Enhancement of solar blind full band absorption in photodetector with Ga2O3 nanopore and Al nanograting.

In this paper, we presented a novel double-layer light-trapping structure consisting of nanopores and nanograting positioned on both the surface and bottom of a gallium oxide-based solar-blind photodetector. Utilizing the finite element method (FEM), we thoroughly investigated the light absorption enhancement capabilities of this innovative design. The simulation results show that the double-layer nanostructure effectively combines the light absorption advantages of nanopores and nanogratings. Compared with thin film devices and devices with only nanopore or nanograting structures, double-layer nanostructured devices have a higher light absorption, achieving high light absorption in the solar blind area.

Effect of Emergency Green Channel Optimization on Ischemic Stroke Patients: Impact on Emergency Response Time, Effectiveness, Anxiety, and Acute Stress.

Objective: The aim was to assess the effectiveness of an optimized emergency green channel in the treatment of acute ischemic stroke (AIS) patients and its effect on emergency response time, effectiveness, anxiety, and acute stress. Methods: A retrospective analysis was conducted on 349 AIS patients treated with intravenous thrombolysis from January 2019 to May 2022. The patients were divided into those who received optimized emergency green channel treatment (155) and those who did not (194). Propensity score matching (PSM) was used to balance the admission pathways, living conditions, insurance methods, and residential locations of the 2 patient groups. The key metrics comprised the times from onset to admission, admission to computed tomography (CT), CT to thrombolysis, admission to thrombolysis (door-to-needle time (DNT)), National Institute of Health Stroke Scale (NIHSS) scores at various intervals post thrombolysis, heart rate, blood pressure, and scores in Self-Rating Anxiety Scale (SAS) and the Stanford Acute Stress Reaction Questionnaire (SASRQ). Results: Post PSM, 118 patients were analyzed (54 control and 64 observation). The observation group showed significantly lower time results than the control group, which included the following: the time from onset to admission (t = 31.428, P < .001), door-to-imaging time (t = 27.317, P < .001), imaging-to-needle time (t = 20.951, P < .001, and DNT (t = 25.954, P < .001). Significant differences were observed in 24 hour-post thrombolysis NIHSS scores, heart rate, blood pressure, SAS, and SASRQ scores (P < .05) but not in NIHSS scores at 7 and 30 days. Conclusion: The optimized emergency green channel process effectively reduced the treatment time for ischemic stroke patients, improved rescue efficiency, and positively influenced the psychological stress levels of patients post treatment.

Efficient Suppression of Persistent Photoconductivity in ß-Ga2O3-Based Photodetectors with Square Nanopore Arrays.

In this work, square nanopore arrays were developed on the surface of ß-Ga2O3 microflakes using focused ion beam (FIB) etching, and solar-blind photodetectors (PDs) were fabricated based on the ß-Ga2O3 microflakes with square nanopore arrays. The ß-Ga2O3 microflake-based device was transformed from a gate voltage depletion mode to an oxygen depletion mode by FIB etching. The developed device exhibited excellent solar-blind PD performance with extremely high responsivity (1.8 × 105 at 10 V), detectivity (3.4 × 1018 Jones at 10 V), and light-to-dark ratio (9.3 × 108 at 5 V) as well as good repeatability and excellent stability. The intrinsic mechanism responsible for this performance was then systematically discussed. This work opens up a new avenue for the fabrication of high-performance ß-Ga2O3-based low-dimensional PDs with high reproducibility by employing the FIB etching process.

Phase I study of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up.

OBJECTIVE: This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase I trial. METHODS: A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg. RESULTS: The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day. CONCLUSIONS: This phase I study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Design, synthesis, and biological evaluation of 6-(imidazo[1,2-a] pyridin-6-yl) quinazolin-4(3H)-one derivatives as potent anticancer agents by dual targeting Aurora kinase and ROR1.

