Pharmacological activities of esculin and esculetin: A review.

Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro studies have demonstrated that both have a variety of pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, and so on. Their underlying mechanisms of action and biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related factor 2 pathway, regulating the cell cycle, inhibiting tumor cell proliferation and migration, promoting mitochondrial pathway apoptosis, inhibiting the NF-κB and MAPK signaling pathways, regulating CD4+ T cells differentiation and associated cytokine release, inhibiting vascular smooth muscle cells, etc. This review aims to provide comprehensive information on pharmacological studies of esculin and esculetin, which is of noteworthy importance in exploring the therapeutic potential of both coumarin compounds.

Active ingredients Isorhamnetin of Croci Srigma inhibit stomach adenocarcinomas progression by MAPK/mTOR signaling pathway.

Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients-Gene Symbols-Disease (I-G-D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients' survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.

Transcutaneous auricular vagus nerve stimulation improves gait and cortical activity in Parkinson's disease: A pilot randomized study.

OBJECTIVE: In this randomized, double-blind, sham-controlled trial, we explored the effect of 20 Hz transcutaneous auricular vagus nerve stimulation (taVNS) on gait impairments in Parkinson's disease (PD) patients and investigated the underlying neural mechanism. METHODS: In total, 22 PD patients and 14 healthy controls were enrolled. PD patients were randomized (1:1) to receive active or sham taVNS (same position as active taVNS group but without releasing current) twice a day for 1 week. Meanwhile, all subjects were measured activation in the bilateral frontal and sensorimotor cortex during usual walking by functional near-infrared spectroscopy. RESULTS: PD patients showed instable gait with insufficient range of motion during usual walking. Active taVNS improved gait characteristics including step length, stride velocity, stride length, and step length variability compared with sham taVNS after completion of the 7-day therapy. No difference was found in the Unified Parkinson's Disease Rating Scale III, Timed Up and Go, Tinetti Balance, and Gait scores. Moreover, PD patients had higher relative change of oxyhemoglobin in the left dorsolateral prefrontal cortex, pre-motor area, supplementary motor area, primary motor cortex, and primary somatosensory cortex than HCs group during usual walking. Hemodynamic responses in the left primary somatosensory cortex were significantly decreased after taVNS therapy. CONCLUSION: taVNS can relieve gait impairments and remodel sensorimotor integration in PD patients.

Rapid classification and identification of chemical components of Astragali radix by UPLC-Q-TOF-MS.

INTRODUCTION: Pharmacological studies indicate that Astragalus (AR) has various bioactivities, including anticancer, antiaging, anti-inflammatory, antiviral, and antioxidant activities. Flavonoids, saponins, amino acids, and polysaccharides are the main active components in AR. However, its complex chemical compositions bring certain difficulties to the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of the chemical constituents in AR. OBJECTIVE: To establish a method for rapid classification and identification of the main components of flavonoids, saponins, and amino acids in AR. METHODS: The samples were analysed with ultra-high-performance liquid chromatography time-of-flight quadrupole mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. Firstly, fragmentation information was obtained in the positive and negative ion modes. Then, to realize the rapid classification and identification of AR components, the characteristic fragmentations (CFs) and neutral losses (NLs) were compared with information described in the literature. RESULTS: A total of 45 chemical constituents were successfully screened out, including 22 flavonoids, 13 saponins, and 10 amino acids. CONCLUSION: The established method realised the efficient classification and identification of flavonoids, saponins, and amino acid compounds in AR, which provided a basis for further study on AR.

Physical activity for treatment of irritable bowel syndrome.

