The acute toxicity and hematological characterization of the effects of tentacle-only extract from the jellyfish Cyanea capillata

To investigate the hematologic changes and the activities of jellyfish venoms other than hemolytic and cardiovascular toxicities, the acute toxicity of tentacle-only extract (TOE) from the jellyfish Cyanea capillata was observed in mice, and hematological indexes were examined in rats. The median lethal dose (LD(50)) of TOE was 4.25 mg/kg, and the acute toxicity involved both heart- and nervous system-related symptoms. Arterial blood gas indexes, including pH, PCO(2), HCO(3) (-), HCO(3)std, TCO(2), BEecf and BE (B), decreased significantly. PO(2) showed a slight increase, while SO(2)c (%) had no change at any time. Na(+) and Ca(2+) decreased, but K(+) increased. Biochemical indexes, including LDH, CK, CK-MB, ALT, AST and sCr, significantly increased. Other biochemical indexes, including BUN and hemodiastase, remained normal. Lactic acid significantly increased, while glucose, Hct% and THbc showed slight temporary increases and then returned to normal. These results on the acute toxicity and hematological changes should improve our understanding of the in vivo pathophysiological effects of TOE from C. capillata and indicate that it may also have neurotoxicity, liver toxicity and muscular toxicity in addition to hemolytic and cardiovascular toxicities, but no kidney or pancreatic toxicity.     

(+)-儿茶素缓解大鼠低氧性肺动脉高压的作用和机制

研究了(+)-儿茶素对SD大鼠低氧性肺动脉高压(PAH)的影响及其机制。采用27只SD雄性大鼠按随机数字表法分为3组(对照组、缺氧模型组、(+)-儿茶素干预组)。通过检测大鼠平均肺动脉压(Mean pulmonary arterialpressure,mPAP)和肺血管阻力(Pulmonaryvascularresistance,PVR)反应体内肺血流动力学变化;处死大鼠后测算右心室肥厚指数(Rightventriclehypertrophyindex,RVHI)及肺动脉血管壁厚度和外周血管直径的比值(Vascular wall thickness of outer circumference ratio,WT%);WB检测肺动脉内皮细胞一氧化氮合酶(eNOS),用NO试剂盒检测NO表达量;用CCK-8法检测肺动脉平滑肌细胞增殖以确定细胞活力,利用WB检测分析肺动脉平滑肌细胞钙敏感受体(CaSR)、荧光探针法检测细胞内总Ca²⁺的浓度。研究结果表明,与缺氧模型组相比,(+)-儿茶素能够显著减缓肺缺氧诱导的肺动脉压力升高(n=9,P<0.05;);通过逆转缺氧引起的肺内皮细胞一氧化氮合酶(eNOS)显著减少(n=3,P<0.05)和NO合成显著减少(n=5,P<0.05),达到抑制肺动脉内皮血管收缩作用;通过下调缺氧诱导的平滑肌细胞内CaSR表达(n=3,P<0.05),逆转缺氧的升钙效应(n=27,P<0.05),达到抑制平滑肌细胞增殖的作用(n=30,P<0.05)。综上可见,(+)-儿茶素通过抑制肺血管收缩和血管平滑肌细胞增殖来缓解缺氧诱导的PAH,为PAH的治疗方法提供了新思路。     

不同磷水平对不同基因型烤烟磷素吸收动力学参数特征的影响

采用砂培营养液培养方法,研究了不同基因型烤烟在缺磷(-P)、适磷(+P)、过磷(++P)处理10 d后对磷吸收情况及(H2PO4--P)吸收动力学参数特征。结果表明:经不同磷水平预处理后,不同基因型烤烟品种对H2PO4--P的吸收符合离子吸收动力学模型,其吸收动力学参数Vmax值与Km值随磷浓度的增加存在较大差异,随磷浓度的增加,K326的Vmax值增大,Km值增加;粤烟97在+P浓度处理时Vmax值最大,Km值最小;粤烟98在++P浓度处理时Vmax值最大,Km值最小。-P处理时,不同烤烟品种对H2PO4--P的吸收速率表现为:K326>粤烟97>粤烟98;+P处理时,对H2PO4--P的吸收速率表现为:K326≈粤烟97>粤烟98;++P处理时,对H2PO4--P的吸收速率表现为:K326>粤烟97≈粤烟98。上述结果表明,不同浓度磷供应对不同品种烤烟H2PO4--P吸收速率影响较大,不同基因型烤烟亲和力水平存在差异;低磷胁迫对K326低亲和力系统H2PO4--P吸收速率具有促进作用,高磷胁迫对粤烟98高亲和力系统H2PO4--P吸收速率具有促进作用,而低磷、高磷胁迫对粤烟97磷吸收速率均存在抑制作用。     

