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Epigenetics, including histone modifications, play a significant role in central nervous system diseases, but the underlying mechanism remains to be elucidated. The aim of this study was to evaluate the role of H3K27me3 in regulating transcriptomic and pathogenic mechanisms following global ischemic stroke. Here, we found that in vivo ischemic/reperfusion (I/R) injury induced marked upregulation of H3K27me3 in the hippocampus. The administration of GSK-126 to rat brains decreased the levels of H3K27me3 in the hippocampus and reduced neuronal apoptosis after experimental stroke. Furthermore, ChIP-seq data demonstrated that the primary role of GSK-126 in the ischemic brain is to reduce H3K27me3 enrichment, mediating negative regulation of the execution phase of apoptosis and the MAPK signaling pathway. Further study suggested that the protective role of GSK-126 in ischemic rats was antagonized by U0126, an inhibitor of ERK1/2. Collectively, we demonstrated the potential of H3K27me3 as a novel stroke therapeutic target, and GSK-126 exerted a neuroprotective function in ischemic brain injury, which might be associated with activation of the MAPK/ERK pathway., (© 2021. The Author(s).)

Stroke, also known as cerebral stroke or cerebrovascular accident, refers to acute ischemic or hemorrhagic encephalopathy caused by a disturbance to cerebral blood flow. Ischemic stroke is the most common type of cerebral stroke, accounting for approximately 80% of the total incidence of clinical stroke. High morbidity, disability, and mortality rates place heavy burdens on the families of patients and society. An increasing number of studies have shown that histone modification plays an important role in the pathogenesis of ischemic stroke, but most studies on histone modification focus on acetylation, and studies on the role of histone methylation in the pathogenesis of ischemic stroke are limited. Here, we review the role of histone methylation and related histone methyltransferase (HMT) inhibitors in the pathogenesis of ischemic stroke and related HMT inhibitors in the treatment of ischemic stroke, which may open up a new avenue to the study of ischemic stroke., (© 2021. University of Navarra.)

Precision medicine has been strongly promoted in recent years. It is used in clinical management for classifying diseases at the molecular level and for selecting the most appropriate drugs or treatments to maximize efficacy and minimize adverse effects. In precision medicine, an in-depth molecular understanding of diseases is of great importance. Therefore, in the last few years, much attention has been given to translating data generated at the molecular level into clinically relevant information. However, current developments in this field lack orderly implementation. For example, high-quality chemical research is not well integrated into clinical practice, especially in the early phase, leading to a lack of understanding in the clinic of the chemistry underlying diseases. In recent years, mass spectrometry (MS) has enabled significant innovations and advances in chemical research. As reported, this technique has shown promise in chemical mapping and profiling for answering "what", "where", "how many" and "whose" chemicals underlie the clinical phenotypes, which are assessed by biochemical profiling, MS imaging, molecular targeting and probing, biomarker grading disease classification, etc. These features can potentially enhance the precision of disease diagnosis, monitoring and treatment and thus further transform medicine. For instance, comprehensive MS-based biochemical profiling of ovarian tumors was performed, and the results revealed a number of molecular insights into the pathways and processes that drive ovarian cancer biology and the ways that these pathways are altered in correspondence with clinical phenotypes. Another study demonstrated that quantitative biomarker mapping can be predictive of responses to immunotherapy and of survival in the supposedly homogeneous group of breast cancer patients, allowing for stratification of patients. In this context, our article attempts to provide an overview of MS-based chemical mapping and profiling, and a perspective on their clinical utility to improve the molecular understanding of diseases for advancing precision medicine., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

GSK-126 is recognized as an inhibitor of enhancer of zeste homolog-2 (EZH2) activity. Because of its inhibition of EZH2 activation, GSK-126 is considered a potential anti-tumor drug. EZH2 is a histone methyltransferase that catalyzes histone 3 tri-methylation at lysine 27 (H3K27me3), resulting in gene silencing. A previous report showed that decreased H3K27me3 levels in the hippocampus may promote seizure susceptibility, possibly restricting the clinical application of GSK-126. The role of GSK-126 in seizure susceptibility was investigated in this study. We first determined a critical concentration of pentamethazol (PTZ) under which mice exhibit no seizures. We then found that mice pretreated with GSK-126 and injected with the same concentration of PTZ experienced marked convulsions. Peripheral injections of GSK-126 decreased H3K27me3 levels in the hippocampus of mice, while some seizure-related genes (Oasl1, Sox7, armcx5, Ncx3, etc.) were found to be differentially expressed in the hippocampus of those mice . These differences in the expression levels might reflect the crucial role of these genes and related pathways in the promotion of seizure susceptibility. Our results suggest that GSK-126 promotes seizure susceptibility due to its role as an EZH2 inhibitor. These findings may provide evidence to support the development of GSK-126 as a clinical drug.

