Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

Effectiveness analysis of comprehensive measures to control the plague in the epidemic areas in Longlin county Guangxi from 2001 to 2010 / 中国地方病学杂志

Objective To evaluating the effectiveness of comprehensive measures to control the plague in epidemic areas in Longlin county Guangxi from 2001 to 2010.Methods Original epidemic places was deratised,indicative animals were investigated,and epidemic clues were searched.Cage trapping method was used to capture rat and rat body fleas were collected in the plague epidemic areas.The flea-carrying rates and flea index of rodents were calculated based on the number of fleas collected from caged rodents.The animals were then subjected to etiological and serological tests to determine the plague infection rate.Results A total of 1008 rats were captured and 571 fleas were collected from 2001 to 2010,of which Rattus Flavipestus accounted tor 81.65％(823/1008) and Xenopsylla Cheopis for 64.10％(366/571).The annual average rodents infected with flea and the index of flea were 23.02％ (177/769) and 0.74,respectively.The annual average density of rodents decreased from 3.99％ (859/21 508,before deratised) to 0.96％ (149/15 600,after deratised).The deratization rate was 75.94％.Conclusion The risk of a plague epidemic in Longlin county is reduced after continued comprehensive measures be taken to deal with the disease.

Plague surveillance and control in Longlin county Guangxi from 2000 to 2009 / 中国地方病学杂志

Objective To analyze the outcome of surveillance results on plague and to provide the evidences for the policy making in Longlin county Guangxi. Methods The epidemic data and the surveillance results of plague were analyzed and assessed with epidemiology methods in Longlin county Guangxi from 2000 to 2009, and the density of rodents, the rodents infected with flea, flea index and other indicators were calculated. Regional composition of the rats and fleas were analyzed. Results A totally of 4829 rats were captured and 4737 fleas were collected in the past 10 years, Rattus Flavipestus(81.92%,3956/4829) and Xenopsylla Cheopis (79.04%,3744/4737) were dominant species. The annual average density of rodents, the rodents infected with flea, index of flea were 3.30%(4829/146 206), 27.99%(1351/4827) and 0.98(4737/4827), respectively. A totally of 4792 rats were examined and 10 strains Yersinia Pestis were isolated. Indirect hemorrhagic assessed(IHA) was used to test the F1 antibody against plague in the blood serum of the rats and indicator animals, and 3 positive rats and 24 positive animals were found, respectively. Twenty seven natural villages in 3 towns had been involved in the plague. Conclusions The plague foci exists in Longlin county of Guangxi province. The plague foci in the areas have the same feature with the plague foci of Rattus Flavipectus. There is a potential risk for plague in this region, we should improve the quality of surveillance, increase indicator animals of the plague, and try to apply new surveillance method.

Expression and regulation of pituitary adenylate cyclase-activating polypeptide mRNA in pregnant rat corpus luteum / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the expression changes and regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in corpus luteum during pregnancy.</p><p><b>METHODS</b>Pregnant rats' ovaries were collected at different time points. The techniques of RT-PCR and in situ hybridization were used to observe expression changes of PACAP mRNA in rat ovaries during pregnancy. To further explore the regulation mechanism of PACAP mRNA expression in corpus luteum, luteal cells were cultured in vitro. Immature (25 - 28 days old) female Sprague-Dawley rats were injected subcutaneously with 50IU pregnant mare serum gonadotrophin (PMSG), and 25IU human chorionic gonadotrophin (hCG) 48 h later, to induce follicular development and luteum formation. On day 6 after hCG administration (the day of hCG administration was the first day), the rats were killed by guillotine and the ovarian luteal cells were collected. After incubation for 24 h, luteal cells were administration with various factors for 24 h. And then expression changes of PACAP mRNA in luteal cells after administration with different factors were detected by RT-PCR, and radioimmunoassay was used to analyze progesterone levels.</p><p><b>RESULTS</b>With the development of pregnancy, the expression of PACAP mRNA increased gradually, reached the peak at pregnancy 19 d, and then decreased. Compared with control group, platelet activating factor (PAF), forskolin and PMA could obviously stimulate PACAP mRNA expression in luteal cells which were cultured with corresponding factors for 24 h. At the same time, progesterone levels in culture media were also elevated.</p><p><b>CONCLUSION</b>PACAP, acting as a local ovary regulator, was closely related to the maintenance of medium-term and late pregnancy. PAF could directly stimulate PACAP mRNA expression in luteal cells, and protein kinase C (PKC) and protein kinase A (PKA) signal pathways could both participate in this process.</p>

