NINJ1: A new player in multiple sclerosis pathogenesis and potential therapeutic target.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination. Current treatment options for MS focus on immunosuppression, but their efficacy can be limited. Recent studies suggest a potential role for nerve injury-induced protein 1 (NINJ1) in MS pathogenesis. NINJ1, a protein involved in cell death and inflammation, may contribute to the infiltration and activation of inflammatory cells in the CNS, potentially through enhanced blood-brain barrier crossing; enhancing plasma membrane rupture during cell death, leading to the release of inflammatory mediators and further tissue damage. This review explores the emerging evidence for NINJ1's involvement in MS. It discusses how NINJ1 might mediate the migration of immune cells across the blood-brain barrier, exacerbate neuroinflammation, and participate in plasma membrane rupture-related damage. Finally, the review examines potential therapeutic strategies targeting NINJ1 for improved MS management. Abbreviations: MS, Multiple sclerosis; CNS, Central nervous system; BBB, Blood-brain barrier; GSDMD, Gasdermin-D; EAE, Experimental autoimmune encephalitis; HMGB-1, High mobility group box-1 protein; LDH, Lactate dehydrogenase; PMR, Plasma membrane rupture; DMF, Dimethyl fumarate; DUSP1, Dual-specificity phosphatase 1; PAMPs, Pathogen-associated molecular patterns; DAMPs, Danger-associated molecular patterns; PRRs, Pattern recognition receptors; GM-CSF, Granulocyte-macrophage colony stimulating factor; IFN-γ, Interferon gamma; TNF, Tumor necrosis factor; APCs, Antigen-presenting cells; ECs, Endothelial cells; TGF-ß, Transforming growth factor-ß; PBMCs, Peripheral blood mononuclear cells; FACS, Fluorescence-activated cell sorting; MCP-1, Monocyte chemoattractant protein-1; NLRP3, Pyrin domain-containing 3; TCR, T cell receptor; ROS, Reactive oxygen species; AP-1, Activator protein-1; ANG1, Angiopoietin 1; BMDMs, Bone marrow-derived macrophages; Arp2/3, actin-related protein 2/3; EMT, epithelial-mesenchymal transition; FAK, focal adhesion kinase; LIMK1, LIM domain kinase 1; PAK1, p21-activated kinases 1; Rac1, Ras-related C3 botulinum toxin substrate 1; ß-cat, ß-caten; MyD88, myeloid differentiation primary response gene 88; TIRAP, Toll/interleukin-1 receptor domain-containing adapter protein; TLR4, Toll-like receptor 4; IRAKs, interleukin-1 receptor-associated kinases; TRAF6, TNF receptor associated factor 6; TAB2/3, TAK1 binding protein 2/3; TAK1, transforming growth factor-ß-activated kinase 1; JNK, c-Jun N-terminal kinase; ERK1/2, Extracellular Signal Regulated Kinase 1/2; IKK, inhibitor of kappa B kinase; IκB, inhibitor of NF-κB; NF-κB, nuclear factor kappa-B; AP-1, activator protein-1; ASC, Apoptosis-associated Speck-like protein containing a CARD; NEK7, NIMA-related kinase 7; NLRP3, Pyrin domain-containing 3; CREB, cAMP response element-binding protein.

A multidimensional pre-operative planning method of unruptured vertebral artery dissecting aneurysms using three-dimensional AWE mapping and hemodynamic simulation.

OBJECTIVE: High-resolution magnetic resonance imaging (HR-MRI) can provide valuable insights into the evaluation of vascular pathological conditions, and 3D digital subtraction angiography (3D-DSA) offers clear visualization of the vascular morphology and hemodynamics. This study aimed to investigate the potential of a multimodal method to treat unruptured vertebral artery dissection aneurysms (u-VADAs) by fusing image data from HR-MRI and 3D-DSA. METHODS: This observational study enrolled 5 patients diagnosed with u-VADAs, who were scheduled for interventional treatment. The image data of HR-MRI and 3D-DSA were merged by geometry software, resulting in a multimodal model. Quantified values of aneurysm wall enhancement (AWE), wall shear stress (WSS), neck velocity, inflow volume, intra-stent flow velocity (ISvelocity), and intra-aneurysmal velocity (IAvelocity) were calculated from the multimodal method. RESULTS: We found the actual lengths of u-VADAs in the multimodal model were longer than the 3D-DSA model. We formulated surgical plannings based on the WSS, IA velocity, and neck velocity. The post-operative value of IAvelocity, neck velocity, and follow-up quantified values of AWE were decreased compared with the pre-operative condition. After that, u-VADAs were complete occlusion in four patients and near-complete occlusion in one patient during the 6th-month follow-up after surgery. CONCLUSION: The multidimensional method combining HR-MRI with 3D-DSA may provide more valuable information for treating VADAs, with the potential to develop effective surgical planning.

