Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Rats ; Rats, Wistar ; Sports

Objective To explore the cause, clinical characteristic and the relation to the alterations of bone metabolism and bone mineral density (BMD) in senile male patients with chronic obstructive pulmonary disease (COPD). Methods Fifty senile male patients with simple stable COPD were divided into moderate and severe groups based on the diagnostic criteria of pulmonary function. Thirty senile male health volunteers were considered as control group. Blood gas analysis, BMD, bone mineral content (BMC), biochemical indexes relative to the bone formation and bone absorption in blood and urine were measured and analyzed. Results Reductions in BMD and BMC were more significant in two COPD groups than those in control group (P

Objective To assess ventricular function of early stage neonates of different gestational ages by tissue doppler imaging(TDI).Methods Pulsed wave TDI velocities were obtained in 36 cases of premature infants with gestational ages of 32 to 36 weeks(premature group) and 33 cases of full-term infants(full-term group) aged 3 to 7 days at the lateral mitral annulus(MA),basal septum,and lateral tricuspid annulus(TA) during ventricular systole(Sa),early diastole(Ea),late diastole(Aa).Tansmitral and transtricuspid inflow were also obtained through pulsed doppler echocardiography.Results Ea and Sa in all of 3 locations were lower in the premature group compared with that of the full-term group,and Ea/Aa in TA was lower in premature group,but Aa and E/Ea showed no difference between 2 groups.Ea and Sa showed a positive correlation with gestational age and birth weight.Conclusions Ventricular systolic and diastolic function in premature infants are poorer than that in full-term infants in the early stage of neonatal period,and ventricular function is related to intra-uterus growth and maturity of the newborn.Diastolic function of the left ventricle in both groups develops rapidly during the early stage of neonatal period.

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.

Aim To explore the effect of shikonin on stemness maintance of glioma stem cells ( GSCs ). Methods After the U87-MG cells were cultured and isolated, the sphere cells were identified by immuno-fluorescent staining. The alteration of stemness of GSCs by shikonin treatment(2 μmol·L - 1 ) for 12 h, 24 h and 48 h was valued by morphological detection using optical microscope and sub-sphere forming assay. Mo-reover, the related markers of stem cells, such as CD133, were detected in shikonin treated GSCs by western blot assay. Protein expression of PI3K, p-PI3K, Akt and p-Akt was detected by western blot af-ter shikonin treatment alone. Furthermore, by combi-nation with insulin-like growth factor-1 ( IGF-1), we observed the alteration of stemness maintance of shiko-nin-treated GSCs. Results The presence of neural stem cell related markers CD133 and nestin proved the characteristics of GSCs. Shikonin treatment significant-ly inhibited the morphology of GSCs and the sub-sphere forming. Besides, the reduced expression of CD133 was detected in shikonin treated GSCs. Though, the expression of PI3K and Akt did not change compared with the control group, the expression of p-PI3K and p-Akt was reduced. Furthermore, the combination of IGF-1 markedly attenuated the inhibitory effect of shikonin on stemness maintance of GSCs. Conclusion The stemness maintance of GSCs can be significantly inhibited by shikonin treatment, in which PI3K/ Akt pathway is involved.

Aim To investigate the signaling mecha-nisms in endothelial monocyte-activating polypeptide-Ⅱ( EMAP-Ⅱ)-induced increase in blood-tumor barri-er ( BTB ) permeability. Methods Relatively pure cerebral microvessel fragments were obtained from the cortex of 3-5 days old Wistar rats by using careful dis-section, enzyme digestion, and dextran centrifugation. Then, these fragments were seeded on dishes and cul-tured primarily. In vitro BTB models were constructed by co-cultivation of rat brain microvascular endothelial cells ( BMECs) with C6 glioma cells. Confluent mono-layers of co-cultured BMECs were divided randomly in-to 5 groups ( each n=6 ): control, EMAP-Ⅱ, H7 +EMAP-Ⅱ, C3 exoenzyme + EMAP-Ⅱ, and C3 ex-oenzyme + H7 + EMAP-Ⅱ groups. Transendothelial electric resistance values and horseradish peroxidase flux were measured to evaluate changes in the BTB permeability . The expression levels of tight junction-re-lated protein occludin and ZO-1 in BMECs were meas-ured by Western blot. Immunofluorescence was used to identify the expression and distribution of occludin and ZO-1 in BMECs. Also, Western blot were used to de-tect the expression levels of myosin light chain ( MLC) and phosphomyosin light chain ( pMLC ) in BMECs. Results Compared with control group, the BTB per-meability of EMAP-Ⅱ group was increased significant-ly. The expression levels of occludin and ZO-1 in BMECs were significantly decreased, accompanied with marked increase in the expression level of pMLC. These above-mentioned effects of EMAP-Ⅱ were sig-nificantly inhibited by pretreatment with H7 ( an inhib-itor of PKC ) or/and C3 exoenzyme ( an inhibitor of RhoA ) . Conclusion Signaling molecules PKC and RhoA play important roles in EMAP-Ⅱ-induced in-crease in BTB permeability; signaling pathways PKC-pMLC and RhoA-pMLC are involved in this process.

Adolescent ; Adult ; Child ; China ; Female ; HIV Infections ; ethnology ; transmission ; virology ; HIV-1 ; classification ; genetics ; isolation & purification ; Humans ; Male ; Middle Aged ; Population Dynamics ; Young Adult

To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
Animals ; Biomarkers ; metabolism ; Doxorubicin ; toxicity ; Energy Metabolism ; Liver ; drug effects ; metabolism ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolic Networks and Pathways ; Metabolomics ; Multivariate Analysis ; Oxidative Stress ; Rats

Bacteremia ; etiology ; Female ; Humans ; Infant, Newborn ; Listeria monocytogenes ; isolation & purification ; Male

Objective] To explore the humoral and cellular immune responses in mice to eukaryotic expression recombinant plasmid encoding histidine rich protein 2 (HRP\|Ⅱ) of Plasmodium falciparum. [Methods] The start and stop codes were introduced into HRP\|Ⅱ gene fragment, the reading frame and the position of start and stop codes in HRP\|Ⅱ were identified by sequencing. HRP\|Ⅱ fragment containing the start and stop codes was cloned into pcDNA3 1(\|) to form pcDNA3 1(\|)/HRP\|Ⅱ. The BALB/c mice were immunized i.m. with the plasmids for 3 times in 3 weeks intervals. Two weeks after the last immunization, the sera and splenocytes were collected to investigate anti\|HRP\|Ⅱ antibodies by ELISA and the splenocytes proliferation response to HRP\|Ⅱ. [Results] Sequence data show that the reading frame and the position of start and stop codes are correct. Restriction enzyme digestion indicated that the HRP\|Ⅱ gene fragment containing start and stop codes was successfully cloned into pcDNA3 1(\|). Mice raised significant anti\|HRP\|Ⅱ antibodies after pcDNA3 1(\|)/HRP\|Ⅱ immunization, and the splenocytes proliferated prominently when stimulated with HRP\|Ⅱ protein. [Conclusion] Eukaryotic expression recombinant plasmid \{encoding\} HRP\|Ⅱ gene can induce significantly humoral and cellular immune response in mice. HRP\|Ⅱ gene may be a good candidate for P.falciparum blood\|stage multiple DNA vaccine.