Effect of Zuoguiyin on expression of ovarian VEGF and SPARC in rats during peri-menopausal period / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of one kind of regulating-qi and Nourishing-yin Chinese herbs Zuoguiyin on the expression of rats ovarian vascular endothelial growth factor (VEGF) and secreted protein acidic rich in cysteine (SPARC) during the period of peri-menopause.</p><p><b>METHOD</b>The animal models of perimenopause rats were established by natural aging. Perimenopause rats were treated by intragastric administration (ig) with low (13.78 g x kg(-1)), middle (20.67 g x kg(-1)) and high (31 g x kg(-1)) dose of Zuoguiyin for 8 weeks. Expression of VEGF and SPARC mRNA were detected by RT-PCR. Immunohistochemistry was used to evaluate expression levels of VEGF protein.</p><p><b>RESULT</b>Compared with that in the control group, ovarian expression levels of VEGF mRNA and its protein in rats during peri-menopause increased significantly (P < 0.01). Middle and high dose of Zuoguiyin could both down-regulate the expression of VEGF in ovaries of praesenilis rats, and the difference has statistical significance (P < 0.01). Expression levels of SPARC mRNA in rat ovaries during peri-menopausal period decreased obviously compared to that in the control group (P < 0.01). Middle and high dose of Zuoguiyin could greatly promote ovarian SPARC mRNA expression of praesenilis rats (P < 0.01).</p><p><b>CONCLUSION</b>The abnormal changes of VEGF and SPARC may play an important role in the aging process of ovary. Zuoguiyin, one kind of regulating-qi and Nourishing-yin Chinese herbs, can improve ovarian vascular formation through down-regulating the expression of VEGF meanwhile up-regulating the expression of SPARC. And it may delay aging by this way.</p>

Role of platelet-activating factor in progesterone synthesis and vascular endothelial growth factor expression in rat luteal cells / 生理学报

The present study aimed to investigate the role of platelet-activating factor (PAF) in progesterone synthesis and vascular endothelial growth factor (VEGF) expression in rat luteal cells. Immature (25-28 days old) female Sprague-Dawley rats were injected subcutaneously with 50 IU pregnant mare serum gonadotrophin (PMSG), and 25 IU human chorionic gonadotrophin (hCG) 48 h later, to induce follicular development and luteum formation. On day 6 after hCG administration (the day of hCG administration was the first day), the rats were killed by guillotine and the ovarian luteal cells were collected. After incubation for 24 h, luteal cells were incubated without or with different doses (0.1 μg/mL, 1 μg/mL, 10 μg/mL) of PAF at 37 °C (5% CO(2)) for 24 h, and then progesterone concentration was evaluated by radioimmunoassay (RIA); apoptotic rate and VEGF mRNA expression in luteal cells were assessed by flow cytometry and RT-PCR, respectively. The results showed that PAF promoted progesterone production, with a maximal effect at 1 μg/mL (P<0.05); PAF increased apoptotic rate but not in a dose-dependent manner, and 10 μg/mL PAF enhanced apoptotic rate significantly (P<0.05); furthermore, PAF stimulated VEGF mRNA expression in luteal cells, especially at 1 μg/mL (P<0.01). It is suggested that PAF regulates progesterone synthesis and VEGF mRNA expression in luteal cells to mediate corpus luteum formation in rat ovary.

Effects of soy isoflavones on the expression of Bax mRNA and Ca(2+)-ATPase activity in ovaries of perimenopause rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of soy isoflavones (SI) on the expression of Bax mRNA and Ca(2+) -ATPase activity in ovaries of perimenopause rats.</p><p><b>METHODS</b>The animal model of perimenopause rats was established by unforced aging. 12 month-old presenilins female Wistar rats were administered by intragastric (ig) with low (500 mg/kg), middle (158 mg/kg) and high (500 mg/kg) does of SI for 8 weeks. The expression of Bax mRNA in ovaries were detected by RT-PCR. Ca(2+) -ATPase activity in ovaries and MDA content and SOD activity in serum were detected by chemi-chromatometry.</p><p><b>RESULTS</b>Intervention of SI could significantly decrease the expression of Bax mRNA in ovaries and MDA content in serum, increase Ca(2+) -ATPase activity in ovaries and SOD activity in serum of presenilins rats (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Soy isoflavones could down-regulate the expression of Bax mRNA and increase Ca(2+) -ATPase activity in aged ovaries. It is probably one of the mechanisms to improve the function of aged ovaries in perimenopause rats.</p>

