Rutin prevents retinal ganglion cell death and exerts protective effects by regulating transforming growth factor-β2/Smad2/3Akt/PTEN signaling in experimental rat glaucoma

Purpose: To investigate the protective effect of rutin against glaucoma in a rat model, and the mechanisms involved. Methods: Sprague-Dawley rats were injected hypertonic saline in the limbal vein for elevation of intraocular pressure (IOP). Rats in the treatment group were administered rutin at doses of 12.5, 25 or 50 mg/kg orally and daily for 21 days. Results: Rutin markedly (p < 0.05) reduced IOP and prevented loss of retinal ganglion cells (RGCs). The expression of apoptotic pathway proteins, i.e., Bcl-xL, Bcl-2, Bad and Bax were significantly (p < 0.05) regulated by rutin. Moreover, rutin caused a substantial decrease in TGF-β2 expression, and also down-regulated p-Smad2 and p-Smad3 dose-dependently (p < 0.05). Raised levels of collagen I, fibronectin and elastin were effectively down-regulated. Rutin substantially up-regulated the Akt pathway involved in cell survival, and markedly improved the survival of RGCs subjected to hypoxia in vitro (p < 0.05). Conclusion: These results reveal that rutin exerts protective effect against glaucoma in a rat model via a mechanism involving regulation of the TGF-β2/Smad2/3Akt/PTEN signaling pathways. Thus, rutin has potentials for use in the management of glaucoma

Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

<p>Abstract</p> <p>Background</p> <p>Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene <it>eIF-5A2 </it>within the 3q26 region. Functional study has demonstrated the oncogenic role of <it>eIF-5A2 </it>in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of <it>eIF-5A2 </it>in an <it>eIF-5A2 </it>transgenic mouse model.</p> <p>Methods</p> <p>An <it>eIF-5A2 </it>transgenic mouse model was generated using human <it>eIF-5A2 </it>cDNA. The <it>eIF-5A2 </it>transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF) were isolated to further investigate molecular mechanism of <it>eIF-5A2 </it>in aging.</p> <p>Results</p> <p>Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in <it>eIF-5A2 </it>mice. Interestingly, we found that activation of <it>eIF-5A2 </it>repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF) cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (<it>p </it>< 0.05) resulted from an increase in the incidences of misaligned and lagging chromosomal materials, anaphase bridges, and micronuclei in the transgenic mice.</p> <p>Conclusion</p> <p>These observations suggest that <it>eIF-5A2 </it>mouse models could accelerate organismal aging by increasing chromosome instability.</p

Optic nerve head astrocytes contribute to vascular associated effects

PurposeThis study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects.MethodsLC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both in vivo and in vitro, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction.ResultsEndothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both in vivo and in vitro. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia.ConclusionsThere is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research

Thoracic endovascular aortic repair under venoarterial extracorporeal membrane oxygenation for acute aortic dissection patients: a case report

BackgroundOpen repair and replacement of the diseased aorta is still the standard treatment for type A aortic dissection (TAAD) in most patients. In endovascular treatment alone, ensuring adequate blood supply to the brain while covering the dissection with a stent is difficult.Case presentationThis study includes a 71-year-old male patient with type A aortic dissection presented at a recent follow-up examination after having undergone thoracic endovascular aortic repair (TEVAR) plus left subclavian artery chimney stent reconstruction for descending aortic dissection 5 years ago. Preoperative computed tomographic angiography, computed tomographic perfusion, and transcranial Doppler showed an intact cerebral arterial ring and good collateral circulation. We successfully performed an endovascular repair of the thoracic aorta with venoarterial extracorporeal membrane oxygenation (V-A ECMO) to protect the craniocerebral blood supply, greatly increase the safety of the operation, and ensure a good prognosis.ConclusionTEVAR under V-A ECMO protection is beneficial for patients with TAAD because of its minimal trauma, rapid recovery, few complications, and low mortality

5-Demethylnobiletin mediates cell cycle arrest and apoptosis via the ERK1/2/AKT/STAT3 signaling pathways in glioblastoma cells

5-Demethylnobiletin is the active ingredient in citrus polymethoxyflavones that could inhibit the proliferation of several tumor cells. However, the anti-tumor effect of 5-Demethylnobiletin on glioblastoma and the underlying molecular mechanisms are remains unknown. In our study, 5-Demethylnobiletin markedly inhibited the viability, migration and invasion of glioblastoma U87-MG, A172 and U251 cells. Further research revealed that 5-Demethylnobiletin induces cell cycle arrest at the G0/G1 phase in glioblastoma cells by downregulating Cyclin D1 and CDK6 expression levels. Furthermore, 5-Demethylnobiletin significantly induced glioblastoma cells apoptosis by upregulating the protein levels of Bax and downregulating the protein level of Bcl-2, subsequently increasing the expression of cleaved caspase-3 and cleaved caspase-9. Mechanically, 5-Demethylnobiletin trigged G0/G1 phase arrest and apoptosis by inhibiting the ERK1/2, AKT and STAT3 signaling pathway. Furthermore, 5-Demethylnobiletin inhibition of U87-MG cell growth was reproducible in vivo model. Therefore, 5-Demethylnobiletin is a promising bioactive agent that might be used as glioblastoma treatment drug

Individuals’ preference on reading pathways influences the involvement of neural pathways in phonological learning

IntroductionExisting behavioral and neuroimaging studies revealed inter-individual variability in the selection of the two phonological routes in word reading. However, it is not clear how individuals’ preferred reading pathways/strategies modulate the involvement of a certain brain region for phonological learning in a new language, and consequently affect their behavioral performance on phonological access.MethodsTo address this question, the present study recruited a group of native Chinese speakers to learn two sets of artificial language characters, respectively, in addressed-phonology training (i.e., whole-word mapping) and assembled-phonology training conditions (i.e., grapheme-to-phoneme mapping).ResultsBehavioral results showed that the more lexical pathways participants preferred, the better they performed on newly-acquired addressed characters relative to assembled characters. More importantly, neuroimaging results showed that participants who preferred lexical pathway in phonological access show less involvement of brain regions for addressed phonology (e.g., the bilateral orbitofrontal cortex and right pars triangularis) in the processing of newly-acquired addressed characters.ConclusionThese results indicated that phonological access via the preferred pathway required less neural resources to achieve better behavioral performance. These above results provide direct neuroimaging evidence for the influence of reading pathway preference on phonological learning

Transgenic CHD1L Expression in Mouse Induces Spontaneous Tumors

Background: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.published_or_final_versio

Two-and three-electrode impedance spectroscopic studies of graphite electrode in the first lithiation

The first lithiation of graphite electrode was investigated by electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM) in a two-electrode button cell and a three-electrode glass cell. The results demonstrate that the study of the variation of EIS feature of the graphite electrode in the two-electrode button cell with electrode polarization potential decreasing in the first lithiation cannot be used to investigate the formation mechanism of the solid electrolyte interphase (SEI) film. However, the formation and growth process of the SEI film can be acquired by investigating the variation of EIS features of the graphite electrode in the three-electrode glass cell with the decrease of electrode polarization potential in the first lithiation. Moreover, the results also point out that the SEI film on graphite electrode is mainly formed between 1.0 and 0.6 V in the first lithiation.Major State Basic Research Development Program of China [2009CB220102