Improved Delivery Performance of n-Butylidenephthalide-Polyethylene Glycol-Gold Nanoparticles Efficient for Enhanced Anti-Cancer Activity in Brain Tumor.

n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.

Pneumonia rebound after stopping steroid in a patient with COVID-19: A case report.

Patients with severe coronavirus disease 2019 (COVID-19) can develop a systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. The current treatment guideline recommends the use of corticosteroids in patients who require supplemental oxygen or are mechanically ventilated. This study reports a patient with severe COVID-19 pneumonia. Initially, the patient was treated with dexamethasone for 10 days and remdesivir for 5 days. There was clinical improvement following the treatments. However, on day 15, the patient experienced rebound pneumonia and clinical deterioration. His clinical condition improved until dexamethasone was re-administered. This case demonstrates the rebound phenomenon after the steroid was discontinued. The duration and timing of steroids are crucial to reduce the risk of prolonged systemic inflammation and rebound pneumonia.

Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection.

Microglia-mediated neuroinflammation is recognized to mainly contribute to the progression of neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG), known as a natural antioxidant in green tea, can inhibit microglia-mediated inflammation and protect neurons but has disadvantages such as high instability and low bioavailability. We developed an EGCG liposomal formulation to improve its bioavailability and evaluated the neuroprotective activity in in vitro and in vivo neuroinflammation models. EGCG-loaded liposomes have been prepared from phosphatidylcholine (PC) or phosphatidylserine (PS) coated with or without vitamin E (VE) by hydration and membrane extrusion method. The anti-inflammatory effect has been evaluated against lipopolysaccharide (LPS)-induced BV-2 microglial cells activation and the inflammation in the substantia nigra of Sprague Dawley rats. In the cellular inflammation model, murine BV-2 microglial cells changed their morphology from normal spheroid to activated spindle shape after 24 h of induction of LPS. In the in vitro free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, EGCG scavenged 80% of DPPH within 3 min. EGCG-loaded liposomes could be phagocytized by BV-2 cells after 1 h of cell culture from cell uptake experiments. EGCG-loaded liposomes improved the production of BV-2 microglia-derived nitric oxide and TNF-α following LPS. In the in vivo Parkinsonian syndrome rat model, simultaneous intra-nigral injection of EGCG-loaded liposomes attenuated LPS-induced pro-inflammatory cytokines and restored motor impairment. We demonstrated that EGCG-loaded liposomes exert a neuroprotective effect by modulating microglia activation. EGCG extracted from green tea and loaded liposomes could be a valuable candidate for disease-modifying therapy for Parkinson's disease (PD).

Very Robust Spray-Synthesized CsPbI3 Quantum Emitters with Ultrahigh Room-Temperature Cavity-Free Brightness and Self-Healing Ability.

Although colloidal lead halide perovskite quantum dots (PQDs) exhibit desirable emitter characteristics with high quantum yields and narrow bandwidths, instability has limited their applications in devices. In this paper, we describe spray-synthesized CsPbI3 PQD quantum emitters displaying strong photon antibunching and high brightness at room temperature and stable performance under continuous excitation with a high-intensity laser for more than 24 h. Our PQDs provided high single-photon emission rates, exceeding 9 × 106 count/s, after excluding multiexciton emissions and strong photon antibunching, as confirmed by low values of the second-order correlation function g(2)(0) (reaching 0.021 and 0.061 for the best and average PQD performance, respectively). With such high brightness and stability, we applied our PQDs as quantum random number generators, which demonstrably passed all of the National Institute of Standards and Technology's randomness tests. Intriguingly, all of the PQDs exhibited self-healing behavior and restored their PL intensities to greater than half of their initial values after excitation at extremely high intensity. Half of the PQDs even recovered almost all of their initial PL intensity. The robust properties of these spray-synthesized PQDs resulted from high crystallinity and good ligand encapsulation. Our results suggest that spray-synthesized PQDs have great potential for use in future quantum technologies (e.g., quantum communication, quantum cryptography, and quantum computing).

Predictive Factors of Cerebral Aneurysm Rerupture After Clipping.