Effects of vitamin E on expression of PS-1 and production of Abeta in the hippocampus of female senile rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the expression of Presenilin-1 (PS-1) and production of amyloid beta-protein (Abeta) in hippocampus of female senile rats and to investigate the effect of vitamin E(VE) on preventing Alzheimer's disease after menopause.</p><p><b>METHODS</b>The animal model was established using female senile rats. Experimental groups (n=8) were respectively given different doses of VE(5 mg/kg, 15 mg/kg, 60 mg/kg) per day. The expression of PS-1 in hippocampus was detected by immunohistochemistry, the level of Abeta in hippocampus was measured by Radioimmunoassay, and neuronal ultrastructure in hippocampal DG area was observed using transmission electron microscope.</p><p><b>RESULTS</b>The expression of PS-1 in rat hippocampus of senile control group was stronger than that of adult control group. PS-1 expressed weakly in three medication groups along with augmentation of dosage. The levels of Abeta were found to correlate statistically with the expression of PS-1. The content of Abeta in VE groups was significantly decreased compared to that in senile control group (P < 0.01). There were some changes in the neuronal ultrastructure of senile rats. Neurons were gradually recovered in VE groups.</p><p><b>CONCLUSION</b>VE may depress the production of Abeta by regulating the expression of PS-1, reducing neuronal injuries. VE may play a role in neuronal protection.</p>

The changing trends of expression of VEGF and its relationship with the levels of NO in rat corpus luteum of pseudopregnant / 中国应用生理学杂志

<p><b>AIM</b>The expression of VEGF in rat ovaries corpus luteum and its expression pattern were observed to investigate the effect of VEGF on luteal formation and regression.</p><p><b>METHODS</b>The model of immature rat of pseudopregnant was established using pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), the expression of VEGF in corpus luteum was detected by immunohistochemistry, the levels of VEGF in corpus luteum was measured by ELISA, and the levels of NO in corpus luteum was measured by chemistry assay.</p><p><b>RESULTS</b>VEGF expressed weakly in rat corpus luteum on the day 1, and enhanced gradually from day 3 to day 5, then went up to the peak on the day 7, and maintained to day 9. On the day 11, the expression of VEGF began to decrease. The levels of VEGF were similar to the expression of VEGF. The levels of NO appeared like double wave. The levels increased gradually from day 1 to day 5, and peaked on the day 7, then decreased on the day 9, while lightly increased on the day 11, and showed significant increase and reached the highest on the day 13, then decreased the lowest on the day 15.</p><p><b>CONCLUSION</b>There is a intimate temporal relationship between the expression of VEGF and angiogenesis in corpus luteum, VEGF may play a role in luteum formation by improving angiogenesis mediated by NO, NO may play a role in luteum regression as a luteolytic during the late luteal phase.</p>

Effect of L-tyrosine on 3beta-HSD activity of rat luteal cells in vitro / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of L-tyrosine on 3beta-HSD activity of rat luteal cells in vitro.</p><p><b>METHODS</b>Luteal cells were isolated from ovary tissues of female rats pretreated with PMSG and hCG. Luteal cells were cultured with 95% oxygen and 5% carbon dioxide in 37 degrees C. 3beta-HSD activity was measured by radioimmunoassay (RIA).</p><p><b>RESULTS</b>(1) 0.2 mmol x L(-1) and 2.0 mmol x L(-1) L-tyrosine significantly inhibited 3beta-HSD activity. (2) 0.2 mmol x L(-1) L-tyrosine exerted different effects on 3beta-HSD activity at different concentrations of pregnenolone (Ph). It increased 3beta-HSD activity at 0.1 micromol x L(-1) and 1 micromol x L(-1) of Pn concentration. With further increase in the concentration of Pn to 100 micromol x L(-1), the stimulating effect of L-tyrosine was switched to suppression effect. (3) L-tyrosine and L-tyrosine hydrazide both inhibited 3beta-HSD activity induced by hCG.</p><p><b>CONCLUSION</b>L-tyrosine affects 3beta-HSD activity of rat luteal cells in vitro. L-tyrosine and tyrosine hydrazide inhibits hCG induced 3beta-HSD activity.</p>

