Annexin A5

膜联蛋白 A5
  • 文章类型: Journal Article
    探讨99mTc-HYNIC-AnnexinV在体内检测细胞凋亡的可行性。通过HYNIC用99mTc标记膜联蛋白V。18只植入VX-2的新西兰兔随机分为对照组(n=8)和紫杉醇(PAC,n=10)组,静脉注射2mL/kg生理盐水或2.4mg/kgPAC。治疗前静脉注射99mTc-HYNIC-AnnexinV,SPECT检测肝肿瘤显像,分别于处理后24小时和48小时。计算肿瘤放射性计数与非肿瘤部位的比例。当最后一次成像完成时,兔子被处死了。肿瘤被取出并分成两部分,一个用于TUNEL免疫组织化学分析,另一个用于流式细胞术(FCM)。我们发现通过HYNIC标记99mTc的膜联蛋白V的比率超过95%,放射化学纯度在95%以上。SPECT显示两组治疗前均无明显肿瘤显像。对照组无明显肿瘤显像,而PAC组在治疗后24h和48h表现出显著的积累。化疗后24h和48hPAC组的肿瘤/非肿瘤(T/NT)与对照组和治疗前PAC组差异有统计学意义。PAC组24h和48h无明显差别。PAC组TUNEL阳性细胞的免疫组织化学检测和FCM检测的细胞凋亡率与对照组相比差异有统计学意义。T/NT与TUNEL阳性细胞和肿瘤的凋亡率显着相关。PAC可诱导兔VX-2肝癌细胞凋亡。紫杉醇化疗后24-48小时是细胞凋亡检测的窗口时间。通过99mTc-HYNIC-AnnexinV,SPECT可以检测体内凋亡细胞。
    To investigate the feasibility of detection of apoptosis in vivo by 99mTc-HYNIC-Annexin V, Annexin V was labeled with 99mTc through HYNIC. 18 New Zealand rabbits implanted VX-2 were randomly divided into control (n = 8) and paclitaxel (PAC, n = 10) groups, given 2 mL/kg of normal saline or 2.4 mg/kg of PAC intravenously. The liver tumor imaging was detected by SPECT through intravenous injection of 99mTc-HYNIC-Annexin V before treatment, 24 hours and 48 hours after treatment respectively. Tumor radioactive count proportion to non-tumor sites was calculated. When the last imaging was finished, the rabbits were sacrificed. The tumor was taken out and divided into two pieces, one for TUNEL immunohistochemical analysis and the other for flow cytometry (FCM). We found that the rate of Annexin V labeled with 99mTc through HYNIC was more than 95%, and radiochemical purity was above 95%. The SPECT showed that two groups had no significant tumor imaging before the treatment. There is no significant tumor imaging in control group, while the PAC group 24 h and 48 h after treatment showed significant accumulation. The Tumor/non-Tumor (T/NT) in PAC group at 24 h and 48 h after chemotherapy was significantly different from that in the control group and PAC group prior to treatment. There was no significant difference between 24 h and 48 h in PAC group. The TUNEL-positive cells detected by immunohistochemistry and apoptotic rate detected by FCM in PAC group were significant different from those in control group. The T/NT was significantly correlated to TUNEL-positive cells and apoptotic rate of the tumor. PAC can induce apoptosis of rabbit VX-2 liver cancer cells. 24-48 h after paclitaxel chemotherapy is a window time for apoptosis detection. Apoptotic cells in vivo can be detected by SPECT through 99mTc-HYNIC-Annexin V.
