated sample tests, the developed biosensor effectively distinguished plasma samples from bacterial infection, non-bacterial infection, and healthy conditions, demonstrating its potential for practical applications in clinical diagnostics.

关键词： Tissue-engineered skin   COL/PRP scaffold   Allogeneic keratinocytes   Immune rejection   Adipose-derived stem cell exosomes  

摘要： Tissue-engineered skin holds promise for repairing severe skin defects, but immune rejection jeopardizes graft survival. Here, we developed a cell-free strategy to enhance allogeneic keratinocyte viability by leveraging exosomes (exosomes) from IFN gamma-primed adipose-derived stem cells (IFN gamma-Exos). These exosomes were integrated with autologous fibroblasts into a collagen/platelet-rich plasma (COL/PRP) scaffold to construct a 3D immunomodulatory artificial skin. The COL/PRP scaffold demonstrated optimal physicochemical properties, supporting robust adhesion and proliferation of both keratinocytes and fibroblasts. IFN gamma-Exos exhibited superior immunosuppressive effects compared to native ADSCs-Exos, inhibiting T-cell activation and expanding regulatory T cells (Tregs) in vivo. This significantly reduced wound inflammation while enhancing collagen remodeling and angiogenesis in a murine full-thickness skin injury model. Proteomic analysis identified the IDO-kynurenine pathway as the key mechanism underlying IFN gamma-Exos-mediated immune tolerance. Our dual-functional system combines the COL/PRP scaffold-providing structural support for cell migration-with IFN gamma-Exos to simultaneously suppress rejection and accelerate tissue regeneration. This approach advances cell-free engineered skin therapies by addressing critical immunological barriers while maintaining reparative efficacy.

关键词： SIRT1   IL-6   Oxycodone tolerance   Deacetylation   MEK/ERK  

摘要： Oxycodone, an opioid analgesic, exhibits limited clinical utility due to the development of tolerance. This study aims to investigate the role of Sirtuin 1 (SIRT1), a histone deacetylase, in oxycodone-induced analgesic tolerance. Adult ICR mice were administered oxycodone subcutaneously once a day for seven consecutive days. The tail-flick test was used to establish a mouse model of oxycodone tolerance. RT-qPCR was employed to assess the mRNA levels of SIRT1-SIRT7. Western blotting was performed to measure the expression levels of SIRT1, interleukin (IL)-6, H3K9ac, H3K14ac, H3K18ac, total/phosphorylated extracellular signal-regulated kinase (ERK) (1/2), and mitogen-activated protein kinase/ERK kinase (MEK) (1/2). ChIP-qPCR were used to localize SIRT1/IL-6 expression, and to quantify histone acetylation at the IL-6 promoter. Mice developed analgesic tolerance by Day 7 of oxycodone administration. Oxycodone significantly reduced SIRT1 mRNA and protein levels in the lumbar spinal cord. Bioinformatics analysis identified IL-6 as the most prominently upregulated gene in the spinal cord. Correspondingly, IL-6 protein levels were elevated, along with increased levels of total H3K9ac (but not H3K14ac or H3K18ac) and enriched H3K9ac at the IL-6 promoter. While total ERK(1/2) and MEK(1/2) levels remained unchanged, their phosphorylated forms were significantly upregulated in tolerant mice. An SIRT1 agonist (SRT1720) inhibited the development of oxycodone tolerance, suppressed IL-6 overexpression, normalized H3K9ac and phospho-ERK/MEK levels, and reduced H3K9ac expression at the IL-6 promoter. Thus, SIRT1 promotes oxycodone tolerance by deacetylating histone H3K9 at the IL-6 promoter and activating the MEK/ERK pathway to upregulate IL-6 expression.

关键词： IL2RG gene   hypomorphic mutation   interstitial lung disease   atypical severe combined immunodeficiency disease   Omenn syndrome   ILD   Interstitial lung disease   SCID   Severe combined immunodeficiency   Treg   Regulatory T  

摘要：

关键词： Renal ischemia-reperfusion injury   Inflammation   NAMPT/NAD plus   SIRT1/PGC-1 alpha/Nrf1/TFAM   NF kappa B/TNF-alpha/IL-6  

