The improvement effect of scFv17 on the gait of triple-transgenic mice / 中国应用生理学杂志

OBJECTIVE@#To observe the gait changes of Alzheimer's disease PS1M146V/APPswe/tauP301L triple-transgenic (3xTg-AD) mice and to investigate the improvement effect of single chain variable domain antibody fragment 17 (scFv17) on the gait.@*METHODS@#In the present study, a selection of 6-month-old 3xTg-AD mice (=18) and C57BL/6 wild-type mice (=24) was performed. First, we observed their gait changes and found that the gait of 12-month-old 3xTg-AD mice was severely damaged. Then, the two groups of mice were randomly divided into four groups:WT+PBS(=12), WT+scFv17(=12), 3xTg-AD+PBS(=9) and 3xTg-AD+scFv17(=9). The gait behavior test and pathological test were performed after 12 weeks'continuous administration of scFv17 (1.5 mg/kg) or an equal volume of PBS (0.01 mol/L) by nasal gavage twice a week.@*RESULTS@#Compared with the same month old wild type mice, the rear track width of 12 month old 3xTg-AD mice was increased(<0.01), swing time percent was decreased (<0.01), stance time percent was increased(<0.01), so the ability of movement coordination and balance was seriously damaged. ScFv17 could improve the coordination and balance ability of 12 month old 3xTg-AD mice(<0.01). The morphological structure of 3xTg-AD mice cerebellar Purkinje cells was improved. The treatment of scFv17 increased the Nissl body number of the cerebellar Purkinje cells of 3xTg-AD mice (<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (<0.01).@*CONCLUSIONS@#The coordination and balance ability of 3xTg-AD mice was significantly impaired. ScFv17 can improve gait behaviour in the 3xTg-AD significantly.The mechanism may be related to the improvement of the structure and protein function of cerebellar Purkinje cells, and the eliminating of the Aβ plaques and the neurofibrillary tangles.

Application of wireless neuronal recording system in fear conditioning of Alzheimer's disease mice - hippocampal Theta oscillation observation / 生理学报

APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer's disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function.

Optimal conditions of bone marrow mesenchymal stem cells on paraquat-induced acute lung injury in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on acute lung injury induced by paraquat (PQ) poisoning in rats, and to identify the optimal transplantation conditions.</p><p><b>METHODS</b>Two hundred female rats were randomly divided into six groups, i.e., PQ group (n = 15), BMSC treatment group 1 (n = 15 for each subgroup), BMSC treatment group 2 (n = 15 for each subgroup), BMSC control group 1 (n = 15 for each subgroup), BMSC control group 2 (n = 15), and normal control group (n = 5). In the PQ group, each rat was intraperitoneally injected with 20% PQ solution (15 mg/kg). In BMSC treatment group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7)or 10(8) BMSCs (1 ml) after 6 hours of PQ exposure. In BMSC treatment group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml) after 1, 6, 12, or 24 hours of PQ exposure. In BMSC control group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7), or 10(8) BMSCs (1 ml). In BMSC control group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml). In the normal control group, each rat was intraperitoneally injected with an equal volume of 0.9% saline. The lung wet/dry weight ratio and plasma tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were measured at 1, 3, and 7 days after various treatments.</p><p><b>RESULTS</b>Compared with the normal control group, the PQ group showed significantly higher lung wet/dry weight ratios at 3 and 7 days after PQ exposure and significantly higher plasma TNF-α and MDA levels at 1, 3, and 7 days after PQ exposure (P < 0.01). Compared with the PQ group, BMSC treatment group 1 showed significantly lower lung wet/dry weight ratios at 7 days after injection of 1×10(6) and 10(7) BMSCs, significantly lower plasma TNF-α levels at 3 and 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs, and significantly lower plasma MDA levels at 3 days after injection of 1×10(6) and 10(7) BMSCs and at 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs (P < 0.05 or P < 0.01). Compared with the PQ group, BMSC treatment group 2 showed significantly lower lung wet/dry weight ratios at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, significantly lower plasma TNF-α levels at 3 and 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, and significantly lower plasma MDA levels at 3 days after injection of BMSCs following 6 hours of PQ exposure and at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure (P < 0.01).</p><p><b>CONCLUSION</b>BMSCs have a protective effect on the lung in rats with PQ poisoning, and the effect is closely related to the transplantation time and number of transplanted BMSCs. After 6 hours of PQ exposure, intravenous injection of 1×10(7) BMSCs can result in significant decreases in lung wet/dry weight ratio and plasma TNF-α and MDA levels.</p>

Characteristics of boningmycin induced cellular senescence of human tumor cells / 药学学报

Cellular senescence is one of the important steps against tumor. This study was to observe the characteristics of boningmycin induced senescence of human tumor cells. MIT method and clone formation assay were used to detect the growth-inhibitory effect. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry. Protein expression was detected by Western blotting. The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells. Comparison to the similar action of doxorubicin, that boningmycin induced the features of cellular senescence in both cell lines, its due to the arrest at G2/M phase and an increase of ROS level. The molecular senescence marker P21 increased significantly after boningmycin treatment at a dosage of 0.1 micromol x L(-1), whereas a higher concentration of it induced apoptosis. The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.

Mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in human breast cancer MCF-7 drug-resistant cells / 药学学报

The mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in both human breast cancer MCF-7 and MCF-7 doxorubicin-resistant cells was studied. MTT assay was used to detect growth-inhibitory effect on the cells. Protein expression was detected by Western blotting. Chromatin condensation was detected by a fluorescent microscope after Hoechst 33342 staining. Cell cycle distribution was analyzed with flow cytometry. Apoptotic cells were detected with Annexin V staining. Nicotinamide (NAM) and Sirtinol, two SIRT1 deacetylase inhibitors, exhibited the similar growth-inhibitory effects on MCF-7/DOX cells and MCF-7 cells, but no potentiation of DOX activities. The arrest at G2/M phase was detected by flow cytometry in both MCF-7 and MCF-7/DOX cells after NAM treatment. Activation of caspase pathway in MCF-7 cells, such as the cleavages of PARP, caspase-6, -7, -9, were observed after exposure to NAM 50 mmol x L(-1), accompanied by the occurrence of chromatin condensation and Annexin V positive cells. However, the cleavages of PARP, caspase-6 and -7 in MCF-7/DOX cells delayed after exposure to NAM for 24 h and obviously increased at 48 h with appearance of chromatin condensation and Annexin V positive cells. SIRT1 deacetylase inhibitors show no cross resistance to MCF-7 drug-resistant cells, and the similar growth-inhibitory actions of them to MCF-7 sensitive and drug-resistant cells by which it is mediated by activation of apoptotic caspase pathway.

A study on the health status of residents affected by flood disasters / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the immediate and long-term effects of disasters caused by floods on residents health status.</p><p><b>METHODS</b>Stratified sampling by ranks of flood disaster occurred in 1996 and 1998, flood disaster areas and control areas were carried out. A retrospective study was also carried out to study all diseases involved during 1996 - 1999.</p><p><b>RESULTS</b>The incident rates of acute infectious disease in flooding areas in 1996 and 1998 were both higher than those of non-flooding areas (863.181/100 000 and 736.591/100 000, respectively). But there was no different between the incident rate of the first years in flooding areas and that of non-flooding areas. The prevalence rates of 8 kinds of chronic diseases related to circulatory system, nervous system, digestive system, injury and poisonous diseases in flooding areas were also higher than that in the non-flooding areas. The highest incidence rates of most diseases were in the mountainous flooding areas, followed by areas collapsed by flooding, and the lowest were seen in soakedareas by floods. The incidence rates of intestinal infectious diseases and respiratory infectious diseases were lower in areas where prevention and control measures were weak.</p><p><b>CONCLUSION</b>Flood could lead to the increase of incidence rates both on acute infectious diseases and non-infectious diseases. Interventions on non-infectious diseases should also be enforced to stop the epidemics when preventing and controlling acute infectious disease.</p>

Study on hospitalization expenses of flood disaster areas' residents of Dongting Lake in Hunan province in 1998 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the expenses of hospitalization among the population in the flood disaster areas of Dongting Lake in Hunan province in 1998.</p><p><b>METHODS</b>Descriptive epidemiologic study were conducted to analyze hospitalization expenses of the residents of 55 villages in flood disaster areas in 1998; single factors analysis and logarithmic linear regression analysis were carried out to explore influencing factors about hospitalization expenses of the residents.</p><p><b>RESULTS</b>The hospitalization rate was 4.59% with an average hospitalization expenses of 667.42 Yuan in the flood disaster areas' residents of Dongting Lake in 1998. Compared with populations without suffering from flood, hospitalization rate and the average hospitalization expenses of flood disaster Areas' residents of Dongting Lake in 1998 were higher and had significant difference. The average hospitalization expenses in 1998 was affected by flood types, family income, gender, age, literacy, occupation, outcome after leaving the hospital and hospital ranks.</p><p><b>CONCLUSION</b>These results implied that the flood disease aggravated inhabitants' burden of disease in Dongting Lake areas; the factors influencing the average hospitalization expenses were multiple, and synthetic measures should be taken in the prevention and control of flood disaster.</p>