Eosinophils and tissue remodeling: Relevance to airway disease.

The ability of human tissue to reorganize and restore its existing structure underlies tissue homeostasis in the healthy airways, but in disease can persist without normal resolution, leading to an altered airway structure. Eosinophils play a cardinal role in airway remodeling both in health and disease, driving epithelial homeostasis and extracellular matrix turnover. Physiological consequences associated with eosinophil-driven remodeling include impaired lung function and reduced bronchodilator reversibility in asthma, and obstructed airflow in chronic rhinosinusitis with nasal polyps. Given the contribution of airway remodeling to the development and persistence of symptoms in airways disease, targeting remodeling is an important therapeutic consideration. Indeed, there is early evidence that eosinophil attenuation may reduce remodeling and disease progression in asthma. This review provides an overview of tissue remodeling in both health and airway disease with a particular focus on eosinophilic asthma and chronic rhinosinusitis with nasal polyps, as well as the role of eosinophils in these processes and the implications for therapeutic interventions. Areas for future research are also noted, to help improve our understanding of the homeostatic and pathological roles of eosinophils in tissue remodeling, which should aid the development of targeted and effective treatments for eosinophilic diseases of the airways.

Ion Pair Catalyst - Pentanidinium.

In this account, we further describe our already developed N-sp2 hybrid guanidinium as an efficient phase-transfer catalyst and ion pair catalysis based on N-sp2 hybrid pentanidinium and its application in some new reactions. The sp3 hybrid quaternary ammonium salt has a tetrahedral structure, which means that three sides of it can be effectively steric, allowing the remaining side to be close to the substrate. However, the sp2 hybrid ammonium salt allows the substrate to form ion pairs from both directions respectively, so it is a greater challenge to control the stereoselectivity of the reaction. Van der Waals forces, such as hydrogen bonds and π - π ${\pi -\pi }$ interactions, have been used to make electrophiles approach from a certain direction, leading to a higher enantioselectivity. Based on the above idea, we designed an N-sp2 hybrid phase-transfer catalyst, pentanidinium. Pentanidinium has five conjugated nitrogen atoms, one of which has a formal positive charge, which is necessary for it to become an ion pair catalyst. We have confirmed that pentanidinium can catalyze α-hydroxylation of 3-substituted-2-oxindoles, Michael addition of 3-alkyloxindoles with vinyl sulfone, and alkylation reactions of sulfenate anions and dihydrocoumarins, desymmetrization of pro-chiral sulfinate to afford enantioenriched sulfinate esters. Pentanidinium with side chain structure changes can also be catalyzed efficiently with enantioconvergent halogenophilic nucleophilic substitution, including azidation and thioesterification. In the reaction catalyzed by pentanidinium, it always attracts us with the advantages of low catalytic load and good enantioselectivity.

Glutaraldehyde-crosslinked Rhizopus oryzae whole cells show improved catalytic performance in alkene epoxidation.

BACKGROUND: Existing methods for alkene epoxidation are based on lipase-catalysed perhydrolysis. However, the inactivation of the expensive lipase enzyme is problematic for enzymatic epoxidation at large scales due to the use of hydrogen peroxide and peracids at high concentrations in the reaction. The immobilisation of whole cells appears to be a promising approach to alleviate this problem. RESULTS: A green oxidation system containing hydrogen peroxide, Na3C6H5O7, an acyl donor, and glutaraldehyde (GA)-crosslinked cells of Rhizopus oryzae was developed for the epoxidation of alkenes. GA-crosslinked cells of Rhizopus oryzae were adopted as a biocatalyst into the epoxidation system. A variety of alkenes were oxidised with this system, with a 56-95% analytical yield of the corresponding epoxides. The catalytic performance of the crosslinked treated cells was substantially improved compared to that of the untreated cells and the initial reaction rate increased from 126.71 to 234.72 mmol/L/h, retaining 83% yields even after four batches of reactions. The addition of 3.5 mmol Na3C6H5O7 not only acts as an acid-trapping reagent to eliminate the negative effect of the carboxylic acid on the alkene oxide but also forms a saturated salt solution with the aqueous phase, affecting the concentration of H2O2 in the three phases and thus the epoxidation reaction. Organic solvents with a logP value > 0.68 were good at producing hydroxy peracids; however, this method is only suitable for oxidation in a two-liquid phase. CONCLUSIONS: Compared with other lipase biocatalysts, the GA-crosslinked whole-cell biocatalyst is inexpensive, readily available, and highly stable. Therefore, it can be considered promising for industrial applications.