摘要： Renal ischemia is a common cause of acute kidney injury (AKI), particularly in critical care settings, and remains a major challenge in nephrology due to the lack of effective therapeutic options. In AKI, there is an overstimulation of NAD+-consuming enzymes leading to NAD+ depletion. To help replenish cellular NAD+ stores, this study explores for the first time the therapeutic potential of activating nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the NAD+ salvage pathway, in a rat model of unilateral renal ischemia-reperfusion injury (IRI). Our findings demonstrate that SBI797812 (SBI)-induced NAMPT activation significantly improves renal function post-IRI, primarily through the NAD+/SIRT1/PGC-1 alpha signaling pathway. NAMPT activation resulted in significant improvement in kidney function, including restored urine flow rate, reduced creatinine and blood urea nitrogen (BUN) levels, and decreased kidney injury biomarkers such as KIM-1 and NGAL. Additionally, SBI led to a reduction in inflammatory markers (NFxB, TNF-alpha and IL-6), oxidative stress markers, and caspase-3, indicating enhanced renal protection. Western blot analysis further revealed upregulation of key mitochondrial biogenesis markers, including SIRT1, PGC-1 alpha, and TFAM, highlighting the link between NAD+ restoration and improved mitochondrial function. In contrast, the inhibition of NAMPT with FK866 exacerbates injury, as indicated by worsened histological features, increased inflammation, and tubular necrosis, confirming the crucial role of NAMPT in mitigating ischemic damage. Considering the importance of NAD metabolism in mitochondrial function and cellular resiliency to tissue injury, these results underscore NAMPT activation as a promising therapeutic strategy for renal IRI, offering new insights for the management of ischemic AKI.

关键词： 膝关节骨性关节炎   丹芎活血片   膝关节功能   白细胞介素-6   肿瘤坏死因子-α  

摘要： 目的探究丹芎活血片治疗膝关节骨性关节炎(KOA)的效果及对患者膝关节功能、关节疼痛、血清炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平的影响。方法选取70例KOA患者为研究对象,随机分成对照组(n=35)和观察组(n=35)。对照组采用塞来昔布胶囊治疗,观察组在此基础上联合丹芎活血片治疗。比较两组中医证候积分、Lysholm膝关节评分、视觉模拟评分法(VAS)评分、血清炎症因子水平。结果治疗4周后,两组主症积分、次症积分及总积分均较治疗前下降,且观察组主症积分(2.06±0.94)分、次症积分(1.56±0.50)分及总积分(3.62±1.43)分均低于对照组的(3.12±1.16)、(1.94±0.65)、(5.06±1.76)分(P<0.05)。治疗4周后,两组闭锁感、肿胀度、上下楼梯、蹲起评分均较治疗前升高,且观察组闭锁感评分(9.86±2.17)分、肿胀度评分(6.57±1.62)分、上下楼梯评分(6.15±1.57)分、蹲起评分(2.98±0.65)分均较对照组的(8.62±2.24)、(5.78±1.43)、(5.24±1.41)、(2.61±0.57)分更高(P<0.05)。与治疗前比较,两组治疗2、4周后VAS评分均下降,且观察组治疗2周后VAS评分(4.65±1.18)分和治疗4周后VAS评分(2.65±0.77)分均较对照组的(4.97±1.34)、(3.12±0.73)分更低(P<0.05)。治疗4周后,两组IL-6、TNF-α水平均较治疗前降低,且观察组IL-6(9.52±1.17)pg/ml、TNF-α(5.28±2.57)pg/ml均较对照组的(12.24±1.26)、(7.02±2.81)pg/ml更低(P<0.05)。结论丹芎活血片治疗KOA患者效果明显,能有效改善关节疼痛和膝关节功能,降低血清IL-6、TNF-α表达。

关键词： 弓形虫   细胞因子   白细胞介素-12   蛋白结合   免疫逃避  

摘要： 旨在探索是否存在直接与宿主白细胞介素(IL)-12结合并调节其功能的弓形虫蛋白,以进一步解析弓形虫免疫逃逸的分子机制。通过免疫沉淀技术(IP)联合液相色谱-串联质谱(LC-MS/MS)分析,从弓形虫速殖子中筛选出39种能与小鼠IL-12结合的候选分子。根据基因注释与功能分析,从39种候选分子中选定弓形虫14-3-3、延伸因子-1α(EF-1α)、Ras相关蛋白1a(Rab1a)、β-微管蛋白(β-tubulin)及假定蛋白(HYP)进行结合验证。分别构建14-3-3、EF-1α、Rab1a、β-tubulin、HYP以及IL-12的真核重组蛋白表达系统并进行正反向免疫共沉淀,发现14-3-3、Rab1a与小鼠IL-12未产生直接结合,而β-tubulin、EF-1α可与IL-12产生正向结合,但无反向结合信号。此外,弓形虫HYP在人胚肾细胞(HEK 293T)表达系统不表达。本研究首次较为系统地探索了弓形虫蛋白与宿主IL-12的直接结合关系,为解析弓形虫免疫调控网络及开发相关干预策略提供了新视角。

关键词： Human β-defensin 1 (hBD-1)   DEFB1 gene   Head and neck squamous cell carcinoma (HNSCC)   IL-17B/IL-17RB/TRAF6/NF-κB signaling pathway   Tumor suppression   Apoptosis  

摘要：

关键词： Autoimmune Liver Disease   Biliary injury   Cellular crosstalk   Gasdermin B   Granzyme A  

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