Oral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. Kouyanqing Granule (KYQG) has been used to treat inflammatory diseases of ...the mouth and throat, including recurrent aphthous stomatitis (RAS), traumatic ulcers, oral leukoplakia and so on. However, the underlying molecular mechanisms of KYQG in treating these diseases are still unclear. We aimed to explore the possible mechanisms in KYQG for the treatment of oral ulcers.
An innovative network pharmacology method was established by incorporating targets searching and fishing, network analysis, and silico validation to discover the pharmacological mechanisms of action of KYQG for the treatment of oral ulcers. Then, we verified the reliability of this method by an animal experiment.
Our data indicated that a total of 47 key targets were screened, which mainly involved in three function modules including the inhibition of inflammation, the regulation of immunological response, and the suppression of oxidative stress. The implementation of these functions relies on the complex multi-pathways network, especially TNF signaling pathway and HIF-1 signaling pathway. The results of the experimental verification indicated that KYQG significantly inhibited the serum levels of cyclooxygenase-2 (COX2), matrix metalloproteinase 9 (MMP9) and tumor necrosis factor-alpha (TNF-α) in rats with oral ulcer.
KYQG exhibited the therapeutic effects on oral ulcers probably by inhibiting inflammation, regulating immunological response, and suppressing oxidative stress through a complex multi-pathways network. Particularly, TNF signaling pathway and HIF-1 signaling pathway may play crucial roles in the protection of KYQG against oral ulcers. This work not only offers a method for understanding the functional mechanisms of KYQG for treating oral ulcer diseases from a multi-scale perspective but also may provide an efficient way for research and development of complex composition formula.
The drug preparations from dried flower of Carthamus tinctorius L. (CTL) are widely used as an adjuvant medication in cardiovascular diseases in China. In this research, Safflower yellow extract ...(SYE), a CTL drug in market, was studied through components analysis and two animal experiments with different dosages to assess its pharmacodynamic effects. The whole constituents of SYE were characterized through ultra-fast liquid chromatography–diode array detector–quadrupole time-of-flight tandem mass spectrometry. Cerebral arteriole thrombus was induced in C57BL/6J mouse by laser irradiation in vivo using two-photon laser-scanning microscopy. The time of thrombus formation and vessel diameter were calculated to evaluate the antithrombotic effect. In the model of blood stasis syndrome, rats were injected with adrenaline injection before and after ice-bath to induce hemorheology disorders. The results identified 29 constituents in SYE and hydroxysafflor yellow A was the main component (19.8%). In the mouse model, SYE inhibited thrombus formation in a dose-dependent manner and postponed the occlusion time in brain arteriole at dosages of 26.0 and 52.0 mg/kg. In the rat model of blood stasis syndrome, SYE significantly decreased the whole blood viscosity, suppressed red blood cell aggregation and platelet aggregation in high-dose (p < 0.01). The activated partial thromboplast in time was prolonged at a dosage of 7.0 mg/kg (p < 0.05) as well. In conclusion, SYE administration could inhibit the thrombus formation and beneficially influence the blood rheologyin blood stasis syndromes at relevant low dosages.
This research confirmed that azalomycin F5a can increase the membrane permeability of MRSA cell, and which had likely achieved by the synergy of its lactone ring binding to the polar head of ...phospholipid and its guanidyl side chain targeting to lipoteichoic acid (LTA). This would subsequently cause the release of cellular substance, and eventually lead to the autolysis of MRSA cells. Nevertheless, it is unknown how azalomycin F5a interacts with MRSA cellular LTA, such as influencing the physiological function of LTA, inhibiting LTA synthase and polymerase, and/or accelerating the release of LTA?
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•Azalomycin F5a can increase cell-membrane permeability to kill Staphylococcus aureus.•Azalomycin F5a disrupts the cell membrane by interacting with phospholipid.•The lactone ring of azalomycin F5a can stably bind to the polar head of phospholipid.•Azalomycin F5a-induced lysis of MRSA can be inhibited by cellular lipoteichoic acid.•The guanidyl chain of azalomycin F5a likely targets to lipoteichoic acid of S. aureus.
