SAP

SAP
  • 文章类型: Journal Article
    已知胁迫相关蛋白(SAP)在植物对非生物胁迫的反应中起重要作用。本研究使用向日葵基因组数据系统地鉴定了向日葵SAP基因家族的成员。使用生物信息学方法分析向日葵SAP基因家族的基因,在盐和干旱胁迫下通过荧光定量(qRT-PCR)评估基因表达。还对数字进行了综合分析,结构,共线性,以及七个菊科植物和其他八个植物SAP基因家族的系统发育。向日葵基因组被发现有27个SAP基因,分布在14条染色体上。进化分析表明,SAP家族基因可以分为三个亚组。值得注意的是,Annus品种显示第3组的SAP基因扩增。在菊科物种中,C.morifolium表现出最高数量的共线性基因对和系统发育树上最近的距离,表明进化过程中的相对保守性。对基因结构的分析表明,第1组表现出最复杂的基因结构,而第2组和第3组中的大多数HaSAP基因缺乏内含子。启动子分析显示存在与ABA相关的顺式作用元件,表明他们参与应激反应。表达分析表明10个基因(HaSAP1,HaSAP3,HaSAP8,HaSAP10,HaSAP15,HaSAP16,HaSAP21,HaSAP22,HaSAP23和HaSAP26)可能参与向日葵耐盐性。然后使用qRT-PCR检查盐和干旱胁迫下这10个基因的表达,并分析了这10个基因的组织特异性表达模式。HaSAP1,HaSAP21和HaSAP23在盐和干旱胁迫下表现出一致的表达模式,表明这些基因在向日葵的耐盐性和抗旱性中起作用。这项研究的发现强调了SAP基因家族对向日葵耐盐性和抗旱性的重要贡献。
    Stress-associated proteins (SAPs) are known to play an important role in plant responses to abiotic stresses. This study systematically identified members of the sunflower SAP gene family using sunflower genome data. The genes of the sunflower SAP gene family were analyzed using bioinformatic methods, and gene expression was assessed through fluorescence quantification (qRT-PCR) under salt and drought stress. A comprehensive analysis was also performed on the number, structure, collinearity, and phylogeny of seven Compositae species and eight other plant SAP gene families. The sunflower genome was found to have 27 SAP genes, distributed across 14 chromosomes. The evolutionary analysis revealed that the SAP family genes could be divided into three subgroups. Notably, the annuus variety exhibited amplification of the SAP gene for Group 3. Among the Compositae species, C. morifolium demonstrated the highest number of collinearity gene pairs and the closest distance on the phylogenetic tree, suggesting relative conservation in the evolutionary process. An analysis of gene structure revealed that Group 1 exhibited the most complex gene structure, while the majority of HaSAP genes in Group 2 and Group 3 lacked introns. The promoter analysis revealed the presence of cis-acting elements related to ABA, indicating their involvement in stress responses. The expression analysis indicated the potential involvement of 10 genes (HaSAP1, HaSAP3, HaSAP8, HaSAP10, HaSAP15, HaSAP16, HaSAP21, HaSAP22, HaSAP23, and HaSAP26) in sunflower salt tolerance. The expression of these 10 genes were then examined under salt and drought stress using qRT-PCR, and the tissue-specific expression patterns of these 10 genes were also analyzed. HaSAP1, HaSAP21, and HaSAP23 exhibited consistent expression patterns under both salt and drought stress, indicating these genes play a role in both salt tolerance and drought resistance in sunflower. The findings of this study highlight the significant contribution of the SAP gene family to salt tolerance and drought resistance in sunflower.
