Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors

Abstract Background Reprogramming of cancers into normal-like tissues is an innovative strategy for cancer treatment. Recent reports demonstrate that defined factors can reprogram cancer cells into pluripotent stem cells. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor in humans. Despite multimodal therapy, the outcome for patients with GBM is still poor. Therefore, developing novel therapeutic strategy is a critical requirement. Methods We have developed a novel reprogramming method that uses a conceptually unique strategy for GBM treatment. We screened a kinase inhibitor library to find which candidate inhibitors under reprogramming condition can reprogram GBM cells into neurons. The induced neurons are identified whether functional and loss of tumorigenicity. Results We have found that mTOR and ROCK kinase inhibitors are sufficient to reprogram GBM cells into neural-like cells and “normal” neurons. The induced neurons expressed neuron-specific proteins, generated action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis showed that the induced neurons had a profile different from GBM cells and were similar to that of control neurons induced by established methods. In vitro and in vivo tumorigenesis assays showed that induced neurons lost their proliferation ability and tumorigenicity. Moreover, reprogramming treatment with ROCK-mTOR inhibitors prevented GBM local recurrence in mice. Conclusion This study indicates that ROCK and mTOR inhibitors-based reprogramming treatment prevents GBM local recurrence. Currently ROCK-mTOR inhibitors are used as anti-tumor drugs in patients, so this reprogramming strategy has significant potential to move rapidly toward clinical trials

Safety and efficacy of etomidate and propofol anesthesia in elderly patients undergoing gastroscopy: A double-blind randomized clinical study

The aim of the present study is to compare the safety, efficacy and cost effectiveness of anesthetic regimens by compound, using etomidate and propofol in elderly patients undergoing gastroscopy. A total of 200 volunteers (65–79 years of age) scheduled for gastroscopy under anesthesia were randomly divided into the following groups: P, propofol (1.5–2.0 mg/kg); E, etomidate (0.15-0.2 mg/kg); P+E, propofol (0.75–1 mg/kg) followed by etomidate (0.075-0.1 mg/kg); and E+P, etomidate (0.075-0.01 mg/kg) followed by propofol (0.75–1 mg/kg). Vital signs and bispectral index were monitored at different time points. Complications, induction and examination time, anesthesia duration, and recovery and discharge time were recorded. At the end of the procedure, the satisfaction of patients, endoscopists and the anesthetist were evaluated. The recovery (6.1±1.2 h) and discharge times (24.8±2.8 h) in group E were significantly longer compared with groups P, P+E and E+P (P<0.05). The occurrence of injection pain in group P+E was significantly higher compared with the other three groups (P<0.05). In addition, the incidence of myoclonus and post-operative nausea and vomiting were significantly higher in group P+E compared with the other three groups (P<0.05). There was no statistical difference among the four groups with regards to the patients' immediate, post-procedure satisfaction (P>0.05). Furthermore, there was no difference in the satisfaction of anesthesia, as evaluated by the anesthetist and endoscopist, among the four groups (P>0.05). The present study demonstrates that anesthesia for gastroscopy in elderly patients can be safely and effectively accomplished using a drug regimen that combines propofol with etomidate. The combined use of propofol and etomidate has unique characteristics which improve hemodynamic stability, cause minimal respiratory depression and less side effects, provide rapid return to full activity and result in high levels of satisfaction

Why Is Maternal Control Harmful? The Relation between Maternal Control, Insecure Attachment and Antisocial Personality Disorder Features in Chinese College Students:A Sequential Mediation Model

Background: Previous work has indicated that a negative parenting style is associated with antisocial personality disorder features in Chinese college students, yet few studies have explored the unique role of negative mothering in children&rsquo;s antisocial personality disorder. Methods: The current study mainly examined the sequential mediation effect of parental antipathy and neglect (PAN) and mother negative loving (a form of insecure attachment) in the association between mother control and adulthood antisocial personality disorder features (ASPD features) in the framework of attachment theory and cognitive&ndash;behavioral theory. A community sample of 1547 Chinese college students filled in the Parental Bonding Instrument, the Childhood Experience of Care and Abuse Questionnaire, the Adult Attachment Questionnaire and the Personality Diagnostic Questionnaire-4+. Results: A sequential mediation model analysis showed that maternal control significantly predicted PAN, mother negative loving, as well as ASPD features. Conclusions: Mother control and mother negative loving appear to advance on the development and exacerbation of ASPD features in college students

Phosphocreatine Preconditioning Attenuates Apoptosis in Ischemia-Reperfusion Injury of Rat Brain

