It has been reported that feeding mice resveratrol activates AMPK and SIRT1 in skeletal muscle leading to deacetylation and activation of PGC-1α, increased mitochondrial biogenesis, and improved running endurance. This study was done to further evaluate the effects of resveratrol, SIRT1, and PGC-1α deacetylation on mitochondrial biogenesis in muscle. Feeding rats or mice a diet containing 4 g resveratrol/kg diet had no effect on mitochondrial protein levels in muscle. High concentrations of resveratrol lowered ATP concentration and activated AMPK in C2C12 myotubes, resulting in an increase in mitochondrial proteins. Knockdown of SIRT1, or suppression of SIRT1 activity with a dominant-negative (DN) SIRT1 construct, increased PGC-1α acetylation, PGC-1α coactivator activity, and mitochondrial proteins in C2C12 cells. Expression of a DN SIRT1 in rat triceps muscle also induced an increase in mitochondrial proteins. Overexpression of SIRT1 decreased PGC-1α acetylation, PGC-1α coactivator activity, and mitochondrial proteins in C2C12 myotubes. Overexpression of SIRT1 also resulted in a decrease in mitochondrial proteins in rat triceps muscle. We conclude that, contrary to some previous reports, the mechanism by which SIRT1 regulates mitochondrial biogenesis is by inhibiting PGC-1α coactivator activity, resulting in a decrease in mitochondria. We also conclude that feeding rodents resveratrol has no effect on mitochondrial biogenesis in muscle.
Background: Progressive macular hypomelanosis is characterized by ill-defined, non-scaly, hypopigmented macules primarily on the trunk of the body.Although numerous cases of progressive macular hypomelanosis have been reported, there have been no clinicopathologic studies of progressive macular hypomelanosis in Korean patients.Objective: In this study we examined the clinical characteristics, histologic findings, and treatment methods for progressive macular hypomelanosis in a Korean population.Methods: Between 1996 and 2005, 20 patients presented to the Department of Dermatology at Busan Paik Hospital with acquired, non-scaly, confluent, hypopigmented macules on the trunk, and with no history of inflammation or infection.The medical records, clinical photographs, and pathologic findings for each patient were examined.Results: The patients included 5 men and 15 women.The mean age of onset was 21.05±3.47years.The back was the most common site of involvement.All KOH examinations were negative.A Wood's lamp examination showed hypopigmented lesions compared with the adjacent normal skin.A microscopic examination showed a reduction in the number of melanin granules in the lesions compared with the adjacent normal skin, although S-100 immunohistochemical staining did not reveal significant differences in the number of melanocytes.Among the 20 patients, 7 received topical drug therapy, 6 were treated with narrow-band ultraviolet B phototherapy, 4 received oral minocycline, and 3 did not receive any treatment.Conclusion: Most of the patients with progressive macular hypomelanosis had asymptomatic ill-defined, nonscaly, and symmetric hypopigmented macules, especially on the back and abdomen.Histologically, the number of melanocytes did not differ significantly between the hypopigmented macules and the normal perilesional skin.No effective treatment is known for progressive macular hypomelanosis; however, narrow-band ultraviolet B phototherapy may be a useful treatment modality.(
PURPOSE: An increase in bone mineral density during adolescence increases resistance to fractures in older age. The Korean Society for Bone and Mineral Research and the Korean Society of Exercise Physiology developed exercise guidelines to increase the peak bone mass (PBM) in adolescents based on evidence through a systematic review of previous research.METHODS: Articles were selected using the systematic method, and the exercise guidelines were established by selecting key questions (KQs) and defining the effects of exercises based on evidence through a literature review for selecting the final exercise method. There were 9 KQs. An online search was conducted on articles published since 2000, and 93 articles were identified.RESULTS: An increase in PBM in adolescence was effective for preventing osteoporosis and fractures in older age. Exercise programs as part of vigorous physical activity (VPA) including resistance and impact exercise at least 5 to 6 months were effective for improving PBM in adolescents. It is recommended that resistance exercise is performed 10 to 12 rep·set<sup>-1</sup> 1-2 set·region<sup>-1</sup> and 3 days·week<sup>-1</sup> using the large muscles. For impact exercises such as jumping, it is recommended that the exercise is performed at least 50 jumps·min<sup>-1</sup>, 10 min·day<sup>-1</sup>, and 2 days·week<sup>-1</sup>.CONCLUSIONS: Exercise guidelines were successfully developed, and they recommend at least 5 to 6 months of VPA, which includes both resistance and impact exercises. With the development of exercise guidelines, the incidence of osteoporosis and fractures in the aging society can be reduced in the future, thus contributing to improved public health.