Efficient Degradation of Alginate and Preparation of Alginate Oligosaccharides by a Novel Biofunctional Alginate Lyase with High Activity and Excellent Thermophilic Features.

The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 U/mg) at 70 °C and pH 8.0, with the sodium alginate used as a substrate. Noticeably, AlyRm3 was stable at 65 °C and also exhibited 30% of maximal activity at 90 °C. These results indicated that AlyRm3 is a thermophilic alginate lyase that efficiently degrades alginate at high industrial temperatures (>60 °C). The FPLC and ESI-MS analyses suggested that AlyRm3 primarily released disaccharides and trisaccharides from the alginate, polyM, and polyG in an endolytic manner. In the saccharification process of sodium alginate (0.5%, w/v), the AlyRm3 yielded numerous reducing sugars (1.73 g/L) after 2 h of reaction. These results indicated that AlyRm3 has a high enzymatic capacity for saccharifying the alginate, and could be used to saccharify the alginate biomass before the main fermentation process for biofuels. These properties make AlyRm3 a valuable candidate for both fundamental research and industrial applications.

A Novel Sodium Alginate-Carnauba Wax Film Containing Calcium Ascorbate: Structural Properties and Preservative Effect on Fresh-Cut Apples.

In order to improve the mechanical properties, nutritional value and fresh-keeping ability of conventional sodium alginate edible composite membranes, a new type of edible composite film was prepared by adding water-blocking agent carnauba wax, plasticizer glycerin, antioxidant and nutritional enhancer sodium ascorbate on a basis of traditional sodium alginate composite film. In this study, the physical, mechanical and structural properties of different film components were investigated. The results showed the components did not simply combine, but produced interaction forces which improved the stability and mechanical properties of composite film. When the amount of calcium ascorbate was 0.4%, the water vapor transmittance of the composite film reached a minimum of 0.65 g·mm/(cm2·d·kPa), and the tensile strength and elongation at break reached the maximum, which were 398.64 MPa and 17.93%, respectively. Additionally, the sodium alginate-carnauba wax film exhibited better performance on the preservation of fresh-cut apples. Compared with other composite films, the color and hardness of fresh-cut apples coated with this composite film were better maintained, and the losses of titration acid content and soluble solid content were reduced. Moreover, the weight loss rate, increase in polyphenol oxidase activity and total colony count were inhibited. All results determined that the edible film has good application value in the field of fresh-cut fruit preservation, which provides a theoretical basis for further research on edible film.

Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma.

BACKGROUND: Hyperactivation of CD4+ T cells in peripheral blood and airway tissues has been suggested to play a key role in the development and maintenance of chronic inflammation in childhood asthma. However, the underlying mechanisms are not yet clear. OBJECTIVE: To investigate alterations in serum levels of T helper cell-related cytokines, mitogen-stimulated CD4+ T cell proliferation and activation-induced cell death (AICD) in childhood asthma. METHODS: 21 children with untreated asthma and 21 healthy volunteers (age and gender matched) participated in this study. Th1/Th2/Th17 cytokines in serum were analyzed by flow cytometry. CD4+ T cells were isolated from participants by using immuno-magnetic beads and were stimulated by phytohemagglutinin (PHA). Cell proliferation was evaluated with a Cell Counting Kit-8 (CCK-8). Activation induced cell death (AICD) of CD4+ T cells was also induced by PHA and apoptosis was assayed by annexin V/PI staining. Quantitative RT-PCR was carried out to analyze Fas and FasL mRNA expression. FLIPL, caspase-8 and Bcl-2 were detected by western blot analysis. RESULTS: In children with asthma, the proliferative capacity of CD4+ T cells was enhanced and AICD was inhibited significantly, while serum IL-4, IL-10 and TNF were markedly higher compared with the control group. Fas mRNA expression in the asthma group was obviously lower than that in the control group, while no change was detected in FasL mRNA expression. Western blot analysis showed that the levels of the anti-apoptotic proteins, FLIPL and Bcl-2 in CD4+ T cells of the asthma group were significantly higher than in the control group. Spearman's correlation tests showed that only IL-4 correlated positively with FLIPL and Bcl-2 expression, while IL-10 and TNF were unrelated to FLIPL and Bcl-2 expression. CONCLUSIONS: These results indicate that enhanced proliferation and defective AICD of CD4+ T cells influence the T cell-mediated inflammatory reaction in childhood asthma and that increased IL-4, FLIPL and Bcl-2 expression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.ression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.

