Surface lipids of Sphaerotheca fuliginea spores

The major components (50%) of the surface lipid extract of fungal spores (5.6% of dry spore wt) of Sphaerotheca fuliginea are esters of primary alcohols and fatty acids. Esters (15%) of primary alcohols and a Δ^2t acid are present. The major acid moieties of the alkyl esters are C₂₂ and C₂₄ and of the Δ^2t alkyl ester is Δ^2t C₂₂; for both classes eicosanol is the major primary alcohol. The major ester of each class was concluded to be eicosanyl docosanoate and eicosanyl trans-2-docosenoate. Minor components are saturated and Δ^2t methyl and diol diesters and free fatty acids. The major acid moieties of the diol diesters are C₂₂ and C₂₄ and the major diol is 1,12-dodecanediol.     

Modification of the intracellular sugar content alters the incidence of freeze-induced membrane lesions of protoplasts isolated from Arabidopsis thaliana leaves

Sugar content and freezing tolerance of protoplasts of Arabidopsis thaliana leaves were manipulated by incubating seedlings in a sucrose solution before protoplast isolation. Incubation in a 400 mM sucrose solution at 2 °C in the dark increased their freezing tolerance equivalent to that achieved after a conventional cold acclimation at 2 °C. The increased freezing tolerance was due to a decrease in the incidence of freeze‐induced lesions: expansion‐induced lysis (EIL) between ?2 and ?4 °C and loss of osmotic responsiveness (LOR) between ?5 and ?12 °C. The concentration of sucrose in the incubation medium required to minimize the incidence of the lesions was substantially different: 10–35 mM for EIL and 30–400 mM for LOR. Incubation in the sucrose solution at 23 °C decreased LOR only at ?5 and ?6 °C but less than that incubated at 2 °C, and there was no effect on EIL. Incubation in sorbitol solutions at 2 °C also decreased LOR at ?5 and ?6 °C but much less than in the sucrose solution. These results suggest that low concentrations of sucrose act as a metabolic substrate for the low‐temperature‐induced alterations required for the amelioration of EIL and, at higher concentrations, sucrose has a direct cryoprotective effect to minimize LOR.     

Neuronal Nogo-A upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina

Nogo-A, an axonal growth inhibitory protein known to be mostly present in CNS myelin, was upregulated in retinal ganglion cells (RGCs) after optic nerve injury in adult mice. Nogo-A increased concomitantly with the endoplasmic reticulum stress (ER stress) marker C/EBP homologous protein (CHOP), but CHOP immunostaining and the apoptosis marker annexin V did not co-localize with Nogo-A in individual RGC cell bodies, suggesting that injury-induced Nogo-A upregulation is not involved in axotomy-induced cell death. Silencing Nogo-A with an adeno-associated virus serotype 2 containing a short hairpin RNA (AAV2.shRNA-Nogo-A) or Nogo-A gene ablation in knock-out (KO) animals had little effect on the lesion-induced cell stress or death. On the other hand, Nogo-A overexpression mediated by AAV2.Nogo-A exacerbated RGC cell death after injury. Strikingly, however, injury-induced sprouting of the cut axons and the expression of growth-associated molecules were markedly reduced by AAV2.shRNA-Nogo-A. The axonal growth in the optic nerve activated by the intraocular injection of the inflammatory molecule Pam3Cys tended to be lower in Nogo-A KO mice than in WT mice. Nogo-A overexpression in RGCs in vivo or in the neuronal cell line F11 in vitro promoted regeneration, demonstrating a positive, cell-autonomous role for neuronal Nogo-A in the modulation of axonal regeneration.     

Honokiol: A non-adipogenic PPARγ agonist from nature

Background

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators.

Methods

We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists.

Results

The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain.

Conclusion

We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo.

General significance

This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.     

