Matrix metalloproteinase-9 (MMP-9) may play an important role in emphysematous change in chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality and morbidity worldwide. We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, attenuates emphysematous change and MMP-9 induction in the lungs of rats exposed to cigarette smoke. However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients. Presently, we examined the related signaling for MMP-9 induction and the inhibitory mechanism of simvastatin on MMP-9 induction in AMs exposed to cigarette smoke extract (CSE). In isolated rat AMs, CSE induced MMP-9 expression and phosphorylation of ERK and Akt. A chemical inhibitor of MEK1/2 or PI3K reduced phosphorylation of ERK or Akt, respectively, and also inhibited CSE-mediated MMP-9 induction. Simvastatin reduced CSE-mediated MMP-9 induction, and simvastatin-mediated inhibition was reversed by farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). Similar to simvastatin, inhibition of FPP transferase or GGPP transferase suppressed CSE-mediated MMP-9 induction. Simvastatin attenuated CSE-mediated activation of RAS and phosphorylation of ERK, Akt, p65, IκB, and nuclear AP-1 or NF-κB activity. Taken together, these results suggest that simvastatin may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of RAS in the signaling pathways, in which Raf-MEK-ERK, PI3K/Akt, AP-1, and IκB-NF-κB are involved.
Six new polyhydroxysteroidal glycosides, anthenosides S1 - S6 (1 - 6), along with a mixture of two previously known related glycosides, 7 and 8, were isolated from the methanolic extract of the starfish Anthenea sibogae. The structures of 1 - 6 were established by NMR and HR-ESI-MS techniques as well as by chemical transformations. All new compounds have a 5α-cholest-8(14)-ene-3α,6β,7β,16α-tetrahydroxysteroidal nucleus and differ from majority of starfish glycosides in positions of carbohydrate moieties at C(7) and C(16) (1 - 4, 6) or only at C(16) (5). The 4-O-methyl-β-d-glucopyranose residue (2) and Δ -cholestane side chain (3) have not been found earlier in the starfish steroidal glycosides. The mixture of 7 and 8 slightly inhibited the proliferation of human breast cancer T-47D cells and decreased the colony size in the colony formation assay.
A new dihydrochalcone 4',6'-dihydroxy-2',3',4-trimethoxydihydrochalcone (1) along with nine known compounds, pashanone (2), dihydropashanone (3), pinostrobin (4), 5-hydroxy-7,4'-dimethoxyflavanone (5), 5-hydroxy-6,7-dimethoxyflavanone (6), 5-hydroxy-7,8-dimethoxyflavanone (7), 24-methylencycloartane-3β,21-diol (8), liriodenine (9) and 3,5-dihydroxy-7,3',4'-trimethoxyflavone (10), were isolated from the extracts, exhibiting cytotoxic activity (n-hexane and ethyl acetate extracts) of Miliusa sinensis. The structure of (1) was elucidated by the analysis of spectral data (IR, HR-MS, EI-MS, 1D and 2D NMR).
Two new aporphine alkaloids: 8-hydroxy-9-methoxy-1,2-methylenedioxyaporphine (1) and 8-hydroxy-3,9-dimethoxy-1,2-methylenedioxyaporphine (2) were isolated from the ethyl acetate extract of Fissistigma poilanei along with five known compounds: oxocrebanine (3), kuafumine (4), (2R,3R)-3',4',5,7-tetrahydroxydihydroflavonol-3-O-α-L-rhamnopyranoside (5), (+)-catechin 3-O-α-L-rhamnopyranoside (6) and quercetine 3,7-dimethoxy-3'-O-α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside (7). These two new aporphine alkaloids exhibited a moderate cytotoxic activity against four human cancer cell lines (KB, Hep-G2, MCF-7, LU) as well as antimicrobial activity against Lactobacillus fermentum, Enterococcus faecium, Staphylococcus aureus and Bacillus subtillis.
There have been many attempts to acquire and culture human keratinocytes for clinical purposes including from keratotome slices in media with fetal calf serum (FCS) or pituitary extract (PE), from skin specimens in media with feeder layers, from suction blister epidermal roofs' in serum-free culture and from human umbilical cord blood (hUCB) mesenchymal stem cells (MSCs) in media with skin feeder layers. Conversely this study was designed to investigate whether keratinocytes could be obtained directly from hUCB MSCs in vitro. It is widely established that mesenchymal stem cells from human umbilical cord blood have multipotent capacity and the ability to differentiate into disparate cell lineages hUCB MSCs were directly induced to differentiate into keratinocytes by using a specific medium composed of primary culture medium (PCM) and serum free medium (SFM) in a ratio 1:9 for a period of 7 days and tested by immunostain p63 and K1-K10. Cells thus cultured were positive in both tests, confirming the possibility to directly obtain keratinocytes from MSCs hUCB in vitro.
BACKGROUND:
Vietnam possesses a vast diversity of rice landraces due to its geographical situation, latitudinal range, and a variety of ecosystems. This genetic diversity constitutes a highly valuable resource at a time when the highest rice production areas in the low-lying Mekong and Red River Deltas are enduring increasing threats from climate changes, particularly in rainfall and temperature patterns.
RESULTS:
We analysed 672 Vietnamese rice genomes, 616 newly sequenced, that encompass the range of rice varieties grown in the diverse ecosystems found throughout Vietnam. We described four Japonica and five Indica subpopulations within Vietnam likely adapted to the region of origin. We compared the population structure and genetic diversity of these Vietnamese rice genomes to the 3,000 genomes of Asian cultivated rice. The named Indica-5 (I5) subpopulation was expanded in Vietnam and contained lowland Indica accessions, which had with very low shared ancestry with accessions from any other subpopulation and were previously overlooked as admixtures. We scored phenotypic measurements for nineteen traits and identified 453 unique genotype-phenotype significant associations comprising twenty-one QTLs (quantitative trait loci). The strongest associations were observed for grain size traits, while weaker associations were observed for a range of characteristics, including panicle length, heading date and leaf width.
CONCLUSIONS:
Our results highlight differences in genome composition and trait associations among traditional Vietnamese rice accessions, which are likely the product of adaption to multiple environmental conditions and regional preferences in a very diverse country. Our results highlighted traits and their associated genomic regions that are a potential source of novel loci and alleles to breed a new generation of sustainable and resilient rice.
New asterosaponin, acanthaglycoside G (1), along with three previously known steroidal oligoglycosides (2-4), were isolated from the ethanolic extract of the starfish Acanthaster planci, collected off the coast of Vietnam. The structure of 1 was mainly elucidated by extensive NMR and ESIMS techniques as sodium 6-O-{-D-fucopyranosyl-(1→2)--D-quinovopyranosyl-(1→4)-[-D-quinovopyranosyl-(1→2)]--D-quinovopyranosyl-(1→3)--D-quinovopyranosyl}-6-hydroxy-5-pregn-9(11)-en-20-one-3-yl sulfate. Compounds 3 and 4 showed slight cytotoxic activities against cancer RPMI-7951, HT-29, and MDA-MB-23 cell lines, but effectively inhibited in nontoxic concentrations colony formation of HT-29 and MDA-MB-231 cells and cell migration of MDA-MB-231 cells. Compounds 1 and 2 were inactive or less active, respectively.
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