Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer’s disease

Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cvtotoxicitv in PC12 cells

Alpinia oxyphylla,a traditional herb,is widely used for its neuroprotective,antioxidant and memory-improving effects.However,the neuroprotective mechanisms of action of its active ingredients are unclear.In this study,we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro.Alpinia oxyphylla was extracted three times with 95%ethanol(representing extracts 1–3).The third 95%ethanol extract was dried and resuspended in water,and then extracted successively with petroleum ether,ethyl acetate and n-butanol(representing extracts 4–6).The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells.The protective effect of the three ethanol extracts(at tested concentrations of 50,100 and 200μg/mL)against cytotoxicity to PC12 cells increased in a concentration-dependent manner.The ethyl acetate,petroleum ether and n-butanol extracts(each tested at 100,150 and 200μg/mL)had neuroprotective effects as well.The optimum effective concentration ranged from 50–200μg/mL,and the protective effect of the ethyl acetate extract was comparatively robust.These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide.Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

Topological analysis of plasma flow control on corner separation in a highly loaded compressor cascade

In this paper, flow behavior and topology structure in a highly loaded compressor cascade with and without plasma aerodynamic actuation （PAA） are investigated. Streamline pattern, total pressure loss coefficient, outlet flow angle and topological analysis are considered to study the effect and mechanism of the plasma flow control on corner separation. Results presented include the boundary layer flow behavior, effects of three types of PAA on separated flows and performance parameters, topology structures and sequences of singular points with and without PAA. Two separation lines, reversed flow and backflow exist on the suction surface. The cross flow on the endwall is an important element for the comer separation. PAA can reduce the undertuming and overturning as well as the total pressure loss, leading to an overall increase of flow turning and enhancement of aerodynamic performance. PAA can change the topology structure, sequences of singular points and their corresponding separation lines. Types II and III PAA are much more efficient in controlling comer separation and enhancing aerodynamic performances than type I.

Neuroprotective effect of the Chinese medicine Tiantai No.1 and its molecular mechanism in the senescence-accelerated mouse prone 8

Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Multiplicity for Nonlinear Elliptic Boundary Value Problems of p-Laplacian Type Without Ambrosetti-Rabinowitz Condition

In this paper, we study the existence of multiple solutions to the following nonlinear elliptic bound- ary value problem of p-Laplacian type：{-△pu=div（｜Du_p-2Du）is the p-Laplacian of u andin W1 0^p（Ω）but f（x,1）dose not satisfy the Ambrosetti-Rabinowitz condition. Under suitable assumptions onPass Theorem under（C）_ccondition. Our main result generalizes a result by N. S. Papageorgiou, E. M. Rochaand V. Staicu in 2008 （Calculus of Variations and Partial Differential Equations, 33： 199-230（2008）） and a result by G. B. Li and H. S. Zhou in 2002 （Journal of the London Mathematical Society, 65：123 138（2002））.

Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents

A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine（1）and evaluated for their anti-HCV activity,taking compound 2 as the lead.SAR revealed that the introduction of a suitable substituent at the N’-end of matrinic amide might greatly enhance the potency.Among them,matrinic acid 17 and N’-substituted matrinic amides 18a-d exhibited promising potency with low micromolar EC50 values ranging from 1.03μmol/L to 7.54 μmol/L,and better therapeutic window with SI from 66 to 132.Moreover,compound 17 displayed an excellent PK and safety profile in vivo,demonstrating good drug-like characteristics.Thus,it has been selected for further investigation,with an advantage of decreased chances of inducing drug-resistance mutations.

Research Progress of hypersonic boundary layer transition control experiments

Hypersonic boundary layer transition is a hot yet challenging problem restricting the development and breakthrough of hypersonic aerodynamics.In recent years,despite great progress made by wind tunnel experiment,transition mechanism and transition prediction,only partial knowledge has been gained so far.In this paper,firstly,the specific scenarios of hypersonic boundary layer transition control are clarified.Secondly,the experimental research progress and mechanism of passive control and active control methods under different hypersonic transition control demands are summarized,with their advantages and disadvantages being analyzed separately.Plasma actuation is easy to produce controllable broadband aerodynamic actuation,which has potential in the field of boundary layer transition control.Hence,the following part of the paper focuses on plasma flow control.The feasibility of plasma actuation to control the hypersonic boundary layer transition is demonstrated and the research ideas are presented.Finally,hypersonic boundary layer transition control methods are summarized and the direction of future research is prospected.

Capture and Identification of Dual Specificity Mitogen-Activated Protein Kinase Kinase 7 as a Direct Proteomic Target of Berberine to Affect the c-JunN-Terminal Kinase Pathway

Seven photoaffinity-based and sixteen biotin-based berberine(BBR)probes were constructed and screened for their effects on c-Jun N-terminal protein kinases(JNK)phosphorylation(p-JNK)suppression at the cellular level.Taking active-photoaffinity probe 7c as a chemical tool,we first identified mitogen-activated protein kinase 7(MAP2K7),an upstream protein on the JNK/stress activated protein kinase(SAPK)pathway,as a direct proteomic target of BBR using activity-based protein profiling(ABPP)and other chemical proteomic techniques.Furthermore,BBR’s inhibitory effect on p-JNK was significantly attenuated in both the MAP2K7-knockdown and models,indicating a MAP2K7-dependent inhibition on the JNK signaling pathway.For the first time,we demonstrate the unique mechanism of BBR that directly targets MAP2K7 to inhibit p-JNK rather than JNK activity with the advantages of multiple activities and a good safety profile.