Gender differences in health promotion behaviors and quality of life among community-dwelling elderly.

The differences of basic attributes, health promotion behaviors, and quality of life between elderly males and females in Taiwan were compared. Several scales were used to examine the gender differences and the factors associated with quality of life. Regression analysis revealed that gender, education level, depression level, and healthy diet were key factors influencing the overall quality of life. The education level of females was lower, and their depression level was higher; however, females had healthier diets. With regards to their satisfaction in the quality of life, elderly males scored higher than females in both the physical and psychological domains.

Higher DHEAS Levels Associated with Long-Term Practicing of Tai Chi.

Tai Chi has many benefits for middle-aged/older individuals including improvements to muscle strength and various body lipid components. DHEAS and testosterone have anti-obesity/anti-aging characteristics and also improve libido, vitality and immunity levels. Thus, the aim of the present study was to investigate the differences between middle-aged Tai Chi practitioners (n = 17) and sedentary individuals (n = 17) in terms of leg strength, blood levels of cholesterol, triglyceride, HDL, as well as DHEAS, testosterone and cortisol. Unpaired t-tests were used to identify significant differences between the two groups. There were no significant differences in body composition, leg strength, blood lipid components and testosterone. However, the Tai Chi practitioners had higher levels of DHEAS (P < 0.01) and lower levels of cortisol (P < 0.05). Thus, Tai Chi practitioners have a higher ratio of DHEAS to cortisol, which might have potential benefits in terms of improving an individual's health-related quality of life during the aging.

ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation.

Cardiomyocyte hypertrophy is an adaptive response of heart to various stress conditions. During the period of stress accumulation, transition from physiological hypertrophy to pathological hypertrophy results in the promotion of heart failure. Our previous studies found that ZAK, a sterile alpha motif and leucine zipper containing kinase, was highly expressed in infarcted human hearts and demonstrated that overexpression of ZAK induced cardiac hypertrophy. This study evaluates, cellular events associated with the expression of two doxycycline (Dox) inducible Tet-on ZAK expression systems, a Tet-on ZAK WT (wild-type), and a Tet-on ZAK DN (mutant, Dominant-negative form) in H9c2 myoblast cells; Tet-on ZAK WT was found to increase cell size and hypertrophic marker BNP in a dose-dependent manner. To ascertain the mechanism of ZAK-mediated hypertrophy, expression analysis with various inhibitors of the related upstream and downstream proteins was performed. Tet-on ZAK WT expression triggered the p38 and JNK pathway and also activated the expression and nuclear translocation of p-GATA4 and p-c-Jun transcription factors, without the involvement of p-ERK or NFATc3. However, Tet-on ZAK DN showed no effect on the p38 and JNK signaling cascade. The results showed that the inhibitors of JNK1/2 and p38 significantly suppressed ZAK-induced BNP expression. The results show the role of ZAK and/or the ZAK downstream events such as JNK and p38 phosphorylation, c-Jun, and GATA-4 nuclear translocation in cardiac hypertrophy. ZAK and/or the ZAK downstream p38, and JNK pathway could therefore be potential targets to ameliorate cardiac hypertrophy symptoms in ZAK-overexpressed patients.

Cell Cycle Regulation in the Estrogen Receptor Beta (ESR2)-Overexpressing Hep3B Hepatocellular Carcinoma Cell Line.

Epidemiological studies and experimental data have shown that the incidences of hepatocellular carcinoma in men are more frequent than in women. Evidence suggests that imbalance of hormones, including estrogen, androgen, prolactin, and growth hormone, modifies liver tumorigenesis. In this present study, we investigated how estrogen and estrogen receptor 2 (ESR2), regulates the cell cycle mechanism in Hep3B hepatocellular carcinoma cell line. Our results showed that ESR2 overexpression in the presence of 10⁻8 M 17-ß-estradiol downregulated c-myc and cyclin D1 expression and simultaneously upregulated p27 expression. However, flow cytometry and MTT assays showed only minor G1 phase arrest without affecting cell viability. Taken together, these observations indicate that ESR2 is required to lower tumorigenesis in males by altering cell cycle proteins in a ligand-dependent manner.

Resistin induces monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression in endothelial cells via p38MAPK-dependent pathway.

