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Background: The CCDC22 gene plays vital roles in regulating the NF-κB pathway, an essential pathway for neuroinflammation, neurodevelopment, and epileptogenesis. Previously, variants in CCDC22 were reported to be associated with intellectual disability. This study aimed to explore the association between CCDC22 and epilepsy., Methods: Trios-based whole-exome sequencing (WES) was performed in a cohort of patients with epilepsy of unknown cause recruited from the China Epilepsy Gene 1.0 Project. Damaging effects of variants were analysed using protein modelling., Results: Hemizygous missense CCDC22 variants were identified in three unrelated cases. These variants had no hemizygous frequencies in controls. All missense variants identified in this study were predicted to be "damaging" by multiple in silico tools and to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients presented with focal epilepsy of varying severity, including one with refractory seizures and focal cortical dysplasia (FCD) and two with seizures responding to antiseizure medicine. Notably, the variant associated with the severe phenotype was located in the coiled-coil domain and predicted to alter hydrogen bonding and protein stability, whereas the two variants associated with mild epilepsy were located outside functional domains and had moderate molecular alterations. Analysis of spatiotemporal expression indicated that CCDC22 was expressed in brain subregions with three peaks in the fetal stage, infancy, and early adulthood, especially in the fetal stage, explaining the occurrence of developmental abnormities., Significance: CCDC22 variants are potentially associated with X-linked focal epilepsy and FCD. The molecular subregional effects supported the occurrence of FCD., Competing Interests: Declaration of competing interest All the authors declare that there are no conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Resection of high-grade glioma with sodium fluorescein can improve the resection rate of the glioma and improve survival. However, it is unclear whether the yellow fluorescence boundary of the high-grade glioma is consistent with the actual boundary of the tumor. This study explores the yellow fluorescence boundary and the actual tumor boundary in high-grade glioma surgery., Methods: This is a retrospective analysis of 10 patients with high-grade gliomas who underwent tumor visualization with sodium fluorescein. After staining of the tumor, random selections of both developed and non-developed yellow fluorescent border tissue at the fluorescence chromogenic boundary were made, followed by pathological examination. Claudin-5, an important component of the tight connections between vascular endothelial cells, was assessed by immunohistochemistry and qRT-PCR in the tumor and surrounding tissues in order to determine the tumor cell content of the tissue, blood-brain barrier damage, and vascular proliferation. The yellow fluorescence boundary was compared with the actual tumor boundary and the results analyzed., Results: Tumor cells were still detected outside the yellow fluorescence boundary during high-grade glioma surgery ( P  <  0.05). Claudin-5 expression was higher in high-grade gliomas than in adjacent normal tissues ( P  < 0.05), while disconnected Claudin-5 expression was associated with intraoperative yellow fluorescence imaging ( r  = 0.67)., Conclusions: There is a difference between the yellow fluorescence boundary and the actual boundary of the tumor in high-grade glioma, and there are glioma cell infiltrations in the brain tissue of the undeveloped yellow fluorescent border. To ensure patient recovery and function, it is recommended that tumor resection be expanded based on yellow fluorescence visualization. Claudin-5 is overall up-regulated in high-grade gliomas, but some Claudin-5 expression is disconnected. This Claudin-5 expression pattern may be related to the development of yellow fluorescence.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-β3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-β3 in order to evaluate its therapeutic effects. The expression pattern of TGF-β3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-β3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

LncRNA growth arrest special 5 (GAS5) and microRNA-106b (miR-106b) have been reported to be involved in the regulation of gliomas. However, their precise mechanisms in regulating the progression and development of gliomas remain unclear. We aimed to investigate the interaction between GAS5 and miR-106b, and their influence on the proliferation, migration, and invasion of gliomas cells. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. The proliferation, migration, and invasion of cells were measured by MTT, wound healing, and transwell assays, respectively. Dual luciferase reporter assay was applied for confirming the binding site between miR-106b and GAS5, miR-106b and PTEN. Significant higher expression of miR-106b, and lower expression of GAS5 and PTEN in the glioma tissues were observed. The binding sites between GAS5 and miR-106b, miR-106b and PTEN were identified. GAS5 could regulate the expression of PTEN through targeting miR-106b, and further influence EMT process, and the proliferation, migration, and invasion of gliomas cells. Meanwhile, PTEN could remarkably inhibited the proliferation, migration and invasion of glioma cells. The influence of PTEN on glioma cells and EMT was similar to GAS5. GAS5 could regulate the EMT process, and the migration of gliomas cells through miR-106b targeting PTEN. Therefore, our findings may provide a new thought for the study of pathogenesis and treatment of glioma., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