BACKGROUND: Current recommendations for people with irritable bowel syndrome (IBS) to partake in physical activity are based on low-level evidence, do not incorporate evidence from all available randomised controlled trials (RCTs) and provide little information regarding potential adverse effects. OBJECTIVES: To assess the benefits and harms of physical activity interventions in adults diagnosed with irritable bowel syndrome and to explore possible effect moderators including type, setting and nature of physical activity interventions. SEARCH METHODS: We searched nine electronic databases including CENTRAL, MEDLINE and Embase to 5 November 2021. We handsearched reference lists and sought unpublished studies through trial registries. SELECTION CRITERIA: We included RCTs involving adults (aged 18 years or older) diagnosed with IBS and conducted in any setting comparing a physical activity intervention with no intervention, usual care or wait-list control group or another physical activity intervention group and assessing a validated measure of symptoms, quality of life or bowel movement. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence. We pooled studies that evaluated similar outcomes using a random-effects meta-analysis, and synthesised data from other studies narratively. MAIN RESULTS: We included 11 RCTs with data for 622 participants. Most (10/11) were set in high- or middle- to high-income countries, with five involving supervised physical activity, three unsupervised activity and three a mix of supervised and unsupervised activity. No trial was at low risk of bias. Four trials specified a minimally important difference for at least one assessed outcome measure. Data for 10 trials were obtained from published journal articles, with data for one obtained from an unpublished Masters degree thesis. Irritable bowel syndrome symptoms Six RCTs assessed the effectiveness of a physical activity intervention compared with usual care on global symptoms of IBS. Meta-analysis of five studies showed an observed improvement in reported symptoms following physical activity (standardised mean difference (SMD) -0.93, 95% confidence interval (CI) -1.44 to -0.42; 185 participants). We rated the certainty of evidence for this outcome as very low due to unclear and high risk of bias, inconsistency and imprecision from sparse data. This means physical activity may improve IBS symptoms but the evidence is very uncertain. The results of the remaining study supported the meta-analysis but were at unclear risk of bias and sample size was small. Two studies assessed the effectiveness of a yoga intervention compared with a walking intervention on global IBS symptoms. Meta-analysis of these two studies found no conclusive evidence of an effect of yoga compared with walking on IBS symptoms (SMD -1.16, 95% CI -3.93 to 1.62; 124 participants). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of yoga interventions compared with walking interventions on IBS symptoms. Two studies assessed the effectiveness of a physical activity intervention (yoga) compared with medication. One reported no observed difference in global IBS symptoms, though CIs were wide, suggesting uncertainty in the observed estimates and risk of bias was high (MD -1.20, 95% CI -2.65 to 0.25; 21 participants). We excluded IBS symptom data for the remaining study as it used a non-validated method. One study compared a yoga intervention with a dietary intervention and reported an observed improvement in symptoms with both interventions but neither intervention was superior to the other. Quality of life Five RCTs assessed the impact of physical activity on self-reported quality of life compared with usual care. Meta-analysis of data from four studies found no improvement in quality of life following a physical activity intervention (SMD 1.17, 95% CI -0.30 to 2.64; 134 participants; very low certainty due to risk of bias, inconsistency and imprecision). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of physical activity interventions on quality-of-life outcomes in people with IBS. One study assessed the impact on quality of life of a yoga intervention compared with walking and observed an improvement in the yoga group (MD 53.45, 95% CI 38.85 to 68.05; 97 participants ).  One study reported no observed difference in quality of life between a yoga and a dietary intervention. Abdominal pain Two trials assessed the impact of physical activity compared with usual care on reported abdominal pain. Meta-analysis found no improvement in abdominal pain with physical activity compared with usual care (SMD 0.01, 95% CI -0.48 to 0.50; 64 participants). We rated the certainty of the evidence as very low due to risk of bias and imprecision, meaning the evidence is very uncertain about the effect of physical activity interventions on abdominal pain in people with IBS. One study assessing the impact of a yoga intervention compared with walking advice reported no observed differences between groups on abdominal pain. One study comparing a yoga intervention with a dietary intervention found neither intervention had a more beneficial impact than the other and both interventions did not conclusively reduce abdominal pain. There was insufficient evidence to adequately assess adverse effects associated with physical activity due to a lack of reporting in trials. One study reported a musculoskeletal injury in a yoga intervention group but this did not result in withdrawal from the study. AUTHORS' CONCLUSIONS: Findings from a small body of evidence suggest that physical activity comprising of yoga, treadmill exercise or support to increase physical activity may improve symptoms but not quality of life or abdominal pain in people diagnosed with IBS but we have little confidence in these conclusions due to the very low certainty of evidence. The numbers of reported adverse events were low and the certainty of these findings was very low for all comparisons, so no conclusions can be drawn. Discussions with patients considering physical activity as part of symptom management should address the uncertainty in the evidence to ensure fully informed decisions. If deemed sufficiently important to patients and healthcare providers, higher quality research is needed to enable more certain conclusions.

