Nonintubated spontaneous ventilation versus intubated mechanical ventilation anesthesia for video-assisted thoracic surgery in terms of perioperative complications and practitioners' workload assessments: a pilot randomized control study.

BACKGROUND: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. METHODS: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. RESULTS: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045-0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29-52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5-38.5], p = 0.814). CONCLUSION: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022.

Manipulating microRNA miR408 enhances both biomass yield and saccharification efficiency in poplar.

The conversion of lignocellulosic feedstocks to fermentable sugar for biofuel production is inefficient, and most strategies to enhance efficiency directly target lignin biosynthesis, with associated negative growth impacts. Here we demonstrate, for both laboratory- and field-grown plants, that expression of Pag-miR408 in poplar (Populus alba × P. glandulosa) significantly enhances saccharification, with no requirement for acid-pretreatment, while promoting plant growth. The overexpression plants show increased accessibility of cell walls to cellulase and scaffoldin cellulose-binding modules. Conversely, Pag-miR408 loss-of-function poplar shows decreased cell wall accessibility. Overexpression of Pag-miR408 targets three Pag-LACCASES, delays lignification, and modestly reduces lignin content, S/G ratio and degree of lignin polymerization. Meanwhile, the LACCASE loss of function mutants exhibit significantly increased growth and cell wall accessibility in xylem. Our study shows how Pag-miR408 regulates lignification and secondary growth, and suggest an effective approach towards enhancing biomass yield and saccharification efficiency in a major bioenergy crop.

PagUNE12 encodes a basic helix-loop-helix transcription factor that regulates the development of secondary vascular tissue in poplar.

Secondary growth in woody plants generates new cells and tissues via the activity of the vascular cambium and drives the radial expansion of stems and roots. It is regulated by a series of endogenous factors, especially transcription factors. Here, we cloned the basic helix-loop-helix (bHLH) transcription factor gene UNFERTILIZED EMBRYO SAC12 (UNE12) from poplar (Populus alba × Populus glandulosa Uyeki) and used biochemical, molecular, and cytological assays to investigate the biological functions and regulatory mechanism of PagUNE12. PagUNE12 mainly localized in the nucleus and possessed transcriptional activation activity. It was widely expressed in vascular tissues, including primary phloem and xylem and secondary phloem and xylem. Poplar plants overexpressing PagUNE12 showed significantly reduced plant height, shorter internodes, and curled leaves compared with wild-type plants. Optical microscopy and transmission electron microscopy revealed that overexpressing PagUNE12 promoted secondary xylem development, with thicker secondary cell walls than wild-type poplar. Fourier transform infrared spectroscopy, confocal Raman microscopy, and 2D Heteronuclear Single Quantum Correlation analysis indicated that these plants also had increased lignin contents, with a lower relative abundance of syringyl lignin units and a higher relative abundance of guaiacyl lignin units. Therefore, overexpressing PagUNE12 promoted secondary xylem development and increased the lignin contents of secondary xylem in poplar, suggesting that this gene could be used to improve wood quality in the future.

Characteristics of PoVIN3, a Key Gene of Vernalization Pathway, Affects Flowering Time.

The tree peony (Paeonia section Moutan DC.) is the candidate flower in China, with abundant germplasm resources and high ornamental value. However, the short and concentrated flowering period severely restricted the improvement of the economic value of tree peonies. Based on the full-length transcriptome database of tree peonies, the PoVIN3 (GenBank ID: OP341879), involved in the flowering regulation of tree peonies were identified and cloned for the first time. The PoVIN3 was also characterized by bioinformatics methods, quantitative real-time PCR (qRT-PCR), and the establishment of a transgenic system. The expression levels of PoVIN3 in seven different petals developmental stages were the highest at the initial flowering stage of the variant cultivar of Paeonia ostii 'Fengdan,' the initial decay stage of the normal flowering Paeonia ostii 'Fengdan,' and the half opening stage of the late flowering Paeonia suffruticosa 'Lianhe.' Tissue-specific expression analysis showed that the relative expression levels of PoVIN3 were the highest in sepals of both normal flowering Paeonia ostii 'Fengdan' and the late flowering Paeonia suffruticosa 'Lianhe,' and the highest expression was in stamens of early flowering mutant Paeonia ostii 'Fengdan.' In addition, the flowering time of pCAMBIA2300-PoVIN3 transgenic plants was significantly earlier than that of the wild-type, indicating that PoVIN3 could promote plant flowering. The results provide a theoretical basis for exploring the role of PoVIN3 in the regulation of flowering in tree peonies.

