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Biomedical subjects

J Ren

Publications and source records attributed to J Ren.

At least 19 recordsLinked to original sources
PubMed2006

The costs and benefits of reforestation in Liping County, Guizhou Province, China.

Reducing greenhouse gases in the atmosphere is becoming a pressing issue for the global community. Afforestation and reforestation are promoted worldwide as an effective means of sequestering carbon. For its national interest and global concerns, China has made great efforts to protect its existing forests and develop programs of afforestation and reforestation. Based on two surveys recently conducted in Liping County, Guizhou province, this paper investigates the economic changes associated with the implementation of the "Grain For Green" policy. Based on the analytical framework of benefit cost analysis, this paper concludes that the implementation of the reforestation of sloping agricultural land policy would not be possible if there were no government subsidies for the peasants. The short term economic returns of land and labour from forestation are substantially lower than those generated from grain or cash crop production on the steep slope lands. The government subsidies provide great economic incentives for peasants to take part in the project. The subsidies in fact have elevated peasant income in rural Liping. The estimated potential economic returns of plantations over the long run indicate that the removal of the government financial subsidies would not create an economic crisis for the peasants if the current market conditions continue.

Agriculture↗
PubMed2006

Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).

BACKGROUND AND PURPOSE: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. KEY RESULTS: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. CONCLUSIONS AND IMPLICATIONS: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.

Animals↗
PubMed2006

Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch.

AIMS/HYPOTHESIS: Obesity is an independent risk factor for heart diseases but the underlying mechanism is not clear. This study examined cardiac contraction, oxidative stress, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and the myosin heavy chain (MHC) isoform switch in obese mice. METHODS: Mechanical properties were evaluated in ventricular myocytes from C57BL/6J lean and Lep/Lep obese mice (formerly known as ob/ob mice), including peak shortening (PS), time to 50 or 90% PS, time to 50 or 90% relengthening (TR50, TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ and its decay (tau). Oxidative stress, lipid peroxidation, protein damage and SERCA activity were assessed by glutathione/glutathione disulfide, malondialdehyde, protein carbonyl and 45Ca2+ uptake, respectively. NADPH oxidase was determined by immunoblotting. RESULTS: Myocytes from Lep/Lep mice displayed depressed PS and +/- dL/dt, prolonged TR50, TR90, elevated resting [Ca2+]i, prolonged tau, reduced contractile capacity at high stimulus frequencies and diminished responsiveness to extracellular Ca2+ compared with lean controls. Cardiac glutathione/glutathione disulfide was decreased whereas malondialdehyde, protein carbonyl, membrane p47(phox) and membrane gp91(phox) were increased in the Lep/Lep group. SERCA isoenzyme 2a was markedly modified by oxidation in Lep/Lep hearts and associated with decreased 45Ca2+ uptake. The MHC isozyme displayed a shift from the alpha to the beta isoform in Lep/Lep hearts. Short-term incubation of angiotensin II with myocytes mimicked the mechanical defects, SERCA oxidation and 45Ca2+ uptake seen in Lep/Lep myocytes. Incubation of the NADPH oxidase inhibitor apocynin with Lep/Lep myocytes alleviated contractile defects without reversing SERCA oxidation or activity. CONCLUSIONS/INTERPRETATION: These data indicate that obesity-related cardiac defects may be related to NADPH oxidase activation, oxidative damage to SERCA and the MHC isozyme switch.

Animals↗
PubMed2006

Cardiac overexpression of catalase rescues cardiac contractile dysfunction induced by insulin resistance: Role of oxidative stress, protein carbonyl formation and insulin sensitivity.

