Activation of hepatic stellate cells (HSCs) is a prominent driver of liver fibrosis. We previously demonstrated that exosomes derived from natural killer (NK) cells (NK-Exo) attenuated TGF-β1-induced ...HSC activation. Herein, this study was designed to investigate the mechanism underlying the action of NK-Exo.
NK-Exo was isolated from NK-92MI cells and then administered into TGF-β1-treated LX-2 (human HSC line) cells. MiR-223 expression in NK-Exo was downregulated by transfecting NK-92MI cells with miR-223 inhibitor followed by exosome isolation. The HSC activation was evaluated by determining cell proliferation using CCK-8 assay and measuring the protein levels of α-SMA and CoL1A1 using western blot in LX-2 cells. The expression of miR-223 was detected by qRT-PCR. The interaction between miR-223 and ATG7 was analyzed by a dual-luciferase activity assay. The autophagy was evaluated by measuring the autophagy-related proteins using western blot.
miR-223 was highly expressed in NK-Exo and inhibition of miR-223 expression in NK-Exo abrogated the inhibitory effect of NK-Exo on TGF-β-induced HSC activation. ATG7 was confirmed as a direct target of miR-223. Furthermore, treatment with the autophagy activator rapamycin and ATG7 overexpression in LX-2 cells abolished the HSC activation-suppressive effect of NK-Exo.
NK-Exo attenuated TGF-β-induced HSC activation by transferring miR-223 that inhibited autophagy via targeting ATG7.
Activation of hepatic stellate cells (HSCs) is a prominent driver of liver fibrosis. This study was designed to investigate the effect of exosomes derived from natural killer (NK) cells on HSC ...activation and liver fibrosis. The exosomes were isolated from NK-92MI cells (NK-Exo) and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Then NK-Exo was administered into TGF-β1-treated LX-2 cells (human HSC line) and mice with CCl
4
-induced liver fibrosis. LX-2 cell proliferation was determined by CCK-8 assay. The levels of α-SMA and CoL1A1 were measured by qRT-PCR and western blot to evaluate HSC activation. Serum levels of AST and ALT were measured. Hematoxylin–eosin, Masson staining, and Sirius Red staining were performed to assess the pathological changes and collagen deposition. Cell supernatant derived from NK-92MI cells inhibited TGF-β1-induced HSC proliferation and activation in LX-2 cells, and this effect was counteracted by the exosome inhibitor GW4869. Further assays confirmed that NK-Exo treatment significantly inhibited TGF-β1-induced HSC proliferation and activation. Moreover, NK-Exo administration alleviated CCl
4
-induced liver fibrosis in mice. NK-Exo inhibited TGF-β1-induced HSC activation and CCl
4
-induced liver fibrosis.
(-)-Epigallocatechin-3-gallate (EGCG), which is the most abundant catechin in green tea, has many potential health benefits, including decreased weight gain and/or adipose tissue weight. Suggested ...mechanisms for body weight reduction by EGCG include: (1) a decrease in calorie intake and (2) activation of AMPK in liver, skeletal muscle, and white adipose tissue. However, only one study supports the AMPK hypothesis. To determine the role of AMPK in EGCG-induced reduction of body weight, we administrated 50 mg/kg and 100 mg/kg per day to mice, together with a high-fat diet (HFD), for 20 weeks. EGCG had a significant effect on obesity and decrease in epididymal adipose tissue weight, and also affected serum lipid characteristics, including triglyceride, cholesterol (CHOL), and high- and low-density lipoprotein CHOL (HDL-C, LDL-C) concentrations. In addition, EGCG increased the excretion of free fatty acids from feces. By measuring the mRNA expression levels of genes involved in lipid metabolism, we found that EGCG inhibited the expression of genes involved in the synthesis of
fatty acids (
,
,
,
β,
γ, and
) and increased the expression of genes associated with lipolysis (
) and lipid oxidization in white adipose tissue, in both the HFD and the EGCG groups. However, EGCG significantly increased the expression of genes involved in the synthesis of
fatty acids compared with the HFD group. Increased AMPK activity was found in both subcutaneous and epididymal adipose tissues. In conclusion, EGCG can decrease obesity and epididymal white adipose tissue weight in mice, only partially
activation of AMPK.