Identification of Potential Drug Targets for Myopia Through Mendelian Randomization.

Purpose: The purpose of this study was to identify potential drug targets for myopia and explore underlying mechanisms. Methods: Mendelian randomization (MR) was implemented to assess the effect of 2684 pharmacologically targetable genes in the blood and retina on the risk of myopia from a genomewide association study (GWAS) for age-at-onset of spectacle wearing-inferred mean spherical equivalent (MSE; discovery cohort, N = 287,448, European), which was further validated in a GWAS for autorefraction-measured MSE (replication cohort, N = 95,619, European). The reliability of the identified significant potential targets was strengthened by colocalization analysis. Additionally, enrichment analysis, protein-protein interaction network, and molecular docking were performed to explore the functional roles and the druggability of these targets. Results: This systematic drug target identification has unveiled 6 putative genetically causal targets for myopia-CD34, CD55, Wnt3, LCAT, BTN3A1, and TSSK6-each backed by colocalization evidence in adult blood eQTL datasets. Functional analysis found that dopaminergic neuron differentiation, cell adhesion, Wnt signaling pathway, and plasma lipoprotein-associated pathways may be involved in myopia pathogenesis. Finally, drug prediction and molecular docking corroborated the pharmacological value of these targets with LCAT demonstrating the strongest binding affinity. Conclusions: Our study not only opens new avenues for the development of therapeutic interventions for myopia but may also help to understand the underlying mechanisms of myopia.

Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol.

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the "free" iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism.

BACKGROUND: Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms. METHODS: All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice. RESULTS: Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol-feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of Prevotella and decreased abundance of Paraprevotella and Romboutsia as detected by 16S rDNA high-throughput sequencing. CONCLUSION: Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota-bile acid-liver axis and protected against alcohol-induced liver injury in vivo.

CAMSAP1 Mutation Correlates With Improved Prognosis in Small Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

Platinum-based chemotherapy is the first-line treatment for small cell lung cancer (SCLC). However, due to patients developing a resistance to the drug, most experience relapse and their cancer can become untreatable. A large number of recent studies have found that platinum drug sensitivity of various cancers is affected by specific gene mutations, and so with this study, we attempted to find an effective genetic biomarker in SCLC patients that indicates their sensitivity to platinum-based drugs. To do this, we first analyzed whole exome sequencing (WES) and clinical data from two cohorts to find gene mutations related to the prognosis and to the platinum drug sensitivity of SCLC patients. The cohorts used were the Zhujiang cohort (N = 138) and the cohort reported by George et al. (N = 101). We then carried out gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate possible molecular mechanisms through which these gene mutations affect patient prognosis and platinum drug sensitivity. We found that for SCLC patients, CAMSAP1 mutation can activate anti-tumor immunity, mediate tumor cell apoptosis, inhibit epithelial-mesenchymal transition (EMT), improve prognosis, and improve platinum drug sensitivity, suggesting that CAMSAP1 mutation may be a potential biomarker indicating platinum drug sensitivity and patient prognosis in SCLC.

Ecofriendly conversion of algal waste into valuable plant growth-promoting rhizobacteria (PGPR) biomass.

