OBJECTIVETo study the mechanism of reversal effect of Curcuma Wenyujin n-Butyl alcohol extract (CWNAE) on multiple drugs resistance (MDR) of SGC7901/VCR cells.

METHODSSGC7901/VCR cells were co-culured with different concentrations CWNAE (80, 40, and 20 μg/mL) and Verapamil (VP, 10 μg/mL) for 24 h, and then acted with Adriamycin (ADM) for 1, 2, and 4 h, respec- tively. SGC7901/VCR cells with no intervention were taken as the vehicle control group. SGC7901/VCR cells treated with ADM alone were taken as the control group. The effect of CWNAE on intracellular ADM concentration was detected by flow cytometry (FCM). Cells were treated as mentioned before without any intervention of ADM. SGC7901/VCR with no ADM intervention were taken as the control group. The effect of CWNAE on the expression of P-glycoprotein (P-gp), lung resistance protein (LRP), and glu- cosylceramide synthase (GCS) was studied by Western blot. The effect of CWNAE on the location and expression quantity of P-gp was further illustrated by immunohistochemistry (IHC).

RESULTSCompared with the ADM group, the expression ratio obviously increased in the W80, W40, W20, and VP10 groups with statistical difference (all P < 0.05). The comparative expression quantity of P-gp, GCS, and LRP in SGC7901/VCR cells was obviously higher than that of non-MDR with statistical difference (all P < 0.05). The expression quantity of P-gp and GCS could be obviously down-regulated by 80 and 40 μg/mL CWN- AE, and 10 μg/mL VP, with no effect on the expression of LRP. Results of IHC proved that P-gp was mainly expressed on the cytomembrane or in the plasma, and it was also expressed on the nuclear membrane. P-gp in different locations could all be down-regulated by CWNAE.

CONCLUSIONSCWNAE could reverse the MDR of SGC7901/VCR cell line probably by inhibiting the expression of P-gp and GCS. CWNAE had no effect on LRP that also highly expressed on SGC7901/VCR. So we supposed that CWNAE could become a potential drug to reverse MDR of highly expressed P-gp and GCS.

ATP-Binding Cassette, Sub-Family B, Member 1 ; Cell Line, Tumor ; Curcuma ; Doxorubicin ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Stomach Neoplasms

Tibetan medicine Asteris Flos is the flowers of Aster souliei, A. flaccidus, and A. asteroides, with the function of clearing away heat and toxic matter, relieving cough, and removing phlegm. In order to control the quality of Asteris Flos, the morphological and chemical methods were established for identification of three origins. The morphological features of three species were described and photographed, and the microscopic characteristics of three drug powders were also described in detail and pictured. The results showed that three origins of Asteris Flos could be easily distinguished by their macro- and micro-morphologic features, and a key for distinguishing the three origins was given. Moreover, a TLC method, with apigenin-7-O-β-D-glucurono pyranoside and chlorogenic acid as chemical references, was also established for the identification of three origins. The results showed that the TLC chromatograms of the flowers of A. souliei and A. flaccidus were very similar, but different from that of A. asteroides. The established macroscopic, powder microscopic and TLC methods for identification of three origins of AF were simple, accurate, and reproducible, and also effective and easy to operate.
Aster Plant ; anatomy & histology ; chemistry ; cytology ; Chlorogenic Acid ; analysis ; Chromatography, Thin Layer ; methods ; Flowers ; anatomy & histology ; chemistry ; cytology ; Medicine, Tibetan Traditional

Mean hemoglobin (Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders (Tibetans, Sherpas, and Ladakhis) was compared with lowlanders (Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness (CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
Adaptation, Physiological ; Altitude ; Asian Continental Ancestry Group ; genetics ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Evolution, Molecular ; Hemoglobins ; genetics ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases ; genetics ; Tibet

Content of osteocyte in bone tissue is the most abundant, the most widely distributed, and embedding the cells in the mineralized bone matrix, the life can be close to the life of the body. Osteocyte formed by the cytoplasm dendritic communication network system between osteocyte and bone surface, is of great significance to maintaining the normal physiological function of bone tissue. Bone cells as the direct receptor of bone mechanical stress, through the release of bioactive factors such as PEG2, NO, ATP and classic Wnt/beta-catenin signaling pathway mechanical stress signal can be converted to bone formation and bone resorption of biochemical signals, and the biochemical signals were transfer to the other type cells of the tissue to regulate its function activities and cause bone reconstruction function. The microcracks surrounding osteocyte can disrupt the microtubule network system,cause surrounding osteocyte autophagy. In addition, osteocyte is very important for regulation of the body mineral balance, fat metabolism, and hematopoietic function.
Animals ; Autophagy ; Hematopoiesis ; Humans ; Minerals ; metabolism ; Osteocytes ; physiology ; Signal Transduction ; Stress, Mechanical

Objective To reinvestigate the value of overnight low-dose dexamethasone suppression test in the diagnosis of Cushing syndrome.Methods Fifty-two patients with Cushing syndrome and 153 patients with simple obesity or essential hypertension in whom Cushing syndrome was excluded were studied retrospectively in order to compare the sensitivity and specificity of different serum cortisol cut-off levels in overnight 1 mg dexamethasone suppression test in the diagnosis of Cushing syndrome.Results The sensitivity of 50% of basal serum cortisol level at 8:00 and of the serum cortisol cut-off levels of 275,200,138,50 nmoL/L at 8:00 after the overnight 1 mg dexamethasone suppression test was 92.3%,92.3%,92.3%,92.3% and 100.0% respectively, and the specificity was 90.8%,98.7%,96.1%,91.5% and 78.4%,respectively.Conclusion The serum cortisol cut-off level of 50 nmol/L in the overnight 1 mg dexamethasone suppression test has very high sensitivity and can be used as a screening test for Cushing syndrome.

