Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Mechanism study on UV-induced photodegradation of nonylphenol ethoxylates by intermediate products analysis

Photodegradation of nonylphenol ethoxylates （NPloEO） was investigated in laboratory scale under UV irradiation. The intermediate photodegradation products were analyzed by LC-ESI-MS. Three kinds of intermediate products including aldehydic compounds, carboxylic compounds and cyclohexanyl compounds were identified. Five main degradation routes involving the oxidation of the alkyl chain and ethoxylate unit, shortening of the alkyl chain and ethoxylate unit, hydrogenation of the benzene ring were proposed.

Chemiluminescence determination of 20 amino acids and the mechanism study

It was found that 20 amino acids could inhibit the intensity of the luminol-H_2O_2-CuSO_4 chemiluminescence system.Using this character,a rapid and sensitive method for the determination of 20 amino acids was developed with flow injection coupled with chemiluminescence detection.Under the optimal conditions,the detection limits of 20 amino acids were in the range of 4.5×10^（-7）- 4.3×10^（-10） mol/L,and the relative standard deviations were less than 3.2%.The proposed method was successfully applied to drug analysis.The possible mechanism was also discussed.

Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

Clinical Observation on Treatment of 78 Patients of B-Thalassemla with Bushen Ylsul (补肾益髓) Method and Study on Its Molecular Mechanism

Objective: To study the treatment of B-Thalas-semia (ThE) with Chinese herbal medicine for Bushen Yisui (BSYS), its theoretical base and molecular mechanism. Methods: Seventy-eight patients with ThE were treated with BSYS recipe (consisted of 11 Chinese herbal drugs as Dogwood fruit, Fleeceflower root, prepared Rehmannia root and turtle shell, etc.) orally taken, 3 times per day, 10 g/time, 3 months as one therapeutic course. Hemoglobin (Hb), red blood cell (RBC), reticulocyte (Ret) and hemoglobin F (HbF) were checked every month. At the same time, PAGE, PVR, PCR-SSCP, RT-PCR, DNA series analysis, mRNA gene expression analysis techniques were used to conduct the systematic gene analysis in patients to study the molecular mechanism of TCM treatment from aspects of gene mutation, gene expression and control-regulation. Results: All the blood criteria in patients after BSYS treatment were improved significantly with clinical symptoms

Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

A Numerical Study on the Mechanisms Producing Forces on Cylinders Interacting with Stratified Shear Environments

A three dimensional(3D)numerical wave flume is used to investigate carefully the ISWs(Internal solitary wave)forces acting on cylinders interacting with a stratified shear environment.Using the Large-Eddy Simulation(LES)approach and analyzing the distribution of shear stress and pressure along the surface of the cylinder,the differential pressure resistance and the viscous force are obtained.The method of multiple linear regression analysis is adopted and a comprehensive influence coefficient is determined accordingly to account for the dimensionless forces acting on the cylinder.Results show that the differential pressure resistance on a square cylinder is 1.5 times higher than that on a circular cylinder in the upper layer,while the differential pressure resistance on a square cylinder is 3.5 times larger than that on a circular cylinder in the lower layer.The viscous force is 1–2 orders of magnitude smaller than the differential pressure resistance,which means that the viscous force could be ignored.The comprehensive influence coefficient shows positive correlation with the relative wave height and negative correlation with upper and lower water depth ratio.

Study on the Mechanism of the Rearrangement Reaction of 3-n-Butylphthalide by Deuterium-Labelling

By the Grignard reaction of 1,1-di-deutero-1-bromobutane with phthalaldehydic acid 1',1'-di-deutero-3-n-butyl phthalide was obtained, which underwent a rearrangement reaction using AlCl3 as catalyst in CS2 to give 1-methyl-5-carboxy-3,4-di-deutero-tetrahydronaphthalene. The mechanism was proposed to be a series of consecutive 1,2- hydride transfers rather than a direct 1,4-hydride transfer.

