Graph Neural Network-Guided Contrastive Learning for Sequential Recommendation.

Sequential recommendation uses contrastive learning to randomly augment user sequences and alleviate the data sparsity problem. However, there is no guarantee that the augmented positive or negative views remain semantically similar. To address this issue, we propose graph neural network-guided contrastive learning for sequential recommendation (GC4SRec). The guided process employs graph neural networks to obtain user embeddings, an encoder to determine the importance score of each item, and various data augmentation methods to construct a contrast view based on the importance score. Experimental validation is conducted on three publicly available datasets, and the experimental results demonstrate that GC4SRec improves the hit rate and normalized discounted cumulative gain metrics by 1.4% and 1.7%, respectively. The model can enhance recommendation performance and mitigate the data sparsity problem.

HSP90-Mediates Liraglutide Preconditioning-Induced Cardioprotection by Inhibiting C5a and NF-κB.

OBJECTIVE: We previously showed that HSP90 is involved in postconditioning cardioprotection by inhibiting complement C5a. Here, we investigated whether HSP90-mediated C5a/NF-κB inhibition is responsible for the cardioprotection conferred by liraglutide. METHODS: Rat hearts underwent a 30 min occlusion of the anterior descending coronary artery, after which reperfusion was performed for 2 h. A total of 100 rats were randomly assigned to the following groups: ischemia/reperfusion (I/R), sham, liraglutide preconditioning (LP, liraglutide, 0.18 mg/kg, intravenously, 12 h before ischemia), HSP90 inhibitor geldanamycin (GA, 1 mg/kg, intraperitoneally, 30 min before ischemia) plus LP, and C5a receptor antagonist PMX53 (1 mg/kg, intravenously, 30 min before ischemia) plus LP. Cardiac injury, C5a/NF-κB activation, and inflammation were investigated. RESULTS: LP significantly attenuated I/R-induced cardiomyocyte apoptosis, infarct size, and secretion of creatine kinase-MB, lactate dehydrogenase and cardiac troponin I. These effects were complemented by decreased C5a levels, nuclear factor (NF)-κB signaling, inflammatory cytokine expression, and increased HSP90 levels. GA, an HSP90 inhibitor, promotes C5a activation, NF-κB signaling, and inflammation and suppresses cardioprotection by LP. By contrast, PMX53, a C5a inhibitor, suppressed C5a activation, NF-κB signaling, and inflammation, and enhanced cardioprotection by LP. CONCLUSION: HSP90 markedly contributes to LP cardioprotection by inhibiting inflammatory responsesand C5a/NF-κB signaling , ultimately attenuating I/R-induced cardiomyocyte apoptosis by suppressing the proapoptotic factor Bax, and inducing the anti-apoptotic factor Bcl2.

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB.

BACKGROUND: Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. METHODS: Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. RESULTS: MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1ß, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. CONCLUSION: HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

Role of HSP90 in suppressing TLR4-mediated inflammation in ischemic postconditioning.

BACKGROUND: Myocardial inflammation mediated by toll-like receptor 4 (TLR4) plays an active role in myocardial ischemia/reperfusion (I/R) injury. Studies show that heat shock protein 90 (HSP90) is involved in ischemic postconditioning (IPostC) cardioprotection. This study investigates the roles of TLR4 and HSP90 in IPostC. METHODS: Rats were subjected to 30 min ischemia, then 2 h reperfusion. IPostC was applied by three cycles of 30 s reperfusion, then 30 s reocclusion at reperfusion onset. Sixty rats were randomly divided into four groups: sham, I/R, IPostC, and geldanamycin (GA, HSP90 inhibitor, 1 mg/kg) plus IPostC (IPostC + GA). RESULTS: IPostC significantly reduced I/R-induced infarct size (40.2±2.1% versus 28.4±2.4%; P < 0.05); the release of cardiac Troponin T, creatine kinase-MB, and lactate dehydrogenase (191.5±3.1 versus 140.6±3.3 pg/ml, 3394.6±132.7 versus 2880.7±125.5 pg/ml, 2686.2±98.6 versus 1848.8±90.1 pg/ml, respectively; P < 0.05); and cardiomyocyte apoptosis (40.3±2.2% versus 27.0±1.6%; P < 0.05). Further, local and circulating IL-1ß, IL-6, TNF-α, and ICAM-1 levels decreased; TLR4 expression and nuclear factor-KB (NF-κB) signaling decreased; and cardiac HSP90 expression increased. Blocking HSP90 function with GA inhibited IPostC protection and anti-inflammation, suggesting that IPostC has a HSP90-dependent anti-inflammatory effect. CONCLUSION: HSP90 may play a role in IPostC-mediated cardioprotection by inhibiting TLR4 activation, local and systemic inflammation, and NF-kB signaling.