ROR1 and Aurora kinase were overexpressed in various cancers and essential for cell proliferation, survive and metastasis. Pharmaceutical inhibition of ROR1 and Aurora kinase abrogated the activation of downstream signaling and induced cancer cell apoptosis. Hence, ROR1 and Aurora kinase considered as attractive therapeutic targets for the development of anticancer drugs. In the present work, three series of novel 6-(imidazo[1,2-a] pyridin-6-yl)-quinazolin-4(3H)-one derivatives were designed and synthesized via bioisosterism and scaffold-hopping strategies guided by FLF-13, an Aurora kinase inhibitor we discovered earlier. Most of compounds in series 2 and series 3 showed submicromolar to nanomolar inhibitory activity against multiple cancer cell lines. More importantly, compounds 12d and 12f in series 3 showed nanomolar inhibitory activity against all test cancer cells. The most promising compound 12d exhibited potent inhibitory activity against Aurora A and Aurora B with IC50 values of 84.41 nM and 14.09 nM, respectively. Accordingly, compounds 12d induced G2/M phase cell cycle arrest at 24 h and polyploidy at 48 h. It's worth noting that 12d also displayed inhibitory activity against ROR1 and induce cell apoptosis. Furthermore, 12d could significantly inhibit the tumor growth in SH-SY5Y xenograft model with tumor growth inhibitory rate (IR) up to 46.31 % at 10 mg/kg and 52.66 % at 20 mg/kg. Overall, our data suggested that 12d might serve as a promising candidate for the development of therapeutic agents for cancers with aberrant expression of ROR1 and Aurora kinases by simultaneously targeting ROR1 and Aurora kinase.

Efficacy and Safety of Sacubitril/Valsartan Compared With ACEI/ARB on Health-Related Quality of Life in Heart Failure Patients: A Meta-Analysis.

BACKGROUND: Data on the effects of sacubitril/valsartan compared with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) on health-related quality of life (HRQoL) are limited. OBJECTIVE: To evaluate the comparative effects between sacubitril/valsartan and ACEI/ARB on HRQoL, a systematic review and meta-analysis were performed. METHODS: PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were searched from inception to March 2, 2022 for randomized controlled trials that compared the HRQoL scores, including Kansas City Cardiomyopathy Questionnaire (KCCQ), Minnesota Living with Heart Failure Questionnaire (MLHFQ), or Medical Outcomes Study Short-Form Health Survey 12 or 36 (SF-12/36), between sacubitril/valsartan and ACEI/ARB. After screening, studies that met the inclusion criteria were eventually included and analyzed. RESULTS: A total of 8 studies with 17 390 patients (8693 patients used sacubitril/valsartan, and 8697 patients used ACEI/ARB) were included in this study. Five of these studies used KCCQ, 1 used SF-12/36, 1 used MLHFQ, and 1 used both KCCQ and SF-12/36. The KCCQ overall summary score and its subscales were significantly higher in sacubitril/valsartan compared with ACEI/ARB in heart failure patients with reduced ejection fraction, but were similar in heart failure patients with preserved ejection fraction. Sacubitril/valsartan conferred similar HRQoL scores in MLHFQ and SF-12/36 to ACEI/ARB. The most frequently reported adverse event for sacubitril/valsartan is hypotension and the risk is higher than for ACEI/ARB. CONCLUSIONS: Sacubitril/valsartan may have the potential to improve HRQoL in heart failure patients with reduced ejection fraction compared with ACEI/ARB. Hypotension is the most common adverse event with sacubitril/valsartan compared with ACEI/ARB. The results of this study may contribute to the rational use of sacubitril/valsartan.