It was shown that different extracts had significant differences in the toxicity of Polygonum multiflorum. In this study, the effect of sample preparation on components and liver toxicity of different extracts from P. multiflorum were determined. Hepatoxic components were discovered based on biomembrane extraction. Comparative chemistry and toxicology between ethanol and water extracts were also performed. The results showed that ethanol extract had much stronger hepatotoxicity, the content of emodin-8-O-β-d-glucopyranoside, physcion-8-O-β-d-glucopyranoside, emodin and physcion was significantly higher in ethanol extract than in water extract, while the human hepatocytes extraction showed that 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucopyranoside, emodin-8-O-β-d-glucopyranoside, physcion-8-O-β-d-glucopyranoside, emodin and physcion had interaction with human hepatocytes. The hepatotoxic effect of these components was investigated on human hepatocytes LO2 cells and emodin-8-O-β-d-glucopyranoside, physcion-8-O-β-d-glucopyranoside, emodin and physcion were finally confirmed to be, at least partial, hepatotoxic components. The results showed that sample preparation has significant effect on components in extracts of P. multiflorum especially the components related to hepatotoxicity. Water extract, the conventional administration form of Chinese herbs, is prefer for phytotherapy before well understanding their chemistry and biological activities., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In the storage of Radix Ophiopogonis, browning often happens to cause potential risk with regard to safety. Previously few reports investigate the browning of Radix Ophiopogonis. In this research, the causes and mechanisms of the browning of Radix Ophiopogonis were preliminarily elucidated. Content determination by high-performance liquid chromatography (HPLC) and spectrophotometry, enzyme activity determination by colorimetry, and morphological observation by electron microscopy were performed in the present study. Uniform design and three-dimensional response surfaces were applied to investigate the relationship between browning and storage factors. The cortex cell wall of browned Radix Ophiopogonis was ruptured. Compared with the normal Radix Ophiopogonis, cellulase and polyphenol oxidase enzymes were activated, the levels of 5-hydroxymethylfurfural (5-HMF), total sugars, and reducing sugars were increased, while the levels of polysaccharides and methylophiopogonanone A were decreased in browned Radix Ophiopogonis. The relationship between the storage factors and degree of browning (Y) could be described by following correlation equation: Y = - 0.625 4 + 0.020 84 × X3 + 0.001 514 × X1 × X2 - 0.000 964 4 × X2 × X3. Accompanied with browning under storage conditions, the chemical composition of Radix Ophiopogonis was altered. Following the activation of cellulase, the rupture of the cortex cell wall and the outflow of cell substances flowed out, which caused the Radix Ophiopogonis tissue to become soft and sticky. The main causes of the browning were the production of 5-HMF, the activation of polyphenol oxidase, Maillard reactions and enzymatic browning. Browning could be effectively prevented when the air relative humidity (HR), temperature, and moisture content were under 25% RH, 12 °C and 18%, respectively., (Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Polygoni Multiflori Radix, He-Shou-Wu in Chinese, is a widely used traditional Chinese medicine. Clinically, water decoction is the major application form of He-Shou-Wu. Therefore, simultaneous determination of bioactive compounds in water extract is very important for its quality control., Results: A pressurized liquid extraction and short-end injection micellar electrokinetic chromatography (MEKC) were first developed for simultaneous determination of seven hydrophilic bioactive compounds in water extract of He-Shou-Wu. The influence of parameters, such as pH, concentration of phosphate, SDS and HP-β-CD, capillary temperature and applied voltage, on the analysis were carefully investigated. Optimum separation was obtained within 14 min by using 50 mM phosphate buffer containing 90 mM SDS and 2% (m/v) HP-β-CD (pH 2.5) at 15 kV and 20°C. All calibration curves showed good linearity (R2>0.9978) within test ranges. The overall LOD and LOQ were lower than 2.0 μg/mL and 5.5 μg/mL, respectively. The RSDs for intra- and inter-day of seven analytes were less than 3.2% and 4.6%, and the recoveries were 97.0%-104.2%., Conclusion: The validated method was successfully applied to the analysis of He-Shou-Wu samples, which is helpful for its quality control.

Polygonum multiflorum is one of the most commonly used Chinese medicines. In this study, an effective pressurized water extraction and HPLC method was developed for first simultaneous determination of 8 hydrophilic compounds, including gallic acid, Hypaphorine, Catechin, Proanthocyanidin B1, Epicatechin, Proanthocyanidin B2, Emodin-8-O-β-d-glucopyranoside, stilbene glycosides, in P. multiflorum. The analysis was performed on a Zorbax SB-AQ column with gradient elution of 0.05% phosphoric acid aqueous solution and acetonitrile in 45 min. All calibration curves showed good linearity (R(2)>0.9994) within test ranges. The LOD and LOQ were lower than 0.2 and 1.0 μg/mL on column, respectively. RSD for intra- and inter-day of 8 analytes were less than 4.1% and 4.0%, respectively, and the overall recovery was 96.0-100.7%. The validated method was successfully applied to quantification of 8 hydrophilic compounds in samples of P. multiflorum from different locations of China. Chemometrics such as principal component analysis (PCA) and hierarchical clustering analysis (HCA) were used to evaluate homogeneity of P. multiflorum in China, which suggested that their quality homogeneity was good., (Copyright © 2012 Elsevier B.V. All rights reserved.)