DSC STUDY ON THE WATER-ABSORBING MECHANISM OF PLASMA POLYMERIZED N-VINYL-2-PYROROLIDONE

Water existing in water-absorbing plasma polymerized N-vinyl-2-pyrrolidone(PPNVP) include pure bulk water, freezable water and non-freezing, or bound, water. The C-N bond of N, N-disubstituted amides in PPNVP was considered as an active binding site for bound water.

An AM1 Study on the Mechanism of Uridine Phospborolysis

We have cd quantum chemical method tO ho the transition states of uridinephosphorolysis reaction under the neutral condition. Comparing the activation energies ofdifferent reaction modes, we conclude that uridine phosphorolysis takes Place mainlyaccording tO a concerted mechanism. The computational are consistent with somecritical experimental factsss.

THE STUDY ON THE MASS TRANSFER MECHANISM OF EUROPIUM ION THROUGH LIQUID SURFACTANT MEMBRANES

The transfer of trivalent europium ion in a liquid surfactant membrane system is investigated in order toclarify the characteristics of liquid membrane separation process and the availability of this technique forrecovering trivalent lanthanides and actinides.A layered structure model for the emulsion globule is sug-gested.The equations describing the relationship among the effective membrane thickness,the time andother factors are derived and verified experimentally.Results show that under certain conditions the decreas-ing concentration of europium ion in the external phase is proportional to the square root of the time,the acidity of the internal phase and the carrier concentration in the membrane phase.The membrane phase consists of kerosene（solvent）,Span-80（surfactant）and di-（2-ethylhexyl） phosphoricacid（HDEHP,carrier）.The internal phase is dilute nitric acid and the external phase is aqueous solu-tion containing Eu（NO3）3.The mass transfer rate of europium in this system is high and the recovery ofeuropium may be more than 99%.

Study on the Protective Mechanism of Acupuncture Regulating ICAM-5 mRNA Expression in Rats with Ischemic Stroke

Objective: The objective is to investigate whether acupuncture can protect brain by regulating the expression of ICAM-5 mRNA in brain tissue. Methods: Male SD rats were used to construct a middle cerebral artery occlusion reperfusion injury (Middle cerebral artery occlusion, MCAO) model, and the rats were randomly divided into 4 groups, namely the normal group (group A) and the sham operation group (group B), MCAO group (group C), MCAO + acupuncture group (group D);real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of ICAM-5 mRNA in the brain tissue of the ischemic area, and HE staining and TUNEL were used to detect the level of neuronal apoptosis to evaluate the therapeutic effect. Results: Acupuncture can improve neuronal morphology and reduce neuronal apoptosis in rats with ischemic stroke. RT-qPCR: compared with group A and group B, the expression level of ICAM-5 mRNA in the brain tissues of group C and group D decreased, while compared with group C, The expression of ICAM-5 mRNA in the brain tissue of group D was significantly up-regulated (P < 0.05). There was no statistical difference between group A and group B (P > 0.05). Conclusion: The effectiveness of acupuncture in the treatment of ischemic stroke may achieve neuroprotection by up-regulating the expression level of ICAM-5 mRNA.

A Numerical Study of the Mechanism for the Effect of Northern Winter Arctic Ice Cover on the Global Short-Range Climate Evolution

By using a nine-layer global spectral model involving fuller parameterization of physical processes, with a rhomboidal truncation at wavenumber 15, experiments are performed in terms of two numerical schemes, one with long-term mean coverage of Arctic ice (Exp.1), the other without the ice (Exp.2). Results indicate that the Arctic region is a heat source in Exp.2 relative to the case in Exp.1. Under the influence of the polar heat source simulated, there still exist stationary wavetrains that produce WA-EUP and weak PNA patterns in Northern winter. That either the Arctic or the tropical heat source can cause identical climatic effects is due to the fact that the anomaly of the Arctic ice cover will directly induce a south-propagating wavetrain, and bring about the redistribution of the tropical heat source / sink. The redistribution is responsible for new wavetrains that will exert impact on the global climate. The simulation results bear out further that the polar region in Exp.2 as a heat source, can produce, by local forcing, a pair of positive and negative difference centers, which circle the Arctic moving eastwards. Observed in the Northern Hemisphere extratropics is a 40-50 day oscillation in relation to the moving pair, both having the same period.

