依达拉奉右莰醇联合丁苯酞治疗对老年大动脉粥样硬化型脑卒中患者血清PTX3、lp-PLA2以及MES的影响

摘要 目的：探讨依达拉奉右莰醇联合丁苯酞对老年大动脉粥样硬化（LAA）型脑卒中患者血清五聚素3（PTX3）、脂蛋白相关磷脂酶A2（Lp-PLA2）以及微栓子信号（MES）的影响。方法：回顾性选取2021年9月-2022年9月在本院收治的120例老年LAA型脑卒中患者,根据其不同治疗方案分为对照组（56例）,采用依达拉奉右莰醇单独治疗,和观察组（64例）,采用依达拉奉右莰醇联合丁苯酞治疗。观察两组患者的临床疗效;对比两组患者治疗前后神经功能[脑卒中量表（NIHSS）及中枢神经特异性蛋白（S-100β）、神经元特异性烯醇化酶（NSE）]状态、炎症因子[血清五聚素3（PTX3）、脂蛋白相关磷脂酶A2（Lp-PLA2）]水平及脑血流微栓子信号（MES）阳性率变化。记录不良反应发生情况。结果：观察组患者治疗有效率为95.31%,高于对照组的78.57%（χ²=7.653 ,P=0.006）;治疗后,观察组患者NIHSS评分、S-100β及NSE水平低于对照组（P＜0.05）;观察组PTX3、Lp-PLA2水平及MES阳性率低于对照组（P<0.05）。观察组与对照组总不良反应发生率比较无差异（6.25 % vs 5.36 %）（Fisher=1.000）。结论：依达拉奉右莰醇联合丁苯酞可有效提高临床疗效,促进老年LAA型患者神经功能恢复,降低PTX3、lp-PLA2水平及MES阳性率,控制病情发展,且安全性较好。     

Levels of serum pentraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis

ObjectiveThe aim of this study was to investigate the relationship between disease severity and biochemical parameters such as pentraxin-3, fetuin-A, IL-6, insulin and HOMA-IR levels in patients with rheumatoid arthritis.MethodsThis study included 60 patients with RA and 20 healthy controls. Serum pentraxin-3, fetuin-A, IL-6 and insulin concentrations were measured. Also, HOMA-IR values were calculated. Disease activity was assessed with Disease Activity Score (DAS28). To evaluate quality of life, the Health Assessment Questionnaire disability index was applied.ResultsThe serum values for ESR, CRP, pentraxin-3 and fetuin-A in patients with RA were found to be higher than control subjects (p values = 0.001, 0.001, 0.000, 0.000, 0.01, 0.02, respectively). A positive correlation was evident between the DAS 28 score and IL6 levels (r = 0.263, p = 0.045). We found no correlation between the DAS28 score and HOMA-IR, the levels of pentraxin 3, fetuin A, insulin (p < 0.05). Fetuin A levels were positively correlated with cumulative steroid dose (r = 0.382, p = 0.035). A statistically significant correlation was evident between presence of cardiovascular disease and HOMA-IR values in RA patients (r = 0.437, p = 0.032).ConclusionElevated levels of pentraxin-3, fetuin-A, CRP, ESR might play a role in the pathogenesis of RA. Levels of fetuin-A, insulin HOMA-IR, pentraxin-3, CRP and ESR were not associated with clinical severity of the RA.     

The Angiogenic Inhibitor Long Pentraxin PTX3 Forms an Asymmetric Octamer with Two Binding Sites for FGF2

The inflammation-associated long pentraxin PTX3 plays key roles in innate immunity, female fertility, and vascular biology (e.g. it inhibits FGF2 (fibroblast growth factor 2)-mediated angiogenesis). PTX3 is composed of multiple protomers, each composed of distinct N- and C-terminal domains; however, it is not known how these are organized or contribute to its functional properties. Here, biophysical analyses reveal that PTX3 is composed of eight identical protomers, associated through disulfide bonds, forming an elongated and asymmetric, molecule with two differently sized domains interconnected by a stalk. The N-terminal region of the protomer provides the main structural determinant underlying this quaternary organization, supporting formation of a disulfide-linked tetramer and a dimer of dimers (a non-covalent tetramer), giving rise to the asymmetry of the molecule. Furthermore, the PTX3 octamer is shown to contain two FGF2 binding sites, where it is the tetramers that act as the functional units in ligand recognition. Thus, these studies provide a unifying model of the PTX3 oligomer, explaining both its quaternary organization and how this is required for its antiangiogenic function.     

