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The present work aimed to explore the role of long non-coding RNA (lncRNA)-AC020978 in postoperative cognitive disorder (POCD) and the underlying mechanism. The POCD mouse model was constructed through isoflurane anesthesia + abbreviated laparotomy. The AC020978 expression in brain tissue was silenced after lentivirus injection, then Morris water maze test was conducted to detect the cognitive disorder level, flow cytometry was performed to analyze M1 macrophage level, ELISA was carried out to measure inflammatory factor levels, H&E, Nissl and immunohistochemical staining was performed to detect the pathological changes in brain tissue, and Western blotting assay was adopted to detect protein expression. In addition, microglial cells were cultured in vitro, after lentivirus infection, the effect of AC020978 on the M1 polarization of microglial cells and glycolysis was observed. AC020978 overexpression promoted POCD progression and aggravated cognitive disorder in mice; in addition, the proportion of peripheral and central M1 cells increased, the inflammatory factor levels were upregulated, and microglial cells were activated. By contrast, AC020978 silencing led to cognitive disorder in mice and suppressed microglial cell activation and M1 polarization. In vitro experimental results indicated that AC020978 promoted the expression and phosphorylation of PKM2, which promoted inflammatory response through enhancing microglial cell glycolysis and M1 polarization. AC020978 interacts with PKM2 to promote the glycolysis and M1 polarization of microglial cells, thus regulating cognitive disorder and central inflammation in POCD. [ABSTRACT FROM AUTHOR]

This work mainly aimed to explore the role and mechanism of advanced glycation end-products (AGEs) in inducing cerebrovascular endothelial cell pyroptosis under oxygen glucose deprivation (OGD) condition. The mouse cerebral microvascular endothelial cells (BMECs and bEnd.3) were used as the objects to construct the OGD model in vitro. Then, cells were pretreated with AGE-modified human serum albumin (AGE-HSA). Thereafter, CCK-8 assay was conducted to detect cell viability, and flow cytometry (FCM) was performed to measure cell pyroptosis level. Meanwhile, the expression of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA). The expression of HIF-α, NLRP3, and RAGE was detected by fluorescence staining. The opening status of cell membrane pore was observed under the electron microscope, and the expression levels of FL-GSDMD, NT-GSDMD, and caspase-1 were measured through Western Blot (WB) assay. Moreover, bEnd.3 cells were treated with siRAN-silenced NLRP3 and HIF-α inhibitor, so as to observe the effect of AGEs on cell pyroptosis level. In the mouse model, the middle cerebral artery occlusion (MCAO) model was constructed by the suture-occluded method. After intraperitoneal injection of AGEs, the pathological changes in mouse brain tissues were detected; the expression levels of NLRP3, ZO-1, and CD31 were determined by histochemical staining, and the levels of inflammatory factors and pyroptosis-related proteins were also detected. Under OGD condition, AGEs induced the pyroptosis of bEnd.3 cells, and the cell pyroptosis rate increased, higher than that of the OGD group. Meanwhile, the levels of inflammatory factors were up-regulated; the expression of HIF-α, NLRP3, and RAGE in cells increased; and the levels of NT-GSDMD and caspase-1 were markedly higher than those of the control and OGD groups. siRNA-NLRP3 or HIF-α inhibitor treatment suppressed pyroptosis and reduced the inflammatory factor levels. In mouse experiments, AGE injection aggravated brain injury in the MCAO mouse model, decreased the expression of ZO-1 and CD31, and elevated the levels of NLRP3 and inflammatory factors. Under cerebral ischemia condition, AGEs can induce endothelial cell pyroptosis via HIF-α-RAGE-NLRP3, thereby further aggravating brain injury. [ABSTRACT FROM AUTHOR]

Purpose: The dysfunction of trophoblast during inflammation plays an important role in PE. Formyl peptide receptor 2 (FPR2) plays crucial roles in the development of inflammation-associated disease. This present study aimed to explore the effect of FPR2 on a trophoblast cellular model of preeclampsia. Methods: The expression of FPR2 in placenta was detected by immunohistochemical staining and western blotting. Transfection of siRNA was used to knockdown FPR2 in HTR-8/SVneo cells. Inflammatory cytokines were detected by ELISA. CCK8, Transwell, wound healing, FACS and tube formation assays were performed to observe the abilities of cell proliferation, migration, invasion, apoptosis and angiogenesis. Western blotting was implemented to clarify that NF-κB signaling pathway was downstream of FPR2. Results: The expression levels of FPR2 were higher in placental tissues of patients with PE. Knockdown of FPR2 expression by siFPR2 or inhibition of its activity by WRW4 decreased the release of proinflammatory cytokines in HTR8/SVneo cells treated with LPS. Knockdown of FPR2 expression or inhibition of its activity further reversed the LPS-induced attenuation of the proliferation, migration, invasion and angiogenesis and increase in apoptosis in HTR8/SVneo cells. Moreover, the NF-κB signaling pathway was activated in both placental tissues of patients with PE and LPS-treated HTR8/SVneo cells. However, the activation was attenuated when FPR2 was knocked down or inhibited. Conclusion: Suppression of FPR2 expression alleviated the effects of inflammation induced by LPS on trophoblasts via the NF-κB signaling pathway, which provided a novel and potential strategy for the treatment of PE. [ABSTRACT FROM AUTHOR]