BACKGROUND: We aimed to estimate the risk of rerupture after first-time aneurysmal clipping surgery, explore the possible related factors, and assess long-term physical functionality. We hypothesized that the modified Rankin scale (mRS) could serve as an effective substitute for Hunter and Hess scale. METHODS: This retrospective study included 171 patients with cerebral aneurysmal rupture who had completed aneurysmal clipping treatment and collected their demographic data and medical records. The outcome assessments include neuroimaging records, Hunter and Hess scale, and the mRS scale during hospitalization and follow-up after discharge. The mean length of follow-up was 4.28 years. RESULTS: After aneurysmal clipping treatment, 83 patients (48.5%) had subsequently ruptured aneurysms. The scores of the reruptured group on the Hunt and Hess scale and mRS were significantly higher than those of the non-reruptured group. Multiple Cox proportional-hazards regression also showed that postoperative mRS >2, smoking, and two or more aneurysms were potentially important risk factors leading to aneurysm rupture again [the corresponding hazard ratios (HRs) were 5.209, 2.109, and 2.775, respectively] in patients. In addition, the location of an aneurysm on the anterior cerebral artery (ACA) or the posterior communicating (Pcom) artery had a higher risk of rerupture (the corresponding HRs were 1.996 and 2.934, respectively). CONCLUSIONS: Nearly half of the collected participants experienced the rerupture episode, who had undergone the second-time clipping surgery. Smoking and multiple aneurysms are potential risk factors for aneurysmal rerupture. Most aneurysms are located along the ICA, but aneurysms located at the ACA or Pcom site are most likely to rerupture. As compared with the Hunter and Hess scale, the mRS scale does not have inferior predicting power in following patients' long-term functionalities.

Full Endoscopic Removal of Cervical Spinal Epidural Abscess: Case Report and Technical Note.

Spinal epidural abscess is a rare disease that is less likely to occur in the cervical region. When it occurs here, cervical spondylodiscitis can develop. Surgical treatment is recommended because of possible life-threatening septic and neurological complications. We present a case of an 81-year-old man who suffered from right side paralysis and was subsequently diagnosed with a C4 to C7 epidural abscess. We utilized full endoscopic surgery for patient management. The traditional surgical methods for treating cervical epidural abscesses may cause spinal instability. There has only been one previous case report on the endoscopic-assisted method. Minimal invasive surgery by a full endoscopic method can be done with a small incision and is associated with minimal blood loss and muscle damage. This is the first report on cervical epidural abscess drainage utilization a full endoscopic method. We recommend this alternative minimally invasive method to manage cervical epidural abscess.

Utilizing real-time contrast medium to detect the fistula of giant spinal arachnoid cyst and treat with minimal invasive surgery.

BACKGROUND: Spinal arachnoid cysts are rare and have varied clinical manifestations depending on the affected spinal region and nerve roots. A complete cyst excision with fistula closure is the first choice of treatment. However, it might be difficult to localize the specific position of the fistula because previous images have no enhancements or the fistula is too tiny to be detected. CASE PRESENTATION: This case is a giant lumbar extradural arachnoid cyst. We administered a lumbar injection with contrast medium into subarachnoid space under digital subtraction angiography (DSA) and disclosed the fistula. Confirming the location of fistula enabled us to perform minimally invasive surgery to ligate the fistula. Surgical intervention for a spinal arachnoid cyst might encounter the problem of the formation of a postoperative cerebrospinal fluid (CSF) fistula. We propose the option of detecting the fistula preoperatively for minimal invasive surgery. Recurrence depends on the long-term follow-up, and more cases are needed to further evaluate our technique. CONCLUSIONS: The real-time contrast medium technique for spinal arachnoid cysts contributes to the complete ligation with minimally invasive surgery.

Percutaneous Endoscopic Lumbar Surgery via the Transfacet Approach for Lumbar Synovial Cyst.