Notoginsenoside R1 induces DNA damage via PHF6 protein to inhibit cervical carcinoma cell proliferation.

Notoginsenoside R1 (NGR1), a monomer of Traditional Chinese medicine, is from the Panax notoginsenoside complex, and has been reported to inhibit the proliferation of various types of cancer. However the mechanism underlying NGR1­mediated inhibition of cervical carcinoma cell proliferation remains unclear. Therefore, the current study aimed to investigate the antitumor effects of NGR1 on cervical carcinoma cell lines (CaSki and HeLa cells) in vitro. The Cell Counting Kit­8 and soft agar cell colony formation assay results revealed that NGR1 suppressed the viability and the number colonies of CaSki and HeLa cells, respectively. Furthermore, the DAPI staining, flow cytometry and western blotting results revealed that NGR1 induced cervical carcinoma cell apoptosis, cell cycle arrest in the S phase, upregulation of cyclin A2 and CDK2 expression levels, and downregulation of cyclin D1 expression levels. To further investigate the mechanisms of NGR1, DNA­damage­related proteins, including H2A.X variant histone (H2AX), ATR serine/threonine kinase (ATR) and p53, and the nucleolus protein, plant homeodomain finger protein 6 (PHF6) were analyzed. The results indicated that NGR1 triggered the phosphorylation of H2AX and ATR in a dose­ and time­dependent manner, and downregulated the expression level of PHF6 and upregulated the expression level of p53 in a dose­ and time­dependent manner. In conclusion, the findings of the present indicated that NGR1 may inhibit the viability of cervical carcinoma cells and induce cell apoptosis via DNA damage, which may be activated by the downregulation of PHF6 expression levels, and the subsequent triggering of the phosphorylation of H2AX and ATR. In addition, NGR1 may exert an ability to arrest cervical carcinoma cells in the S phase and upregulate the expression levels of cyclin A2 and CDK2. Therefore, NGR1 may serve as a novel chemotherapeutic agent for cervical carcinoma.

Development of liquiritigenin-phospholipid complex with the enhanced oral bioavailability.

In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL-1, reaction time for 15 min, reaction temperature of 30 ℃, a ratio of 1∶4.5 (W/W) drug-to-phospholipid and anhydrous ethanol as reaction solvent. Compared to liquiritigenin, the AUC0-t of the LPC was increased by 239%. The liquiritigenin-phospholipid complex significantly increase the lipid solubility and bioavailability of liquiritigenin, suggesting that it is an effective formulation for further development and clinical applications.

Protective effects of collagen polypeptide from tilapia skin against injuries to the liver and kidneys of mice induced by d-galactose.

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight <3 kDa) in alleviating liver and kidney injuries in aging mice induced by d-galactose (d-gal) and its underlying mechanism of action. First, we characterized TSCP. TSCP was passed through a 3-kDa ultrafiltration membrane, desalted in water by a solid-phase extraction column, purified further by reverse phase-high performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. TSCP contained 17 types of amino acids (AAs) and 41 peptide chains of length 7 AAs to 22 AAs. The content of free AAs and total AAs of TSCP was 13.5% and 93.79%, respectively. Next, we undertook animal experiments. Mice were injected once-daily with D-gal (300 mg/kg body weight, s.c.) for 8 weeks, and TSCP was administered simultaneously once-daily by intragastric gavage. TSCP could visibly improve the decreased body weight, depressed appetite, and mental deterioration of mice triggered by d-gal. TSCP could also alleviate d-gal-induced damage to the liver and kidneys according to histopathology (especially high-dose TSCP). Consistent with these macroscopic and pathologic changes, TSCP could also prevent d-gal-induced increases in serum levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, lipid peroxidation, creatinine and uric acid, as well as decreases in serum levels of immunoglobulin (Ig)G and IgM. Moreover, TSCP improved the activities of superoxide dismutase, catalase, and glutathione peroxidase, but also inhibited the increases in the levels of malondialdehyde and inducible nitric oxide synthase expression in the liver and kidneys of d-gal-treated mice. These results suggest that TSCP can alleviate the injuries to the liver and kidneys in aging mice induced by d-gal, and that its mechanism of action might be, at least partially, associated with attenuation of oxidative stress and enhancement of immune function.

