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The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.

Yangmai-13 (YM13) is a wheat cultivar with weak gluten fractions. In contrast, Zhenmai-168 (ZM168) is an elite wheat cultivar known for its strong gluten fractions and has been widely used in a number of breeding programs. However, the genetic mechanisms underlying the gluten signatures of ZM168 remain largely unclear. To address this, we combined RNA-seq and PacBio full-length sequencing technology to unveil the potential mechanisms of ZM168 grain quality. A total of 44,709 transcripts were identified in Y13N (YM13 treated with nitrogen) and 51,942 transcripts in Z168N (ZM168 treated with nitrogen), including 28,016 and 28,626 novel isoforms in Y13N and Z168N, respectively. Five hundred and eighty-four differential alternative splicing (AS) events and 491 long noncoding RNAs (lncRNAs) were discovered. Incorporating the sodium-dodecyl-sulfate (SDS) sedimentation volume (SSV) trait, both weighted gene coexpression network analysis (WGCNA) and multiscale embedded gene coexpression network analysis (MEGENA) were employed for network construction and prediction of key drivers. Fifteen new candidates have emerged in association with SSV, including 4 transcription factors (TFs) and 11 transcripts that partake in the post-translational modification pathway. The transcriptome atlas provides new perspectives on wheat grain quality and would be beneficial for developing promising strategies for breeding programs. [ABSTRACT FROM AUTHOR]

Persistent neuropathic pain (NP) causes future development of neurodegenerative diseases, e.g., Alzheimer' disease, and thus needs to be optimally treated. Surgically-induced neuropathic pain (SNPP) is a persistent pain that occurs in nearly half of the individuals after common operations. Here, we showed that specific activation of 5-hydroxytryptamine (5-HT) type 2A receptors by systemic administration of TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide] improved the function of potassium chloride cotransporter 2 (KCC2), resulting in reduction in neuropathic pain after chronic constriction injury (CCI), a rat model that mimics SNPP. Moreover, TCB-2 administration attenuated both mechanical and thermal hyperalgesia, likely through augmentation of dorsal horn KCC2 levels, since this effect was abolished by intrathecal provision of dihydroindenyl oxy alkanoic acid (DIOA), which blocked the effects of KCC2. Furthermore, TCB-2-mediated re-activation of KCC2 likely reduces future development of neurodegeneration in rats. Together, our data support further studies on the possibility of using this strategy to reduce postoperative pain and future neurodegenerative disorders in clinic. [ABSTRACT FROM AUTHOR]

Purpose: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. Methods: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. Results: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. Conclusions: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression. [ABSTRACT FROM AUTHOR]

Since anoctamin 1 ANO1 ( TMEM16A) was found to be a molecular component of Ca2+-activated Cl− channels, its role in tumorigenesis has gained attention at a fast pace. ANO1 overexpression frequently occurs in the cancer tissues along with 11q13 chromosome amplification. Poor prognosis of many types of cancers has been closely correlated with ANO1 gene amplification and protein overexpression. ANO1 is now considered an excellent biomarker for certain cancers. Recent research suggests that it is the channel function of ANO1 that is involved in the tumorigenesis. However, how the overexpression of the functional ANO1 causes malignant transformation of tissues via signaling pathways, for example, MAPK remains to be investigated. Clarification of the reasons in future will avail to make ANO1 as a target for cancer treatment. [ABSTRACT FROM AUTHOR]

Background  Intraventricular extension of a parenchymal hemorrhage is an independent predictor of poor outcome and might be complicated by delayed hydrocephalus. We describe a method for the rapid and effective removal of a lateral ventricular hematoma via catheter-based puncture and aspiration. Methods  A catheter-based aspiration of a ventricular hematoma via a frontal eminence (FE) puncture was performed in 10 patients with thalamic and ganglionic hemorrhage perforating into the lateral ventricle. Paralleling the long axis of the lateral ventricle, a flexible silicone catheter was moved anteroposteriorly and rotated simultaneously to facilitate clot aspiration and removal. Computed tomography scans before and after surgery were compared for assessment of ventricular clot volume, Graeb score, and the ventriculocranial ratio (VCR). The Glasgow Coma Scale (GCS) score and Glasgow Outcome Scale (GOS) score were assessed at 14 days and 12 months following surgery, respectively. Results  In all 10 patients, catheter-based aspiration resulted in substantial hematoma removal with a clearance rate of 64.9%, a reduced Graeb score by 61.8%, and an elevated GCS score by 52.7%. The procedure was performed safely without occurrence of another hemorrhage, infection, and catheter obstruction in any case. At 12-month follow-up, VCR was reduced by 22.5%, no delayed hydrocephalus occurred, and a favorable outcome with an average GOS of 4.6 was observed in this small cohort of patients. Conclusion  Catheter-based aspiration of a ventricular hematoma via FE puncture rapidly, efficiently, and safely reduced the clot in the ventricular system, prevented delayed hydrocephalus sufficiently, and produced a favorable outcome., (Georg Thieme Verlag KG Stuttgart · New York.)

Since anoctamin 1 ANO1 (TMEM16A) was found to be a molecular component of Ca(2+) -activated Cl(-) channels, its role in tumorigenesis has gained attention at a fast pace. ANO1 overexpression frequently occurs in the cancer tissues along with 11q13 chromosome amplification. Poor prognosis of many types of cancers has been closely correlated with ANO1 gene amplification and protein overexpression. ANO1 is now considered an excellent biomarker for certain cancers. Recent research suggests that it is the channel function of ANO1 that is involved in the tumorigenesis. However, how the overexpression of the functional ANO1 causes malignant transformation of tissues via signaling pathways, for example, MAPK remains to be investigated. Clarification of the reasons in future will avail to make ANO1 as a target for cancer treatment., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To construct a recombinant adenoviral vector carrying and co-expressing vascular endothelial growth factor 165 (VEGF165) and stromal cell derived factor 1 (SDF-1) and explore its co-expression in ischemic brain tissue in rats., Methods: The VEGF165 and SDF-1 genes were directionally connected with internal ribosome entry site (IRES). And the double gene co-expression recombinant shuttle plasmid pDC316-VEGF165-IRES-SDF-1 was built with homologous recombination. The resultant plasmid pDC316-VEGF165-IRES-SDF-1 and backbone plasmid pBHGlox_E1, 3Cre were transfected into HEK293 cells by liposome and the recombinant adenoviral particles capable of infection were acquired. With the rounds of amplification, the purified adenoviral vector Ad5-VEGF165-IRES-SDF-1 was obtained with a titer of up to 1×10(10) IU/ml. The rat model of middle cerebral artery occlusion (MCAO) was established by intra-luminal suturing. And the viral vectors were transfused into the lateral ventricle by a stereotactic microinjection. The expressions of VEGF165 and SDF-1 in ischemic brain tissue were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot., Results: The results of PCR, double enzyme digestion and gene sequencing showed that both the recombinant plasmid and the constructed adenoviral vector were expressed. And the adenoviral vector Ad5-VEGF165-IRES-SDF-1 could mediate a co-expression of VEGF165 and SDF-1 in ischemic cerebral tissue., Conclusion: The recombinant adenoviral vector carrying VEGF165 and SDF-1 are successfully constructed. And Ad5-VEGF165-IRES-SDF-1 may mediate a co-expression of VEGF165 and SDF-1 in ischemic cerebral tissue of rats.