With the development of marine biorefinery concept, utilisation of algal waste during industrial processing as well as some "green tide" waste biomass has become an important research topic. In this work, a single-step microwave process was used to hydrolyse Laminaria japonica processing waste (LJW) and Enteromorpha prolifera (EP), producing a growth medium suitable for microbial cultivation. The medium contained a range of mono- and polysaccharides as well as macro- and micronutrients that could be used by the microbes. The cultivation behavior of three plant growth-promoting rhizobacteria (PGPR) strains (Bacillus subtilis strain Tpb55, Bacillus amyloliquefaciens strain Cas02, and Burkholderia pyrrocinia strain Lyc2) in the two media were investigated. LJW hydrolysate from 180 °C and EP hydrolysate from 150 °C performed better cultivation efficiency than those hydrolysates from other microwave conditions. Saccharide analysis showed that microbes metabolized some monosaccharide such as glucose, mannose during cultivation, leaving polysaccharide unused in the medium. Furthermore, hydrolysate-strain cultivation mixtures were applied to pepper growth. The EP hydrolysate-Cas02 broth showed better plant growth-promoting effect compared to other treatments, which might be attributed to the higher indole-3-acetic acid (IAA) production of Cas02 in the EP hydrolysate. This work shed lights on the conversion of algal waste to PGPR biomass as well as the co-application of algal hydrolysates- strains cultivation broth for a better plant growth promotion.

Structural characterization and neuroprotective effect of a polysaccharide from Corydalis yanhusuo.

In the present study, we investigated the neuroprotective effects of a purified Corydalis yanhusuo polysaccharide (CYP) on Aß (25-35)-induced neurotoxicity and explored its underlying molecular mechanisms in PC12 cells. The results showed pretreatment with CYP (25, 50, and 100 µg/ml) prior to Aß (25-35) exposure significantly protected PC12 cells from Aß (25-35)-induced cell death, lactate dehydrogenase (LDH) release, DNA fragmentation, mitochondrial dysfunction and mitochondrial cytochrome c release. Moreover, Aß (25-35)-induced increase of ratio between Bax and Bcl-2 protein expression was dramatically reversed by CYP pretreatment. Furthermore, the addition of CYP led to a significant repressing effect on the elevated protein expression of cleaved caspase-8, caspase-9, and caspase-3 in Aß (25-35)-treated PC12 cells. Taken together, these findings indicated that protective effect of CYP against Aß (25-35)-induced toxicity in PC12 cells was probably mediated by inhibition of apoptosis via both mitochondrial apoptotic pathway and death receptor pathway.

Structures, properties and application of alginic acid: A review.

Alginic acid is a natural polysaccharide, which has been widely concerned and applied due to its excellent water solubility, film formation, biodegradability and biocompatibility. This paper briefly describes the source, properties, structure and application of sodium alginate by summarizing and analyzing the current literature. This paper reviews the application of sodium alginate in the fields of food industry, catalyst, health, water treatment, packaging, immobilized cells, and looks forward to its application prospects.

Impact of short-term application of seaweed fertilizer on bacterial diversity and community structure, soil nitrogen contents, and plant growth in maize rhizosphere soil.

The effects of the short-term application of Ascophyllum nodosum-fermented seaweed fertilizer on the bacterial community, soil nitrogen contents, and plant growth in maize rhizosphere soil were evaluated. The changes in the bacterial community composition and nitrogen contents including those of total nitrogen (TN), nitrate nitrogen (NO3--N) and ammonium nitrogen (NH4+-N) in rhizosphere soils in response to treatment with seaweed fertilizer were determined. Furthermore, soil enzymatic activity and crop biomass were analyzed. The relative abundance of the dominant phyla varied regularly with fertilization, and bacterial α-diversity was apparently influenced by seaweed fertilizer amendment. The TN contents of all soil samples decreased gradually, and the NO3--N and NH4+-N contents of the soils treated with seaweed fertilizer were much higher than those of the control soils. Similarly, the enzymatic activities of dehydrogenase, nitrite reductase, urease, and cellulase in the soil were significantly increased on day 3, day 8, and day 13 after the application of seaweed fertilizer to the maize rhizosphere soil. However, there was no difference in the activity of soil sucrase between the treatment group and the control group. In this study, the growth of maize seedlings was confirmed to be greatly promoted by the utilization of seaweed fertilizer. These results deepen our understanding of plant-microbe interactions in agroecosystems and should benefit the wide use of seaweed fertilizer in sustainable agricultural production.

A Novel Pectic Polysaccharide of Jujube Pomace: Structural Analysis and Intracellular Antioxidant Activities.

