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Background: We examined the clinical and epidemiological characteristics of 30 cases of human infection with avian influenza A(H7N9) virus in Hangzhou and investigated their external environments to provide evidence for contact tracing and disease prevention and control., Methods: The cases confirmed from April 1 through May 1, 2013 were studied. Field epidemiologic surveys were conducted to collect the clinical and epidemiologic data. Case-related and environmental specimens were collected for etiologic detection., Results: Thirty cases of human infection with avian influenza A(H7N9) virus were confirmed in Hangzhou from April 1 through May 1, 2013, including one pregnant woman and three deaths. The median age of the patients was 62 years (range: 38-86 years). Twenty-three of the patients were men (76.67%). The median duration between disease onset and occurrence of respiratory failure and confirmed diagnosis was 5 and 6 days, respectively. Maximum medical observation of 666 close contacts of the patients revealed no irregularity. Of 314 external environmental specimens, the overall positive detection rate of H7N9 nucleic acid was 28.98%. Eight districts of Hangzhou city had positive detections in the external environments, the highest rate being in Yuhang District (78.13%). Statistical analysis of the specimen collection locations indicates a significant difference between the case-linked locations and the non-case locations (χ2 = 16.563, p < 0.05) in terms of H7N9 viral nucleic acid detection rate. No epidemiologic link has been found among the 30 cases., Conclusions: Most of the infected were retired individuals aged 60 years or older. Men made the majority. The cases are sporadic at present, with no evidence of human-to-human transmission. Exposures to poultry and live poultry markets may be important sources of infection.

Background: Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China., Materials and Methods: We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS., Results: Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of 57.7±10.6 (mean±SD) and 57.6±11.1 years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC., Conclusions: Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region.

With an estimate of 380 000 new cases each year, gastric cancer (GC) is one of the most frequently occurring cancers in China. Genes encoding proinflammatory and anti-inflammatory cytokines are good candidates for the study of susceptibility to GC. We tested the hypothesis that the polymorphisms of interleukin 1B (IL-1B) and IL-1RN contribute toward host susceptibility to GC. In a matched case-control design, we enrolled 308 pairs of GC and control participants between October 2010 and August 2011. We sequenced IL-1B +3954 C/T, IL-1RN -9876 G/A, -9739 A/G, and IL-1RN -9091 A/C using MALDI-TOF MS and collected demographic data as well as lifestyle factors using a questionnaire. GC patients reported statistically significantly greater proportions with family history of cancer (29.9 vs. 10.7%, P<0.01) and alcohol drinking (54.5 vs. 43.2%, P<0.01) than the controls. The proportion of irregular eaters was statistically higher among the patients than among the controls (66.7 vs. 24.4%, P<0.01). The IL-1B +3954 CT or the TT variant genotype was statistically significantly associated with a risk of GC [adjusted odds ratio (OR), 2.94; 95% confidence interval (CI), 1.06-8.15], whereas variants of IL-1RN -9876 G/A, IL-1RN -9739 A/G, and IL-1RN -9091 A/C were not associated (adjusted OR, 1.29, 95% CI, 0.77-2.16; adjusted OR, 1.25, 95% CI, 0.75-2.07; adjusted OR, 1.09, 95% CI, 0.71-1.67, respectively). Haplotypes established from the three polymorphisms of IL-1RN were not associated with a risk of GC. The IL-1B +3954 C/T polymorphism is associated with a risk of GC in our study. Lifestyle and environmental factors such as drinking, eating irregularly, and family history of cancer increase the risk.

Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 μg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 μg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.

The PAKs (p21-activated kinases) are highly conserved serine/threonine protein kinases which comprise six mammalian PAKs. PAK5 (p21-activated kinase 5) is the least understood member of PAKs that regulate many intracellular processes when they are stimulated by activated forms of the small GTPases Cdc42 and Rac. PAK5 takes an important part in multiple signal pathways in mammalian cells and controls a variety of cellular functions including cytoskeleton organization, cell motility and apoptosis. The main goal of this review is to describe the structure, mechanisms underlying its activity regulation, its role in apoptosis and the likely directions of further research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Several Chinese herbs, namely, Pu-Gong-Ying, Gan-Cao, Chai-Hu, Mu-Xiang, Gua-Lou and Huang-Yao-Zi, are frequently used in complex traditional Chinese medicing formulas for breast hyperplasia and breast tumor therapy. The pharmacological effects of these Chinese herbs are all described as 'clearing heat-toxin and resolving masses' in traditional use. However, the chemical profiles of anti-breast cancer constituents in these herbs has not been investigated so far. In this study, a bioactivity-oriented screening platform, which was based on a human breast cancer MCF-7 cellular model, semi-preparative high performance liquid chromatography coupled with ultraviolet spectrophotometry and ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometer, was developed to rapidly screen the six Chinese herbs. Two potential anti-breast cancer compounds, which were costunolide (Cos) and dehydrocostus lactone (Dehy), were identified in Mu-Xiang. Combination of the two compounds showed a synergism on inhibiting the proliferation of MCF-7 cells in vitro, which exhibits a potential application prospect for breast cancer therapy. This bioactivity-oriented screening strategy is rapid, economical, reliable and specific for screening potential anti-breast cancer compounds in traditional Chinese medicines., (Copyright © 2013 John Wiley & Sons, Ltd.)

To investigate and report on the clinical and epidemiological characteristics of the first case of human infection with avian influenza A(H7N9) virus in Hangzhou, China. A field epidemiological survey was used to study the first case in Hangzhou. The patient was a 39-year-old male chef with a history of exposure to a farm product market and to poultry prior to the onset of disease on 15 March 2013. He had diarrhea, chills, pyrexia, and intermittent cough with freshly red foamy bloody sputum early in his disease. His fever > 39 °C continued for a week with rapid progression. Computed tomography findings showed extensive bilateral consolidation, followed by multiorgan failure. The patient died on the morning of 27 March. His infection was eventually confirmed 1 week later on 3 April. Flu-like symptoms including fever and cough were found in 46 of his 138 close contacts. This was the first case of human infection with avian influenza A(H7N9) virus in Hangzhou. None of the close contacts had onset of the disease. The case patient's condition progressed rapidly. The source of infection might be his exposure to the farm product market, but the mode of exposure remains unclear.