Ischemic postconditioning attenuates the inflammatory response in ischemia/reperfusion myocardium by upregulating miR­499 and inhibiting TLR2 activation.

Toll-like receptor 2 (TLR2)-mediated myocardial inflammation serves an important role in promoting myocardial ischemic/reperfusion (I/R) injury. Previous studies have shown that miR­499 is critical for cardioprotection after ischemic postconditioning (IPostC). Therefore, the present study evaluated the protective effect of IPostC on the myocardium by inhibiting TLR2, and also assessed the involvement of microRNA (miR)­499. Rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The IPostC was 3 cycles of 30 sec of reperfusion and 30 sec of re­occlusion prior to reperfusion. In total, 90 rats were randomly divided into six groups (n=15 per group): Sham; I/R; IPostC; miR­499 negative control adeno­associated virus (AAV) vectors + IPostC; miR­499 inhibitor AAV vectors + IPostC; and miR­499 mimic AAV vectors + IPostC. It was identified that IPostC significantly decreased the I/R­induced cardiomyocyte apoptotic index (29.4±2.03% in IPostC vs. 42.64±2.27% in I/R; P<0.05) and myocardial infarct size (48.53±2.49% in IPostC vs. 66.52±3.1% in I/R; P<0.05). Moreover, these beneficial effects were accompanied by increased miR­499 expression levels (as demonstrated by reverse transcription­quantitative PCR) in the myocardial tissue and decreased TLR2, protein kinase C (PKC), interleukin (IL)­1ß and IL­6 expression levels (as demonstrated by western blotting and ELISA) in the myocardium and serum. The results indicated that IPostC + miR­499 mimics significantly inhibited inflammation and the PKC signaling pathway and enhanced the anti­inflammatory and anti­apoptotic effects of IPostC. However, IPostC + miR­499 inhibitors had the opposite effect. Therefore, it was speculated that IPostC may have a miR­499­dependent cardioprotective effect. The present results suggested that miR­499 may be involved in IPostC­mediated ischemic cardioprotection, which may occur via local and systemic TLR2 inhibition, subsequent inhibition of the PKC signaling pathway and a decrease in inflammatory cytokine release, including IL­1ß and IL­6. Moreover, these effects will ultimately lead to a decrease in the myocardial apoptotic index and myocardial infarct size via the induction of the anti­apoptotic protein Bcl­2, and inhibition of the pro­apoptotic protein Bax in myocardium.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation.

PURPOSE: To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). METHODS: The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß and c-Jun N-terminal kinase (JNK) were assessed. RESULTS: Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1ß, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. CONCLUSION: HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Assessment of persistent organic pollutants (POPs) in sediments of the Eastern Indian Ocean.

