Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.

The value of 3D-FIESTA MRI in detecting non-iatrogenic cerebrospinal fluid rhinorrhoea: correlations with endoscopic endonasal surgery.

BACKGROUND: In this study, we investigated the value of three-dimensional (3D) fast-imaging employing steady-state acquisition (FIESTA) magnetic resonance imaging (MRI) in detecting non-iatrogenic cerebrospinal fluid (CSF) rhinorrhoea and compared it with regular MRI and 3D magnetisation prepared rapid acquisition gradient echo (MPRAGE) MRI sequences, as well as high-resolution computed tomography (HRCT) imaging. We also present the endoscopic experiences of such cases. METHOD: From June 2011 to Feb 2016, 17 patients with non-iatrogenic cerebrospinal fluid rhinorrhoea were included. Seven patients had spontaneous rhinorrhoea, three patients had invasive tumours, and the remaining patients had traumatic aetiologies. All the patients underwent HRCT, regular MRI sequence imaging, 3D-MPRAGE MRI sequence imaging and 3D-FIESTA MRI sequence imaging for the preoperative evaluations of the leakages. For each patient, the CSF fistula site was confirmed by intraoperative neuronavigation and endoscopic findings. Statistical analyses were performed. All patients underwent endoscopic multilayer repair. RESULTS: The sensitivities of the HRCT, regular MRI (T1 and T2), 3D-MPRAGE and 3D-FIESTA modalities for identifying CSF leakage were 58.8 %, (11.8 % and 29.4 %), 74.7 %, and 88.2 %, respectively. The origins of the leakages included the cribriform plate (18 %), ethmoidal fovea (23 %), lateral recess of the sphenoid (17 %), sellar floor (12 %), ethmoidal roof (12 %), junction of the fovea and cribriform plate (6 %) and the junction of sellar and sphenoidal planum (6 %). Two patients required repair. The first was under local anaesthesia when the nasal packing was removed, and the second underwent repair at the same site a half-year later due to hydrocephalus. Lumbar drainage was performed in all cases. No major complications were encountered. CONCLUSIONS: The endoscopic endonasal approach is safe and effective for the treatment of CSF rhinorrhoea. The 3D-FIESTA MR modality is superior to 3D-MPRAGE MR and HRCT in the depiction of the CSF fistula site. Due to its non-invasive and reliable properties, 3D-FIESTA MR should be the preferred preoperative examination for the patients with non-iatrogenic CSF rhinorrhoea.

Mechanism of inhibition of TLR4/NFκB/NLRP3 inflammatory pathway against AD based on the network pharmacology of Erjing Pills.

Alzheimer disease is an irreversible neurodegenerative disease, and its pathogenesis involves various mechanisms such as neuroinflammation and ß-amyloid deposition. Erjing Pills can inhibit neuroinflammation by inhibiting toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3; however, qualitative analysis of the material basis is lacking. Therefore, it is necessary to analyze and explore the material basis of network pharmacology research. This study employed a multifaceted approach, including drug-like screening, molecular docking, and bioinformatic analysis. Preliminary screening identified 59 drug ingredients in Erjing Pills that met the Absorption, Distribution, Metabolism, Excretion and Toxicity screening criteria. Among these, 7 ingredients, including diosgenin, exhibited superior binding properties compared with the positive drugs in molecular docking. Gene ontology annotation and pathway analysis revealed their involvement in crucial biological processes, such as hormone response, insulin resistance, and steroid hormone biosynthesis signaling pathways, which are known for their anti-inflammatory and cognitive enhancement effects. A meta-analysis of relevant literature corroborated the anti-inflammatory activities of diosgenin and 5 other ingredients. These 5 ingredients, with diosgenin as a prominent candidate, exert anti-inflammatory effects by targeting key components of the toll-like receptor 4/nuclear factor kappa-B/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein 3 inflammatory pathway, thereby presenting potential efficacy in the treatment of Alzheimer disease.

The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model.

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients' clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia. Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice. Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect. Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD's maximal therapeutic response, there existed a hysteresis. WDD's effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats. Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.

Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. METHODS: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. RESULTS: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CONCLUSIONS: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.