Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

Quercetin prevents bone loss in hindlimb suspension mice via stanniocalcin 1-mediated inhibition of osteoclastogenesis.

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

Effects of miR-503-5p on apoptosis of human pulmonary microvascular endothelial cells in simulated microgravity.

Recent studies have shown that microRNA (miRNAs) can play important roles in the regulation of endothelial cell (EC) function. However, the expression profile of miRNAs and their effects on the apoptosis of ECs under microgravity conditions remains unclear. In this study, the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) under simulated microgravity was identified by Annexin V and propidium iodide double staining and transmission electron microscopy. miRNA microarray assay was used to screen the differentially expressed miRNAs in HPMECs under simulated microgravity, and eight differentially expressed miRNAs were identified. Specifically, miR-503-5p, which was found to be most significantly upregulated in both microarray and quantitative reverse-transcription polymerase chain reaction assays, was selected for further functional investigation. Overexpression of miR-503-5p induced apoptosis of HPMECs under normal gravity and aggravated the negative effects of simulated microgravity on HPMECs. Furthermore, silencing of miR-503-5p expression effectively attenuated the negative effects of simulated microgravity on HPMECs. Further experiments showed that the mRNA and protein expression of anti-apoptotic factor B-cell lymphoma-2 (Bcl-2), which has been confirmed as a direct target of miR-503-5p, was inhibited by the upregulation of miR-503-5p and increased by the downregulation of miR-503-5p. Taken together, our findings demonstrate, for the first time, that miR-503-5p can induce apoptosis of HPMECs under simulated microgravity through, at least in part, inhibiting the expression of Bcl-2.

Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Our previous studies have proven that Trillium tschonoskii Maxim. (TTM), a traditional Chinese medicine, possesses potent anti-tumor effect. However, the detailed components and molecular mechanism of TTM in anti-NSCLC are still unknown. In the present experiment, polyphyllin VI (PPVI) was successfully isolated from TTM with guidance of the anti-proliferative effect in A549 cells, and the cell death of PPVI treated A549 and H1299 cells was closely linked with the increased intracellular ROS levels. In addition, PPVI induced apoptosis by promoting the protein expression of Bax/Bcl2, caspase-3 and caspase-9, and activated autophagy by improving LC3 II conversion and GFP-LC3 puncta formation in A549 and H1299 cells. The mechanism study found that the activity of mTOR which regulates cell growth, proliferation and autophagy was significantly suppressed by PPVI. Accordingly, the PI3K/AKT and MEK/ERK pathways positively regulating mTOR were inhibited, and AMPK negatively regulating mTOR was activated. In addition, the downstream of mTOR, ULK1 at Ser 757 which downregulates autophagy was inhibited by PPVI. The apoptotic cell death induced by PPVI was confirmed, and it was significantly suppressed by the overexpression of AKT, ERK and mTOR, and the induced autophagic cell death which was depended on the Atg7 was decreased by the inhibitors, such as LY294002 (LY), Bafilomycin A1 (Baf), Compound C (CC) and SBI-0206965 (SBI). Furthermore, the mTOR signaling pathway was regulated by the increased ROS as the initial signal in A549 and H1299 cells. Finally, the anti-tumor growth activity of PPVI in vivo was validated in A549 bearing athymic nude mice. Taken together, our data have firstly demonstrated that PPVI is the main component in TTM that exerts the anti-proliferative effect by inducing apoptotic and autophagic cell death in NSCLC via the ROS-triggered mTOR signaling pathway, and PPVI may be a promising candidate for the treatment of NSCLC in future.

Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats.

BACKGROUND: Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI. RESULTS: CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats. CONCLUSION: CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.

Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer.

Bone is one of the prone metastatic sites of lung cancer. Osteoclast plays an important role in bone resorption and the growth of bone metastases of lung cancer. In order to treat bone metastases of lung cancer, we reported a docetaxel (DTX)-loaded nanoparticle, DTX@AHP, which could target dually at osteoclasts and bone metastatic tumor cells. The in vitro drug release from DTX@AHP exhibited pH and redox responsive characteristics. DTX@AHP displayed high binding affinity with bone matrix. In addition, DTX@AHP significantly inhibited the differentiation of RAW264.7 into osteoclast and effectively inhibited the proliferation of osteoclasts and tumor cells in in-vitro 3D bone metastases model of lung cancer. DTX@AHP could accumulate in bone metastases sites in vivo. Consequently, DTX@AHP not only markedly inhibited the growth of bone metastases of lung cancer but also reduced osteolysis in tumor-bearing mice. DTX@AHP exhibited great potential in the treatment of bone metastases of lung cancer.

