Search

Background: Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats., Methods: Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n = 6) and MI-GFP group (n = 6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n = 6) and S-GFP group (n = 6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting., Results: Primary rat myoblasts were retrovirally transduced to secrete rhIGF-1 and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted consistent levels of hIGF (0.4 - 1.2 µg×BAM(-1)×d(-1)). When implanted into syngeneic rat, IGF-BAMs secreted and delivered rhIGF. Four weeks after therapy, the hemodynamics was improved significantly in MI rats treated with IGF-BAMs compared with those treated with GFP-BAMs. The levels of serum IGF-1 were increased significantly in both MI and sham rats treated with IGF-BAM. The mRNA expression of bax was lower and Bcl-2 expression was higher in MI-IGF group than MI-GFP group (P < 0.05). Western blotting assay showed TNF-α and caspase 3 expression was lower in MI-IGF group than MI-GFP group after therapy., Conclusions: rhIGF-1 significantly improves left ventricular function and suppresses cardiomyocyte apoptosis in rats with chronic heart failure. Genetically modified tissue-engineered BAMs provide a method delivering recombinant protein for the treatment of heart failure.

In this study, stepwise behavioral responses of Japanese medaka (Oryzias latipes) under the joint stress of two organphosphorus pesticides (Trichlorfon and Parathion) were discussed. BEWs was used to record the data of behavior strength, to analyze behavioral response of Japanese medaka. The differences of the behavioral responses time in 20, 10, 5, land 0.1 TU were: 1.4, 4.8, 6.4, 32.2 and 43.0 h separately, which were significant. And evident difference of the behavioral responses time was not detected in different proportions of the pesticides. The results suggested that the stepwise behavioral responses of Japanese medaka were affected by both chemical concentration and exposure time. But the stepwise behavioral responses in different proportions of two organphosphorus pesticides were almost the same as each other, and the evident difference of the behavioral responses time was not detected. It proved that the toxicity effects of the joint stress of two organphosphorus pesticides on the stepwise behavioral responses of Japanese medaka were simple additivity.

Background: Experimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF., Methods: Primary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n = 6) and CHF treatment group (n = 6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n = 6) and sham treatment group (n = 6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligation of the left coronary artery or sham operation was performed. Eight weeks after the treatment, echocardiography was performed. hGH, insulin-like growth factor-1 (IGF-1) and TNF-alpha levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry., Results: Primary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted 1 to 2 microg of bioactive rhGH per day. When implanted into syngeneic rat, GH-BAMs secreted and delivered rhGH. Eight weeks after therapy, LV ejection fraction (EF) and fractional shortening (FS) were significantly higher in CHF rats treated with GH-BAMs than in those treated with GFP-BAMs ((65.0 +/- 6.5)% vs (48.1 +/- 6.8)%, P < 0.05), ((41.3 +/- 7.4)% vs (26.5 +/- 7.1)%, P < 0.05). LV end-diastolic dimension (LVEDD) was significantly lower in CHF rats treated with GH-BAM than in CHF rats treated with GFP-BAM (P < 0.05). The levels of serum GH and IGF-1 were increased significantly in both CHF and sham rats treated with GH-BAM. The level of serum TNF-alpha decreased more significantly in the CHF treatment group than in the CHF control group., Conclusions: rhGH significantly improves LV function and prevents cardiac remodeling in rats with CHF. Genetically modified tissue-engineered bioartificial muscle provides a method delivering recombinant protein for the treatment of heart failure.

Objective: To observe the antioxidant effects of water extract of Carthamus tinctorius on ox-LDL induced injury in rat cardiac microvascular endothelial cell and detecting oxygen derived free radicals (OFR) to explore the antioxidant mechanisms., Method: By using the third generation of rat cardiac microvascular endothelial cells (rCMEC), the protection of water extract of C. tinctorius was investigated after ox-LDL (100 mg x L(-1) induced damage. The supernatant was collected for detecting lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD), glutathione peroxidase (GSH-Px), nitric oxide (NO), nitric oxide synthase (NOS) activity, and cell suspension was collected for detecting reactive oxygen species (ROS) by electron spin resonance (ESR)., Result: Water extract of C. tinctorius increased the rCMEC survival rate, reduced LDH, MDA and XOD levels, and improved SOD, GSH-Px and NOS activity, while in the cell suspension ROS signal decreased significantly., Conclusion: Water extract of C. tinctorius has antioxidation. The mechanisms are likely related with scavenging of free radicals, enhancing its clearance, enhancing endogenous antioxidant activity.

