Celastrol prevents cadmium‐induced neuronal cell death via targeting JNK and PTEN‐Akt/mTOR network

Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative diseases. Celastrol, a plant‐derived triterpene, has shown neuroprotective effects in various disease models. However, little is known regarding the effect of celastrol on Cd‐induced neurotoxicity. Here, we show that celastrol protected against Cd‐induced apoptotic cell death in neuronal cells. This is supported by the findings that celastrol strikingly attenuated Cd‐induced viability reduction, morphological change, nuclear fragmentation, and condensation, as well as activation of caspase‐3 in neuronal cells. Concurrently, celastrol remarkably blocked Cd‐induced phosphorylation of c‐Jun N‐terminal kinase (JNK), but not extracellular signal‐regulated kinases 1/2 and p38, in neuronal cells. Inhibition of JNK by SP600125 or over‐expression of dominant negative c‐Jun potentiated celastrol protection against Cd‐induced cell death. Furthermore, pre‐treatment with celastrol prevented Cd down‐regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and activation of phosphoinositide 3′‐kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling in neuronal cells. Over‐expression of wild‐type PTEN enhanced celastrol inhibition of Cd‐activated Akt/mTOR signaling and cell death in neuronal cells. The findings indicate that celastrol prevents Cd‐induced neuronal cell death via targeting JNK and PTEN‐Akt/mTOR network. Our results strongly suggest that celastrol may be exploited for the prevention of Cd‐induced neurodegenerative disorders.

     

Infection-associated nuclear degeneration in the rice blast fungus Magnaporthe oryzae requires non-selective macro-autophagy

Background

The rice blast fungus Magnaporthe oryzae elaborates a specialized infection structure called an appressorium to breach the rice leaf surface and gain access to plant tissue. Appressorium development is controlled by cell cycle progression, and a single round of nuclear division occurs prior to appressorium formation. Mitosis is always followed by programmed cell death of the spore from which the appressorium develops. Nuclear degeneration in the spore is known to be essential for plant infection, but the precise mechanism by which it occurs is not known.

Methodology/Principal Findings

In yeast, nuclear breakdown requires a specific form of autophagy, known as piecemeal microautophagy of the nucleus (PMN), and we therefore investigated whether this process occurs in the rice blast fungus. Here, we report that M. oryzae possesses two conserved components of a putative PMN pathway, MoVac8 and MoTsc13, but that both are dispensable for nuclear breakdown during plant infection. MoVAC8 encodes a vacuolar membrane protein and MoTSC13 a peri-nuclear and peripheral ER protein.

Conclusions/Significance

We show that MoVAC8 is necessary for caffeine resistance, but dispensable for pathogenicity of M. oryzae, while MoTSC13 is involved in cell wall stress responses and is an important virulence determinant. By functional analysis of ΔMoatg1 and ΔMoatg4 mutants, we demonstrate that infection-associated nuclear degeneration in M. oryzae instead occurs by non-selective macroautophagy, which is necessary for rice blast disease.     

表达神经营养因子Neurturin的骨髓间充质干细胞的构建及体外活性检测

研究神经营养因子Neurturin(NTN)在由于神经元损伤而造成的神经退行性疾病中对神经元的保护和修复作用。利用重组腺病毒载体将NTN基因转入恒河猴骨髓间充质干细胞(rMSC),通过RT-PCR、IF及Western blot方法检测NTN的转录和表达,并采用鸡胚背根神经节体外培养实验和胚胎大鼠中脑多巴胺能神经元存活实验对NTN进行体外活性检测。结果表明NTN在rMSC中稳定表达和分泌,并具有体外生物学活性,为由于神经元损伤造成的神经退行性疾病的干细胞移植治疗奠定了一定的基础。     

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab- CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)

ABSTRACT: BACKGROUND: The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS: Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. RESULTS: Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001). CONCLUSIONS: Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.     