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  • 文章类型: Journal Article
    骨关节炎(OA)是一种具有挑战性的退行性关节疾病。先前的研究表明,无细胞脂肪提取物(CEFFE)可能具有治疗OA的潜力。这项研究调查了CEFFE中膜联蛋白A5(AnxA5)在调节巨噬细胞极化和保护软骨细胞中的作用。体外实验表明,AnxA5通过促进Toll样受体(TLR)4内化和通过钙依赖性内吞作用的溶酶体降解,有效抑制M1巨噬细胞极化。这一进程下降了TLR4的表达,抑制促炎介质释放,并减少了活性氧的产生。此外,AnxA5对软骨细胞坏死和凋亡具有保护作用。在体内,研究表明,在碘乙酸钠诱导的骨关节炎大鼠模型中,关节内给予AnxA5改善了疼痛症状。组织学分析表明,AnxA5治疗后,滑膜炎症反应减少,软骨损伤减轻。这些结果强调了AnxA5由于其调节巨噬细胞极化和维持软骨细胞活力的能力而作为OA的治疗选择的潜力。进一步研究AnxA5的具体机制和临床应用可能有助于改善OA的管理。
    Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. In vitro experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. In vivo, studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.
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  • 文章类型: Journal Article
    背景:肾缺血再灌注损伤(IRI)是急性肾损伤的原因之一。膜联蛋白A5(AnxA5),钙依赖性细胞膜结合蛋白,在各种器官IRI模型中显示保护作用。本研究探讨外源性AnxA5单体蛋白对肾脏IRI的治疗作用及其潜在作用机制。
    结果:静脉注射不同剂量的AnxA5治疗SD大鼠双侧肾IRI。该模型证实了AnxA5对肾脏结构和功能的保护作用。体外,HK-2细胞缺氧12小时,然后恢复正常氧气供应以模拟IRI。体外实验通过测量细胞活性和通透性证明了AnxA5的作用机制。突变AnxA5蛋白M23的比较和无钙培养基的应用通过形成网络结构进一步验证了AnxA5的保护作用。
    结论:外源性AnxA5单体通过与受损的肾小管上皮细胞膜结合来预防肾IRI,形成一个二维网络结构,以保持细胞膜的完整性,并最终防止细胞死亡。
    BACKGROUND: Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5), a calcium-dependent cell membrane-binding protein, shows protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism of action.
    RESULTS: Different doses of AnxA5 were injected intravenously to treat bilateral renal IRI in SD rats. This model confirmed the protective effects of AnxA5 on kidney structure and function. In vitro, HK-2 cells were subjected to hypoxia for 12 h, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments demonstrated the mechanism of action of AnxA5 by measuring cellular activity and permeability. A comparison of the mutant AnxA5 protein M23 and the application of a calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure.
    CONCLUSIONS: Exogenous AnxA5 monomers prevented renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)继续在癌症相关的发病率和死亡率发挥重要作用,主要是由于其明显的肿瘤异质性和复发倾向。这强调了对其高度恶性机制进行深入检查的迫切需要。膜联蛋白A5(ANXA5),被认为是一种标志性的肿瘤蛋白,由于其在HCC预后中的模糊功能和机制,已成为关注的焦点。本研究旨在通过采用将常规实验方法与RNA测序相结合的综合方法,全面了解ANXA5在人类HCC细胞恶性进展中的作用。
    使用免疫荧光评估HCC组织和相应非肿瘤组织之间的ANXA5表达差异(n=25)。随后进行相关分析以评估ANXA5表达与临床病理特征之间的关联(n=65)。使用迁移和侵袭测定以及Ki-67指数在体外以及基于节点小鼠异种移植模型的体内探索了ANXA5在具有ANXA5基因敲除和过表达的人HCC细胞系中的作用。使用人脐静脉内皮细胞(HUVEC)进行管形成测定,以证明ANXA5在HCC中的血管生成作用。使用单细胞和批量RNA测序来进一步研究所涉及的潜在机制。
    这项研究表明,ANXA5在HCC患者中高表达,并与不良预后相关。迁移分析,入侵,基于人HCC细胞系中ANXA5基因敲除和过表达系统的增殖已经证明ANXA5在体外和体内增强HCC恶性程度。HUVEC的管形成测定表明ANXA5促进血管生成并将内皮细胞募集到HCC细胞。单细胞和批量RNA测序数据分析进一步证实,ANXA5在HCC中的表达与肝细胞代谢有关,免疫反应激活,和各种致癌信号通路。
    这项研究揭示了肿瘤组织中ANXA5表达升高与HCC患者预后不良之间有意义的关联。此外,ANXA5通过促进侵袭和血管生成促进HCC恶性。因此,ANXA5已成为HCC的有希望的治疗靶标,并有可能改善患者的预后。
    UNASSIGNED: Hepatocellular carcinoma (HCC) continues to play a substantial role in cancer-related morbidity and mortality, largely owing to its pronounced tumor heterogeneity and propensity for recurrence. This underscores the pressing need for in-depth examination of its highly malignant mechanisms. Annexin A5 (ANXA5), recognized as a hallmark tumor protein, has emerged as a focal point of interest because of its ambiguous function and mechanism in HCC prognosis. This study aimed to provide a comprehensive understanding of the role of ANXA5 in the malignant progression of human HCC cells by employing an integrative approach that combines conventional experimental methods with RNA sequencing.