After extraction from jujube pomace and purification by two columns (DEAE-Sepharose Fast Flow and Sepharcyl S-300), the structure of SAZMP4 was investigated by HPGPC, GC, FI-IR, GC-MS, NMR, SEM, and AFM. Analysis determined that SAZMP4 (Mw = 28.94 kDa) was a pectic polysaccharide mainly containing 1,4-linked GalA (93.48%) with side chains of 1,2,4-linked Rha and 1,3,5-linked Ara and terminals of 1-linked Rha and 1-linked Ara, which might be the homogalacturonan (HG) type with side chains of the RG-I type, corresponding to the results of NMR. In AFM and SEM images, self-assembly and aggregation of SAZMP4 were respectively observed indicating its structural features. The antioxidant activity of SAZMP4 against H2O2-induced oxidative stress in Caco-2 cells was determined by activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as malondialdehyde (MDA) and reactive oxygen species (ROS) levels, indicating SAZMP4 can be a natural antioxidant. Also, a better water retention capacity and thermal stability of SAZMP4 was observed based on DSC analysis, which could be applied in food industry as an additive.

Degradation of different molecular weight fucoidans and their inhibition of TGF-ß1 induced epithelial-mesenchymal transition in mouse renal tubular epithelial cells.

In order to investigate the anti-fibrotic effect of different molecular weight (Mw) fucoidans on TGF-ß1-induced mouse renal tubular epithelial cell (MTEC) mode. Oxidative degradation method was used to obtain fucoidans with different molecular weights and the reaction time, reaction temperature and the concentration of oxidants were investigated. Cell viability was detected by CCK-8, and EMT markers expression was detected by Western-bolt and Cell immunofluorescence assay. As a result, after chemical analysis of three independent batches of prepared samples, one batch of fucoidan sample (LHX 1-9) which chemical contents are similar but Mw ranging from 3.3 KDa to 49.3 KDa were selected to do further research. We found LHX1 (Mw = 3.3 KDa) and LHX 3-9 (Mw = 6.6 KDa, 8.3 KDa, 11.3 KDa, 14.9 KDa, 25.2 KDa, 35.4 KDa, 49.3 KDa) could resist the TGF-ß1-induced depithelial-mesenchymal transition (EMT) by decreased expression of Fn and CTGF and maintained epithelial cell morphology in MTEC. However, the relationship between the Mw of fucoidans and their anti-EMT effect is not simply linear. Among the samples, LHX 1, 5 and 8 showed significant anti-EMT effects than others by de-regulated Fn and CTGF expression on MTEC cells.

Fucoidan isolated from Ascophyllum nodosum alleviates gut microbiota dysbiosis and colonic inflammation in antibiotic-treated mice.

Antibiotic treatment, as an important therapeutic intervention, can cause damage to the host microbiome and the intestinal mucosal barrier. In order to find a way to alleviate the side effects of antibiotics, the present study investigated the effects of fucoidan (ANP) isolated from Ascophyllum nodosum on gut microbiota dysbiosis and colonic inflammation induced by ciprofloxacin-metronidazole (CiMe) in C57BL/6J mice. Our results showed that dietary ANP prevented colon shortening, alleviated the colonic tissue damages, and partially reversed the alteration of gut microbiota by increasing the abundance of potentially beneficial bacteria, e.g., Ruminococcaceae_UCG_014 and Akkermansia and decreasing the abundance of harmful bacteria, e.g., Proteus and Enterococcus. ANP also suppressed the overproduction of TNF-α, IL-1ß, and IL-6 and promoted the expression of IL-10. In addition, ANP reversed the decreased production of short-chain fatty acids in CiMe-treated mice. Furthermore, correlation analysis indicated the presence of critical gut microbiota, which played important roles in reducing the inflammation-related indices. Thus, the present study suggests that fucoidan isolated from Ascophyllum nodosum is effective in providing protection against the negative effects of antibiotics on gut microbiota and colonic health.