Constitutive Expression of Pentraxin 3 (PTX3) Protein by Human Amniotic Membrane Cells Leads to Formation of the Heavy Chain (HC)-Hyaluronan (HA)-PTX3 Complex

Heavy chain (HC)-hyaluronan (HA), a complex formed by the covalent linkage between HC1 from the inter-α-trypsin inhibitor (IαI) and HA, purified from the human amniotic membrane (AM), is responsible for the anti-inflammatory, antiscarring, and antiangiogenic actions of the AM. This HC-HA complex is produced by constitutive expression of TNF-stimulated gene 6 and endogenous production of IαI by AM cells. Pentraxin 3 (PTX3), a prototypic long pentraxin that plays a non-redundant role in innate immunity against selected pathogens, also helps stabilize HC-HA to ensure female fertility. Here we noted strong positive PTX3 staining in the AM epithelium and compact stroma. PTX3 was constitutively expressed and secreted by cultured AM epithelial and stromal cells and, further, greatly up-regulated by TNF and IL-1β. Using an agarose overlay to trap the HA-containing matrix, the HC-HA-PTX3 complex was formed, as analyzed by Western blot analysis, by AM cells but not human skin fibroblasts, despite being cultured in the presence of serum and TNF. However, exogenous PTX3 helps human skin fibroblasts form the HC-HA-PTX3 complex with an agarose overlay. Furthermore, PTX3 can be coimmunoprecipitated with the HC-HA complex from agarose-overlaid AM cell extracts by an anti-human IαI antibody. Such a HC-HA-PTX3 complex can be reconstituted in vitro and exhibit similar effects as those reported for AM HC-HA-PTX3 on polarization of M2 macrophages. The tight binding between PTX3 and AM HC-HA withstands four runs of CsCl ultracentrifugation in the presence of 4 m GnHCl. These results indicate that PTX3 is constitutively expressed and secreted by AM cells as an integral component of the AM HC-HA-PTX3 complex and contributes to the biological function of AM HC-HA-PTX3.     

Clinical value of plasma pentraxin 3 levels for predicting cardiac troponin elevation after percutaneous coronary intervention

Aims

Post-procedural myocardial necrosis manifested by elevated cardiac troponin T (cTnT) often complicates percutaneous coronary intervention (PCI). Plasma pentraxin 3 (PTX3) levels are increased in patients with arterial inflammation and especially unstable angina pectoris (UAP). This study tested whether plasma PTX3 levels can predict post-PCI cTnT elevation.

Main methods

We evaluated 94 consecutive patients with AP and normal pre-PCI cTnT levels who underwent PCI. Pre-PCI virtual histology-intravascular ultrasound was performed to assess culprit plaque composition. Plasma PTX3 and serum hs-CRP levels were measured pre-PCI. Patients were divided into 2 groups according to presence (Group I, n = 34) or absence (Group II, n = 60) of post-PCI cTnT elevation > 3 × the upper limit of normal at 24 h after PCI.

Key findings

Plasma PTX3 (4.06 ± 2.05 ng/ml vs 2.17 ± 1.02 ng/ml, p < 0.001), serum hs-CRP levels (0.25 ± 0.03 vs 0.16 ± 0.03 mg/dl, p = 0.048), plaque burden (80.9 ± 5.3 vs 75.4 ± 10.6%, p = 0.047), presence of positive remodeling (59 vs 25%, p = 0.034), and percent necrotic core area (19.0 ± 7.4 vs 14.0 ± 5.9%, p = 0.046) were significantly higher in Group I than in Group II. Receiver-operating characteristic curve analysis showed that with a best cut-off value of 2.83 ng/ml, plasma PTX3 level (AUC 0.823) predicted post-PCI cardiac TnT elevation better than did serum hs-CRP level (AUC 0.618). Multiple logistic regression analysis showed that plasma PTX3 level was the most independent predictor of post-PCI cardiac cTnT elevation (OR: 2.65; 95% CI: 1.56–10.1; p = 0.003).

