Gallic acid-mitochondria targeting sequence-H3R9 induces mitochondria-targeted cytoprotection

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H3R9 exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy.In viability assays, GA-MTS-H3R9 showed a better rescue action compared to that of MTS-H3R9 . GA-MTS-H3R9 dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H3R9 towards mitochondria in AC16 cells.Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTSH3R9 alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H3R9 showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H3R9 . We showed that GA-MTS-H3R9 can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

Branching Patterns and Anatomical Course of the Common Fibular Nerve

OBJECTIVE: To present the branching patterns and anatomical course of the common fibular nerve (CFN) and its relationship with fibular head (FH).METHODS: A total of 21 limbs from 12 fresh cadavers were dissected. The FH width (FH_width), distance between the FH and CFN (FH_CFN), and thickness of the nerve were measured. The ratio of the FH_CFN to FH_width was calculated as follows: < 1, cross type and ≥1, posterior type. Angle between the CFN and vertical line of the lower limb 5 cm proximal to the tip of the FH was measured. Branching patterns of the lateral cutaneous nerve of the calf (LCNC) were classified into four types according to its origin and direction as follows: type 1a, lateral margin of the CFN; type 1b, medial margin of the CFN; type 2, lateral sural cutaneous nerve (LSCN); and type 3, CFN and LSCN.RESULTS: In the cross type (15 cases, 71.4%), the ratio of FH_CFN/FH_width was 0.83 and the angle was 13.0°. In the posterior type (6 cases, 28.6%), the ratio was 1.04 and the angle was 11.0°. In the branching patterns of LCNC, type 2 was the most common (10 cases), followed by types 1a and 1b (both, 5 cases).CONCLUSION: Location of the CFN around the FH might be related to the development of its neuropathy, especially in the cross type of CFN. The LCNC showed various branching patterns and direction, which could be associated with difficulties of electrophysiologic testing.

Diagnosis of Pure Ulnar Sensory Neuropathy Around the Hypothenar Area Using Orthodromic Inching Sensory Nerve Conduction Study: A Case Report

Ulnar neuropathy at the wrist is an uncommon disease and pure ulnar sensory neuropathy at the wrist is even rarer. It is difficult to diagnose pure ulnar sensory neuropathy at the wrist by conventional methods. We report a case of pure ulnar sensory neuropathy at the hypothenar area. The lesion was localized between 3 cm and 5 cm distal to pisiform using orthodromic inching test of ulnar sensory nerve to stimulate at three points around the hypothenar area. Ultrasonographic examination confirmed compression of superficial sensory branch of the ulnar nerve. Further, surgical exploration reconfirmed compression of the ulnar nerve. This case report demonstrates the utility of orthodromic ulnar sensory inching test.

Harmless effects of argon plasma on caudal fin regeneration and embryogenesis of zebrafish: novel biological approaches for safe medical applications of bioplasma

The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology and dentistry, and it is considered a promising tool for cancer therapy. However, the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and there are no biological tools to determine the appropriate clinical dosages of Ar-PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to induce cell death in two-dimensional (2D) cell culture systems. By contrast, no detrimental effects of Ar-PJ were shown in our 3D zebrafish systems composed of 2D cells. The Ar-PJ-treated caudal fins grew by an average length of 0.7 mm, similar to the length of the normally regenerating fins. Remarkably, Ar-PJ did not affect the expression patterns of Wnt8a and β-Catenin, which play important roles in fin regeneration. In the embryo system, 85% of the Ar-PJ-treated embryos hatched, and the lateral length of these embryos was ~3.3 mm, which are equivalent to the lengths of normal embryos. In particular, vasculogenesis, which is the main cellular process during tissue regeneration and embryogenesis, occurred normally under the Ar-PJ dose used in this study. Therefore, our biosafety evaluation tools that use living model systems can be used to provide an experimental guideline to determine the clinically safe dosage of Ar-PJ.

Neurochemical Profile Quantification of Regional Adult Mice Brain Using: ex vivo 1H High-Resolution Magic Angle Spinning NMR Spectroscopy / 의학물리

The purpose of this study is to quantitate regional neurochemical profile of regional normal adult mice brain and assess regional metabolic differences by using ex vivo 1H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HR-MAS NMRS). The animals were matched in sex and age. The collected brain tissue included frontal cortex, temporal cortex, thalamus, and hippocampus. Quantitative 1D spectra were acquired on 40 samples with the CPMG pulse sequence (8 kHz spectral window, TR/TE = 5500/2.2 ms, NEX = 128, scan time: 17 min 20 sec). The mass of brain tissue and D2O+TSP solvent were 8~14 mg and 7~13 mg. A total of 16 metabolites were quantified as follow: Acet, NAA, NAAG, tCr, Cr, tCho, Cho, GPC + PC, mIns, Lac, GABA, Glu, Gln, Tau and Ala. As a results, Acet, Cho, NAA, NAAG and mIns were showed significantly different aspects on frontal cortex, hippocampus, temporal cortex and thalamus respectively. The present study demonstrated that absolute metabolite concentrations were significantly different among four brain regions of adult mice. Our finding might be helpful to investigate brain metabolism of neuro-disease in animal model.

Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimer's disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Abeta binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.