Scalable, Dual-Band Metasurface Array for Electromagnetic Energy Harvesting and Wireless Power Transfer.

A dual-band metasurface array is presented in this paper for electromagnetic (EM) energy harvesting in the Wi-Fi band and Ku band. The array consists of metasurface unit cells, rectifiers, and load resistors. The metasurface units within each column are interconnected to establish two channels of energy delivery, enabling the transmission and aggregation of incident power. At the terminals of two channels, a single series diode rectifier and a voltage doubler rectifier are integrated into them to rectify the energy in the Wi-Fi band and the Ku band, respectively. A 7 × 7 prototype of the metasurface array is fabricated and tested. The measured results in the anechoic chamber show that the RF-to-dc efficiencies of the prototype at 2.4 GHz and 12.6 GHz reach 64% and 55% accordingly, when the available incident power at the surface is 3 dBm and 14 dBm, respectively.

Development and Characterization of Microsatellite Markers Based on the Chloroplast Genome of Tree Peony.

Tree peony (Paeonia suffruticosa Andr.) is a famous ornamental and medicinal flowering species. However, few high-efficiency chloroplast microsatellite markers have been developed for it to be employed in taxonomic identifications and evaluation of germplasm resources to date. In the present study, a total of 139 cpSSR loci were identified across eleven tree peony plastomes. Dinucleotide repeat SSRs (97.12%) were most abundantly repeated for the AT motif (58.27%), followed by the TA motif (30.94%) and the TC motif (7.91%). Twenty-one primer pairs were developed, and amplification tests were conducted for nine tree peony individuals. Furthermore, 19 cpSSR markers were amplified on 60 tree peony accessions by a capillary electrophoresis test. Of 19 cpSSR markers, 12 showed polymorphism with different alleles ranging from 1.333 to 3.000. The Shannon's information index and polymorphism information content values ranged from 0.038 to 0.887 (mean 0.432) and 0.032 to 0.589 (mean 0.268), respectively. The diversity levels for twelve loci ranged from 0.016 (at loci cpSSR-8 and cpSSR-26) to 0.543 (at locus cpSSR-15), averaging 0.268 for all loci. A total of 14 haplotypes (23.33%) were detected in the three populations. The haplotypic richness ranged from 0.949 to 1.751, with a mean of 1.233 per population. The genetic relationship suggested by the neighbor-joining-based dendrogram divided the genotypes into two clusters. The Jiangnan population was allotted to Cluster II, and the other two populations were distributed into both branches. These newly developed cpSSRs can be utilized for future breeding programs, population genetics investigations, unraveling the genetic relationships between related species, and germplasm management.

Identification of differentially expressed miRNAs and their target genes in response to brassinolide treatment on flowering of tree peony (Paeonia ostii).

Tree peony is a famous flower plant in China, but the short and concentrated flowering period limits its ornamental value and economic value. Brassinolide (BR) plays an important role in plant growth and development including flowering. There have been a large number of reports on the molecular aspects of the flowering process, but the genetic mechanism that was responsible for miRNA-guided regulation of tree peony is almost unclear. In this study, the leaves of tree peony cultivar, 'Feng Dan', were sprayed with different concentrations of BR, and the obvious bloom delay was found at the treatment with BR 50 µg/L. The small RNA sequencing and transcriptome sequencing were performed on the petals of tree peony under an untreated control (CK) and the treatment with BR 50 µg/L during four consecutive flowering development stages. A total of 22 known miRNAs belonging to 12 families were identified and 84 novel miRNAs were predicted. Combined with transcriptome data, a total of 376 target genes were predicted for the 18 differentially expressed known miRNAs and 177 target genes were predicted for the 23 differentially expressed novel miRNAs. Additionally, the potential miRNAs and their target genes were identified, including miR156b targeting SPL, miR172a_4 targeting AP2 and four novel miRNAs targeting SPA1, and revealed that they might affect the flowering time in tree peony. Collectively, these results would provide a theoretical basis for further analysis of miRNA-guided regulation on flowering period in tree peony.

