Mechanism of LncRNA FOXC2-AC1 promoting lung cancer metastasis by regulating miR-107.

OBJECTIVE: Previous studies have shown that long non-coding RNA (lncRNA) FOXC2-AC1 is one of cancer-promoting genes. However, the role of FOXC2-AC1 in lung cancer (LCa) has not been reported. This study aimed to investigate the expression characteristics of FOXC2-AC1 in LCa, and to further explore the mechanism by which it accelerates the metastasis of LCa. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the level of FOXC2-AC1 in 62 pairs of LCa tissues and adjacent normal tissues, and the relationship between FOXC2-AC1 and LCa pathological parameters as well as the prognosis of patients were analyzed. Meanwhile, FOXC2-AC1 level was further verified in LCa cells by qRT-PCR. In addition, FOXC2-AC1 knockdown and overexpression models were constructed using lentivirus in LCa cell lines including H1299 and SPCA1, and the effect of FOXC2-AC1 on the biological function of LCa cells was analyzed by cell counting kit-8 (CCK-8) test along with transwell invasion and migration assay. Finally, the potential mechanism was explored using Western blotting assay. RESULTS: In this study, qRT-PCR results indicated that the expression level of FOXC2-AC1 in LCa was considerably higher than that in normal tissues, with statistically significant differences. Compared with patients with low expression of FOXC2-AC1, patients with high expression of FOXC2-AC1 had higher incidence of distant metastasis and lower overall survival rate. Compared with the control group, the cell proliferation, invasion and metastasis capacities of FOXC2-AC1 overexpressing group were considerably enhanced, while opposite results were observed in the FOXC2-AC1 silencing group. In addition, miR-107 expression was found significantly reduced no matter in LCa cell lines or in tissues and showed a negative correlation with FOXC2-AC1. Subsequently, luciferase reporter gene assay demonstrated that overexpression of miR-107 significantly attenuated the luciferase activity of the wild-type FOXC2-AC1 vector without reducing the activity of the mutant vector or empty vector, further proving that FOXC2-AC1 could be targeted by miR-107 through this binding site. In addition, rescue experiment also found that FOXC2-AC1 and miR-107 have mutual regulation, which jointly affected the malignant progression of LCa. CONCLUSIONS: These studies indicate that LncRNA FOXC2-AC1 is notably upregulated in LCa and is significantly correlated with LCa distant metastasis as well as poor prognosis. Therefore, it is suggested that lncRNA FOXC2-AC1 may promote malignant progression of LCa through the mutual regulation of miR-107.

Antifungal metabolite with a new carbon skeleton from Keissleriella sp. YS4108, a marine filamentous fungus.

In addition to four known metabolites (4-acetyl-6,8-dihydroxy-5-methylisocoumarin, 6,8-dihydroxy-3-methylisocoumarin, 6,8-dihydroxy-3,5,7-trimethylisocoumarin and 3,3'-oxy-(5-methyl)-phenol), bioassay-guided fractionation of the culture of Keissleriella sp., a marine filamentous fungus (strain number: YS 4108), afforded an antifungal metabolite with a new carbon skeleton whose structure was elucidated spectrometrically as 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4H)-one. In vitro antifungal assays of all isolates revealed that the new metabolite and 3,3'-oxybis[5-methylphenol] were inhibitory to the growth of the human pathogenic fungi Candida albicans, Tricophyton rubrum and Aspergillus niger with MICs of the former being 40, 20 and 80 microg/ml, and those of the latter 10, 30 and 50 microg/ml, respectively.

New macrocyclic diterpenoids from Euphorbia esula.

The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear).

Distance perception across spatial discontinuities.

We investigated the use of nested contact relations in perceiving the relative distance of locations on discontinuous surfaces. Observers viewed computer-generated displays under monocular static conditions and adjusted a marker to match the perceived distance of a cube. The marker and cube were raised above the ground by two different platforms separated by a gap. The relative heights and distances of the platforms were varied. We found the following: (1) When spatially discontinuous surfaces are coplanar, locations of objects resting on these surfaces appear to be compared directly, bypassing relations with the underlying ground plane. (2) Spatial displacement between the platforms produces a bias, in the direction of the displacement, in the perceived relative locations of objects resting on the platforms. This suggests that local spatial relations between objects and their platforms are only partially integrated with more global spatial relations between the discontinuous surfaces of the platforms.