AIMS/HYPOTHESIS: Insulin resistance leads to oxidative stress and cardiac dysfunction. This study examined the impact of catalase on insulin-resistance-induced cardiac dysfunction, oxidative damage and insulin sensitivity. METHODS: Insulin resistance was initiated in FVB and catalase-transgenic mice by 12 weeks of sucrose feeding. Contractile and intracellular Ca2+ properties were evaluated in cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), half-width duration (HWD), maximal velocity of shortening/relengthening (+/-dL/dt), fura-fluorescence intensity change (DeltaFFI) and intracellular Ca2+ clearance rate (tau). Reactive oxygen species (ROS) and protein damage were evaluated with dichlorodihydrofluorescein and protein carbonyl formation. RESULTS: Sucrose-fed mice displayed hyperinsulinaemia, impaired glucose tolerance and normal body weight. Myocytes from FVB sucrose-fed mice exhibited depressed PS and +/-dL/dt, prolonged TR90 and tau, and reduced DeltaFFI associated with normal TPS and HWD compared with those from starch-fed control mice. ROS and protein carbonyl formation were elevated in FVB sucrose-fed mice. Insulin sensitivity was reduced, evidenced by impaired insulin-stimulated 2-deoxy-D: -[3H]glucose uptake. Western blot analysis indicated that sucrose feeding: (1) inhibited insulin-stimulated phosphorylation of insulin receptor and Akt; (2) enhanced protein-tyrosine phosphatase 1B (PTP1B) expression; and (3) suppressed endothelial nitric oxide synthase (eNOS) and Na+-Ca2+ exchanger expression without affecting peroxisome proliferator-activated receptor gamma (PPARgamma), sarco(endo)plasmic reticulum Ca2+-ATPase isozyme 2a and phospholamban. Catalase ablated insulin-resistance-induced mechanical dysfunction, ROS production and protein damage, and reduced eNOS, but not insulin insensitivity. Catalase itself decreased resting FFI and enhanced expression of PTP1B and PPARgamma. CONCLUSIONS/INTERPRETATION: These data indicate that catalase rescues insulin-resistance-induced cardiac dysfunction related to ROS production and protein oxidation but probably does not improve insulin sensitivity.

Animals↗
PubMed2006

Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in rats.

After comparing mortality and clinical signs in rats receiving different dexamethasone treatments, we investigated whether 0.5 mg/kg/d dexamethasone could delay pulmonary fibrosis induced by bleomycin and its time course (1, 3, 7, 14, 21 and 28 days). Tissue injury was assessed by apoptosis, lactate dehydrogenase (LDH) release, malondialdehyde content, and protein content; and inflammation was measured in terms of myeloperoxidase (MPO) activity, inflammatory cell count, and the mRNA expression of pro/inflammatory cytokines. Fibrogenic activity was analyzed by measuring the mRNA expression of fibrotic cytokines in tissue, and the promotion of fibroproliferation and synthesis of collagen type I by bronchoalveolar lavage fluids in vitro; and fibrosis was assessed by measuring the hydroxyproline content and collagen-I mRNA expression, and by histology. Bleomycin treatment induced tissue injury, inflammation and fibrogenic activity in lung, and led to fibrosis. Treatment with dexamethasone diminished the extent of fibrosis by strongly reducing inflammation, lung damage, and fibrogenic activity. These results demonstrate that the progression of bleomycin-induced pulmonary fibrosis in rats can be delayed by dexamethasone treatment, which appeared to alleviate not only inflammation but also lung damage and fibrogenic activity, indicating a possible new role for dexamethasone in the treatment of fibrosis.

Animals↗
PubMed2006

MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90.

The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by most human carcinomas. The MUC1 C-terminal subunit localizes to mitochondria and blocks stress-induced activation of the intrinsic apoptotic pathway. How MUC1 is delivered to mitochondria is not known. The present studies demonstrate that MUC1 forms intracellular complexes with HSP70 and HSP90. We show that the MUC1 cytoplasmic domain binds directly to HSP70 in vitro. By contrast, binding of MUC1 to HSP90 in vitro is induced by c-Src-mediated phosphorylation of the MUC1 cytoplasmic domain. c-Src also increases binding of MUC1 to HSP90 in cells. In concert with these results, we show that heregulin (HRG), a ligand for ErbB receptors, activates c-Src and, in turn, stimulates binding of MUC1 to HSP90. We also show that inhibitors of c-Src or HSP90 block HRG-induced targeting of MUC1 to mitochondria and integration of MUC1 into the mitochondrial outer membrane. These findings indicate that MUC1 is delivered to mitochondria by a mechanism involving activation of the ErbB receptor-->c-Src pathway and transport by the molecular chaperone HSP70/HSP90 complex.

