Exploring the mechanism of active ingredients of Smilacis Glabrae Rhizoma in treating migraine headache through network pharmacology and animal experiments

Background:To explore the potential mechanism of action of the active ingredients of Smilacis Glabrae Rhizoma(SGR)in the treatment of migraine using network pharmacology and in vivo experiments.Methods:Through the search of Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,Genecards,Drugbank and other databases,we obtained active ingredients,targets of SGR and related disease targets of migraine,and took the intersection for protein-protein interactions analysis.After constructing the network diagram,network topology analysis was performed to derive the core targets and key active ingredients,and Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Finally,molecular docking was performed and validated by in vivo experiments.In vivo experiments,18 male BALB/c mice were selected,and the SGR group was fed with SGR drinking tablet concentrate,and nitroglycerin injection was used to construct a mouse model of migraine.Enzyme-linked immunosorbent assay test was used to detect the levels of TNF-α,IL-1β,IL-6,and AKT1 in plasma.Results:The results showed that the core targets of SGR for the treatment of migraine were TNF-α,IL-1β,IL-6,and AKT1.These core targets and key active ingredients had better binding ability.Compared with the blank group,the number of head scratching in the model group increased.Compared with the model group,there was a significant reduction of the number of head scratching in the SGR group.In comparison with the blank group,the protein level in the plasma in the model group was markedly higher.Compared with the model group,the protein level in the SGR group was significantly lower.Conclusion:SGR has the characteristics of improving migraine based on multi-targets,multi-components and multi-pathways,and the mechanism of action may be related to the inhibition of the release of inflammatory factors,neuron protection,and interference with apoptosis and other processes.

Negatively regulating mechanism of Sirpal in hepatocellular carcinoma:an experimental study

BACKGROUND: Signal regulatory protein ( Sirp) is a recently isolated, cloned and identified inhibitor receptor distributed in the membrane of hematopoietic and nonhema-topoietic cells. Sirp alphal ( Sirpα1) is a member of Sirp families. Sirpal can bind SHP-2 in the form of tyrosine phosphorylation by SH2 effect and negatively regulate growth factor, oncogene, or insulin-induced responses as its substrate. This study aimed to preliminarily clarify the negatively regulating proliferation mechanism of Sirpal in liver cancer. METHODS: pLXSN, Sirpα1 and Sirpα1Δ4Y2 plasmids were respectively transfected into Sk-Hepl liver cancer cell line, and various stable Sk-Hepl cell lines were obtained with screening agent of G418 (1200 μg/ml). The expressing levels of cyclin D1, CDK4, Fas, β-catenin and gankyrin in various cell lines were determined with Western blotting. Cell cycles were determined at 0, 12 and 24 hours with flow cytotnetry after various synchronous cell lines were cultured without serum for 72. Cell apoptosis induced with agent of TNF-α (50 ng/ml) was determined with flow cytotnetry at 0,0.5,1,3,6 and 12 hours. RESULTS: Sirpα1 could significantly decrease the expression of cyclin D1, β-catenin and gankyrin, but it couldn't affect the expression level of CDK4 and Fas. When synchronous cells were cultured for 12 hours, S phase Sk-Hep1 cell transfected with Sirpal plasmid was the lowest [(31.92 ± 0.22)% vs. other cell lines, P <0.05], and the cell line was highly sensitive to TNF-α agent for 1 hour. (59.31 ±0.59)% of apoptotic cells occurred (vs. the other time points, P < 0.05). CONCLUSIONS: Sirpal might block the cell cycle of liver cancer, inhibit cell proliferation, promote cell apoptosis by decreasing the expression of cyclin D1, β-catenin and gankyrin. It is one of the important mechanisms inhibiting the occurrence and development of hepatocellular carcinoma.

Study on the Long-term Mechanism of Building Innovative Practice Bases for Full-time Civil Engineering Postgraduate Training

In order to implement the quality of full-time professional degree postgraduate education cultivation,the necessity of building an innovative base for cultivating professional degree postgraduates in civil engineering is discussed.Based on the problems ofthe integrated cultivation mode of industry-university-research,the effective mechanism for cultivating an innovative practice base for professional degree postgraduates in civil engineering is elaborated from the construction of the cultivation mode,system construction,daily management,and improvement of the rights and responsibilities of both parties,which provides guiding significance for better realizing the need to adapt to the development of high-level talents in society.

