Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation

Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-kappa B and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL-1 receptor domain-containing adaptor-inducing interferon-beta. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation

Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cell, but not Adipose Tissue-Derived Stem Cell, Ameliorated the Neonatal Hypoxic-Ischemic Brain Injury by Changing Cerebral Inflammatory State in Rat

Perinatal hypoxic-ischemic (HI) brain injury occurs in 1 in 1,000 live births and remains the main cause of neurological disability and death in term infants. Cytotherapy has recently emerged as a novel treatment for tissue injury. In particular, mesenchymal stem cells (MSCs) are thought to have therapeutic potential, but little is known about the differences according to their origin. In the current study, we investigated the therapeutic effects and safety of intravenous injection of allogeneic bone marrow-derived MSCs (BM-MSCs) and adipose-derived stem cells (ADSCs) in a rat model of HI brain injury. HI models were generated by ligating the left carotid artery of postnatal day 7 Wistar/ST rats and exposing them to 8% hypoxia for 60 min. Bone marrow and adipose tissue were harvested from adult green fluorescent protein transgenic Wistar rats, and cells were isolated and cultured to develop BM-MSCs and ADSCs. At passaging stages 2–3, 1 × 105 cells were intravenously injected into the external right jugular vein of the HI rats at 4 or 24 h after hypoxia. Brain damage was evaluated by counting the number of cells positive for active caspase-3 in the entire dentate gyrus. Microglial isotypes and serum cytokines/chemokines were also evaluated. Distribution of each cell type after intravenous injection was investigated pathologically and bio-optically by ex vivo imaging (IVIS®) with a fluorescent lipophilic tracer DiR. The mortality rate was higher in the ADSC group compared to the BM-MSC group, in pups injected with cells 4 h after hypoxia. The number of active caspase-3-positive cells significantly decreased in the BM-MSC group, and the percentage of M1 microglia (a proinflammatory isotype) was also lower in the BM-MSC vs control group in the penumbra of the cortex. Moreover, BM-MSC administration increased anti-inflammatory cytokine and growth factor levels, while ADSCs did not. Each injected cell type was mainly distributed in the lungs and liver, but ADSCs remained in the lungs longer. Pathologically, pulmonary embolisms and diffuse alveolar hemorrhages were seen in the ADSC group. These results indicated that injection of allogeneic BM-MSCs ameliorated neonatal HI brain injury, whereas ADSCs induced severe lung hemorrhage and higher mortality

Chloroplast acquisition without the gene transfer in kleptoplastic sea slugs, Plakobranchus ocellatus

Some sea slugs sequester chloroplasts from algal food in their intestinal cells and photosynthesize for months. This phenomenon, kleptoplasty, poses a question of how the chloroplast retains its activity without the algal nucleus. There have been debates on the horizontal transfer of algal genes to the animal nucleus. To settle the arguments, this study reported the genome of a kleptoplastic sea slug, Plakobranchus ocellatus, and found no evidence of photosynthetic genes encoded on the nucleus. Nevertheless, it was confirmed that light illumination prolongs the life of mollusk under starvation. These data presented a paradigm that a complex adaptive trait, as typified by photosynthesis, can be transferred between eukaryotic kingdoms by a unique organelle transmission without nuclear gene transfer. Our phylogenomic analysis showed that genes for proteolysis and immunity undergo gene expansion and are up-regulated in chloroplast-enriched tissue, suggesting that these molluskan genes are involved in the phenotype acquisition without horizontal gene transfer

Tonsillar metastasis of gastric cancer

Metastasis from a malignant tumor to the palatine tonsils is rare, with only 100 cases reported in the English-language literature. Tonsillar metastasis from a gastric cancer is very rare. We report here a case of palatine tonsillar metastasis after gastric cancer surgery. The patient was an 88-year-old woman who had gastric cancer with abdominal wall invasion. She had undergone a distal gastrectomy with abdominal wall resection and D2 lymph node dissection. Histologically, the tumor was primarily a moderately differentiated adenocarcinoma. It was stage IV (T4, N1, M0) using TNM clinical classification. The patient developed pharyngeal discomfort and abdominal pain and was hospitalized during the follow-up period, 1 year 9 months post-operatively. Multiple lung metastases, Virchow’s lymph node metastasis, and adrenal metastasis were observed. A mass of 2.5 cm was also observed in the right palatine tonsil. It was diagnosed as a moderately differentiated adenocarcinoma, a metastasis from gastric cancer. There was a concern of asphyxiation due to hemorrhage of the tumor; however, the tumor dislodged approximately 10 days after biopsy and tonsillar recurrence was not observed. The patient died 1 year 10 months post-operatively. In the literature there are cases with tonsillar metastases where surgical treatment, radiotherapy, and chemotherapy were performed and extension of survival was seen. Tonsillar metastasis is a form of systemic metastasis of a malignant tumor, and there is a high risk for asphyxiation from tumor dislodgement or hemorrhage. Thus, it is important to recognize tonsillar metastasis as an oncologic emergency

Effects of Alkali Leaching on Composition and Surface Structure of Cu-Al Alloy Layer Produced by Powder-Metallurgical Method

In order to produce a Raney copper catalyst on the inner wall of microchannels, alkali leaching of Cu-Al alloy microchannel lining layers was investigated. Aluminum concentration of the lining layer decreased with leaching time when the lining-layer surface was exposed to a leaching solution. Furthermore, a fine copper structure was formed where aluminum was leached. This result indicates a possibility of fabrication of Raney copper catalyst