[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Monoterpenoid indole alkaloid adducts and dimers from Melodinus fusiformis.

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP +-injured primary cortical neurons.

Mismatch Repair Protein hMLH1, but not hMSH2, Enhances Estrogen-Induced Apoptosis of Colon Cancer Cells.

BACKGROUND: Epidemiological studies suggest a protective role of estrogen against colon carcinogenesis; this effect appears to be dependent on mismatch repair (MMR) status. However, the underlying mechanism remains unclear. This study investigated the role of MMR proteins in apoptosis of colon cancer cells in the presence or absence of estrogen. METHODS: Two major MMR proteins, human mutL homolog 1 (hMLH1) and mutS homolog 2 (hMSH2), as well as estrogen receptor-ß (ERß), were transiently expressed in either hMLH1-deficient HCT116 cells or hMSH2-deficient LoVo cells. Effects of estradiol on cell viability and apoptosis were assessed. Furthermore, we examined the apoptotic status of epithelial cells in colonic mucosa taken from previous healthy female subjects with menopausal syndrome before and after 6-month hormone replacement therapy (HRT). RESULTS: In hMLH1-deficient HCT116 cells, re-expression of hMLH1 led to a significantly decreased cell viability and increased apoptosis, which were further enhanced by estradiol, including marked increase of activated caspase-3 and caspase-9, as well as Bax and P53. The effect of hMLH1 overexpression in LoVo cells resulted in a similar increase in apoptosis that was greatly stimulated by estradiol. The enhanced apoptosis by hMLH1 and estradiol was further validated by FACS analyses of Annexin V expression. Re-expression of hMSH2 or overexpression of ERß in HCT116 cells also enhanced apoptosis; however, the effects were independent of estradiol. Furthermore, studies on healthy menopausal women before and after 6-month HRT demonstrated a significant HRT-mediated upregulation of the hMLH1 expression, with concomitant elevation of caspase-3 and caspase-9 activation in the colonic mucosa. CONCLUSION: We present the first evidence that hMLH1 and hMSH2 have similar but distinct roles in the apoptosis of colon cancer cells: an increased expression of either one can promote apoptosis, while only the effect of hMLH1 but not hMSH2 is estradiol-dependent. Our data suggest that MMR status should be assessed before hormone replacement therapy or future application of estrogen-based chemoprevention.

Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-ß.

Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-ß (ERß), under the treatment with 17ß-estradiol or ß-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERß, through a transcriptional activation process. Furthermore, we identified that ERß exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERß.

[Scale effect of Li-Xiang Railway construction impact on landscape pattern and its ecological risk].

As a large corridor project, plateau railway has multiple points and passes various sensitive environments along the railway. The determination of the scope of impact on ecological environment from railway construction is often controversial in ecological impact assessment work. Taking the Tangbu-Jiantang section of Li-Xiang Railway as study object, and using present land use map (1:10000) in 2012 and DEM as data sources, corridor cutting degree index ( CCI) and cumulative effect index of corridor (CCEI) were established by topology, buffer zone and landscape metrics methods. Besides, the ecological risk index used for railway construction was improved. By quantitative analysis of characteristics of the spatio-temporal change of landscape pattern and its evolution style at different spatial scales before and after railway construction, the most appropriate evaluation scale of the railway was obtained. Then the characteristics of the spatio-temporal variation of ecological risk within this scale before and after railway construction were analyzed. The results indicated that the cutting model and degree of railway corridor to various landscape types could be effectively reflected by CCI, and the exposure and harm relations between risk sources and risk receptors of railway can be measured by CCEI. After the railway construction, the railway corridor would cause a great deal of middle cutting effect on the landscape along the railroad, which would influence wood land and grassland landscape most greatly, while would cause less effect of edge cutting and internal cutting. Landscape indices within the 600 m buffer zone demonstrated the most obvious scale effect, therefore, the 600 m zone of the railway was set as the most suitable range of ecological impact assessment. Before railway construction, the low ecological risk level covered the biggest part of the 600 m assessment zone. However, after the railway construction, the ecological risk increased significantly, and the most part of the study area was at the moderate ecological risk level. The ecological risk presented ring-shaped and multi-kernel patterns, and was lower in the southern part than in the northern part of the study area.

[Evaluation of Off-label Use of Oral Glucocorticoids in Outpatients].

OBJECTIVE: To investigate the off-label use of oral glucocorticoids in outpatients. METHODS: The information of outpatient glucocorticoids prescriptions from January 1st to June 30th in 2012 were collected from the information system in our hospital, then the software of Excel was employed to statistically analyze the data including the amount of drugs used in different departments,as well as the age, sex, and diagnosis of the patients. The diagnoses were compared with those included in the labels approved by China Food and Drug Administration and US Food and Drug Administration and domestic and foreign guidelines. RESULTS: It was found that 16.53% of the cases were off-label use,and dexamethasone had the highest proportion (60.50%) of off-label use. Most of the off-label use had evidence support, such as multiple myeloma and myasthenia gravis, while some cases did not, such as epilepsy and sudden deafness. CONCLUSION: The management of off-label use should be further strengthened to promote the safe and rational use of glucocorticoids.

Optimal dose of busulfan for depleting testicular germ cells of recipient mice before spermatogonial transplantation.

Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug, busulfan (Myleran), is commonly used for preparing a recipient mouse before transplantation, the optimal dose of this drug has not yet been defined. The present study investigated the effects of different doses of busulfan (10-50 mg per kg body weight) on survival rate, testicular mass and histomorphology, and on the haploid spermatids and spermatozoa of male BALB/c mice. The results suggest that a dosage of 30 mg kg(-1) is optimal for the ablative treatment with busulfan used to prepare the recipient mice. This dose results in an adequate depletion of the host germ cells for colonization of donor-derived spermatogonial stem cells and causes the lowest death rate of the animals.