Resistin, firstly reported as an adipocyte-specific hormone, is suggested to be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. The adhesion of circulating monocytes to endothelial cells is a critical step in the early stages of atherosclerosis. The purpose of the present study was to investigate the effect of resistin on the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Our results showed that resistin caused a significant increase in monocyte adhesion. In exploring the underlying mechanisms of resistin action, we found that resistin-induced monocyte adhesion was blocked by inhibition of p38MAPK activation using SB203580 and SB202190. Furthermore, resistin increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by HUVECs and these effects were also p38MAPK-dependent. Resistin-induced monocyte adhesion was also blocked by monoclonal antibodies against ICAM-1 and VCAM-1. Taken together, these results show that resistin increases both the expression of ICAM-1 and VCAM-1 by endothelial cells and monocyte adhesion to HUVECs via p38MAPK-dependent pathways.

Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling.

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.

Exercise training augments Sirt1-signaling and attenuates cardiac inflammation in D-galactose induced-aging rats.

Exercise is known to be beneficial in controlling aging associated disorders however, the consequence of long-term exercise on cardiac health among aging population is not much clear. In this study the protective effect of exercise on aging associated cardiac disorders was determined using a D-galactose-induced aging model. Eight weeks old Sprague Dawley rats were given intraperitoneal injection of 150 mL/kg D-galactose. Swimming exercise was provided in warm water for 60 min/day for five days per week. Hematoxylin and eosin staining of cardiac tissue sections revealed cardiomyocyte disarrangements in the aging rat hearts but long-term exercise training showed improvements in the cardiac histology. Exercise training also enhanced the expression levels of proteins such as SIRT1, PGC-1α and AMPKα1 that are associated with energy homeostasis and further suppressed aging associated inflammatory cytokines. Our results show that long-term exercise training potentially enhances SIRT1 associated anti-aging signaling and provide cardio-protection against aging.

Exercise training exacerbates tourniquet ischemia-induced decreases in GLUT4 expression and muscle atrophy in rats.

The current study determined the interactive effects of ischemia and exercise training on glycogen storage and GLUT4 expression in skeletal muscle. For the first experiment, an acute 1-h tourniquet ischemia was applied to one hindlimb of both the 1-week exercise-trained and untrained rats. The contralateral hindlimb served as control. For the second experiment, 1-h ischemia was applied daily for 1 week to both trained (5 h post-exercise) and untrained rats. GLUT4 mRNA was not affected by acute ischemia, but exercise training lowered GLUT4 mRNA in the acute ischemic muscle. GLUT4 protein levels were elevated by exercise training, but not in the acute ischemic muscle. Exercise training elevated muscle glycogen above untrained levels, but this increase was reversed by chronic ischemia. GLUT4 mRNA and protein levels were dramatically reduced by chronic ischemia, regardless of whether the animals were exercise-trained or not. Chronic ischemia significantly reduced plantaris muscle mass, with a greater decrease found in the exercise-trained rats. In conclusion, the exercise training effect on muscle GLUT4 protein expression was prevented by acute ischemia. Furthermore, chronic ischemia-induced muscle atrophy was exacerbated by exercise training. This result implicates that exercise training could be detrimental to skeletal muscle with severely impaired microcirculation.

Acute effect of exercise-hypoxia challenge on GLUT4 protein expression in rat cardiac muscle.

Altitude training is a frequently used method for enhancing endurance performance in athletes. But its acute effect on carbohydrate metabolism in cardiac muscle is unknown. In this study, we determined the acute effect of an exercise-hypoxia challenge on glycogen storage and GLUT4 protein expression in heart muscle. Sixteen male Sprague-Dawley rats were assigned to one of two groups: control (CTRL) and exercise-hypoxia (EX+HY). The exercise protocol consisted of swimming for 180 min twice, with a 45-min rest interval. Five hours after the exercise, the EX+HY rats were exposed to a 14% O(2) systemic hypoxia under normobaric condition for 12 h. After this hypoxia exposure, the EX+HY and control rats were given glucose orally (1 g/kg body weight) with stomach tube and recovered under normal condition for 16 h. Ventricular portion of the heart was used to determine the levels of glycogen, GLUT4 mRNA, and GLUT4 protein after recovery. We found that myocardial glycogen level was lowered by the exercise-hypoxia challenge (51% below control, p < 0.05), while GLUT4 mRNA was dramatically elevated (approximately 400% of the control level, p < 0.05). The acute exercise-hypoxia treatment did not affect GLUT1 protein level in the same tissue. The novel finding of the study was that the exercise-hypoxia treatment significantly induced GLUT4 gene expression in the cardiac muscle. This acute response appears to be associated with a sustained glycogen depletion of the muscle.

