In vivo anti-hepatitis B activity of Artemisia argyi essential oil-loaded nanostructured lipid carriers. Study of its mechanism of action by network pharmacology and molecular docking.

BACKGROUND: Hepatitis B virus (HBV) infection remains a major global health burden, due to the increasing risk of complications, such as cirrhosis and hepatocellular carcinoma. Novel anti-HBV agents are critical required. Our previous study suggested that Artemisia argyi essential oil (AAEO) significantly inhibited the replication of HBV DNA and especially the secretion of hepatitis B antigen in vitro. PURPOSE: The aim of this study was to prepare AAEO loaded nanostructured lipid carriers (AAEO-NLCs) for the delivery of AAEO to the liver, investigated the therapeutic benefits of AAEO-NLCs against HBV in a duck HBV (DHBV) model and explored its potential mechanism. STUDY DESIGN AND METHODS: AAEO-NLCs were prepared by hot homogenization and ultrasonication method. The DHBV-infected ducks were treated with AAEO (4 mg/kg), AAEO-NLCs (0.8, 4, and 20 mg/kg of AAEO), and lamivudine (20 mg/kg) for 15 days. The DHBV DNA levels in the serum and liver were measured by quantitative Real-Time PCR. Pharmacokinetics and liver distribution were performed in rats after oral administration of AAEO-NLCs and AAEO suspension. The potential antiviral mechanism and active compounds of AAEO were investigated by network pharmacology and molecular docking. RESULTS: AAEO-NLCs markedly inhibited the replication of DHBV DNA in a dose-dependent manner and displayed a low virologic rebound following withdrawal the treatment in DHBV-infected ducks. Moreover, AAEO-NLCs led to a more pronounced reduction in viral DNA levels than AAEO suspension. Further investigations of pharmacokinetics and liver distribution in rats confirmed that NLCs improved the oral bioavailability and increased the liver exposure of AAEO. The potential mechanisms of AAEO against HBV explored by network pharmacology were associated with signaling pathways related to immune response, such as tumor necrosis factor, nuclear factor kappa B, and sphingolipid signaling pathways. Furthermore, a total of 16 potential targets were obtained, including prostaglandin-endoperoxide synthase-2 (PTGS2), caspase-3, progesterone receptor, etc. Compound-target docking results confirmed that four active compounds of AAEO had strong binding interactions with the active sites of PTGS2. CONCLUSIONS: AAEO-NLCs displayed potent anti-HBV activity with improved oral bioavailability and liver exposure of AAEO. Thus, it may be a potential therapeutic strategy for the treatment of HBV infection.

Development and assessment of machine learning models for predicting recurrence risk after endovascular treatment in patients with intracranial aneurysms.

Intracranial aneurysms (IAs) remain a major public health concern and endovascular treatment (EVT) has become a major tool for managing IAs. However, the recurrence rate of IAs after EVT is relatively high, which may lead to the risk for aneurysm re-rupture and re-bleed. Thus, we aimed to develop and assess prediction models based on machine learning (ML) algorithms to predict recurrence risk among patients with IAs after EVT in 6 months. Patient population included patients with IAs after EVT between January 2016 and August 2019 in Hunan Provincial People's Hospital, and an adaptive synthetic (ADASYN) sampling approach was applied for the entire imbalanced dataset. We developed five ML models and assessed the models. In addition, we used SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. A total of 425 IAs were enrolled into this study, and 66 (15.5%) of which recurred in 6 months. Among the five ML models, gradient boosting decision tree (GBDT) model performed best. The area under curve (AUC) of the GBDT model on the testing set was 0.842 (sensitivity: 81.2%; specificity: 70.4%). Our study firstly demonstrated that ML-based models can serve as a reliable tool for predicting recurrence risk in patients with IAs after EVT in 6 months, and the GBDT model showed the optimal prediction performance.

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/ß-Catenin Signaling Pathway.