Design and application of the intraoperative protective device for patients undergoing interventional therapy via the femoral artery approach.

BACKGROUND: Femoral artery puncture is still the most used surgical approach. Because the operation requires local anaesthesia, the patient may not be able to exert full self-control, and their upper and lower limbs and trunk need to be constrained by a protection device. OBJECTIVE: To explore the safe application effect of a new type of anti-movement protection device for upper and lower extremities, shoulders and chest in patients undergoing interventional therapy via the femoral artery approach. METHODS: This is a prospective randomised controlled study. A total of 230 patients were randomly divided into two groups: the study group (n= 115) and the control group (n= 115). The time needed to implement the restraint operation and the loosening of the restraint device in the two groups was recorded, and the satisfaction of surgeons and nurses was investigated. RESULTS: The time needed to perform restraint operation in the study group was significantly less than that in the control group (4.06 ± 0.61 min vs. 7.01 ± 0.76 min, P< 0.05). The satisfaction of surgeons and nurses with the use of the new protective device was significantly better than that of the conventional restraint band (P< 0.05). CONCLUSION: The new anti-movement protection device for upper and lower limbs, shoulders and chest can conveniently and quickly achieve effective protection and braking of patients, ensure the safety of surgery and improve satisfaction.

Application of intraarterial superselective indocyanine green angiography in bypass surgery for adult moyamoya disease.

Background: Extracranial-intracranial (EC-IC) bypass surgery is the main treatment approach to moyamoya disease, and an accurate assessment of the patency of anastomosis is critical for successful surgery. So far, the most common way to do this is the intraoperative intravenous indocyanine green (ICG) video-angiography. Intra-arterial ICG-VA has been applied to treat peripheral cerebral aneurysms, spinal arteriovenous fistulas, and dural arteriovenous fistulas, but few reports have concerned the use of arterial injection of ICG to evaluate anastomotic patency. This research aims to explore the feasibility and effects of catheter-guided superficial temporal artery injection of ICG in the evaluation of anastomotic patency after bypass surgery. Methods: In this study, 20 patients with moyamoya disease or syndrome who underwent bypass surgery were divided into two groups, one who received intravenous ICG angiography and the other who received intra-arterial ICG angiography, to compare the two injection methods for vascular anastomosis patency. We conducted conventional intraoperative digital subtraction angiography (DSA) in a hybrid operating room during extracranial-intracranial (EC-IC) bypass surgery, including the additional step of injecting ICG into the main trunk of the superficial temporal artery (STA) through a catheter. Results: Intra-arterial injection of indocyanine green video-angiography (ICG-VA) indicated good patency of the vascular anastomosis when compared with conventional digital subtraction angiography (DSA) and intravenous ICG-VA, confirming the feasibility of using the arterial injection of ICG for assessing anastomotic patency. And intra-arterial ICG-VA results in faster visualization than intravenous ICG-VA (p < 0.05). Besides, ICG-VA through arterial injection provided valuable information on the vascular blood flow direction after the bypass surgery, and allowed for visual inspection of the range of cortical brain supply from the superficial temporal artery and venous return from the cortex. Moreover, arterial injection of ICG offered a rapid dye washout effect, reducing the repeat imaging time. Conclusion: This study indicates that intra-arterial ICG-VA has good effects in observing the direction of blood flow in blood vessels and the range of cortical brain supply from the STA, which reflects blood flow near the anastomosis and provides additional information that may allow the postoperative prediction of cerebral hyperperfusion syndrome. However, the procedure of intra-arterial ICG-VA is relatively complicated compared to intravenous ICG-VA.

Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation.