Outcome of manipulation under anesthesia with or without intra-articular steroid injection for treating frozen shoulder: A retrospective cohort study.

ABSTRACT: Manipulation under anesthesia (MUA) combined with intra-articular steroid injection (ISI) is preferred in management of the refractory frozen shoulder (FS). This study aimed to evaluate the effect of MUA with ISI or not on pain severity and function of the shoulder.Data on 141 patients receiving MUA with primary FS refractory to conservative treatments for at least 1 month were retrospectively obtained from medical records. We performed propensity score matching analysis between patients receiving MUA only and those receiving MUA plus ISI, and then conducted logistic regression analysis to identify the risk factors for the need to other treatments during 6-month follow-up.More improvement in terms of the SPADI pain scores and passive ROM at 2 weeks after first intervention remained in patients receiving MUA plus ISI after matching. The need to other treatments during 6-month follow-up occurred in 10.6% patients (n = 141). Logistic regression analysis revealed that a repeat MUA 1 week after first intervention was a protective factor (OR 0.042; 95% CI 0.011-0.162; P = .000) and duration of disease was the only one risk factor (OR 1.080; 95% CI 1.020-1.144; P = .008) for the need to other treatments during follow-up.ISI immediately following MUA provided additional benefits in rapid relief of pain and disability for patients with refractory FS. Pain and disability of the shoulder may be rapidly alleviated by an earlier MUA from the onset of the symptoms and a repeat MUA 1 week after first intervention.

Comparison of Bispectral Index-Guided Individualized Anesthesia with Standard General Anesthesia on Inadequate Emergence and Postoperative Delirium in Elderly Patients Undergoing Esophagectomy: A Retrospective Study at a Single Center.

BACKGROUND Elderly patients are susceptible to general anesthetics, with a higher bispectral index (BIS) at loss of consciousness (LOC) achieved by propofol infusion compared with young patients. Overexposure to general anesthetics can have adverse effects such as inadequate emergence and postoperative delirium (PD). This study aimed to compare the effects of BIS-guided individualized anesthesia with standard general anesthesia on emergence and delirium after esophagectomy. MATERIAL AND METHODS Data on 161 elderly patients undergoing esophagectomy for cancer were retrospectively obtained from electronic medical records. We performed propensity score matching analysis between patients receiving individualized anesthesia (BIS value maintained at about 10 less than the value at LOC) and those receiving standard anesthesia (BIS value maintained at 40-60). In addition, we conducted univariate and multivariate logistic -analyses in the entire cohort. RESULTS Patients receiving individualized anesthesia had higher BIS values and a lower propofol requirement during surgery than those receiving standard general anesthesia (P<0.05). The overall incidences of inadequate emergence and PD were 37.9% and 18.0% (n=161), respectively. Logistic regression analysis revealed that the independent risk factors for PD were organic brain disease (odds ratio [OR] 6.308; 95% confidence interval [CI] 2.458-16.187) and inadequate emergence (OR 4.063; 95% CI 1.645-10.033). CONCLUSIONS BIS-guided individualized anesthesia (lighter) does not reduce inadequate emergence or PD compared with standard general anesthesia in elderly patients undergoing esophagectomy. Independent risk factors for PD include organic brain disease and inadequate emergence.

Author Correction: Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Addition of dexmedetomidine to epidural morphine to improve anesthesia and analgesia for cesarean section.