A chemical investigation of the EtOAc-soluble fraction from the ethanol extract of the medullae of Juncus effusus led to the isolation of three new 9,10-dihydrophenanthrenes, juncuenins E-G (1-3); two new phenanthrenes, dehydrojuncuenins D-E (4-5); one new feruloylated glycoside (6); and one known 9,10-dihydrophenanthrene (7). The structures of these compounds were determined by analyzing their spectroscopic data. Metabolites 1-4 and 7 were further evaluated for their in vitro cytotoxic activities against seven human cancer lines (A549, MCF-7, BEL-7402, HeLa, COLO205, BGC-823, and SK-OV-3). Among them, compound 1 exhibited weak cytotoxicity against MCF-7 and HeLa cell lines. Compound 7 showed moderate cytotoxicity against MCF-7 and HeLa cell lines, with IC50 values of 9.17 and 19.6 µM, respectively., (Georg Thieme Verlag KG Stuttgart · New York.)

A carbon-nanotube (CNT)/silver/polymer composite fiber was fabricated using carbon nanotube fiber (CNTF) to infiltrate silver-paste liquid for effective reinforcement of electrical conductivity and strength of the CNT fibers. The as-obtained composite fiber is still flexible with a content of 43 wt% CNTs. Scanning electronic microscopy (SEM) observation shows that the silver-paste layer covering on the surface of the CNTF and polymer infiltrated into the CNTFs. The electrical conductivity and strength of the achieved composite fiber were effectively improved. Mechanical measurement of the composite fiber gave a strength of 940 MPa, 2.7 times that of a reference CNTF. The electrical conductivity of the composite fiber is 5.0 × 10(5) S m(-1), 2.6 times that of the referenced CNTF. Additionally, through control of the fabrication process, a coaxial fiber comprising a silver-paste "tube" and pure CNT fiber can be achieved. This route for making composite fibers is easy and controllable, apt for development of high-performance fibers.

Objectives: Interleukin (IL) -10 is a potent cytokine with a dual ability to immunosuppress or immunostimulate. We aimed to explore the association of IL10 promoter polymorphisms with risk of gastric cancer (GC) in a Han population in Southwestern China., Methods: We enrolled 308 pairs of GC and control subjects from four hospitals and a community between October 2010 and August 2011 in a 1:1 matched case-control design. Demographic information was collected using a designed questionnaire. IL10-592 A>C and IL10-1082 A>G polymorphisms were determined by Sequenom MassARRAY analysis., Results: Patients with GC reported statistically higher proportions of family history of cancer (29.9% versus 10.7%, P<0.01) and alcohol drinking (54.6% versus 43.2%, P<0.01) than did controls. Similar results were observed in comparison between non-cardia GC patients and controls (P<0.01 and P=0.03). Variant genotypes of IL10-592 A>C and IL10-1082 A>G were not associated with overall GC risk (adjusted OR, 0.94, 95% CI, 0.66-1.33; adjusted OR, 1.00, 95% CI, 0.62-1.60). Sub-analysis showed that the IL10-592 AC/CC variant genotype was associated with decreased non-cardia GC risk (adjusted OR, 0.58; 95% CI, 0.36-0.95). No association was found between any of the IL10 haplotypes established from two polymorphisms and risk of non-cardia GC., Conclusions: In conclusion, our data do not link the two SNPs of IL10-592 and IL10-1082 with overall GC risk. We demonstrate that IL10-592 polymorphism is associated with protective effect against non-cardia GC. Our findings may offer insight into risk associated with the development of GC in this region.

Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk., Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs)., Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]., Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

The performance of carbon nanotube fibers (CNTFs) significantly depends on the packing styles of carbon nanotube (CNT) bundles. Revealing the structures and characterizations of CNT bundles is contributive to understanding the structures, properties and even the formation of CNTFs during chemical vapor deposition (CVD) processing. In this paper, bundles consisting of collapsed double-walled carbon nanotubes (CDWNT) in continuous CNTFs fabricated from CVD processing were characterized and analyzed by transmission electronic microscopy (TEM) and x-ray diffraction (XRD). TEM observations show that the continuous CNTFs are composed of CDWNT-bundle units. CDWNT-bundle units of 10-20 nm in thickness contain near numbers of collapsed tubes. The degree of collapse of the CDWNTs varies with their location in the bundle and their own diameter. CDWNT-bundle units pack side by side or face to face, assembling into super-bundles with diameters of 200-300 nm. XRD patterns show that three novel and strong peaks appear at 10°-15°, 21.3° and 23.7°, respectively, corresponding to CDWNT two side pores (10°-15°) and CDWNT layers (21.3° and 23.7°), which indicates the collapsed tube structures in CNTFs are common characterizations. Finally, a collapse mechanism is discussed from the observation and analysis.

Objective: To compare the difference in the clinical efficacy on nonspecific low back pain (NLBP) treated with the dragon-tiger fighting needling method, the uniform reinforcing-reducing method and the intermediate frequency physiotherapy., Methods: Ninety cases of NLBP were randomly divided into a dragon-tiger fighting needling group (group A), an uniform reinforcing-reducing needling group (group B) and an intermediate frequency physiotherapy group (group C), 30 cases in each one. In the group A, the dragon-tiger fighting needling method was used. In the group B, the uniform reinforcing-reducing method was applied. Two groups of acupoints were prescribed. One group included Shenshu (BL 23), Dachangshu (BL 25), Weizhong (BL 40) and Ashi points. The other group included Qihaishu (BL 24), Guanyuanshu (BL 26), Kunlun (BL 60), Yaoyangguan (GV 3). These two groups of acupoints were used alternatively in the above two groups. In the group C, the intermediate frequency physiotherapy was adopted in the pain area of the lumbar region. The treatment was given once per day in each group. Six treatments made one session. Totally, 2 sessions were required. The Visual Analogue Scale (VAS), the Oswestry Disability Index (ODD and the clinical efficacy were observed in each group., Results: The scores of VAS and ODI were reduced obviously after treatment in each group (P < 0.05, P < 0.01). The score reducing in the group A was much more remarkable than those in the other two groups (all P < 0.05). The clinical curative rate was 30.0% (9/30), 23.3% (7/30) and 16.7% (5/30) in the group A, the group B and the group C, respectively. In comparison, the clinical efficacy in the group A was superior to that in either of the other groups (all P< 0.05)., Conclusion: The dragon-tiger fighting needling method achieves the much better efficacy on NLBP compared with either the uniform reinforcing-reducing method or the intermediate frequency physiotherapy. It is one of the more effective needling method for analgesia.