We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by bisulfite pyrosequencing. Among them, 18 pairs of case-control samples were used for WBC mRNA detection, 32 pairs were used for WBC MTA1 protein measurement, and 50 pairs were used for plasma inflammatory factor analysis. Lipopolysaccharide (LPS) treatment was used to induce an inflammatory injury cell model of human brain microvascular endothelial cells (BMECS). 5-Aza-2'-deoxycytidine (5-AZA), nicotinic acid (NA), and MTA1 siRNAs were used in functional experiments to examine BMECS behaviors. RT-qPCR, Western blot, and ELISA or cytometric bead arrays were used to measure the expression levels of MTA1, cytokines, and signaling pathway proteins in human blood or BMECS. The degree of MTA1 promoter methylation was reduced in BAVM compared with the control group and was inversely proportional to MTA1 expression. Plasma ApoA concentrations in BAVM patients were significantly lower than those in controls and correlated positively with MTA1 promoter methylation and negatively with MTA1 expression. The expression of cytokine was markedly higher in BAVM than in controls. Cell experiments showed that 5-AZA decreased the methylation level of MTA1 and increased the expression of MTA1 protein. LPS treatment significantly increased cytokine concentrations (p < 0.05). NA and MTA1 silencing could effectively reverse the LPS-mediated increase in IL-6 and TNF-α expression through the NF-κB pathway. Our study indicated that NA may regulate MTA1 expression by affecting promoter DNA methylation, improve vascular inflammation through the NF-κB pathway, and alleviate the pathological development of BAVM.

Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent.

Fisetin, a natural flavonoid, possesses numerous biological activities that have been extensively studied in various diseases. When it comes to cancer, fisetin exhibits a range of biological effects, such as suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration. Moreover, fisetin has the ability to enhance the effectiveness of chemotherapy. The anticancer properties of fisetin can be attributed to a diverse array of molecules and signaling pathways, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1. Consequently, fisetin holds promise as a therapeutic agent for anticancer treatment. In this review, we place emphasis on the biological functions and various molecular targets of fisetin in anticancer therapy.

New aneurysm formation after endovascular embolization of a vertebral epidural AV fistula: a rare sequelae of NF AV fistulae.

Background: Neurofibromatosis type 1 (NF-1) is a dominant genetic disorder often accompanied by lesions of the neurovascular system. Patients with NF-1 are predisposed to unique vertebral artery fistula (AVF). Case description: We report on a rare case of multiple neurovascular abnormalities in a 47-year-old man with neurofibromatosis. He was admitted due to a sudden headache and was found to have suffered a subarachnoid hemorrhage from a left vertebral arteriovenous fistula. He underwent two endovascular procedures complicated by a delayed extraspinal mass 7 days after treatment. Angiography revealed a new vascular abnormality, and although we performed another embolization, it failed to respond to further embolization. Conclusion: Vascular abnormalities in patients with NF-1 can be complex. Endovascular intervention remains feasible for NF-1 related AVF, however, partial occlusion of the fistula should be avoided to limit and iatrogenic damage to the blood vessels.

The mechanism of ferroptosis in early brain injury after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a cerebrovascular accident with an acute onset, severe disease characteristics, and poor prognosis. Within 72 hours after the occurrence of SAH, a sequence of pathological changes occur in the body including blood-brain barrier breakdown, cerebral edema, and reduced cerebrovascular flow that are defined as early brain injury (EBI), and it has been demonstrated that EBI exhibits an obvious correlation with poor prognosis. Ferroptosis is a novel programmed cell death mode. Ferroptosis is induced by the iron-dependent accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis involves abnormal iron metabolism, glutathione depletion, and lipid peroxidation. Recent study revealed that ferroptosis is involved in EBI and is significantly correlated with poor prognosis. With the gradual realization of the importance of ferroptosis, an increasing number of studies have been conducted to examine this process. This review summarizes the latest work in this field and tracks current research progress. We focused on iron metabolism, lipid metabolism, reduction systems centered on the GSH/GPX4 system, other newly discovered GSH/GPX4-independent antioxidant systems, and their related targets in the context of early brain injury. Additionally, we examined certain ferroptosis regulatory mechanisms that have been studied in other fields but not in SAH. A link between death and oxidative stress has been described. Additionally, we highlight the future research direction of ferroptosis in EBI of SAH, and this provides new ideas for follow-up research.

Application of intraoperative infrared thermography in bypass surgery for adult moyamoya syndrome: A preliminary study.

