Targeted metabolomics profiling in pregnancy associated with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is common in pregnancy, however, its effects has not been fully elucidated. Here, we conducted targeted metabolomics profiling to study the relationship. METHODS: This study enrolled 111 pregnant women, including sufficient group (n = 9), inadequate group (n = 49) and deficient group (n = 53). Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabonomics were used to characterize metabolite profiles associated with vitamin D deficiency in pregnancy. RESULTS: Many metabolites decreased in the inadequate and deficient group, including lipids, amino acids and others. The lipid species included fatty acyls (FA 14:3, FA 26:0; O), glycerolipids (MG 18:2), glycerophospholipids (LPG 20:5, PE-Cer 40:1; O2, PG 29:0), sterol lipids (CE 20:5, ST 28:0; O4, ST 28:1; O4). Decreased amino acids included aromatic amino acids (tryptophan, phenylalanine, tyrosine) and branched-chain amino acids (valine, isoleucine, leucine), proline, methionine, arginine, lysine, alanine, L-kynurenine,5-hydroxy-L-tryptophan, allysine. CONCLUSIONS: This targeted metabolomics profiling indicated that vitamin D supplementation can significantly affect lipids and amino acids metabolism in pregnancy.

Microbial community interactions determine the mineralization of soil organic phosphorus in subtropical forest ecosystems.

In subtropical forest ecosystems with few phosphorus (P) inputs, P availability and forest productivity depend on soil organic P (Po) mineralization. However, the mechanisms by which the microbial community determines the status and fate of soil Po mineralization remain unclear. In the present study, soils were collected from three typical forest types: secondary natural forest (SNF), mixed planting, and monoculture forest of Chinese fir. The P fractions, Po-mineralization ability, and microbial community in the soils of different forest types were characterized. In addition, we defined Po-mineralizing taxa with the potential to interact with the soil microbial community to regulate Po mineralization. We found that a higher labile P content persisted in SNF and was positively associated with the Po-mineralization capacity of the soil microbial community. In vitro cultures of soil suspensions revealed that soil Po mineralization of three forest types was distinguished by differences in the composition of fungal communities. We further identified broad phylogenetic lineages of Po-mineralizing fungi with a high intensity of positive interactions with the soil microbial community, implying that the facilitation of Po-mineralizing taxa is crucial for soil P availability. Our dilution experiments to weaken microbial interactions revealed that in SNF soil, which had the highest interaction intensity of Po-mineralizing taxa with the community, Po-mineralization capacity was irreversibly lost after dilution, highlighting the importance of microbial diversity protection in forest soils. In summary, this study demonstrates that the interactions of Po-mineralizing microorganisms with the soil microbial community are critical for P availability in subtropical forests.IMPORTANCEIn subtropical forest ecosystems with few phosphorus inputs, phosphorus availability and forest productivity depend on soil organic phosphorus mineralization. However, the mechanisms by which the microbial community interactions determine the mineralization of soil organic phosphorus remain unclear. In the present study, soils were collected from three typical forest types: secondary natural forest, mixed planting, and monoculture forest of Chinese fir. We found that a higher soil labile phosphorus content was positively associated with the organic phosphorus mineralization capacity of the soil microbial community. Soil organic phosphorus mineralization of three forest types was distinguished by the differences in the composition of fungal communities. The positive interactions between organic phosphorus-mineralizing fungi and the rest of the soil microbial community facilitated organic phosphorus mineralization. This study highlights the importance of microbial diversity protection in forest soils and reveals the microbial mechanism of phosphorus availability maintenance in subtropical forest ecosystems.

Combining Network Pharmacology with Experimental Validation to Elucidate the Mechanism of Salvianolic Acid B in Treating Diabetic Peripheral Neuropathy.