An electrically conductive and electrochemically active composite paper of graphene nanosheet (GNS) coated cellulose fibres was fabricated via a simple paper-making process of dispersing chemically synthesized GNS into a cellulose pulp, followed by infiltration. The GNS nanosheet was deposited onto the cellulose fibers, forming a coating, during infiltration. It forms a continuous network through a bridge of interconnected cellulose fibres at small GNS loadings (3.2 wt%). The GNS/cellulose paper is as flexible and mechanically tough as the pure cellulose paper. The electrical measurements show the composite paper has a sheet resistance of 1063 Ω□(-1) and a conductivity of 11.6 S m(-1). The application of the composite paper as a flexible double layer supercapacitor in an organic electrolyte (LiPF(6)) displays a high capacity of 252 F g(-1) at a current density of 1 A g(-1) with respect to GNS. Moreover, the paper can be used as the anode in a lithium battery, showing distinct charge and discharge performances. The simple process for synthesising the GNS functionalized cellulose papers is attractive for the development of high performance papers for electrical, electrochemical and multifunctional applications.

With the intensive application of sulfonamides in aquaculture and animal husbandry and the increase of sulfonamides discharged into the environments, there is an increasing need to find a way to remediate sulfonamide-contaminated environments. Two bacterial strains capable of degrading sulfonamides, HS21 and HS51, were isolated from marine environments. HS21 and HS51 were identified as members of Escherichia sp. and Acinetobacter sp., respectively, based on 16S rRNA gene sequencing. Degradation of each sulfonamide by Escherichia sp. HS21 and Acinetobacter sp. HS51 was characterized using capillary electrophoresis. About 66 or 72% of sulfapyridine and 45 or 67% of sulfathiazole contained in the media was degraded by Escherichia sp. HS21 or Acinetobacter sp. HS51, respectively, after incubation for 2 days. The supernatant from culture of Escherichia sp. HS21 or Acinetobacter sp. HS51 grown in sulfapyridine or sulfathiazole contained media had much attenuated cytotoxicity against HeLa cells. These results suggest that Escherichia sp. HS21 and Acinetobacter sp. HS51 are new bacterial resources for biodegrading sulfonamides and indicate the potential of isolated strains for the bioremediation of sulfonamide-polluted environments.

Objective: Gastric cancer remains a major health problem in China. We hypothesized that XRCC1 Arg194Trp and ADPRT Val762Ala may be associated with risk., Methods: We designed a multicenter 1:1 matched case- control study of 307 pairs of gastric cancers and controls between October 2010 and August 2011. XRCC1 Arg194Trp and ADPRT Val762Ala were sequenced, and demographic data as well as lifestyle factors were collected using a self-designed questionnaire., Results: Individuals carrying XRCC1 Trp/Trp or Arg/Trp variant genotype had a significantly increased risk of gastric cancer (OR, 1.718; 95% CI, 1.190-2.479), while the OR for ADPRT Val762Ala variant genotype (Ala/Ala or Val/Ala) was 1.175 (95% CI, 0.796-1.737). No gene-gene or gene-environment interactions were found. In addition, family history of cancer and drinkers proportion were higher among cases than among controls (P<0.05)., Conclusions: XRCC1 194 Arg/Trp or Trp/Trp genotype, family history of cancer, and drinking are suspected risk factors of gastric cancer from our study. Our findings may offer insight into further similar large gene-environment and gene-gene studies in this region.

Objective: Gastric cancer (GC) is one of the most common malignancies and its mortality ranks third among all cancers in China. We previously noted that XRCC1 Arg194Trp was associated with GC risk in Western China in a study on XRCC1 Arg194Trp and ADPRT Val762Ala. We aimed to further explore the association of these polymorphisms with risk of the noncardia subtype., Methods: We enrolled 176 noncardia GC patients and 308 controls from four hospitals and a community between October 2010 and August 2011. Genotyping was performed in a 384-well plate format on the Sequenom MassARRAY platform. A self-designed questionnaire was utilized to collect epidemiological data from the subjects regarding demographic factors and potential risk factors., Results: Subjects were aged 56.8±11.8 (mean±standard deviation) and 57.6±11.1 years in the case and control groups, respectively. Individuals carrying the XRCC1 Trp/Trp or Arg/Trp variant genotype were at significantly increased risk of noncardia GC (adjusted OR, 1.48; 95% CI, 1.00-2.17), after adjustment for family history of cancer, drinking, and smoking. The increased risk of XRCC1 Arg194Trp variant genotype was more pronounced among subjects below 60 years old (adjusted OR, 1.78; 95% CI, 1.07-2.96), compared to older individuals. ADPRT Val762Ala variants (Ala/Ala or Val/Ala) were not associated with noncardia GC (adjusted OR, 1.03; 95% CI, 0.69-1.54)., Conclusions: Our study suggests that XRCC1 Arg194Trp is a genetic susceptibility factor for developing noncardia GC in Han Chinese in Western China. In particular, individuals with the XRCC1 Arg194Trp variant genotype are at increased risk for GC below 60 years old.

To explore the roles of three novel genes BM390716, BI274487 and AA963863 and the correlation between them during liver regeneration of rats, eight kinds of liver cells were isolated using the combined percoll density gradient centrifugation and immunomagnetic bead method. Rat genome 230 2.0 array was used to detect the changes in expression of genes involved in metabolism of extracellular matrix and the novel genes in rat genome. Correlation between sequence homology, co-expression of the above genes and the physiological activities they involed in were analyzed using Microsoft Excel and BLAST software. The results showed that BM390716 was homologous to and co-expressed with pparα, BI274487 was homologous to and co-expressed with timp2, and AA963863 was homologous to and co-expressed with csgalnact1. It is predicted that BM390716, BI274487, and AA963863 were involved in extracellular matrix metabolism in eight types of rat regenerating liver cells.