The concentrations of persistent organic pollutants (POPs) in sediments from the Eastern Indian Ocean were analyzed by GC-MS/MS to explore the status of contamination, distribution and their potential sources and risk. The average (±SD) concentrations of total polycyclic aromatic hydrocarbons (∑16PAHs), polybrominated diphenyl ethers (∑10PBDEs), dechlorane plus (∑2DP), organochlorine pesticides (∑22OCPs) and polychlorinated biphenyls (∑31PCBs) in sediments were 79,900 ± 31,400, 173 ± 62, 42 ± 24, 1051 ± 305 and 147 ± 24 pg g-1 dw (or 11,200 ± 7200, 28 ± 26, 6 ± 6, 168 ± 121 and 24 ± 17 ng g-1 organic carbon), respectively. The concentrations of POPs in sediments were generally at low to median levels compared to those recorded in other ocean sediments. Composition analyses suggest that PAHs originate from both petrogenic and pyrogenic sources, while dichlorodiphenyltrichloroethane (DDT) mainly comes from technical-DDT, hexachlorocyclohexane (HCH) from lindane, and chlordane from fresh inputs. The risk assessments show that the targeted chemicals except for chlordane and naphthalene in sediments do not pose potential biological effects to the organisms in the Eastern Indian Ocean. The present study contributes to the very rare data on PAHs, PBDEs, DP, OCPs and PCBs in the vast deep-ocean and will deepen our knowledge of the fate of POPs in ocean environments.

Identification of protein targets for the antidepressant effects of Kai-Xin-San in Chinese medicine using isobaric tags for relative and absolute quantitation.

Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital (approval No. X5-2016-07) on March 5, 2016.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

AG36 Inhibits Human Breast Cancer Cells Proliferation by Promotion of Apoptosis In vitro and In vivo.

AG36 is the biotransformation product of triterpenoid saponin from Ardisia gigantifolia stapf. In this study, the antitumor activity and underlying molecular mechanisms of AG36 against human breast MCF-7, MDA-MB-231, and SK-BR-3 cancer cells were investigated. AG36 inhibited the viability of MCF-7, MDA-MB-231, and SK-BR-3 cells in a dose and time-dependent manner, with an IC50 of approximately 0.73, 18.1, and 23.4 µM at 48 h, respectively. AG36 obviously induced apoptosis and G2/M arrest of all the three breast cancer cells. Moreover, AG36 decreased the protein expression of cycle regulatory proteins cyclin B1 or cyclin D1. In MCF-7 and MDA-MB-231 cells, AG36 strongly increased the cleaved caspase-3 and -8 protein expressions, while in SK-BR-3 cells, AG36 only increased the protein expression of cleaved caspase-3. In all the three breast cancer cells, the ratio of Bax/Bcl-2 and cytosolic cytochrome c content increased significantly compared with control group. The death receptor-related proteins Fas/FasL, TNFR1, and DR5 were detected by Western blot, it showed that different breast cancer cells activated the death receptor-mediated extrinsic caspase-8 pathway through different receptors. In addition, the caspase-8 inhibitor z-IETD-fmk could significantly block AG36-triggered MCF-7 cells apoptosis. The in vivo studies showed that AG36 significantly inhibited the growth of MCF-7 xenograft tumors in BALB/c nude mice comparing with control. In conclusion, AG36 inhibited MCF-7, MDA-MB-231, and SK-BR-3 cells proliferation by the intrinsic mitochondrial and the extrinsic death receptor pathways and AG36 might be a potential breast cancer therapeutic agent.

Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways.

Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3ß (GSK3ß) and pGSK3ß are associated with the antidepressive effect of KXS. In total, 24 male Wistar rats were randomly divided into three groups, including control (n=8, no treatment), induced with chronic unpredictable mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for cell survival and proliferation assays. In KXS rats, increased protein expression levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the hippocampus and prefrontal cortex, compared with the CMS model group. Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3ß were also detected in the hippocampus and prefrontal cortex of KXS-treated rats compared with CMS model rats and in primary hippocampal neuronal cells treated with KXS. These results suggest that pCREB and upstream components, including TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect induced by KXS. Further studies are required to confirm these findings.

UPLC-Q-TOF-MS(E) analysis of the constituents of Ding-Zhi-Xiao-Wan, a traditional Chinese antidepressant, in normal and depressive rats.