Background and objectives: Cerebral revascularization surgery is the mainstay of treatment for moyamoya syndrome (MMS) today, and intraoperative determination of the patency of the revascularized vessel is a critical factor in the success of the procedure. Currently, major imaging modalities include intraoperative indocyanine green (ICG) videoangiography (ICG-VA), digital subtraction angiography (DSA), and vascular ultrasound Doppler. Infrared thermography is a modern imaging modality with non-contact devices for the acquisition and analysis of thermal data. We aimed to investigate the feasibility and advantages of infrared thermography in determining anastomotic patency during MMS surgery. Methods: Indocyanine green videoangiography and infrared thermography were performed simultaneously in 21 patients with MMS who underwent bypass surgery. The detection result of vessel patency was compared, and the feasibility and advantages of infrared thermography were assessed. Results: The patency of the anastomosis was accurately determined in 21 patients using either ICG angiography or infrared thermography. In 20 patients, the results of infrared thermography showed that the vascular anastomosis was unobstructed, and there was an agreement with the subsequent results of ICG-VA. In one patient, we suspected inadequate patency after testing the anastomosis with infrared thermography, and the results of ICG-VA evaluation of the anastomosis confirmed that there was indeed an anastomotic obstruction. Conclusion: Compared with ICG-VA, infrared thermography might offer an alternative non-invasive, contrast-free option in assessing anastomosis patency compared with ICG-VA, and it is likely to become more widely used in the clinic in the near future.

The global change of gene expression pattern caused by PTEN mutation affects the prognosis of glioblastoma.

Glioblastoma (GBM), an aggressive primary tumor, is common in humans, accounting for 12-15% of all intracranial tumors, and has median survival of fewer than 15 months. Since a growing body of evidence suggests that conventional drugs are ineffective against GBM, our goal is to find emerging therapies that play a role in its treatment. This research constructs a risk model to predict the prognosis of GBM patients. A set of genes associated with GBM was taken from a GBM gene data bank, and clinical information on patients with GBM was retrieved from the Cancer Genome Atlas (TCGA) data bank. One-way Cox and Kaplan-Meier analyses were performed to identify genes in relation to prognosis. Groups were classified into high and low expression level of PTEN expression. Prognosis-related genes were further identified, and multi-factor Cox regression analysis was used to build risk score equations for the prognostic model to construct a survival prognostic model. The area under the ROC curve suggested that the pattern had high accuracy. When combined with nomogram analysis, GJB2 was considered an independent predictor of GBM prognosis. This study provides a potential prognostic predictive biological marker for GBM patients and confirms that GJB2 is a key gene for GBM progression.

Whole-genome resequencing of the wheat A subgenome progenitor Triticum urartu provides insights into its demographic history and geographic adaptation.

Triticum urartu is the progenitor of the A subgenome in tetraploid and hexaploid wheat. Uncovering the landscape of genetic variations in T. urartu will help us understand the evolutionary and polyploid characteristics of wheat. Here, we investigated the population genomics of T. urartu by genome-wide sequencing of 59 representative accessions collected around the world. A total of 42.2 million high-quality single-nucleotide polymorphisms and 3 million insertions and deletions were obtained by mapping reads to the reference genome. The ancient T. urartu population experienced a significant reduction in effective population size (Ne) from ∼3 000 000 to ∼140 000 and subsequently split into eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations during the Younger Dryas period. A map of allelic drift paths displayed splits and mixtures between different geographic groups, and a strong genetic drift towards hexaploid wheat was also observed, indicating that the direct donor of the A subgenome originated from northwestern Syria. Genetic changes were revealed between the eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations in genes orthologous to those regulating plant development and stress responses. A genome-wide association study identified two single-nucleotide polymorphisms in the exonic regions of the SEMI-DWARF 37 ortholog that corresponded to the different T. urartu ecotype groups. Our study provides novel insights into the origin and genetic legacy of the A subgenome in polyploid wheat and contributes a gene repertoire for genomics-enabled improvements in wheat breeding.

Hyperoside: A review on its sources, biological activities, and molecular mechanisms.

Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.

Fructus arctii: an overview on its traditional uses, pharmacology and phytochemistry.

OBJECTIVES: Fructus arctii (F. arctii) is the dried ripe fruit of Arctium lappa Willd (Asteraceae). It is being used as a traditional medicine in China, Japan, Iran, Europe, Afghanistan, India, etc. for cough, inflammation, clearing the heat, detoxification, cancer and diabetes. This review summarized the botanical description, distribution, ethnopharmacology, bioactive constituents and pharmacological actions of F. arctii including methods to assess its quality. In addition, this review also provides insights into future research directions on F. arctii to further explore its bioactive constituents, mechanism involved in pharmacological activity, and clinical use including the development of new analytical methods for assessing the quality. KEY FINDINGS: The comprehensive analysis of the literature revealed that F. arctii contains lignans, volatile oil, flavonoids, sesquiterpenoids, triterpenes, phenolic acids, etc. Experimental studies on various extracts and drug formulations showed that it has antioxidant, antimicrobial, hypoglycaemic, lipid-lowering, anti-inflammatory, analgesic, antiviral, anti-tumour activity, etc. SUMMARY: The pharmacological activity of a few major constituents in F. arctii have been identified. However, there are still need more studies and more new technologies to prove the pharmacological activity and the effective mechanism of the other constituents that undergoing uncertain. Except for the animal experiments, clinical studies should be carried out to provide the evidence for clinical application.

Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms.

DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The PTBP1 levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (p = 0.001), CpG2 (p < 0.001), CpG3 (p = 0.037), CpG4 (p = 0.003), CpG5 (p = 0.006), CpG6 (p = 0.02), and mean methylation (p < 0.001). The mRNA level of PTBP1 in the blood was much lower in IAs compared with controls (p = 0.002), and the PTBP1 expression was significantly associated with DNA methylation promoter levels in individuals (r = -0.73, p < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in PTBP1 than non-smokers (p = 0.002). However, no statistical difference in PTBP1 methylation was found between ruptured and unruptured IA groups (p > 0.05). The ROC analyses of curves revealed that PTBP1 methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, p < 0.0001; male, AUC = 0.76, p = 0.002; female, AUC = 0.79, p < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the PTBP1 gene, which further decreased PTBP1 gene expression and participated in the pathogenesis of IA. The methylation of PTBP1 may be a potential predictive marker for the occurrence of IA.

Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage.

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Brucea javanica: A review on anticancer of its pharmacological properties and clinical researches.

BACKGROUND: The dried fruits of Brucea javanica (L.) Merr (BJ) is being widely investigated, both in lab and in clinic, to explore its potential anticancer activity and molecular mechanism involved. PURPOSE: We appraised the available literature and suggested the future research directions to improve the medicinal value of BJ. METHOD: In this review, we have summarized the scientific findings from experimental and clinical studies regarding the anticancer activity and mechanisms. RESULTS: Numerous studies have reported that BJ exerts anticancer effect on various types of cancer lines through inhibiting cell proliferation, inducing apoptosis, inhibiting migration/invasion, inducing autophagy and restraining angiogenesis. Brucea javanica triggers the generation of reactive oxygen species (ROS), release of cytochrome C, activation of mitochondrial apoptosis pathway and regulation of a series of signal pathways and proteins related to cancer. The molecular mechanism involved are inhibiting the PI3K/Akt/mTOR, NF-κB and Nrf2-Notch1 pathways; up or down modulating the levels of p53, p62, p21, Bax, and Bcl-2 respectively, and inhibiting the expression of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Brucea javanica's efficacy in treating cancer patients either as a main or supportive treatment is also discussed in this review. CONCLUSION: This review will serve as a comprehensive resource of BJ's potential as anticancer agent and its molecular pathways. The analysis of the literature suggests that BJ can serve as a potential candidate for the treatment of cancer.

Novel LncRNA OXCT1-AS1 indicates poor prognosis and contributes to tumorigenesis by regulating miR-195/CDC25A axis in glioblastoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) contribute to multiple biological processes in human glioblastoma (GBM). However, identifying a specific lncRNA target remains a challenge. In this study, bioinformatics methods and competing endogenous RNA (ceRNA) network regulatory rules were used to identify GBM-related lncRNAs and revealed that OXCT1 antisense RNA 1 (OXCT1-AS1) is a potential therapeutic target for the treatment of glioma. METHODS: Based on the Gene Expression Omnibus (GEO) dataset, we identified differential lncRNAs, microRNAs and mRNAs and constructed an lncRNA-associated ceRNA network. The novel lncRNA OXCT1-AS1 was proposed to function as a ceRNA, and its potential target miRNAs were predicted through the database LncBase Predicted v.2. The expression patterns of OXCT1-AS1 in glioma and normal tissue samples were measured. The effect of OXCT1-AS1 on glioma cells was checked using the Cell Counting Kit 8 assay, cell colony formation assay, Transwell assay and flow cytometry in vitro. The dual-luciferase activity assay was performed to investigate the potential mechanism of the ceRNA network. Finally, orthotopic mouse models of glioma were created to evaluate the influence of OXCT1-AS1 on tumour growth in vivo. RESULTS: In this study, it was found that the expression of lncRNA OXCT1-AS1 was upregulated in both The Cancer Genome Atlas (TCGA) GBM patients and GBM tissue samples, and high expression of OXCT1-AS1 predicted a poor prognosis. Suppressing OXCT1-AS1 expression significantly decreased GBM cell proliferation and inhibited cell migration and invasion. We further investigated the potential mechanism and found that OXCT1-AS1 may act as a ceRNA of miR-195 to enhance CDC25A expression and promote glioma cell progression. Finally, knocking down OXCT1-AS1 notably attenuated the severity of glioma in vivo. CONCLUSION: OXCT1-AS1 inhibits glioma progression by regulating the miR-195-5p/CDC25A axis and is a specific tumour marker and a novel potential therapeutic target for glioma treatment.

