CD38 is a key enzyme for the survival of mouse microglial BV2 cells

CD38 is a multifunctional enzyme that can not only generate cyclic adenosine diphosphate-ribose (cADPR) - a key Ca(2+) -mobilizing second messenger - by consuming NAD(+), but also hydrolyze extracellular NAD(+). There have been only a small number of studies on the functions of CD38 in the CNS. Brain inflammation plays critical roles in ischemic brain injury and multiple other neurological diseases, in which microglia activation is a key event. In this study we determined the roles of CD38 in the basal survival of mouse BV2 microglia cells by applying CD38 siRNA. Our study found that silencing of CD38 led to significantly decreased survival of the cells. We also found that decreased CD38 levels can lead to apoptosis of the microglial cells, as assessed by flow cytometry-based Annexin V/7-AAD assay, caspase-3 immunostaining and Hoechst staining assays. Our study has further indicated that the CD38 silencing-induced apoptosis is mainly caspase 3-dependent. Collectively, our study has provided the first evidence suggesting that CD38 plays a critical role in the basal survival of microglia, and decreased CD38 can lead to caspase 3-dependent apoptosis of the cells. These results suggest that CD38 may become a therapeutic target for modulating microglial survival in neurological diseases.     

History of Childhood Abuse,Sensation Seeking,and Intimate Partner Violence under/Not under the Influence of a Substance: A Cross-Sectional Study in Russia

Objectives

To examine correlates of perpetration and victimization of intimate partner violence (IPV) under and not under the influence of a substance, we conducted a study among women in Russia.

Methods

In 2011, a cross-sectional survey was conducted among patients receiving services at a clinic for sexually transmitted infections in St. Petersburg, Russia. Multinomial logistic regression was used for analysis.

Results

Of 299 women, 104 (34.8%) and 113 (37.8%) reported a history of IPV perpetration and victimization, respectively. Nearly half (47.1%) of perpetrators and 61.1% of victims reported that the latest IPV event (perpetration and victimization, respectively) was experienced under the influence of a substance. Factors independently associated with IPV victimization under the influence of a substance were alcohol misuse and a higher number of lifetime sex partners, whereas only experience of childhood abuse (emotional and physical abuse) was independently associated with IPV victimization that did not occur under the influence of a substance. Childhood physical abuse, lower age of first sex, sensation seeking, and alcohol misuse were independently associated with IPV perpetration under the influence of a substance, while only childhood abuse (emotional and physical abuse) was independently associated with IPV perpetration that did not occur under the influence of a substance.

Conclusions

IPV under and not under the influence of a substance had different correlates (e.g., alcohol misuse and sensation seeking). Despite the strong association between substance use and IPV, experience of childhood abuse is an important predictor of IPV perpetration and victimization in Russia, above and beyond substance use.     

过硫酸化岩藻多糖硫酸酯

岩藻多糖硫酸酯(fucoidan或fucan sulfate,FS)是一种硫酸多糖,具有多种生物活性。硫酸基团对多糖活性起重要作用,并且多糖活性与硫酸基团含量呈正相关。近些年,国内外研究者对SF进行硫酸化修饰以获得高硫酸基团含量和高活性的过硫酸化岩藻多糖硫酸酯。为促进对FS硫酸化修饰的深入了解,本文对FS活性与硫酸基团含量及位置的关系、过硫酸化方法及过硫酸化岩藻多糖硫酸酯活性的研究进展进行了综述。     

Identification of two core genes in glioblastomas with different isocitrate dehydrogenase mutation status

Molecular Biology Reports - Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been...     

Simvastatin prevents dopaminergic neurodegeneration in experimental parkinsonian models: the association with anti-inflammatory responses

Background

In addition to their original applications to lowering cholesterol, statins display multiple neuroprotective effects. N-methyl-D-aspartate (NMDA) receptors interact closely with the dopaminergic system and are strongly implicated in therapeutic paradigms of Parkinson''s disease (PD). This study aims to investigate how simvastatin impacts on experimental parkinsonian models via regulating NMDA receptors.

Methodology/Principal Findings

Regional changes in NMDA receptors in the rat brain and anxiolytic-like activity were examined after unilateral medial forebrain bundle lesion by 6-hydroxydopamine via a 3-week administration of simvastatin. NMDA receptor alterations in the post-mortem rat brain were detected by [³H]MK-801(Dizocilpine) binding autoradiography. 6-hydroxydopamine treated PC12 was applied to investigate the neuroprotection of simvastatin, the association with NMDA receptors, and the anti-inflammation. 6-hydroxydopamine induced anxiety and the downregulation of NMDA receptors in the hippocampus, CA1(Cornu Ammonis 1 Area), amygdala and caudate putamen was observed in 6-OHDA(6-hydroxydopamine) lesioned rats whereas simvastatin significantly ameliorated the anxiety-like activity and restored the expression of NMDA receptors in examined brain regions. Significant positive correlations were identified between anxiolytic-like activity and the restoration of expression of NMDA receptors in the hippocampus, amygdala and CA1 following simvastatin administration. Simvastatin exerted neuroprotection in 6-hydroxydopamine-lesioned rat brain and 6-hydroxydopamine treated PC12, partially by regulating NMDA receptors, MMP9 (matrix metalloproteinase-9), and TNF-a (tumour necrosis factor-alpha).

