Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear. This study aimed to elucidate the role of high mobility group box 1 (HMGB1) in NETs involved in the pathogenesis of PE. The concentration of NETs was detected in the plasma of patients with PE using enzyme-linked immunosorbent assay (ELISA). Placental samples were collected from patients with PE to detect the expression of HMGB1 through Western Blot and PCR. For in vitro experiments, human trophoblast HTR-8/SVneo cells were treated with NETs, and their proliferation, invasion, migration, and apoptosis ability; degree of oxidative stress; and secretion of inflammatory factors were detected. Compared with that in normal pregnant women, an increase in the release of NETs was observed in the peripheral blood of patients with PE. HMGB1 was increased in the placenta of PE patients and colocalized with NETs. The treatment of human trophoblast HTR-8/SVneo cells with NETs resulted in the inhibition of HTR-8/SVneo cell invasion and migration and increases in the release of reactive oxygen species (ROS), and several inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). These damaging effects can be reversed by the HMGB1 scavenger glycyrrhizin, which indicates that NETs can mediate trophoblast damage and the expression of several inflammatory factors through HMGB1. NETs can cause trophoblast inflammation-related functional damage through HMGB1 during the occurrence and development of preeclampsia. HMGB1 produces a marked effect in the PE cascade of oxidative stress involving NETs. Inhibiting HMGB1 to suppress NETs damage is a possible approach for the future treatment of PE.
DNA vaccine against human immunodeficiency virus type‐1 (HIV‐1) can induce substantial levels of HIV‐1‐specific humoral and cell‐mediated immunity. To develop more potent HIV‐1 DNA vaccine formulations, we used a murine model to explore the immunomodulatory effects of an interleukin‐2 (IL‐2) expression plasmid on an HIV‐1 DNA vaccine following intranasal administration of the combination. When the vaccine and expression plasmid were incorporated into cationic liposomes and administered to mice, the HIV‐1‐specific delayed‐type hypersensitivity response and cytotoxic T lymphocyte activity were significantly increased. Restimulated immune lymphoid cells showed enhanced production of both IL‐2 and interferon‐γ and reduced secretion of IL‐4. The level of total antibody to HIV‐1 antigen was not greatly changed by coadministration of the DNA vaccine and IL‐2 expression plasmid. An analysis of serum HIV‐1‐specific IgG subclasses showed a significant drop in the IgG1/IgG2a ratio in the group that received the plasmid–vaccine combination. These results demonstrate that the IL‐2 expression plasmid strongly enhances the HIV‐1‐specific immune response via activation of T helper type‐1 cells.
To study the impact of the COVID-19 pandemic on in vivo microstructural and functional placental development using intra-voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI, respectively. This is prospective, observational study of pregnant women with singleton gestations during the COVID-19 pandemic (May 2020-present), compared to pre-pandemic historical controls (July 2014-February 2020). Placental imaging was identical for pandemic and pre-pandemic cohorts: including T2W anatomic images, PGSE sequences for IVIM [TE/TR=53.8/8000ms with 9 b-values (0-900s/mm2)], gradient-echo planar imaging sequences for BOLD imaging (TE/TR=60/2000ms) using a 6 minute maternal hyperoxia design, followed by 6 minutes of normoxia as return to baseline. 28 pregnant women during COVID-19 were included and compared to 100 pre-pandemic healthy controls (IVIM) and 57 pre-pandemic healthy controls (BOLD). The average gestational age (GA) was 28.6±6.0, 29.2±5.8 and 30.1±3.9, respectively. IVIM metrics trended higher for placental diffusion and lower for placental perfusion compared to pre-pandemic controls (Table 1). BOLD functional MRI revealed significantly lower placental oxygenation during minutes 2-6 of maternal hyperoxia and during minutes 1-3 of return to resting state (post hyperoxia) compared to pre-pandemic controls (Figure 1). Respiratory pandemics have been associated with altered intrauterine programing that can result in fetal onset of adult diseases. While the mechanisms are unclear, the placenta is a critical organ that mediates maternal well-being with fetal development. We report altered microstructural and functional placental development during the COVID-19 pandemic in COVID-19 negative women. Neurodevelopmental assessments of these infants are ongoing to determine the short- and long-term effects of these changes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)
To investigate the cell types infected by severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in lung tissues and explore the mechanism of lung injury in SARS.In-situ hybridization(ISH) and immunohistochemistry(IHC) double staining was applied to study the lung tissues from 7 SARS cases of Beijing and one of Anhui province. According to SARS-CoV genome sequence, the cDNA probe was synthesized and labelled by digoxin. Immunohistochemically, antibodies of cytokeratin(CK), CD34, CD68, Vimentin and CD3 were applied to demonstrate bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, fibroblasts and T cells respectively.The positive results of in-situ hybridization showed that the lung tissues of all cases expressed SARS-CoV RNA, and positive signals displayed in cytoplasms (purple-blue, NBP-BCIP. ISH-IHC double staining showed that positive signals of both ISH (purple-blue NBT-BCIP and IHC (red-brown, AEC expressed in the cytoplasms (purple and red). The positive results of double staining indicated that bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, fibroblasts and T lymphocytes were diffusely infected by SARS-CoV.This study of ISH-IHC double staining in lung tissues of SARS patients showed that bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, T lymphocytes and fibroblasts were attacked diffusely in SARS lungs. Various types of cells damaged by SARS-CoV and inflammatory mediators released by those cells play an important role in the pathogenesis of lung injury in SARS.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