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  • 文章类型: Journal Article
    免疫抑制和营养不良在脑出血(ICH)的并发症中起关键作用,并且与卒中相关性肺炎(SAP)的发展密切相关。炎症标志物,包括NLR(中性粒细胞与淋巴细胞之比),SII(全身免疫炎症指数),SIRI(全身炎症反应指数),和SIS(全身炎症评分),连同营养指数,如CONUT(控制营养状况)和PNI(预后营养指数),是影响ICH后炎症状态的关键指标。在这项研究中,我们的目的是比较炎症和营养指标对ICH患者SAP的预测效果,旨在确定和探索其在早期肺炎检测中的临床实用性。从重症监护医学信息集市IV(MIMIC-IV)数据库中筛选需要入住ICU的严重ICH患者。结果包括SAP的发生和院内死亡。接收机工作特性(ROC)分析,多元逻辑回归,平滑曲线分析,采用分层分析探讨CONUT指数与重度ICH患者临床结局之间的关系.总共348名患者被纳入研究。SAP的发生率为21.3%,住院死亡率为17.0%。在这些指标中,多元回归分析显示,CONUT,PNI,和SIRI与SAP独立相关。进一步的ROC曲线分析表明,CONUT(AUC0.6743,95%CI0.6079-0.7408)对ICH患者的SAP表现出最可靠的预测能力。阈值分析显示,当CONUT<6时,CONUT增加1点与SAP风险增加1.39倍相关。同样,我们的研究结果表明,CONUT有可能预测ICH患者的预后.在炎症和营养标志物中,CONUT是ICH患者SAP最可靠的预测指标。此外,它被证明是评估ICH患者预后的一个有价值的指标.
    Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079-0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.
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  • 文章类型: Journal Article
    已实施了增强手术后恢复(ERAS)方案,以减少阿片类药物的使用并减少患者住院时间(LOS,days).锯齿前平面(SAP)阻滞麻醉T2至T9的乳房皮区,可以在手术中应用。这项研究的目的是比较对照组之间的术后阿片类药物(OME)消耗和LOS,一个ERAS组,和ERAS/局部麻醉鸡尾酒组在接受基于植入物的乳房重建的患者中。
    在这项研究中,在2004年至2020年之间进行了基于植入物的乳房重建的142名妇女被分为A组(46名患者),历史队列;B组(73例患者),ERAS/无阻滞对照组;和C组(23例患者),ERAS/麻醉鸡尾酒研究组。感兴趣的主要结果是麻醉后监护病房(PACU),住院和医院OME总消耗量,和PACULOS。
    在PACULOS中,从A组到C组观察到显着降低(103.3与80.2vs.70.5;p=0.011),OME使用(25.1与11.4vs.5.7;p<0.0001),和总医院OME(120.3vs.95.2vs.35.9;p<0.05)。三组之间的住院OME无差异(95.2vs.83.8vs.30.8;p=0.212)。尽管没有达到统计意义,在PACU中,C组每位患者平均消耗的阿片类药物比B组少50-60%,住院,和总医院OME。
    局部麻醉阻滞是ERAS方案的重要组成部分。我们的结果表明,在ERAS方案中,局部阻滞与局部麻醉混合物的组合可以减少基于植入物的乳房重建中的阿片类药物消耗。
    UNASSIGNED: Enhanced recovery after surgery (ERAS) protocols have been implemented to decrease opioid use and decrease patient hospital length of stay (LOS, days). Serratus anterior plane (SAP) blocks anesthetize the T2 through T9 dermatomes of the breast and can be applied intraoperatively. The purpose of this study was to compare postoperative opioid (OME) consumption and LOS between a control group, an ERAS group, and an ERAS/local anesthetic cocktail group in patients who underwent implant-based breast reconstruction.
    UNASSIGNED: In this study, 142 women who underwent implant-based breast reconstruction between 2004 and 2020 were divided into Group A (46 patients), a historical cohort; Group B (73 patients), an ERAS/no-block control group; and Group C (23 patients), an ERAS/anesthetic cocktail study group. Primary outcomes of interest were postanesthesia care unit (PACU), inpatient and total hospital OME consumption, and PACU LOS.