Antiproliferative Activity of a New Quinazolin-4(3H)-One Derivative via Targeting Aurora Kinase A in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype. Although chemotherapy and targeted therapy are used for the treatment of patients with NSCLC, the survival rate remains very low. Recent findings suggested that aurora kinase A (AKA), a cell cycle regulator, is a potential target for NSCLC therapy. Previously, we reported that a chemical entity of quinazolin-4(3H)-one represents a new template for AKA inhibitors, with antiproliferative activity against cancer cells. A quinazolin-4(3H)-one derivative was further designed and synthesized in order to improve the pharmacokinetic properties and antiproliferation activity against NSCLC cell lines. The derivative, BIQO-19 (Ethyl 6-(4-oxo-3-(pyrimidin-2-ylmethyl)-3,4-dihydroquinazolin-6-yl)imidazo [1,2-a]pyridine-2-carboxylate), exhibited improved solubility and antiproliferative activity in NSCLC cells, including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant NSCLC cells. BIQO-19 effectively inhibited the growth of the EGFR-TKI-resistant H1975 NSCLC cells, with the suppression of activated AKA (p-AKA) expression in these cells. The inhibition of AKA by BIQO-19 significantly induced G2/M phase arrest and subsequently evoked apoptosis in H1975 cells. In addition, the combination of gefitinib and BIQO-19 exhibited synergistic antiproliferative activity in NSCLC cells. These findings suggest the potential of BIQO-19 as a novel therapeutic agent for restoring the sensitivity of gefitinib in EGFR-TKI-resistant NSCLC cells.

Rationally designed carboxymethylcellulose-based sorbents crosslinked by targeted ions for static and dynamic capture of heavy metals: Easy recovery and affinity mechanism.

A separable spherical bio-adsorbent (CMC-Cr) was prepared for capturing heavy metal ions by simple coordination and cross-linking between targeted ions of Cr3+ and carboxymethyl cellulose (CMC). A simple alternation of the CMC incorporation allowed the interconnected networks within the microspheres of preformed solid CMC to be adjusted. The excellent network structure could achieve the maximum collision between the adsorbent and the heavy metal cations in the wastewater. Through investigations, CMC-Cr-2 beads were determined as the optimal adsorbent. The adsorption performance of novel materials was evaluated by examining their adsorption behavior on Pb(II) and Co(II) under both static and dynamic conditions. The results showed that the adsorption behavior of CMC-Cr-2 beads on both two heavy metal cations could be fully reflected by the Freundlich model. Under the theoretical conditions, the maximum adsorption capacities were 97.26 and 144.74 mg/g. The kinetic results for the adsorption of two heavy metal cations on CMC-Cr-2 beads were consistent with the Pseudo-second-order kinetic model. Moreover, the correlation coefficient of the Thomas model was significant in the dynamic adsorption performance tests. Five regeneration cycle studies were successfully carried out on CMC-Cr-2 beads to evaluate reusability and stability. The applicability of CMC-Cr-2 beads in authentic aqueous solutions (both the single and binary pollutant systems) was also studied, and the results indicated that CMC-Cr-2 beads had a high potential for practical implementation. Furthermore, by analyzing the surface interactions of two heavy metal cations with the CMC-Cr-2 beads based on FTIR and XPS characterization, a basic understanding of the interaction between bio-sorbents and pollutants in wastewater can be obtained.

Biochar/Mg-Al spinel carboxymethyl cellulose-La hydrogels with cationic polymeric layers for selective phosphate capture.

Recently, biochar-related phosphate sorbents have been extensively investigated and achieved significant progress; however, there is still much room for enhancement on capturing performance and recovery of powdery ones after sorption. Herein, a new kind of adsorbent, in which biochar/Mg-Al spinel encapsulated in carboxymethyl cellulose-La hydrogels with cationic polymeric layers, was fabricated, aiming for integrating multi-advantages of each component for enhanced phosphate capture. Batch static experiments were correlated to the phosphate adsorption performance of the adsorbent. The maximum phosphate adsorption capacity of the adsorbent was 89.65 mg P/g at pH = 3. The Langmuir isotherm model and the pseudo-second-order kinetic model fitted well with the adsorption behavior of the adsorbent. More importantly, this composite adsorbent that integrated with biochar, Mg-Al spinel, cationic polymeric components exhibited favorable selectivity over coexisting anions (Cl-, SO42-, HCO3- and NO3-) and performed good reusability after five consecutive cycles. By virtue of the bead-like feature, fixed-bed column experiments demonstrated that the Thomas model fitted the breakthrough curves well under varied experimental conditions. The adsorption mechanism of phosphate on the designed composite adsorbent with multi-components could be described as the electrostatic attraction, ligand exchange and inner-sphere complexation, which might account for the efficient phosphate capturing performance.