Mitochondria-targeted antioxidant delivery for precise treatment of myocardial ischemia-reperfusion injury through a multistage continuous targeted strategy.

Efficient delivery of antioxidant drugs into mitochondria of ischemic cardiomyocytes where reactive oxygen species largely induced is a major challenge for precise treatment of myocardial ischemia-reperfusion injury. Herein, we report a smart dual-shell polymeric nanoparticle, MCTD-NPs, which utilizes multistage continuous targeted strategy to deliver reactive oxygen species scavenger specifically to mitochondria of ischemic cardiomyocytes upon systemic administration. In vitro experiments indicated that the intracellular uptake of MCTD-NPs was specifically enhanced in hypoxia reoxygenation injured H9c2 cells. MCTD-NPs selectively delivered resveratrol to mitochondria of hypoxia reoxygenation injured H9c2 cells. In addition, MCTD-NPs increased the viability of H/R injured H9c2 cell through eliminating mitochondrial ROS, decreasing mPTP opening and blocking mitochondria-dependent apoptotic pathway. In vivo experiments revealed that MCTD-NPs increased the distribution of resveratrol in the ischemic myocardium and subsequently reduced infarct size in MI/RI rats. These results demonstrated a novel platform for specific delivery of antioxidant to mitochondria to treat MI/RI.

Charge Reversible and Mitochondria/Nucleus Dual Target Lipid Hybrid Nanoparticles To Enhance Antitumor Activity of Doxorubicin.

The experiment aims to increase antitumor activity while decreasing the systemic toxicity of doxorubicin (DOX). Charge reversible and mitochondria/nucleus dual target lipid hybrid nanoparticles (LNPs) was prepared. The in vitro experimental results indicated that LNPs released more amount of DOX in acidic environment and delivered more amount of DOX to the mitochondria and nucleus of tumor cells than did free DOX, which resulted in the reduction of mitochondrial membrane potential and the enhancement of cytotoxicity of LNPs on tumor cells. Furthermore, the in vivo experimental results indicated that LNPs delivered more DOX to tumor tissue and significantly prolonged the retention time of DOX in tumor tissue as compared with free DOX, which consequently resulted in the high antitumor activity and low systemic toxicity of LNPs on tumor-bearing nude mice. The above results indicated that charge reversible mitochondria/nucleus dual targeted lipid hybrid nanoparticles greatly enhanced therapeutic efficacy of DOX for treating lung cancer.

The enhancement of siPLK1 penetration across BBB and its anti glioblastoma activity in vivo by magnet and transferrin co-modified nanoparticle.

In order to enhance the penetration of small interference RNA against the polo-like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf) modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1 significantly inhibited the growth of U87 glioblastoma spheroids and markedly increased the BBB penetration efficiency of siPLK1 with the application of external magnetic field in in-vitro BBB model. The in vivo experiments indicated that siPLK1 selectively accumulated in the brain tissue, and markedly reduced tumor volume and prolonged the survival time of GBM-bearing mice after Tf-PEG-PLL/MNP@siPLK1 was injected to GBM-bearing mice via tail vein. The above data indicated that magnet and transferrin co-modified nanoparticle enhanced siPLK1 penetration across BBB and increased its anti GBM activity in vivo.

Advances in paper-based sample pretreatment for point-of-care testing.

In recent years, paper-based point-of-care testing (POCT) has been widely used in medical diagnostics, food safety and environmental monitoring. However, a high-cost, time-consuming and equipment-dependent sample pretreatment technique is generally required for raw sample processing, which are impractical for low-resource and disease-endemic areas. Therefore, there is an escalating demand for a cost-effective, simple and portable pretreatment technique, to be coupled with the commonly used paper-based assay (e.g. lateral flow assay) in POCT. In this review, we focus on the importance of using paper as a platform for sample pretreatment. We firstly discuss the beneficial use of paper for sample pretreatment, including sample collection and storage, separation, extraction, and concentration. We highlight the working principle and fabrication of each sample pretreatment device, the existing challenges and the future perspectives for developing paper-based sample pretreatment technique.

Mitochondria and Nucleus Dual Delivery System To Overcome DOX Resistance.