Phosphocreatine (PCr) is an endogenous compound containing high-energy phosphate bonds. It has been confirmed that PCr is effective in preventing and treating cardiac and renal ischemia-reperfusion injury. In this study, rat cerebral ischemia-reperfusion injury models were constructed. Apoptotic cells in the cortex region were measured by TUNEL method. Malondialdehyde (MDA) content was detected by chromatometry, and calmodulin (CaM) activity was detected by ELISA. Compared with sham-operated group (sham group), TUNEL-positive cells, MDA, and level of CaM activity increased in ischemia-reperfusion group (I/R group) and PCr preconditioning group (PCr group); compared with I/R group, TUNEL-positive cells, MDA content, and level of CaM activity decreased in PCr group. This study indicated that PCr can decrease the morphological damage and the neuron apoptosis of the ischemia-reperfusion injury brain through attenuating abnormalities of calcium balance and production of oxygen free radicals

Research and application of rapid detection of amylopectin in wine industry

Sorghum is the main raw material for Chinese liquor brewing, and the brewing Strong or Sauce-flavor liquor has more special requirements for the original cooking properties. In order to shorten the time and reduce the human error effectively during the operation of amylopectin detection, a rapid detection method was established for the detection of amylopectin content in this experiment, the performance evaluation of the method and instrument was carried out, and the rapid detection method was compared with the national standard method, the results showed that there was no significant difference between the two methods

Study of Highly Pixelated CdZnTe Detector for PET Applications

AbstractWe are investigating the feasibility of a high-resolution PET insert device based on a Cadmium Zinc Telluride (CdZnTe) detector with 350μm anode pixel pitch to be integrated into a conventional animal PET scanner to improve its image resolution to sub-500 micrometer range. In this work, we have used a simplified version of the future 2048-pixel CdZnTe planar detector with 250μm anode pixel size and 100μm gap. This simplified 9 anode pixel structure makes it possible to conduct experiments without a complete ASIC readout system (with 2048 channels) that is still under development. We characterized this CdZnTe detector by investigating it charge sharing, spatial resolution, and energy resolution. We imaged a Na-22 point source using the coincidence events between this 350μm pixelated CdZnTe detector and a lutetium oxyorthosilicate (LSO) based Siemens Inveon PET detector. The reconstructed PET image shows a resolution of 590μm full width at half maximum (FWHM) by using single-pixel events. When we included double-pixel charge sharing events in the image reconstruction, the image resolution was degraded to 655μm, but the sensitivity of the coincidence system increased 2.5 to 3 times

Effects of a Chinese Herbal Medicine, Guan-Jen-Huang (Aeginetia indica Linn.), on Renal Cancer Cell Growth and Metastasis

Aeginetia indica Linn. (Guan-Jen-Huang, GJH), a traditional Chinese herb, has the potential to be an immunomodulatory agent. The purpose of this study was to explore the effect of GJH in the treatment of renal cancer. Concentration-effect curves for the influence of GJH on cellular proliferation showed a biphasic shape. Besides, GJH had a synergistic effect on cytotoxicity when combined with 5-fluorouracil (5-FU)which may be due to the alternation of the chemotherapeutic agent resistance-related genes and due to the synergistic effects on apoptosis. In addition, treatment with GJH extract markedly reduced 786-O cell adherence to human umbilical vein endothelial cells (HUVECs) and decreased 786-O cell migration and invasion. In a xenograft animal model, GJH extract had an inhibitory effect on tumor cell-induced metastasis. Moreover, western blot analysis showed that the expression of intercellular adhesion molecule-1 (ICAM-1) in 786-O cells was significantly decreased by treatment with GJH extract through inactivation of nuclear factor-κB (NF–κB). These results suggest that GJH extract has a synergistic effect on apoptosis induced by chemotherapeutic agents and an inhibitory effect on cell adhesion, migration, and invasion, providing evidence for the use of water-based extracts of GJH as novel alternative therapeutic agents in the treatment of human renal cancer

Learning from Rich Semantics and Coarse Locations for Long-tailed Object Detection

Long-tailed object detection (LTOD) aims to handle the extreme data imbalance in real-world datasets, where many tail classes have scarce instances. One popular strategy is to explore extra data with image-level labels, yet it produces limited results due to (1) semantic ambiguity -- an image-level label only captures a salient part of the image, ignoring the remaining rich semantics within the image; and (2) location sensitivity -- the label highly depends on the locations and crops of the original image, which may change after data transformations like random cropping. To remedy this, we propose RichSem, a simple but effective method, which is robust to learn rich semantics from coarse locations without the need of accurate bounding boxes. RichSem leverages rich semantics from images, which are then served as additional soft supervision for training detectors. Specifically, we add a semantic branch to our detector to learn these soft semantics and enhance feature representations for long-tailed object detection. The semantic branch is only used for training and is removed during inference. RichSem achieves consistent improvements on both overall and rare-category of LVIS under different backbones and detectors. Our method achieves state-of-the-art performance without requiring complex training and testing procedures. Moreover, we show the effectiveness of our method on other long-tailed datasets with additional experiments. Code is available at \url{https://github.com/MengLcool/RichSem}.Comment: Accepted by NeurIPS202