Phosphorus in energy storage has received widespread attention in recent years. Both the high specific capacity and ion mobility of phosphorus may lead to a breakthrough in energy storage materials. ...Black phosphorus, an allotrope of phosphorus, has a sheet-like structure similar to graphite. In this review, we describe the structure and properties of black phosphorus and characteristics of the conductive electrode material, including theoretical calculation and analysis. The research progress in various ion batteries, including lithium-sulfur batteries, lithium–air batteries, and supercapacitors, is summarized according to the introduction of black phosphorus materials in different electrochemical applications. Among them, with the introduction of black phosphorus in lithium-ion batteries and sodium-ion batteries, the research on the properties of black phosphorus and carbon composite is introduced. Based on the summary, the future development trend and potential of black phosphorus materials in the field of electrochemistry are analyzed.
Mass spectrometry is considered the most informative technique for components identification and has been widely adopted in plant sciences. However, the spatial distribution of compounds in the ...plant, which is vital for the exploration of plant physiological mechanisms, is missed in MS analysis. In recent years, mass spectrometry imaging has brought a great breakthrough in plant analysis because it can determine both the molecular compositions and spatial distributions, which is conducive to understand functions and regulation pathways of specific components in plants. Mass spectrometry imaging analysis of plant tissue is toward high sensitivity, high spatial resolution, and even single‐cell analysis. Despite many challenges and technical barriers, such as difficulties of sample pretreatment caused by morphological diversity of plant tissues, obstacles for high spatial resolution imaging, and so on, lots of researches have contributed to remarkable progress, including improvement in tissue preparation, matrix innovation, and ionization mode development. This review focuses on the advances of mass spectrometry imaging analysis of plants in the last 5 years, including commonly used ionization techniques, technical advances, and recent applications of mass spectrometry imaging in plants.
Human epidermal growth factor receptor 2 (HER2) plays a critical role in breast cancer progression in patients with HER2 overexpression, thereby driving the development of targeted drugs and ...advancing therapy strategies targeting this gene. Pyrotinib is a novel irreversible pan-ErbB kinase inhibitor, primarily suppresses the downstream MAPK and PI3K/AKT pathways. Alpelisib, a selective PI3K p110α inhibitor, has been approved for clinical application in HR+, HER2-, PIK3CA mutated breast cancers and is also being developed for use in other breast cancer subtypes. In this study, we hypothesised that combining pyrotinib with alpelisib would yield superior results compared to single-drug treatment. Our data demonstrated that the combination of alpelisib and pyrotinib exhibited a synergistic effect in HER2+ breast cancer both in vitro and in vivo. This combination led to decreased cell proliferation and migration, G0-G1 cell cycle arrest, and increased apoptosis rates. Additionally, the deactivation of ErbB receptors and sustained activation of PI3K/AKT pathway by upstream compensatory pathways induced acquired pyrotinib resistant cells resistant to pyrotinib treatment, thus alpelisib combined with pyrotinib showed a tremendous synergistic effect and reverse pyrotinib resistance in acquired pyrotinib resistant cells by suppressing the activated PI3K/AKT pathway. Our results revealed a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether sensitive or resistant to pyrotinib treatment.
