Physical activity plays a crucial role in multidomain intervention for frailty prevention.

BACKGROUND AND AIMS: Taiwan is one of the most rapidly aging countries worldwide. Both physical activity and frailty affect older adults, and multidomain interventions prevent frailty. This study investigated the associations between physical activity, frailty, and the effects of multidomain intervention. METHODS: This study enrolled individuals aged 65 years or older. The physical activity level was assessed using the Physical Activity Scale for the Elderly (PASE). Enrollees participated in a multidomain intervention program that consisted of twelve 120-min sessions administered over a 12-week period that included health education, cognitive training, and exercise programs. The effects of the intervention were evaluated using the instrumental activities of daily living scale (IADL), Mini Nutritional Assessment short form (MNA-SF), five-item Geriatric Depression Scale (GDS-5), Mini-Mental State Examination (MMSE), timed up and go test (TUGT), and Fried's frailty phenotype. RESULTS: In total, 106 older adults (aged 65-96 years) were enrolled in this study. The mean age was 77.47 ± 7.19 years, and 70.8% of participants were women. PASE scores were significantly lower among participants who were of older age, frail, and had a history of falls in the last 12 months. Frailty could be improved by multidomain interventions and was significantly positively correlated with depression, and negatively correlated with physical activity, mobility, cognition and daily living skills. Moreover, daily living skills were significantly positively correlated with cognition, mobility and physical activity, and negatively correlated with age, sex, and frailty. However, multidomain interventions did not affect daily living skills suggesting daily living skills may need to be maintained from a young age. Finally, results from multiple regressions suggest that physical activity, mobility and depression may be predictors of frailty. CONCLUSIONS: Physical activity has an important role in frailty, may be a predictor of frailty, and strongly contributes to reducing frailty through multidomain intervention. Policies that encourage healthy aging should focus on increasing physical activity, maintaining basic daily living skills and reducing frailty.

APOBEC3G exerts tumor suppressive effects in human hepatocellular carcinoma.

In this study, we collected 44 hepatitis B virus surface antigen positivity HBsAg (+) tumor and nontumor hepatocellular tissues from hepatocellular carcinoma (HCC) patients during hepatectomy, and quantified the APOBEC3G (A3G) mRNA by using a real-time PCR. Our results showed higher expression of A3G mRNA in the nontumor tissues than in the tumor tissues of the HBsAg (+) HCC patients. To further investigate this phenomenon, we constructed a pLV-A3G vector and transfected it into the human HCC cell line, Hep 3B. The results of an immunofluorescence analysis showed the overexpression of A3G in the cytoplasm. We then evaluated A3G cytotoxicity by using a cell viability assay (MTS assay), the results of which showed that Hep 3B cell viability was 88 and 58% after the transfection of pLV and pLV-A3G, respectively, indicating the growth inhibitory effects of A3G on Hep 3B cells. To further evaluate the tumor suppressive effects of A3G, we used a plastic pipette tip to scratch Hep 3B cells grown on a culture dish (to 70-80% confluence) after transfection with pLV-A3G. Our data indicated a ratio of wound closure of 100% in the control cells and in the pLV-expressing cells, compared with 43% in the pLV-A3G-overexpressing cells, 72 h after the wound scratch, as observed using phase-contrast microscopy. These results indicated that A3G inhibits wound healing in Hep 3B cells. Overall, our results suggest that A3G inhibits the growth of human hepatoma cells.

Participation in Sports Clubs during College Is an Important Factor Associated with School Counselors' Participation in Leisure Time Activities.