    UNASSIGNED: Differences in ANXA5 expression between HCC tissues and corresponding nontumor tissues were evaluated using immunofluorescence (n = 25). Correlation analysis was subsequently performed to assess the association between ANXA5 expression and clinicopathological features (n = 65). The role of ANXA5 in human HCC cell lines with ANXA5 gene knockout and overexpression was explored in vitro using migration and invasion assays and Ki-67 indices and in vivo based on node mice xenograft model. A tube formation assay using human umbilical vein endothelial cells (HUVECs) was conducted to demonstrate the angiogenic effects of ANXA5 in HCC. Single-cell and bulk RNA sequencing was used to further investigate the underlying mechanisms involved.
    UNASSIGNED: This study revealed that ANXA5 is highly expressed in patients with HCC and correlates with poor prognosis. Assays for migration, invasion, and proliferation based on ANXA5 gene knockout and overexpression systems in human HCC cell lines have demonstrated that ANXA5 enhances HCC malignancy in vitro and in vivo. Tube formation assays of HUVECs indicated that ANXA5 facilitates angiogenesis and recruits endothelial cells to HCC cells. Single-cell and bulk RNA sequencing data analysis further confirmed that ANXA5 expression in HCC is associated with hepatocyte metabolism, immune response activation, and various oncogenic signaling pathways.
    UNASSIGNED: This study revealed a meaningful association between elevated ANXA5 expression in tumor tissues and an unfavorable prognosis in patients with HCC. In addition, ANXA5 promotes HCC malignancy by promoting invasion and angiogenesis. Thus, ANXA5 has emerged as a promising therapeutic target for HCC and has the potential to improve patient outcomes.
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  • 文章类型: Journal Article
    糖尿病伤口愈合的关键障碍之一是活动性炎症的持续存在。我们先前证明了无细胞脂肪提取物(CEFFE)促进糖尿病伤口愈合的潜力,膜联蛋白A5(A5)是CEFFE中至关重要的抗炎蛋白。本研究旨在评估A5在糖尿病伤口中的治疗潜力。
    将A5加载到GelMA水凝胶中,并在体内应用于糖尿病小鼠的皮肤伤口。用GelMA-A5处理的糖尿病伤口观察14天并通过组织学分析进行评估。通过抗CD68染色进行炎症调节,抗CD86和抗CD206染色,和伤口组织的qRT-PCR。在A5的存在下,脂多糖(LPS)在体外刺激的巨噬细胞,并通过qRT-PCR检测,流式细胞术,和免疫荧光染色。此外,上皮细胞与A5共培养,通过CCK-8测定和细胞迁移测定进行上皮化调节。
    A5可能通过促进巨噬细胞从M1表型向M2表型转变来促进糖尿病创面愈合和调节炎症。体外实验表明,A5对降低促炎因子和抑制巨噬细胞从M0向M1表型的极化具有显著作用。A5明显增进了上皮细胞的迁徙。
    膜联蛋白A5对调节巨噬细胞炎症和促进上皮化具有显着影响。
    UNASSIGNED: One of the key obstacles to the healing of diabetic wound is the persistence of active inflammation. We previously demonstrated the potential of cell-free fat extract (CEFFE) to promote the healing of diabetic wounds, and annexin A5 (A5) is a crucial anti-inflammatory protein within CEFFE. This study aimed to evaluate the therapeutic potential of A5 in diabetic wounds.