THE STUDY ON TRE KINETICS AND MECHANISM OF THE REACTIONS OF METAL IONS WITH PnAO

The kinetics and the mechanism of the formation reactions of M(PnAO)^(2+)(M=Ni,Co,Cu)were studied with UV Spectrophotometer and Stopped Flow Spectrophotometer and a three steps mechanism was suggested.

LIRR's Project of “Study on Spalling Mechanism Mechanism of Dense Refractory Castables by Rapid Heating-up” Being Obtained the Support from National Natural Natural Science Foundation of China

LIRR＇s Priject of ＂Research on Spalling Mechanism Due to Rapid Heating-up of Dense Refractory Castables＂ declared by Wang Zhanmin,vice-president of LIRR,will gain the fund support from National Natural Science Foundation of China in 2011.

STUDY ON THE SEPARATION AND EXTRACTION MECHANISM OF RARE EARTH ELEMENTS BY MEANS OF REVERSED-PHASE PAPER CHROMATOGRAPHY

Reversed-phase paper chromatography technique is used for study on the extraction mechanism and sep- aration of rare earth elements.As the stationary phase,chromatographic paper strips are impregnated with a solution of monomyristyl phosphoric acid (MPA) in chloroform.Mineral acids are used as developers. The effect of concentration of acids and/or salts upon R_f has been investigated.According to the re- sults of R_f values for a given rare earth element in various acids,the order of extraction ability is HCl>HNO_3>H_2SO_4.A tetrad effect is clearly observed.for the R_f value of rare earth elements.The effects of other parameters on the R_f value,such as the quantities of extractant retained by the paper and the temperature are also examined.Based on the determination of the molar ratio of MPA to rare earth elements and the number of H^+ ions released in extraction reaction,a reasonable mechanism is proposed.The mutual separation of heavy rare earth elements will be better than that of the light rare earth group because of the larger separation coefficient of the former.A mixture of Ho-Er-Tm-Lu is successfully separated by the present method.

Mechanism of Wulan Shisanwei Decoction in Treating Hypertension Complicated with Hyperlipidemia Based on Network Pharmacology

[Objectives]To screen out the main effective components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia based on the method of network pharmacology,predict the target and explore the possible mechanism.[Methods]13 components of Wulan Shisanwei Decoction were searched on the TCMSP data platform,the corresponding active components were found and the corresponding targets were searched in Pubchem database.GeneCards database was used to screen the corresponding targets of hypertension and hyperlipidemia.The core target PPI network of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was constructed by processing in STRING database.The effective data were imported into Cytoscape 3.8.0 to analyze the network topology parameters,and they were screened according to the degree value greater than the average value.Finally,the relevant information about the core target of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was obtained.GO enrichment analysis and KEGG pathway analysis were carried out for core targets in DAVID database.The visualization map of"drug-component-target-disease"was drawn by Cytoscape 3.8.0.[Results]A total of 85 active components were obtained from Wulan Shisanwei Decoction,and there were 1532 corresponding targets.A total of 303 key targets were obtained by intersecting corresponding drug targets with disease targets.3178 biological processes were obtained by GO analysis(P<0.05)and 192 signaling pathways were obtained by KEGG enrichment analysis(P<0.05).[Conclusions]It was predicted that the main active components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia were stigmasterol,acacetin,pectolinarigenin,isorhamnetin,alizarin,quercetin,nordamnacanthal,kaempferol,luteolin,glyceollin,kushenol,t,3-methylkempferol,ellagic acid,etc.20 core targets were selected in the treatment of hypertension complicated with hyperlipidemia:SRC,STAT3,HSP90AA1,MAPK1,MAPK3,PIK3R1,HRAS,GRB2,PIK3CA,AKT1,PTPN11,ESR1,LCK,EGFR,FYN,EP300,RELA,JUN,LYN,RHOA.These targets were involved in PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycan in cancer,Ras signaling pathway,etc.to exert a response to oxidative stress,cellular response to chemical stress,peptidyl-tyrosine phosphorylation and peptide tyrosine modification,and can intervene in the early stage of the disease.It may be the potential mechanism of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia.