Exploring the Mechanism Whereby Sinensetin Delays the Progression of Pulmonary Fibrosis Based on Network Pharmacology and Pulmonary Fibrosis Models

The incidence of pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with sinensetin. The PPIs (protein–protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of sinensetin with the PI3K protein using the AutoDock4 software. The results showed that sinensetin could fit well into several binding sites of the PI3K protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of bleomycin and then intragastrically administered different concentrations of sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the body weight of model mice increased slightly compared with that of PF mice after intragastric sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of collagens I and III, as well as hydroxyproline in the lung tissues, was reduced to a certain extent. IL-6 levels in the serum and BALF decreased markedly. The expression of vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest sinensetin causes an effective delay in the progression of pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling

Electrical conductivity adjustment for interface capacitive-like storage in sodium-ion battery

Sodium-ion battery (SIB) is significant for grid-scale energy storage. However, a large radius of Na ions raises the difficulties of ion intercalation, hindering the electrochemical performance during fast charge/discharge. Conventional strategies to promote rate performance focus on the optimization of ion diffusion. Improving interface capacitive-like storage by tuning the electrical conductivity of electrodes is also expected to combine the features of the high energy density of batteries and the high power density of capacitors. Inspired by this concept, an oxide-metal sandwich 3D-ordered macroporous architecture (3DOM) stands out as a superior anode candidate for high-rate SIBs. Taking Ni-TiO2 sandwich 3DOM as a proof-of-concept, anatase TiO2 delivers a reversible capacity of 233.3 mAh g^-1 in half-cells and 210.1 mAh g^-1 in full-cells after 100 cycles at 50 mA g^-1. At the high charge/discharge rate of 5000 mA g^-1, 104.4 mAh g^-1 in half-cells and 68 mAh g^-1 in full-cells can also be obtained with satisfying stability. In-depth analysis of electrochemical kinetics evidence that the dominated interface capacitive-like storage enables ultrafast uptaking and releasing of Na-ions. This understanding between electrical conductivity and rate performance of SIBs is expected to guild future design to realize effective energy storage

Anti-Hepatitis B Virus Effect and Possible Mechanism of Action of 3,4-O-Dicaffeoylquinic Acid In Vitro and In Vivo

The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 μg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 μg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression

Isolation, Identification and Determination of Six Nucleosides and Two Amino Acids from Bamboo Shoots of Gramineae Phyllostachys prominens (W Y Xiong)

Purpose: To develop a method to identify and quantify the compounds in the shoots of four Phyllostachys bamboo species (Gramineae Phyllostachys prominens W. Y. Xiong, Gramineae Phyllostachys iridescins C. Y. Yao Gramineae Phyllostachys pubescens (Carr.) Mitford, Gramineae Phyllostachys praecox C. D. Chu et C. S. Chao. ).Methods: The compounds in bamboo shoots were isolated and identified by ultraviolet (UV) spectroscopy, mass spectrometry (MS), and nuclear magnetic resonance (NMR). Quantitative analysis was performed by reversed-phase high performance liquid chromatography (RP-HPLC) using a C18 column and a mixture (1:1ratio) of acetonitrile and 15 mM ammonium acetate (pH 6.0) as mobile phase. This method was validated for its reproducibility, chemical stability, and recovery.Results: Six nucleosides and two amino acids were isolated from bamboo shoots, including guanosine, 2’-deoxyguanosine, adenosine, thymidine, uridine, cytidine, tryptophan, and phenylalanine. The HPLC method was rapid and reproducible. The intraday and interday concentrations of the eight identified compounds showed good linearity in the range of 0.22 - 60.00 μg/mL. The relative standard deviation (RSD) for intraday and interday precision for reproducibility and stability was < 3 %. The validated method was successfully applied to determine the content of the eight compounds in four different Phyllostachys species.Conclusion: Adenosine was isolated from bamboo shoots previously, but the isolation of the other seven compounds are reported here for the first time. The method proposed is sensitive and reproducible, and would facilitate studies of nutritional/medicinal compounds in bamboo shoot.Keywords: Bamboo shoots, Phyllostachys prominens, Guanosine, 2’ Deoxyguanosine, Adenosine, Thymidine, Uridine, Cytidine, Tryptophan, Phenylalanin

miR-133a Regulates Adipocyte Browning In Vivo.

Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose tissue (BAT) and regulates the thermogenic gene program of subcutaneous white adipose tissue (SAT) in mice. Here we show that miR-133a, a microRNA that is expressed in both BAT and SATs, directly targets the 3′ UTR of Prdm16. The expression of miR-133a dramatically decreases along the commitment and differentiation of brown preadipocytes, accompanied by the upregulation of Prdm16. Overexpression of miR-133a in BAT and SAT cells significantly inhibits, and conversely inhibition of miR-133a upregulates, Prdm16 and brown adipogenesis. More importantly, double knockout of miR-133a1 and miR-133a2 in mice leads to elevations of the brown and thermogenic gene programs in SAT. Even 75% deletion of miR-133a (a1−/−a2+/−) genes results in browning of SAT, manifested by the appearance of numerous multilocular UCP1-expressing adipocytes within SAT. Additionally, compared to wildtype mice, miR-133a1−/−a2+/− mice exhibit increased insulin sensitivity and glucose tolerance, and activate the thermogenic gene program more robustly upon cold exposure. These results together elucidate a crucial role of miR-133a in the regulation of adipocyte browning in vivo

Isospin fractionation in the nucleon emissions and fragment emissions in the intermediate energy heavy ion collisions

The degree of isospin fractionation is measured by $(N/Z)_{n}$ / $(N/Z)_{N_{imf}}$, where $(N/Z)_{n}$ and $(N/Z)_{N_{imf}}$ are the saturated neutron-proton ratio of nucleon emissions (gas phase) and that of fragment emissions (liquid phase) in heavy ion collision at intermediate energy . The calculated results by using the isospin-dependent quantum molecular dynamics model show that the degree of isospin fractionation is sensitive to the neutron-proton ratio of colliding system but insensitive to the difference between the neutron-proton ratio of target and that of projectile. In particular, the degree of isospin fractionation sensitively depends on the symmetry potential. However its dependences on the isospin dependent in-medium nucleon-nucleon cross section and momentum dependent interaction are rather weak. The nucleon emission (gas phase) mainly determines the dynamical behavior of the degree of isospin fractionation in the isospin fractionation process, compared to the effect of fragment emission. In this case, we propose that $(N/Z)_{n}$ / $(N/Z)_{N_{imf}}$ or $(N/Z)_{n}$ can be directly compared with the experimental data so that the information about symmetry potential can be obtaine