BACKGROUND: There are currently no high-quality studies on the optimal therapeutic approach for juxtafacet cyst, as treatment guidelines have not been developed. Herein, a novel technique in which we used an endoscopic transfacet approach to treat a patient with symptomatic lumbar synovial cyst is presented. CASE DESCRIPTION: An 87-year-old man presented with severe dull pain in the right anterior thigh. Lumbar magnetic resonance imaging revealed disc extrusion over the central canal zone at the L2-L3 and L4-L5 levels and an ovoid lesion with a hyperintense center plus a hypointense rim on the T2-weighted image. The lesion was located over the medial side of the right juxtafacet region at the L2-L3 level, causing thecal sac compression. After the operation, the visual analog pain scale improved with a value of 0-1/10, and straight leg raise test was negative. Microscopically, cystic fibrous tissue with focal myxoid degeneration, fibrin exudate, and scant synovial-like lining was observed. These findings were consistent with clinical synovial cyst. Three months later, lumbar magnetic resonance imaging was performed, and no evidence of cyst was disclosed. Lumbar computed tomography revealed the upper part of left L2-L3 facet joint was removed. The patient did not report any radicular pain during the 6-month follow-up period. CONCLUSIONS: Percutaneous endoscopic lumbar surgery could be a new option for the management of lumbar synovial cysts, especially when general anesthesia is not appropriate for the patient.

Full Endoscopic Interlaminar Approach for Nerve Root Decompression of Sacral Metastatic Tumor.

BACKGROUND: Endoscopic surgery has been successfully applied in treatment of degenerative spinal disease, but few studies have assessed its use in treating sacral metastasis. We report a successful full endoscopic interlaminar approach for sacral nerve root decompression of a sacral metastatic tumor. CASE DESCRIPTION: An 80-year-old man with a history of hepatocellular carcinoma presented with buttock pain with radiation to the right lower leg for 1 week. There was also decreased muscle power of the right lower extremity. Lumbosacral magnetic resonance imaging revealed metastasis of the sacral spine and right iliac bone with S1 exiting nerve root compression. S1 nerve root decompression via a full endoscopic interlaminar approach under local anesthesia was performed. Under fluorescence guidance, a working sleeve with a beveled opening was placed in the interlaminar space of L5-S1. We entered the sacral canal and identified the S1 exiting nerve root. A laminotomy was performed from the internal edge of the right sacral laminae toward the lateral recess. During decompression of the nerve root, buttock and leg pain improved gradually. There was almost complete resolution of leg pain after surgery, and the patient recovered the ability to walk. Visual analog scale score for pain decreased from 8 to 2 after 3 months of follow-up. CONCLUSIONS: For patients with sacral metastasis without spinal instability or difficulty lying in prone position under local anesthesia, the full endoscopic interlaminar approach for nerve root decompression of sacral metastasis may be a suitable method.

PLGA Microspheres Loaded with ß-Cyclodextrin Complexes of Epigallocatechin-3-Gallate for the Anti-Inflammatory Properties in Activated Microglial Cells.

Although epigallocatechin-3-gallate (EG) is well-known as a potent antioxidant and free radical scavenger for neurodegenerative diseases, it still has disadvantages that reduce its treatment effectiveness due to low bioavailability, slow absorption, and water solubility. Therefore, the aim of this study is to improve the bioavailability of EG and increase the effectiveness of anti-inflammatory properties to microglial cells by using Poly(Lactide-co-Glycolide) (PLGA) microspheres as carriers. In this study, we used UV⁻Vis spectroscopy to show the formation of the complex of ß-cyclodextrin (ß-CD) and EG (CD-EG). The loading efficiency of EG in PLGA microspheres was optimized by the addition of ß-CD. The highest loading efficiency of 16.34% was found among other formulations. The results of Fourier transform infrared spectroscopy indicated the loading of CD-EG in PLGA microspheres. The scanning electron microscopic images demonstrated the spherical PLGA particles with controlled particles size ranging from 1⁻14 µm. Moreover, the in vitro release of EG was conducted to explore the sustained release property of the PLGA formulations. In the in vitro model of mouse microglial cells (BV-2 cells) stimulated by lipopolysaccharide, the cytotoxicity test showed that for up to 1 mg/mL of PLGA microspheres no toxicity to BV-2 cells was found. PLGA microspheres can significantly suppress the nitric oxide production from BV-2 cells, indicating EG loaded in PLGA microspheres can suppress the inflammation of activated microglial cells. Furthermore, the intracellular iNOS in BV-2 cells was also found to be down regulated. In summary, we have successfully shown that the use of ß-CD can increase the loading efficiency of EG in PLGA microspheres and provide neuroprotective effect on the activated microglial cells.

