Ginsenoside CK (GCK), as a metabolite of ginsenoside Rb1, has been studied for its anti-cancer activity. However, its in-depth anti-cancer mechanism on cervical cancer (CC) HeLa cells has not been ...fully elucidated. This study found that GCK inhibited the proliferation of CC HeLa cells and caused alteration in cell morphology with an IC
50
of 45.95 μM. At the same time, GCK treatment blocked the cell cycle in the G0/G1 phase, elevated the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (Δ
ψ
m
), contributed to Ca
2+
leakage, inhibited HeLa cell metastasis, and stimulated the key markers related to apoptosis, mitochondrial and endoplasmic reticulum pathways. GCK altered the regulation of the Caspase family, Bak/Bcl-xl and down-regulated the endoplasmic reticulum pathways (PERK and IRE1α). Starting from flow cytometry and the protein level, we found that autophagy inhibitors inhibited autophagy while promoting apoptosis, and apoptosis inhibitors reduced the rate of apoptosis while promoting autophagy, which proved that GCK can be used as a suitable novel natural product for CC treatment.
Ginsenoside CK inhibits the cervical cancer HeLa cell
Via
blocking the cell cycle in the G0/G1 phase, and inducing apoptosis by the endoplasmic reticulum pathway.
BACKGROUND:GTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase uncoupling in endothelial dysfunction. MicroRNAs (miRs) are a class of regulatory RNAs that ...negatively regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation.
METHODS:Endothelial function was assessed by measuring acetylcholine-induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization.
RESULTS:We first demonstrated that GCH1 mRNA is a target of miR-133a. In endothelial cells, miR-133a was robustly induced by cytokines/oxidants and inhibited by lovastatin. Furthermore, lovastatin upregulated GCH1 and tetrahydrobiopterin, and recoupled endothelial nitric oxide synthase in stressed endothelial cells. These actions of lovastatin were abolished by enforced miR-133a expression and were mirrored by a miR-133a antagomir. In mice, hyperlipidemia- or hyperglycemia-induced ectopic miR-133a expression in the vascular endothelium, reduced GCH1 protein and tetrahydrobiopterin levels, and impaired endothelial function, which were reversed by lovastatin or miR-133a antagomir. These beneficial effects of lovastatin in mice were abrogated by in vivo miR-133a overexpression or GCH1 knockdown. In rats, multiple cardiovascular risk factors including hyperglycemia, dyslipidemia, and hyperhomocysteinemia resulted in increased miR-133a vascular expression, reduced GCH1 expression, uncoupled endothelial nitric oxide synthase function, and induced endothelial dysfunction, which were prevented by lovastatin.
CONCLUSIONS:Statin inhibits aberrant miR-133a expression in the vascular endothelium to prevent endothelial dysfunction by targeting GCH1. Therefore, miR-133a represents an important therapeutic target for preventing cardiovascular diseases.
In hyperspectral image (HSI) processing, a fundamental issue is to restore HSI data from various degradations such as noise corruption and information missing. However, most existing methods more or ...less ignore the abundant prior knowledge on HSIs and the embedded noise, leading to suboptimal performance in practice. In this article, we propose a novel HSI restoration method by fully considering the intrinsic image structures and the complex noise characteristics. For HSIs, the global correlation is captured by the Kronecker-basis-representation-based tensor low-rankness measure, which integrates the insights delivered by both CP and Tucker decompositions; the local regularity is depicted by a plug-and-play spatial-spectral convolutional neural network with strong fitting ability to complex image features. For realistic noise, its statistical characteristics are encoded by a nonidentical and nonindependent distributed mixture of Gaussians distribution with flexible fitting capability. Then, we incorporate these image and noise priors into a probabilistic model based on the maximum a posteriori principle, and develop a solving scheme by combining expectation-maximization and alternating direction method of multipliers. Extensive experimental results on both simulated and real scenarios demonstrate the effectiveness of the proposed method and its superiority over the compared state-of-the- arts.
Condensation of benzene-1,3,5-tricarbohydrazide with benzene-1,4-dicarboxaldehyde generated a new covalent organic framework, COF-ASB (1), in which the organic units are held together via hydrazone ...linkage to form porous frameworks. COF-ASB (1) is highly crystalline and displays good chemical and thermal stability and is permanently porous. In addition, 1 can be an ideal support to load Ru nanoparticles (Ru NPs) to generate Ru@COF-ASB (2). The obtained composite material is able to highly promote one-pot tandem synthesis of imine products from benzyl alcohols and corresponding amines under solvent-free conditions in air.
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IJS, KILJ, NUK, PNG, UL, UM
A smart H-phosphonate-mediated synthetic strategy for the sulfonylation of heteroaromatic N-oxides has been developed, by which a large variety of 2-sulfonyl quinolines/pyridines were synthesized ...starting from easily available sulfonyl chlorides, diisopropyl H-phosphonate and pyridine/quinoline N-oxides in one pot under metal-free conditions at room temperature.
This study sought to explore the association between Life's Simple 7 (LS7) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathological biomarkers in the cognitively normal northern Chinese ...population.
From the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, 1106 cognitively normal participants were enrolled. The mean age was 62.34 years, and 39.6% were female. LS7 scores were summed with each metric assigned 0, 1, or 2 scores. The multiple linear regression models were used to investigate the association between LS7 scores and CSF AD biomarkers.