    UNASSIGNED: A significant decrease was observed from Group A to C in PACU LOS (103.3 vs. 80.2 vs. 70.5; p = 0.011), OME use (25.1 vs. 11.4 vs. 5.7; p < 0.0001), and total hospital OME (120.3 vs. 95.2 vs. 35.9; p < 0.05). No difference was observed in inpatient OMEs between the three groups (95.2 vs. 83.8 vs. 30.8; p = 0.212). Despite not reaching statistical significance, Group C consumed an average of 50-60 % less opioids per patient than did Group B in PACU, inpatient, and total hospital OMEs.
    UNASSIGNED: Local anesthetic blocks are important components of ERAS protocols. Our results demonstrate that a combination regional block with a local anesthetic cocktail in an ERAS protocol can decrease opioid consumption in implant-based breast reconstruction.
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  • 文章类型: Journal Article
    在次生流出物排入受纳水体之前对其进行进一步处理可以缓解水体富营养化。在这项研究中,在膜光生物反应器中培养蛋白小球藻以进一步从次级流出物中除去氮。研究了水力停留时间(HRT)对微藻生物量产量和养分去除的影响。结果表明,在低HRT条件下,悬浮液中可溶性藻产物浓度降低,从而减轻微藻生长抑制。此外,较低的HRT通过逐步淘汰与氮相关的功能细菌来降低蛋白质小球藻生长的氮限制。因此,蛋白小球藻的生产率从HRT为24小时时的6.12mg/L/天增加到HRT为8小时时的20.18mg/L/天。最高去除率为19.7mg/L/天,23.8毫克/升/天,在总氮(TN)的HRT为8小时时达到105.4mg/L/天,氨,和化学需氧量(COD),分别。然而,在去除率方面,当HRT为24小时时,TN和COD最大,分别为74.5%和82.6%。当HRT为8小时时,氨氮的最大去除率为99.2%。
    Further treatment of secondary effluents before their discharge into the receiving water bodies could alleviate water eutrophication. In this study, the Chlorella proteinosa was cultured in a membrane photobioreactor to further remove nitrogen from the secondary effluents. The effect of hydraulic retention time (HRT) on microalgae biomass yields and nutrient removal was studied. The results showed that soluble algal products concentration reduced in the suspension at low HRT, thereby alleviating microalgal growth inhibition. In addition, the lower HRT reduced the nitrogen limitation for Chlorella proteinosa\'s growth through the phase-out of nitrogen-related functional bacteria. As a result, the productivity for Chlorella proteinosa increased from 6.12 mg/L/day at an HRT of 24 hr to 20.18 mg/L/day at an HRT of 8 hr. The highest removal rates of 19.7 mg/L/day, 23.8 mg/L/day, and 105.4 mg/L/day were achieved at an HRT of 8 hr for total nitrogen (TN), ammonia, and chemical oxygen demand (COD), respectively. However, in terms of removal rate, TN and COD were the largest when HRT is 24 hr, which were 74.5% and 82.6% respectively. The maximum removal rate of ammonia nitrogen was 99.2% when HRT was 8 hr.
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  • 文章类型: Journal Article
    背景:大黄素是一种在传统中草药中发现的化合物。它具有抗炎和许多其他药理作用。我们先前的研究表明,大黄素可显着减轻重症急性胰腺炎(SAP)的炎症作用。然而,其溶解性差,高毒性和有限的胰腺保留时间阻碍了其临床应用。
    目的:我们旨在制备具有改善的生物利用度的大黄素纳米胶囊,以通过靶向巨噬细胞实现大黄素的控释。Further,探讨了负载大黄素的甘露糖偶联壳聚糖包被的脂质纳米胶囊(M-CS-E-LNC)治疗SAP的机制。
    方法:通过相转化法制备了M-CS-E-LNC,并进行了少量修饰。ELISA法检测M-CS-E-LNC的炎症介质表达和抗炎作用,巨噬细胞和LPS诱导的SAP小鼠中的IHC和IF。应用IVIS光谱成像和HPLC探索M-CS-E-LNC在胰腺中的控释。进行LC-MS/MS用于巨噬细胞的脂质组学分析。此外,基于载体的短发夹RNA(shRNA)方法用于沉默巨噬细胞中CTP1基因的表达.