Protective effects of therapeutic hypothermia on renal injury in an asphyxial cardiac arrest rat model

Cardiac arrest (CA) is a leading cause of mortality worldwide. Most of post-resuscitation related deaths are due to post-cardiac arrest syndrome (PCAS). After cardiopulmonary resuscitation (CPR), return of spontaneous circulation (ROSC) leads to renal ischemia-reperfusion injury, also known as PCAS. Many studies have focused on brain and heart injuries after ROSC, but renal failure has largely been ignored. Therefore, we investigated the protective effects of therapeutic hypothermia (TH) on asphyxial CA-induced renal injury in rats.Thirty rats were randomly divided into five groups: 1) the control group (sham); 2) the normothermic CA (nor.); 3) a normothermic CA group that received TH immediately within 2 h after CPR (Hypo. 2 hrs); 4) a normothermic CA group that received TH within 4 h after CPR (Hypo. 4 hrs); and 5) a normothermia CA group that received TH within 6 h after CPR (Hypo. 6 h). One day after CPR, all rats were sacrificed. Compared with the normothermic CA group, the TH groups demonstrated significantly increased survival rate (P < 0.05); decreased serum blood urea nitrogen, creatinine, and lactate dehydrogenase levels; and lower histological damage degree and malondialdehyde concentration in their renal tissue. Terminal deoxynucleotidyl transferase dUTP nick end labeling stain revealed that the number of apoptotic cells significantly decreased after 4 h and 6 h of TH compared to the results seen in the normothermic CA group. Moreover, TH downregulated the expression of cyclooxygenase-2 in the renal cortex compared to the normothermic CA group one day after CPR. These results suggest that TH exerts anti-apoptotic, anti-inflammatory, and anti-oxidative effects immediately after ROSC that protect against renal injury.     

失神经骨骼肌萎缩的研究现状及进展

当今骨科领域,周围神经损伤一直影响着患者疗效。肌萎缩的发生,细胞凋亡导致骨骼肌萎缩,神经-肌肉接头处营养因子的代谢发生障碍,肌卫星细胞的减少,生长因子以及线粒体和各种酶的变化都是失神经骨骼肌萎缩的机制。电刺激法,保护神经元,生长因子,神经植入提高神经再生速度以及被动活动可以有效治疗患者。失神经骨骼肌萎缩的研究进展也趋于完善。     

急性出血坏死性胰腺炎肝损伤中TLR2, 4mRNA和蛋白的表达

目的:观察急性出血坏死性胰腺炎肝损伤中TLR-2、TLR4的表达水平,分析TLR2和TLR4在AHNP肝损伤中的表达意义。方法:48只成年Wistar大鼠作为实验动物,随机分为对照组和造模组各24只,造模组利用牛磺胆酸钠建立AHNP模型,在造模后3 h、12 h以及24 h时,每组分别各取8只大鼠,应用RT-PCR法检测TLR2、TLR4mRNA表达水平,应用Western blot检测肝脏组织中TLR2、TLR4蛋白表达水平。结果:造模后,造模组TLR2mRNA、TLR4mRNA、TLR2蛋白、TLR4蛋白显著升高,且在造模后12 h出现峰值,与同时段对照组相比差异显著(P0.01)。结论:急性出血坏死性胰腺炎肝损伤组织中TLR2、TLR4mRNA和蛋白表达水平异常升高,TLR2、TLR4可能参与了急性出血坏死性胰腺炎肝损伤发生发展过程。     

野战微创介入方舱内实施对脾脏损伤的快速救治实验

目的:探讨在战争或自然灾害等野战特定条件下,使用野战微创介入方舱,现场对脾脏创伤实施快速微创介入栓塞救治的可行性及效果,形成介入方舱内对脾脏进行快速介入栓塞救治的流程。方法:野战条件下,展开野战介入方舱,在血管造影机下对大动物(狗)脾动脉进行血管内穿刺造模,建立脾动脉损伤模型,按照方舱内快速微创介入救治的流程,对脾动脉受损伤的动物(狗)实施腹部内受损脾动脉的栓塞止血术式。结果:按照设定的预案,对脾损伤的模型动物实施早期介入栓塞脾动脉止血治疗,全部实验动物2周存活率为100%。结论:野战条件下,考虑到转运风险时或者伤情十分紧急时,靠近事发现场展开野战微创介入方舱,对腹部脾脏损伤开展紧急介入栓塞止血救治,不仅可为病人后续的治疗争取宝贵时间,大幅降低一线伤死率,而且脾脏的保全也提高伤员愈后的生活质量。     

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s).