郑州主要植物春季物候变化及其对气温变化的响应

根据1983—2004年期间郑州市的物候和气温资料,分析了郑州市4种木本植物和2种草本植物的春季物候变化趋势及其对气温变化的响应。结果表明,自1983年以来,郑州春季主要植物物候呈偏早趋势,其物候变化具有同步性和顺序性的基本特征。郑州主要植物始花期与早春（3—4月）平均气温的相关性达到极显著,而毛白杨和垂柳2种植物始花期与冬季平均气温的关系也达到极显著; 代表性植物的始花期随3—4月平均气温的升高而提前,气温每升高1 ℃,刺槐、垂柳、蒲公英和车前始花期分别提前4.17、3.69、8.16和13.0 d。此外,始花前4旬是始花期对气温变化反应最敏感的时间段。     

典型滨岸草地生态系统碳稳定同位素组成及分布特征

通过测定上海市青浦区东风港百慕大、白花三叶草、高羊茅和白茅等4种典型滨岸草本植物各组织以及不同垂直深度土壤有机质δ¹³C值,对滨岸草地生态系统的植物-土壤碳稳定同位素特征进行了分析.结果表明: 白花三叶草、高羊茅属于C3植物,百慕大、白茅属于C4植物,其茎叶、凋落物和根系各组织间δ¹³C值无显著差异.C3和C4植物样带表层土壤有机质δ¹³C值随着土壤深度递增而呈现截然不同的变化特征,这与样带本底δ¹³C值以及碳稳定同位素分馏效应有关,同时还受植物根系分布深度的影响.植物输入是土壤有机碳(SOC)的最主要来源,植物有机体δ¹³C组成对土壤有机质δ¹³C值有直接影响,植物各组分δ¹³C值与土壤有机质δ¹³C值均存在极显著相关.4种草本植物样带SOC含量与δ¹³C值均呈极显著相关,其中,C3植物样带SOC含量与δ¹³C值呈线性负相关,C4植物样带SOC含量与δ¹³C值呈线性正相关.     

西藏小型猪与高原藏猪的血液生理生化值的比较

目的比较西藏小型猪与高原藏猪的血液生理、生化指标的差异。方法采用全自动血液细胞和生化分析仪测定21个血液生理生化指标。结果藏猪与西藏小型猪之间,红细胞、白细胞、血小板计数、总胆固醇、血清甘油三酯指标的测定差异有显著性,谷草转氨酶、血清总蛋白、血清清蛋白、葡萄糖、肌酸激酶指标的测定差异极显著。其中红细胞、白细胞、谷草转氨酶、肌酸激酶的值藏猪高于西藏小型猪,而血小板计数、血清总蛋白、血清清蛋白、葡萄糖、总胆固醇、血清甘油三酯的值藏猪低于西藏小型猪。结论不同的生活环境、气候条件和营养水平会对动物的血液生理、生化值的测定造成一定的影响。     

Impacts of cell surface characteristics on population dynamics in a sequencing batch yeast reactor treating vegetable oil-containing wastewater

Ten yeast strains acquired from different sources and capable of utilizing vegetable oil or related compounds (fatty acid or oleic acid) as sole carbon sources were inoculated into a sequencing batch reactor (SBR) for the treatment of high-strength vegetable oil-containing wastewater. The SBR system stably removed >89% of chemical oxygen demand (COD) and >99% of oil when fed with wastewater containing 15 g/L COD and 10 g/L oil in average. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified 26S rRNA genes showed that among the ten yeast strains, only Candida lipolytica, Candida tropicalis, and Candida halophila were dominant in the system. To elucidate the major factors affecting the selection of yeast strains in the SBR system, the three dominant strains were compared with two non-dominant strains in terms of COD removal performance, biomass yield, cell settleability, cell flocculation ability, cell emulsification ability, and surface hydrophobicity. Results showed that hydrophobicity and emulsification ability of yeast cells were the two most important factors determining the selection of yeast strains in the treatment of high-strength oil-containing wastewater.     

Enhancement of centelloside production from cultured plants of Centella asiatica by combination of thidiazuron and methyl jasmonate

In order to produce centellosides from whole plant cultures of Centella asiatica (L.) Urban, we evaluated the synergistic effects of thidiazuron (TDZ) and methyl jasmonate (MJ) on whole plant growth and centelloside production. After 4 weeks of treatment with 0.025 mg/L of TDZ coupled with 0.1 mM MJ, the production of madecassoside and asiaticoside from whole plant cultures was estimated to be 2.40- and 2.44-fold, respectively, above that of MJ elicitation alone. When whole plants were treated with a growth regulator and an elicitor, the growth of whole plants, as compared to the controls, did not differ. Additionally, total phytosyterol content in the leaves of whole plants co-treated with MJ and TDZ was 1.08-fold greater than those of MJ alone. These results demonstrate that combined treatments not only stimulate the accumulation of centellosides in the leaves but also inhibit the reduction of phytosterol levels caused by MJ elicitation.