The tumor metastasis is the major hurdle for the treatment of advanced hepatocellular carcinoma (HCC), due in part to the lack of effective systemic treatments. DEPDC1, a novel oncoantigen upregulated in HCC, is thought to be a molecular-target for novel therapeutic drugs. Artemisia argyi is a traditional Chinese medicine with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Artemisia argyi essential oil (AAEO) in suppressing metastasis of HCC by targeting DEPDC1. Assessment of AAEO cytotoxicity was performed by MTT assay. Anti-metastatic effects of AAEO were investigated in vitro using wound healing and transwell assays. The HepG2 cells were transduced with lentiviral vector containing luciferase (Luc). A metastasis model of nude mice was established by tail vein injection of HepG2-Luc cells. The nude mice were treated with AAEO (57.5, 115, and 230 mg/kg) or sorafenib (40 mg/kg). Metastasis of HCC cells was monitored via in vivo bioluminescence imaging. After treatment for 21 days, tissues were collected for histological examination and immunohistochemistry analysis. Gene and protein levels were determined by real-time quantitative PCR and western blotting. The results revealed that AAEO significantly inhibits the migration and invasion in vitro in a concentration-dependent manner. In vivo assays further confirmed that AAEO markedly inhibits HCC metastasis into lung, brain, and femur tissues and exhibits low toxicity. Our results suggested that AAEO significantly downregulates the mRNA and protein expression of DEPDC1. Also, AAEO attenuated Wnt/ß-catenin signaling through reduction of Wnt1 and ß-catenin production. Moreover, AAEO prevented epithelial-mesenchymal transition (EMT) by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that DEPDC1 promoted HCC migration and invasion via Wnt/ß-catenin signaling pathway and EMT. These results demonstrate that AAEO effectively inhibits HCC metastasis via attenuating Wnt/ß-catenin signaling and inhibiting EMT by suppressing DEPDC1 expression. Thus, AAEO likely acts as a novel inhibitor of the DEPDC1 dependent Wnt/ß-catenin signaling pathway.

Effects of 25-hydroxycholecalciferol supplementation in maternal diets on reproductive performance and the expression of genes that regulate lactation in sows.

One hundred Yorkshire × Landrace sows were randomly assigned to one of two dietary treatments (diet ND: 6,000 IU vitamin D3 /d feed; diet 25-D: 200 µg/day 25OHD3 feed). The experiment began on d 90 of gestation and continued until weaning on day 21 of lactation. In sows that received 25OHD3 , the growth rate of the piglets before weaning was significantly accelerated (0.266 kg/day, p < .05). Sow serum was collected after weaning, and those in the 25OHD3 group were found to have significantly higher serum calcium (CA) and phosphorus (PI) levels (p < .05). Interestingly, the oestrus cycle of sows fed 25OHD3 was significantly shortened (p < .05), the oestrus time was concentrated on the fifth day after weaning, and the piglets were born with a higher degree of uniformity (p < .05). Colostrum was collected on the day of delivery, and the colostrum of sows fed 25OHD3 contained higher milk fat content than the control group (p < .05). 25OHD3 supplementation increased the mRNA and protein expression of INSIG1 and SREBP1, which regulate milk fat synthesis, in the mammary gland of lactating sows (p < .05). In conclusion, 25OHD3 supplementation in maternal diets improved reproductive performance, milk fat content and the mRNA and protein levels of genes regulating milk fat synthesis in lactating sows.

Vitamin B6 Prevents Endothelial Dysfunction, Insulin Resistance, and Hepatic Lipid Accumulation in Apoe (-/-) Mice Fed with High-Fat Diet.

Backgrounds. VitB6 deficiency has been associated with a number of adverse health effects. However, the effects of VitB6 in metabolic syndrome are poorly understood. Methods. VitB6 (50 mg/kg/day) was given to Apoe (-/-) mice with hkdigh-fat diet (HFD) for 8 weeks. Endothelial dysfunction, insulin resistance, and hepatic lipid contents were determined. Results. VitB6 administration remarkably increased acetylcholine-induced endothelium-dependent relaxation and decreased random blood glucose level in Apoe (-/-) mice fed with HFD. In addition, VitB6 improved the tolerance of glucose and insulin, normalized the histopathology of liver, and reduced hepatic lipid accumulation but did not affect the liver functions. Clinical and biochemical analysis indicated that the levels of VitB6 were decreased in patients with fatty liver. Conclusions. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in Apoe (-/-) mice fed with HFD. Supplementation of VitB6 should be considered to prevent metabolic syndrome.

Risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children.

OBJECTIVES: The aim of this study was to explore the risk factors associated with failed sonographically guided saline hydrostatic intussusception reduction in children. METHODS: We retrospectively reviewed the medical records and sonograms of 288 cases of intussusception over a 3-year period. Logistic regression was used for the analysis of the clinical data (sex, age, duration of symptoms, and presence or absence of emesis or bloody stool) and sonographic features (initial location and intussusception length, presence or absence of free peritoneal fluid, and trapped fluid in the intussusception). RESULTS: The sex, age, and duration of symptoms showed no significant impact on the hydrostatic reducibility. The success rate became significantly lower for the intussusception cases with the presence of bloody stool, free peritoneal fluid, and trapped fluid in the intussusception (P < .05). The success rate was also lower when the intussusceptions were located in the left side of the abdomen (P < .05). For the above risk factors, the odds ratios from multivariate logistic regression analysis were 174.68 for initial intussusception location in the descending colon/rectum, 36.06 for the presence of peritoneal fluid, 13.22 for trapped fluid in the intussusception, and 9.27 for the presence of bloody stool. CONCLUSIONS: An initial intussusception location in the descending colon/rectum, the presence of peritoneal fluid, trapped fluid in the intussusception, and bloody stool are the most important risk factors for failure of sonographically guided saline hydrostatic intussusception reduction.