Human epidermal growth factor receptor 2 (HER2) testing has great value for cancer diagnosis, prognosis and treatment selection. However, the clinical utility of HER2 is frequently tempered by the uncertainty regarding the accuracy of the methods currently available to assess HER2. The development of novel methods for accurate HER2 testing is in great demand. Considering the visualization features of in situ imaging and the quantitative capability of mass spectrometry, integration of the two components into a molecular mapping approach has attracted increasing interest. In this work, we reported an integrated chemical mapping approach using a photocleavable peptide-tagged mass probe for HER2 detection. The probe consists of four functional domains, including the recognition unit of an aptamer to catch HER2, a fluorescent dye moiety (FITC) for fluorescence imaging, a reporter peptide for mass spectrometric quantification, and a photocleavable linker for peptide release. After characterization of this novel probe ( e.g. , conjugation efficiency, binding affinity and specificity, and photolysis release efficiency), the probe binding and photolysis release conditions were optimized. Then, fluorescence images were collected, and the released reporter peptide after photolysis was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A limit of quantification (LOQ) of 25 pM was obtained, which very well meets the requirements for clinical laboratory testing. Finally, the developed assay was applied for HER2 testing in four breast cancer cell lines and 42 pairs of human breast primary tumors and adjacent normal tissue samples. Overall, this integrated approach based on a photocleavable peptide-tagged mass probe can provide chemical mapping including both quantitative and visual information of HER2 reliably and consistently, and may pave the way for clinical applications in a more accurate manner., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Objectives: This study aims to investigate the diagnostic and prognostic values of EpCAM, TGM2, and HE4 in endometrial cancer (EC). Methods: In this study, 42 patients diagnosed with EC (EC group), 41 patients diagnosed with myoma (benign group), and 43 healthy women (healthy group), who applied to Affiliated Hospital of Xuzhou Medical University between March 2018 - September 2019 were recruited. Serum EpCAM, TGM2, and IL-33 levels were measured by ELISA, while serum HE4 and CA-125 levels were measured by ECLIA. The serum markers listed above were also measured in 12 paired pre- and post-operative EC patients. The diagnostic and prognostic values of serum markers were analyzed. Results: The serum EpCAM, TGM2, HE4, CA-125, and IL-33 levels were significantly higher in the EC group. The sensitivity and specificity of combined detection of EpCAM and HE4 was 92.86 and 69.05%, which were significantly higher than using a single marker or other combinations. Among these markers, serum HE4 levels were significantly higher in patients with myometrial invasion, metastasis, and lymphovascular invasion ( p = 0.006, p = 0.0004, p = 0.0004, respectively). And serum TGM2 levels were significantly decreased in post-operative than that of pre-operative EC patients ( p < 0.001). Conclusions: The combination of EpCAM and HE4 showed the highest specificity and sensitivity in the diagnosis of EC. HE4 was successful in the detection of high-risk individuals preoperatively. Additionally, TGM2 might be a prognostic factor for EC., (Copyright © 2020 Lan, Mu, Wang, Wang, Li, Mai, Li, Xu, Gu, Luo and Ma.)

The objective of this study was to investigate the effects of different sources and levels of zinc (Zn) on growth performance, nutrient digestibility, serum biochemical parameters, and fur quality in growing-furring male mink. Animals in the control group were fed a basal diet with no Zn supplementation. Mink in the other nine treatments were fed the basal diet supplemented with Zn from either grade Zn sulfate (ZnSO 4 ·7H 2 O), Zn glycinate (ZnGly), or Zn pectin oligosaccharides (ZnPOS) at concentrations of either 100, 300, or 900 mg Zn/kg dry matter. One hundred and fifty healthy 15-week-old male mink were randomly allocated to ten dietary treatments (n = 15/group) for a 60-day trial from mid-September to pelting in December. Mink in the Zn-POS groups had higher average daily gain than those in the control group (P < 0.05). Zn source slightly improved the feed/gain (P = 0.097). N retention was increased by Zn addition (P < 0.05). Mink supplemented with dietary Zn had higher (P < 0.05) pancreas Zn level than the control group. Fur length was greater (P < 0.05) in ZnGly and ZnPOS groups compared with the control. In addition, fur length and fur density increased (linear, P < 0.05) with Zn supplementation in the diet. In conclusion, our data show that dietary Zn addition improves growth performance by increasing nitrogen retention and fat digestibility in growing-furring mink and Z-POS is equally bioavailable to mink compared to ZnGly.