Ding-Zhi-Xiao-Wan (DZXW) is a traditional Chinese medicine widely used for treating depression. To clarify the bioactive constituents of DZXW, a new rapid ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS(E)) method was established in this study, with the whole extract of the formula separated into multiple components to facilitate the analytical process. In total, 97 compounds were detected and 88 were identified in DZXW. Based on their exact masses, fragmentation characteristics, and retention times, 85 of the 88 compounds were confirmed either conclusively or tentatively, and three potentially novel compounds were identified. In addition, following a three-day oral administration of DZXW, 60 and 28 compounds were observed in the plasma of normal and depressive rats, respectively. Finally, by combining our data with pharmacological information, 10 compounds were predicted as the likely bioactive constituents of DZXW as an antidepressant agent. Our approach provided a rapid method for characterising the chemical constituents of DZXW, and we were the first to screen for bioactive indexes in the plasma of depressive rats. Furthermore, our results provide useful chemical information that could be employed for further study of the pharmacodynamic material basis of DZXW's antidepressant effects.

[Identification of the metabolites of Dingzhi Xiaowan extract in depressive rat plasma, urine, feces and bile after intragastric administration].

Dingzhi Xiaowan is a widely used traditional Chinese medicine in treating depression, which is a similar formula of Kaixinsan. In this research, a rapid ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method was established to analyze the metabolites of Dingzhi Xiaowan in depressive model rat plasma, bile, urine and feces. After we established Chronic unpredictable mild stress (CUMS) model rats and orally administrated Dingzhi Xiaowan, rat plasma, bile, urine and feces samples were collected and prepared. Using Waters Cortects UPLC C18 column (2.1 mm x 50 mm, 1.6 µm), acetonitrile-0.1% formic acid mobile phase gradient, these samples were analyzed and 33 metabolites of nine bioactive compounds were detected and tentatively identified by Metabolynx. Among the 33 metabolites, three metabolites were identified from plasma sample, three came from bile sample, and 27 metabolites were identified from urine and feces samples. This approach provided a rapid method for characterizing the metabolites of Dingzhi Xiaowan and gave the truly active structures and the action mechanism of their antidepressant effects.

Efficacy and safety of sorafenib for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. METHODS: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. RESULTS: Results reported from 6 RCTs involving 2,748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96-1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. CONCLUSIONS: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

Two new isoflavone glycosides from the vine stem of Millettia dielsiana.

Two new isoflavone glycosides, millesianins F (1) and G (2), along with 11 known ones (3-13) have been isolated from the n-butanol extract of the vine stems of Millettia dielsiana Harms. The structures of 1 and 2 were established as cladrastin 7-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranoside (1) and fujikinetin 7-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranoside (2) by means of spectroscopic analysis and chemical methods. Some isolates (compounds 1, 3, 4, 5, 6, and 11) were tested for their effects on the proliferation of hematopoietic progenitor cell, and the preliminary results showed that all of investigated compounds had moderate activities but not in dose-dependent manners.

[Effect of oligosaccharide esters and polygalaxanthone Ill from Polygala tenuifolia willd towards cytochrome P450].

Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.

Chemical constituents from the leaves of Aglaia odorata.

A new dammarane triterpene, 3-acetoxy aglinin C (1), and a new aglain, 10-oxo-aglaxiflorin D (2), along with five known compounds, 3-7, were isolated from the leaves of Aglaia odorata using chromatographic methods. The structures of 1 and 2 were determined on the basis of spectroscopic analyses. Bioactivities of 1-7 against AGZY 83-a (human lung cancer cell line) and SMMC-7721 (human liver cancer cell line) cells were determined.

Perfusion heterogeneity in breast tumors for assessment of angiogenesis.