Effect Mechanisms of Hygrothermal Environments on Failure of Single-Lap and Double-Lap CFRP-Aluminum Bolted Joints

The high demands for load-carrying capability and structural efficiency of composite-metal bolted joints trigger in-depth investigations on failure mechanisms of the joints in hygrothermal environments.However,few studies have been presented to exhaustively reveal hygrothermal effects on the failure of CFRP-metal bolted joints,which differ from CFRP-CFRP or metal-metal bolted joints because of the remarkably different material properties of CFRPs and metals.In this paper,hygrothermal effects on tensile failures of single-lap and double-lap CFRP-aluminum bolted joints were experimentally and numerically investigated.A novel numerical model,in which a hygrothermal-included progressive damage model of composites was established and elastic-plastic models of metals were built,was proposed to predict the failures of the CFRP-metal bolted joints in hygrothermal environments and validated by corresponding experiments.Different failure mechanisms of single-lap and double-lap CFRP-aluminum bolted joints,under 23°C/Dry and 70°C/Wet conditions,were revealed,respectively.It follows that both the collapse failures of the single-lap and double-lap bolted joints were dominated by the bearing failure of the CFRP hole laminate in the two conditions,indicating that the hygrothermal environment did not change the macro failure modes of the joints.However,the hygrothermal environment considerably shortened the damage propagation processes and reduced the strength of the joints.Besides,the hygrothermal environment weakened the load-transfer capability of the single-lap joint more severely than the double-lap joint because it aggravated the secondary bending effects of the single-lap joint obviously.

Mechanism on the Effect of Al upon the γ→ε Martensite Transformation in the Fe-Mn Alloys

The structure of the solid solution treated and deformed Fe-25Mn-(0-3.11)Al-0.15C alloys was examined by means of metallograph and X-ray diffraction, which has confirmed that Al restrains the γ→ε transformation in the Fe-Mn alloys. The mechanism on the restraining effect of Al has been discussed on the basis of the efFect of Al upon the stacking fault energy in the Fe-Mn alloys.Aluminium increases thermodynamically the stability of the Fe-Mn austenite and the driving force limit necessitated to be overcome for the γ→ε transformation, because the thermodynamicalcalculation indicates that Al increases the stacking fault energy in the Fe-Mn alloys at 300 K.Al will decrease the number and the size for the ε-martensite nucleus according to the stacking fault mechanism of the ε-martensite nucleation

Protective Effects of Ginsenoside Rb1 on Septic Rats and Its Mechanism

This study aims to observe the protective effects of ginsenoside Rbl on liver and lung in rats with septic shock and reveal its mechanism. Rats were randomly divided into three groups： sham, cecal ligation and puncture （CLP）, and CLP with ginsenoside Rb1. Then, the survival rate, arterial blood pressure, TLR4 mRNA, and TNF-α levels were determined. The liver and lung tissues were stained with hematoxylin-eosin （HE）. The overall survival rate of the Rb1 group was significantly higher than that of the CLP group. Mean arterial blood pressure went down in both the CLP and Rb1 groups after CLP, and there was a significant difference both in the sham and Rb1 groups when compared with the CLP group. The Rb1 treatment group had markedly lower TLR4 mRNA expression and TNF-a levels than the CLP group. In the CLP group, pathology showed swelling, degeneration, necrosis, and neutrophii infiltration in the liver and alveolar epithelial cells. However, in the Rb1 group, there was mild degeneration and slight neutrophil infiltration, but no obvious necrosis. Rb1 may improve the survival rate, ameliorate arterial blood pressure, and protect the liver and lung in septic shock rats by downregulating the expression of TLR4 mRNA and inhibiting the production of TNF-α.

Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update

Obesity has become one of the most prevalent health issues of our time. According to a 2012 WHO report, around 3.4 million adults die each year as a result of being overweight or obese. Humans are in fact superorganisms composed of both human and microbial cells with 2 sets of genes, those encoded in our own genome and those encoded in our microbiota. All these cells and genes have the potential to influence our health.

Growth mechanism and modification of electronic and magnetic properties of silicene

Silicene, a monolayer of silicon atoms arranged in a honeycomb lattice, has been undergoing rapid development in recent years due to its superior electronic properties and its compatibility with mature silicon-based semiconductor technology. The successful synthesis of silicene on several substrates provides a solid foundation for the use of silicene in future microelectronic devices. In this review, we discuss the growth mechanism of silicene on an Ag(111) surface, which is crucial for achieving high quality silicene. Several critical issues related to the electronic properties of silicene are also summarized, including the point defect effect, substrate effect, intercalation of alkali metal, and alloying with transition metals.