Background: Salvianolic acid B (Sal B) is a bioactive component of Radix Salviae, which has antiinflammation and antiapoptotic activity in diabetic complications. However, the molecular mechanism of action of Sal B on diabetic peripheral neuropathy (DPN) is unknown. This study was designed to identify a mechanism for Sal B in the treatment of DPN by using a pharmacology network, molecular docking, and in vitro experiments. Methods: Sal B and DPN-related targets from Gene Cards and OMIM platforms were retrieved and screened. Then, an analysis of possible targets with STRING and Cytoscape software was conducted. KEGG signaling pathways were determined using the R software. Subsequently, the binding capacity of Sal B to target proteins was analyzed by molecular docking and in vitro experiments. Results: A total of 501 targets related to Sal B and 4662 targets related to DPN were identified. Among these targets, 108 intersection targets were shared by Sal B and DPN. After topological and cluster analysis, 11 critical targets were identified, including p38MAPK. KEGG analysis revealed that the AGE-RAGE signaling pathway likely plays an important role in Sal B action on DPN. The p38MAPK protein is a key target in the AGE-RAGE signaling pathway. Molecular docking results suggested that Sal B and p38MAPK have excellent binding affinity (<-5 kcal/mol). The in vitro experiments revealed that Sal B downregulates the expressions of p-P38MAPK, inflammatory cytokines, and apoptosis targets, which are upregulated by hyperglycemia. Conclusion: Sal B may alter DPN by inhibiting inflammation and apoptosis activated by p38MAPK.

A Panax notoginseng phosphate transporter, PnPht1;3, greatly contributes to phosphate and arsenate uptake.

The crisis of arsenic (As) accumulation in rhizomes threatens the quality and safety of Panax notoginseng (Burk.) F.H. Chen, which is a well-known traditional Chinese herb with a long clinical history. The uptake of arsenate (AsV) could be suppressed by supplying phosphate (Pi), in which Pi transporters play important roles in the uptake of Pi and AsV. Herein, the P . notoginseng Pi transporter-encoding gene PnPht1;3 was identified and characterised under Pi deficiency and AsV exposure. In this study, the open reading frame (ORF) of PnPht1;3 was cloned according to RNA-seq and encoded 545 amino acids. The relative expression levels revealed that PnPht1;3 was significantly upregulated under phosphate deficiency and AsV exposure. Heterologous expression in Saccharomyces cerevisiae MB192 demonstrated that PnPht1;3 performed optimally in complementing the yeast Pi-transport defect and accumulated more As in the cells. Combined with the subcellular localisation prediction, it was concluded that PnPht1;3 encodes a functional plasma membrane-localised transporter protein that mediates putative high-affinity Pi/H+ symport activity and enhances the uptake of Pi and AsV. Therefore, a better understanding of the roles of the P . notoginseng Pi transporter could provide new insight for solving As accumulation in medicinal plants.

Alteration of lung tissues proteins in birch pollen induced asthma mice before and after SCIT.

Subcutaneous immunotherapy (SCIT) is a classic form of allergen-specific immunotherapy that is used to treat birch pollen induced allergic asthma. To investigate the underlying molecular mechanisms of SCIT, we aimed to profile lung samples to explore changes in the differential proteome before and after SCIT in mice with allergic asthma. Fresh lungs were collected from three groups of female BALB/c mice: 1) control mice, 2) birch pollen-induced allergic mice, and 3) birch pollen-induced allergic mice with SCIT. Tandem mass tag (TMT) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the lung proteome in the mice. Ingenuity pathway analysis (IPA) and Gene Ontology (GO) classification analysis were applied to identify differentially expressed proteins (DEPs) and crucial pathways. The screened DEPs were validated by immunohistochemistry analysis. A total of 317 proteins were upregulated and 184 proteins were downregulated in the asthma group compared to those of the control group. In contrast, 639 DEPs (163 upregulated and 456 downregulated proteins) were identified after SCIT in comparison with those of the asthma group. Among the 639 DEPs, 277 proteins returned to similar levels as those of the relative non-asthma condition. Bioinformatic analysis revealed that the 277 proteins played a significant role in the leukocyte extravasation signaling pathway. The leukocyte extravasation signaling pathway and related DEPs were of crucial importance in birch pollen SCIT.

Identification and First Report of Fusarium andiyazi Causing Sheath Rot of Zizania latifolia in China.