Marine-Derived Quorum-Sensing Inhibitory Activities Enhance the Antibacterial Efficacy of Tobramycin against Pseudomonas aeruginosa

Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs). Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI) activity against acyl homoserine lactone (AHL)-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (−63%) and in pre-established, mature P. aeruginosa PAO1 biofilms (−33%). KS8 supernatant also caused a 0.97-log reduction (−89%) and a 2-log reduction (−99%) in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC) of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC) was observed over the concentration range tested (MBC > 16 mg/mL). Sub-MIC concentrations (1 mg/mL) of KS8 crude organic extract significantly reduced the quorum sensing (QS)-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments.     

Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist,Antillatoxin

Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Na_v1.1–Na_v1.9), Na_v1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Na_v1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNa_v1.7 α-subunit, ATX produced a robust membrane depolarization with an EC₅₀ value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNa_v1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC₅₀ values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNa_v1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNa_v1.7 antagonists.     

Frajunolides L-O, four new 8-Hydroxybriarane diterpenoids from the Gorgonian Junceella fragilis

Four new 8-hydroxybriarane diterpenoids, frajunolides L-O (1-4), were isolated from the Taiwanese gorgonian Junceella fragilis. The structures of compounds 1-4 were elucidated based on spectroscopic analysis, especially 2D NMR ((1)H-(1)H COSY, HSQC, HMBC and NOESY) and HRMS. Compounds 1 and 4 showed weak anti-inflammatory activity as tested by superoxide anion generation and elastase release by human neutrophil in response to fMLP/CB. Compound 3 showed selective inhibition on elastase release in vitro.     

The effect of intermittent hypoxia on bodyweight, serum glucose and cholesterol in obesity mice

This article tests mice's indicators of body nutritional metabolism under tolerable hypoxic conditions, in order to explore the effects of moderate intermittent hypoxia on the bodyweight, blood sugar and blood cholesterol of obese mice and to identify the role of leptin in these effects; this study applies high-fat diet to establish Mice Obesity Models and observes the intervention effects of intermittent hypoxic training in this Model. Small healthy mice are classified in 4 groups at random, that is, Group A (Normal), Group B (Normal Hypoxia) fed with normal foods and undergoing Intermittent Hypoxic Training (IHT), Group C (Fatty-diet) fed with High-Fat and High-Sugar (HFHS) foods without IHT and Group D (Fatty-diet and Hypoxia) fed with HFHS foods with IHT. After 40 days of feeding and hypoxic training, weigh the mice, measure the levels of blood sugar and blood cholesterol with a full automatic biochemical analyzer, measure serum leptin concentration by enzyme-linked immunosorbent assay (ELISA) technique, inspect liver leptin receptor expression and liver fat slice by immunohistochemistry. It is found that compared to control group, after experiment, the average bodyweight, blood sugar, blood cholesterol and serum leptin concentration in Group C is increased significantly and numerous fat cells are distributed in the liver, which indicates that hyperlipemia model has been successfully established; after intermittent hypoxic training, the average bodyweight, blood sugar, blood cholesterol and liver fat cells distribution density and scope in Group B and D are lower than those in Group A and C, while serum leptin concentration is increased significantly; liver leptin receptor expression in Group D is higher than that in Group C. And hypoxia groups have no trauma conclusion. Moderate intermittent hypoxia can reduce bodyweight by increasing leptin concentration and enhancing liver leptin expression and it can also reduce the level of blood sugar and blood cholesterol and meanwhile prevent steatosis in liver cells effectively.     

New Briarane diterpenoids from the gorgonian coral Junceella juncea

Chemical investigation of Junceella juncea has resulted in the isolation of three new briaranes designated juncenolides M-O (1-3). The structures of these compounds were determined by spectroscopic analysis including 2D-NMR (COSY, HMBC and NOESY) and HRMS. Compound 1 is a new chlorinated briarane while compound 3 contains a rare methyl ester at C-16. The anti-inflammatory activities tested on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB were evaluated.     