Antifungal highly oxygenated guaianolides and other constituents from Ajania fruticulosa.

Three highly oxygenated guaianolides were isolated from the aerial parts of Ajania fruticulosa along with 17 known phytochemicals including a triterpene (alpha-amyrin), two plant sterols (beta-sitosterol, daucosterol), four flavonoids (axillarin, centaureidin, santin and 5,7,4'-trihydroxy-3,3'-dimethoxyflavone), and ten sesquiterpenes [1alpha-hydroperoxy-4beta,8alpha,10alpha,13-tetrahydroxyguaia-2-en-12,6alpha-olide, 1alpha-hydroperoxy-4alpha,10alpha-dihydroxyguaia-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 3beta,4alpha-dihydroxyguaia-11(13),10(14)-dien-12,6alpha-olide, 1alpha,4alpha,10alpha-trihydroxy-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxy-guaia-11(13)-en-12,6alpha-olide and 2-oxo-8alpha-hydroxyguaia-1(10),3,11(13)-trien-12,6alpha-olide, ketoplenolide B, alantolactone, 9beta-hydroxyeudesma-4,11(13)-dien-12-oic acid and 9beta-acetoxyeudesma-4,11(13)-dien-12-oic acid]. The structures of the three guaianolides were elucidated by a combination of spectroscopic methods (EIMS, HREIMS, COSY, HMQC, HMBC and NOESY) as 1beta,2beta-epoxy-3beta,4alpha,8beta,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (1), 1beta,2beta-epoxy-3beta,4alpha,9alpha,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (2) and 1beta,2beta-epoxy-10alpha-hydroperoxy-3beta,4alpha,8beta-trihydroxyguaia-11(13)-en-12,6alpha-olide (3), respectively. Antifungal bioassay of all isolates showed that guaianolides 1, 2, 3, and 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxyguaia-11(13)-en-12,6alpha-olide were inhibitory to the growth of Candida albicans with MICs being 20, 20, 20, and 40 microg/ml, respectively.

Distance perception mediated through nested contact relations among surfaces.

In complex natural scenes, objects at different spatial locations can usually be related to each other through nested contact relations among adjoining surfaces. Our research asks how well human observers, under monocular static viewing conditions, are able to utilize this information in distance perception. We present computer-generated naturalistic scenes of a cube resting on a platform, which is in turn resting on the ground. Observers adjust the location of a marker on the ground to equal the perceived distance of the cube. We find that (1) perceived distance of the cube varies appropriately as the perceived location of contact between the platform and the ground varies; (2) variability increases systematically as the relating surfaces move apart; and (3) certain local edge alignments allow precise propagation of distance information. These results demonstrate considerable efficiency in the mediation of distance perception through nested contact relations among surfaces.

Metabolites of Colletotrichum gloeosporioides, an endophytic fungus in Artemisia mongolica.

A new antimicrobial metabolite, named colletotric acid (1), was isolated from a liquid culture of Colletotrichum gloeosporioides, an endophytic fungus colonized inside the stem of Artemisia mongolica. The structure was determined using spectroscopic methods (EIMS and FABMS,(1)H and (13)C NMR, (1)H-(1)H COSY, HMBC, and HMQC). Compound 1 inhibited the growth of Bacillus subtilis, Staphylococcusaureus, and Sarcina lutea with minimal inhibitory concentrations (MICs) of 25, 50, and 50 microg/mL, respectively, and the crop pathogenic fungus Helminthosporium sativum (MIC: 50 microg/mL).

New antimicrobial mono- and sesquiterpenes from Soroseris hookeriana subsp. erysimoides.

