Mitochondrial Mutations in Adenoid Cystic Carcinoma of the Salivary Glands

Background: The MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas. Methodology: The entire mitochondrial genome of 22 salivary gland adenoid cystic carcinomas (ACC) of salivary glands and matched leukocyte DNA was sequenced to determine the frequency and distribution of mitochondrial mutations in ACC tumors. Principal Findings: Seventeen of 22 ACCs (77%) carried mitochondrial mutations, ranging in number from 1 to 37 mutations. A disproportionate number of mutations occurred in the D-loop. Twelve of 17 tumors (70.6%) carried mutations resulting in amino acid changes of translated proteins. Nine of 17 tumors (52.9%) with a mutation carried an amino acid changing mutation in the nicotinamide adenine dinucleotide dehydrogenase (NADH) complex. Conclusions/Significance: Mitochondrial mutation is frequent in salivary ACCs. The high incidence of amino acid changing mutations implicates alterations in aerobic respiration in ACC carcinogenesis. D-loop mutations are of unclear significance

The Astrocyte-Targeted Therapy by Bushi for the Neuropathic Pain in Mice

BACKGROUND: There is accumulating evidence that the activation of spinal glial cells, especially microglia, is a key event in the pathogenesis of neuropathic pain. However, the inhibition of microglial activation is often ineffective, especially for long-lasting persistent neuropathic pain. So far, neuropathic pain remains largely intractable and a new therapeutic strategy for the pain is still required. METHODS/PRINCIPAL FINDINGS: Using Seltzer model mice, we investigated the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal hyperalgesia and mechanical allodynia, as well as that of morphological changes in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we analyzed the pattern of progression in the pain behaviors, and found that the pain consisted of an "early induction phase" and subsequent "late maintenance phase". We next analyzed the temporal changes in spinal glial cells, and found that the induction and the maintenance phase of pain were associated with the activation of microglia and astrocytes, respectively. When Bushi, a Japanese herbal medicine often used for several types of persistent pain, was administered chronically, it inhibited the maintenance phase of pain without affecting the induction phase, which was in accordance with the inhibition of astrocytic activation in the spinal cord. These analgesic effects and the inhibition of astrocytic activation by Bushi were mimicked by the intrathecal injection of fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the direct effect of Bushi on astrocytic activation, and found that Bushi suppressed the IL-1β- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro. CONCLUSIONS: Our results indicated that the activation of spinal astrocytes was responsible for the late maintenance phase of neuropathic pain in the Seltzer model mice and, therefore, the inhibition of astrocytic activation by Bushi could be a useful therapeutic strategy for treating neuropathic pain

Mimosine in Leucaena as a potent bio-herbicide

Mimosine [$\alpha$-amino-$\beta$-(3-hydroxy-4-oxo-1,4-dihydropyridin-1-yl)-propanoic acid] is a major constituent of Leucaena (Leucaena leucocephala de Wit) and responsible for the strong allelopathic potential of the legume tree. Mimosine showed strong herbicidal activities on six plants in a bioassay. All plant parts of Leucaena contain mimosine. The quantity of mimosine in the young leaves and mature seeds was the greatest, 2.66 and 2.38% of dry weight, respectively, while the quantity in the root xylems and xylems was the lowest: 0.18 and 0.11% of dry weight, respectively. Younger plant parts of Leucaena contained greater amounts of mimosine than the mature parts. Mimosine released from young parts and the seeds of Leucaena was proportional to the quantity of soaking water. Compared with the mature seeds, other mature parts of the plant did not give any mimosine through exuding. In soil to which mimosine was added, about 60% of the mimosine was adsorbed in 1–5 days, and only a minor volume of mimosine was decomposed: 5.30 and 0.16% after 1 and 5 days, respectively. Using a mixture of FeCl3 and mimosine in a 4:6 ratio may be the most effective and economical method of lowering the toxicity of mimosine in Leucaena leaves, giving a safer cattle feed and decreasing the soil toxicity caused by mimosine in areas where Leucaena is grown. On the other hand, the incorporation of mimosine leaves into cultivated soils may be helpful for the biological control of weeds. The findings of this research reveal that mimosine may be useful for the development of bio-herbicides