Purification of Single Photons from Room-Temperature Quantum Dots.

Single photon emitters are indispensable to photonic quantum technologies. Here, we demonstrate waveform-controlled high-purity single photons from room-temperature colloidal quantum dots. The purity of the single photons does not vary with the excitation power, thereby allowing the generation rate to be increased without compromising the single-photon quality.

Regulation of miR-21 expression in human melanoma via UV-ray-induced melanin pigmentation.

Excessive environmental ultraviolet (UV) radiation produces genetic mutations that can lead to skin cancer. This study was designed to assess the potential inhibitory activity of microRNA-21 (miR-21) on the UV irradiation-stimulated melanogenesis signal pathway in melanoma cells. The molecular mechanism of miR-21-induced inhibitory activity on UV-ray-stimulated melanogenesis-regulating proteins was examined in A375.S2 human melanoma and B16F10 mouse melanoma cells. UV irradiation for 30 min induced melanogenesis signal pathway by increasing melanin production and the number of A375.S2 cells. Similarly, UV radiation increased the expression of α-melanocyte-stimulating hormone (α-MSH) protein and decreased the melanogenesis-regulating signal, such as EGFR and Akt phosphorylation. Notably, miR-21 overexpression in UV-ray-stimulated A375.S2 cells decreased α-MSH expression and increased EGFR and Akt phosphorylation levels. Furthermore, miR-21 on UV-ray- induced melanogenesis was down-regulated by the Akt inhibitor and the EGFR inhibitor (Gefitinib). Results suggest that the suppressive activity of miR-21 on UV-ray-stimulated melanogenesis may involve the down-regulation of α-MSH and the activation in both of EGFR and Akt.

Full-Endoscopic Transforaminal Approach for Removal of a Spontaneous Spinal Epidural Hematoma.

BACKGROUND: The incidence of spinal epidural hematoma (SEH) is estimated to be 1 per 1,000,000 patients per year; SEH can be classified as idiopathic, spontaneous, and secondary. The cause of spontaneous SEH is uncertain but it may be associated with minor trauma. SEH can compress surrounding structures, shown by clinical symptoms and signs that affect the spinal cord or nerve roots. Surgical treatment may be considered if medical treatment fails. CASE DESCRIPTION: A 26-year-old man presented with lower back pain and significant radicular symptoms on the left side for a week. He denied previous lumbar trauma or the use of anticoagulation drugs. We used the full-endoscopic transforaminal approach (extraforaminal technique) to remove the SEH under local anesthesia. The patient was discharged home 2 days after surgery and the radicular pain disappeared completely. Three months later, follow-up magnetic resonance imaging showed that the dark-brown lesion had been totally removed. CONCLUSIONS: Spontaneous SEHs are uncommon. Although lumbar laminectomy is the mainstream treatment in those with neurologic deficits caused by epidural hematomas, the percutaneous full-endoscopic transforaminal approach may be an option for certain SEHs.

Early diagnosis of spinal tuberculosis.

Spinal tuberculosis (STB) is a common manifestation of extrapulmonary tuberculosis (TB). STB accounts for around 2% of all cases of TB and around 15% of extrapulmonary TB cases. The World Health Organization has proposed a global strategy and targets for TB prevention, care, and control after 2015. Under this strategy, patients will receive standard care according to the recommendations and guidelines after confirmation of STB diagnosis. However, current recommendations and guidelines focus on disease and medication therapy management, and recommendations for early detection or decision-making algorithms regarding STB are lacking. In this review, we identified five key components for early diagnosis: (1) risk factors for STB; (2) common symptoms/signs of STB; (3) significant neuroradiological findings of STB; (4) significant laboratory findings of STB, including positive interferon-γ release assays and nonpyogenic evidence in initial laboratory data; and (5) significant clinical findings of STB. Individualized consideration for each patient with STB is essential, and we hope that the algorithm established in this review will provide a valuable tool for physicians who encounter cases of STB.