    结果:用M-CS-E-LNC治疗后,巨噬细胞中炎症介质的水平明显降低。通过对血清淀粉酶水平的分析,在SAP小鼠中检测到相同的抗炎作用,TNF-α和IL-6。重要的是,M-CS-E-LNC允许大黄素选择性地积聚在胰腺和胃肠道组织,从而表现出针对性的释放。机械上,M-CS-E-LNC治疗组显示肉碱棕榈酰转移酶1(CPT1)蛋白的表达上调,促进细胞内长链脂肪酸的转运,从而促进巨噬细胞的M2表型极化。
    结论:M-CS-E-LNC具有显著改善的生物利用度和水溶性,这对巨噬细胞极化有更大的治疗作用。我们的发现还表明,第一次,CPT1可能是SAP治疗的新治疗靶点。
    BACKGROUND: Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application.
    OBJECTIVE: We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored.
    METHODS: M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells.
    RESULTS: The levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages.
    CONCLUSIONS: M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.
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  • 文章类型: Journal Article
    在同一天收获并加工车前草假茎。该过程开始于手动分离鞘(80.85%)和芯(19.14%)。使用桨叶对护套进行机械切碎处理,提取2.20%的木质纤维素纤维和2.12%的树液,与鞘的新鲜重量相比。洗涤纤维,干,梳理,并在其原始状态下旋转并进行蒸汽爆炸处理,同时对树液进行过滤和蒸发。在核心的情况下,它受到手动切割,干燥,研磨,和筛分分离12.81%的淀粉和6.39%的木质纤维素短纤维,与核心的新鲜重量相比。使用蒸汽爆炸的表面改性方法成功地去除来自垫片的纤维中的低比例的半纤维素和木质素。根据傅里叶变换红外光谱(FT-IR)显示的结果,热重分析(TGA),和差示扫描量热法(DSC),从拉伸试验中获得增加的σmax和ε,并且与其天然状态相比具有更大的热稳定性。树液通过FT-IR表现出吸湿行为,TGA表现出最高的热稳定性,而来自核心的淀粉呈现最低的吸湿性和热稳定性。尽管假茎提供了两种类型的纤维,在来自核心的木质素含量较低。最后,纱线是通过使用处于天然和蒸汽爆炸状态的护套纤维来加工的,识别加工中的差异以及它们各自的物理和机械性能。
    A plantain pseudostem was harvested and processed on the same day. The process began with manually separating the sheaths (80.85%) and the core (19.14%). The sheaths were subjected to a mechanical shredding process using paddles, extracting 2.20% of lignocellulosic fibers and 2.12% of sap, compared to the fresh weight of the sheaths. The fibers were washed, dried, combed, and spun in their native state and subjected to a steam explosion treatment, while the sap was subjected to filtration and evaporation. In the case of the core, it was subjected to manual cutting, drying, grinding, and sieving to separate 12.81% of the starch and 6.39% of the short lignocellulosic fibers, compared to the fresh weight of the core. The surface modification method using steam explosion succeeded in removing a low proportion of hemicellulose and lignin in the fibers coming from the shims, according to what was shown by Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC), achieving increased σmax and ε from the tensile test and greater thermal stability compared to its native state. The sap presented hygroscopic behavior by FT-IR and the highest thermal stability from TGA, while the starch from the core presented the lowest hygroscopic character and thermal stability. Although the pseudostem supplied two types of fibers, lower lignin content was identified in those from the core. Finally, the yarns were elaborated by using the fibers of the sheaths in their native and steam-exploded states, identifying differences in the processing and their respective physical and mechanical properties.