Objective: To identify the risk factors associated with cardiovascular disease (CVD) in Chinese chronic kidney disease (CKD) patients., Methods: As part of a multicenter Chinese cohort study, the clinical data associated with CVD of 1239 patients with CKD (stage 2 - 5) hospitalized in 7 grade 3A hospitals distributed in 5 regions of China 2002 - 2003 were collected. Logistic regression model was used to analyze the association between CVD and the demographic variables, lifestyle, medical history, medication, physical examination, and laboratory variables., Results: (1) Increase of serum C-reactive protein (CRP, cut off > 10 mg/L) was an independent risk factor for development of coronary artery disease (CAD) (OR 2.13; 95% confidence interval [CI], 1.32 - 3.43). 21.5% of the patients in this group showed a value of CRP > 10 mg/L. (2) Being female, anemia, and systolic hypertension were the major determinants of the development of left ventricular hypertrophy (OR 2.99, CI 2.09 - 4.26; OR 2.66, CI 1.19 - 3.57; and OR 1.02, CI 1.00 to -1.02). 54.2% of the patients in this group had their systolic pressure controlled under 140mmHg, and only 15% of the patients in this group had their hemoglobin remain at the level >or= 110 g/L. (3) There was a significant interaction between the calcium-phosphate product and congestive heart failure (CHF) (OR 1.023, CI 1.01 - 1.03). 25.9% of the patients in this cohort had their calcium-phosphate product >or= 55. (4) Hypoalbuminemia (OR 6.01, CI 1.25 - 28.96) and diastolic hypertension (OR 1.05, CI 1.00 - 1.09) played major role in determining cerebrovascular accidents (CVA). In these cohort the prevalence of hypoalbuminemia was 37.3%. (5) Diabetes was associated with CAD (OR 2.34), CHF (OR 1.97), and CVA (OR 4.40), although its prevalence was lower in Chinese CKD patients (20%). Age was the risk factors of CAD (OR 1.04) and CVA (OR 1.22). Hypertension was associated with LVH (OR 1.016), CHF (OR 1.02), and CVA (OR 1.04)., Conclusion: CKD is associated with nontraditional risk factors for the development of CVD, including chronic inflammation, malnutrition and calcium-phosphate disorders. Particular care must be taken to give optimal treatment for the most important CVD risk factors active in Chinese CKD patients, e.g. anemia and hypertension.

Objective: The mice surviving acute exposure to low dose of perfluoroisobutylene (PFIB) could tolerant to lethal dose of PFIB. Discovering the gene related with the tolerance would be significant to find preventive agents for PFIB., Methods: By static exposure to PFIB for 3 times, the survival animals could tolerate to lethal dose of PFIB. Three anchoring primers and 4 arbitrary primers were applied in differential display reverse transcription PCR (DDRT-PCR) of lung tissues and the products were analyzed by sequencing PAGE and silver staining. The differential DNA fragments were cloned and sequenced., Results: There were obvious differences of gene expression between control and tolerant animals. Three expressed sequence tags (EST) have been cloned and sequenced,which were homologous to some mouse gene in Genbank., Conclusion: Specific gene up-regulation might be the cause of tolerance to PFIB, and they are very important to clarity the tolerant mechanisms to PFIB.

Samples of coals, fly ashes, slags and tiny fly ashes with different sizes, collected from a large power plant, were studied. It shows that Se tends not to be enriched in coarse fly ash and slag, but to be enriched in fine fly ashes especially in fine fly ash with size > 19.0 microm. This kind of distribution is shaped by: 1) volatility and organic-occurrence of Se in coal; 2) residence time in flue gases; 3) morphology of particles [holes on the surface of particles ( > 19.0 microm) may adsorb more Se]. Sequence leaching test shows that Se is mainly organic-bonded (69.7%) in coal. Mass balance calculation of burned coal indicates that 16.5% of Se in coal may be disposed into air directly. The environmental impacts of Se in fine fly ashes can be ignored because of its small proportion and distributional character (mainly in particles with sizes > 19.0 microm). Se in slag may cause little environmental impacts. Se in coarse fly ash is partially mobile and may be used to benefit the soil which is lack of Se.

Objective: Cardiovascular (CV) disease (CVD) is the single most important cause of death among Chinese dialysis patients, accounting for 51% of overall mortality. The study was performed to investigate the prevalence and the spectrum of CVD in Chinese chronic kidney disease (CKD) patients., Methods: The multicenter Chinese cohort study examined 1239 CKD patients from 7 main medical centers (distributed in 5 regions of China) who were hospitalized between 2002 and 2003., Results: (1) The most prevalent pathological form of CVD was left ventricular (LV) hypertrophy (LVH), accounting for 58.5% of total patients. The prevalence of coronary artery disease (CAD), congestive heart failure (CHF), and cerebrovascular accidents (CVA) was 16.5%, 27.7% and 5.6%, separately. (2) The cohort with minor renal dysfunction (stage 2-3) had higher prevalence of CAD (5.9%) and CVA (1.0%) compared with general population in the same regions. Up to 41.2% of minor CKD patients were complicated with LVH, and 13.8% of them had clinical evidence of CHF. The prevalence of CAD, LVH and CHF increased as glomerular filtration decline. (3) The prevalence of CAD (20.0%) was much lower and the prevalence of CVA (5.4%) was higher in Chinese dialysis patients than that in American dialysis population. There was significant geographical variations in CAD prevalence, but it was not different between genders., Conclusion: The CV risk is significantly increased in patients with CKD. Even minor CKD has a major impact on the CV risk. The prevalence of CAD in Chinese dialysis patients is markedly lower than that in American dialysis population.