We found that LS7 scores were significantly associated with CSF AD pathologies, including Aβ42/40 (β = 0.034, P = .041), p-tau181 (β = - 0.043, P = .006), and t-tau (β = - 0.044, P = .003). In subscales, the biological metrics (blood pressure, cholesterol, glucose) were significantly related to CSF tau-related biomarkers. These associations were observed in the APOE ε4 allele non-carriers, yet not in carriers. The relationship of behavior metrics was found in the middle age and males.
Improving LS7 scores might do a favor to alleviate the pathology of AD in the preclinical stage, especially among the APOE ε4 allele non-carriers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new homochiral BINAPDA-Zr-MOF was prepared by a new chiral organic linker of (R)-4,4′-(6,6′-dichloro-2,2′-diethoxyl-1,1′-binaphthalene-4,4′-diyl)dibenzoic acid (R -L) and ZrCl4 under solvothermal ...conditions. Its structure was determined by Pawley refinement on the basis of the measured PXRD pattern determined for BINAPDA-Zr-MOF, and it showed that the obtained chiral MOF crystallized in the F23 space group with the same topological structure as that of UiO-66. The obtained BINAPDA-Zr-MOF can be a very active catalyst to catalyze aldehyde cyanosilylation. In addition, the chiral BINAPDA-Zr-MOF was a typical solid catalyst, which was proved by a hot leaching test; moreover, it could be reused at least five times without loss of its catalytic activity and enantioselectivity.
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IJS, KILJ, NUK, PNG, UL, UM
Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular ...mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.
•HD promotes Aβ phagocytosis and degradation through activating autophagy flux.•HD improved cognitive impairment and attenuated the pathology of AD through inducing autophagy and activating ...TFEB.•PPARα played an important role in HD activating TFEB and alleviating AD.
Autophagic flux is coordinated by a network of master regulatory genes, which centered on transcription factor EB (TFEB). The disorders of autophagic flux are closely associated with Alzheimer's disease (AD), and thus restoring autophagic flux to degrade pathogenic proteins has become a hot therapeutic strategy. Hederagenin (HD), a triterpene compound, isolated from a variety food such as Matoa (Pometia pinnata) Fruit, Medicago sativa, Medicago polymorpha L. Previous studies have shown that HD has the neuroprotective effect. However, the effect of HD on AD and underlying mechanisms are unclear.
To determine the effect of HD on AD and whether it promotes autophagy to reduce AD symptoms.
BV2 cells, C. elegans and APP/PS1 transgenic mice were used to explore the alleviative effect of HD on AD and the molecular mechanism in vivo and in vitro.
The APP/PS1 transgenic mice at 10 months were randomized into 5 groups (n = 10 in each group) and orally administrated with either vehicle (0.5% CMCNa), WY14643 (10 mg/kg/d), low-dose of HD (25 mg/kg/d), high-dose of HD (50 mg/kg/d) or MK-886 (10 mg/kg/d) + HD (50 mg/kg/d) for consecutive 2 months. The behavioral experiments including morris water maze test, object recognition test and Y maze test were performed. The effects of HD on Aβ deposition and alleviates Aβ pathology in transgenic C. elegans were operated using paralysis assay and fluorescence staining assay. The roles of HD in promoting PPARα/TFEB-dependent autophagy were investigated using the BV2 cells via western blot analysis, real-time quantitative PCR (RT-qPCR), molecular docking, molecular dynamic (MD) simulation, electron microscope assay and immunofluorescence.
In this study, we found that HD upregulated mRNA and protein level of TFEB and increased the distribution of TFEB in the nucleus, and the expressions of its target genes. HD also promoted the expressions of LC3BII/LC3BI, LAMP2, etc., and promoted autophagy and the degradation of Aβ. HD reduced Aβ deposition in the head area of C. elegans and Aβ-induced paralysis. HD improved cognitive impairment and pathological changes in APP/PS1 mice by promoting autophagy and activating TFEB. And our results also showed that HD could strongly target PPARα. More importantly, these effects were reversed by treatment of MK-886, a selective PPARα antagonist.
Our present findings demonstrated that HD attenuated the pathology of AD through inducing autophagy and the underlying mechanism associated with PPARα/TFEB pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Phosphorus (P) is an essential element for plant growth and yield. Improving phosphorus use efficiency of crops could potentially reduce the application of chemical fertilizer and alleviate ...environmental damage. Soybean (Glycine max (L.) Merr.) is sensitive to phosphorus (P) in the whole life history. Soybean cultivars with different P efficiencies were used to study P uptake and dry matter accumulation under different P levels. Under low P conditions, the P contents of leaf in high P efficiency cultivars were greater than those in low P efficiency cultivars at the branching stage. The P accumulation in stems of high P efficiency cultivars and in leaves of low P efficiency cultivars increased with increasing P concentration at the branching stage. At the late podding stage, the P accumulation of seeds in high and low P efficiency cultivars were 22.5 and 26.0%, respectively; and at the mature stage were 69.8 and 74.2%, respectively. In average, the P accumulation in whole plants and each organ was improved by 24.4% in high P efficiency cultivars compared to low P efficiency cultivars. The biomass between high and low P efficiency cultivars were the same under extended P condition, while a significant difference was observed at late pod filling stage. At the pod setting stage, the biomass of high P efficiency cultivars were significant greater (17.4%) than those of low P efficiency cultivars under high P condition. Meanwhile, under optimum growth conditions, there was little difference of biomass between the two types of cultivars, however, the P agronomic efficiency and P harvest index were significant higher in high P efficiency cultivars than those in low P efficiency cultivars.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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