Conclusions/Significance

Our results provide strong evidence that NMDA receptor modulation after simvastatin treatment could partially explain its anxiolytic-like activity and anti-inflammatory mechanisms in experimental parkinsonian models. These findings contribute to a better understanding of the critical roles of simvastatin in treating PD via NMDA receptors.     

Acidosis Potentiates Oxidative Neuronal Death by Multiple Mechanisms

Both acidosis and oxidative stress contribute to ischemic brain injury. The present study examines interactions between acidosis and oxidative stress in murine cortical cultures. Acidosis (pH 6.2) was found to potentiate markedly neuronal death induced by H2O2 exposure. To determine if this effect was mediated by decreased antioxidant capacity at low pH, the activities of several antioxidant enzymes were measured. Acidosis was found to reduce the activities of glutathione peroxidase and glutathione S-transferase by 50-60% (p < 0.001) and the activity of glutathione reductase by 20% (p < 0.01) in lysates of the cortical cultures. Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity. Because acidosis may accelerate hydroxyl radical production by the Fenton reaction, the effect of iron chelators was also examined. Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions. These results suggest that the increased cell death produced by severe acidosis during cerebral ischemia may result in part from exacerbation of oxidative injury. This exacerbation may result from both impaired antioxidant enzyme functions and increased intracellular free iron levels.     

Na+吸收对干旱导致的棉花叶片光合系统损伤的缓解作用

以盆栽棉花为材料,在植株高约20 cm时用不同浓度Na Cl溶液浇透后进行持续干旱处理。在干旱处理期间测定叶片叶绿素荧光参数、光合气体交换参数的变化以及植株水分状况和Na+含量,以分析土壤Na Cl施入引起的棉花Na+吸收和积累量的增加对干旱胁迫导致的叶片光合系统损伤的缓解作用及可能原因。结果表明,未用Na Cl处理的棉花植株,其叶片净光合速率随着干旱的延续而持续下降、光合机构在干旱处理后期出现了严重损伤;而Na Cl处理的棉花植株,其叶片净光合速率下降幅度明显小于未用Na Cl处理的,光合机构受损伤程度也较轻或无明显损伤。对各处理棉花植株Na+的吸收和水分状况的测定分析表明,Na Cl处理的植株,其叶片Na+积累显著增加、渗透势降低,细胞膨压显著高于未用Na Cl处理的植株。由此可见,在土壤浇灌Na Cl溶液后的持续干旱条件下,棉花植株吸收和积累Na+增加,降低了组织渗透势、维持了一定的细胞膨压,从而有效缓解了干旱胁迫对叶片光合机构的损伤。     

Prostaglandin E2 binding peptide: a potential modulatory agent which acts through suppressing NF-kappaB signaling in RA

In an earlier study, we found PBP inhibited the progress of adjuvant-induced arthritis (AA). This study was aimed at evaluating the inhibitory effects of PBP in terms of NF-κB activation by using immunohistochemical and immunofluorescent technique in vitro and in vivo. IL-1β and TNF-α in serum were detected by method of ELISA. Immunofluorescent results showed that PBP inhibited NF-κB p65 translocation into nucleus. In vivo imaging showed that treatment with PBP decreased the enzyme labeling signal of NF-κB p65. Immunohistochemical staining revealed that PBP suppressed production of NF-κB p65 subunit in the joints and attenuated the productions of IL-1β and TNF-α in serum from AA. Moreover, NF-κB p65 nucleus translocation was prevented by simultaneous incubation with PBP and PGE2 was decreased by PBP through a feedback cycle. We report the first confirmation of the mimotope of PGE2 receptor EP4 modulatory action.     

Molecular dynamics simulation of carboxy and deoxy human cytoglobin in solution

Cytoglobin (Cgb), the fourth member of the vertebrate heme globin family, is widely expressed in mammalian tissues, and reversibly binds to CO, O₂ and other small ligands. The diverse functions of Cgb may include ligand transport, redox reactions and enzymatic catalysis. Recent studies indicate that Cgb is a potential gene medicine for fibrosis and cancer therapy. In the present work, molecular dynamics (MD) simulations were performed to investigate the functionally related structural properties and dynamic characteristics in carboxy and deoxy human Cgb. The simulation results showed that the loop regions and internal cavities were significantly affected through the binding of an exogenous ligand. The AB, GH and EF loops were found to undergo significant rearrangement and this led to distinct cavity adjustments in Xe2, Xe4 and the distal pocket. In addition, solvent accessibility and torsion angle analyses revealed an interactive distal network comprised of His⁸¹(E7), Leu⁴⁶(B10) and Arg⁸⁴(E10). The MD study of carboxy and deoxy human Cgb revealed that CO-ligated Cgb modulates the protein conformation primarily by loop and cavity rearrangements rather than the heme sliding mechanism found in neuroglobin (Ngb). The significant differences between Cgb and Ngb in the loop and cavity properties are presumably linked to their various biological functions.     

A new species report of Caroperla Kohno, 1946 (Plecoptera: Perlidae) from China

A brief taxonomic synopsis of the genus Caroperla Kohno, 1946 is presented and its further generic delimitation is defined along with a new species, C. siveci sp. n. from the Wuyishan Mountain of Fujian, China. It represents the first report of the genus from China and the third species of the genus. The morphological comparison of the new species with the two other known species is given.