Development of a semi-mechanistic allergenic pollen emission model.

Modeling pollen emission processes is crucial for studying the spatiotemporal distributions of airborne allergenic pollen. A semi-mechanistic emission model was developed based on mass balance of pollen grain fluxes in the surroundings of allergenic plants. The emission model considers direct emission and resuspension and accounts for influences of temperature, wind velocity, and relative humidity. Modules of this emission model have been developed and parameterized with multiple years of pollen count observations to provide pollen season onset and duration, hourly flowering likelihood, and vegetation coverage for oak and ragweed, as two examples. The simulated spatiotemporal pattern of pollen emissions generally follows the corresponding pattern of area coverage of allergenic plants and diurnal pattern of hourly flowering likelihood. It is found that oak pollen emissions start from the Southern part of the Contiguous United States (CONUS) in March and then shift gradually toward the Northern CONUS, with a maximum emission flux of 5.8 × 106 pollen/(m2 h). On the other hand, ragweed pollen emissions start from the Northern CONUS in August and then shift gradually toward the Southern CONUS. The mean ragweed emission flux during August to September can increase up to 2.4 × 106 pollen/(m2 h). This emission model is robust with respect to the input parameters for oak and ragweed. Qualitative evaluations of the model performance indicated that the simulated pollen emission is strongly correlated with the plant coverages and observed pollen counts. This model could also be applied to other pollen species given the relevant parameters.

Bakuchiol exhibits anti-metastasis activity through NF-κB cross-talk signaling with AR and ERß in androgen-independent prostate cancer cells PC-3.

Androgen-independent prostate cancer (PCa) is a developed tumor derived from the local androgen dependent PCa, which often affects elderly men. Psoralea corylifolia L, a traditional Chinese medicine, has been widely used for PCa treatment as an important part of a common prescription, while the mechanism remains unclear. Our study was aimed to investigate the tumor-inhibitory effect of its main component bakuchiol in androgen-independent PCa cell line PC-3 cells. Bakuchiol significantly suppressed PC-3 cell proliferation and migration; the expressions of PCNA and MMP-9 were consistently down regulated as well. Meanwhile, both the constitutive and LPS-induced NF-κB activation were significantly inhibited by bakuchiol. The inhibitory effects of bakuchiol on cell proliferation, migration and invasion were recovered when LPS were added together with bakuchiol. SiRNA against androgen receptor (AR) or estrogen receptor ß (ERß) were transfected and the regulation of bakuchiol-suppressed proliferation, invasion, NF-κB signaling and MMP-9 secretion in response to LPS were blocked. Taken together, our data demonstrated that bakuchiol inactivated NF-κB signaling via AR and ERß, which contributes to inhibition of PC-3 cell proliferation and migration, indicating that bakuchiol is one of the key component from P. corylifolia L for PCa treatment and has a potential as anti-prostate cancer drug candidates.

Nanostructures and Dynamics of Isochorically Confined Amorphous Drug Mediated by Cooling Rate, Interfacial, and Intermolecular Interactions.

The production and stabilization of amorphous drugs by the nanoconfinement effect has recently become a research hotspot in pharmaceutical sciences. Herein, two guest/host systems, indomethacin (IMC) and griseofulvin (GSF) confined in anodic aluminum oxide (AAO) templates with different pore diameters (25-250 nm) are investigated by differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). The crystallization of the confined drugs is suppressed, and their glass transition temperatures show an evident pore-size dependency. Moreover, a combination of dielectric and calorimetric results demonstrates that the significant change in the temperature dependence of the structural relaxation time during the cooling process is attributed to the vitrification of the interfacial molecules and the local density heterogeneity under isochoric confinement. Interestingly, compared with the case of IMC/AAO, which can be described by a typical two-layer model, GSF/AAO presents an rare scenario of three glass transition temperatures under fast cooling (40-10 K/min), indicating that there exists a thermodynamic nonequilibrium interlayer between the bulk-like core and interfacial layer. In contrast, the slow cooling process (0.5 K/min) would lead confined GSF into the stable core-shell nanostructure. Using surface modification, the interfacial effect is confirmed to be an important reason for the different phenomena between these two guest/host systems, and intermolecular hydrogen bonding is also suggested to be emphasized considering the long-range effect of interfacial interactions. Our results not only provide insight into the glass transition behavior of geometrically confined supercooled liquids, but also offer a means of adjusting and stabilizing the nanostructure of amorphous drugs under two-dimensional confinement.