    UNASSIGNED: A5 was loaded into GelMA hydrogels and applied to skin wounds of diabetic mice in vivo. The diabetic wounds with the treatment of GelMA-A5 were observed for 14 days and evaluated by histological analysis. Accessment of inflammation regulation were conducted through anti-CD68 staining, anti-CD86 and anti-CD206 staining, and qRT-PCR of wound tissue. In presence of A5, macrophages stimulated by lipopolysaccharide (LPS) in vitro, and detected through qRT-PCR, flow cytometry, and immunocytofluorescence staining. Besides, epithelial cells were co-cultured with A5 for epithelialization regulation by CCK-8 assay and cell migration assay.
    UNASSIGNED: A5 could promote diabetic wound healing and regulate inflammations by promoting the transition of macrophages from M1 to M2 phenotype. In vitro experiments demonstrated that A5 exerted a significant effect on reducing pro-inflammatory factors and inhibiting the polarization of macrophages from M0 toward M1 phenotype. A5 significantly promoted the migration of epithelial cells.
    UNASSIGNED: Annexin A5 has a significant impact on the regulation of macrophage inflammation and promotion of epithelialization.
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  • 文章类型: Journal Article
    白血病是造血系统的恶性疾病,其中克隆性白血病细胞由于不受控制的增殖和凋亡受损而在骨髓和其他造血组织中积累并抑制正常造血,在其他机制中。在这项研究中,从五味子中提取的化合物(SGP-17-S)的抗白血病作用,一种具有抗炎作用的植物,抗菌和抗肿瘤作用,进行了评估。MTT法证明SGP-17-S对白血病细胞活力的影响,细胞周期,通过流式细胞术使用PI染色和膜联蛋白V/PI双重染色评估细胞凋亡。网络药理学和细胞热转移测定(CETSA)与蛋白质印迹的组合用于验证作用于白血病靶标的试剂。结果表明,SGP-17-S以时间和剂量依赖的方式抑制白血病细胞的生长。SGP-17-S在G2期阻断HEL细胞,诱导细胞凋亡,Bcl-2和caspase-8蛋白表达降低,并增加Bax和caspase-3的表达。此外,CETSA揭示PARP1是抑制HEL细胞生长的重要靶基因,SGP-17-S通过靶向PARP1对白血病细胞发挥作用。因此,本研究可能为白血病的治疗提供新的解决方案和思路。
    Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.
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  • 文章类型: Journal Article
    作为人体内重要的功能性蛋白质分子,人膜联蛋白A5(hAnxA5)广泛存在于人体细胞和体液中。hAnxA5,最小的膜联蛋白,通过以钙依赖性方式可逆和特异性结合磷脂酰丝氨酸(PS)来执行多种生物学功能,并在许多人体生理和病理过程中发挥重要作用。游离态hAnxA5以单体形式存在,在发挥生物活性时通常以特定的自组装方式形成聚合物。这篇综述从三个角度系统地讨论了hAnxA5的当前知识和理解:病理生理相关性,诊断价值,和治疗效用。hAnxA5影响许多病理生理过程的发生和发展。此外,hAnxA5可独立或组合用作用于诊断某些疾病的病理生理现象的生物标志物。重要的是,基于hAnxA5的特性,已经设计并制备了许多新的候选药物以用于实际的医疗实践中。然而,hAnxA5研究也存在一些空白和不足。这项深入研究不仅将扩大对结构和功能关系的理解,还将促进hAnxA5在生物医学领域的应用。
    As an important functional protein molecule in the human body, human annexin A5 (hAnxA5) is widely found in human cells and body fluids. hAnxA5, the smallest type of annexin, performs a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calcium-dependent manner and plays an important role in many human physiological and pathological processes. The free state hAnxA5 exists in the form of monomers and usually forms a polymer in a specific self-assembly manner when exerting biological activity. This review systematically discusses the current knowledge and understanding of hAnxA5 from three perspectives: physiopathological relevance, diagnostic value, and therapeutic utility. hAnxA5 affects the occurrence and development of many physiopathological processes. Moreover, hAnxA5 can be used independently or in combination as a biomarker of physiopathological phenomena for the diagnosis of certain diseases. Importantly, based on the properties of hAnxA5, many novel drug candidates have been designed and prepared for application in actual medical practice. However, there are also some gaps and shortcomings in hAnxA5 research. This in-depth study will not only expand the understanding of structural and functional relationships but also promote the application of hAnxA5 in the field of biomedicine.
