Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A₂-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation.     

The septins FaCdc3 and FaCdc12 are required for cytokinesis and affect asexual and sexual development,lipid metabolism and virulence in Fusarium asiaticum

Septins are a highly conserved family of GTP‐binding proteins that contribute to many cellular and metabolic functions, including cell polarity, cytokinesis, cell morphogenesis and pathogenesis. In this study, we characterized the septins FaCdc3 and FaCdc12 in the filamentous fungus Fusarium asiaticum. The functions of FaCdc3 and FaCdc12 were evaluated by constructing deletion mutants of FaCdc3 and FaCdc12, designated ΔFaCdc3‐5 and ΔFaCdc12‐71, respectively. The deletion mutants exhibited a reduced rate of mycelial growth, increased aerial hyphae formation, irregularly shaped hyphae, reduced conidiation and a lack of sexual reproduction in wheat kernels. Histochemical analysis revealed that the conidia and hyphae of ΔFaCdc3‐5 and ΔFaCdc12‐71 formed large lipid droplets (LDs). ΔFaCdc3‐5 and ΔFaCdc12‐71 also exhibited increased resistance to agents that induce osmotic stress and damage the cell membrane and cell wall. In addition, the hyphae and conidia of the two mutants formed fewer septa than those of the wild‐type and exhibited aberrant nuclear distribution. Pathogenicity assays showed that ΔFaCdc3‐5 and ΔFaCdc12‐71 exhibited reduced virulence on wheat spikelets, which was indirectly correlated with a reduced level of deoxynivalenol accumulation. All of these defects were restored by genetic complementation of the two mutants with the parental FaCdc3 and FaCdc12. These results indicate that FaCdc3 and FaCdc12 play a critical role in various cellular processes in F. asiaticum.     

无功能垂体瘤的术后评估

垂体瘤是常见的颅内良性肿瘤,患病率高,预后较好。在我国,其发病率仅次于胶质瘤和脑膜瘤。无功能垂体瘤约占垂体瘤22.5%,手术是其首选的治疗方式,以解除肿瘤的占位效应,减少对正常垂体组织的压迫。然而手术本身可能引起垂体功能减退,术后应对患者垂体功能的监测并予以处理。同时,由于手术及患者个体身体、心理原因,患者术后的生活质量也越来越受到重视。本文综述了无功能垂体瘤患者术后各内分泌轴功能的临床检测方法,以帮助临床医生对术后患者的垂体功能进行评估并重建;同时对术后患者生活质量的评估加以讨论,帮助指导患者恢复生理及心理健康。     

消水散联合利尿剂治疗癌性腹水的疗效及对患者免疫功能的影响

目的:探讨自拟消水散联合利尿剂治疗癌性腹水的临床疗效。方法:选取恶性肿瘤伴癌性腹水患者84例,按随机数字表法分组,分别为42例,对照组予以常规利尿剂治疗,研究组予以自拟消水散联合利尿剂治疗。观察并比较两组患者治疗前后血清TNF-α,IL-2,IL-4,IL-6,CD3~+,CD4~+及CD4~+/CD8~+含量的变化情况以及临床疗效。结果:与治疗前对比,两组治疗后血清TNF-α,IL-2,IL-4及IL-6均降低,CD3~+,CD4~+及CD4~+/CD8~+均升高,CD8~+均降低,CEA,CA125,CA153及CA199均降低(P0.05);与对照组对比,研究组治疗后血清TNF-α,IL-2,IL-4,IL-6较低,CD3~+,CD4~+及CD4~+/CD8~+较高,CD8~+较低,CEA,CA125,CA153及CA199较低(P0.05);研究组治疗有效率高于对照组,差异具有统计学意义(P0.05)。结论:消水散联合利尿剂治疗癌性腹水的疗效确切,能显著降低炎症指标及肿瘤标志物,提高机体免疫功能。     

不同麻醉方法对食管癌手术患者免疫及认知功能的影响

目的:探讨全麻或全麻复合硬膜外麻醉对食管癌手术患者的T细胞水平及术后认知功能的影响。方法:选择2014年1月至2015年12月于我院择期行开胸手术的食管癌患者100例为研究对象,根据手术时间顺序分为观察组(全麻复合硬膜外麻醉)和对照组(全麻),每组50例,观察记录两组患者诱导前、插管时、术中1 h、拔管后的平均动脉压(MAP)、血氧饱和度(Sp O2)和心率(HR);两组患者术前30 min、术后2 h、术后2 d和术后7 d的T细胞亚群水平,包括CD3~+、CD4~+、CD8~+、CD4~+/CD8~+;两组患者术前1 d,术后6 h,术后1 d,术后3 d的认知功能;术后认知功能障碍(POCD)发生率。结果:诱导前观察组和对照组患者的MAP、Sp O2和HR比较,差异均不显著(P0.05),插管时、术中1h和拔管后观察组患者的MAP和HR水平均明显低于对照组(P0.05),而Sp O2明显高于对照组(P0.05)。术后2 h,观察组和对照组的CD3~+、CD4~+、CD8~+、CD4~+/CD8~+值均较术前30 min明显降低(P0.05),但两组间各指标值无显著性差异(P0.05);术后2 d,观察组的CD3~+、CD4~+、CD8~+、CD4~+/CD8~+值均明显高于对照组(P0.05)。术后7 d,两组的T细胞亚群水平均较术前30 min无显著性差异(P0.05)。术后6 h和术后1 d,两组的MMSE评分均较术前1 d明显下降(P0.05),观察组术后1 d、3 d和7 d的MMSE评分均明显高于对照组(P0.05)。术后6 h,观察组的POCD发生率明显低于对照组(P0.05),术后1 d和3 d观察组的POCD发生率低于对照组,但无统计学差异(P0.05)。结论:与单凭全麻比较,全麻复合硬膜外麻醉对食管癌手术患者的T细胞水平及术后认知功能的影响较小,术后恢复快。     