Background: This study adopted a new multi-layer approach of measuring myocardial deformation by two-dimensional (2D) speckle tracking imaging to examine whether a transmural gradient exists in normal subjects and cardiac diseases., Methods: Eighty patients were included with 20 in each group: (1) normal control; (2) acute coronary syndrome (ACS) with ejection fraction (EF) >45%; (3) right ventricular apical (RVA) pacing with EF>45%; (4) systolic heart failure (SHF) with EF<45%. Circumferential strain (ε-circum), torsion (Tor) and systolic dyssynchrony defined as the maximal difference in the time to peak circumferential strain were measured in the subendocardial and subepicardial myocardium layers (QLab 6.0, Philips)., Results: In all the 4 groups, a subendocardial to subepicardial gradient was present in both ε-circum (-20.7 ± 7.6 vs. -14.9 ± 5.6%, p<0.001) and Tor (12.0 ± 6.0 vs. 9.3 ± 4.7°, p<0.05), with higher values in the subendocardial layer. However, it was significantly narrowed for ε-circum (2.7 ± 1.2%) and Tor (0.8 ± 0.9°) in SHF patients (all p ≤ 0.001 vs. other groups). On the contrary, systolic dyssynchrony measured in the 2 layers showed no difference (264 ± 107 vs. 273 ± 110 ms, p = NS) and a homogenous distribution in ε-circum was observed from basal to apical planes (-17.0 ± 6.8 vs. -18.1 ± 7.4 vs. -18.1 ± 7.8%, all p = NS)., Conclusions: A transmural gradient exists in circumferential strain and torsion, with higher values in the subendocardial layer. It might be reduced when systolic function is impaired. Therefore, the multi-layer approach of 2D speckle tracking imaging provides further information on assessment of myocardial diseases., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

We designed to investigate the effects of down-regulating the tumor susceptibility gene 101 (TSG101) on the proliferation and apoptosis of the human breast cancer MCF-7 cell line, and the role of the MAPK/ERK signal pathway in this process. The siRNA against TSG101 was transfected into the breast cancer MCF-7 cell line using Lipofectamine 2000. After TSG101 knockdown, the proliferation of MCF-7 cells was measured by the MTT assay. The cell cycle distribution and apoptosis were examined by using flow cytometry while cell migration was measured using a transwell assay. The protein level of p-ERK was further assessed by immunofluorescence and western blotting. Our results are as following, the MCF-7 cells transfected with TSG101 siRNA proliferated significantly slower and exhibited significantly increased rates of apoptosis compared to the control cells. In the TSG101 siRNA transfected cells, the percentage of cells in the G₀/G₁ and S phase of the cell cycle was significantly higher and lower, respectively, compared to the control cells. Moreover, the migration ability of TSG101 siRNA transfected cells was lower than the control groups. Lastly, the level of p-ERK protein in TSG101 siRNA transfected cells was significantly decreased compared with the control cells. In conclusion, TSG101 knockdown in breast cancer cells induces apoptosis and inhibits proliferation. The TSG101 depleted cells are arrested at the G₁/S transition of the cell cycle. The migration of breast cancer cells is also impaired by TSG101 siRNA. TSG101 may play a biological role through modulation of the MAPK/ERK signaling pathway in breast cancer.

The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

Seven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear. In this study, our aims were to examine the relationship between SIAH1 and Bcl-2-interacting mediator of cell death (Bim) and to explore the effects of SIAH1 on the breast carcinogenesis. Immunohistochemical analysis in 231 cases of breast tissues showed that the expression of SIAH1 and Bim were significantly decreased in the breast carcinogenesis. Moreover, SIAH1 expression was significantly correlated with Bim. Both SIAH1 and Bim expression were significantly higher in well to moderately differentiated and in early-stage breast cancer. Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blot analysis in paired breast cancer tissues and breast cell lines found that the expression of SIAH1 was lower in the breast cancer tissues and cell lines. SIAH1 inducing apoptosis of the breast cancer cells was dependent on Bim. However, SIAH1 inhibiting invasion of the breast cancer cells was independent of Bim. The increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer. Restoration of the function of SIAH1 may be a new therapeutic target of human breast cancer., ((c) 2010 Wiley-Liss, Inc.)

Sonic Hedgehog (Shh) plays an essential role in vertebrate organogenesis as well as the development of some cancers, including breast cancer. The aim of the present study was to characterize more precisely its role in breast carcinogenesis and elucidate its regulation mechanisms. The expression of Shh was investigated in 97 breast carcinomas and 22 paired non-tumorous tissues (distant from the primary tumor) by immunohistochemistry and in four breast cell lines by Western blotting. We also analyzed the methylation status of the Shh gene with methylation-specific PCR and assessed whether nuclear factor-kappa B (NF-kappaB) and Gli1 were expressed in breast tissues by immunohistochemistry. Our results showed that Shh protein expression in breast carcinomas was significant higher than that in normal breast tissues (P < 0.01). The up-regulation of Shh in breast carcinomas was correlated significantly with early clinical stage (P < 0.05). In addition, we found a substantial increase in Shh expression at both the mRNA and protein levels in several human breast carcinoma cell lines. The expression level of nuclear Gli1 was positively associated with the expression level of Shh in breast tissues (P < 0.001). Promoter region hypomethylation (43/61, 70.5%) was frequently observed in breast carcinomas and significantly associated with Shh up-regulation (P < 0.05). The DNA methyltransferase inhibitor 5-azacytidine (5-Aza) reduced the methylation of Shh promoter and increased the expression of Shh protein in MDA-MB-435 and MCF-10A cells. Furthermore, most of the breast carcinoma cases with Shh up-regulation had increased expression of NF-kappaB (35/49, 71.4%; P < 0.001). Taken together, these observations suggest that Shh overexpression is a critical event in breast carcinogenesis, and Shh promoter hypomethylation and NF-kappaB up-regulation are responsible for the up-regulation of Shh.