This study explored the physical activity participation, barriers to physical activity, attitudes toward physical activity, and physical activity levels of full-time school counselors at junior high schools in Kaohsiung City, Taiwan. The survey was conducted by means of a questionnaire. A total of 156 questionnaires were distributed, 137 were returned, and 130 were valid. The reliability and constructed validity of the questionnaire were analyzed using Cronbach's alpha coefficient and factor analysis, respectively. The participants' International Physical Activity Questionnaire (IPAQ) scores were estimated to assess their physical activity levels. Simple and multiple regression analyses were performed to analyze the effects of independent variables on the respondents' physical activity levels and attitude toward physical activity. Of the respondents surveyed, 44.6%, 36.9%, and 18.5% had low, moderate, and high levels of physical activity according to their IPAQ scores, respectively. In total, 55.4% of the school counselors met the World Health Organization criteria for physical activity. Moreover, the results of the Kruskal-Wallis test showed that respondents with high levels of physical activity, aged ≥41, and who perceived themselves to be healthy were more likely to have participated in sports clubs during their college years. Furthermore, participation in sports clubs during college years and self-perceived health were significant predictors of attitude toward physical activity. In conclusion, participation in sports clubs during college was an important factor related to school counselors' physical activity.

The Effects of Integrated Step Training into the Physical Education Curriculum of Children with Intellectual Disabilities.

(1) Background: This study investigated the changes in step frequency, walking ability, and standing posture of students with intellectual disabilities by integrating step training into the students' physical education curriculum; (2) Methods: The centroid formula was used to estimate the geometric center of the students' bodies in video footage of each participant. Each participant's stepping frequency per minute was recorded. After training, the teachers involved were interviewed regarding the participants' everyday activities in school. Each step training session was recorded by two video cameras. Each step training session was observed and photographed by a senior physical education teacher with special education qualifications; (3) Results: The step training increased the stability of the participants' body axes. The participants' average steps per minute of the participants significantly improved from 24.200 ± 7.554 to 28.700 ± 8.629. Additionally, despite the students exhibiting anxious behavior (e.g., squeezing their hands and grasping at their clothes) at baseline, the frequency of these behaviors decreased significantly from week 4. Overall, the students' daily activities, motivation, interpersonal interaction, self-confidence, and anxiety behaviors improved; (4) Conclusions: After the 8-week step program, the participants with intellectual disabilities improved their step frequency, movement stability, ability to perform daily activities, walking speed, motivation, interpersonal interaction, and self-confidence, and they exhibited a lower level of anxiety-related behaviors.

Interleukin-6 Response of C2C12 Myotubes Stimulated with Lipopolysaccharide and Lipoic Acid.

Our previous study explored the dual effect of lipoic acid on the regulation of IL-6 expression in C2C12 myotubes. However, the specific mechanism remains unclear. To evaluate IL-6 signaling in skeletal muscle, pCMV6-IL-6 was overexpressed in C2C12 myotubes. The real-time quantitative polymerase chain reaction was used to detect mRNA expression. Immunohistochemistry and a DeadEnd colorimetric TUNEL system were used to detect IL-6 localization and analyze the apoptosis in IL-6-overexpressing cells, respectively. A caspase-3/CPP32 colorimetric assay and Western blotting were used to analyze caspase-3 activity and protein expression, respectively. Our results showed the overexpressed IL-6 was not only located in the cytosol but also on the intracellular side of the cell membrane. Moreover, the nucleus did not demonstrate IL-6 overexpression. The DeadEnd colorimetric apoptosis detection assay results demonstrated that apoptotic nuclei were present in IL-6-overexpressing cells. However, the overexpressed IL-6 failed to promote caspase-3 activity. Notably, the exogenous pyrogen lipopolysaccharide (LPS) significantly promoted IL-6 mRNA expression and caspase-3 activity but did not induce apoptotic cell formation. Moreover, lipoic acid significantly upregulated IL-6, IL-6Ra, and gp130 mRNA expression and significantly increased caspase-3 activity but did not induce apoptotic cell formation. Lipoic acid significantly increased the p-Akt level in untreated cells but not in LY294002-treated cells. Taken together, our results suggesting that the overexpressed IL-6-induced apoptosis may not be mediated by caspase-3. LPS-induced IL-6 mRNA expression may not be involved in IL-6 classical signaling or trans-signaling in C2C12 myotubes. Lipoic acid-induced IL-6 mRNA expression may be mediated by IL-6 classical signaling in C2C12 myotubes. [Figure: see text].

