Extracts of Flavoparmelia sp. Inhibit Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation

BACKGROUND: Osteoporosis is a geriatric disease with diminished bone density. The increase in the number of patients and medical expenses due to a global aging society are recognized as problems. Bone loss is the most common symptom of bone disease, not only osteoporosis but Paget's disease, rheumatoid arthritis, multiple myeloma, and other diseases. The main cause of this symptoms is excessive increase in the number and activity of osteoclasts. Osteoclasts are multinucleated giant cells that can resorb bone. They are differentiated and activation from monocytes/macrophages in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). METHODS: The effect of extract of Flavoparmelia sp. (EFV), a genus of lichenized fungi within the Parmeliaceae, on the differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts was examined by phenotype assay and the cell cytotoxicity was evaluated by cell counting kit-8. The osteoclast differentiation-related genes and proteins were investigated by real-time polymerase chain reaction and immunoblotting. The functional activity of osteoclast in response to EFV treatment was evaluated by an Osteo Assay plate. RESULTS: In this study, we found that EFV, a genus of lichenized fungi within the Parmeliaceae, inhibited osteoclast formation. And we investigated its inhibitory mechanism. EFV reduced RANKL-mediated osteoclast formation and activation by inhibiting expression of nuclear factor of activated T cells 1, a key factor of osteoclastogenesis. CONCLUSIONS: Taken together, our results show that EFV is a promising candidate for health functional foods or therapeutic agents that can help treat bone diseases such as osteoporosis.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to β-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-κB activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-κB-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-κB and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

Sensory Axon Regeneration: A Review from an in vivo Imaging Perspective

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.

Clinical Application of Unilateral-Ring Hybrid Fixation Using DynaExtor(R) / 대한정형외과학회잡지

PURPOSE: We have used a hybrid fixation, in which DynaExtor(R) and Ilizarov rings are connected each other with special connectors. Here, we report upon the technical tips learned and the clinical outcomes of the first twenty five consecutive cases treated using this method. MATERIALS AND METHODS: Between May 1997 and December 1999, 25 patients were treated using hybrid fixation aimed at simple lengthening (8 patients), concomitant deformity correction and lengthening (12), deformity correction alone (3), and fracture fixation (2). RESULTS: In the group requiring simple lengthening, the healing index (H.I.) was 38.3 day/cm (23.6-66.8 day/cm). For concomitant deformity correction and lengthening, the mean amount of angular correction was 33.8degrees (15-75degrees) and the length gain, 4.7 cm (2.2-8.9 cm). For deformity correction alone, the amount of angular correction was 50.1degrees (15-120degrees). For fracture fixation, the mean external fixation time was 59.5 days (26-93 days). Complications included mild pin-tract infection in 8 patients, a temporary stiff joint in 5, and equinus of the foot and delayed union in one patient each. CONCLUSION: The DynaExtor(R) hybrid-fixation system is an effective and convenient method that can be selectively applied to cases that need deformity correction, lengthening, or fixation of the long bone.

Study of the Allelic Frequency on Polymorphic Loci in the Short Arm of Chromosome 3 in Normal Koreans / 대한비뇨기과학회지

The results of allelic frequency of polymorphic loci in the short arm of chromosome 3 in normal Koreans are shown using a polymerase chain reaction (PCR) based restriction fragment length polymorphism analysis on blood samples of 20 males and 20 females without any tumor or hereditary diseases. The allelic frequency of two loci, D3S2 (MspI) and D3F15S2 (Hind III ) was quite different between renal cell carcinoma in Koreans and Caucasians, but THRB (MspI) locus was similar This suggests the importance of determining specific loci to Koreans. The study of tumor suppressor gene on these genetic loci due to D3S2 (MspI) and THRB (EcoRI) loci showed high constitutional heterozygosity, contrast to D3F15S2 (Hind III), THRB (BamHI) and THRB (MspI) loci where low constitutional heterozygosity were seen. Therefore, the study of tumor suppressor gene should be directed to investigate. This study showed the allelic distribution of Koreans differing from Caucasians and the genetic locus with the high frequency of heterozygosity among the polymorphic loci comparable to Koreans were due to the difference of heterozygosity frequency according to genetic loci. Therefore, the author thinks that the need for the detection of specific genetic loci for Koreans to study the correlation among many cases for classifying the tumorigenesis and active research should be initiated to find other genetic locus related to multi-step tumorigenesis.

Clinical Study on the Patients with Cerebrovascular Accident and Myocardial Infarction

Thirty patients who coincided with CVA and MI, from january 1980 to August 1984, at Department of Internal Medicine, Kyung Hee University Hospital, were studied. And the following results were obtained; 1) The ratio of male to female was 2:1. The average age was 61.6 years. The in-hospital mortality rate was higher than cerebrovascular accident or myocardial infarction alone. 2) The most common risk factor was hypertension(83%), smoking(64%), hyperlipidemia(57%) and diabetes mellitus(33%) in order of frequency. 3) Fifteen cases of 30 patients had acute episode of MI and CVA during hospitalization and showed highest in -hospital mortality rate(66.7%). 4) There was no difference in mortality rate between cereral infarction and cerebral hemorrhage.