Normobaric hypoxia-induced brain damage in wistar rat

The biochemical indicators of wistar rat under low oxygen concentration, such as brain water content, necrosis, lactic acid and Na+-K+-ATPase, was detected to evaluate normobaric hypoxia-induced brain damage and to investigate the mechanism of wistar rat brain injury. Histopathological changes in brain tissue induced by hypoxia were investigated via hematoxylin and eosin stain (HE). Hypoxia induced factor-1α (HIF-1α) expression in brain was confirmed using immunohistochemistry. The results showed that the level of lactic acid was positively correlated with the degree of hypoxia, while concentration-dependent decrease in total Na+-K+-ATPase activity was observed. Compared with the control group, hypoxia group had a significant difference on brain water content under severe hypoxic conditions, the rate of brain necrosis increased obviously, followed by the increase of lactic acid level and the decrease of Na+-K+-ATPase activity. Histopathological analysis of brain confirmed that there was neuronal cell death in hippocampal gyrus. HIF-1α expression enhanced the hypoxia adaptation capability of the rat model through regulating the expressions of multiple genes. Lactic acid, Na+-K+-ATPase and HIF- 1α played an important role in brain injury as a possible mechanism.

Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism

The limited treatment options for advanced prostate cancer(PCa)lead to the urgent need to discover new anticancer drugs.Mannose,an isomer of glucose,has been reported to have an anticancer effect on various tumors.However,the anticancer effect of mannose in PCa remains unclear.In this study,we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro,and mannose was observed to have an anticancer effect in mice without harming their health.Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential,increased mitochondrial and cellular reactive oxygen species(ROS)levels,and reduced adenosine triphosphate(ATP)production in PCa cells.Mannose treatment of PCa cells induced changes in mitochondrial morphology,caused dysregulated expression of the fission protein,such as fission,mitochondrial 1(FIS1),and enhanced the expression of proapoptotic factors,such as BCL2-associated X(Bax)and BCL2-antagonist/killer 1(Bak).Furthermore,lower expression of mannose phosphate isomerase(MPI),the key enzyme in mannose metabolism,indicated poorer prognosis in PCa patients,and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose.This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.

Preparation of poly（N-isopropylacrylamide） brush grafted silica particles via surface-initiated atom transfer radical polymerization used for aqueous chromatography

Thermoresponsive poly（N-isopropylacrylamide） （PNIPAAm） brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymeriza- tion （SI-ATRP）. The grafting reaction started from the surfaces of 2-bromoisobutyrate- functionalized silica particles in 2-propanol aqueous solution at ambient temperature using CuCIICuCI21N, N,N＇,N＇,N”.pentamethyldiethylenetriamine （PMDETA） as the catalytic system. Based on thermogravimetric analysis （TGA） results, the grafting amount and grafting density of PNIPAM chains on the surface of silica were calculated to be 1.29 mg/ m^2 and 0.0215 chains/nm^2, respectively. The gel permeation chromatography （GPC） result showed the relatively narrow molecular weight distribution （MwlMn= 1.21） of the grafted PNIPAAm. The modified silica particles were applied as high-performance liquid chromatography （HPLC） packing materials to successfully separate three aromatic compounds using water as mobile phase by changing column temperature. Temperature- dependent hydrophilic/hydrophobic property alteration of PNIPAAm brushes grafted on silica particles was determined with chromatographic interaction between stationary phase and analytes. Retention time was prolonged and resolution was improved with increasing temperature. Baseline separation with high resolution at relatively low temperatures was observed, demonstrating dense PNIPAAm brushes were grafted on silica surfaces.

Enantiomeric separations of four basic drugs containing N-alkyl groups by a RP-HPLC system using SBE-β-CD as chiral mobile phase additive

The chiral separations of four pharmaceutical racemates which contain N-alkyl groups were satisfactorily resolved using SBE-β-CD as a chiral mobile phase additive （CMPA） in a RP-HPLC system （the resolution is 2.701 for ondansetron hydrochloride, 1.996 for sulpiride, 1.293 for clenbuterol hydrochloride and 0.816 for omeprazole）. In addition, the effects of different parameters such as CD type and CD concentration were investigated. The separation mechanism arises through the combination of several potential interactions, including electrostatic interactions as well as hydrogen bonding interactions and hydrophobic inclusion interactions, which allow for the SBE-β-CD-drug complexation with strong stereoselectivity and stability. The resolution also relates to the number and location of N atoms in the enantiomers. This method will be applicable to the isolation of various types of biologically imoortant enantiomers containing N-alkyl groups.

AN EFFICIENT RED BLOOD CELL MODEL IN THE FRAME OF IB-LBM AND ITS APPLICATION

A two-dinmnsional red blood cell （RBC） membrane model based on elastic and Euler- Bernoulli beam theories is introduced in the frame of immersed boundary-lattice Boltz- mann method （IB-LBM）. The effect of the flexible membrane is handled by the immersed boundary method in which the stress exerted by the RBC on the ambient fluid is spread onto the collocated grid points near the boundary. The fluid dynamics is obtained by solving the discrete lattice Boltzmann equation. A ＂ghost shape＂, to which the RBC returns when restoring, is introduced by prescribing a bending force along the bound- ary. Numerical examples involving tumbling, tank-treading and RBC aggregation in shear flow and deformation and restoration in poiseuille flow are presented to verify the method and illustrate its efficiency. As an application of the present method, a ten-RBC colony being compressed through a stenotic microvessel is studied focusing the cell-cell interaction strength. Quantitative comparisons of the pressure and velocity on speci- fled microvessel interfaces are made between each aggregation case. It reveals that the stronger aggregation may lead to more resistance against blood flow and result in higher pressure difference at the stenosis.

Dragon’s Blood Protect Rat Blood-Brain Barrier Dysfunction Induced by Simulated Microgravity Effect

Dragon’s blood(DB)has shown a protective effect on neurological diseases.Microgravity(MG)or simulated MG(SMG)can induce blood-brain barrier(BBB)dysfunction,which is a characteristic feature of neurological disorders.This study’s purpose was to evaluate the effect of DB on SMG-induced BBB dysfunction and explore its signaling pathway.Both DB and vitamin C(Vc)were administered orally for tail-suspended rats within 3 weeks.DB and Vc solutions were added to human brain microvascular endothelial cells(HCMEC/D3)cells,which were then exposed to SMG for 24 h.The protective effect of DB was assessed by hematoxylin and eosin and Nissl staining,ultrastructure observation,and permeability in rats.Cell apoptosis and the distribution of tight junction(TJ)and adherens junction(AJ)proteins and filamentous actin(F-actin)were examined in HCMEC/D3.The oxidative stress and inflammation,and TJ and AJ protein expressions were determined in rat brain and HCMEC/D3.The focal adhesion kinase(FAK)signaling pathway proteins were determined.DB protected SMG-induced rat BBB disruption by improving neuronal apoptosis,repairing widened intercellular space,and decreasing BBB permeability.DB effectively relieved SMG-induced HCMEC/D3 damage by inhibiting cell apoptosis and restoring F-actin spindle distribution.High doses of DB upregulated TJ and AJ protein expressions and decreased oxidative stress and proinflammatory cytokine levels in rat brain and HCMEC/D3.DB enhanced the expressions of FAK signal transduction proteins and F-actin/globular actin(G-actin)ratio in rat brain and HCMEC/D3,suggesting that DB promotes actin cytoskeleton polymerization,benefits the endothelial cell-cell and cell-extracellular matrix adhesion,and,in consequence,contributes to BBB integrity.