OBJECTIVES: The purpose of this study was to investigate the perfusion heterogeneity of malignant and benign breast tumors and assay their vascular architecture changes and molecular expression, thereby evaluating the relevance between imaging and histologic characteristics of angiogenesis. METHODS: Real-time grayscale contrast-enhanced sonography was performed in 310 women with 317 breast tumors. The enhancement patterns and perfusion parameters for malignant and benign tumors were analyzed by contrast-enhanced sonography with microvascular imaging and quantitative time-intensity curve analysis. Structural characteristics were observed by light and electron microscopy. The microvessel density, vascular endothelial growth factor (VEGF) expression, and human kinase insert domain-containing receptor (KDR) expression for all tumors were assessed by immunohistochemical staining of CD31, KDR, and VEGF. RESULTS: Surgical pathologic analysis showed 163 malignant and 154 benign tumors. Significant morphologic differences, including perfusion defects, vessel distortion, vessel dilatation, and heterogeneous enhancement, were observed between the malignant and benign groups (P < .05). The mean perfusion parameters (peak intensity, ascending slope, area under the curve, and wash-out time) were greater in the malignant tumors (P < .05). There were significant differences in the peak intensity, ascending slope, area under the curve, and wash-out time between peripheral and central regions of the malignant tumors (P < .05) but none in the benign tumors. Vessels had various morphologic and distributional characteristics in the peripheral and central regions of the malignant tumors. The microvessel density and VEGF and KDR expression were significantly higher in the malignant group (P < .05), especially in the peripheral regions. CONCLUSIONS: Perfusion heterogeneity was closely associated with the tumor microvascular architecture and molecular expression. Perfusion features, especially regional morphologic and hemodynamic features, can provide valuable information for differentiating malignant from benign breast tumors.

Antidepressant effects of the extract YZ-50 from Polygala tenuifolia in chronic mild stress treated rats and its possible mechanisms.

YZ-50 is an active fraction obtained from the root of Polygala tenuifolia Willd. (Polygalaceae) extract and it has been reported previously to exert beneficial effects on mental health in depressed sufferers, however, its mechanism of action remains unresolved. This study utilized the chronic mild stress (CMS) model of depression in Sprague-Dawley rats to evaluate the effects of YZ-50 on depressive behaviors. Furthermore, we tested the hypothesis that the capacity of YZ-50 to reverse the harmful effects of CMS is relative to the hypothalamo-pituitary-adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Repeated administration of YZ-50 for 28 days at the doses of 140 and 280 mg/kg in CMS, YZ-50 reversed the CMS-induced changes in sucrose consumption, plasma corticosterone levels and open field activity. In addition, CMS significantly decreased hippocampal BDNF mRNA levels. However, YZ-50 counteracted a decrease in hippocampal BDNF mRNA caused by CMS. In conclusion, YZ-50 reversed the harmful effects of CMS on mood and behaviors in rats and it possesses an antidepressant property that is at least in part mediated by the neuroendocrine and neuropropective systems, and it is likely that the HPA system plays an important role in this process.

Antioxidant activity of oligosaccharide ester extracted from Polygala tenuifolia roots in senescence-accelerated mice.

The constituents of the ethanol extract from the root of Polygala tenuifolia Willd. (Polygalaceae) were investigated for antioxidant activity in senescence-accelerated mice. Consequently, two relevant samples were obtained, a fraction separated by macroporous resin (YZ-OE), and a major pure crystal of 3,6'-disinapoyl sucrose (DISS). Based on HPLC-ESI-MS analysis, the most constituents in the YZ-OE fraction from the extract of P. tenuifolia were oligosaccharide esters. The antioxidant activities of these two samples were evaluated using the accelerated senescence-prone, short-lived mice (SAMP) in vivo. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased significantly in SAMP mice fed oligosaccharide esters (YZ-OE 50 mg/kg) and its constituents (DISS 50 mg/kg). However, the content of malondialdehyde (MDA) was increased in the blood and liver of SAMP mice. But when given YZ-OE, it could be decreased, by 44.3% and 47.5%, respectively, compared with the SAMP model. Results from the analyses indicated that the oligosaccharide esters (YZ-OE) from roots of P. tenuifolia had a high in vivo antioxidant activity.