Null effect of ginsenoside Rb1 on improving glycemic status in men during a resistance training recovery.

BACKGROUND: Ginsenoside Rb1, a principle active ingredients of Panax ginseng, has been shown to lower blood glucose in animals and increase insulin secretion in cultured insulinoma cells. The aim of this study was to determine the effects of daily ginsenoside Rb1 supplementation on circulating glucose and insulin levels in men during a 5-day recovery period after an acute bout of resistance exercise. METHODS: Twelve gymnasts (20.5 ± 0.3 years of age) participated in this double blind placebo-controlled crossover trial. They were challenged by a lower-limb resistance exercise at a weight load of 85 % one-repetition maximal (1-RM) for 10 repetitions, six sets of the movement. Rb1 (1 ng/kg) or Placebo was orally delivered to participants daily during a 5-day recovery period after challenge. Circulating insulin, glucose and heart rate variability (HRV) were measured under fasted condition in the morning at Days 1, Day 3, and Day 5 during recovery. RESULTS: No significant effect of Rb1 on circulating glucose and insulin levels were found among participants during the 5-day recovery period. A persistent elevation in sympathetic nervous activity, indicated by increased HRV-low frequency/high frequency (HRV-LF/HF) power, during the Rb1 trial was observed. CONCLUSIONS: The result of the study suggests that the null effect of Rb1 supplementation on lowering glucose and insulin levels of participants may be associated with chronic sympathetic activation.

Prolactin protects cardiomyocytes against intermittent hypoxia-induced cell damage by the modulation of signaling pathways related to cardiac hypertrophy and proliferation.

OBJECTIVES: Prolactin (PRL) is a multifunctional hormone that influences multiple physiological processes. It has been shown to have a protective effect on the cardiovascular system; however, the mechanisms of this effect are poorly understood. The purpose of the study was to elucidate the role of PRL in intermittent hypoxia (IH)-induced apoptosis in the cardiovascular system. METHOD AND RESULTS: We established a hyperprolactinemic rat model by implanting two anterior pituitary (AP) glands into the renal capsule of male Sprague-Dawley rats. The rats were kept under normoxic conditions for 4weeks after implantation in order to reach the expression plateau of PRL in the plasma, and then treated with IH for 7 or 14days. Their hearts were then removed for histological and protein expression analyses. Cerebral cortex (CX)-grafted control rats challenged with IH displayed unique phenotypes such as a thicker heart wall, an abnormal myocardial architecture and an increased interstitial space of the left ventricle. They exhibited reduced expressions of p-JAK2, p-STAT5, cell cycle-dependent proteins (cyclin D1, cyclin E and cyclin A), IGF-IRα, PI3Kα, p-AKT and p-ERK1/2 in cardiomyocytes at 7days. CONCLUSIONS: Our comprehensive analysis suggested that high plasma PRL can protect rat cardiomyocytes against IH through (1) the p-JAK2 and p-STAT5 pathways for transient cell proliferation, (2) the PI3Kα/AKT and MAPK survival pathways through IGF-I, and (3) the downregulation of IGF-II and ERK5, which inhibit cell hypertrophy.

Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53.

AIM: To investigate the effects of 17ß-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. METHODS: LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test. RESULTS: The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10(-8) mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17ß-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17ß-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17ß-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human LoVo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17ß-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17ß-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in LoVo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on LoVo cells. That E2 and/or ER agonists may impair LoVo cell migration by modulating migration-related factors via the p53 tumor suppressor gene. CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.

Dangshen (Codonopsis pilosula) activates IGF-I and FGF-2 pathways to induce proliferation and migration effects in RSC96 Schwann cells.