花生－油菜轮作模式下硼肥及其后效对作物产量的影响

通过田间试验研究硼砂（B,Na2B4O7?10H2O）、Ulexite granular（UB,NaCaB5O9?8H2O）、Etibor-48（EB, Na2B4O7?5H2O）和Colemanite（CB, Ca2B6O11?5H2O）四种硼肥在花生-油菜轮作中的肥效及其后效对作物产量的影响。结果表明,按正常施硼量（纯硼用量1.70 kg/hm2）基施硼砂、UB、EB和CB四种硼肥,花生和油菜产量均有不同程度的提高;两倍施硼量（纯硼用量3.40 kg/hm2）与正常施硼量相比,不同硼肥处理作物增产率均有不同程度降低,其中土壤有效硼含量0.49 mg/kg时,作物增产率并不随施硼量的继续增加而升高。基施四种硼肥,三季作物收获后土壤有效硼含量均高于0.5 mg/kg,秸秆硼含量与作物产量也显著高于不施硼处理。基施硼肥可以改善土壤有效硼状况,具有较强缓释性的硼肥UB和CB在第二季和第三季具有较好的增产效果。在农业生产上可以根据土壤有效硼状况和硼肥本身的缓效性作为基施长效硼肥合理推广利用。     

Response of potato tubers to hypoxia followed by re-aeration

Summary Potato tubers kept under hypoxia (1%) showed improved viability in comparison to anoxia, which was associated with the maintenance of intermediate adenylate energy charge values (A.E.C.=0.6) and stable adenylate pools at 50% of the initial levels. Re-admission of oxygen to the tuber resulted in an almost full recovery of adenylate energy charge and total adenylates after up to 3 days of hypoxic pretreatment. Tubers exhibited a mixed fermentation. The high lactate, ethanol and acetaldehyde levels proved to be non toxic. Ethanol was degraded to acetaldehyde during re-aeration. Posthypoxic lipid peroxidation was indicated by malondialdehyde and ethane formation. Both products occurred with a temporary delay and in lower amounts compared to post-anoxia. Ethylene release was also considerably smaller. Severe hypoxia and posthypoxia postponed tissue death compared to anoxia. Survival was correlated with an improved energy supply which stabilized membranes.     

Pacific-Ciguatoxin-2 and Brevetoxin-1 Induce the Sensitization of Sensory Receptors Mediating Pain and Pruritus in Sensory Neurons

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.     

Rare Chromones from a Fungal Mutant of the Marine-Derived Penicillium purpurogenum G59

Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3) and isoconiochaetone C (4), along with three known remisporine B (1), coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6) were isolated from a mutant from the diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. The structures of 2–4 including the absolute configurations were determined by spectroscopic methods, especially by NMR analysis and electronic circular dichroism (ECD) experiments in conjunction with calculations. The absolute configuration of the known remisporine B (1) was determined for the first time. Compounds 2 and 3 have a rare feature that has only been reported in one example so far. The compounds 1–6 were evaluated for their cytotoxicity against several human cancer cell lines. The present work explored the great potential of our previous DES mutagenesis strategy for activating silent fungal pathways, which has accelerated the discovery of new bioactive compounds.     

Identification of Two Novel Anti-Fibrotic Benzopyran Compounds Produced by Engineered Strains Derived from Streptomyces xiamenensis M1-94P that Originated from Deep-Sea Sediments

The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.     

Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

In this work, we designed and synthesized a series of amide derivatives (1–13), benzoxazine derivatives (16–28) and amino derivatives (29–30) from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35) were evaluated for their protection against H₂O₂-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC₅₀ values of them and the leading compound 31 (xyloketal B) were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA) was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B) were further to examine in the JC-1 mitochondrial membrane potential (MMP) assay of HUVECs using flow cytometry (FCM). The result indicated that 23 and 24 significantly inhibited H₂O₂-induced decrease of the cell mitochondrial membrane potential (ΔΨm) at 25 μM. Collectively, the protective effects of xyloketals on H₂O₂-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.     

Nitric Oxide Synthase in the Central Nervous System and Peripheral Organs of Stramonita haemastoma: Protein Distribution and Gene Expression in Response to Thermal Stress

Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing structural and functional characteristics with nNOS or iNOS depending on the species. The present paper is focused on the constitutive Ca²⁺/calmodulin-dependent nNOS recently sequenced by our group in the neogastropod Stramonita haemastoma (ShNOS). In this paper we provide new data on cellular distribution of ShNOS in the CNS (pedal ganglion) and peripheral organs (osphradium, tentacle, eye and foot) obtained by WB, IF, CM and NADPHd. Results demonstrated that NOS-like proteins are widely expressed in sensory receptor elements, neurons and epithelial cells. The detailed study of NOS distribution in peripheral and central neurons suggested that NOS is both intracellular and presynaptically located. Present findings confirm that NO may have a key role in the central neuronal circuits of gastropods and in sensory perception. The physiological relevance of NOS enzymes in the same organs was suggested by thermal stress experiments demonstrating that the constitutive expression of ShNOS is modulated in a time- and organ-dependent manner in response to environmental stressors.     