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  • 文章类型: English Abstract
    Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.
    目的: 在类中性粒细胞模型中,探讨尿激酶型纤溶酶原激活物受体(PLAUR)基因对中性粒细胞活化及凋亡的影响。 方法: 采用体外培养的人急性髓系粒细胞白血病细胞株HL60作为研究对象,全反式维甲酸(ATRA)诱导HL60细胞分化为类中性粒细胞。构建干扰人PLAUR基因的慢病毒载体,转染入类中性粒细胞(siRNA组),并设置磷酸盐缓冲液(PBS)组(未转染)和空白对照(NC组,转染空白质粒)作为对照(n=3)。饥饿培养、加入白细胞介素-17干预后,流式细胞术检测细胞膜CD11b表达,以及酶联免疫吸附法检测细胞培养液上清中髓过氧化物(MPO)、中性粒细胞胞外诱捕网(NETs)水平,了解类中性粒细胞活化情况。Annexin V/PI染色流式细胞术检测细胞凋亡,并用Western蛋白印迹法检测凋亡相关蛋白caspase-3、bax、bcl-2表达。 结果: 流式细胞术检测siRNA组HL60细胞细胞膜CD11b表达(32.37±8.17)较另两组下降(PBS组46.27±1.54,NC组53.07±8.14)(P<0.05)。siRNA组细胞培养液上清中MPO和NETs水平(33.37±1.11、57.69±3.03)也均较PBS组(41.64±2.20、77.60±4.33)和NC组(40.84±5.11、76.15±2.10)下降,差异均有统计学意义(均P<0.05)。流式细胞术检测siRNA组凋亡率(20.42%±2.45%)较PBS组(11.91%±2.23%)和NC组(11.13%±2.56%)升高(P<0.05)。siRNA组caspase-3和bax蛋白表达(0.84±0.05、0.83±0.04)较PBS组(0.68±0.02、0.63±0.08)和NC组(0.71±0.01、0.66±0.10)高,差异有统计学意义(P<0.05);抗凋亡蛋白bcl-2表达量减少(siRNA组:0.38±0.02,PBS组:0.73±0.05,NC组:0.69±0.06)(P<0.05)。 结论: PLAUR可促进类中性粒细胞活化,抑制其凋亡。.
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  • 文章类型: Journal Article
    目的:评估复发性流产(RM)妇女抗膜联蛋白A5抗体(aAnxA5)中位数倍数(MOM)与随后的妊娠结局之间的相关性。
    方法:完全,本研究包括310名RM妇女,并根据其通过ELISA确定的孕前aAnxA5循环水平的MOM分组。采用多因素logistic回归分析aAnxA5对妊娠结局的影响。结果包括早期流产(妊娠10周前),晚期流产(10至24周),持续怀孕(超过10周),和活产(24周后),其特征是怀孕并有胎儿心跳。
    结果:对于aAnxA5MOM的每增加一个单位,24周后活产和持续妊娠的几率降低了40.2%(OR=.598;95CI0.406-0.882,P=.010)和38.1%(OR=.619;95CI0.424-0.904,P=.013),分别,在调整人口统计学和临床特征后。aAnxA5MOM的升高与早期流产(OR=1.616;95CI1.106-2.361,P=0.013)和流产(早期+晚期流产)(OR=1.671;95CI1.134-2.464,P=.010)的风险增加相关。进一步的亚组分析显示,在两个亚组中,妊娠24周后活产率的风险降低:产妇年龄≥35岁(OR=0.131;95CI0.026-0.652),既往妊娠丢失≥3(OR=.381;95CI0.173-0.837)。
    结论:RM女性的孕前aAnxA5MOM水平较高可能与24周后活产风险降低和早期流产风险增加有关。尤其是年龄≥35岁或既往妊娠损失≥3岁的个体。
    OBJECTIVE: To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM).
