Neuroprotection against CCl4 induced brain damage with crocin in Wistar rats

Owing to its lipophilic property, carbon tetrachloride (CCl₄) is rapidly absorbed by both the liver and brain. We investigated the protective effects of crocin against brain damage caused by CCl₄. Fifty rats were divided into five groups of ten: control, corn oil, crocin, CCl₄ and CCl₄ + crocin. CCl₄ administration decreased glutathione (GSH) and total antioxidant status (TAS) levels, and catalase (CAT) activity, while significant increases were observed in malondialdehyde (MDA) and total oxidant status (TOS) levels and superoxide dismutase (SOD) activity. The cerebral cortex nuclear lamina developed a spongy appearance, neuronal degeneration was observed in the hippocampus, and heterochromatic and pyknotic neurons with increased cytoplasmic eosinophilia were observed in the hippocampus after CCl₄ treatment. Because crocin exhibits strong antioxidant properties, crocin treatment increased GSH and TAS levels and CAT activities, and decreased MDA and TOS levels and SOD activity; significant improvements also were observed in histologic architecture. We found that crocin administration nearly eliminated CCl₄ induced brain damage by preventing oxidative stress.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko‐Batuangus Nature Reserve,Sulawesi, Indonesia

In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared‐teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared‐teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the relevance of the social style concept in the assessment of the degree of tolerance/despotism in social systems. Am. J. Primatol. 75:361‐375, 2013. © 2013 Wiley Periodicals, Inc.     

Mutants impaired in vacuolar metal mobilization identify chloroplasts as a target for cadmium hypersensitivity in Arabidopsis thaliana

Cadmium (Cd) is highly toxic to plants causing growth reduction and chlorosis. It binds thiols and competes with essential transition metals. It affects major biochemical processes such as photosynthesis and the redox balance, but the connection between cadmium effects at the biochemical level and its deleterious effect on growth has seldom been established. In this study, two Cd hypersensitive mutants, cad1‐3 impaired in phytochelatin synthase (PCS1), and nramp3nramp4 impaired in release of vacuolar metal stores, have been compared. The analysis combines genetics with measurements of photosynthetic and antioxidant functions. Loss of AtNRAMP3 and AtNRAMP4 function or of PCS1 function leads to comparable Cd sensitivity. Root Cd hypersensitivities conferred by cad1‐3 and nramp3nramp4 are cumulative. The two mutants contrast in their tolerance to oxidative stress. In nramp3nramp4, the photosynthetic apparatus is severely affected by Cd, whereas it is much less affected in cad1‐3. In agreement with chloroplast being a prime target for Cd toxicity in nramp3nramp4, the Cd hypersensitivity of this mutant is alleviated in the dark. The Cd hypersensitivity of nramp3nramp4 mutant highlights the critical role of vacuolar metal stores to supply essential metals to plastids and maintain photosynthetic function under Cd and oxidative stresses.     

Differential effect of long-term drug selection with doxorubicin and vorinostat on neuroblastoma cells with cancer stem cell characteristics

Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells'' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients.     

Effects of curcumin on methyl methanesulfonate damage to mouse kidney

Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the effects of curcumin on MMS treated mouse kidneys. Twenty-four mice were divided into four equal groups: controls injected with saline, a group injected with 40 mg/kg MMS, a group injected with 40 mg/kg MMS and given 100 mg/kg curcumin by gavage, and a group given 100 mg/kg curcumin by gavage. MMS caused congestion and vacuole formation, and elevated the apoptotic index significantly, but had no other effect on kidney tissue. Curcumin improved the congestion and vacuole formation caused by MMS and decreased the apoptotic index. Curcumin administered with MMS appears to decrease the deleterious effects of MMS on the kidney.     

Characterization of SPACR, a sialoprotein associated with cones and rods present in the interphotoreceptor matrix of the human retina: immunological and lectin binding analysis

Rod and cone photoreceptors project from the outer retinal surface into a carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM glycoconjugates are distributed around rods and cones. Wheat germ agglutinin (WGA) strongly decorates the rod matrix domains and weakly decorates the cone matrix domains. This study characterizes the major WGA-binding glycoprotein in the human IPM, which we refer to as SPACR (sialoprotein associated with cones and rods). SPACR, which has a molecular weight of 147 kDa, was isolated and purified from the IPM by lectin affinity chromatography. A polyclonal antibody to SPACR was prepared that colocalizes in tissue preparations with WGA-binding domains in the IPM. Sequential digestion of SPACR with N- and O- glycosidases results in a systematic increase in electrophorectic mobility, indicating the presence of both N- and O-linked glycoconjugates. Complete deglycosylation results in a reduction in the relative molecular mass of SPACR by about 30%. Analysis of lectin binding allowed us to identify some of the structural characteristics of SPACR glycoconjugates. Treatment with neuraminidase exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA), specific for alpha2-6 linked sialic acid, does not, indicating that the dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate, NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR suggests that this glycoprotein may contribute substantially to the polyanionic nature of the IPM. The carbohydrate chains present on SPACR could also provide sites for extensive crosslinking and participate in the formation of the ordered IPM lattice that surrounds the elongate photoreceptors projecting from the outer retinal surface.      

每搏量变异度在围手术期容量治疗监测中的应用

每搏量变异度是动态的容量监测指标.机械通气患者心肺的相互作用是每搏量变异度的产生基础,通过动脉压力波形分析技术可以进行连续监测.每搏量变异度能够准确预测容量治疗反应,与静态的血流动力学参数相比,对于优化心输出量和组织氧供更有优势,但也存在一定的局限性.每搏量变异度受多种因素影响且不能用于自主呼吸和心律失常的患者.临床应用时应该综合考虑其影响因素,结合其他的指标和方法指导容量治疗.     

白马雪山国家级自然保护区典型森林生态系统服务

生态系统服务是近年来生态学研究的热点领域,对关键区域生态系统服务的研究具有重要意义.云南省白马雪山国家级自然保护区地处青藏高原南延部分,拥有独特的地理位置,是生物多样性保护的热点区域.本文对该保护区森林生态系统的生物量与生产力、水源涵养、营养物质循环等3项服务的功能量进行了评估.结果表明:保护区森林总生物量2215.86×104t,生产力171.84×104t·a-1;水源涵养量11964.56×104m3;N、P、K年吸收量分别为26025.94t、2638.57t、12016.85 t.研究表明,保护区森林生态效益显著,对于维持当地以及周边地区的生态安全具有重要意义.