Traditional uses, phytochemistry, and pharmacology of Ficus hispida L.f.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hispida L.f. (Moraceae) has long been used as a traditional medicine in India, China, Sri Lanka, Australia, and Myanmar in the treatment of diarrhea, ulcer, anemia, diabetes, inflammation, and cancer. AIM OF THE REVIEW: This review provides a systematic comment on the botany, traditional uses, and phytochemical and pharmacological studies of F. hispida, with an aim to make critical update of the current knowledge and obtain opportunities for further therapeutic potential. MATERIALS AND METHODS: The information was derived from scientific literature databases including PubMed, Baidu Scholar, Google Scholar, Web of Science, and Science Direct. Additional information was gathered from books, Ph.D. and M.Sc. dissertations, and unpublished materials. RESULTS AND DISCUSSION: F. hispida is used especially in Chinese and Indian traditional medical systems as a remedy for skin disorders, respiratory diseases, and urinary diseases. Wound healing, anti-inflammatory, antinociceptive, sedative, antidiarrheal, antiulcer, antimicrobial, antioxidant, hepatoprotective, antineoplastic, and antidiabetic activities have been reported for crude extracts and isolated metabolites, but the methodologies in these studies often have inadequate design and low technical quality. More than 76 compounds have been isolated from F.hispida, including sesquiterpenoids and triterpenoids, flavonoids, coumarins, phenylpropionic acids, benzoic acid derivatives, alkaloids, steroids, other glycosides, and alkanes, but the method of bioassay-guided fractionation is seldom applied in the isolation from F. hispida. CONCLUSION: F. hispida is used widely in traditional medicines and has multiple pharmacological effects that could support traditional uses. However, pharmacological studies should be viewed with caution because of the inappropriate experimental design. More in vitro and in vivo research is urgently needed to study the molecular mechanisms and assess the effective and safe dose of F. hispida.

Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling.

Ischemia/reperfusion (I/R) injury in cardiomyocytes is related to excess reactive oxygen species (ROS) generation and can be modulated by nitric oxide (NO). We have previously shown that grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant, decreased ROS and may potentially stimulate NO production. In this study, we investigated whether GSPE administration at reperfusion was associated with cardioprotection and enhanced NO production in a cardiomyocyte I/R model. GSPE attenuated I/R-induced cell death [18.0 +/- 1.8% (GSPE, 50 microg/ml) vs. 42.3 +/- 3.0% (I/R control), P < 0.001], restored contractility (6/6 vs. 0/6, respectively), and increased NO release. The NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 200 microM) significantly reduced GSPE-induced NO release and its associated cardioprotection [32.7 +/- 2.7% (GSPE + L-NAME) vs. 18.0 +/- 1.8% (GSPE alone), P < 0.01]. To determine whether GSPE induced NO production was mediated by the Akt-eNOS pathway, we utilized the Akt inhibitor API-2. API-2 (10 microM) abrogated GSPE-induced protection [44.3% +/- 2.2% (GSPE + API-2) vs. 27.0% +/- 4.3% (GSPE alone), P < 0.01], attenuated the enhanced phosphorylation of Akt at Ser473 in GSPE-treated cells and attenuated GSPE-induced NO increases. Simultaneously blocking NOS activation (L-NAME) and Akt (API-2) resulted in decreased NO levels similar to using each inhibitor independently. These data suggest that in the context of GSPE stimulation, Akt may help activate eNOS, leading to protective levels of NO. GSPE offers an alternative approach to therapeutic cardioprotection against I/R injury and may offer unique opportunities to improve cardiovascular health by enhancing NO production and increasing Akt-eNOS signaling.

[Value of intra-operative ultrasound in detecting the boundaries of intra cranial gliomas].

OBJECTIVE: To evaluate the application of intra-operative ultrasound (IOUS) in detecting the boundaries of intracranial gliomas. METHODS: One hundred and five consecutive patients with supra-tentorial glioma were included, male: 42 cases, female: 46 cases, age ranged from 15 - 67 years (mean 41 yrs), intra-operative ultrasound B was used to detect tumour boundaries before and after resection in 88 cases, tissues with suspicious echo was taken for verification by histological examination. And repeated MRI scan was received within 3 day after operation to judge the resection extent. The result was judged by Ultrasound doctor, neurosurgeon and pathologist, respectively. RESULTS: Eighty-eight patients were operated assisted by IOUS B. Tumour was nearly total removed in 83 cases and subtotal removed in 5 cases. Histological examination showed WHO Grade II 30 cases, Grade III 31 cases and Grade IV 27 cases. One hundred and twenty samples were taken and 101 were verified as tumours. And residual tumours were found in 17 cases and brain contusion and laceration was found in 1 case. The sensitivity of IOUS was 80.1% and the specificity was 69.8%. CONCLUSIONS: IOUS could produce a marked effect in judging boundaries of glioma, especially in low grade gliomas. IOUS could be a routine technique in intracranial glioma operation.