Although still under debate, observations generally suggest that dwarf spheroidal (dSph) galaxies exhibit large constant-density cores in the centers, which can hardly be explained by dissipationless cold dark matter simulations without baryonic feedback. Wave dark matter (ψDM), characterized by a single parameter, the dark matter particle mass m ψ , predicts a central soliton core in every galaxy arising from quantum pressure against gravity. Here we apply Jeans analysis assuming a soliton core profile to the kinematic data of eight classical dSphs so as to constrain m ψ , and obtain m ψ = 1.18 +0.28 −0.24 × 10 −22 eV and m ψ = 1.79 +0.35 −0.33 × 10 −22 eV (2σ) using the observational data sets of Walker et al. (2007) andWalker et al. (2009b), respectively. We show that the estimate of m ψ is sensitive to the dSphs kinematic data sets and is robust to various models of stellar density profile. We also consider multiple stellar subpopulations in dSphs and find consistent results. This mass range of m ψ is in good agreement with other independent estimates, such as the high-redshift luminosity functions, the reionization history, and the Thomson optical depth to the cosmic microwave background.
DNA studies of the translocation t(15;17) in acute promyelocytic leukemia (APL) have shown that the retinoic acid receptor alpha (RARA) gene on chromosome 17 is juxtaposed to the promyelocytic leukemia (PML) gene on chromosome 15. The PML breakpoints have been mapped to 3 clusters: bcr1, bcr2, and bcr3. We have examined the PML breakpoint distribution in a series of 33 Chinese patients with APL. Twenty-two patients fell within bcr1, 2 within bcr2, and 9 within bcr3. The primary structure of the reciprocal chromosome translocation joints of one patient and that of their normal counterparts have been determined and compared to those of 2 previously reported cases. These studies revealed possible topoisomerase II cleavage sites close to the breakpoints and suggested implications of DNA attachment sites to nuclear matrix. We propose that these features are relevant to the process of illegitimate recombination generating the translocation.
Chemical investigation of the marine soft coral Sarcophyton tenuispiculatum resulted in the isolation of a 1,4-dihydrobenzoquinone, sarcotenuhydroquinone (1), three new cembranoids, sarcotenusenes A‒C (2‒4), and ten previously reported metabolites 5–14. The chemical structures of all isolated metabolites were determined by detailed spectroscopic analyses. In biological assays, anti-inflammatory, cytotoxic, and peroxisome proliferator-activated receptor γ (PPAR-γ) transcription factor assays of all compounds were performed. None of the isolated compounds were found to exhibit activity in the PPAR-γ transcription factor assay. The anti-inflammatory assays showed that (+)-7α,8β-dihydroxydeepoxysarcophine (13) inhibited the production of IL-1β to 56 ± 1% at a concentration of 30 µM in lipopolysaccharide (LPS)-stimulated J774A.1 macrophage cells. In addition, 1 and 2 were found to exhibit cytotoxicity towards a panel of cancer cell lines.
Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.
The anticancer effect of pomegranate polyphenolic extract POMx in oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced ATP depletion, subG1 accumulation, and annexin V/Western blotting-detected apoptosis in these three oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial superoxide (MitoSOX) generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions in oral cancer cells. POMx downregulated mitochondrial mass, mitochondrial DNA copy number, and mitochondrial biogenesis gene mRNA/protein expression in oral cancer cells. Moreover, POMx induced both PCR-based mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of oral cancer cells through mechanisms of mitochondrial impairment.
Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed.
Further chemical investigation of the ethyl acetate extract of the soft coral Sarcophyton tortuosum has led to the isolation of ten terpenoidal metabolites, including six new compounds, secoditerpenes secotortuosenes A and B (1 and 2), diterpenes tortuosenes C and D (3 and 4) and tortuosumol (5), and a biscembranoid bisotortuolide cyclobutane A (6), along with four known compounds, ketoemblide (7), sartrolide G (8), emblide (9), and sarcrassin E (10). Compounds 5 and 6 are metabolites of intra- and intermolecular [2+2] cyclizations, respectively. Notably, 1 and 2 are 12-membered carbocyclic compounds possessing a 2-methyl-3-oxopentanyl side chain and representing an unprecedented molecular skeleton, while compound 6 possesses a unique cyclobutanyl biscembranoid skeleton. The absolute configurations of 1 and 5 were determined by TDDFT ECD calculations. Bioassays showed that compound 5 exhibited selective cytotoxicity against the growth of the Molt-4 cell line, while 6 exhibited inhibitory activity against P388, K562, and HT-29 cancer cell lines. Compounds 3 and 5–7 showed effects for inhibition toward the generation of superoxide anion, while 3, 6, and 7 displayed inhibition activity against elastase release in fMLF/CB-induced neutrophils. In addition, compounds 6, 7, and 10 exhibited anti-inflammatory activity by inhibiting nitric oxide generation in the LPS-induced RAW 264.7 cell assay.
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