Background: With the changes in lifestyle and diet structure, the incidence of obesity has increased year by year, and obesity is one of the inducements of many chronic metabolic diseases. ...Epigallocatechin gallate (EGCG), which is the most abundant component of tea polyphenols, has been used for many years to improve obesity and its complications. Though it has been reported that EGCG can improve obesity through many molecular mechanisms, EGCG may have many mechanisms yet to be explored. In this study, we explored other possible mechanisms through molecular docking and in vitro experiments. Methods: AutoDock Vina was selected for conducting the molecular docking analysis to elucidate the interaction between EGCG and Notch1, while molecular dynamics simulations were employed to validate this interaction. Then, the new regulation mechanism of EGCG on obesity was verified with in vitro experiments, including a Western blot experiment, immunofluorescence experiment, oil red O staining, and other experiments in 3T3-L1 adipocytes. Results: The molecular docking results showed that EGCG could bind to Notch1 protein through hydrogen bonding. In vitro cell experiments demonstrated that EGCG can significantly reduce the sizes of lipid droplets of 3T3-L1 adipocytes and promote UCP-1 expression by inhibiting the expression of Notch1 in 3T3-L1 adipocytes, thus promoting mitochondrial biogenesis. Conclusions: In this study, molecular docking and in vitro cell experiments were used to explore the possible mechanism of EGCG to improve obesity by inhibiting Notch1.
The mechanism by which Notopterygium (NE) regulates the nucleotide‐binding, oligomerization domain (NOD)‐like receptor family and pyrin domain-containing 3 (NLRP3) inflammasome to treat rheumatoid ...arthritis (RA) was investigated to reveal the scientific implications of NE in RA treatment.
Adjuvant arthritis (AA) rats were replicated. After NE intervention, the anti-inflammatory efficacy of NE in vivo was determined. The mechanism of NE in RA treatment was predicted by network pharmacology, and the key target for further experiments was found through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). The effect of NE on the NLRP3 inflammasome in AA rats was verified. Furthermore, with the induction of inflammation in RAW264.7 cells by lipopolysaccharide (LPS), several techniques, such as Griess assay, enzyme linked immunosorbent assays, electron microscopy, and fluorescence probe technology, were used to investigate the anti-inflammatory and related mechanisms of NE in RA treatment.
NE could inhibit inflammation in AA rats. KEGG results showed that NLRP3 participated in the top three pathways of NE in RA treatment. Through Western blotting and immunofluorescence assays, this study demonstrated that NE can regulate NLRP3, pro-Caspase-1, Caspase-1, and CD11b in the ankle joint of AA rats. NE may significantly reduce the LPS-induced inflammatory response of RAW264.7 cells by alleviating mitochondrial damage, reducing the number of mitochondrial deoxyribonucleic Acid and mitochondrial reactive oxygen species, inhibiting NLRP3 inflammasome activation.
The anti-inflammatory and antirheumatic effect of NE may involve regulating NLRP3 inflammasome activation through mitochondria. NLRP3 is probably the key target molecule of NE in the treatment of RA.
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•Notopterygium exerts a anti-inflammatory effect in treating rheumatoid arthritis.•Mitochondrion-NLRP3 inflammasome is involved in rheumatoid arthritis progression.•NLRP3 is probably the key target molecule of Notopterygium for rheumatoid arthritis.•The mechanism was explored by integrated network pharmacology and experiments strategy.
Abstract
Based on the South China Sea deepwater high temperature and high pressure gas reservoir LS25 gas field, 3D geological model and a numerical reservoir model of LS25 gas field are established. ...Through numerical simulation of gas reservoir production, quantitative analysis of water invasion characteristics of 11 wells has been completed. The whole process of water invasion in space is as follows: bottom water conies in the early stage, forming water cone shape, the scale of the water body to the ridge increases, and the horizontal section completely emerges. Through comparative study, it is concluded that the combined water control technology of variable density screen pipe has the best water control effect. According to the prediction and analysis of the final production plan of variable density technology, it can prolong the water-free gas production period of the gas reservoir by 0.7 years, prolong the total production time by 1.9 years, increase the gas production by 1.9×10
8
m
3
, and increase the recovery factor by 10.5% compared with that without water control measures. The research results are aimed to establish an optimal water control development model for buried hill gas reservoirs, and provide a good technical support for reasonable and scientific water control research of horizontal wells in offshore buried hill fractured gas reservoirs.
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