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  • 文章类型: Journal Article
    今天,人们利用植物治疗各种疾病,改善人类健康。药用植物之一是Betadine植物(JatrophamultifidaL.)。Betadine植物有许多功能,尤其是sap,叶子,水果和种子该化合物在Betadine茎汁中的含量,作为抗菌剂是有效的,是皂苷,单宁,黄酮类化合物和拉巴汀。引起感染的细菌之一是铜绿假单胞菌。这些细菌可引起机会性和医院感染。
    这项研究是一个真正的实验实验室,仅采用测试后的对照组设计。本研究使用浓度为25%的Betadine茎汁提取物,50%,75%,100%,10%庆大霉素乳膏作为阳性对照,和二甲基亚砜(DMSO)溶液作为阴性对照。本研究使用Kirby-Bauer扩散方法,将细菌铜绿假单胞菌在营养琼脂培养基上生长,然后孵育24小时并使用卡尺计算。使用单向ANOVA检验分析研究数据。
    最高抑制区为50%组(12.725±0.2500mm),而最低抑制区为100%组(8.675±0.5620mm)。
    Betadine茎提取物具有抑制铜绿假单胞菌生长的抗菌活性,其中50%浓度对抑制铜绿假单胞菌细菌的生长最有效。
    UNASSIGNED: Today, people use plants to treat various types of diseases and improve human health. One of the medicinal plants is the Betadine plant ( Jatropha multifida L.). Betadine plants have many functions, especially the sap, leaves, fruit and seeds. The compound contents in Betadine stem sap, which is efficacious as an antimicrobial, are saponins, tannins, flavonoids and labaditin. One of the bacteria that cause infection is Pseudomonas aeruginosa. These bacteria can cause opportunistic and nosocomial infections.
    UNASSIGNED: This study was a true experimental laboratory with a post-test only control group design. This study used Betadine stem sap extract with concentrations of 25%, 50%, 75%, 100%, gentamicin cream 10% as positive control, and dimethyl sulfoxide (DMSO) solution as negative control. This study used the Kirby-Bauer diffusion method and the bacterium Pseudomonas aeruginosa was grown on nutrient agar media, then incubated for 24 hours and calculated using calipers. Research data were analyzed using one-way ANOVA test.
    UNASSIGNED: The highest inhibition zone was group 50% (12.725 ± 0.2500 mm) while the lowest inhibition zone was group 100% (8.675 ± 0.5620 mm).
    UNASSIGNED: Betadine stem extract had antibacterial activity in inhibiting the growth of Pseudomonas aeruginosa bacteria, with the 50% concentration being the most effective in inhibiting the growth of Pseudomonas aeruginosa bacteria.
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  • 文章类型: Journal Article
    恶性胰岛素瘤是一种极为罕见的功能性胰腺神经内分泌肿瘤,恶性程度高,转移发生率高。然而,目前尚不清楚恶性胰岛素瘤是如何发展和转移的。血清淀粉样蛋白P成分(SAP),Pentraxin蛋白家族的成员,是肝细胞分泌的急性期蛋白。SAP在胰岛素瘤中的作用及相关机制尚不清楚。为了确定SAP对胰岛素瘤的影响,我们穿过Rip1-Tag2小鼠,自发发展为胰岛素瘤,和SAP敲除(KO)小鼠以产生Rip1-Tag2;SAP-/-小鼠。我们发现SAP删除显著促进了增长,通过癌相关成纤维细胞(CAFs)分泌的C-X-C基序趋化因子配体12(CXCL12)侵袭和转移恶性胰岛素瘤。进一步的研究表明,SAP缺失通过CXCR4/p38/ERK信号通路促进CAFs分泌CXCL12。这些发现揭示了SAP在恶性胰岛素瘤中的新作用和机制,并提供了SAP可能是该疾病的治疗药物的直接证据。
    Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.