    METHODS: Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat.
    RESULTS: For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837).
    CONCLUSIONS: Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.
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  • 文章类型: Journal Article
    背景:小胶质细胞增生在促进和维持中枢神经系统的体内平衡中起着至关重要的作用,它与神经精神疾病有关。在重度抑郁症(MDD)的情况下,小胶质细胞增生如何受到影响仍然难以捉摸。在这项研究中,我们假设海马中的小胶质细胞增生在MDD的慢性未预测轻度应激(CUMS)模型中受损,参与MDD的开发。
    方法:通过CUMS诱导成年雄性小鼠的抑郁样行为,并通过行为测试证实。使用海马切片和与凋亡细胞共培养的原代小胶质细胞的免疫荧光染色来评估小胶质细胞的有效增殖。采用免疫印迹和RT-qPCR检测吞噬作用相关分子和炎症相关细胞因子的蛋白和mRNA水平,分别。注射膜联蛋白V以模拟小胶质细胞增生的损害。TREM2-siRNA进一步用于原代小胶质细胞以检查有效细胞增多相关的信号通路。
    结果:CUMS小鼠小胶质细胞被激活,促炎细胞因子表达增加,而小胶质细胞增生和相关分子减少。TREM2/Rac1通路的抑制损害了小胶质细胞增生。膜联蛋白V注射液抑制小胶质细胞增生,海马体炎症和抑郁样行为增加。
    结论:未评估TREM2/Rac1通路上调的潜在抗抑郁作用。
    结论:小胶质细胞增生的损害与抑郁样行为的发展有关,随着TREM2/Rac1途径的下调和炎症的增加。这些结果可能会增加我们对与MDD相关的病理生理机制的理解,并为治疗干预提供新的靶点。
    BACKGROUND: Microglial efferocytosis plays a crucial role in facilitating and sustaining homeostasis in the central nervous system, and it is involved in neuropsychiatric disorders. How microglial efferocytosis is affected under the condition of major depressive disorder (MDD) remains elusive. In this study, we hypothesized that microglial efferocytosis in the hippocampus is impaired in the chronic unpredicted mild stress (CUMS) model of MDD, which is involved in the development of MDD.
    METHODS: Depressive-like behavior in adult male mice was induced by CUMS and confirmed by behavioral tests. Microglial efferocytosis was evaluated using immunofluorescence staining of hippocampal slices and primary microglia co-cultured with apoptotic cells. The protein and mRNA levels of phagocytosis-related molecules and inflammation-related cytokines were detected using western blotting and RT-qPCR, respectively. Annexin V was injected to mimic impairment of microglial efferocytosis. TREM2-siRNA was further used on primary microglia to examine efferocytosis-related signaling pathways.
    RESULTS: Microglia were activated and the expression of proinflammatory cytokines was increased in CUMS mice, while microglial efferocytosis and efferocytosis-related molecules were decreased. Inhibition of the TREM2/Rac1 pathway impaired microglial efferocytosis. Annexin V injection inhibited microglial efferocytosis, increased inflammation in the hippocampus and depressive-like behavior.
    CONCLUSIONS: The potential antidepressant effect of the upregulation of the TREM2/Rac1 pathway was not evaluated.
    CONCLUSIONS: Impairment of microglial efferocytosis is involved in the development of depressive-like behavior, with downregulation of the TREM2/Rac1 pathway and increased inflammation. These results may increase our understanding of the pathophysiological mechanisms associated with MDD and provide novel targets for therapeutic interventions.
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