A new monoterpene and a new guaianolide were isolated from the aerial parts of the Tibetan medicinal plant Soroseris hookeriana subsp. erysimoides (Asteraceae), in addition to (1R,4R,5R)-5-hydroxybornan-2-one 5-O-beta-D-glucopyranoside, beta-sitosterol, daucosterol, diosmetin, isoluteolin, p-methoxybenzoic acid, isovanillic acid, two phenylmethanol derivatives (vanilioloside and phenylmethanol glucopyranoside), and five guaianolides [3 beta,8 beta-dihyroxyguaia-4(15),10(14),11(13)-triene-12,6 alpha-olide, dentalactone, 10 alpha-hydroxy-8-deoxy-10,14-dihydrodeacylcinaropicrin, glucozaluzanin C and 8-epideacylcinaropicrin glucoside]. By a combination of spectroscopic methods (IR, EI-MS, 1H- and 13C-NMR, and DEPT), the structure of the new guaianolide was established as 3 beta,8 beta-dihydroxy-11 alpha H-guaia-4(15),10(14)-diene-12,6 alpha-olide, and that of the new monoterpene as (1R,4R,5R)-5-benzoyloxybornan-2-one. The antimicrobial activity of all isolates except the two sterols were measured using Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Candida albicans, Aspergillus niger, and Trichophyton rubrum as test microorganisms. The new guaianolide was shown to be equally active (MIC: 50 micrograms/ml) against E. coli, B. subtilis and A. niger. The new monoterpene inhibited exclusively the growth of B. subtilis with MIC at 25 micrograms/ml. p-Methoxybenzoic acid and isovanillic acid were inhibitory against A. niger (MIC: 25 micrograms/ml), the latter being also active against B. subtilis with MIC at 25 micrograms/ml. The flavonoids diosmetin and isoluteolin almost equally inhibited the growth of B. subtilis (MIC: 25 micrograms/ml) and the human pathgenic fungus T. rubrum (MIC: 50 micrograms/ml).

Phytochemical investigation of some traditional chinese medicines and endophyte cultures.

For many social and environmental reasons, over the last few decades, there has been an increase in chronic and life-threatening diseases including mycoses, hyperuricemia-related disorders and some mental illnesses such as depression, anxiety and Parkinson's disease. In order to fight these diseases, compounds acting on various biological targets, including enzymes such as xanthine oxidase or monoamine oxidase, have to be screened. The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in hyperuricemiarelated disorders such as gout and renal stones. One of the therapeutic approaches to treat these diseases is the use of xanthine oxidase inhibitors that block the production of uric acid. Monoamine oxidases (E.C.1.4.3.4) A and B catalyse the oxidative deamination of monoamines in the central nervous system and peripheral tissues. Inhibitors of MAO A are clinically useful to treat anxiety and depression since they are expected to increase both noradrenalin and serotonin levels in the brain. On the other hand, inhibition of MAO B appears to be an effective approach for the prevention and adjunct treatment of Parkinson's disease. In traditional Chinese medical practice, many medicinal herbs have been used to treat chronic diseases such as fungal infections, hyperuricemia-based disorders and mental illnesses. This usage is indicative for the presumable presence of antifungal phytochemicals and inhibitors of xanthine and monoamine oxidases. Plants do not represent the only source for interesting natural products; some endophytes ('special' microorganisms living inside the healthy host plant) are also known to produce secondary metabolites of promising pharmaceutical and/or agricultural potential. The above observations prompted us to search for natural antifungal compounds and inhibitors of xanthine and monoamine oxidases in different Chinese plants and endophyte cultures. The active constituents isolated were mainly mono-, sesqui-, di-, and triterpenes, sterols, coumarins, flavonoids, phenylethanoids, stilbenoids, alkaloids and alcohols.

[Clinical observation on efficacy of ivermectin in the treatment of intestinal nematode infections].

A total of 166 cases were divided into 3 groups: group A comprised 55, group B 54 and group C 57 cases. Group A received ivermectin 0.1 mg/kg orally at a single dose, the cure rates were 100%, 3.8% and 50% for ascaris, hookworm and trichuris, infections respectively: group B received ivermectin 0.2 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 11.8% and 76.5% respectively; group C received pyrantel pamoate 10 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 29.6% and 31.6% respectively. Although the cure rates were very low for hookworm infection in both group A and B, however, a number of adult worms of Ancylostoma duodenale and Necator americanus were expelled aster medication; It indicates that ivermectin has some effects on these two species of human hookworm. Side effects were mild and transient in all groups.

Stagnation and transonic effects in thermal blooming.

The effects of slewed high-energy beams on an absorbing medium are considered near regions where the relative air velocity is (a) zero and (b) transonic. Limiting effects on the density changes are buoyancy and sound speed changes, respectively. In both cases, the immediate environs of the singular point are greater contributors to phase changes in the beam than are the singularities themselves. Detailed hydrodynamic calculations are carried out for the stagnation region and the steady near-sonic region and compared (in the case of the stagnation region) with a perturbation calculation. Moment methods are used to estimate stagnation-region effects on the subsequent development of the beam.