Effects of Chuanxiongqin hydrochloride on increasing the fluidity of brain cell membrane and scavenging free radicals in model rats with ischemia/reperfusion injury

BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to high rigidity and low fluidity of cell membrane, and the conditions can be changed by Chuanxiongqin. OBJECTIVE: To observe the effect and mechanism of Chuanxiongqin hydrochloride on the fluidity of brain cell membrane in rat models of ischemia/reperfusion. DESIGN: A completely randomized controlled animal trial. SETTINGS: Institute of Brain Sciences; Department of Physiology, Medical College, Datong University. MATERIALS: Twenty male grade Ⅰ Wistar rats of 170-220 g were randomly divided into model group (n =10) and control group (n =10). Chuanxiongqin hydrochloride (molecular mass was 172.2) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (batch number: 0817-9803); Spin labelers: 5-doxyl-stearlic acid methylester (5DS), 16-doxyl-stearlic acid methylester (16DS), xanthine, xanthine oxidase (XOD) and 5,5-dimeth-1-pyrroline- N-oxide (DMPO) from Sigma Company; Bruker ESP 300 electron paramagnetic resonance (EPR) spectrometer by Bruker Company (Germany). METHODS: The experiments were carried out in the State Key Laboratory of Natural and Biomimetic Drugs, Peking University from June 2001 to July 2002. In the model group, rats were made into models of cerebral ischemia by 30-minute ligation and 2-hour reperfusion of common carotid arteries; The rats in the control group were not made into models. The order parameter (S) and rotational correlation time (τc) were detected with the ESR spectrometer by means of spin labeling. The greater the S and τc, the smaller the fluidity. Meanwhile, the clearance rate of free radicals was detected with ESR spin trapping. The measurement data were compared using the t test. MAIN OUTCOME MEASURES: The S, τc and clearance rates of O2 · and OH· free radicals were compared between the model group and control group. RESULTS: The S and τc in the model group [0.738 4±0.003 5; (8.472±0.027)×10-10 s/circle] were obviously different from those in the control group [0.683 9±0.008 3; (7.945±0.082)×10-10 s/circle, t =5.731, 5.918, P < 0.05], which suggested that ischemia/reperfusion injury decreased the fluidity of brain cell membrane. After adding Chuanxiongqin hydrochloride, there were no obvious differences between the model group [0.688 5±0.030 5; (7.886±0.341)×10-10 s/circle] and control group (P > 0.05), indicating that Chuanxiongqin hydrochloride could recover the fluidity of brain cell membrane after ischemia/reperfusion injury close to the level in the normal control group. Chuanxiongqin hydrochloride could directly scavenge the O2 · and OH· free radicals, and the maximal clearance rates were 83.92% and 44.99% respectively. CONCLUSION: Chuanxiongqin hydrochloride increases the fluidity of membrane of ischemia-injured brain cell by scavenging both O2 ·and OH· free radicals.

The application of open disk-like structures as model membrane and drug carriers

The objective of this review is to outline the application of bicelles(or called bilayer micelles)and bilayer nanodisks in pharmaceutics,pharmaceutical analysis and biochemistry.The application of open disk-like structures as model membrane and drug carrier has been described.The exploration of many reports in different fields suggested that these open disk-like structures have great potential in studying interactions between drug-membrane and structure/function studies of membrane-bound proteins.Furthermore,they could be applied as promising carriers for in vivo delivery of drugs,protein and peptide.

Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

Symmetrical adhesion of two cylindrical colloids to a tubular membrane

With the full treatment of the Helfrich model we theoretically study the symmetrical adhesion of two cylindrical colloids to a tubular membrane. The adhesion of the rigid cylinders with different radius from the membrane tube surface can produce both shallow wrapping with relatively small wrapping angle and deep wrapping with big wrapping angle. These significant structural behaviors can be obtained by analyzing the system energy. A second order adhesion transition from the desorbed to weakly adhered states is found, and a first order phase transition where the cylindrical colloids undergo an abrupt transition from weakly adhered to strongly adhered states can be obtained as well.

Simplified mathematical model of proton exchange membrane fuel cell based on horizon fuel cell stack

This paper presents a simplified zero-dimensional mathematical model for a self-humidifying proton exchange membrane(PEM)fuel cell stack of 1 k W.The model incorporates major electric and thermodynamic variables and parameters involved in the operation of the PEM fuel cell under different operational conditions.Influence of each of these parameters and variables upon the operation and the performance of the PEM fuel cell are investigated.The mathematical equations are modeled by using Matlab-Simulink tools in order to simulate the operation of the developed model with a commercial available 1kW horizon PEM fuel cell stack(H-1000),which is used for the purposes of model validation and tuning of the developed model.The model can be extrapolated to higher wattage fuel cells of similar arrangements.New equation is presented to determine the impact of using air to supply the PEM fuel cell instead of pure oxygen upon the concentration losses and the output voltage when useful current is drawn from it.

