Effects of Body Mass Index on Ankle Joint Muscle Function and Dynamic Proprioceptive Control

PURPOSE Increased body mass index (BMI) increases ankle instability and adversely affects human movement. This study aims to compare and analyze the muscle function and proprioception of the ankle joint based on Body Mass Index (BMI) to determine potential differences. METHODS Twenty-eight healthy male and female college students were categorized into overweight (≥ BMI 23) and normal (< BMI 23) groups. Measurements included BMI, isokinetic strength of dorsiflexion, plantarflexion, eversion, inversion, ankle joint range of motion, and ankle joint proprioception. RESULTS In dorsiflexion, right 30°/sec (p=.035), left 30°/sec (p=.009) and right 120°/sec (p=.011); in plantarflexion, left 30°/sec (p<.001), right 120°/sec (p=.007) and left 120°/sec (p=.006) in ankle inversion, left 30°/sec (p=.001), right 120°/sec (p=.021) and left 120°/sec (p=.007), left 30°/sec (p=.014), 120°/sec (p=.001) in ankle inversion-eversion ratio, right (p=.003) and left (p=.003) in ankle joint range of motion, right (p<.001) and left (p=.022) in total proprioception, and left (p<.001) in left-right proprioception were significantly different between the normal and overweight groups. CONCLUSIONS It was found that the overweight group had lower muscle strength, joint range of motion, and proprioceptive control function of the ankle joint than the normal group according to BMI. Therefore, exercise programs should be provided to strengthen the periarticular muscles involved in ankle movement, such as the tibialis anterior, soleus, and peroneus longus, and to control dynamic proprioception to prevent ankle injuries and function of the ankle joint according to BMI

Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice

Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery

Loss of Autophagy Diminishes Pancreatic β Cell Mass and Function with Resultant Hyperglycemia

SummaryAutophagy is a cellular degradation-recycling system for aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in various diseases including neurodegeneration, its role in pancreatic β cells and glucose homeostasis has not been described. We produced mice with β cell-specific deletion of Atg7 (autophagy-related 7). Atg7 mutant mice showed impaired glucose tolerance and decreased serum insulin level. β cell mass and pancreatic insulin content were reduced because of increased apoptosis and decreased proliferation of β cells. Physiological studies showed reduced basal and glucose-stimulated insulin secretion and impaired glucose-induced cytosolic Ca2+ transients in autophagy-deficient β cells. Morphologic analysis revealed accumulation of ubiquitinated protein aggregates colocalized with p62, which was accompanied by mitochondrial swelling, endoplasmic reticulum distension, and vacuolar changes in β cells. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic β cells, and its impairment causes insulin deficiency and hyperglycemia because of abnormal turnover and function of cellular organelles

Acute viral gastroenteritis in children hospitalized in Iksan, Korea during December 2010-June 2011

PurposeViral etiology is common in cases of children with acute diarrhea, and antibiotic therapy is usually not required. Therefore, it is important to determine the distribution of common viruses among children hospitalized with acute diarrhea.MethodsWe included 186 children who suffered from acute diarrhea and were hospitalized at the Wonkwang University Hospital Pediatric ward from December 1, 2010 to June 30, 2011 in this study. Stool samples were collected and multiplex reverse transcriptase polymerase chain reaction (multiplex RT-PCR) was used to simultaneously determine the viral etiology such as rotavirus, norovirus, astrovirus, or adenovirus.ResultsCausative viruses were detected in 72 of the 186 cases (38.7%). The mean age of the virus-positive cases was 1 year and 9 months (range, 1 month to 11 years). Rotavirus was detected in 50/186 (26.9%); norovirus, in 18/186 (9.7%); and astrovirus, in 3/186 cases (1.6%). Adenovirus was not detected in any of the cases. Proportions of norovirus genogroups I and II were 21.1% and 78.9%, respectively. Four of the 51 rotavirus-positive cases (7.8%) had received rotavirus vaccination at least once. The mean duration of diarrhea was 2.8 days (range, 1 to 10 days) and vomiting occurred in 39 of the 72 cases (54.2%).ConclusionViral etiology was confirmed in about one-third of the children with acute diarrhea, and the most common viral agent was rotavirus, followed by norovirus

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis

Roles of Arrest-Defective Protein 1225 and Hypoxia-Inducible Factor 1α in Tumor Growth and Metastasis

Background Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A225) acetylates HIF-1??, triggering its degradation, and thus may play a role in decreased expression of VEGFA.Methods We generated ApcMin/+/mARD1A225 transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A225 were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A 225 acetylation of Lys532 in HIF-1??, we injected B16F10-mARD1A225 cell lines stably expressing mutant HIF-1??/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than. 05 were considered statistically significant.Results ApcMin/+/mARD1A225 transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc Min/+ mice (n = 21) (number of intestinal polyps per mouse: Apc Min/+ mice vs ApcMin/+/mARD1A225 transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P &lt;. 001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A225-overexpressing cells than in mice injected with control cells (P &lt;. 01). Moreover, overexpression of mARD1A 225 decreased VEGFA expression and microvessel density in tumor xenografts (P &lt;. 04) and ApcMin/+ intestinal polyps (P =. 001). Mutation of lysine 532 of HIF-1?? in B16F10-mARD1A225 cells prevented HIF-1?? degradation and inhibited the antimetastatic effect of mARD1A225 (P &lt;. 001).Conclusion mARD1A225 may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells

A Nationwide Survey of Lymphangioleiomyomatosis in Korea: Recent Increase in Newly Diagnosed Patients

In 2007, the Korean Interstitial Lung Disease Society had collected clinical data of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990 through nationwide survey, which showed that LAM patients had increased sharply after 2004. The present study was performed to show the clinical features of Korean patients with LAM, and to establish the reason for the recent increase in the diagnosis. All 63 patients were women and the mean age at diagnosis was 36 yr. The most common presenting symptom was dyspnea and 8 patients had tuberous sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared with patients diagnosed after 2004 (n=34), the patients diagnosed before 2004 (n=29) complained with dyspnea more (P=0.016) and had lower FEV1% predicted (P=0.003), and DLco% predicted (P=0.042). The higher proportion of patients diagnosed after 2004 showed the normal chest radiography, and they were detected by routine chest CT screening (P=0.016). This study showed that clinical features of Korean patients with LAM were not different from those reported elsewhere. It is concluded that the reason for the increase of newly diagnosed patients is the result of increase in detection of the early stage LAM by the widespread use of chest CT screening