The experiment was conducted to investigate the effects of zinc pectin oligosaccharides (Zn-POS) chelate on growth performance, nutrient digestibility, and tissue zinc concentrations of Arbor Acre broilers aged from 1 to 42 days. A total of 576 1-day-old broilers were randomly assigned into 4 groups with 9 replicates per group and 16 chicks per replicate. Chicks were fed either a basal diet (control) or basal diet supplemented with Zn-POS at 300 (Zn-POS-300), 600 (Zn-POS-600), or 900 mg/kg (Zn-POS-900), respectively, for 42 days. A 3-day metabolism trial was conducted during the last week of the experiment feeding. The average daily gain and the average daily feed intake of Zn-POS-600 were significantly higher (P < 0.05) than those of either the control, Zn-POS-300, or Zn-POS-900. Zn-POS-600 had the highest apparent digestibility of dry matter, crude protein, and metabolic energy among all groups. The control group had the lowest apparent digestibility of dry matter (P < 0.05), whereas the apparent digestibility of dry matter in Zn-POS-600 was higher (P < 0.05) than that of Zn-POS-300. The apparent digestibility of crude protein in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) compared to Zn-POS-300 or the control. The apparent digestibility of metabolic energy in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) than that of Zn-POS-300. Zn-POS-600 had the highest liver zinc concentrations (P < 0.05), while Zn-POS-900 had the highest pancreatic zinc concentrations (P < 0.05). Our data suggest that the supplementation of 600 mg/kg Zn-POS is optimal in improving the average daily gain and the average daily feed intake, utilization of dietary dry matter and crude protein, and increasing tissue zinc concentrations in liver and pancreas of broilers.

A new method for the detection of β2 adrenergic agonists was developed based on the chemiluminescence (CL) reaction of β2 adrenergic agonist with potassium ferricyanide-luminol CL. The effect of β2 adrenergic agonists including isoprenaline hydrochloride, salbutamol sulfate, terbutaline sulfate and ractopamine on the CL intensity of potassium ferricyanide-luminol was discovered. Detection of the β2 adrenergic agonist was carried out in a flow system. Using uniform design experimentation, the influence factors of CL were optimized. The optimal experimental conditions were 1 mmol/L of potassium ferricyanide, 10 µmol/L of luminol, 1.2 mmol/L of sodium hydroxide, a flow speed of 2.6 mL/min and a distance of 1.2 cm from 'Y2 ' to the flow cell. The linear ranges and limit of detection were 10-100 and 5 ng/mL for isoprenaline hydrochloride, 20-100 and 5 ng/mL for salbutamol sulfate, 8-200 and 1 ng/mL for terbutaline sulfate, 20-100 and 4 ng/mL for ractopamine, respectively. The proposed method allowed 200 injections/h with excellent repeatability and precision. It was successfully applied to the determination of three β2 adrenergic agonists in commercial pharmaceutical formulations with recoveries in the range of 96.8-98.5%. The possible CL reaction mechanism of potassium ferricyanide-luminol-β2 adrenergic agonist was discussed from the UV/vis spectra., (Copyright © 2014 John Wiley & Sons, Ltd.)

Skull base chordoma are still challenging. Between May 1993 and June 2005, 106 consecutive patients with skull base chordoma underwent surgical removal at Skull Base Division of Neurosurgery, Beijing Tiantan Hospital, China. Retrospective analysis included medical charts and images. The age of the patients ranged from 7 to 65 years old, with an average age of 35.6 years. Sixty patients were male; the other 46 were female (1.3:1). Follow up data were available in 79 cases ranging from 10 to 158 months (average 63.9 months) after operation. The prognostic factors for recurrence and survival were analyzed with Kaplan-Meier, Cox regression and t-test. Overall, 1, 3, 5 and 10 years survival rates were 87.2%, 79.4%, 67.6%and 59.5% respectively. One, 3, 5 and 10 year recurrent rates were 19.1%, 34.7%, 52.9% and 88.3%, respectively. The long term outcome of the skull base chordomas is poor. The previous radiotherapy or surgery, dedifferentiated pathology, and less tumor resection are risk factors for longterm survival and recurrence (p < 0.05). Although there is no statistic significant role of tumor adherent to vital structure for outcome (p = 0.051), it can not exclude its importance for favorable outcome. Gender, age, tumor size and staging are not independent risk factors for outcome. Surgical technique leading to radical tumor resection with less morbidity is advocatory and beneficial for patients with skull base chordoma with long term outcome, if the tumor could be exposed and resected completely, the recurrence rate was very low for most benign chordomas.