Zizania latifolia is a perennial plant native to East Asia. The swollen culm of Z. latifolia is a popular vegetable and traditional herbal medicine consumed in China and some other Asian countries. From 2019 to 2021, a sheath rot disease was found in Zhejiang Province of China. Symptoms mainly occurred in the leaf sheath showing as brown necrotic lesions surrounded by yellow halos. The pathogen fungal isolates were isolated from the affected sheaths. Ten representative isolates were selected for morphological and molecular identification by phylogenetic analyses of the translation elongation factor 1-α (TEF1) and the RNA polymerase II subunit beta (RPB2) gene regions. Based on the combined datasets, the fungal isolates were identified as Fusarium andiyazi. Koch's postulates were confirmed by pathogenicity test, re-isolation and re-identification of the fungal isolates. To the best of our knowledge, this is the first report of sheath rot caused by F. andiyazi in Z. latifolia in China.

Shrubs magnify soil phosphorus depletion in Tibetan meadows: Conclusions from C:N:P stoichiometry and deep soil profiles.

Globally, the proliferation of shrubs within grasslands stimulates soil phosphorus (P) cycling and increases topsoil P storage beneath their canopies. However, little is known regarding the impact of shrub encroachment on subsoil P storage, and whether shrubs mediate changes in soil stoichiometry, like increasing P cycling. In grazed meadows on the Tibetan Plateau, soil and roots were sampled to 1 m depth in shrubby Hippophae rhamnoides ssp. sinensis groves and the surrounding grassy areas. Shrubs had higher P content than grasses, but lower C:P ratios in their leaves, litter, and roots. Similarly, shrubs had higher microbial P content than grasses, but lower microbial biomass C:P and N:P ratios in the soil. The larger microbial P stock in the 1 m of soil beneath shrubs responded to the larger root P stock there as well. Thus, both the plants and microbes acquired more P in shrubby areas than in grassy areas by accelerating P mineralization. The greater net production of available P in the topsoil and the synthesis of microbial P throughout the profile under shrubs increased the P solubility. Total P, inorganic P, and organic P stocks were lower under shrubs than under grasses in the top 1 m of soil. This decrease in soil P storage beneath shrubs is most likely attributable to P leaching due to higher P solubility, heavy rainfall, and larger soil gaps. Moreover, shrubs also had larger plant biomass P stock compared to grasses, and thus the depletion of P from the top 1 m of soil was further magnified via plant biomass removal. We concluded that shrubs increase P cycling to overcome the stoichiometric imbalance between their P requirement and the supply in the soil, and the fast P cycling under shrubs magnify P depletion within the rooted soil depth in alpine meadows.

Association between serum vitamin D levels and venous thromboembolism (VTE): A systematic review and meta-analysis of observational studies.

OBJECTIVE: Although many studies have attempted to unravel the relationship between vitamin D deficiency and the incidence of VTE, the results remained inconsistent. To address this discrepancy, we performed a systematic review and meta-analysis to precisely disentangle the relationship between serum vitamin D levels and VTE risk. METHODS: The Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases were searched for all available observational studies that reported the risk of venous thromboembolism (VTE) based on serum vitamin D levels categories. The search was performed up to March 2020. RESULTS: Seven studies were included. The overall analysis showed a significantly increased risk of VTE in subjects with low levels of serum vitamin D compared with those with normal vitamin D levels (RR = 1.34; 95% CI: 1.07-1.69; P = 0.011). In a sensitivity analysis, we did not observe a significant effect of any individual study on the combined effect sizes. Nevertheless, significant heterogeneity was present among the studies (Cochrane Q test, p = 0.018, I2 = 61%). In the stratified analysis, low vitamin D levels were positively associated with an increased risk of VTE in prospective population-based studies (RR = 1.31; 95% CI: 1.06-1.61; P = 0.010) and in subjects below 60 years old (RR = 1.28; 95% CI: 1.07-1.54; P = 0.060). CONCLUSION: our systematic review and meta-analysis showed that a low serum vitamin D level was indeed associated with an increased risk of VTE.

