ABSTRACT
Epilepsy is not well controlled by current anti-seizure drugs (ASDs). High mobility group box 1 (HMGB1) is a DNA-binding protein in the nucleus regulating transcriptional activity and maintaining chromatin structure and DNA repair. In epileptic brains, HMGB1 is released by activated glia and neurons, interacting with various receptors like Toll-like receptor 4 (TLR4) and downstream glutamatergic NMDA receptor, thus enhancing neural excitability. But there is a lack of small-molecule drugs targeting the HMGB1-related pathways. In this study we evaluated the therapeutic potential of inflachromene (ICM), an HMGB-targeting small-molecule inhibitor, in mouse epilepsy models. Pentylenetetrazol-, kainic acid- and kindling-induced epilepsy models were established in mice. The mice were pre-treated with ICM (3, 10 mg/kg, i.p.). We showed that ICM pretreatment significantly reduced the severity of epileptic seizures in all the three epilepsy models. ICM (10 mg/kg) exerted the most apparent anti-seizure effect in kainic acid-induced epileptic status (SE) model. By immunohistochemical analysis of brain sections from kainic acid-induced SE mice, we found that kainic acid greatly enhanced HMGB1 translocation in the hippocampus, which was attenuated by ICM pretreatment in subregion- and cell type-dependent manners. Notably, in CA1 region, the seizure focus, ICM pretreatment mainly inhibited HMGB1 translocation in microglia. Furthermore, the anti-seizure effect of ICM was related to HMGB1 targeting, as pre-injection of anti-HMGB1 monoclonal antibody (5 mg/kg, i.p.) blocked the seizure-suppressing effect of ICM in kainic acid-induced SE model. In addition, ICM pretreatment significantly alleviated pyramidal neuronal loss and granule cell dispersion in kainic acid-induced SE model. These results demonstrate that ICM is an HMGB-targeting small molecule with anti-seizure potential, which may help develop a potential drug for treating epilepsy.
Subject(s)
Epilepsy , HMGB1 Protein , Mice , Animals , Kainic Acid/adverse effects , Kainic Acid/metabolism , Epilepsy/chemically induced , Epilepsy/drug therapy , Epilepsy/metabolism , Hippocampus/metabolism , HMGB Proteins/metabolism , HMGB Proteins/pharmacology , HMGB1 Protein/metabolism , Disease Models, AnimalABSTRACT
BACKGROUND: Granulocytic sarcoma (GS) is a rare malignant tumor, and relapse is even rarer in the breast and dorsal spine following allogeneic hematopoietic stem cell transplantation. Currently, a standard treatment regimen is not available. CASE SUMMARY: A rare case of GS of the right breast and dorsal spine after complete remission of acute myelogenous leukemia is reported here. A 55-year-old female patient presented with a palpable, growing, painless lump as well as worsening dorsal compressive myelopathy. She had a history of acute myelomonocytic leukemia (AML M4) and achieved complete remission after chemotherapy following allogeneic hematopoietic stem cell transplantation. Imaging examinations showed the breast lump and C7-T1 epidural masses suspected of malignancy. Histologic results were compatible with GS in both the right breast and dorsal spine, which were considered extramedullary relapse of the AML treated 4 years earlier. CONCLUSION: A rare case of GS relapse following allogeneic hematopoietic stem cell transplantation and guidelines for treatment are discussed.
ABSTRACT
This study used Tenax TA absorption tubes to sample volatile aromatic compounds from different emission sources and functional zones in Taiyuan City, Shanxi Province, China. Thermal desorption-gas chromatography-isotope ratio mass spectrometry (TD-GC-IRMS) was subsequently employed to analyze the stable carbon isotope characteristics of the volatile aromatic compounds. The results revealed that the stable carbon isotope ratio (δ13C) of the volatile aromatic compounds emitted through diesel, gasoline, and solvent volatilization, vehicle exhaust, and domestic coal combustion ranged from (-30.79±0.98) to (-29.10±0.14), (-30.96±0.88) to (-28.02±1.77), (-32.13±0.59) to (-27.67±0.49), (-27.58±0.16) to (-25.50±0.75), and (-25.14±0.93) to (-23.44±1.32), respectively. The δ13C value of styrene was (-23.44±1.32), which was only detected in the fumes emitted through domestic coal combustion. Additionally, the sample analysis based on data collected from four different functional zones of Taiyuan City revealed the following:â the δ13C values of the atmospheric volatile aromatic compounds in the mixed residential and traffic zone ranged from (-25.61±2.20) to (-23.91±0.78). Compared with other functional zones, the emissions in this zone were enriched with13C; and â¡ the δ13C values measured in the industrial zone ranged from (-29.15±1.06) to (-24.53±1.07); the emissions in this functional zone were relatively low in 13C compared with other zones. A comparison of the δ13C values of the atmospheric volatile aromatic compounds and emission sources indicated that the main sources of volatile aromatic compounds at the four sampling points in Taiyuan were vehicle exhausts and domestic coal combustion, while the air sampled in the industrial functional zone was heavily affected by the volatilization of solvents.
ABSTRACT
AIM: To record multifocal electroretinogram from different dosage of N(2)O(4) injected mice. In order to provide a foundation for further study. METHODS: Normal winstar mice which were injected by different dosage of N(2)O(4) were studied for recording multifocal electroretinogram in the same time in the evening after N(2)O(4) injection. RESULTS: The latency and amplitude density of "b" wave of each ring of multifocal electroretinogram was studied. The latency of "b" wave of each ring of multifocal electroretinogram of each group varies to each other. But the difference of the amplitude of "b" wave of multifocal electroretinogram of each ring between each group had no significance. CONCLUSION: Recording multifocal electroretinogram of N(2)O(4) injected mice will give more support for further study in related science and clinic research.