MULTIPLE SCATTERING THEORY OF EFFECTIVE MECHANICAL PROPERTIES OF INHOMOGENEOUS MEDIA

The rate of hydrothermal reaction of SiO_2 and/or A1_2O_3 in the system of CaO-Al_2O_3-SiO_2-H_2O at 200℃ and the factors which influence the reactions are investigated by determining the reaction ratio.The rate of reactions depends on the reactive activities of raw materials, initial composition of mixture and relative activity of SiO_2 and A12O3. The hydrothermal reaction can be accelerated by sodium hydroxide,in the case of silica,which has low activity, this is quite obvious.

STUDIES ON FLUORESCENCE ENHANCING EFFECT AND ALKALINE DEGRADATION MECHANISM OF DOXYCYCLINE AND METHACYCLINE

Degradation reaction of doxycycline or methacycline was carried out in KOH solution and intense fluorescence was obtained.A degradation mechanism of doxycycline or methacycline was suggested.

MECHANISM OF PROMOTING EFFECTS OF RIBOFLAVIN DEFICIENCY ON CARCINOGENESIS OF NITROSAMINES (EFFECTS ON RAT LIVER GLUTATHIONE CONTENT)

The effects of riboflavin deficiency and simultaneously nitrosodimethylamine (NDMA) given by gastric intubation on the hepatic glutathione (GSH) content were examined in rats. On different days of the experiment, hepatic GSH content of the riboflavin deficient rats decreased to 55-61% of the control rats. When NDMA was given 6 mg kg by gastric intubation to riboflavin deficient rats, hepatic GSH content decreased markedly to 39-43% of the control rats. After supplying riboflavin, hepatie GSH content of the deficient rats recovered to the level of the control rats. These results suggest that alterations of rat hepatic GSH content during riboflavin deficiency may imply as one of the promoting effects of riboflavin deficiency on the carcinogenesis of nitrosamines.

Exploration on the Effect and Mechanism of Shenfu Injection (参附注射液) on Resuscitation from General Anesthesia

Objective: To investigate the effect and the mechanism of Shenfu injection (SFI, ) on the resuscitation from general anesthesia . Methods: Forty patients who received selective abdominal surgery with general anesthesia for 3-4 hrs and ASA grade Ⅰ-Ⅱ were divided into two groups, the trial group and the control group, 20 patients in each group. After being sent into the postanesthesia care unit (PACU), the trial group was treated with intravenous dripping of SFI 1.0 ml/kg and the control group was treated with intravenous dripping of equal volume of normal saline. All patients were observed in double blindly manner, the self ventilation recovery time, extubation time, the time of leaving PACU and their Glasgow coma scale (GCS) were recorded and compared. 2 ml of peripheral venous blood were taken to determine the plasma β-endorphin (β-EP) content at the time points of before (T1), 5min (T2), 15min (T3) and 30 min (T4) after dripping. Results: The self ventilation recovery time, extubation time and time of leaving PACU in the trial group were all shorter than those in the control group (P<0 01), the GCS in the trial group was better than that in the control group (P<0 01). The plasma content of β-EP raised gradually along the recovering of patients consciousness, as compared with the content before dripping (T1), it showed insignificant difference at time point T2 but significant difference at T3 and T4, comparison at the corres ponding time point showed that the content at T1 and T2 were similar in the two groups (P>0 05), but at T3 and T4, the content was higher in the trial group than that in the control group respectively (P<0 01). There was insignificant difference between T1 and before treatment ( P>0 05), but significant difference was found when compared T3, T4 and before treatment (P<0 01).Conclusion: SFI could accelerate the resuscitation after general anesthesia, the mechanism may be related with its action in raising plasma β-EP level.

The Effect and Mechanism of Nano-Cu Lubricating Additives on the Electroless Deposited Ni-W-P Coating

The coating and deposition process with excellent anti wear and suitable for industrial application were developed, and the optimum bath composition and process were obtained by studying the influence of the bath composition, temperature and pH value on the deposition rate and the plating solution stability. Moreover, the tribological properties of nano-Cu lubricating additives and electroless deposited Ni-W-P coating as well as their synergistic effect are researched using ring-block abrasion testing machine and energy dispersive spectrometer. Research results show that Ni-W-P alloy coating and nano-Cu lubricating additive have excellent synergistic effect, e g, the wear resistance of Ni-W-P alloy coating （with heat treatment and the oil with nano-Cu additives） has increased hundreds times than 45 steel as the metal substrate with the basic oil, and zero wear is achieved, which breaks through the bottleneck of previous separate research of the above-mentioned two aspects.

