Exercise training-induced PPARβ increases PGC-1α protein stability and improves insulin-induced glucose uptake in rodent muscles

This study aimed to investigate the long-term effects of training intervention and resting on protein expression and stability of peroxisome proliferator-activated receptor β/δ (PPARβ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), glucose transporter type 4 (GLUT4), and mitochondrial proteins, and determine whether glucose homeostasis can be regulated through stable expression of these proteins after training. Rats swam daily for 3, 6, 9, 14, or 28 days, and then allowed to rest for 5 days post-training. Protein and mRNA levels were measured in the skeletal muscles of these rats. PPARβ was overexpressed and knocked down in myotubes in the skeletal muscle to investigate the effects of swimming training on various signaling cascades of PGC-1α transcription, insulin signaling, and glucose uptake. Exercise training (Ext) upregulated PPARβ, PGC-1α, GLUT4, and mitochondrial enzymes, including NADH-ubiquinone oxidoreductase (NUO), cytochrome c oxidase subunit I (COX1), citrate synthase (CS), and cytochrome c (Cyto C) in a time-dependent manner and promoted the protein stability of PPARβ, PGC-1α, GLUT4, NUO, CS, and Cyto C, such that they were significantly upregulated 5 days after training cessation. PPARβ overexpression increased the PGC-1α protein levels post-translation and improved insulin-induced signaling responsiveness and glucose uptake. The present results indicate that Ext promotes the protein stability of key mitochondria enzymes GLUT4, PGC-1α, and PPARβ even after Ext cessation

Haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia

Severe aplastic anemia (SAA) is a life-threatening disorder for which allogeneic hematopoietic stem cell transplantation (HSCT) is the current available curative treatment. HSCT from matched sibling donors (MSDs) is the preferred therapy for children with acquired SAA. For patients who lack MSDs, immunosuppressive therapy (IST) is widely accepted as a first-line treatment before considering HCT from an unrelated donor (URD). Given the recent progress in HSCT using URDs for childhood SAA, well-matched URDs became a realistic alternative for pediatric patients who have no suitable related donors and who are refractory to IST. However, it is quite challenging to treat patients with refractory SAA who lack suitable related or URDs. Even though haploidentical HSCT from genetically mismatched family members seemed to be an attractive procedure with the amazing benefit of readily available donors for most patients, early attempts were disappointing because of refractory graft-versus-host disease (GVHD) and excessively high transplant-related mortality. Recent advances with effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcome of haploidentical transplant. Besides considerable progress in the treatment of malignant diseases, recent emerging evidences for haploidentical HSCT in SAA has provided additional therapeutic options for patients with refractory diseases. Further improvements to decrease the rates of graft failure, GVHD, and infectious complications will facilitate the emergence of haploidentical HSCT as a front-line therapy for treating acquired SAA in children and adolescents who have no suitably matched donors

Acanthopanax koreanum Fruit Waste Inhibits Lipopolysaccharide-Induced Production of Nitric Oxide and Prostaglandin E2 in RAW 264.7 Macrophages

The Acanthopanax koreanum fruit is a popular fruit in Jeju Island, but the byproducts of the alcoholic beverage prepared using this fruit are major agricultural wastes. The fermentability of this waste causes many economic and environmental problems. Therefore, we investigated the suitability of using A. koreanum fruit waste (AFW) as a source of antiinflammatory agents. AFWs were extracted with 80% EtOH. The ethanolic extract was then successively partitioned with hexane, CH2Cl2, EtOAc, BuOH, and water. The results indicate that the CH2Cl2 fraction (100 μg/mL) of AFW inhibited the LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 cells by 79.6% and 39.7%, respectively. These inhibitory effects of the CH2Cl2 fraction of AFWs were accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and iNOS and COX-2 mRNA in a dose-dependent pattern. The CH2Cl2 fraction of AFWs also prevented degradation of IκB-α in a dose-dependent manner. Ursolic acid was identified as major compound present in AFW, and CH2Cl2 extracts by high performance liquid chromatography (HPLC). Furthermore using pure ursolic acid as standard and by HPLC, AFW and CH2Cl2 extracts was found to contain 1.58 mg/g and 1.75 mg/g, respectively. Moreover, we tested the potential application of AFW extracts as a cosmetic material by performing human skin primary irritation tests. In these tests, AFW extracts did not induce any adverse reactions. Based on these results, we suggest that AFW extracts be considered possible anti-inflammatory candidates for topical application

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Comparative Study for the Differentiation of Allergic and Irritant Contact Dermatitis in Mice

Our study was performed to compare the differences between allergic and irritant contact dermatitis in BALB/c mice. Allergic reaction was induced by a sensitizing regimen of 2,4-dinitro-l-fluorobenzene (DNFB) and irritant reaction by 10% sodium lauryl sulfate (SLS). The following differences were noted: 1) the mice with irritant reaction showed an earlier peak of ear swelling, 2) increasing number of Langerhans cells (LCs) in allergic reaction but decreasing number of LCs in irritant reaction was observed at 48 hr after challenge of DNFB or SLS, and 3) induction of Ia (+) keratinocytes was found only in allergic reaction. It was suggested that Ia (+) keratinocytes play an active role in the mechanism of allergic contact dermatitis

Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo

Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP–containing vesicles and protein by 62% (P < 0.05), occurring rapidly and progressively over 25 min of contraction. However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice. In conclusion, resting skeletal muscles contain IL-6–positive vesicles that are expressed throughout myofibers. Contractions stimulate the rapid reduction of IL-6 in myofibers, occurring through an AMPKα2-independent mechanism. This novel imaging methodology clearly establishes IL-6 as a contraction-stimulated myokine and can be used to characterize the secretion kinetics of other putative myokines

Increase of Ceftazidime- and Fluoroquinolone-Resistant Klebsiella pneumoniae and Imipenem-Resistant Acinetobacter spp. in Korea: Analysis of KONSAR Study Data from 2005 and 2007

PURPOSE: Antimicrobial resistance monitoring could be a useful source of information for treating and controlling nosocomial infections. We analyzed antimicrobial resistance data generated by Korean Hospitals and by a commercial laboratory in 2005 and 2007. MATERIALS AND METHODS: Susceptibility data for 2005 and 2007 were collected from 37 and 41 hospitals, respectively, and from one commercial laboratory. Intermediate susceptibility was not included in the calculation of resistance rates. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) (64%), third-generation cephalosporin-resistant Klebsiella pneumoniae (29%), fluoroquinolone-resistant Escherichia coli (27%), Pseudomonas aeruginosa (33%), and Acinetobacter spp. (48%), and amikacin-resistant P. aeruginosa (19%) and Acinetobacter spp. (37%) were prevalent in hospitals in 2007. A gradual increase of vancomycin-resistant Enterococcus faecium and imipenem-resistant Acinetobacter spp. was observed. Higher incidences of thirdgeneration cephalosporin-resistant E. coli and K. pneumoniae and imipenemresistant P. aeruginosa were found in the commercial laboratory than in the hospitals. CONCLUSION: Methicillin-resistant S. aureus, third-generation cephalosporin- resistant K. pneumoniae, and fluoroquinolone-resistant E. coli, P. aeruginosa and Acinetobacter spp. remain prevalent in Korea, while the incidence of vancomycin-resistant E. faecium and imipenem-resistant Acinetobacter spp. has increased gradually. The higher prevalences of third-generation cephalosporinresistant E. coli and K. pneumoniae, and imipenem-resistant P. aeruginosa in the commercial laboratory are a new concern.ope