Beta-Bungarotoxin induction of neurite outgrowth in NB41A3 cells.

In this study, different concentrations of beta-Bgt were used to treat cultured NB41A3 cells. Inverted phase contrast microscopy was then used 24h after treatment to observe the outgrowth of neurite. We found a clear outgrowth of neurite at beta-Bgt concentrations of 357 nM. However, using a cytotoxicity assay to study apoptosis, we found no significant difference in the rate of cell death in cell cultures treated with either 357 nM or 714 nM. Western blotting showed that after treatment with beta-Bgt, there was a notable decrease in small G protein Cdc42 and a marked increase in RhoA protein. Flow cytometry revealed that beta-Bgt did not alter the calcium influx in NB41A3 cells. The neurite outgrowth induced by beta-Bgt was not affected by extracellular EGTA, suggesting that the internalization of beta-Bgt from extracellular was independent of phospholipase. Taken together, our results suggest the beta-Bgt-induced outgrowth of neurite from NB41A3 cells may be mediated by small G proteins.

Negative correlation between serum uric acid and kidney URAT1 mRNA expression caused by resveratrol in rats.

SCOPE: This study established a hyperuricemic rat model to elucidate the effect of resveratrol on the transport of UA in the kidney. METHODS AND RESULTS: Hyperuricemia was induced in rats through daily oral gavage of a potassium oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol significantly reduced the serum UA levels but not creatinine, c-creative protein, alanine aminotransferase, or aspartate aminotransferase levels in these rats. Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in the rats treated with allopurinol than in those with no treatment. Therefore, allopurinol not only inhibited UA production but also mediated renal URAT1 and OAT1 expression. The correlation analysis revealed that UA levels correlated negatively with renal IL-6 mRNA expression in rats treated with allopurinol. Moreover, URAT1 showed strong immunoreactivity in the distal convoluted tubule of rats treated with allopurinol or resveratrol and in hyperuricemic treated with allopurinol. Finally, in the rats treated with resveratrol, UA levels correlated negatively with renal URAT1 mRNA expression; thus, resveratrol reduced URAT1 mRNA expression under high UA levels, thereby reducing UA reabsorption in renal cells. CONCLUSION: Resveratrol contributes to URAT1 expression, which is potentially useful in therapeutic strategies aimed at treating hyperuricemia.

KChIP3: a binding protein for Taiwan banded krait beta-bungarotoxin.

Using B1 chain of beta-bungarotoxin (beta-Bgt) as bait in yeast two-hybrid screen, we found that KChIP3 was a binding protein of B1 chain. Thus, protein-protein interaction between beta-Bgt and KChIP3 is investigated in the present study. Pull-down assay showed that recombinant KChIP3 proteins were associated with beta-Bgt as well as B1 chain, whereas the inability of KChIPs 1, 2 and 4 to bind with beta-Bgt was observed. Although Ca2+ was not a crucial factor essential for the binding of KChIP3 with beta-Bgt and B1 chain, their interaction could be enhanced by the addition of Ca2+. Alternatively, the association of A1 chain of beta-Bgt with KChIP3 was marginally detected. The dissociation constant of beta-Bgt with KChIP3 were 12.2 and 6.08 microM in the absence and presence of 2mM Ca2+, respectively. Moreover, native KChIP3 from rat brain was to be isolated by beta-Bgt-Sepharose. These observations indicate that KChIP3 is a binding protein of beta-Bgt. In view of the multiple functions of KChIP3 in neuronal cells, the interaction of KChIP3 with beta-Bgt may represent an event for the manifestation of the biological activities of beta-Bgt.

Lipoic Acid Exerts Antioxidant and Anti-inflammatory Effects in Response to Heat Shock in C2C12 Myotubes.