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  • 文章类型: Journal Article
    信号淋巴细胞激活分子(SLAM)受体家族(SLAMF)由9种糖蛋白组成,这些糖蛋白属于含免疫球蛋白(Ig)结构域分子的CD2超家族。SLAMF受体调节多种免疫细胞的分化和活化。单个SLAMF受体在造血干细胞表面表达,造血祖细胞,B细胞,T细胞,NK细胞,NKT细胞,单核细胞,巨噬细胞,树突状细胞,中性粒细胞,和血小板。在正常B细胞成熟过程中研究了SLAMF受体的表达。在B淋巴来源的癌细胞系和B细胞慢性淋巴增殖性疾病(B-CLPD)患者的病理B细胞中也检测到几种SLAMF受体,成人中最常见的血液恶性肿瘤。这篇综述总结了SLAMF受体及其衔接蛋白SAP和EAT-2在B-CLPD中表达的最新知识。几种SLAMF受体可以被认为是潜在的诊断和鉴别诊断标志物。预后因素,以及B-CLPD患者新药开发的目标。
    The signaling lymphocytic activation molecule (SLAM) receptor family (SLAMF) consists of nine glycoproteins that belong to the CD2 superfamily of immunoglobulin (Ig) domain-containing molecules. SLAMF receptors modulate the differentiation and activation of a wide range of immune cells. Individual SLAMF receptors are expressed on the surface of hematopoietic stem cells, hematopoietic progenitor cells, B cells, T cells, NK cells, NKT cells, monocytes, macrophages, dendritic cells, neutrophils, and platelets. The expression of SLAMF receptors was studied during normal B cell maturation. Several SLAMF receptors were also detected in cancer cell lines of B-lymphoid origin and in pathological B cells from patients with B cell chronic lymphoproliferative disorders (B-CLPD), the most frequent hematological malignancies in adults. This review summarizes current knowledge on the expression of SLAMF receptors and their adaptor proteins SAP and EAT-2 in B-CLPD. Several SLAMF receptors could be regarded as potential diagnostic and differential diagnostic markers, prognostic factors, and targets for the development of novel drugs for patients with B-CLPD.
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  • 文章类型: Journal Article
    在系统性红斑狼疮(SLE)中,T滤泡(TFH)和外周辅助(TPH)细胞已越来越被认为是CD4T细胞的致病亚群。SLAM相关蛋白(SAP)通过与介导T细胞-B细胞相互作用的共刺激信号淋巴细胞活化分子家族(SLAMF)受体结合来调节TFH和TPH功能。SAP和SLAMF对于TPH依赖性B细胞成熟为表征SLE发病机理的产生自身抗体的浆细胞至关重要。我们假设表达SAP的TPH细胞参与了狼疮性肾炎(LN)的发病机理。
    使用密度梯度分离从全血中分离外周血单核细胞(PBMC)。对细胞表面标记进行染色,然后进行细胞内SAP的透化和染色以进行光谱流式细胞术分析。我们还使用可用的单细胞RNA测序(scRNAseq)加速药物伙伴关系(AMP)SLE数据集分析了肾脏浸润性LNT细胞的SAP表达。
    30例SLE患者的PBMC(34±10岁,83%女性),包括10名LN患者,进行了分析。我们发现与对照组相比,SLE中总SAP阳性CD4和CD8T细胞增加(55.5±2.6vs.41.3±3.4,p=0.007,和52.5±3.0vs.39.2±2.8,p=0.007)。在CD4T细胞中,SAP表达最高的是TPH亚群。循环中SAP+TPH的频率与疾病活动相关;患有肾脏疾病的SLE患者的循环SAP+TPH水平较高,在调整年龄后仍然显著,性别,种族,低互补,和升高的抗dsDNA(p=0.014)。LN中肾浸润性T细胞的scRNA-seq数据鉴定SAP表达定位到TFH样CD4簇和GZMK+CD8簇。LN中SAP表达的增加与SLAMF3和SLAMF7以及颗粒酶K和EOMES的差异表达有关。存在两个主要的SAP表达子集,TFH样CD4T细胞,和GZMK+效应CD8T细胞,使用来自15个主要器官的人类转录组学图谱的scRNA-seq数据进行验证。
    在我们的队列中,表达SAP的T辅助细胞的扩增与LN相关,并使用肾浸润性T细胞的scRNA-seq数据进行了验证。改进的SLAM和SAP信号传导理解可以识别LN中的新治疗靶标。
    T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN).
    Peripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset.
    PBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs.
    The expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN.
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