Herba Siegesbeckiae: A review on its traditional uses, chemical constituents, pharmacological activities and clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Siegesbeckiae, mainly includes Sigesbeckia orientalis L, Sigesbeckiae pubescens Makino and Sigesbeckiae glabrescens Makino. Herba Siegesbeckiae, also known as 'Xi-Xian Cao' (Chinese: ), has been regarded as an important traditional Chinese medicine since Tang dynasty. The dried aerial parts of Herba Siegesbeckiae are also being used as a herbal medicine in many countries such as Japan, Korea and Vietnam. In China, Herba Siegesbeckiae has been used for the treatment of rheumatic arthralgia with aching and weakness of loins and knees, as well as numbness of limbs. AIM OF THIS REVIEW: The aim of this review was to provide critical analysis on the scientific evidence to support the traditional uses of Herba Siegesbeckiae. The information available on its in botanical characteristics, traditional uses, chemical constituents, pharmacological activities, clinical studies, toxicity and quality control was summarized to understand the current research and provided the leas for future study. MATERIALS AND METHODS: The search terms "Herba Siegesbeckiae", "Sigesbeckia orientalis", "Sigesbeckia pubscens" and "Sigesbeckia glabrescens" were used to obtain the information from electronic databases such as Web of Science, China National Knowledge Infrastructure, PubMed, Google Scholar and SciFinder Scholar and other web search instruments (Springer, Yahoo search). The information provided in this review was based on peer-reviewed papers in English and Chinese. Besides, information was also collected from ancient documents. RESULT: The studies showed that Herba Siegesbeckiae contains sesquiterpenoids, diterpenoids, flavonoids and organic acids, etc. Due to these constituents, it displayed numerous pharmacological activities, such as anti-inflammatory, antitumor, antiallergic, antioxidant, antithrombotic and antibacterial activities. In addition, it showed effects in protecting myocardial and cerebral ischemia injury. CONCLUSIONS: According to its traditional uses, chemical constituents, pharmacological activities and clinic studies, Herba Siegesbeckiae is regarded as a promising medical plant with various chemical compounds and numerous pharmacological activities. However, fewer experimental studies were focused on toxicity and quantitative study of 3 species. It suggested that further in-depth study of toxicity and quality control were critical for future evaluation of drug efficacy and safety.

Atomistic Insights into Aluminum Doping Effect on Surface Roughness of Deposited Ultra-Thin Silver Films.

Ultra-thin and continuous metallic silver films are attracting growing interest due to the applications in flexible transparent conducting electrodes. The surface morphology and structure of silver film are very important for its electrical resistivity and optical loss. Therefore, roughness control is essential for the production of ultra-thin metallic electrode film. We have investigated the effect of aluminum doping on the improvement of surface morphology of ultra-thin silver films using molecular dynamics simulations. Al-doped silver films showed smaller surface roughness than pure silver films at various substrate temperatures. When the temperature of the substrate was 600 K, the roughness of Al-doped silver film first decreased, and then increased with the increase of the incident velocity of silver atoms. Silver atoms were more likely to agglomerate on the surface of the substrate after adding aluminum atoms, as aluminum dopants promoted the immobilization of silver atoms on SiO2 substrate due to the anchoring effect. The smoother surface could be attributable to the reduced mean free path of silver due to the cage effect by the aluminum dopant.

DNA methylation of AHCY may increase the risk of ischemic stroke.

Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (AHCY) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of AHCY was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in AHCY methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), p < 0.0001], and these associations remained significant in both male (p = 0.003) and female (p = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated AHCY in the case group than the control group in all age groups (age < 60 years, p = 0.007; age ≥ 60 years, p < 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for AHCY methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, p = 0.0001], male patients (AUC = 0.67, p = 0.004), and female patients (AUC = 0.75, p = 0.0002). Our study confirmed a significant association between the AHCY DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.