The aim of the present study was to evaluate the effectiveness and safety of the combination of epidural dexmedetomidine and morphine in providing anesthesia during cesarean surgery and analgesia for post-cesarean pain relief when added to epidural ropivacaine. A total of 80 females at term scheduled for elective cesarean delivery were randomly assigned to two groups (n=40/group): In the morphine group (group M), patients received an epidural injection of 0.75% ropivacaine (12 ml) and morphine (2 mg) for surgical anesthesia, and epidural infusion of morphine (2 mg) in 100 ml 0.2% ropivacaine at 2 ml/h for 48-h post-operative analgesia; and in the morphine combined with dexmedetomidine group (group DM), patients received an epidural injection of 0.75% ropivacaine (12 ml) and morphine (2 mg) combined with dexmedetomidine (0.5 µg/kg) for surgical anesthesia, and epidural infusion of morphine (2 mg) and dexmedetomidine (200 µg) in 100 ml 0.2% ropivacaine at 2 ml/h for 48-h post-operative analgesia. The primary outcomes included blockade and analgesic effects, sedation and adverse reactions associated with the drugs. Neonatal outcome was also assessed by determining the Apgar score and umbilical cord blood analysis. There was no significant difference between the groups in the cephalad levels of sensory blockade at 20 min post-injection, or in muscle relaxation scores or pain intensity scores at rest or upon movement at 4, 12, 24 or 48 h post-injection (P>0.05). The maternal patients in the DM group experienced more complete motor blockade at 20 min post-injection, better sedation during surgery and following delivery, and less visceral pain caused by peritoneal traction during surgery and by uterine contraction after delivery, compared with those in group M (P<0.05). The patients in group M had a lower incidence and severity score of post-operative nausea than those in the DM group (P<0.05). There was no significant difference between the groups in terms of Apgar score or umbilical cord blood gas values (P>0.05). In conclusion, epidural dexmedetomidine reduces intra-operative and post-operative visceral pain and produces better sedation during surgery and following delivery, without any significant influence on morphine-associated side effects and post-operative analgesia, in females undergoing elective cesarean section under epidural anesthesia with morphine and ropivacaine (registration number ChiCTR1900027942; retrospectively registered with the Chinese Clinical Registry Center on December 6, 2019).

Efficient Agrobacterium-Mediated Transformation of the Commercial Hybrid Poplar Populus Alba × Populus glandulosa Uyeki.

Transgenic technology is a powerful tool for gene functional characterization, and poplar is a model system for genetic transformation of perennial woody plants. However, the poplar genetic transformation system is limited to a number of model genotypes. Herein, we developed a transformation system based on efficient Agrobacterium-mediated transformation for the hybrid poplar Populus Alba × Populus glandulosa Uyeki, which is a fast-growing poplar species that is suitably grown in the northern part of China. Importantly, we optimized many independent factors and showed that the transformation efficiency was improved significantly using juvenile leaf explants. Explants were infected by an Agrobacterium suspension with the OD600 = 0.6 for 15 min and then co-cultured in dark conditions for 3 days. Using the improved transformation system, we obtained the transgenic poplar with overexpression of ß-glucuronidase (GUS) via direct organogenesis without callus induction. Furthermore, we analyzed the GUS gene in the transgenic poplars using PCR, qRT-PCR, and GUS staining. These analyses revealed that the GUS gene was efficiently transformed, and it exhibited various expression levels. Taken together, these results represent a simple, fast, and efficient transformation system of hybrid poplar plants. Our findings may facilitate future studies of gene functions in perennial woody plants and tree breeding via transgenic technology assisted design.

Erratum: Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer's disease.

[This corrects the article DOI: 10.3892/etm.2017.5620.].

Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer's disease.

Alzheimer's disease is associated with cognitive impairments that affect memory and executive functions. Simvastatin is a cholesterol-lowering statin drug that is used to control levels of cholesterol in the blood, particularly in cases of hypercholesterolemia, and may be used in the treatment of aneurysmal subarachnoid hemorrhage. Previous results have indicated that the apoptosis of hippocampal cells may serve a critical role in the progression of Alzheimer's disease. In the present study, it was determined whether Simvastatin inhibited the apoptosis of hippocampal cells in vitro and in vivo. The therapeutic effects of Simvastatin were evaluated in 24-month-old triple-transgenic Alzheimer's disease (3×Tg-AD) mice, and the efficacy of Simvastatin in attenuating memory and cognitive impairment was investigated. Levels of apoptosis-related gene expression in the hippocampus and hippocampal cells of experimental mice were also detected. In addition, neuron excitability was assessed in the functionally relevant brain regions in the hippocampus. The data indicated that Simvastatin significantly suppressed the apoptosis of hippocampal cells in 3×Tg-AD model mice compared with controls (P<0.01). Furthermore, treatment with Simvastatin improved the dementia status of 3×Tg-AD mice, as determined by a learning task in which mice exhibited significantly reduced attention impairment, impulsivity and compulsivity (P<0.01). In addition, results demonstrated that Simvastatin significantly inhibited hippocampal damage and significantly improved neuronal loss in hippocampal structures classically associated with attentional performance when compared with untreated mice (P<0.01). Thus, Simvastatin prevented cognitive impairment by decreasing hippocampal cell apoptosis and improving learning-memory ability. Simvastatin treatment also increased the expression of anti-apoptotic genes and decreased the expression pro-apoptotic genes (P<0.01), which may have been associated with improved motor attention and cognitive competence in 3×Tg-AD mice. Collectively, these preclinical data indicated that Simvastatin was efficient in attenuating memory lapse and hippocampal cell apoptosis in a 3×Tg-AD mouse model. Thus, Simvastatin may be useful in improving the clinical outcome of patients with Alzheimer's disease.