Eight somaclonal variants with enhanced drought tolerance were isolated from regenerated plants of triploid bermudagrass (Cynodon dactylon x Cynodon transvaalensis cv., TifEagle). Three of them (10-17, 89-02, 117-08) with strong drought tolerance were selected for investigations of physiological responses to drought stress. Compared to the parent control, TifEagle, the somaclonal variants had higher relative water contents and relative growth, and lower ion leakages in the greenhouse tests, while no difference in evapotranspirational water losses and soil water contents was observed between the variants and TifEagle. The variants also had less leaf firing in the field tests under drought stress. Superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activities decreased gradually in responses to drought stress in all plants and exhibited negative correlations with ion leakage, indicating that the declined activities of these antioxidant enzymes were associated with drought injury in the triploid bermudagrass. However, CAT activities were significantly higher in all three variants than in TifEagle during drought stress. Two variants, 10-17 and 89-02, also had significantly higher APX activities than TifEagle before and during the first 4 days of drought treatments. These two lines also showed higher SOD activities after prolonged drought stress. Proline, total soluble sugars and sucrose were accumulated under drought stress in all plants and exhibited positive correlations with ion leakage. More proline and sugars were accumulated in TifEagle than in the variants. The results indicated that higher activities of the antioxidant enzymes in the variants during drought stress are associated with their increased drought tolerance.

A protocol was established for in vitro selection of salinity tolerant somaclonal variations from suspension cultured calli of triploid bermudagrass cv. TifEagle. To induce somaclonal variations the calli were subcultured for 18 months and were then subject to three-round selections for salt-tolerant calli by placing on solid medium containing 0.3 M NaCl for 10 days followed by a recovery for 2 weeks. The surviving calli were regenerated on regeneration medium containing 0.1 M NaCl. Three somaclonal variant lines (2, 71, and 77) were obtained and analyzed. The selected somaclonal lines showed higher relative growth and less injury than TifEagle under salt stress, indicating that they increased salt tolerance. In addition, they had higher relative water content and lower electrolyte leakage than TifEagle after withholding irrigation, indicating that they also increased drought tolerance. The three somaclonal variant lines had higher proline content than TifEagle under normal growth condition. The line 71 had a higher K(+)/Na(+) ratio, whereas the lines 2 and 77 had higher CAT activity under control and salt stress conditions, indicating that different mechanisms for salt tolerance might exist in these three lines.

Objective: To explore the factors which induce differentiation of embryonic neural stem cells., Methods: Rat embryonic neural stem cells were co-cultured with newborn rat Schwann cells in serum-free medium. The phenotype and specific-markers including tubulin-beta, glial fibrillary acidic protein (GFAP) and galactorcerebroside (GalC), were demonstrated by phase contrast microscopy and double immunofluorescence staining., Results: Overall, 80% +/- 5% of neural stem cells protruded several elongated processes and expressed tubulin-beta antigen at high levels, while 20 +/- 3% of them protruded several short processes and were GalC or GFAP positive., Conclusion: The factors secreted by Schwann cells could induce rat embryonic neural stem cell to differentiate.

Objective: To determine cell proliferation and nestin expression in the ependyma of adult rat spinal cord after injury., Methods: Rat spinal cord injury models were established by aneurysm clip compression, and nestin expression and proliferation of ependymal cells at different times were shown with pathological and immuno-histochemical staining., Results: Ependymal cells adjacent to the injured site demonstrated a dramatic increase in nestin expression 24 hours after compression. Proliferating cell nuclear antigen was positive, and significant proliferation was observed after 7 days. Nestin expression was down regulated as time went by., Conclusion: Normally quiescent mature ependymal cells appear to revert to an embryonic state in response to spinal cord injury.