Seven in absentia homolog 1 (SIAH1), a homologue of Drosophila seven in absentia (Sina), has emerged as a tumor suppressor and plays an important role in regulating cell apoptosis. To investigate the role and possible mechanism of SIAH1 in breast cancer cells, we up-regulated the expression of SIAH1 using pcDNA3-myc-SIAH1 and knocked down SIAH1 using SIAH1 siRNA. We found that the overexpression of SIAH1 induced cell apoptosis by up-regulating the level of Bim through the activation of the JNK signaling pathway, and the suppression of SIAH1 expression increased cell invasion via the activation of the ERK signaling pathway in breast cancer cells. All these results indicate that the JNK and ERK signaling pathways may play an important role in the SIAH1-dependent biological behavior of breast cancer, and it may be a good molecular therapeutic target to increase the expression level of SIAH1 through promoting cell apoptosis and inhibiting cell invasion in human breast cancer.

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg(-1), TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C(max) and AUC(0-)(t) of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration-time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C(max) and AUC(0-)(t) of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and testes. TSIIA was metabolized by rat CYP2C, 3A and 2D, as ticlopidine, ketoconazole and quinidine all inhibited TSIIA metabolism in rat liver microsomes. Taken collectively, these findings indicate that multiple factors play important roles in determining the pharmacokinetics of TSIIA.

Quantitative structure-activity relationship models for the prediction of the mean and the maximum atmospheric degradation half-life values of persistent organic pollutants were developed based on the linear heuristic method (HM) and non-linear gene expression programming (GEP). Molecular descriptors, calculated from the structures alone, were used to represent the characteristics of the compounds. HM was used both to pre-select the whole descriptor sets and to build the linear model. GEP yielded satisfactory prediction results: the square of the correlation coefficient r(2) was 0.80 and 0.81 for the mean and maximum half-life values of the test set, and the root mean square errors were 0.448 and 0.426, respectively. The results of this work indicate that the GEP is a very promising tool for non-linear approximations.

The 14-3-3sigma, upregulated by p53 in response to DNA damage, can have a positive-feedback impact driving p53 activities and is a human cancer epithelial marker downregulated in various tumors. However, the precise roles of 14-3-3sigma during tumorigenesis are not well characterized. Here, we show that 14-3-3sigma is a critical regulator of murine double minute oncogene (MDM2). 14-3-3sigma interacts with MDM2 at the RING domain. The C-terminal region of 14-3-3sigma binds to MDM2 very efficiently. Importantly, 14-3-3sigma overexpression leads to destabilization of MDM2 through enhancing MDM2 self-ubiquitination and accelerating turnover rate. Conversely, loss of 14-3-3sigma results in a significant increase in MDM2 protein. Moreover, live-cell images indicated that 14-3-3sigma can affect the location of MDM2 from the nucleus to the cytoplasm, and that MDM2-mediated cytoplasmic localization of p53 can be reversed by the presence of 14-3-3sigma. Significantly, we further showed that 14-3-3sigma causes MDM2 downregulation, thereby stabilizing p53 and inhibiting tumor growth in animal tumors. Also, 14-3-3sigma blocks MDM2-mediated retinoblastoma degradation and p53 NEDDylation. Our results provide evidence that 14-3-3sigma is a pivotal MDM2 regulator involved in blocking a variety of activities of MDM2.

Objective: The aim of this study was to review our experience with diagnosis and surgical management of intestinal malrotation in adult patients., Patients and Methods: A retrospective review of the surgical outcome of adults with intestinal malrotation was performed. Twelve patients were observed and treated between July 1996 and July 2006 (4 women and 8 men; the mean age of the patients was 28.5 years). Surgical outcomes, including postoperative complications, deaths, and resolution of preoperative symptoms, were measured., Results: A diagnosis of malrotation was made preoperatively in five patients by upper gastrointestinal contrast study, barium enema, or computed tomography scan. The anomaly was discovered incidentally at laparotomy in seven patients. All cases were proved to be malrotation intraoperatively. Nine patients underwent laparotomy and three underwent laparoscopic surgery (one converted to an open procedure). Follow-up ranged from 2 months to 118 months. Three patients had complications: one had wound infection, one had delayed gastric emptying, and one developed adhesive ileus. There were only two recurrences detected and one patient with recurrence required reoperation. No one died., Conclusions: Intestinal malrotation is a rare but important cause of abdominal pain in adults. It may present with chronic or acute symptoms. Laparotomy and laparoscopy are alternative and feasible techniques with low rates of complications for the treatment of intestinal malrotation in adults.

1. We have isolated a novel human erythrocyte-derived depressing factor (EDDF) that has a significant antihypertensive effect in various rat models of hypertension. The aim of the present study was to examine the mechanisms of action of EDDF on vascular function in two-kidney, one-clip (2K1C) renovascular hypertensive rats. 2. The EDDF was prepared from human erythrocytes. Experiments were performed in 18 male Wistar rats. The vascular ring perfusion assay and a two-photon laser scanning fluorescence microscope (TMP) were used to evaluate the vascular contractile response. The effects of EDDF on phenylephrine (PE)- and noradrenaline (NA)-induced vascular contraction were evaluated in 2K1C hypertensive rats. The proliferation and DNA synthesis in vascular smooth muscle cells (VSMC) were determined using the [3H]-TdR (thymidine) incorporation and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Flow cytometry, reverse transcription-polymerase chain reaction and western blots were used to measure cell cycle and apoptotic profiles, platelet-derived growth factor (PDGF)-A expression and the activity of extracellular signal-regulated kinase (ERK)-1/2, as well as the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4. 3. At 10(-5) g/mL, EDDF significantly decreased the PE- and NA-induced hypertensive vascular contraction. In addition, EDDF inhibited DNA synthesis in primary VSMC from 2K1C rats. The mRNA expression of PDGF-A in VSMC was twofold higher in 2K1C rats compared with control rats, whereas EDDF significantly inhibited the increment in PDGF-A mRNA expression. In addition, EDDF inhibited the phosphorylation of ERK1/2 and decreased the expression of cyclin D1 and CDK4; p21 (Cip1) levels were increased after treatment with EDDF. 4. In conclusion, EDDF inhibits VSMC proliferation in 2K1C rats through G0/G1 cell cycle arrest. The effects may be mediated, in part, by enhanced expression of p21 (Cip1) and the inhibition of ERK1/2 phosphorylation and the expression of cyclin D1/CDK4 and PDGF-A.