PDM3, a pentatricopeptide repeat-containing protein, affects chloroplast development.

The chloroplast, as the photosynthetic organelle of plants, plays a crucial role in plant development. Extensive studies have been conducted on chloroplast development; however, the related regulatory mechanism still remains elusive. Here, we characterized a mutant with defective chloroplasts in Arabidopsis, termed pigment-defective mutant3 (pdm3), which exhibits a distinct albino phenotype in leaves, eventually leading to pdm3 seedling lethality under autotrophic growth conditions. Electron microscopy demonstrated that the number of thylakoids was reduced and the structure of those thylakoids was disrupted in the pdm3 mutant, which eventually led to the breakdown of chloroplasts. Sequence analysis showed that PDM3 encodes a chloroplast protein consisting of 12 pentratricopeptide repeat domains that belongs to the P subgroup. Both confocal microscopic analysis and immunoblotting in the chloroplast protein fraction showed that PDM3 was located in the stroma. Furthermore, analysis of the transcript profiles of chloroplast genes revealed that plastid-encoded polymerase-dependent transcript levels were markedly reduced, while nuclear-encoded polymerase-dependent transcript levels were increased in pdm3 mutants. In addition, we found that the splicing of introns in trnA, ndhB, and clpP-1 is also affected in pdm3. Taken together, we propose that PDM3 plays an essential role in chloroplast development in Arabidopsis.

Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

Targeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits anti-oxidative and anti-cancer activities at levels exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. Herein, we demonstrate that MSA inhibited angiogenesis at 2 µM, which falls in the range of moderate Se nutritional status. We found that MSA treatments at 2 µM increased cell adherence, while inhibiting cell migration and tube formation of HUVECs in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin ß3 at the levels of mRNA and protein, and disrupted clustering of integrin ß3 on the cell surface. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB. Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels not only by down-regulating the expression of integrin ß3 but also by disorganizing the clustering of integrin ß3, which further inhibited the phosphorylation involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy in clinical settings.

Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation.

BACKGROUND: Selenium (Se) is an essential micronutrient trace element and an established nutritional antioxidant. Low Se status exacerbates inflammatory bowel diseases progression, which involves hyper inflammation in the digestive tract. Se nanoparticles (SeNPs) exhibit anti-inflammatory activity accompanied by low toxicity, especially when decorated with natural biological compounds. Herein, we explored the beneficial effects of SeNPs decorated with Ulva lactuca polysaccharide (ULP) in mice subjected to the acute colitis model. RESULTS: We constructed SeNPs coated with ULP (ULP-SeNPs) in average diameter ~130 nm and demonstrated their stability and homogeneity. Supplementation with ULP-SeNPs (0.8 ppm Se) resulted in a significant protective effect on DSS-induced acute colitis in mice including mitigation of body weight loss, and colonic inflammatory damage. ULP-SeNPs ameliorated macrophage infiltration as evidenced by decreased CD68 levels in colon tissue sections. The anti-inflammatory effects of ULP-SeNPs were found to involve modulation of cytokines including IL-6 and TNF-α. Mechanistically, ULP-SeNPs inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which drives the transcription of these pro-inflammatory cytokines. CONCLUSIONS: ULP-SeNPs supplementation may offer therapeutic potential for reducing the symptoms of acute colitis through its anti-inflammatory actions.

Inhibition of long non-coding RNA IGF2AS protects apoptosis and neuronal loss in anesthetic-damaged mouse neural stem cell derived neurons.