Reproductive parameters of wild Trachypithecus leucocephalus: seasonality, infant mortality and interbirth interval.

Understanding the reproductive parameters of endangered primate species is vital for evaluating the status of populations and developing adequate conservation measures. This study provides the first detailed analysis of the reproductive parameters of wild white-headed langurs (Trachypithecus leucocephalus), based on demographic data collected over an 8-year period in the Nongguan Karst Hills in Chongzuo County, Guangxi, China. From 1998 to 2002, a total of 133 live births were recorded in the population based on systematic censuses. Births occurred throughout the year, but the temporal pattern was highly correlated with seasonal variation in temperature and rainfall, with the birth peak coinciding with the dry and cold months of November-March. The average birthrate was 0.47+/-0.13 births per female per year and mortality for infants younger than 20 months was 15.8%. From 1998 to 2006, 14 females gave birth to 41 infants in four focal groups. The average age at first birth for female langurs was 5-6 years (n = 5) and the interbirth interval (IBI) was 23.2+/-5.2 months (median = 24.5 months, n = 27). Infants are weaned at 19-21 months of age. The IBI for females with infant loss before weaning was significantly shorter than those for females whose infants survived. It appears that birth seasonality in the white-headed langurs is influenced by seasonal changes in food availability. The timing of conceptions was found to coincide with peak food availability. The reproductive parameters for white-headed langurs reported here are quite similar to those reported for other colobine species. One major difference is our observation of lower infant mortality in Trachypithecus.

Social organization of white-headed langurs (Trachypithecus leucocephalus) in the Nongguan Karst Hills, Guangxi, China.

The number of males per group is the most variable aspect of primate social organization and is often related to the monopolizability of females, which is mainly determined by the number of females per group and their reproductive synchrony. Colobines show both inter-specific and intra-specific variations in the number of males per group. Compared with other colobine species, little is known about the social organization of white-headed langur (Trachypithecus leucocephalus), despite its endangered status and unusual limestone habitat. As a part of a long-term study of the white-headed langurs in the Nongguan Karst Hills, Guangxi, China, we quantitatively investigated their social organization by analyzing census data from 1998 to 2003. The population censuses revealed that the predominant social organization of bisexual groups was the one-male group, similar to a previous report on this species and many other Asian colobines. In such groups, one adult male associated with 5.1 adult females, 0.1 sub-adult males, 2.6 juveniles and 2.9 infants on average, with a mean group size of 11.7 individuals. In addition, three multi-male groups were recorded, consisting of 2-3 adult males, 1-5 adult females, 0-2 sub-adult males, 0-7 juveniles and 0-2 infants. They did not contain more adult females than the one-male groups and were unstable in group membership. The langurs outside bisexual groups were organized into small nonreproductive groups or lived as solitaries. The nonreproductive groups averaged 1.3 adult males, 1.3 sub-adult males and 2.6 juveniles. Juvenile females were present in such groups on 52.4% of all occasions. As predicted by the monopolization model, the prevalence of the one-male pattern in this species may mainly be attributed to the small number of females in the group. The possible reasons for the occurrence of multi-male groups and the presence of juvenile females in nonreproductive groups are also discussed.

[Influence of estradiol benzoate on fluid reabsorption capacity of rat efferent ductuli].

OBJECTIVE: To study the influence of estradiol benzoate (E2B) on the fluid reabsorption capacity of rat efferent ductuli. METHODS: Newborn male Sprague-Dawley rats were injected subcutaneously with E2B (0.2 mg/5 g body weight), and the histological morphology of efferent ductulus, epithelial ultrastructure, and immunoexpression of AQP-1 were investigated on postnatal day 14, 21, 28, 42 and 56, respectively. Vehicle was given to the controls. RESULTS: After exposure to E2B, the lumina of the efferent ductuli dilated greatly (P < 0.05), and the epithelium height decreased significantly (P < 0.01), microvilli of nonciliated cells short and sparse, endocytic apparatus implicated in fluid reabsorption scarce, and with no AQP-1 expression. CONCLUSION: High dosage of E2 B neonatally administrated to rats damages the fluid reabsorption capacity of efferent ductuli.

[Influence of estradiol benzoate on the testis development of rats].

OBJECTIVE: To study the influence of estradiol benzoate (E2B) on the testis development of Sprague-Dawley (SD) rats. METHODS: Newborn male SD rats were injected subcutaneously with E2B (0.2 mg/5 g body weight). At days 14, 21, 28, 42 and 56 after birth, the rats were sacrificed after anaesthesia, and their testes were taken out and weighed. The cranial and caudal SEH and TD were measured respectively, the TD/SEH ratio in each part of the testis and the caudal SEH/cranial SEH ratio were calculated, and different stages of spermatogenesis were analysed. RESULTS: In the experimental group, the testis weight was significantly lower than that of the control (P < 0.01), the testes constantly remained in the abdominal cavity, and there was much fluid retention in the rete testis all the time. From day 21 on, the TD/SEH ratio in the cranial testis was much higher than in the control (P < 0.01), and so was the caudal SEH/cranial SEH ratio (P < 0.01). And spermatogenesis was obviously retarded as compared with the control (P < 0.01). CONCLUSION: Exposure of newborn male SD rats to E2B can cause fluid retention in the testis and cryptorchid, which in turn may retard spermatogenesis.