Amino Acid Sequence↗
PubMed2006

Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy.

Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation.

Animals↗
PubMed2006

Schistosoma japonicum triose-phosphate isomerase plasmid DNA vaccine protects pigs against challenge infection.

The protective efficacy of a Schistosoma japonicum, Chinese strain, triose-phosphate isomerase (TPI) plasmid DNA vaccine was examined in naïve pigs. Pigs were vaccinated with the TPI DNA-plasmid alone, or in conjunction with IL-12 as pcDNA3.1-P35, pcDNA3.1-P40 plasmids via intramuscular injection. Control pigs were immunized with equivalent amounts of pcDNA3.1. Pigs were immunized 3 times at 21-day intervals and challenged 30 days after the final boost. Forty-five days post-challenge, pigs were sacrificed and perfused to compare adult worm burdens, female worm burdens, liver egg burdens and granuloma size. We found that pigs vaccinated with SjCTPI DNA alone had adult worm burdens reduced by 48.3% and that a further decrease in adult worm burdens was not seen in the group vaccinated with SjCTPI DNA in conjunction with IL-12 (46.2% reduction). The SjCTPI DNA vaccines had a more pronounced effect on reducing female worm burdens i.e. 53.6% SjCTPI alone and 59.6% for SjCTPI+IL-12. Vaccination with SjCTPI-DNA reduced liver eggs by 49.4% and this response was significantly enhanced by the addition of IL-12 (65.8% reduction in liver eggs). In addition to the dramatic protective effects seen in vaccinated pigs, we also noted that granuloma size was reduced by 42% in both groups. Thus, vaccination of pigs and other large animals in China with SjCTPI DNA vaccine will likely reduce transmission by reducing adult worm burdens and worm egg output and simultaneously reduce hepatic egg-associated pathology.

Animals↗
PubMed2006

Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments.

AIM: Ginkgo biloba extract is a natural product used widely for cerebral and cardiovascular diseases. It is mainly composed of terpene lactones (ginkgolide A and B) and flavone glycosides (eg quercetin and kaempferol). To better understand the cardiac electromechanical action of Ginkgo biloba extract in normal and diabetic states, this study was designed to examine the effect of ginkgolide B on cardiomyocyte contractile function under normal and high-glucose environments. METHODS: Isolated adult rat ventricular myocytes were cultured for 6 h in a serum-free medium containing either normal (NG; 5.5 mmol/L) or high (HG; 25.5 mmol/L) glucose with or without ginkgolide B (0.5-2.0 microg/mL). Mechanical properties were evaluated using the IonOptix MyoCam system. Contractile properties analyzed included peak shortening (PS), maximal velocity of shortening/relengthening (+/-dl/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Levels of essential Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), phospholamban (PLB) and Na(+)-Ca(2+) exchanger (NCX) were assessed by Western blotting. RESULTS: Ginkgolide B nullified HG-induced prolongation in TR90. However, ginkgolide B depressed PS, +/-dl/dt and shortened TPS in NG and HG cells. Ginkgolide B also prolonged TR90 in NG cells. Western blot analysis revealed that HG upregulated SERCA2a and downregulated PLB expression without affecting that of NCX. Ginkgolide B disrupted the NG-HG response pattern in SERCA2a and NCX without affecting that of PLB. CONCLUSION: Ginkgolide B affects cardiomyocyte contractile function under NG or HG environments in a paradoxical manner, which may be attributed to uneven action on Ca(2+) regulatory proteins under NG and HG conditions.