Bi-layered hollow amphoteric composites: Rational construction and ultra-efficient sorption performance for anionic Cr(VI) and cationic Cu(II) ions.

Here, we have developed a novel bilayer hollow amphiphilic biosorbent (BHAB-3) with large adsorption capacity, rapid adsorption kinetics, and cost-effective for the removal of Cr(VI) and Cu(II) from aqueous solutions. The synthesis was based on the clever use of freeze-drying to fix the structure, secondary modification of the carboxymethyl cellulose microspheres with polyethyleneimine and cross-linking by glutaraldehyde. The consequences of pH, initial concentration, contact time and temperature on adsorption were investigated. The Langmuir model fits showed that the maximum adsorption capacities of the two target heavy metal ions reached 835.91 and 294.79 mg/g, respectively. Moreover, BHAB-3 was characterized by SEM, FT-IR, TGA, and XPS synergistically, showing that it exhibits a strong complexation ability for Cu(II) and a strong electrostatic effect for Cr(VI). Adsorption and desorption experiments showed only a slight decrease in the adsorption capacity of the BHAB-3 for Cr(VI) and Cu(II) ions after 5 and 26 cycles, respectively. Given the excellent properties of this adsorbent, it is a promising candidate for heavy metal ion removal.

Facile transformation of carboxymethyl cellulose beads into hollow composites for dye adsorption.

Novel millimeter hollow microspheres were fabricated from carboxymethyl cellulose microspheres and polyethyleneimine using glutaraldehyde as a crosslinking agent. The hollow microspheres prepared with different polyethyleneimine usages and different polyethyleneimine treatment time were investigated deeply and characterized via SEM-EDX, FT-IR, and BET surface area analysis. It was shown that polyethyleneimine could break the coordination bonds between the carboxyl and Al (III) in carboxymethyl cellulose microspheres, leading to the formation of hollow structures. Most importantly, the usage and treatment time of polyethyleneimine can distinctly tailor the structure of the carboxymethyl cellulose microspheres, resulting in the formation of different hollow microspheres with varied shell thickness and size. Most importantly, we found that the prepared hollow microspheres have excellent adsorption performance toward targeted methyl blue under testing conditions. By virtue of the large accessible amount of -NH2 groups and its unique hollow structure, this type of millimeter hollow microspheres have broad application prospects in the treatment of emerging contaminants in wastewater.

Design, synthesis, and biological evaluation of novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives as potential anticancer agents via PI3K inhibition.

Abnormal activation of the PI3K/Akt pathway is demonstrated in most of human malignant tumors via regulation of proliferation, cell cycle, and apoptosis. Therefore, drug discovery and development of targeting the PI3K/Akt pathway has attracted great interest of researchers in the development of anticancer drugs. In this study, fifteen 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives were designed and synthesized. Anticancer activities of the synthetic compounds were evaluated and the potential mechanisms were explored. Several compounds showed certain proliferation inhibitory activity against the tested cancer cells including human non-small cell lung cancer (NSCLC) HCC827, human neuroblastoma SH-SY5Y and hepatocellular carcinoma LM3 cells. Among them, compound 7i and 7m showed the best inhibitory activity against all the cancer cell lines and more active against HCC827 cells with IC50 values of 1.12 µM and 1.20 µM, respectively. In addition, 7i and 7m showed lower inhibitory activity against H7702 cells (human normal liver cells) with IC50 values of 8.66 µM and 10.89 µM, respectively, nearly 8-fold lower than that in HCC827 cells. These results suggested that compounds 7i and 7m had certain selectivity to tumor cells, compared to human normal cells. Further biological studies indicated 7i induced G2/M phase arrests and cell apoptosis of HCC827 cells via PI3K/Akt and caspase dependent pathway. Together, these novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives such as compound 7i and 7m might be lead compounds for development of potential anti-cancer drugs.

Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder.

Previous genome-wide association studies (GWAS) have identified potential genetic variants associated with the risk of major depressive disorder (MDD), but the underlying biological interpretation remains largely unknown. We aimed to prioritize genes that were pleiotropically or potentially causally associated with MDD. We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and gene expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta). We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleiotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in the immune response. Our SMR analysis indicated that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provided important leads to a better understanding of the mechanism of MDD and revealed potential therapeutic targets for the prevention and effective treatment of MDD.

Effect of rifampicin on anticoagulation of warfarin: A case report.

BACKGROUND: The drug interaction between warfarin and rifampicin is widely known, but there are still some difficulties in managing the combination of the two drugs. CASE SUMMARY: A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin. The dose of warfarin was increased to 350% in 3 mo before reaching the lower international normalized ratio treatment window. No obvious adverse reaction occurred during the drug-adjustment period. This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range. CONCLUSION: Anticoagulation for valve replacement in Chinese patients differs from that in other races. Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.

Carboxymethyl cellulose-based cryogels for efficient heavy metal capture: Aluminum-mediated assembly process and sorption mechanism.

Heavy metal ions pollution is a terrible issue that needs to be efficiently treated as a matter of priority to construct our sustainable society. However, the easy-to-handling of high-performance biomass-derived sorbents with fascinating features like high sorption capacity, favorable separation and recycling remain challenging. Herein, the development of a novel bead-like adsorbent with above features, that is, Al(III)-assembled carboxymethyl cellulose beads were used for the removal of Pb(II), Ni(II) and Co(II) from aqueous solution. Characterization methods like FT-IR, SEM, XPS and TGA were employed to confirm its physicochemical properties. Removal of the three heavy metal ions at different pH values, initial concentration and contact time were discussed at batch adsorption experiments. Meanwhile, regeneration was also discussed deeply. The results revealed that the adsorption capacity of the sorbents for three heavy metals increases with increasing pH and the initial concentration. The adsorption isotherm could be described well by the Freundlich model, and the maximum adsorption capacity for Pb(II), Ni(II) and Co(II) were 550, 620 and 760 mg/g, respectively. Kinetics study indicated that the Pseudo-second-order model described the best correlation with experimental data, this suggested that the complexation may participated in the adsorption process. More significantly, this type of bead-like adsorbents displayed excellent reusability after four sequential cycles.

Modifying alginate beads using polycarboxyl component for enhanced metal ions removal.

Designing desirable adsorbent for highly efficient removal of heavy metal ions is of practical significance, given the cost-effectiveness, environmental benign, natural abundance and easy-handling collection features. Herein, a bead-like adsorbent with high adsorption capacity was prepared by modifying alginate beads using polyacrylate with high density of carboxyl groups. The developed alginate/polyacrylate beads were collaboratively characterized by FT-IR, TGA, SEM, XPS, etc., and various adsorption conditions were tested including the pH of the solution, contact time and the initial concentration. The experimental data were fitted well by the Freundlich isotherm model, and the maximum adsorption capacity was obtained from the Langmuir model was 611.0 mg/g, and adsorption process followed the Pseudo-second-order kinetic model. The adsorption mechanisms conformed to multi-layer adsorption, and mainly dominated by chemical interactions. The bead-like adsorbent exhibited excellent reusability after eight sequential cycles and displayed higher adsorption capacity towards lead ions. This type of adsorbent might possess promising role in treating heavy metals from water by virtue of degradable, cost-effective component and high adsorption efficiency.

Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition.