Doxorubicin (DOX) is a broad-spectrum chemotherapy drug to treat tumors. However, severe side effects and development of DOX resistance hinder its clinical application. In order to overcome DOX resistance, DOX/TPP-DOX@Pasp-hyd-PEG-FA micelles were prepared by using newly synthesized comb-like amphiphilic material Pasp-hyd-PEG-FA. Drug released in vitro from micelles showed a pH-dependent manner. DOX/TPP-DOX@Pasp-hyd-PEG-FA induced more apoptosis in KB cell and MCF-7/ADR cell than DOX@Pasp-hyd-PEG-FA. Confocal laser scanning microscopy experiment indicated that DOX/TPP-DOX@Pasp-hyd-PEG-FA delivered TPP-DOX and DOX to the nucleus and mitochondria of the tumor cell simultaneously. Thus, DOX/TPP-DOX@Pasp-hyd-PEG-FA could significantly damage the mitochondrial membrane potential. DOX/TPP-DOX@Pasp-hyd-PEG-FA markedly shrinked the tumor volume in tumor-bearing nude mice grafted with MCF-7/ADR cell as compared with the same dose of free DOX. DOX was mainly accumulated in tumor tissue after DOX/TPP-DOX@Pasp-hyd-PEG-FA was injected to tumor-bearing nude mice by tail vein. After free DOX was injected to tumor-bearing nude mice by tail vein, DOX widely distributed through the whole body. Therefore, mitochondria and nucleus dual delivery system has potential in overcoming DOX resistance.

Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.

Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity.

As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino)ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity.

Risk/benefit profile of panitumumab-based therapy in patients with metastatic colorectal cancer: evidence from five randomized controlled trials.

This study aims to evaluate the risk and benefit profiles of panitumumab-based therapy (PBT) in patients with metastatic colorectal cancer (mCRC). Relevant randomized controlled trials were identified by searching PubMed, Medline, EMBASE and Cochrane Library. Data on progression-free survival (PFS), overall survival (OS), all grade and severe (grade ≥3) adverse events were extracted and pooled to calculate hazard ratios (HRs) and risk ratios (RRs) with 95 % confidence intervals (CIs). Number needed to treat (NNT) for PFS and number needed to harm (NNH) for significantly changed toxicities were calculated. A total of 4,155 patients were included in the analysis. PBT significantly improved PFS (HRrandom = 0.66, 95 % CI = 0.45-0.95) but not OS (HRfixed = 0.93, 95 % CI = 0.83-1.04) when used in the subsequent-line setting. The effect on PFS was more evident in patients with wild-type KRAS (HRrandom = 0.64, 95 % CI = 0.47-0.87) and the NNT for PFS is 11 to 23at 1 year. PBT did not benefit patients when used in the first-line setting. In addition, PBT significantly increased the risk of skin toxicity, infections, diarrhea, dehydration, mucositis, hypokalemia, fatigue, hypomagnesemia, pulmonary embolism and paronychia. The NNHs for skin toxicity, diarrhea, infection, hypokalemia and mucositis are less than 23. In conclusion, when used in the subsequent-line setting, PBT can improve the disease progression, especially in mCRC patients with wild-type KRAS. Regarding the adverse events associated with the PBT, close monitoring and necessary preparations are recommended during the therapy.

Combination of 2-methoxy-3-phenylsulfonylaminobenzamide and 2-aminobenzothiazole to discover novel anticancer agents.

The fragment of 2-substituted-3-sulfonylaminobenzamide has been proposed to replace the fragment of 2-substituted-3-sulfonylaminopyridine in PI3K and mTOR dual inhibitors to design novel anticancer agents based on bioisostere. The combination of the fragment of 2-substituted-3-sulfonylaminobenzamide with the fragment of 2-aminobenzothiazole or 2-aminothiazolo[5,4-b]pyridine, or 2-amino[1,2,4]triazolo[1,5-a]pyridine produced the novel structures of anticancer agents. As a result, nineteen target compounds were synthesized and characterized. Their antiproliferative activities in vitro were evaluated via MTT assay against four human cancer cell lines including HCT-116, A549, MCF-7 and U-87 MG. The SAR of target compounds was preliminarily discussed. Compound 1g with potent antiproliferative activity was examined for its effect on the AKT and p-AKT(473). The anticancer effect of 1g was evaluated in established nude mice HCT-116 xenograft model. The results suggested that compound 1g can block PI3K/AKT/mTOR pathway and significantly inhibit tumor growth. These findings strongly support our assumption that the fragment of benzamide can replace the pyridine ring in some PI3K and mTOR dual inhibitor to design novel anticancer agents.

[Synthesis and antifatigue activities of new benzamide derivatives].

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

[Chemical constituents of leaf of Eucommia ulmoides].