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.

Effect and mechanism of adrenomedullin on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury

Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-

Effects of signal regulatory proteinα1 on proliferation of hepatocellular carcinoma: a preliminary study

BACKGROUND: Signal regulatory protein alpha1 (Sirpα1) is a negative regulatory factor, and inhibits receptor tyro- sine kinase-dependent cell proliferating signal. This study was undertaken to observe the effect of signal regulatory proteinα1 ( Sirpα1) on gankyrin, cyclin D1, CDK4 and Fas expression in Sk-hep1 mouse hepatoma carcinoma cell line. METHODS: BOSC 23 packed cells were respectively trans- fected by means of recombinated retrovirus including pLX- SN, pLXSN-Sirpα1 and pLXSN-Sirpα1Δ4Y2 with lipofec- tin, and various plasmid virus media (viral titer 2.1 × 106 CFU/ml) were collected and infected respectively in 80% confluent Sk-hepl cells. Transfected Sk-hep1 cells were se- lectively screened with G418 (1200 μg/ml), and Sk-hep1 cell lines transfected with various plasmids were obtained. The protein expressions of gankyrin, cyclin D1, CDK4 and Fas in various Sk-hep1 lines were determined by Western blotting. Various Sk-hep1 lines were recovered to culture with 10% fetal bovine serum at 12 hours and 24 hours after starving culture with free serum for 72 hours, and cells were collected to determine the percentage of S phase cells of proliferating cycle by flow cytometry. RESULTS: Sirpα1 transfection remarkably downregulated gankyrin and cyclin D1 expression. Sirpα1Δ4Y2 downregu- lation of gankyrin expression was greater than that of Sirpα1(P <0.05), but no significant effect of Sirpα1 and Sirpα1Δ4Y2 on CDK4 and Fas protein expression was ob- served in transfected Sk-hep1 lines (P >0.05). The per- centage of S phase cells significantly decreased in Sk-hep1 cells transfected with Sirpα1 and Sirpα1Δ4Y2 plasmids (vs pLXSN Sk-hep1, P <0.05). The percentage of S phase cells in various Sk-hep1 cells increased when recovering to culture with 10% fetal bovine serum at 12 hours, but the percentage of S phase cells in Sk-hep1 cells transfected with Sirpα1 was the lowest ( vs pLXSN and Sirpα1Δ4Y2 Sk- hepl, P<0.05). The percentage of S phase cells in trans- fected pLSXN Sk-hep1 cells was the largest (vs Sirpα1 and Sirpα1Δ4Y2 Sk-hepl, P <0. 05). There was no significant difference between the transfected Sirpα1 Sk-hepl cells and Sirpα1Δ4Y2 Sk-hep1 cells (P>0.05). CONCLUSIONS: Sirpα1 decreases gankyrin and cyclin D1 expression, and inhibits proliferation of liver carcinoma cells. It may be one of the forms for an Sirpα1 negative regulation of carcinogenesis and development of hepatocel- lular carcinoma.

Quantum Boltzmann equation solved by Monte Carlo method for nano-scale semiconductor devices simulation

A two-dimensional （2D） full band self-consistent ensemble Monte Carlo （MC） method for solving the quantum Boltzmann equation, including collision broadening and quantum potential corrections, is developed to extend the MC method to the study of nano-scale semiconductor devices with obvious quantum mechanical （QM） effects. The quantum effects both in real space and momentum space in nano-scale semiconductor devices can be simulated. The effective mobility in the inversion layer of n and p channel MOSFET is simulated and compared with experimental data to verify this method. With this method 50nm ultra thin body silicon on insulator MOSFET are simulated. Results indicate that this method can be used to simulate the 2D QM effects in semiconductor devices including tunnelling effect.

Influence of air pressure on mechanical effect of laser plasma shock wave

The influence of air pressure on mechanical effect of laser plasma shock wave in a vacuum chamber produced by a Nd：YAG laser has been studied. The laser pulses with pulse width of 10ns and pulse energy of about 320mJ at 1.06μm wavelength is focused on the aluminium target mounted on a ballistic pendulum, and the air pressure in the chamber changes from 2.8 × 10^ 3 to 1.01 × 10^5pa. The experimental results show that the impulse coupling coefficient changes as the air pressure and the distance of the target from focus change. The mechanical effects of the plasma shock wave on the target are analysed at different distances from focus and the air pressure.