The 14-3-3sigma (sigma) protein is a human cancer marker downregulated in various tumors, but its function has not been fully established. 14-3-3sigma is a negative regulator of cell cycle when overexpressed, but it is not clear whether 14-3-3sigma regulates cyclin-dependent kinase inhibitor p27(Kip1) to negatively affect cell cycle progression. Protein kinase B/Akt is a crucial regulator of oncogenic signal and can phosphorylate p27(Kip1) to enhance p27(Kip1)degradation, thereby promoting cell growth. Here, we show that 14-3-3sigma-mediated cell cycle arrest concurred with p27(Kip1) upregulation and Akt inactivation. We show that 14-3-3sigma blocks Akt-mediated acceleration of p27(Kip1) turnover rate. 14-3-3sigma inhibits Akt-mediated p27(Kip1) phosphorylation that targets p27(Kip1) for nuclear export and degradation. 14-3-3sigma inhibits cell survival and tumorigenicity of Akt-activating breast cancer cell. Low expression of 14-3-3sigma in human primary breast cancers correlates with cytoplasmic location of p27(Kip1). These data provide an insight into 14-3-3sigma activity and rational cancer gene therapy by identifying 14-3-3sigma as a positive regulator of p27 and as a potential anticancer agent.

14-3-3 sigma is induced by tumor suppressor protein p53 in response to DNA damage. p53 can directly transactivate the expression of 14-3-3 sigma to cause a G(2) cell cycle arrest when cell DNA is damaged. The expression of 14-3-3 sigma protein is down-regulated in various tumors, but its function has not been fully established. Protein kinase B/Akt, a crucial regulator of oncogenic signal involved in cell survival and proliferation, is deregulated in many types of cancer. Akt activation can enhance p53 degradation, but its role in DNA damage response is not clear. Here, we show that Akt activation is diminished when p53 and 14-3-3 sigma is up-regulated in response to DNA damage. Evidence is provided that 14-3-3 sigma binds and inhibits Akt. In keeping with this concept, Akt-mediated cell survival is inhibited by 14-3-3 sigma. Significantly, we show that 14-3-3 sigma inhibits Akt-mediated cell growth, transformation, and tumorigenesis. Low expression of 14-3-3 sigma in human primary breast cancers correlates with Akt activation. These data provide an insight into Akt regulation and rational cancer gene therapy by identifying 14-3-3 sigma as a molecular regulator of Akt and as a potential anticancer agent for Akt-activated cancers.

Objective: To examine the serum fatty acid composition, serum cholesterol levels, and dietary fat intake associated with body composition in primary school children of both urban and rural regions in Taiwan., Design: Subjects were randomly stratified by region and primary school. The sample consisted of 870 children aged 10 and 11 y old. The sample was equally distributed between an urban region (Kaohsiung City) and a rural region (Yunlin County). The gender ratio of samples from each area was matched. Food record-assisted 24-h dietary recalls and serum lipid measurements were collected for each child, and associations between serum total cholesterol (TC) and fatty acids composition as well as between body mass index (BMI) and triceps skinfold (TSF) were evaluated for both urban and rural regions., Results: Compared with students in the urban region, those in the rural region had significantly lower total fat intake, BMI, TSF, TC, and LDL cholesterol (LDL-C) and higher HDL-cholesterol (HDL-C) (P<0.05). Increased total fat (P<0.05) as a proportion of total energy was associated with increased TC and LDL-C. Lauric, myristic, and oleic acid levels in the serum of urban boys were significantly higher (P=0.0001, 0.0003, and 0.0398, respectively) than those of rural boys. In girls, the different fatty acid compositions affected TC concentrations, and palmitic and stearic acids of serum in the high-TC group were significantly lower (P=0.0179 and 0.0001, respectively) than those in the low-TC group., Conclusions: Urban children had a dietary fat intake that both quantitatively and qualitatively differed from the traditional rural Chinese diet in Taiwan as reflected in rural children. Consumption of total fat was positively associated with BMI, TSF, TC, and LDL-C levels in Taiwanese children aged 10 and 11 y., Sponsorship: This study was partly sponsored by a research grant from the Department of Health, Taiwan, ROC.

The 14-3-3 sigma (sigma) protein, a negative regulator of the cell cycle, is a human mammary epithelium-specific marker that is downregulated in transformed mammary carcinoma cells. It has also been identified as a p53-inducible gene product involved in cell cycle checkpoint control after DNA damage. Although 14-3-3 sigma is linked to p53-regulated cell cycle checkpoint control, detailed mechanisms of how cell cycle regulation occurs remain unclear. Decreased expression of 14-3-3 sigma was recently reported in several types of carcinomas, further suggesting that the negative regulatory role of 14-3-3 sigma in the cell cycle is compromised during tumorigenesis. However, this possible tumor-suppressive role of 14-3-3 sigma has not yet been characterized. Here, we studied the link between 14-3-3 sigma activities and p53 regulation. We found that 14-3-3 sigma interacted with p53 in response to the DNA-damaging agent adriamycin. Importantly, 14-3-3 sigma expression led to stabilized expression of p53. In studying the molecular mechanism of this increased stabilization of p53, we found that 14-3-3 sigma antagonized the biological functions of Mdm2 by blocking Mdm2-mediated p53 ubiquitination and nuclear export. In addition, we found that 14-3-3 sigma facilitated the oligomerization of p53 and enhanced p53's transcriptional activity. As a target gene of p53, 14-3-3 sigma appears to have a positive feedback effect on p53 activity. Significantly, we also showed that overexpression of 14-3-3 sigma inhibited oncogene-activated tumorigenicity in a tetracycline-regulated 14-3-3 sigma system. These results defined an important p53 regulatory loop and suggested that 14-3-3 sigma expression can be considered for therapeutic intervention in cancers.