Biological Efficacy and Safety of Niacinamide in Patients With ADPKD.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement, leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses. METHODS: We conducted an open-label, single-arm intervention trial (study 1, N = 10), and a randomized, double blinded, placebo-controlled trial (study 2, N = 36) to assess the biological activity and safety of niacinamide. Patients with ADPKD were given 30 mg/kg oral niacinamide or placebo, for 12 months. The primary endpoint was the ratio of acetylated p53 to total p53 protein in peripheral blood mononuclear cells (PBMCs). RESULTS: There was no sustained effect of niacinamide on acetylated/total p53 in either study and no difference between placebo and niacinamide arms. There was no difference in the change in height-adjusted total kidney volume over 12 months between niacinamide and placebo. Niacinamide was generally well tolerated. The most common adverse effects were nausea, diarrhea, gastroesophageal reflux, headache, and acneiform rash but there was no difference in their incidence between niacinamide and placebo. CONCLUSIONS: In conclusion, niacinamide is safe and well-tolerated in patients with ADPKD. However, we were unable to detect a sustained inhibition of sirtuin activity over 12 months of treatment, and there was no signal to suggest a beneficial effect on any efficacy measure.

Systems Pharmacology-Dissection of the Molecular Mechanisms of Dragon's Blood in Improving Ischemic Stroke Prognosis.

MATERIALS AND METHODS: (1) Based on system-pharmacology platform, the potential active compounds of DB are screened out according to ADME. (2) The ischemic stroke-related targets are predicted by utilizing these active compounds as probes, mapping the targets to the CTD database to establish a molecular-target-disease network. (3) To analyze the mechanism of DB treatment for the prognosis of ischemic stroke, we used the Metascape and DAVID databases to construct "ischemic stroke pathways". (4) PC12 cells were used to explore the protective effect of loureirin B on oxygen-glucose deprivation/reperfusion (OGD/R) injury, and BV-2 cells were used to determine the anti-inflammation effect of 4',7-dihydroxyflavone. RESULTS: Finally, we obtained 38 active compounds and 58 stroke-related targets. Network and pathway analysis indicate that DB is effective in the treatment of ischemic stroke by enhancing cell survival and inhibiting inflammatory and antiplatelet activation. In in vitro experiments, the main component loureirin B promoted the expression of HO-1 and Bcl-2 via positive regulation of PI3K/AKT/CREB and Nrf2 signaling pathways in PC12 cells against OGD/R damage. And the anti-inflammatory activity of 4',7-dihydroxyflavone was related to the inhibition of COX-2, TNF-α, and IL-6 in LPS-induced BV-2 cells. CONCLUSIONS: In our study, the results illustrated that DB in improving ischemic stroke prognosis may involve enhancing cell survival and antioxidant, anti-inflammation, and antiplatelet activities.

Coupling of non-point source pollution and soil characteristics covered by Phyllostachys edulis stands in hilly water source area.

The non-point source pollution of drinking water source areas is a global issue which is mainly caused by unreasonable management of the commercial forests growing in the upstream areas. However the occurrence and specific mechanism of runoff pollution in these areas have not been approached. In order to clarify the factors influencing the non-point source pollution in the area, the test plot in Fushi Reservoir watershed covered by Phyllostachys edulis plantations with pure and modified stands was chosen, and the characteristics of soil chemical properties, enzyme activities and the coupling between soil factors and surface runoff of were initially analyzed, the relationship between soil factors and surface runoff pollutants was examined using redundancy analysis. The results showed that pH, soil nitrate reductase (S-NR) and catalase (S-CAT) were the key factors affecting the differentiation of water quality in surface runoff. The total nitrogen (TN) concentration in surface runoff was positively correlated with S-NR but negatively correlated with pH, TN and alkali-hydrolyzed nitrogen (AN) concentrations in soil. The total phosphorus (TP) concentration was negative correlation with soil pH and TP. In addition, the permanganate index (CODMn) concentration has positive correlation with urease (S-UE), acid phosphatase (S-ACP) and organic matter (SOM) in soil. These results suggest that soil enzyme activities are more sensitive than soil nutrient status, and could be used as indicators of non-point source pollution assessing. Moreover, pollution in this area could be effectively controlled by enhancing vegetation coverage and ameliorating soil environment.

