Circadian rhythms of blood pressure in hypertensive patients with cerebral microbleeds.

BACKGROUND: Whether the circadian rhythms of blood pressure (BP) contribute to the presence of cerebral microbleeds (CMBs) remains unknown. This study aimed to assess the relationship between nocturnal BP and CMBs in hypertensive patients. METHODS: This prospective case-control study recruited 51 hypertensive patients with CMBs and 51 hypertensive patients without CMBs, matched with age and gender, serving as controls. A 24-h ambulatory BP monitoring was conducted in all subjects. Differences in ambulatory BP parameters between the two groups were compared. Logistic regression analyzes were conducted to investigate the relationship between the ambulatory BP parameters and presence of CMBs. RESULTS: Patients with CMBs had a significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate. Two logistic models were constructed to explore the association between ABPM indices and the presence of CMBs, adjusted with history of ischemic stroke and smoking. In model 1, higher nocturnal mean SBP positively correlated with presence of CMBs [standardized ß = 0.254, odds ratio (OR) = 1.029, p = .041]. In model 2, the relative nocturnal SBP dipping rate was negatively correlated with CMBs (standardized ß = -.363, OR = 0.918, p = .007). Only patients with deep CMBs had significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate in comparison with those without CMBs. CONCLUSIONS: Higher nocturnal SBP and lower relative nocturnal SBP dipping rate may be associated with CMBs in hypertensive patients.

[Study of molecular mechanism of tanshinone II A inducing differentiation in acute promyelocytic leukemia NB4 cells].

OBJECTIVE: To investigate molecular mechanism of tanshinone II A inducing differentiation and apoptosis in acute promyelocytic leukemia NB4 cells. METHOD: NB4 cells were cultured in vitro and treated with tanshinone II A and observed cellular morphology, cell category and the cellular proliferation. DNA microarray technique was used to analyze the gene expression profiles of NB4 cells induced by tanshinone II A. RESULT: 92.8% of NB4 cells treated with 0.5 mg x L(-1) tanshinone II A were induced into mature neutrophils, in which myetocytes and melamyetocytes were 27.0%, banded and segmented neutrophits 68.2%. Cell growth were inhibited. cDNA microarray showed the enormously expressed 183 genes including 23 differentiation associated genes, and other interrelated genes. CONCLUSION: Tanshinone II A inducing differentiation in NB4 cells may be via regulation of many kinds of genes, especially differentiation associated genes expression. This partially explained the molecular mechanism of tanshinone II A inducing differentiation.

Growth inhibition of high-intensity focused ultrasound on hepatic cancer in vivo.

AIM: To investigate the damaging effect of high-intensity focused ultrasound (HIFU) on cancer cells and the inhibitory effect on tumor growth. METHODS: Murine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length of time in vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically. RESULTS: The death rate of cancer cells treated with HIFU at 1 000 W/cm2 for 0.5, 1, 2, 4, 8, and 12 s was 3.11+/-1.21%, 13.37+/-2.56%, 38.84+/-3.68%, 47.22+/-5.76%, 87.55+/-7.32%, and 94.33+/-8.11%, respectively. A positive relationship between the death rates of cancer cells and the length of HIFU treatment time was found (r = 0.96, P<0.01). The death rate of cancer cells treated with HIFU at the intensity of 100, 200, 400, 600, 800, and 1 000 W/cm2 for 8 s was 26.31+/-3.26%, 31.00+/-3.87%, 41.97+/-5.86%, 72.23+/-8.12%, 94.90+/-8.67%, and 99.30+/-9.18%, respectively. A positive relationship between the death rates of cancer cells and the intensities of HIFU treatment was confirmed (r = 0.98, P<0.01). The cancer cells treated with HIFU at 1 000 W/cm2 for 8 s were inoculated into mice ex vivo. The tumor inhibitory rate was 90.35% compared to the control (P<0.01). In the experimental group inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 0.5 s, the tumor inhibitory rate was 22.9% (P<0.01). By pathological examination, tumor growth was confirmed in 8 out of 14 mice (57.14%, 8/14) inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 8 s, which was significantly lower than that in the control (100%, 15/15, P<0.05). CONCLUSION: HIFU is effective on killing or damage of H22 hepatic cancer cells in vitro and on inhibiting tumor growth in mice ex vivo.

[Alteration of activities of telomerase in tanshinone IIA inducing apoptosis of the leukemia cells].

OBJECTIVE: To investigate the effect of tanshinone IIA on HL-60 and K562 cells apoptosis, and to assay the inhibition of the telomerase activities in the leukemia cell apoptosis induced by Tanshinone. METHOD: Using the techniques of cell culture in vitro, flow cytometry and PCR-TRAP observed the telomerase activities and apoptosis of HL-60 and K562 cells which treated by Tan IIA. RESULT: 0.5 microg x mL(-1) Tan IIA could obviously inhibit HL-60 and K562 cell lines growth (P < 0.05), down-regulate c-myc, bcl-2 gene and up-regulate c-fos and p53 gene expression as well as induce leukemia cell apoptosis, the apoptotic rates of HL-60 and K562 cells were 11.8% and 21.8% respectively. The telomerase activities significant decreased, the inhibiting rates in HL60 and K562 cells were 30.8% and 50.8% respectively. CONCLUSION: Tan IIA could significantly inhibit the proliferation and telomerase activities of HL-60 and K562 cells and induce the leukemia cell apoptosis.

Potential involvement of leptin in carcinogenesis of hepatocellular carcinoma.