A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway.

7-hydroxy-5,4'-dimethoxy-2-arylbenzofuran (Ary) is purified from Livistona. It has been demonstrated to have anticancer activity to various tumors in including cervical cancer, but its mechanism is still unclear. In the present, we show that Ary induces cervical cancer cells apoptosis through mitochondria degradation and mediates cervical cancer cell arrest. Further, Ary-inducing cell cycle G1/S-phase arrest is associated with increased cyclin A2 and cyclin dependent kinase 2 (Cdk2) proteins. Knockdown of cyclin A2 using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced G1/S-phase arrest. Moreover, Ary sustainedly induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). And ERK1/2 phosphorylation inhibition using specific inhibitor U0126 effectively suppressed cyclin A2 expression, and reduced G1/S-phase arrest induced by Ary. All the experiments in vitro and in vivo verified that Ary has an anticancer effect on cervical cancer. These data provide novel evidences that Ary induces cervical cancer cells apoptosis through mitochondria degradation and cell G1/S-phase arrest. These findings also suggest that ERK-mediated Cdk2/cyclin A signaling pathway is involved in Ary-induced G1/S-phase arrest.

Chemical profiling of Qixue Shuangbu Tincture by ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry (UPLC-QTOF/MS).

The present study was designed to develop and validate a sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method to separate and identify the chemical constituents of Qixue Shuangbu Tincture (QXSBT), a classic traditional Chinese medicine (TCM) prescription. Under the optimized UPLC and QTOF/MS conditions, 56 components in QXSBT, including chalcones, triterpenoids, protopanaxatriol, flavones and flavanones were identified and tentatively characterized within a running time of 42 min. The components were identified by comparing the retention times, accurate mass, and mass spectrometric fragmentation characteristic ions, and matching empirical molecular formula with that of the published compounds. In conclusion, the established UPLC-QTOF/MS method was reliable for a rapid identification of complicated components in the TCM prescriptions.

Allergenic pollen season variations in the past two decades under changing climate in the United States.

Many diseases are linked with climate trends and variations. In particular, climate change is expected to alter the spatiotemporal dynamics of allergenic airborne pollen and potentially increase occurrence of allergic airway disease. Understanding the spatiotemporal patterns of changes in pollen season timing and levels is thus important in assessing climate impacts on aerobiology and allergy caused by allergenic airborne pollen. Here, we describe the spatiotemporal patterns of changes in the seasonal timing and levels of allergenic airborne pollen for multiple taxa in different climate regions at a continental scale. The allergenic pollen seasons of representative trees, weeds and grass during the past decade (2001-2010) across the contiguous United States have been observed to start 3.0 [95% Confidence Interval (CI), 1.1-4.9] days earlier on average than in the 1990s (1994-2000). The average peak value and annual total of daily counted airborne pollen have increased by 42.4% (95% CI, 21.9-62.9%) and 46.0% (95% CI, 21.5-70.5%), respectively. Changes of pollen season timing and airborne levels depend on latitude, and are associated with changes of growing degree days, frost free days, and precipitation. These changes are likely due to recent climate change and particularly the enhanced warming and precipitation at higher latitudes in the contiguous United States.

Comparison of Synechocystis sp. PCC6803 and Nannochloropsis salina for lipid production using artificial seawater and nutrients from anaerobic digestion effluent.

The potential use of Synechocystis sp. PCC6803 (Synechocystis sp.) for lipid production using artificial seawater (ASW) medium supplemented with anaerobic digestion effluent (ADE) was investigated and compared to marine microalgae, Nannochloropsis salina (N. salina). Synechocystis sp. showed growth rates 83% and 20% higher than N. salina at 3% and 6% ADE loading ratios, respectively, achieving the highest biomass productivity of 212 mg L(-1) d(-1) in semi-continuous cultivation. The rapid growth of Synechocystis sp. was offset by its low lipid content, resulting in lipid productivities 7-28% lower than N. salina. The lipid productivity of Synechocystis sp. may be further improved by decreasing the harvesting interval during semi-continuous cultivation. Fatty acid analysis showed that lipids extracted from Synechocystis sp. contained higher palmitic acid (60.3±2.0%) and linoleic acid (20.0±1.6%), and had a higher cetane number and oxidative stability than those from N. salina.