BACKGROUND: In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells. METHODS: Murine E18.5 brain-derived neural stem cells were cultured in vitro. During neural differentiation stage, ketamine-induced gene expression changes of IGF2 and IGF2AS were recorded by qRT-PCR. Neural stem cell culture was then infected by IGF2AS siRNA. The protective effect of IGF2AS inhibition on ketamine-induced apoptosis and neurite loss was assessed by TUNEL and neurite growth assays. BDNF and Akt, two candidates of downstream signaling pathways associated with IGF2AS inhibition, were further examined by western blot in neural stem cell culture. RESULTS: In neural stem cell culture, IGF2 was downregulated, but IGF2AS upregulated by in vitro treatment of ketamine in dose-dependent manner. Transfection of IGF2AS-specific siRNA effectively downregulated endogenous IGF2AS expression in neural stem cells. In addition, IGF2AS inhibition significantly alleviated ketamine-induced neuronal apoptosis and neurite loss in neural stem cell-derived neurons. Western blot study revealed that IGF2AS inhibition upregulated downstream pro-neuronal signaling pathway proteins BDNF and Akt. CONCLUSIONS: Inhibiting endogenous IGF2AS can protect anesthetic-induced neurotoxicity in neural stem cells, possibly through complimentary IGF2 upregulation and its associated downstream signaling pathways.

The prognostic value of MGMT promoter status by pyrosequencing assay for glioblastoma patients' survival: a meta-analysis.

BACKGROUND: The prognostic value of the status of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation measured by pyrosequencing assay (PSQ) among glioblastoma (GBM) patients was examined in meta-analysis. METHODS: Eligible studies that reported the association between the status of MGMT promoter methylation by PSQ and prognostic value of GBM patients from three electronic databases, like PubMed, EMBASE, and Cochrane library were involved in meta-analysis. Using Stata 11.0, the summarized hazard ratios (HRs) for overall survival (OS) and the progression-free survival (PFS) with 95 % confidence interval (CI) were calculated. RESULTS: Eleven studies were included to evaluate the relationship between the status of MGMT promoter methylation and GBM patients' survival. Overall, regardless of the cut-off value of methylation status of MGMT promoter by PSQ, methylated-positive patients were evidently associated with an improved HRs for OS (HRs = 0.50, 95 % CI = 0.35-0.66). For summary, progression-free survival (PFS) from four studies, the prognostic effect was also found (HRs = 0.56, 95 % CI = 0.32-0.80). CONCLUSION: Methylation positivity of MGMT promoter by PSQ was related to an increased survival in GBM patients. Thus, the status of MGMT promoter methylation by PSQ might be used to be a prognostic biomarker, and GBM patients might have a vested interest in clinical application of standardized PSQ.

Inhibition of long non-coding RNA IGF2AS has profound effect on inducing neuronal growth and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion neurons.

BACKGROUND: Long non-coding RNA IGF2AS was initially identified as a cancer regulator in wilm's tumors. In this study, IGF2AS was investigated of its functions in inducing neural development and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion (DRG) in spinal cord. METHODS: Explant of mouse spinal cord DRG was transfected with IGF2AS specific siRNA. The effect of IGF2AS inhibition on neural development was assessed by neurite growth assay, qRT-PCR and western blot assay, respectively. IGF2AS-downregulated DRG explant was then exposed to local anesthetic agent, lidocaine in vitro. The possible protective effects of IGF2AS inhibition on lidocaine-induced DRG neuron apoptosis and neurite loss were further assessed by TUNEL assay, neurite growth assay, qRT-PCR and western blot assays. RESULTS: SiRNA-mediated IGF2AS inhibition promoted neuronal growth, and induced IGF2, BDNF and NT3 upregulations at both gene and protein expressions. In lidocaine-exposed DRG neurons, endogenous IGF2AS inhibition was effective to protect local-anesthetic induced neuronal apoptosis and neurite loss. Further molecular characterization demonstrated that the neuronal protection of IGF2AS inhibition was also associated with upregulations of IGF2, BDNF and NT3 in DRG neurons. CONCLUSIONS: Inhibiting endogenous IGF2AS may promote neuronal growth and protect local-anesthetic induced neurotoxicity in DRG neurons, possibly through complimentary IGF2 upregulation and autocrine activation neurotrophin genes.