Ten compounds were isolated from the leaf of Eucommia ulmoides by means of recrystallization and chromatographic techniques such as D-101 macroporous resin, MCI resin, ODS gel, Sephadex LH-20 and Rp-HPLC. Their structures were identified by NMR spectral analyses as kaempferide 3-O-beta-D-glucoside (1), quercetin-3-O-beta-D-glucoside (2), quercetin (3), quercetin-3-O-beta-D-xylosyl-(1-->2)-beta-D-galactoside (4), kaempferol-3-O-alpha-L-rhamnosyl-(1-->6)-beta-D-glucoside (5), (2S,3S)-taxifolin 3-O-beta-D-glucoside (6) ,4-hydroxy cinnamic acid (7), (+)-cycloolivil (8), pinoresinol beta-D-glucoside (9), squalene (10). Among them compounds 1,5-7,10 were isolated from the Eucommia genus for the first time. In the DPPH free radical scavenging assay, compound 2 exhibited significant activity (IC50 13.7 micromol x L(-1)), compared with vitamin C (IC50 59.9 micromol x L(-1)); compounds 1, 3 and 9 showed moderate activity (IC50 161,137, 214 micromol x L(-1)), compared with 2,6-di-tert-butyl-4-methylphenol (IC50 236 micromol x L(-1)); compound 4 and 6 showed weak activity (IC50 264, 299 micromol x L(-1)).

[Characteristics of inorganic elements in Panacis Majoris Rhizoma and relationship with its Daodi habitat].

OBJECTIVE: To investigate the Daodi habitat of Panacis Majoris Rhizoma by analyzing the characteristics of inorganic elements in Panacis Majoris Rhizoma from different habitats. METHODS: The contents of inorganic elements in Panacis Majoris Rhizoma from different habitats were determined by ICP-AES. The characteristics of inorganic elements in Panacis Majoris Rhizoma were analyzed by correlation analysis, principal component analysis and cluster analysis. RESULTS: It was showed that there was a correlation between the contents of inorganic elements and the medicine quality of Panacis Majoris Rhizoma; Fe, Cr, Al, Mg, Cd, Ca and Zn were principal components of Panacis Majoris Rhizoma; and the contents of inorganic elements in Panacis Majoris Rhizoma existed regional differences. CONCLUSION: The contents of inorganic elements Ca, Fe and Zn,especially the content of the essential trace elements Fe and Zn, can be used as one of the key reference for medicinal quality evaluation of Panacis Majoris Rhizoma; as well, Shaanxi Province is probably the Daodi habitat of Panacis Majoris Rhizoma.

[Chemical constituents of Jasminum giraldii and their antioxidant activity].

Ten compounds were isolated from the barks of Jasminum giraldii by means of various of chromatographic techniques such as silica gel, Sephadex LH-20 and Rp-HPLC. Their structures were identified by spectroscopic data analysis as (+)-medioresinol (1), (+) -syringaresinol (2), syringaresinol-4'-O-beta-D-glucopyranoside (3), oleanic acid (4), 3-methoxy-4-hydroxy-trans-cinnamaldehyde (5), trans-sinapaldehyde (6), syringaldehyde (7), 1-(4-methoxy -phenyl) -ethanol (8), trans-cinnamic acid (9), and 4-(1-methoxyethyl) -phenol (10). Among them, compounds 1-3, 5-8 and 10 were isolated from the J. genus for the first time and compounds 4 and 9 were obtained from J. giraldii for the first time. In the DPPH free radical scavenging assay, compound 1 exhibited significant activity (IC50 55.1 micromol x L(-1)), compared with vitamin C(IC50 59.9 micromol x L(-1)); and compound 2 showed moderate activity (IC50 79.0 micromol x L(-1)), compared with 2, 6-di-tert-butyl4-methylphenol (IC50 236 micromol x L(-1)).

[The effects of microgravity on blood vessels and vascular endothelial cells].

The dysfunction of vascular system is one of the main causes of orthostatic intolerance induced by microgravity. Vascular endothelial cell is a single layer on the inner wall of the blood vessel and is the important component of the blood vessel wall. Vascular endothelial cell plays a pivotal role in the regulation of vascular functions, such as serving as a permeability barrier, regulating vasoconstriction and vasodilatation. Recent studies have demonstrated that microgravity may have different effects on vascular sys- tem and vascular endothelial cells in different parts of the body, such as increasing vasoconstrictor reactivity and decreasing vasodilator reactivity of cerebral arteries, decreasing vasoconstrictor and vasodilator reactivity of carotid and abdominal aortic arteries, decreasing vasoconstrictor reactivity and increasing vasodilator reactivity of pulmonary arteries, decreasing vasoconstrictor reactivity of mesenteric arteries and veins and lower extremity arteries. In addition, microgravity can promote the growth of vascular endothelial cells in the large vessels and inhibit the growth of microvascular endothelial cells. This paper summarized the research progress in the effects of microgravity on blood vessels and vascular endothelial cells.