This study evaluates the proliferative and migrative effects of dangshen on RSC96, Schwann cells. We investigated the molecular signaling pathways, which include: (1) survival signaling, IGFs-IGFIR-Akt-Bcl2 and proliferative signaling, cell cycle factors and MAPK pathways. (2) migrate and anti-scar signaling, FGF-2-uPA-MMPs. After treatment with different concentrations (20 microg/ml, 40 microg/ml, 60 microg/ml, 80 microg/ml, and 100 microg/ml) of dangshen. We observed a dose dependent proliferative effect using PCNA Western blotting assay, MTT assay and the wound healing test. We also found that dangshen stimulates the protein expressions of IGF-I pathway regulators, cell cycle controlling proteins and excites the MAPK signaling pathway regulators ERK and P38. Dangshen even stimulates the FGF-2-uPA-MMP 9 migration pathway in RSC 96 Schwann cells. Using MAPK chemical inhibitors, U0126, SB203580, and SP600125, the proliferative effects of dangshen on RSC 96 cells were identified to be ERK- and P38- dependent. Based on these results, applying an appropriate dose of dangshen with biomedical materials would be a potential approach for enhancing neuron regeneration.

Short-term regulation of tumor necrosis factor-alpha-induced lipolysis in 3T3-L1 adipocytes is mediated through the inducible nitric oxide synthase/nitric oxide-dependent pathway.

TNF-alpha has several effects on adipocytes that may be related to the development of type 2 diabetes in obese subjects. Many studies demonstrated that long-term treatment with TNF-alpha increases lipolysis in adipocytes. However, the short-term (<4 h) effects of TNF-alpha on lipolysis have not been well investigated. The aim of this study was to investigate the short-term regulatory mechanism of TNF-alpha-induced lipolysis in 3T3-L1 adipocytes. Well-differentiated 3T3-L1 adipocytes were used. Lipolysis was determined by measuring glycerol release. Expression of inducible nitric oxide (iNOS) and nitric oxide (NO) production were measured, respectively, by Western blots and the Griess reagent. A selective iNOS inhibitor (s-ethylisothiourea . HBr), an adenylyl cyclase inhibitor (SQ22536), and a guanylyl cyclase inhibitor (LY83583) were used to investigate the involvement of iNOS, cAMP, and cGMP in TNF-alpha-induced lipolysis. Transient transfection with iNOS short hairpin RNA was performed to confirm the involvement of iNOS in TNF-alpha-induced lipolysis. Phosphorylation of hormone-sensitive lipase (HSL) was measured by immunoprecipitation and Western blotting. Results showed that short-term TNF-alpha treatment significantly increased lipolysis, iNOS expression, and NO production in a time- and dose-dependent manner. Furthermore, treatment with the NO donor S-nitroso-N-acetylpenicillamine also stimulated lipolysis and HSL phosphorylation in 3T3-L1 adipocytes. Moreover, pretreatment with inhibitors of iNOS and guanylate cyclase, but not an adenylate cyclase inhibitor, abolished TNF-alpha-induced lipolysis and HSL phosphorylation. Suppression of TNF-alpha-induced iNOS expression using short hairpin RNA significantly reduced TNF-alpha-induced lipolysis. In conclusion, short-term TNF-alpha treatment induces lipolysis in 3T3-L1 adipocytes by increasing iNOS expression and NO production, which activates the guanylyl cyclase/cGMP-dependent pathway and induces phosphorylation of HSL.

Altitude hypoxia increases glucose uptake in human heart.

Chen, Chi-Hsien, Yuh-Feng Liu, Shin-Da Lee, Wen-Chih Lee, Ying-Lan Tsai, Chien-Wen Hou, Chih-Yang Huang, and Chia-Hua Kuo. Altitude hypoxia increases glucose uptake in human heart. High Alt. Med Biol. 10:83-86, 2009.-Cardiac muscle is a highly oxygenated tissue that produces ATP mainly from fat oxidation. However, when the rate of oxygen demand exceeds oxygen supply, energy reliance on the carbohydrate substrate becomes crucial for sustaining normal cardiac function. In this study, the effect of acute altitude hypoxia on glucose uptake from circulation was determined, for the first time, in the human heart, using [18F]-2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) in a simulated altitude condition (14% O(2), corresponding to approximately 3000 m above sea level) or room air (21% O(2)). Our results showed that subjects (n = 6) started to experience difficulty in sustaining the hypoxic condition at approximately 45 min. This was concurrent with a substantially increased blood lactate concentration, which reflects an accelerated rate of anaerobic glycolysis. Hypoxia elevated FDG uptake above control by approximately 70% in heart, but not in limbs (representing primarily skeletal muscle), brain, and liver. This study provides the first human evidence for the hypoxia-stimulated glucose uptake in heart. At this hypoxia level, the previously observed hypoxia-stimulated glucose uptake in rat skeletal muscle was not confirmed in the human study.