Azalomycin F5a was a polyhydroxy macrolide produced by streptomycete strains. Our preliminary researches indicated that it could kill methicillin-resistant Staphylococcus aureus (MRSA) likely by increasing the permeability of cell membrane, and that cell-membrane phospholipids were likely important targets. To confirm this, membrane permeability assay was performed and visualized by fluorescence staining, and then the detailed interactions between azalomycin F5a and model membranes prepared with 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) were determined using attenuated total reflectance fourier transform infrared spectroscopy and 31P nuclear magnetic resonance techniques. The results indicated that there were strong interactions between azalomycin F5a and model membranes, especially between azalomycin F5a and the polar head of phospholipid. For further evidence and details, the molecular dynamics (MD) simulation of the interactions between azalomycin F5a and DPPG or lysyl-DPPG were performed using Amber16 software package. A strong interaction between the lactone ring of azalomycin F5a and the polar head of DPPG or lysyl-DPPG had been clearly observed. Moreover, a larger distribution probability out of phospholipid bilayer had been discovered for the guanidyl side chain of azalomycin F5a, especially when probable anion molecules anchoring on the cytoplasmic membrane occurred. Therefore, lipoteichoic acid (LTA), a vital component of gram-positive bacterial envelope, was investigated for its probable interactions with azalomycin F5a using broth microdilution method. The results showed that azalomycin F5a-induced MRSA lysis could be prevented by LTA. This deduced that there were some interactions between azalomycin F5a, more likely its guanidyl side chain, and LTA. Thereby, azalomycin F5a increasing the cell-membrane permeability of MRSA had likely achieved by the synergy of its lactone ring binding to the polar head of phospholipid and its guanidyl side chain targeting to LTA, and which had eventually led to the autolysis of MRSA cells.
•A new permeability model for sediment with compound morphology hydrate is proposed.•A THMC fully coupling simulation model for hydrate decomposition is developed.•The roughness of capillary has ...negative effect on hydrate gas production.•The impacts of hydrate morphology on gas production are identified.
Hydrate sediments usually have both pore-filling and grain-coating morphology, but current permeability models consider either pore-filling or grain-coating morphology. This paper proposes a dynamic permeability model for compound morphology in hydrate sediment with rough capillary. After it is verified with permeability experiments and existing permeability models, this dynamic permeability model is incorporated into our thermal-hydraulic-mechanical-chemical fully coupling model for hydrate decomposition. This fully coupling model is verified by the analytical solution of Terzaghi's one-dimensional consolidation and the Masuda's hydrate decomposition experiment. The simulation results showed that the difference between phase equilibrium pressure and reservoir dynamic pressure is an important indicator to ensure the stable and efficient production of hydrate. Capillary roughness mainly affects gas production peak rate during gas hydrate decomposition. Greater capillary roughness will make smaller gas production peak rate appear at later time. Cumulative gas production and sediment dynamic permeability increase with increase of the volume fraction of grain-coating hydrate.
Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, there are still no specific treatments. ...Recently, traditional Chinese medicine (TCM) was proposed as a potential therapeutic strategy for the prevention and treatment of COVID-19. The present study aims to explore the potential of Hypericum japonicum Thunb. ex Murray against COVID-19 based on network pharmacology and molecular docking methods. Potential targets of H. japonicum were collected from available databases for protein-protein interaction analysis. Further GO and KEGG pathway analysis were performed to reveal the corresponding mechanism. Molecular docking was employed to evaluate the binding energy between the components in H. japonicum and three target proteins (ACE2, Mpro and PLP). Finally, a total of 45 core targets were screened. GO and KEGG pathway analysis revealed that several key pathways were involved in the potential beneficial effects of H. japonicum against COVID-19. Molecular docking results showed that most components in H. japonicum have a binding affinity to ACE2, Mpro and PLP molecules less than −5 kcal/mol, indicating good binding capacity to these target proteins. Vincetoxicoside B, bijaponicaxanthone and quercetin possess the top binding activity to ACE2, Mpro and PLP, respectively. The molecular docking results and the traditionally known possible functions of H. japonicum, including stabilizing blood oxygen environment, preventing inflammatory storms, regulating immune response and inhibiting viral infections, hereby indicate the potential of H. japonicum against COVID-19.