Quality indices of Jew's mallow and spinach during frozen storage

In this study, Jew's mallow and spinach were heat treated and kept frozen, at –18°C, for 3 months. Analysis of some chemical components and enzymatic activities as well as a sensory evaluation were undertaken. At the end of the storage period, blanched spinach showed no PPO (polyphenyloxidase) activity at all, but still contained PO (peroxydase) and LO (lipoxygenase) activities. The untreated spinach stored under the same conditions showed high activities of PO, PPO and LO. The heat treated mallow still contained high enzyme activities which decreased slowly during frozen storage. Statistical analysis of the chemical composition and the sensory evaluation results indicated that heat treatments of mallow caused significant differences in total solids, pH, chlorophylla and total chlorophyll, while frozen storage, of samples of the same treatment for 3 months caused no significant differences in moisture, ash, oxalic acid, pH, chlorophylla and total chlorophyll. No significant differences could be noticed in the overall acceptability between mallow samples mixed with hot water and those mixed in the overall acceptability between mallow samples mixed with hot water and those mixed with a hot 0.1% MgCO₃ solution. Significant differences were found between the heat treated and the untreated mallow. Changes of the chemical composition and the overall acceptability of blanched spinach during frozen storage showed almost the same trend noticed for the Jew's mallow.     

Evaluation of the Effect of Photosynthesis on Biomass Production with Simultaneous Analysis of Growth and Continuous Monitoring of CO2 Exchange in the Whole Plants of Radish,cv Kosena under Ambient and Elevated CO2

Abstract

The effects of elevated CO₂ (approximate doubling of atmospheric CO₂ concentration) on the rate of photosynthesis estimated from continuous monitoring of CO₂ exchange in whole plants were investigated in radish cv. Kosena accompanied with simultaneous analysis of growth for 6 days from 15 to 21 days after planting (DAP). The elevated CO₂ increased the dry weights of hydroponically grown radish plants by 59% at 21 DAP.

The increase in dry weight was due to a combined effect of increased leaf area and increased photosynthetic rate per unit leaf area. Leaf area and the photosynthetic rate were increased by elevated CO₂ by 18-43% and 9-20%, respectively, during 15 to 21 DAP. Namely, an increase in the rate of photosynthesis is accompanied by an increase in leaf area, both having a significant effect on biomass production.     

Management of peanut pod rot II: Comparison of calendar and threshold-based fungicide timings

Peanut pod rot, which can be caused by Pythium spp. and Rhizoctonia solani, is difficult to manage with fungicides. The objective of this study was to compare the effects of a calendar-based (CB) versus threshold-based (INC) fungicide application timings on pod rot incidence, yield, value of the crop, and returns minus fungicide cost. Large plot replicated trials were conducted in five fields with a history of pod rot. Pod rot was assessed weekly throughout the season following development of pods. Disease incidence was reduced by the preventative CB compared with INC or the non-fungicide treated control (NONE) in three of five sites. Disease was very low in the remaining two sites. Yield was not affected by treatment at individual sites, but in a combined analysis, INC at 1–2% incidence had higher yields than CB treated with mefenoxam or NONE. Occurrence of segregation 2 kernels, which results in a substantial reduction in price, was more frequent with INC and NONE than with CB at two sites. CB and INC had a higher value/ha than NONE, but there were no differences in return minus fungicide costs. CB had less pod rot during the season and a lower risk of segregation 2 kernels at harvest than INC. These results suggest that preventative CB applications made at early pegging should be used to manage pod rot. This recommendation is based on the reduction of risk to segregation 2 kernels, not because of a higher value/ha of the crop.     

Effects of storage on the physico-chemical properties of corn tortillas prepared with glycerol and salt

Corn tortillas have a short shelf life due to increased firmness and microbial spoilage. Commercial corn tortillas use carboxymethyl cellulose (CMC) to delay staling; however this gum is expensive when compared to the rest of the tortilla ingredients. Glycerol has been added to bread and wheat tortillas to increase pliability and salt has been shown to mask the flavor of glycerol in corn tortillas. The possibility to reduce staling in corn tortillas by adding glycerol/salt as an alternative to CMC was investigated by monitoring changes in physico-chemical properties during 2 weeks of storage at 25 °C. Molecular and macroscopic changes were followed using thermal and mechanical analysis. During storage an increase in amylopectin recrystallization was observed in all samples. The “freezable” water content of all tortillas decreased over the first 3–5 days of storage with an increase after 7 days, while moisture content and water activity remained constant. Glycerol/salt tortillas exhibited a sharper transition region in the DMA temperature scan suggesting a more homogenous sample. CMC tortillas were significantly stiffer than glycerol tortillas after 14 days of storage. Glycerol/salt combinations may offer at least a partial replacement for CMC since it helped control the stiffness, water homogeneity and distribution during storage.