Significance

Plasma PTX3 level may be a useful marker for predicting post-PCI cardiac cTnT elevation, which is associated with inflammatory status of culprit lesions.     

The canine mast cell activation via CRP

We report here canine mastocytoma-derived cell (CMMC) activation via two pentraxin, limulus- and human-CRP. Mast cell chemotaxis was measured by Boyden's blindwell chamber. To confirm that the cell migration was chemotactic, "checkerboard" analysis was performed. We used Fura-2 to investigate CRP-mediated cytosolic calcium elevation. To examine whether CRP-induced stimulation is mediated through G-proteins, CMMC were incubated with pertussis toxin (PTx) before use in chemotaxis assay and Ca(2+) mobilization. CMMC migration in response to CRP was both chemokinetic and chemotactic. Limulus-CRP induced a transient Ca(2+)-mobilization dose-dependently. Preincubation of the cells with PTx inhibited CRP chemotaxis and Ca(2+)-mobilization, suggesting that G-proteins of the Gi-class are involved in the chemotaxis. We suggest that CRP may participate in the migration of mast cells to inflamed tissues during an acute-phase response. CRP-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.     

New insights into the role of serum amyloid P component, a novel lipopolysaccharide-binding protein

Serum amyloid P component (SAP) is a highly preserved plasma protein named for its ubiquitous presence in amyloid deposits. Although SAP is described to bind many ligands, no clear biological function has been ascribed to it as yet. This review summarizes the current knowledge about the protein SAP, its ligands and functional properties. Finally, the author focuses on the recent finding of the binding of SAP to lipopolysaccharide (LPS) and Gram-negative bacteria and the possible functional consequences of these interactions.     

慢性牙周炎患者龈沟液ICAM-1、PTX3、S100A12、Shh蛋白与牙周指标和炎症反应的相关性分析

摘要 目的：探讨慢性牙周炎患者龈沟液细胞间黏附分子-1（ICAM-1）、正五聚蛋白3（PTX3）、钙结合蛋白S100A12（S100A12）、音猬因子( Shh)蛋白与牙周指标和炎症反应的关系。方法：选择2017年4月~2021年6月期间我院收治的慢性牙周炎患者120例作为观察组,另选取牙周健康的志愿者90例作为对照组,对比对照组、观察组龈沟液ICAM-1、PTX3、S100A12、Shh蛋白水平,对比观察组不同病情严重程度患者龈沟液ICAM-1、PTX3、S100A12、Shh蛋白、牙周指标和血清炎症因子。Pearson相关性分析龈沟液ICAM-1、PTX3、S100A12、Shh蛋白与牙周指标和血清炎症因子的相关性。结果：观察组龈沟液ICAM-1、PTX3、S100A12、Shh蛋白水平高于对照组,组间对比差异有统计学意义（P<0.05）。重度组、中度组龈沟液ICAM-1、PTX3、S100A12、Shh蛋白水平,血清白介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平,附着丧失（AL）、探诊深度（PD）、牙龈指数（GI）均高于轻度组,且重度组以上指标均高于中度组,差异均有统计学意义（P<0.05）。Pearson相关性分析结果显示,龈沟液ICAM-1、PTX3、S100A12、Shh蛋白与IL-6、TNF -α、AL、PD、GI均呈正相关（P<0.05）。结论：ICAM-1、PTX3、S100A12、Shh蛋白可作为判断慢性牙周炎患者病情严重程度的辅助指标,且其与牙周指标和炎症反应均有一定的相关性。