Objective To evaluate the overall effect of transsphenoidal microsuegery for 23 patients with non-adenomas disease intrasellar region.Methods A toal of 23 patients with non-adenomas disease in- trasellar region,7 cases of Rathke's cleft cyst,3 cases of craniopharyngiomas,2 cases of meningiomas,2 ca- ses of pituitary tuberculous granuloma,5 cases of pituitary abscess,2 cases of empty sella,2 cases of chord- mas,were treated via sublabio-septo-sphenoidal microsurgery.Results There were among the 23 patients, groos total removal of the disease were achieved in 14 cases,subtotal removal in 7 cases,and partial removal in remain 2 cases.Diminished visual activity and visual field defects were improved in 13 cases.Menstrual disorder in all female cases and sexual disturbance in male were improved.There was no death in group. Conclusion Microsurgical technique via transsphenoidal approach is a safe and effective one for the treatment of patients with non-adenomas disease intrasellar region.

Objective:Based on the occupational cohort of Beijing Medical Examination Center, to explored the relevant factors of nonalcoholic fatty liver disease (NAFLD), and to provide scientific basis for screening and early diagnosis of NAFLD in high-risk population.Methods:Based on the cohort of occupational population who underwent physical examination in Beijing physical examination center from January to December 2009, the physical examination indexes were collected, and a retrospective survival cohort with a follow-up period of 3 years was established.According to the idea of nested case-control study, each case was randomly matched with the same gender, age and physical examination time in the same month by using the method of random sampling without putting back.Conditional logistic regression model was established by using the matched data.The diagnostic value of related indicators for NAFLD was analyzed by receiver operating characteristic curve (ROC).Results:A total of 1 194 subjects were included, including 684 males (57.3%, 684/1 194) and 510 females (42.7%, 510/1 194). The age was (50.8±11.6) years.The age ranged from 24.0 to 88.0 years.There were 597 patients with NAFLD, including 342 males and 255 females.Logistic regression analysis showed that body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid and urea nitrogen were statistically significant in male model (all P<0.05). Body mass index( OR=1.242, 95% CI 1.143-1.349, P<0.001), hemoglobin( OR=1.034, 95% CI 1.015-1.053, P<0.001), platelet( OR=1.005, 95% CI 1.002-1.009, P=0.005), uric acid( OR=1.004, 95% CI 1.001-1.006, P=0.004), high density lipoprotein cholesterol( OR=0.377, 95% CI 0.184-0.775, P=0.008) and urea nitrogen( OR=0.807, 95% CI 0.693-0.938, P=0.005) were protective factors for NAFLD in male patients..Body mass index( OR=1.552, 95% CI 1.366-1.762, P<0.001), triglyceride ( OR=2.606, 95% CI 1.616-4.204, P<0.001), blood glucose( OR=2.199, 95% CI 1.332-3.631, P=0.002), uric acid( OR=1.005, 95% CI 1.001-1.010, P=0.024) in female model were statistically significant ( P<0.05), and were risk factors for NAFLD in female patients. Conclusion:The incidence rate of NAFLD was different among different gender and age, body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid, urea nitrogen, triglyceride and blood glucose were closely related to the incidence of NAFLD.

Atrophy ; Disability Evaluation ; Humans ; Kidney

This study was purposed to observe the changes of caspase-3 activity during apoptosis of HL-60 cells induced by an iron chelator, DFO (deferoxamine), and to explore the mechanism underlying apoptosis in HL-60 cells. The HL-60 cells treated with DFO were examined by light microscopy, flow cytometry (FCM) and DNA agarose gel electrophoresis; the activity of caspase-3 was determined by cellular immunohistochemistry; the transcription of the apoptotic gene of bax was detected by hybridization in situ. The results showed that the typical morphological character of apoptosis cells, DNA ladder and FCM assay confirmed that DFO could induce the apoptosis in HL-60 cells. The apoptotic rate increased in dose-and time-dependent manner. When cells had been cultivated with 100 micromol DFO for 12 hours, a few caspase-3 positive cells were found. In the process of time, the rate of caspase-3 positive cells was progressively higher than that in control (P < 0.05), while the level of bax transcription was also higher than that in the control. It is concluded the activation of caspase-3 and gene bax may be involved in the apoptosis of HL-60 cells induced by DFO.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Deferoxamine ; pharmacology ; HL-60 Cells ; Humans ; bcl-2-Associated X Protein ; biosynthesis ; genetics

The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.
Acetylcholinesterase ; metabolism ; Benzimidazoles ; chemical synthesis ; chemistry ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Phenylcarbamates ; chemistry ; Rivastigmine ; Structure-Activity Relationship