Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model.

BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS Serum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression. CONCLUSIONS The findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.

Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion).

BACKGROUND The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. MATERIAL AND METHODS Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. RESULTS Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. CONCLUSIONS GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

[Analysis on animal models of experimental hyperlipidemia].

Hyperlipidemia is a major risk factor for fatty liver, atherosclerosis, hyperviscosily, coronary artery disease and acute myocardial infarction. In recent years, the incidence of hyperlipidemia was gradually increased and showed younger trend. It has been a research hot point to study the etiology and pathogenesis of hyperlipidemia and develop a new drug reduced blood lipid. It is very important to prepare the animal model of hyperlipidemia for displaying the advantage of traditional Chinese medicine characteristic. However, the success of replicating animal model of hyperlipidemia is one of the key of research in experimental hyperlipidemia. The ideal animal model of hyperlipidemia should be similar to human disease, high repeatability, simple and high generalization. It will affect the reliability of the results and the accuracy of the whole experiment process to copy successfully animal models of hyperlipidemia. This review focused on the recent research progress on copying methods of animal models of experimental hyperlipidemia, which will provide reference and basis for the hypolipidemic developers who choose rationally and effectively replication methods of hyperlipidemia animal models.

[Comparison on polysaccharide content and PMP-HPLC fingerprints of polysaccharide in stems and leaves of Dendrobium officinale].

In order to provide scientific basics for exploitation and sufficient application of Dendrobium officinale leaves resources, the phenol-sulfuric acid method was applied to determine the polysaccharide content. The monosaccharides were derivated by PMP and the derivatives were identified by HPLC-DAD-ESI-MS(n) and the contents of mannose and glucose were determined simultaneously. Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2004A) was employed to generate the mean chromatogram and similarity analysis of the samples was carried out. The results demonstrated that polysaccharide content, monosaccharide compositions and composition ratio had an obvious difference between stems and leaves. The polysaccharide content of stems was higher than that of leaves. Monosaccharide composition in leaf was significantly different from that in stem. The polysaccharide from stems was composed of mannose and glucose, however the polysaccharide of leaves was acid heteropolysaccharide and was mainly composed of five monosaccharides, including mannose, galacturonic acid, glucose, galactose and arabinose. The similarity value of the 14 batches was above 0.9, indicating that similarity of fingerprints among different samples was high. The study can provide evidence for expanding the medicinal parts of D. officinale.

Development and validation of a clinically applicable deep learning strategy (HONORS) for pulmonary nodule classification at CT: A retrospective multicentre study.

PURPOSE: To propose a practical strategy for the clinical application of deep learning algorithm, i.e., Hierarchical-Ordered Network-ORiented Strategy (HONORS), and a new approach to pulmonary nodule classification in various clinical scenarios, i.e., Filter-Guided Pyramid NETwork (FGP-NET). MATERIALS AND METHODS: We developed and validated FGP-NET on a collection of 2106 pulmonary nodules on computed tomography images which combined screened and clinically detected nodules, and performed external test (n = 341). The area under the curves (AUCs) of FGP-NET were assessed. A comparison study with a group of 126 skilled radiologists was conducted. On top of FGP-NET, we built up our HONORS which was composed of two solutions. In the Human Free Solution, we used the high sensitivity operating point for screened nodules, but the high specificity operating point for clinically detected nodules. In the Human-Machine Coupling Solution, we used the Youden point. RESULTS: FGP-NET achieved AUCs of 0.969 and 0.847 for internal and external test. The AUCs of the subsets of the external test set ranged from 0.890 to 0.942. The average sensitivity and specificity of the 126 radiologists were 72.2 ±â€¯15.1 % and 71.7 ±â€¯15.5 %, respectively, while a higher sensitivity (93.3 %) but a relatively inferior specificity (64.0 %) were achieved by FGP-NET. HONORS-guided FGP-NET identified benign nodules with high sensitivity (sensitivity,95.5 %; specificity, 72.5 %) in the screened nodules, and identified malignant nodules with high specificity (sensitivity, 31.0 %; specificity, 97.5 %) in the clinically detected nodules. These nodules could be reliably diagnosed without any intervention from radiologists, via the Human Free Solution. The remaining ambiguous nodules were diagnosed with high performance, which however required manual confirmation by radiologists, via the Human-Machine Coupling Solution. CONCLUSIONS: FGP-NET performed comparably to skilled radiologists in terms of diagnosing pulmonary nodules. HONORS, due to its high performance, might reliably contribute a second opinion, aiding in optimizing the clinical workflow.

Diagnostic value and imaging features of multi-detector CT in lung adenocarcinoma with ground glass nodule patients.

This study investigated the application value and imaging features of multi-detector CT (MDCT) in the treatment of lung adenocarcinoma with ground glass nodules (GGN). The medical data of 168 patients with pulmonary GGN in Shengli Oilfield Central Hospital from January 2013 to June 2015 were analyzed. Patients with microinvasive adenocarcinoma and invasive adenocarcinoma were included in group A (invasive lung adenocarcinoma, n=98), while patients with atypical adenomatous hyperplasia and adenocarcinoma in situ were included in group B (pre-invasive lung adenocarcinoma, n=70). The imaging features of MDCT were compared. ROC curves of the size of nidus and the size of solid component were drawn for the diagnosis of invasive lung adenocarcinoma. Logistic multivariate regression analysis was used to analyze the risk factors that affected invasive lung adenocarcinoma. There were significant differences in nidus, burr, and lobes of the patients between groups A and B. The size of nidus and the size of solid component of the patients in group A were significantly higher than those of the patients in group B. The AUCs of the size of the nidus and the size of the solid component of the invasive lung adenocarcinoma were 0.891 and 0.902, respectively. The AUC of the combined diagnosis was 0.984. Size of the nidus, size of the solid component, nature of the lesion, burr, and lobes were all risk factors for invasive lung adenocarcinoma. In patients with GGN, size of the nidus and size of the solid component can be used as excellent diagnostic parameters for invasive lung adenocarcinoma, and nidus size (≥9.8 mm), size of the solid component (≥0.9 mm), the mixed GGN nature of the nidus, burr and lobes can distinguish invasive lung adenocarcinoma and pre-invasive lesions.

Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis.

BACKGROUND: Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive. AIM: To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms. METHODS: In the present study, the Sprague-Dawley rats were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis. RESULTS: Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin. CONCLUSION: In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.

Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury.

Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure. In addition, DMY dramatically attenuated the alcohol-triggered elevation of the level of inflammatory cytokines and partially recovered hepatic pathological changes. Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1 in the liver and simultaneously ameliorated disordered nuclear localization of NF-κB and Nrf2 to exert its hepatoprotective effects. Further mechanistic exploration suggested that DMY activated Nrf2, possibly mediated through the autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2 demonstrated that the p62 upregulation caused by DMY contributes to a positive feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and the inflammatory response in the pathological progression of ALD.

Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats.

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.

Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High-Fat High-Cholesterol Diet in Rats.

The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 1 (CXCL1), were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

Therapeutic effects of 5-fluorouracil sustained-release particles in 81 malignant pericardial effusion patients.

This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU) sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE). A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01). The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.

Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells.

Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.