Application and evaluation of PBL in experimental teaching of circulatory physiology / 中华医学教育探索杂志

Toinvestigate the implementation mode and effectiveness of Problem-Based Learning (PBL) in experimental teaching of physiology,PBL was applied in experimental teaching of circulatory physiology. Comparison of test scores and Dundee Ready Education Environment Measure (DREEM) were used to evaluate teaching quality and teaching environment respectively. The results showed that both test and DREEM scores were higher in PBL group than in control group (P

Effect of gamma-aminobutyric acid on the sperm acrosin activity / 中华男科学杂志

<p><b>OBJECTIVES</b>To investigate the effect of gamma-aminobutyric acid (GABA) on the sperm acrosin activity in normal men and positive antisperm antibody (AsAb) men.</p><p><b>METHODS</b>Sperm acrosin activity was detected by BAEE/ADH method.</p><p><b>RESULTS</b>GABA could increase the sperm acrosin activity in normal and AsAb positive patients (P < 0.01). The results also indicated that GABA significantly increased Na(+)-K(+)-ATPase activity (P < 0.01), Ca(2+)-ATPase activity (P < 0.05) and SOD activity (P < 0.01) of sperm.</p><p><b>CONCLUSIONS</b>The results demonstrated that GABA could influence the sperm acrosin activity.</p>

Study on the expression of the gene deleted in colorectal carcinoma in ovarian carcinoma / 中华妇产科杂志

Objective The purpose of this study was to explore the relationship between the loss of the gene deleted in colorectal carcinoma (DCC) gene expression in ovarian carcinoma and the transformation, progression of the tumor and its clinicopathological factors. Methods DCC gene mRNA expression were examined by reverse transcription polymerase chain reaction (RT-PCR) in 34 malignant, 10 benign and 10 normal ovarian samples. To clarify the expression of DCC gene by the DNA cloning and the DNA sequencing analysis in normal ovarian sample. Results The expression of DCC gene was lost in no normal ovarian tissues, in 2 (2/10) benign lesions, while the loss of DCC gene expression was found in 19(19/34,56%) carcinomas ( P

DEGRADATION AND TRANSFORMATION OF COTTON SEED HULLS BY COPRINUS COMATUS / 微生物学通报

Coprinus comatus cultivated on cotton seed hull medium decomposed lignocellulose straggly and was high of absolute biological efficiency. Lignocellulose is the main carbon source for the fruiting stage of the fungus. There existed the positive correlation between the degradation rates of the cellulose and hemicellulose in the medium and the activities of extracellular CMCase (carboxymenthelcel lulase), FPase (filter paper cellulase) and HCase (hemicellu-lase), there also existed the positive correlation between the degradation rate of the lignin in the medium and the activity of extracellular laccase, but no correlation between the degradatio rate of the lignin in the medium and the activity of peroxidase. The activity of extracellular amylase was comparatively high at mycelial growth stage, and the protease activity peek was at teh time when the fruitbody matured.

STUDIES ON COMPOSITION,ANTIOXIDATION AND HYPOGLYCEMIC EFFECTS OF POLYSACCHARIDES FROM GREEN TEA, OOLONG TEA AND BLACK TEA NI / 营养学报

Objective: To compare tea polysaccharides(TPS) characteristics and their role in scavenging free radicals and reducing blood glucose(BG) in diabetic mice(DM). Methods: TPS was extracted from green,Oolong and black tea which were made from the same fresh leaves from Hubei,Fujian and Yunnan. Then the recovery rate of TPS, contents of neutral sugar, uronic acid and protein were analysed, and scavenging rate of -2Oand 稯H in vitro and hypoglycemic effect were also determined. Results: 1. The yield and contents of neutral sugar, uronic acid and protein of green tea TPS were the highest, and those of black tea TPS were the lowest. Oolong tea TPS acted the best in scavenging-2O and 稯H . 2. The hypoglycemic effect of TPS from Hubei tea was the best . The effect of TPS extracted from semi-fermented Oolong tea and fermented black tea was better than that of non-fermented green tea. 3. There were obvious differences in yield, free radical scavenging rate and effect of reducing BG among TPS extracted from tea in different regions. TPS extracted from Fujian tea had the best effect in reducing BG,but that from Yunnan tea had not. Conclusion: There was remarkable effect of region and process on physico-chemical characteristics,effect of scavenging radical and reducing blood sugar TSP.