Establishing the role of detoxifying enzymes in field‐evolved resistance to various insecticides in the brown planthopper (Nilaparvata lugens) in South India

The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide resistance leading to frequent control failures in the field. The aim of the present study was to evaluate resistance in the field populations of N. lugens from major rice growing states of South India to various insecticides. We also determined the activity of detoxifying enzymes (esterases [ESTs], glutathione S‐transferases [GSTs], and mixed‐function oxidases [MFOs]). Moderate levels of resistance were detected in the field populations to acephate, thiamethoxam and buprofezin (resistance factors 1.05–20.92 fold, 4.52–14.99 fold, and 1.00–18.09 fold, respectively) as compared with susceptible strain while there were low levels of resistance to imidacloprid (resistance factor 1.23–6.70 fold) and complete sensitivity to etofenoprox (resistance factor 1.05–1.66 fold). EST activities in the field populations were 1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity was found to be correlated to acephate resistance (r = 0.999, P ≥ 0.001). The high selection pressure of organophosphate, neonicotinoid, and insect growth regulator (IGR) in the field is likely to be contributing for resistance in BPH to multiple insecticides, leading to control failures. The results obtained will be beneficial to IPM recommendations for the use of effective insecticides against BPH.     

Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479

Use of the tools of SBDD including crystallography led to the discovery of novel and potent 6,5 heterobicyclic MEKi’s [J. Med. Chem. 2012, 55, 4594]. The core change from a 5,6 heterobicycle to a 6,5 heterobicycle was driven by the desire for increased structural diversity and aided by the co-crystal structure of G-925 [J. Med. Chem. 2012, 55, 4594]. The key design feature was the shift of the attachment of the five-membered heterocyclic ring towards the B ring while maintaining the key hydroxamate and anilino pharamcophoric elements in a remarkably similar position as in G-925. From modelling, changing the connection point of the five membered ring heterocycle placed the H-bond accepting nitrogen within a good distance and angle to the Ser212 [J. Med. Chem. 2012, 55, 4594]. The resulting novel 6,5 benzoisothiazole MEKi G-155 exhibited improved potency versus aza-benzofurans G-925 and G-963 but was a potent inhibitor of cytochrome P450’s 2C9 and 2C19. Lowering the log D by switching to the more polar imidazo[1,5-a] pyridine core significantly diminished 2C9/2C19 inhibition while retaining potency. The imidazo[1,5-a] pyridine G-868 exhibited increased potency versus the starting point for this work (aza-benzofuran G-925) leading to deprioritization of the azabenzofurans. The 6,5-imidazo[1,5-a] pyridine scaffold was further diversified by incorporating a nitrogen at the 7 position to give the imidazo[1,5-a] pyrazine scaffold. The introduction of the C7 nitrogen was driven by the desire to improve metabolic stability by blocking metabolism at the C7 and C8 positions (particularly the HLM stability). It was found that improving on G-868 (later renamed GDC-0623) required combining C7 nitrogen with a diol hydroxamate to give G-479. G-479 with polarity distributed throughout the molecule was improved over G-868 in many aspects.     

Learning-Induced Expression of Meningeal Ependymin mRNA and Demonstration of Ependymin in Neurons and Glial Cells

Abstract: The turnover of a CNS-specific cell adhesion glycoprotein, ependymin, has earlier been found to increase during periods of neuronal plasticity. Here, ependymin mRNA expression was analyzed by semiquantitative in situ hybridization in goldfish. Learning of an active avoidance response resulted in a significant increase in ependymin mRNA expression 20 min to 4 h after acquisition of the task. In contrast, yoked control animals that were exposed to the same numbers of conditioned and unconditioned stimuli in a random, unpaired manner exhibited a strong down-regulation of ependymin mRNA. Hybridization signals were also increased by injection of anti-ependymin antiserum into brain ventricles. Ependymin mRNA was exclusively localized to reticular-shaped fibroblasts of the inner endomeningeal cell layer. Immunoelectron microscopic investigation, however, revealed ependymin also in distinct neuronal and glial cell populations in which no ependymin mRNA had been detected. Uptake of meningeal protein factors into glial and neuronal cells may therefore be of functional importance for plastic adaptations of the CNS.     

Phytoplankton and physical-chemical features of Tavropos Reservoir,Greece

Phytoplankton biomass values in Tavropos Reservoir, ranging from 92 to 1071 mg m^–3, are within a range characteristic of oligotrophic waters. The seasonal sequence of biomass shows three annual peaks, differing from the monoacmic pattern seen in oligotrophic lakes. This sequence was profoundly affected by changes in water withdrawal and inflow rates. Diatoms, cryptophytes, chrysophytes and dinoflagellates, in that order, were the major constituents of the reservoir phytoplankton. The succession, from diatoms and chrysophytes in late winter-spring, to centric diatoms in late spring-summer and again to diatom-chrysophytes in late autumn was similar to that in oligotrophic lakes.     

Effect of streptococcal pyrogenic exotoxin on rabbit macrophage functions in vitro: mediation by splenic lymphocytes

Streptococcal pyrogenic exotoxin (SPE) showed no direct effect on rabbit macrophage functions in vitro. However, when splenic lymphocytes were added to macrophage cultures, SPE caused marked augmentation of glucose consumption and superoxide anion production, and concomitant inhibition of phagocytosis without loss of cell viability. The SPE effects were demonstrated to be mediated by a soluble factor(s) released from the splenic lymphocytes in response to SPE stimulus.