Identification of species and materia medica within Saussurea subg. Amphilaena based on DNA barcodes.

Saussurea is one of the most species-rich genera in the family Asteraceae, where some have a complex evolutionary history, including radiation and convergent evolution, and the identification of these species is notoriously difficult. This genus contains many plants with medical uses, and thus an objective identification method is urgently needed. Saussurea subg. Amphilaena is one of the four subgenera of Saussurea and it is particularly rich in medical resources, where 15/39 species are used in medicine. To test the application of DNA barcodes in this subgenus, five candidates were sequenced and analyzed using 131 individuals representing 15 medical plants and four additional species from this subgenus. Our results suggested that internal transcribed spacer (ITS) + rbcL or ITS + rbcL + psbA-trnH could distinguish all of the species, while the ITS alone could identify all of the 15 medical plants. However, the species identification rates based on plastid barcodes were low, i.e., 0% to 36% when analyzed individually, and 63% when all four loci were combined. Thus, we recommend using ITS + rbcL as the DNA barcode for S. subg. Amphilaena or the ITS alone for medical plants. Possible taxonomic problems and substitutes for medicinal plant materials are also discussed.

Transcutaneous Electrical Acupoint Stimulation Accelerates the Recovery of Gastrointestinal Function after Cesarean Section: A Randomized Controlled Trial.

BACKGROUND: Gastrointestinal functional recovery is an important factor affecting postoperative outcome. The aim of this study was to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on gastrointestinal function in women undergoing cesarean section. METHODS: 150 pregnant women undergoing cesarean section were randomly allocated into TEAS, nonacupoint stimulation (sham group), and no stimulation (control group). The primary outcome was indications of gastrointestinal functional recovery and the secondary outcomes included time to first mobilization, postoperative hospital stay, daily living activities at one week after surgery, postoperative side-effects, and serum levels of gastroenterological hormones. RESULTS: The time to first flatus in TEAS group was significantly shorter compared to control (P=0.004) and sham groups (P=0.003). The time to first oral liquid and solid intake was significantly shorter than that in control (P<0.001; P=0.021) and sham group (P=0.019; P=0.037). Besides, postoperative hospital stay was shorter in TEAS group than in control group (P=0.031) and sham group (P<0.001). TEAS also promoted daily living activities (P=0.001 versus control group and P=0.015 versus sham group). Postoperative complications were similar among all the groups except for the incidence of abdominal distention 24 h after surgery (P=0.013; P=0.040). The motilin level was increased by TEAS (P=0.014 versus control group and P=0.020 versus sham group). CONCLUSION: TEAS accelerated gastrointestinal functional recovery after cesarean section, by reducing postoperative hospital length, and improved daily living activities after surgery. This effect was partially mediated by regulation of the gastroenterological hormones.

In silico-based screen synergistic drug combinations from herb medicines: a case using Cistanche tubulosa.

Neuroinflammation is characterized by the elaborated inflammatory response repertoire of central nervous system tissue. The limitations of the current treatments for neuroinflammation are well-known side effects in the clinical trials of monotherapy. Drug combination therapies are promising strategies to overcome the compensatory mechanisms and off-target effects. However, discovery of synergistic drug combinations from herb medicines is rare. Encouraged by the successfully applied cases we move on to investigate the effective drug combinations based on system pharmacology among compounds from Cistanche tubulosa (SCHENK) R. WIGHT. Firstly, 63 potential bioactive compounds, the related 133 direct and indirect targets are screened out by Drug-likeness evaluation combined with drug targeting process. Secondly, Compound-Target network is built to acquire the data set for predicting drug combinations. We list the top 10 drug combinations which are employed by the algorithm Probability Ensemble Approach (PEA), and Compound-Target-Pathway network is then constructed by the 12 compounds of the combinations, targets, and pathways to unearth the corresponding pharmacological actions. Finally, an integrating pathway approach is developed to elucidate the therapeutic effects of the herb in different pathological features-relevant biological processes. Overall, the method may provide a productive avenue for developing drug combination therapeutics.