Close association of intestinal autofluorescence with the formation of severe oxidative damage in intestine of nematodes chronically exposed to Al(2)O(3)-nanoparticle.

In nematodes, acute exposure (24-h) to 8.1-30.6 mg/L Al(2)O(3)-nanoparticles (NPs) or Al(2)O(3) did not influence intestinal autofluorescence, whereas chronic exposure (10-d) to Al(2)O(3)-NPs at concentrations of 8.1-30.6 mg/L or Al(2)O(3) at concentrations of 23.1-30.6 mg/L induced significant increases of intestinal lipofuscin accumulation, and formation of severe stress response and oxidative damage in intestines. Moreover, significant differences of intestinal autofluorescence, stress response and oxidative damage in intestines of Al(2)O(3)-NPs exposed nematodes from those in Al(2)O(3) exposed nematodes were detected at examined concentrations. Oxidative damage in intestine was significantly correlated with intestinal autofluorescence in exposed nematodes, and oxidative damage in intestine was more closely associated with intestinal autofluorescence in nematodes exposed to Al(2)O(3)-NPs than exposed to Al(2)O(3). Thus, chronic exposure to Al(2)O(3)-NPs may cause adverse effects on intestinal lipofuscin accumulation by inducing the formation of more severe oxidative stress in intestines than exposure to Al(2)O(3) in nematodes.

Na/K-ATPase mimetic pNaKtide peptide inhibits the growth of human cancer cells.

Cells contain a large pool of nonpumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. A supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces the activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness of pNaKtide and suggest that the defect in Na/K-ATPase-mediated signal transduction may be targeted for developing new anticancer therapeutics.

Aluminum nanoparticle exposure in L1 larvae results in more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes.

Toxicity of Al(2)O(3)-NPs, as compared to that of Al(2)O(3), to L1-larval, L4-larval or young adult nematodes was evaluated. When exposure was performed at L1-larval stage, the significant increases of lethality, stress response, and intestinal lipofuscin autofluorescence were observed in 6.3-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. In contrast, when exposure was performed at L4-larval or young adult stage, the significant increases of lethality and intestinal lipofuscin autofluorescence were observed in 12.7-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes, and the significant inductions of stress response were detected in 25.5-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. Moreover, the lethality was significantly correlated with the stress response and the intestinal lipofuscin autofluorescence in Al(2)O(3)-NPs exposed nematodes. These data imply that Al(2)O(3)-NPs exposure in L1 larvae causes more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes.

[Research on SCR denitrification of MnOx/Al2O3 modified by CeO2 and its mechanism at low temperature].

The Al2O3,which has large specific surface area and is used as carrier,was prepared by sol-gel method in this study. Series catalysts of MnOx, CeO2 plus MnOx supported on Al2O3 by isometric impregnation method. The SCR denitrification experimental conditions were as follows: NH3 as reductive agent, certain gas velocity and suitable ratio of gas mixed was setup. Furthermore, the experiments of BET, XRD and SEM were also carried out respectively in order to obtain physicochemical properties of the prepared catalysts. The experimental results showed that the loading of active component and calcination temperature made a big difference to the catalysts' performance. With appropriate addition of CeO2, MnOx/Al2O3 exhibits better activity and stability. For MnOx/Al2O3, the catalytic activity on NO was greatly influenced by its loaded content, and 7% MnOx/Al2O3 showed superior catalytic activity among the MnOx/Al2O3. The addition of CeO2 could greatly improve the dispersibility of MnOx on the carrier and increase its catalytic activity. The 4% CeO2 addition was the optimum loaded mass precent. Forthermore, 550 degrees C is the best calcination temperature, as MnOx formed different crystalline phases with temperature, at the same time, the addition of CeO2 could affect MnOx crystalline phase. The catalytic mechanism of SCR on NO was also discussed.