Aurora A kinase, a member of the Aurora kinase family, is frequently overexpressed in various human cancers. In addition, Overexpression of Aurora A kinase is associated with drug resistance and poor prognosis in many cancers including breast cancer. Therefore, Aurora A kinase has been considered as an attractive anticancer target for the treatment of human cancers. Herein, A series of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives were designed, synthesized, and evaluated as Aurora A kinase inhibitors. The cell-based cytotoxicity assays showed that compound 16h was the most potent cytotoxic agent against all tested cancer cells and had a lower IC50 value than ENMD-2076 against MDA-MB-231 cells. Meanwhile, Aurora A kinase assay and Western blot analysis showed that 16h inhibited Aurora A kinase with an IC50 value of 21.94 nM and suppressed the phosphorylation of Histone H3 on Ser10 and Aurora A kinase on Thr288, which were consistent with the activation of Aurora A kinase. Accordingly, 16h caused aberrant mitotic phenotypes and obvious G2/M phase arrest in MDA-MB-231 cells and induced caspase-dependent apoptosis in MDA-MB-231 cells. These results demonstrated that 16h is a potential candidate for the development of anticancer agents targeting Aurora A kinase.

Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype.

Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage.

Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation.

BACKGROUND: Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy. Panaxatriol saponin (PTS), the main components extracted from Panax notoginseng, has been shown to be efficacious in the prevention and treatment of ischemic stroke in China. The aim of this study is to determine the anti-platelet activity and explore the underlying mechanisms. METHODS: Inhibitory effect of PTS and its main ginsenosides on agonists-induced platelet aggregation was determined using rabbit or human platelets. Intracellular Ca(2+) concentration ([Ca(2+)]i) mobilization was detected with fura-2/AM probe. MAPKs phosphorylation was determined by Western blotting. RESULTS: Our results showed PTS inhibited the rabbit platelet aggregation induced by various agonists (collagen, thrombin and ADP). The three main ginsenosides (Rg1, Re and R1) existing in PTS also showed anti-platelet activity, while their combination exhibited no synergistic effect on rabbit platelet aggregation. Further study demonstrated that PTS and its main ginsenosides also exhibited inhibitory effect on human platelet aggregation. Mechanism study demonstrated that pre-treatment with PTS inhibited the agonists-induced intracellular calcium mobilization. Moreover, PTS significantly suppressed the activation of both ERK2 and p38 by the agonists via reducing the phosphorylation of ERK2 and p38. CONCLUSION: We proved that PTS is effective in anti-platelet aggregation, which may, at least in part, be related to the suppression of intracellular calcium mobilization and ERK2/p38 activation. This study may provide one reasonable explanation for the efficacy of PTS on the prevention and treatment of ischemic stroke.

Panaxatriol saponins attenuated oxygen-glucose deprivation injury in PC12 cells via activation of PI3K/Akt and Nrf2 signaling pathway.

Panaxatriol saponins (PTS), the main components extracted from Panax notoginseng, have been shown to be efficacious in the prevention and treatment of cerebrovascular diseases in China. NF-E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant and cytoprotective responses to oxidative stress, has received particular attention as a molecular target for pharmacological intervention of ischemic diseases. The aim of this study was to characterize the effect of PTS on the activation of Nrf2 signaling pathway and the potential role in its protective effect. We found that PTS induced heme oxygenase-1 (HO-1) expression in PC12 cells via activating Nrf2 signaling pathway. Phosphatidylinositol 3-kinase (PI3K)/Akt kinase was involved in the upstream of this PTS activated pathway. Moreover, combination of the main components in PTS significantly enhanced the expression of Nrf2 mediated phase II enzymes. Importantly, the protective effect of PTS against oxygen-glucose deprivation-reperfusion (OGD-Rep) induced cell death was significantly attenuated by PI3K inhibitor and antioxidant response element (ARE) decoy oligonucleotides, suggesting that both PI3K/Akt and Nrf2 signaling pathway are essential during this protective process. Taken together, our results suggest that PTS may activate endogenous cytoprotective mechanism against OGD-Rep induced oxidative injury via the activation of PI3K/Akt and Nrf2 signaling pathway.