Underlying mechanisms and effects of hydrated lime and selenium application on cadmium uptake by rice (Oryza sativa L.) seedlings.

A pot experiment was conducted to investigate the effects of selenium (Se) and hydrated lime (Lime), applied alone or simultaneously (Se+Lime), on growth and cadmium (Cd) uptake and translocation in rice seedlings grown in an acid soil with three levels of Cd (slight, mild, and moderate contamination). In the soil with 0.41 mg kg-1 Cd (slight Cd contamination), Se addition alone significantly decreased Cd accumulation in the root and shoot by 35.3 and 40.1%, respectively, but this tendency weakened when Cd level in the soil increased. However, Se+Lime treatment effectively reduced Cd accumulation in rice seedlings in the soil with higher Cd levels. The results also showed that Se application alone strongly increased Cd concentration in the iron plaque under slight Cd contamination, which was suggested as the main reason underlying the inhibition of Cd accumulation in rice seedlings. Se+Lime treatment also increased the ability of the iron plaques to restrict Cd uptake by rice seedlings across all Cd levels and dramatically decreased the available Cd concentration in the soil. These results suggest that Se application alone would be useful in the soil with low levels of Cd, and the effect would be enhanced when Se application is combined with hydrated lime at higher Cd levels.

Anticystogenic activity of a small molecule PAK4 inhibitor may be a novel treatment for autosomal dominant polycystic kidney disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary renal disease with no currently available targeted therapies. Based on the established connection between ß-catenin signaling and renal ciliopathies, and on data from our and other laboratories showing striking similarities of this disease and cancer, we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD. Treatment of PKD-derived cells with this compound not only reduces PAK4 steady-state protein levels and regulates ß-catenin signaling, but also inhibits nicotinamide phosphoribosyl transferase, the rate-limiting enzyme in a key NAD salvage pathway. KPT-9274 can attenuate cellular proliferation and induce apoptosis associated with a decrease in active (phosphorylated) PAK4 and ß-catenin in several Pkd1-null murine cell lines, with a less pronounced effect on the corresponding phenotypically normal cells. Additionally, KPT-9274 shows inhibition of cystogenesis in an ex vivo model of cyclic AMP-induced cystogenesis as well as in the early stage Pkd1flox/flox:Pkhd1-Cre mouse model, the latter showing confirmation of specific anti-proliferative, apoptotic, and on-target effects. NAD biosynthetic attenuation by KPT-9274, while critical for highly proliferative cancer cells, does not appear to be important in the slower growing cystic epithelial cells during cystogenesis. KPT-9274 was not toxic in our ADPKD animal model or in other cancer models. Thus, this small molecule inhibitor could be evaluated in a clinical trial as a viable therapy of ADPKD.

A screen for Fli-1 transcriptional modulators identifies PKC agonists that induce erythroid to megakaryocytic differentiation and suppress leukemogenesis.

The ETS-related transcription factor Fli-1 affects many developmental programs including erythroid and megakaryocytic differentiation, and is frequently de-regulated in cancer. Fli-1 was initially isolated following retrovirus insertional mutagenesis screens for leukemic initiator genes, and accordingly, inhibition of this transcription factor can suppress leukemia through induction of erythroid differentiation. To search for modulators of Fli-1, we hereby performed repurposing drug screens with compounds isolated from Chinese medicinal plants. We identified agents that can transcriptionally activate or inhibit a Fli-1 reporter. Remarkably, agents that increased Fli-1 transcriptional activity conferred a strong anti-cancer activity upon Fli-1-expressing leukemic cells in culture. As opposed to drugs that suppress Fli1 activity and lead to erythroid differentiation, growth suppression by these new Fli-1 transactivating compounds involved erythroid to megakaryocytic conversion (EMC). The identified compounds are structurally related to diterpene family of small molecules, which are known agonists of protein kinase C (PKC). In accordance, these PKC agonists (PKCAs) induced PKC phosphorylation leading to activation of the mitogen-activated protein kinase (MAPK) pathway, increased cell attachment and EMC, whereas pharmacological inhibition of PKC or MAPK diminished the effect of our PKCAs. Moreover, in a mouse model of leukemia initiated by Fli-1 activation, the PKCA compounds exhibited strong anti-cancer activity, which was accompanied by increased presence of CD41/CD61 positive megakaryocytic cells in leukemic spleens. Thus, PKC agonists offer a novel approach to combat Fli-1-induced leukemia, and possibly other cancers,by inducing EMC in part through over-activation of the PKC-MAPK-Fli-1 pathway.