AIM: To investigate the potential involvement of leptin in carcinogenesis of hepatocellular carcinoma (HCC) and to elucidate the etiology, carcinogenesis and progress of HCC. METHODS: Expressions of Ob gene product, leptin and its receptor, Ob-R were investigated in 36 cases of HCC specimens and corresponding adjacent non-tumorous liver tissues with immunohistochemical staining. The effect of leptin on proliferation of Chang liver cell line and liver cancer cell line SMMC-7721 was studied with cell proliferation assay (MTT). RESULTS: Leptin expression was detected in 36 cases of adjacent non-tumorous liver tissues (36/36, 100%) with moderate (++) to strong (+++) intensity; and in 72.22%(26/36) of HCC with weaker (+) intensity (P<0.05). Thirty of 36 (83.33%) cases of adjacent non-tumorous liver tissues were positive for Ob-R, with moderate (++) to strong (+++) intensity. In HCC, 11/36 (30.56%) cases were positive, with weak (+) intensity (P<0.05). In cell proliferation assay, leptin inhibited the proliferation of Chang liver cells. The cell survival rate was 10-13% lower than that of the untreated cells (P>0.05). Leptin had little effect on the proliferation of liver cancer cells (P>0.05). CONCLUSION: High level expression and decreased or absent expression of leptin and its receptor in adjacent non-tumorous liver cells and HCC cells, inhibitory effect of leptin on the proliferation of normal Chang liver cells and no effect of leptin on proliferation of liver cancer cells, may provide new insights into the carcinogenesis and progression of human HCC. It could be assumed that leptin acting as an inhibitor and/or promoter, is involved in the process of carcinogenesis and progress of human HCC.

Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells.

AIM: To evaluate the effects of tanshinone II-A on inducing growth inhibition and apoptosis of human hepatocellular carcinoma (HCC) cells. METHODS: The human hepatocellular carcinoma cell line SMMC-7721 was used for the study. The cells were treated with tanshinone II-A at different doses and different times. Cell growth and proliferation were measured by MTT assay, cell count and colony-forming assay. Apoptosis induction was detected by microscopy, DNA ladder electrophoresis and flow cytometry. RESULTS: In MTT assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48, 72 and 96 h after treatment with tanshinone II-A, and the most significant effect was observed at 72 h. On the other hand, the increase of doses (0.125, 0.25, 0.5, 1.0 mg/L tanshinone II-A) resulted in enhanced inhibitory effect. The growth and proliferation of SMMC-7721 cells were obviously suppressed in a dose- and time-dependent manner. The results of cell count were similar to that of MTT assay. In colony-forming assay, the colony-forming rates were obviously inhibited by tanshinone II-A. In tanshinone II-A group, the morphology of cellular growth inhibition and characteristics of apoptosis such as chromatin condensation, crescent formation, margination and apoptotic body were observed under light and transmission electron microscopes. DNA ladder of cells was presented in electrophoresis. The apoptosis index (AI) was 16.9% (the control group was 4.6%) in flow cytometry. The cells were arrested in G(0)/G(1) phase, and the expressions of apoptosis-related genes bcl-2 and c-myc were down-regulated and fas, bax, p53 up-regulated. CONCLUSION: Tanshinone II-A could inhibit the growth and proliferation of HCC cell effectively in vitro by apoptosis induction, which was associated with up-regulation of fas, p53, bax, expression and down-regulation of bcl-2 and c-myc.

[Anticancer effect of tanshinone and its mechanisms].

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, which is a traditional herbal medicine that is used to treat cardiovascular diseases. Recent studies showed that Tanshinone IIA possesses cytotoxic activity against many kinds of human carcinoma cell lines, induces differentiation and apoptosis and inhibits invasion and metastasis of cancer cells. Its mechanisms are thought as inhibiting DNA synthesis and proliferation of cancer cells, regulating the expression of genes related to proliferation, differentiation, and apoptosis, inhibiting the telomerase activity of cancer cells, and changing the expression of cellular surface antigen.

The expression of c-src gene in the carcinogenesis process of human cardia adenocarcinoma.

AIM:To investigate the activation, expression of c-src gene and its role in the carcinogenetic process of human cardia adenocarcinoma (CA).METHODS:Fifty six cases of CA, 34 cases of normal, 36 cases of protiferative epithelia adjacent to carcinoma, and 20 cases of lymph node metastases of CA were studied for PP60(c-src),the expression product of c-src gene immunohistochemically by using the specific monoclonal antibody,Mab327.RESULTS: The positive rates of PP60(c-src) in the normal epithelia,protiferative epithelia, CA and lymph node metastases were 29.4% (10/34), 94.4% (34/36), 71.4% (40/56) and 60.0%(12/20), respectively, among them, the differences of the positive rates were statistically significant (P < 0.01). The expression levels of PP60(c-src) in CA and proli ferative epithelia were significantly higher than that in the normal epithelia(P< 0.01).The PP60(c-src) positive rates in the papillary, tubular, poorly different-tiated and mucous adenocarcinoma were 75.0% (6/8), 81.8% (18/22), 50.0% (10/20) and 100.0% (6/6), respectively, whereas those of tubular and mucous adenocarcinomas were significantly higher than those of papillary and poorly differentiated adenocar-cinomas (P < 0.05), and the PP60(c-src) expression levels of tubular and mucous adenocarcinomas were also significantly higher than those of papillary and poorly differentiated adenocarcinomas (P< 0.01).CONCLUSION:The activation and expression of c-src gene are associated with the initiation and development of human CA; the protein amount of PP60(c-src)increased during the process of carcinogenesis; and PP60(c-src) expression is also related to lymph node metastases.

Reversing effect of Tanshinone on malignant phenotypes of human hepatocarcinoma cell line.

AIM:To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS:Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation wasdetected.RESULTS:The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid.Flow cytometric assay demonstrated that S phase cells decreased and G(0)/G(1) phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased. CONCLUSION:Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.