A 55-year-old man who had been monitored for Liddle syndrome in the nephrology division for 15 years visited again Inje University Sanggye Paik Hospital for a newly developed electrolyte disorder. Because his blood pressure was normal and he showed hypomagnesemia and hypokalemia, a renal clearance test and renal biopsy were conducted for suspected Gitelman syndrome. The patient was diagnosed with Gitelman syndrome, which has been previously reported 12 cases in South Korea. The renal clearance test revealed a disorder of the Na-Cl cotransporter (NCCT) in the distal tubule, while the renal biopsy revealed partial expression of NCCT, typical of Gitelman syndrome. Currently, the patient is being monitored, and is receiving oral administration of calcium and magnesium.
Cathepsin K (Cat K) is expressed in cancer cells, but the effect of Cat K on apoptosis is still elusive. Here, we showed that inhibition of Cat K sensitized the human carcinoma cells to anti-cancer drug through up-regulation of Bim. Inhibition of Cat K increased USP27x expression, and knock down of USP27x markedly blocked Cat K-induced up-regulation of Bim expression. Furthermore, inhibition of Cat K induced proteasome-dependent degradation of regulatory associated protein of mammalian target of rapamycin (Raptor). Down-regulation of Raptor expression increased mitochondrial ROS production, and mitochondria specific superoxide scavengers prevented USP27x-mediated stabilization of Bim by inhibition of Cat K. Moreover, combined treatment with Cat K inhibitor (odanacatib) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reduced tumor growth and induced cell death in a xenograft model. Our results demonstrate that Cat K inhibition enhances anti-cancer drug sensitivity through USP27x-mediated the up-regulation of Bim via the down-regulation of Raptor.
The objective of this study was to analyze the concurrent treatment effects of ursolic acid (UA) and low-intensity treadmill exercise and to confirm the effectiveness of UA as an exercise mimetic to safely improve muscle atrophy-related diseases using Sprague-Dawley (SD) rats with skeletal muscle atrophy. Significant muscle atrophy was induced in male SD rats through hind limb immobilization using casting for 10 days. The muscle atrophy-induced SD rats were group into four: SED, sedentary; UA, daily intraperitoneal UA injection, 5 mg/kg; EX, low-intensity (10-12 m/min, 0° grade) treadmill exercise; and UEX, daily intraperitoneal UA injection, 5 mg/kg, and low-intensity (10-12 m/min, 0° grade) treadmill exercise. After 8 weeks of treatment, endurance capacity was analyzed using a treadmill, and tissues were extracted for analysis of visceral fat mass, body weight, muscle mass, expression of muscle atrophy- and hypertrophy-related genes, and endurance capacity. Although the effects of body weight gain control, muscle mass increase, and endurance capacity improvement were inadequate in the UA group, significant results were confirmed in the UEX group. The UEX group had significantly reduced body weight and visceral fat, significantly improved mass of tibialis anterior and gastrocnemius muscles, and significantly decreased atrophy-related gene expression of MuRF1 and atrogin-1, but did not have significant change in hypertrophy-related gene expression of Akt and mTOR. The endurance capacity was significantly improved in the EX and UEX groups. These data suggest that concurrent treatment with low-intensity exercise and UA is effective for atrophy-related physical dysfunctions.
Background: An increase in bone mineral density during adolescence increases resistance to fractures in older age.The Korean Society for Bone and Mineral Research and the Korean Society of Exercise Physiology developed exercise guidelines to increase the peak bone mass (PBM) in adolescents based on evidence through a systematic review of previous research.Methods: Articles were selected using the systematic method, and the exercise guidelines were established by selecting key questions (KQs) and defining the effects of exercises based on evidence through a literature review for selecting the final exercise method.There were 9 KQs.An online search was conducted on articles published since 2000, and 93 articles were identified.Results: An increase in PBM in adolescence was effective for preventing osteoporosis and fractures in older age.Exercise programs as part of vigorous physical activity (VPA) including resistance and impact exercise at least 5 to 6 months were effective for improving PBM in adolescents.It is recommended that resistance exercise is performed 10 to 12 rep•set -1 1-2 set•region -1 and 3 days•week -1 using the large muscles.For impact exercises such as jumping, it is recommended that the exercise is performed at least 50 jumps•min -1 , 10 min•day -1 and 2 days•week -1 .Conclusions: Exercise guidelines were successfully developed, and they recommend at least 5 to 6 months of VPA, which includes both resistance and impact exercises.With the development of exercise guidelines, the incidence of osteoporosis and fractures in the aging society can be reduced in the future, thus contributing to improved public health.
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