The cell tropism of enterovirus 71 (Enteroviridae) in neuronal, glial and laryngeal cells. The 4643 strain, an enterovirus 71 isolate from a patient in Taiwan, was used to infect three human cell lines representing neuronal cells (SK-N-SH, neuroblastoma), glial cells (U373MG, glioblastoma), and laryngeal cells (HEp-2, larynx epidermoid carcinoma). Immunofluorescent staining and transmission electron microscopy (TEM) were used to detect mature enterovirus 71 4643 virions in these cell lines. The three cell lines were also compared for presence of virus-mediated cytopathic effect (CPE), synthesis of infected cell-specific proteins, viral (-) RNA, and virus replication rate. Virus particles were detected by TEM, and viral replication increased over time, indicating the existence and release of mature viruses from all three infected cell lines. The most severe CPE and the highest viral replication rate were observed in the SK-N-SH cells. Further screening of the infected cell lines by microarray analysis revealed that the neuron growth factor receptor (NGFR) gene was uniquely upregulated in infected SK-N-SH cells, implying that the receptor encoded by this gene may be involved in cell tropism. The data show that neurons are vulnerable to enterovirus 71 4643 infection and are consistent with the clinical observation that enterovirus 71 4643 targets mainly neuronal cells but is also found in many organs in conjunction with an inflammatory reaction., (Copyright 2003 Wiley-Liss, Inc.)

Peanut pods (Tainan 12, a Spanish cultivar, Arachis hypogaea L.) have been obtained from peanuts grown in a newly developed aquatic floating cultivation system without artificial aeration or periodic renewal of the solution. The system provided a convenient status for examination of root and pod development. Compared to field-grown peanuts of the same cultivar, the aquatic-cultivated peanut pods and seeds were smaller, whereas seed/pod weight ratios, crude fat and protein contents, and SDS-PAGE protein patterns varied within similar ranges. During cultivation, the highest detected temperature of the aquatic solution was higher than the field-soil temperature. After gas chromatographic analysis of the fatty acid compositions, the oleic acid/linoleic acid ratio of the aquatic-cultivated seeds was higher than that of field-cultivated ones. When the peanut roots were collected, cleaned, dried, weighed, pulverized, and subjected to resveratrol analysis, dry root weights were 4.2 +/- 0.1 and 2.2 +/- 1.1 g/plant and resveratrol contents were 0.074 +/- 0.009 and 0.114 +/- 0.212 mg/g for the aquatic- and field-cultivated peanut roots, respectively. This indicates that the aquatic-cultivated peanut roots could be a potent and consistent source of resveratrol.

Objective: To compare the action mechanisms of human and porcine derived erythrocyte-derived depressing factor (h-EDDF and p-EDDF) as well as the effects on blood pressure., Methods: The experiments were carried out in spontaneously hypertensive rats (SHR, n = 5) and two kidney-one click renal hypertensive rats (2K-1C, n = 7). The acute and chronic effects of h-EDDF and p-EDDF on blood pressure were observed, blood pressure test using tail plethysmography under unanaesthetic state. Both EDDF were administrated via jugular vein and/or oral respectively. The isolated thoracic aorta ring perfusion assay was used to examine the effect of EDDF on the asodilation. Primary cultured VSMCs were prepared from the thoracic aorta media of 2K-1C and normal Wistar rats. The effect of EDDF on proliferation of VSMCs were determined by MTT assay. The cell cycle of VSMCs was evaluated by flow cytometric., Results: Both h-EDDF and p-EDDF could significantly decrease blood pressure of Wistar rats through intravenous administration and/or orally (P < 0.01 and P < 0.05 respectively). The contractile response of aorta in 2K-1C rats to PE was significantly enhanced compared with that of the control (P < 0.01) and both EDDF (10(-3) g/ml) remarkably induced a vasodilation with endothelium-dependent manner in SHR and 2K-1C rats (P < 0.05). h-EDDF and p-EDDF could significantly inhibit the proliferation of VSMCs from 2K-1C and control rats. After 24 hours of exposure to EDDFs the cell number of G0/G1 phase obviously increased and cell number in S phase was decreased (P < 0.01, respectively)., Conclusions: It seems that the effects of h-EDDF and p-EDDF on blood pressure and vasodilation as well as inhibition of VSMCs proliferation and regulation of cell cycle have no significant difference.

Carboxyfullerene (C60) is known as a photosensitizer for virus inactivation. Its regioisomer with C3 symmetry, named the C3 isomer, could also inactivate the dengue-2 virus without light when the dose of C3 isomer was increased to 40 microM, indicating the possible involvement of a light-independent mechanism. Further analysis showed that the C3 isomer blocked viral replication at the attachment and penetration stages, suggesting that a direct interaction between the C3 isomer and the virion is required for inactivation. The C3 isomer with a bipolar structure showed better lipid interaction and dengue-2 virus suppression than D3, another isomer that contains evenly distributed hydrophilic side chains. Moreover, the C3 isomer selectively inactivated enveloped viruses (viz., dengue-2 virus and Japanese encephalitis virus) instead of nonenveloped viruses (viz., enterovirus 71 and coxsackievirus B3). Collectively, these findings support the hypothesis that C3 isomer suppression of enveloped viruses is effected through its hydrophobic interaction with the viral lipid envelope. Our report, which demonstrates the light-dependent and -independent mechanisms of C60 on viral inactivation, will aid in the development of novel anti-viral agents for use against enveloped viruses., (Copyright 2000 Academic Press.)

1. Increases in cell proliferation and DNA synthesis were observed in vascular smooth muscle cells (VSMC) from old rats. These effects were significantly enhanced by noradrenaline but were inhibited by nifedipine. 2. Ginsenosides, traditional Chinese drugs, inhibited the proliferation and DNA synthesis in VSMC from old rats. Cytosolic and nuclear Ca2+ levels, as well as calmodulin activity, were clearly higher in old rats compared with young rats. 3. Both Ca2+ and calmodulin levels rose abruptly in the late G1 phase in the VSMC cell cycle in old rats. 4. The increase in inositol phosphate levels stimulated by phenylephrine in VSMC was greater in old than in young rats. 5. The platelet-derived growth factor (PDGF) gene was overexpressed in old rats. The results indicate that vascular ageing is related to enhanced proliferation of VSMC. Abnormal Ca2+ homeostasis as well as overexpression of the PDGF gene may be responsible. 6. Nifedipine and ginsenosides may inhibit VSMC proliferation with age.

The changes of activities of myosin light chain kinase (MLCK) and Ca2+/CaM-PP in different arterial vessels from hypertensive and normotensive rats were studied. The results were as follows. The MLCK activity of different arteries of spontaneous hypertensive rats (SHR) was different with the order of aorta (A) >> caudal artery (CA) >> mesenteric artery (MA), while in WKY rats the order of activity among different arteries is A << CA and MA and MA Ca2+/CaM-PP is obviously higher than in SHR. In renal hypertensive rats the activities of Ca2+/CaM-PP in different arteries are not quite different from those of the Wistar rats. The above results suggest that higher activities of MLCK or/and lower activity might be related to vasocontraction and hypertension.

We previously demonstrated the presence of a long-acting antihypertensive factor (AHF) in the erythrocytes of essential hypertensive subjects (EHS). The present investigation demonstrates further that the AHF is also capable of producing a rapid and transient blood pressure lowering effect in stroke prone spontaneously hypertensive rats (from 26.8 +/- 1.7 to 20.1 +/- 1.5 kPa by 10-30 s, P < 0.001). An even more stronger antihypertensive effect could be found if the AHF prepared from normal subjects or rats was used. We also found that some hypertensive factor was present in EHS plasma, but not in normal subjects. The results of the present paper suggest that AHF deficiency and higher level of pressor substance may play an important role in the development of essential hypertension.

The effects of antihypertensive factor (AHF) from erythrocytes of essential hypertensive human subjects on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), Wistar-Kyoto rats (WKY) and Wistar rats were examined. Single intraperitoneal injection of AHF (1.6 mg/kg body weight) resulted in a significant decrease in SBP of SHR and RHR. At 10 min postinjection, AHF lowered the SBP in SHR by 34.0 mmHg. SBP recovered to the original level at 3 h. The maximal decrease of SBP in RHR by 92.5 mmHg was at 24h postadministration and the SBP did not recover until the 9th day. When AHF was administered via femoral vein (0.8 mg/kg body weight), the maximal decrease values of the SBP and the DBP were 42.8 and 48.2 mmHg in SHR at 12 min and 38.3 and 42.5 mmHg in RHR at 25 min postinjection respectively. The DBP in Wistar rats decreased considerably (from 96.7 +/- 12.9 to 83.3 +/- 11.7 mmHg) at 5 min postadministration of AHF, but no effect on DBP in WKY rats was observed. The depressor effect of AHF on SBP in RHR was dose-dependent. AHF could also antagonize the pressor effect of norepinephrine in Wistar rats.

This study observed the depressor effects of erythrocyte antihypertensive factor (AHF) from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats on SHR, renal hypertensive rats (RHR) and their control animals. Blood pressure (BP) tests were carried out in two parts. Chronic experiment: Six-month-old male rats weighing 200-300 g were divided into six groups: (1) Stroke prone SHR (SHRsp, n = 5); (2) WKY (n = 4); (3) RHR (n = 4); (4) Wistar (n = 4). The rats in each group were given intraperitoneal injections of AHF (10 mg/100 g BW) once. The rats in groups (5) and (6) were injected with normal saline as control. BP was measured just prior to injection and at 0.5, 1, 3, 6, 24 h and 24 h intervals thereafter. BP in SHRsp dropped (from 180.0 +/- 11.5 to 145.0 +/- 12.6, P less than 0.05). Within 24 h there was a further reduction, and the average value of the fall was 65 mmHg (P less than 0.01). BP remained significantly depressed for 4 days and did not recover until the seventh day. In contrast to the effect of this extract on SHR, the BP in WKY rats did not appear to be affected. Normal saline injected intraperitoneally did not lower BP in either SHRsp or WKY rats. BP in RHR rats showed a profound decrease within 3 h, with the average value for the drop being 56 mmHg (P less than 0.001). BP recovered to normal at 6 h. Acute group: Three SHRsp rats with BP 180.0 +/- 5.8 mmHg and weighing 231.0 +/- 11.2 g were anesthetized with sodium pentobarbital. AHF was injected into the femoral vein (0.35 mg/100 g BW). The results showed that the BP markedly decreased after administration of the extract, and the average value for the drop was 35 mmHg (P less than 0.05). The BP did not show any obvious change after injection of WKY rat extract.

The effects of a partially purified antihypertensive factor (AHF) from erythrocytes of spontaneously hypertensive rats (SHR) on the blood pressure (BP) and Ca2+ influx of vascular smooth muscle (VSM) in rats were studied. The results indicated that AHF could produce a marked prolonged depressor effect and significantly inhibit the Ca2+ influx dose-dependently on both SHR and renal hypertensive rat (RHR) either in acute or in chronic experiments, but not on normotensive rats. It suggested that the inhibition of Ca2+ influx might be one of the important mechanisms for AHF as an endogenous depressor substance.

Aorta segments (A) and mesenteric arteries (MA) from stroke prone spontaneously hypertensive rats (SHRsp) and control Wistar Kyoto rats (WKY) were used in the present study to assess the effect of AHF on Ca2+ influx in vascular smooth muscle (VSM). The results indicated that Ca2+ influx in VSM of SHRsp was much higher than that of WKY rats (P less than 0.05). AHF at 10(-7), 10(-6) and 10(-5) g/ml can significantly inhibit Ca2+ influx in a dose-dependent manner in VSM of both A and MA (P less than 0.05 and less than 0.01). The suppression effect of AHF on Ca2+ influx and the concentration-dependent relationship were more obvious in MA than in A. The Ca2+ influx in VSM of WKY rats was unaffected by administration of AHF.