Edaravone protects against lung injury induced by intestinal ischemia/reperfusion in rat

Intestinal ischemia/reperfusion (I/R) is a critical and triggering event in the development of distal organ dysfunction, frequently involving the lungs. Respiratory failure is a common cause of death and complications after intestinal I/R. In this study we investigated the effects of edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) on the prevention of lung injury induced by intestinal I/R in rats. Edaravone has been used for protection against I/R injury in patients with cerebral infarction. When rats were subjected to 180 min of intestinal ischemia, a high incidence of mortality was observed within 24 h. In this situation, intravenous administration of edaravone just before the start of reperfusion reduced the mortality in a dose-dependent manner. To examine the efficacy of edaravone on the lung injury induced by intestinal I/R in more detail, we performed 120 min of intestinal ischemia followed by 120 min of reperfusion. Edaravone treatment decreased the neutrophil infiltration, the lipid membrane peroxidation, and the expression of proinflammatory cytokine interleukin-6 mRNA in the lungs after intestinal I/R compared to the I/R-treated rat lungs without edaravone treatment. Histopathological analysis also indicated the effectiveness of edaravone. In conclusion, edaravone ameliorated the lung injury induced by intestinal I/R, resulting in a reduction in mortality.     

Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells

Dendrite morphology of neurons provides a structural basis for their physiological characteristics, and is precisely regulated in a cell type-dependent manner. Using a unique transposon-mediated gene transfer system that enables conditional and cell-type specific expression of exogenous genes, we investigated the role of cadherin on dendritic morphogenesis of horizontal cells in the developing chicken retina. We first visualized single horizontal cells by overexpressing membrane-targeted EGFP, and confirmed that there were three subtypes of horizontal cells, the dendritic terminals of which projected to distinct synaptic sites in the outer plexiform layer. Expression of a dominant-negative cadherin decreased the dendritic field size, and perturbed the termination of dendritic processes onto the photoreceptor cells. The cadherin blockade also impaired the accumulation of GluR4, a postsynaptic marker, at the cone pedicles. We thus provide in vivo evidence that cadherin is required for dendrite morphogenesis of horizontal cells and subsequent synapse formation with photoreceptor cells in the vertebrate retina.     

Articulospora sp. produces Art1, an inhibitor of bacterial histidine kinase

A two-component system (TCS) comprising a histidine kinase (HK) sensor and a response regulator (RR) plays important roles in regulating the virulence of many pathogenic bacteria. We used a new screening method to isolate novel inhibitor Art1 against bacterial sensory HK from an acetone extract of solid cultures of Articulospora sp., an aquatic hypomycete. Art1 inhibited the ATP-dependent autophosphorylation of recombinant glutathione S-transferase-fusion protein SasA, a cyanobacterial HK, with an IC50 value of 9.5 microg/ml.     

Two forms of secreted and thermostable luciferases from the marine copepod crustacean, Metridia pacifica

We cloned two forms of the secreted and thermostable luciferase genes, MpLuc1 and MpLuc2, from the marine copepod, Metridia pacifica. The 840-bp MpLuc1 cDNA comprised a 630-bp open reading frame encoding a 210-amino acid polypeptide (22.7 kDa). MpLuc1 had the closest homology with Metridia longa luciferase. The 753-bp MpLuc2 cDNA consisted of a 567-bp open reading frame (20.3 kDa), and it had the closest homology with Gaussia princeps luciferase. Single-specimen genomic PCR confirmed the presence of two luciferase genes in M. pacifica, and single-specimen RT-PCR revealed that both luciferase mRNAs were expressed. Both MpLuc1 and MpLuc2 (MpLucs) specifically reacted with the substrate coelenterazine producing identical bioluminescent spectra (lambdamax, 485 nm), but with different kinetics. Adding salt such as MgCl2 and CaCl2 to the reaction mixture significantly enhanced MpLuc1 and MpLuc2 activities. Wild-type MpLucs were remarkably thermostable; MpLuc1 retained about 60% of the original activity even after incubation at 90 degrees C for 30 min. MpLucs expressed in NIH-3T3 and HeLa cells were largely secreted into the culture medium. Continuous monitoring of secreted MpLuc1 driven by the c-fos promoter demonstrated the potential usefulness of MpLuc1 in nondisruptive reporter assays.     

1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors

Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC₅₀ values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one ( 2 ) (IC₅₀=134.35±11.38 μM) exhibiting slightly better IC₅₀ value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one ( 15 ) (IC₅₀=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one ( 18 ) (IC₅₀=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one ( 22 ) (IC₅₀=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.     

Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents

Various dietary antioxidants, including vitamins, flavonoids, curcumin, and a coumarin, were conjugated with paclitaxel (1) through an ester linkage. The newly synthesized compounds were evaluated for cytotoxic activity against several human tumor cell lines as well as the corresponding normal cell lines. Interestingly, most tested conjugates selectively inhibited the growth of 1A9 (ovarian) and KB (nasopharyngeal) tumor cells without activity against other cell lines. Particularly, conjugates 16 and 20 were highly active against 1A9 (ED(50) value of 0.005 microg/mL) as well as KB (ED(50) values of 0.005 and 0.14 microg/mL, respectively) cells. Compound 22b, the glycinate ester salt of vitamin E conjugated with 1, appears to be a promising lead for further development as a clinical trial candidate as it exhibited strong inhibitory activity against Panc-1 (pancreatic cancer) with less effect on the related E6E7 (normal) cell line.     

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

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Leptin reduces Atlantic salmon growth through the central pro-opiomelanocortin pathway

Leptin (Lep) is a key factor for the energy homeostasis in mammals, but the available data of its role in teleosts are not conclusive. There are large sequence differences among mammalian and teleost Lep, both at the gene and protein level. Therefore, in order to characterize Lep function in fish, the use of species-specific Lep is crucial. In this study, the cDNA sequence of salmon leptin a1 (lepa1) was used to establish a production protocol for recombinant salmon LepA1 (rsLepA1) in Escherichia coli, that enabled a final yield of 1.7 mg pure protein L^?1 culture. The effects of 20-day administration of rsLepA1 on growth and brain neuroendocrine peptide gene expression [npy, cart, agrp (-1 and -2), pomc (-a1, -a2, -a2s, and -b)] were studied in juvenile, immature Atlantic salmon (96.5 ± 2.1 g) fed a commercial diet to satiation. Intraperitoneal osmotic pumps were used to deliver rsLepA1 at four different concentrations (calculated pumping rates were 0, 0.1, 1.0 and 10 ng g^?1 h^?1). In the highest dosage group (10 ng g^?1 h^?1), the growth rate was significantly reduced, and pomc-a1 gene expression was higher than in controls. The results support the lipostatic hypothesis and suggest that sLepA1 reduces growth in Atlantic salmon by affecting food intake through the central pro-opiomelanocortin pathway.     

Life cycle environmental and economic impact of a food waste recycling-farming system: a case study of organic vegetable farming in Japan

Purpose

Bio-based recycling systems and agricultural production using recycled materials are often evaluated separately. This study performs an environmental and socio-economic life cycle assessment (LCA) of a food waste treatment and spinach farming system in Japan. The environmental and economic tradeoffs of introducing a recycling system and the net environmental benefit of the substitution of market fertilizer considering operation changes are also examined.

Methods

Three scenarios were developed and compared. In the conventional (CV) scenario, food waste is collected, incinerated, and disposed of in landfill, and the farmer uses market organic fertilizer. The on-site composting (OC) scenario processes food waste using an on-site garbage disposer and transports compost to a nearby spinach farmer. Food waste in the centralized composting (CC) scenario is transported to a centralized composting facility and resultant compost is sent to the farm. Primary data were obtained from field experiments and interviews. Non-greenhouse gas (GHG) emissions from the field and nitrogen leaching to water systems were simulated using the denitrification–decomposition (DNDC) model.

The environmental LCA targeted climate change, eutrophication, and waste landfill. An input–output analysis estimated socio-economic indicators, namely gross added value and employment inducement effect.

Results and discussion

The scenario with the lowest impact is the CC scenario. Climate change and eutrophication impacts are highest in the OC scenario and waste landfill impacts are most significant in the CV scenario. The weighted impact by LIME2 can be reduced by 47% in the CC scenario and 17% in the OC scenario due to the recycling of food waste instead of dumping in the landfill. The difference in socio-economic indicators between the scenarios was relatively small, although the CV scenario encouraged more employment. The substitution effect of composting, as well as the environmental impact reduction of replacing market organic fertilizer with compost, will result in 28.7% of the avoided impacts in GHG emissions.

Conclusions

Both composting scenarios are feasible from an environmental and socio-economic perspective when compared with conventional organic production, although there is a tradeoff between waste landfill and GHG emissions for the on-site composting system. However, the OC scenario needs to save electricity to improve its environmental competitiveness with the CV scenario. When considering the substitution effect of composting, it is recommended to take into account that agricultural operation also changes.