This study explored that lipoic acid treatment for 24 h significantly upregulated and promoted heat shock-induced catalase expression and downregulated GPx1 messenger RNA (mRNA) expression, indicating that lipoic acid exhibits antioxidant activity in the decomposition of hydrogen peroxide by upregulating catalase expression. Moreover, lipoic acid treatment for 3 h increased and promoted heat shock-induced interleukin (IL)-6 mRNA and protein levels and that for 24 h downregulated IL-6 mRNA expression, suggesting a dual effect of lipoic acid on IL-6 regulation. Lipoic acid alone failed to increase or reduce tumor necrosis factor (TNF)-α mRNA and protein levels, whereas heat shock alone downregulated TNF-α mRNA and protein expression. These data suggest that lipoic acid does not have a proinflammatory role and that heat shock acts as an anti-inflammatory agent by downregulating TNF-α expression in C2C12 myotubes. Moreover, lipoic acid or heat shock alone upregulated the IL-6 receptor (IL-6R-α) and glycoprotein 130 (gp130) mRNA expression followed by IL-6 expression; these data indicate that the regulation of lipoic acid or heat shock is mediated by IL-6R signaling, thus suggesting that C2C12 myotubes possesses a mechanism for regulating IL-6R and gp130 expression following lipoic acid treatment or heat shock.

APOBEC3B: a potential factor suppressing growth of human hepatocellular carcinoma cells.

BACKGROUND: To realize the role of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) in hepatocellular carcinoma (HCC) occurrence, mRNAs of APOBEC3B from tumor and non-tumor tissues of patients with hepatectomy were isolated and in vitro studies were designed. MATERIALS AND METHODS: Seventy-two tumor and non-tumor tissue samples, as well as clinical data, were collected from HCC patients during hepatectomy. The mRNA of APOBEC3B was assessed by real-time polymerase chain reaction. The viability of pLV-APOBEC3B-transfected Hep 3B cells was then determined. Cell growth of pLV-APOBEC3B-transfected Hep 3B cells was evaluated by in vitro migration assay. RESULTS: The real-time polymerase chain reaction results indicated a higher expression of APOBEC3B mRNA in tumor tissues than in non-tumor tissues of patients with HBsAg+ HCC. The expression of APOBEC3B in tumor or non-tumor tissue was not found to be a risk factor of recurrence in patients with HCC. The cell viability assay results indicated the growth-inhibitory effects of APOBEC3B on Hep 3B cells. The cell migration results indicated that APOBEC3B inhibits wound healing in Hep 3B cells. CONCLUSION: Based on these observations, we infer that APOBEC3B is a potential factor contributing to suppression of tumor growth in HCC.

Chemical modification of arginine residues of Notechis scutatus scutatus notexin.

Notexin, a presynaptic phospholipase A2 (PLA2) neurotoxin isolated from Notechis scutatus scutatus venom, was inactivated by arginine-specific reagents, phenylglyoxal and 1,2-cyclohexanedione. Kinetic analyses of the modification reaction revealed that the inactivation of notexin followed pseudo-first order kinetics and the loss of PLA2 activity was correlated with the incorporation of one molecule of modification reagent per toxin molecule. However, the results of amino acid analysis and sequence determination revealed that two arginine residues at positions 43 and 79 of notexin were modified simultaneously. Modification of the arginine residues was accompanied with a decrease in the ability to inhibit the indirectly evoked contraction of chick biventer cervicis muscle and bind with synaptic membranes. The secondary structure of the toxin molecule did not significantly change after modification with phenylglyoxal as revealed by the CD spectra. The modified derivative retained its affinity for Ca2+, indicating that the modified arginine residues did not participate in Ca2+ -binding. Together with the notion that Arg-43 and Arg-79 of notexin are located in the proximity of its catalytic site and toxic site, respectively, our results suggest that modification of Arg-43 and Arg-79 should differently contribute to the observed decrease in the PLA2 activity and neurotoxic effect of notexin.