Ginsenoside Rb1 prevents high glucose-induced Schwann cell injury through the mitochondrial apoptosis pathway.

OBJECTIVE: To investigate the effects of ginsenoside Rb1 on high glucose-induced neurotoxicity and the underlying molecular mechanism in primary cultured Schwann cells (SCs). METHODS: Cultured SCs were divided into six groups that received (a) normal glucose, (b) osmotic control, (c) high glucose, (d) high glucose plus 1 µM ginsenoside Rb1, (e) high glucose plus 10 µM ginsenoside Rb1, or (f) high glucose plus 100 µM alpha lipoic acid (ALA). Intracellular reactive oxygen species (ROS) generation and mitochondrial transmembrane potential (ΔΨm) were detected by flow cytometric analyses. Apoptosis was confirmed by the annexin V-FITC/propidium iodide (PI) method, and the concentration of 8-hydroxy-2-deoxy guanosine (8-OHdG) was detected by an enzyme-linked immunosorbent assay. Western blotting was performed to analyze the expression levels of important transcription factors such as cytochrome c, bcl-2, bax, activated caspase-3, and activated poly (ADP-ribose) polymerase (PARP). RESULTS: Ginsenoside Rb1 inhibited high glucose-induced oxidative stress by decreasing ROS and 8-OHdG levels as well as mitochondrial depolarization in SCs. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide and annexin V-FITC/PI assays showed that incubating SCs with high glucose decreased cell viability and increased the number of apoptotic cells, whereas treatment with ginsenoside Rb1 protected SCs against high glucose-induced cell damage. Furthermore, ginsenoside Rb1 down-regulated the expression of high glucose-induced bax and cytochrome c release but up-regulated bcl-2 expression. In addition, ginsenoside Rb1 attenuated high glucose-induced activation of caspase-3 and minimized cleavage of PARP in SCs. CONCLUSION: These results suggest that ginsenoside Rb1 antagonizes high glucose-induced oxidative stress and activation of the mitochondrial apoptosis pathway in SCs.

Differential responses of soil nematode community to pig manure application levels in Ferric Acrisols.

Excessive pig manure application probably degrades arable soil quality in some intensive pig farming areas. The responses of the nematode community to dosages of pig manure were investigated in Ferric Acrisols under 3-season peanut monoculture. Varying dosages of manure (1.75, 3.5, 7, 14 and 28 t·ha-1·yr-1) in combination with chemical fertilizer were applied to field plots, and chemical fertilizer alone was also applied as a control. With increasing manure application, the abundance of bacterivores and omnivores-predators increased, the abundance of plant parasites decreased, and fungivores abundance exhibited hump-shaped variation. Simpson diversity index and plant parasite index/maturity index of the nematode communities increased to a maximum level at a manure application rate of 3.5 t·ha-1·yr-1 and then sharply decreased. The changes in the soil nematode community were further determined to be correlated with chemical properties; available phosphorus had the strongest quadratic correlation with the two indices, implying that available phosphorus had a better indicative effect than other soil properties to nematode community. Available phosphorus in soil was deduced from 49 to 64 mg·kg-1 with the best nematode communities. Our results emphasized the importance of regular applications of manure in agriculture field to balance nematode diversity and build healthy agro-ecosystems.