Animals↗
PubMed2006

Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice.

The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca(2+) transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca(2+) release upon electrical stimulus associated with a slowed intracellular Ca(2+) decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca(2+) hemostasis and ultrastructural derangement in ventricular myocytes.

Animals↗
PubMed2006

Cardiac health and diabetes mellitus in women: problems and prospects.

Cardiovascular disease is the leading cause of morbidity and mortality in both genders. Although premenopausal women display a lower prevalence in cardiovascular diseases compared with age-matched men, they lose this ''female advantage'' following menopause. There are significant gender differences in a wide spectrum of cardiovascular incidence, ranging from delayed disease onset to higher prevalence of comorbid diseases for females. Several factors have been suggested to contribute to such difference in cardiovascular incidence including sex hormones, gender-specific intrinsic organ function, difference in body size and cardiovascular risk factor profiles (e.g., use of tobacco and alcohol, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle and atherogenic diet). A gender difference also exists for diabetes and diabetic complications. Heart diseases exhibits a 2-fold and a 5-fold increase in men and women with diabetes, respectively. Although female hearts are usually more tolerable to stress insults than their male counterparts, female sex hormone such as estrogen interacts with diabetic risk factors to precipitate cardiomyopathy. This review aims at recaping our knowledge on gender difference in diabetic heart disease with an emphasis on disease pathogenesis. Deficits and obstacles to optimal risk factor management in diabetic women are also discussed in an effort to improve the overall cardiovascular health of diabetic women.

Diabetes Complications↗
PubMed2005

Angiotensin II promotes smooth muscle cell proliferation and migration through release of heparin-binding epidermal growth factor and activation of EGF-receptor pathway.

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 (20 microM), a specific inhibitor of MMPs or AG1478 (10 microM), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

Angiotensin II↗
PubMed2005

Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARgamma and c-Jun.

AIMS/HYPOTHESIS: Insulin resistance is concomitant with metabolic syndrome, oxidative stress and cardiac contractile dysfunction. However, the causal relationship between oxidative stress and cardiac dysfunction is unknown. This study was designed to determine the impact of overexpression of the cardiac antioxidant metallothionein on cardiac dysfunction induced by insulin resistance in mice. METHODS: Whole-body insulin resistance was generated in wild-type FVB and metallothionein transgenic mice by feeding them with sucrose for 12 weeks. Contractile and intracellular Ca(2+) properties were evaluated in ventricular myocytes using an IonOptix system. The contractile indices analysed included: peak shortening (PS), time to 90% PS (TPS(90)), time to 90% relengthening (TR(90)), half-width duration, maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), fura-fluorescence intensity change (DeltaFFI) and decay rate (tau). RESULTS: The sucrose-fed mice displayed glucose intolerance, enhanced oxidative stress, hyperinsulinaemia, hypertriglyceridaemia and normal body weight. Compared with myocytes in starch-fed mice, those from sucrose-fed mice exhibited depressed PS, +dL/dt, -dL/dt, prolonged TR(90) and decay rate, and reduced DeltaFFI associated with normal TPS(90) and half-width duration. Western blot analysis revealed enhanced basal, but blunted insulin (15 mU/g)-stimulated Akt phosphorylation. It also showed elevated expression of insulin receptor beta, insulin receptor tyrosine phosphorylation, peroxisome proliferator-activated receptor gamma, protein tyrosine phosphatase 1B and phosphorylation of the transcription factor c-Jun, associated with a reduced fold increase of insulin-stimulated insulin receptor tyrosine phosphorylation in sucrose-fed mice. All western blot findings may be attenuated or ablated by metallothionein. CONCLUSIONS/INTERPRETATION: These data indicate that oxidative stress may play an important role in cardiac contractile dysfunction associated with glucose intolerance and possibly related to alteration in insulin signalling at the receptor and post-receptor levels.

Animals↗