Integration of molecular dynamic simulation and free volume theory for modeling membrane VOC/gas separation

Gas membrane separation process is highly unpredictable due to interacting non-ideal factors, such as composition/pressure-dependent permeabilities and real gas behavior. Although molecular dynamic （MD） simulation can mimic those complex effects, it cannot precisely predict bulk properties due to scale limitations of calculation algorithm. This work proposes a method for modeling a membrane separation process for volatile organic compounds by combining the MD simulation with the free volume theory. This method can avoid the scale-up problems of the MD method and accurately simulate the performance of membranes. Small scale MD simulation and pure gas permeation data are employed to correlate pressure-irrelevant parameters for the free volume theory; by this approach, the microscopic effects can be directly linked to bulk properties （non-ideal permeability）, instead of being fitted by a statistical approach. A lab-scale hollow fiber membrane module was prepared for the model validation and evaluation. The comparison of model predictions with experimental results shows that the deviations of product purity are reduced from 10% to less than 1%, and the deviations of the permeate and residue flow rates are significantly reduced from 40% to 4%, indicating the reliability of the model. The proposed method provides an efficient tool for process engineering to simulate the membrane recovery process.

A new artificial bee swarm algorithm for optimization of proton exchange membrane fuel cell model parameters

An appropriate mathematical model can help researchers to simulate,evaluate,and control a proton exchange membrane fuel cell (PEMFC) stack system.Because a PEMFC is a nonlinear and strongly coupled system,many assumptions and approximations are considered during modeling.Therefore,some differences are found between model results and the real performance of PEMFCs.To increase the precision of the models so that they can describe better the actual performance,opti-mization of PEMFC model parameters is essential.In this paper,an artificial bee swarm optimization algorithm,called ABSO,is proposed for optimizing the parameters of a steady-state PEMFC stack model suitable for electrical engineering applications.For studying the usefulness of the proposed algorithm,ABSO-based results are compared with the results from a genetic algo-rithm (GA) and particle swarm optimization (PSO).The results show that the ABSO algorithm outperforms the other algorithms.

A MEMBRANE ELEMENT MODEL WITH BENDING MODIFICATION FOR ONE STEP INVERSE METHOD

A membrane element model with bending modification based on element moment equilibrium is proposed for the first time by the authors, who apply the element model in one step inverse method and simulate the forming process of a flower-shaped box using the membrane element model with and without this modification. The numerical results are compared with those of the incremental method to verify the validity of the element model developed in this paper.

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides （CER）[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid （OA） and isopropyl myristate （IPM） on the lipid nanostrueture. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. 2H NMR spectroscopy was used to study the impact of the ceramides＇ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The 2H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix. The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum comeum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases （assigned as phase A and B） appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

Numerical Simulation of Fluid Membranes in Two-Dimensional Space

The membrane’s dynamics is very important for cells.A membrane in 2-dimensional space can be seen as an incompressible closed curve in a plane or a cylindrical surface in 3-dimensional space.In this paper,we design a second-order accurate numerical algorithm to simulate the shape transformation of the membrane.In the algorithm,we use the tangent angles to present the curve and avoid the difficulties from the constraint of curve’s incompressible condition.A lot of interesting phenomena are obtained.Some of them are very like the life processes of cells,such as exocytosis and endocytosis.Furthermore,we can see the relation between two dynamic models clearly.At last,considering the influence of the inner incompressible fluids partially,we add a constraint:the area circled by the membrane maintain invariable.The numerical results show the dynamic motions of a curve remaining its local arc length and inner area constant.

A linear quadratic regulator control of a stand-alone PEM fuelcell power plant

This paper introduces a technique based on linear quadratic regulator （LQR） to control the output voltage at the load point versus load variation from a stand- alone proton exchange membrane （PEM） fuel cell power plant （FCPP） for a group housing use. The controller modifies the optimal gains ki by minimizing a cost function, and the phase angle of the AC output voltage to control the active and reactive power output from an FCPP to match the terminal load. The control actions are based on feedback signals from the terminal load, output voltage and fuel cell feedback current. The topology chosen for the simulation consists of a 45 kW proton exchange membrane fuel cell （PEMFC）, boost type DC/ DC converter, a three-phase DC/AC inverter followed by an LC filter. Simulation results show that the proposed control strategy operated at low commutation frequency （2 kHz） offers good performances versus load variations with low total harmonic distortions （THD）, which is very useful for high power applications.