The injection and atomization process of a liquid fuel jet is critical for an ignition start of a scramjet engine. Airwall-mounted crossflow injection strategy is widely used in scramjet combustors, ...avoiding high total pressure loss and allowing the liquid fuel to rapidly undergo atomization, mixing, and evaporation. In this review, research progress on a liquid jet in supersonic crossflow was evaluated from aspects of atomization mechanism and spray characteristics. When a liquid jet is injected into a supersonic crossflow, primary and secondary breakups occur successively. The surface instability of liquid can significantly affect the breakup process. This review discusses the current understanding of the breakup process and spray characteristics of a liquid jet in supersonic crossflow including the mechanism of atomization and the characteristics of distribution and atomization. The development of windward Rayleigh-Taylor (R-T) unstable waves is the main factor in column breakup. The development of Kelvin-Helmholtz (K-H) unstable waves along the circumferential direction of the jet or droplets is the main factor of surface and droplet breakups. The liquid–gas momentum ratio is the most important factor affecting the penetration depth. The span width of the liquid jet is affected by the windward area. Breakup and coalescence lead to a transformation of the size distribution of droplets from S- or C-shaped to I-shaped, and the velocity distribution of the droplets on the central symmetry plane has a mirrored S-shape. The droplet distribution on the spanwise cross-section retains a structure similar to an “Ω” shape. At last, some promising recommendations have been proposed, namely a theoretical predictive model which can describe the breakup mechanism of a liquid jet, the distribution characteristics and droplets size distribution of a liquid jet under a cavity combustion chamber, especially for enthalpy flows with complex wave structures.
The mixing and evaporation process of a liquid kerosene jet in a scramjet combustor with dual-cavity is investigated by two-phase Large Eddy Simulation. The gas-droplet flow system is solved through ...a two-way coupled Eulerian-Lagrangian method. The primary and secondary breakup processes of the liquid fuel jet are taken into account. The Langmuir-Knudsen evaporation model, which considers the non-equilibrium effect, is used to calculate the evaporation process of the droplets. The penetration depth of the jet is in good agreement with the experimental value. The dynamic process of the liquid jet breakup, spray evaporation, and fuel transportation within the combustor are well described by the numerical results. The distribution and evaporation characteristics of the spray are analyzed and most droplets are evaporated within 30 mm downstream of the jet orifice. However, a small portion of droplets with high velocity and low temperature can survive for a long distance. The influence of injection pressure on the mixing process near the cavity is also analyzed, and it is found that the injection pressure affects the total quantity of fuel entrained into the cavity by affecting the fuel distribution in the near-wall region and the total fuel mass flow rate. The local distribution of the liquid and gas phase fuels, local temperature and turbulence characteristics in the cavity are analyzed, and the ignition environment on the development path of the flame kernel is discussed. The results indicate that the injection pressure and the distance between the cavity and the orifice have a critical effect on the quantity of the kerosene entrained into the cavity, which then have a great influence on the ignition environment in the cavity.
A highly sensitive and specific electrospray ionization (ESI) liquid chromatography–tandem mass spectrometry (LC/MS/MS) method for quantitation of naringenin (NAR) and an explanation for the double ...peaks phenomenon was developed and validated. NAR was extracted from rat plasma and tissues along with the internal standard (IS), hesperidin, with ethyl acetate. The analytes were analyzed in the multiple-reaction-monitoring (MRM) mode as the precursor/product ion pair of
m/
z 273.4/151.3 for NAR and
m/
z 611.5/303.3 for the IS. The assay was linear over the concentration range of 5–2500
ng/mL. The lower limit quantification was 5
ng/mL, available for plasma pharmacokinetics of NAR in rats. Accuracy in within- and between-run precisions showed good reproducibility. When NAR was administered orally, only little and predominantly its glucuronidation were into circulation in the plasma. There existed double peaks phenomenon in plasma concentration–time curve leading to the relatively slow elimination of NAR in plasma. The results showed that there was a linear relationship between the AUC of total NAR and dosages. And the double peaks are mainly due to enterohepatic circulation.
The gas production from stacked gas deposits with coalbed, shale, and tight sandstone reservoirs in the coal measure is an effective new technology to enhance per well gas production. However, ...previously developed numerical models for stacked gas deposits usually target one or two reservoir types. The contribution and impact mechanism of crossflow and two-phase flow on gas production from stacked gas deposits are unclear for the stacked gas deposits with coalbed, shale, and tight sandstone reservoirs in the coal measure. This paper develops a numerical simulation model for the gas production from stacked deposits with shale, coalbed, and tight sandstone reservoirs. This numerical simulation model considers the two-phase flow, gas diffusion in different porosity, pore deformation, and interlayer crossflow. After verification with available data from the literature, this numerical simulation model is used to explore the effects of crossflow across interlayers and two-phase flow on gas transport and production efficiency. The simulation results show that the main sources of gas production from stacked deposits are shale and coalbed reservoirs. The gas in these two reservoirs can be rapidly transported to the wellbore through the tight sandstone reservoir. The gas production from stacked deposits will be underestimated without the interlayer crossflow and overestimated if the two-phase flow is ignored. The gas production efficiency can be effectively improved through the enhancement of the crossflow rate at the interlayer and the decrease of the water saturation in the reservoir.
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