Risk factors associated with postcraniotomy meningitis: A retrospective study.

Postcraniotomy meningitis (PCM) is a major challenge in neurosurgery, and changing patterns of infectious agents in PCM have been noted. The limited epidemiological data and urgent clinical needs motivated this research. We conducted this study to determine a risk assessment for PCM and the current pattern of infectious agents.We performed a retrospective case-control study of significant cases of postcraniotomy meningitis in the Changhua Christian Hospital System between January 1, 2008, and December 31, 2012. Postcraniotomy meningitis was diagnosed in 22 out of 4392 surgical patients; this data was reviewed for risk assessment.This study assessed the risk factors for postcraniotomy meningitis and found that it was more frequently seen in patients who were elderly (OR = 1.57, 95% CI = 1.32-2.98, P = 0.013), underwent emergency procedures (OR = 4.82, 95% CI = 1.50-14.53, P = 0.008), had leak of cerebrospinal fluid (OR = 4.62, 95% CI = 2.03-10.50, P = 0.012), had external ventricular drainage (OR = 4.68, 95% CI = 2.46-8.87, P = 0.006), were admitted to the intensive care unit (OR = 2.41, 95% CI = 1.53-8.08, P = 0.012), had used drain placement >72 hours (OR = 2.66, 95% CI = 1.04-4.29, P = 0.007), had surgery >4.5 hours (OR = 2.38, 95% CI = 1.39-4.05, P = 0.005), had repeat operations (OR = 2.74, 95% CI = 1.31-5.73, P = 0.018), endured trauma (OR = 5.97, 95% CI = 1.57-17.61, P = 0.007), or had 30-days mortality (OR = 5.07, 95% CI = 2.20-11.48, P = 0.001). The predominant pathogens isolated from cerebrospinal fluid were Staphylococcus aureus in 8 patients (36.7%) and Acinetobacter baumannii in 7 patients (31.8%). In our study, the mortality rate was 5.1% among all postcraniotomy patients.Accurate risk assessment, early diagnosis, and choice of appropriate antibiotics in accordance with epidemiologic information are the cornerstones of reducing mortality and morbidity in PCM. The changing pattern of infectious agents in PCM over time suggests the necessity of further studies to provide the most up-to-date insight to physicians.

A cross sectional study in patients with confirmed spinal tuberculosis in central Taiwan: Analysis of preliminary clinical presentation and neuroradiological findings.

Spinal tuberculosis (STB) can cause significant functional impairment. The purpose of the present study was to analyze the factors at preliminary presentation and the neuroradiological findings in STB patients. We performed a retrospective cross-sectional analysis of cases with a definitive diagnosis of STB. Four patients with confirmed mycobacterial infection and histopathological findings confirming TB were identified. We noted two key clinical indicators. We also identified seven key neuroradiological findings associated with STB lesions. A high degree of clinical suspicion along with nine neuroradiological findings described in this study are important for STB diagnosis and for starting treatment with antituberculosis agents.

Glucose Transporter Type 4 Redistribution on the Membrane Induced by Insulin through Akt in Hydrocortisone Treatment in Rat Skeletal Muscles.

Hydrocortisone is a growth hormone frequently used in the treatment of low back pain. Hydrocortisone treatment has an anti-inflammation effect, which also inactivates glucose transporter type 4 (GLUT4) by p38 mitogen-activated protein kinase (MAPK) inhibition. Translocation of GLUT4 regulates body glucose homeostasis and muscle repair and is induced by insulin. In this study, 56 SD rats were divided into seven groups, and were treated with insulin or hydrocortisone in sedentary or exercise training groups. The muscle proteins and biochemical blood parameters were analyzed after 7 days of treatments. The results showed that the serum glucose increased in hydrocortisone treatment accompanied by GLUT4 inactivation in both the sedentary and exercise training rats. In the exercise training groups, GLUT4 was redistributed on the plasma membrane on co-treatment with insulin and hydrocortisone through Akt phosphorylation. Insulin treatment exerted a compensatory feedback effect on the GLUT4 translocation on hydrocortisone co-treatment, which was the cause of GLUT4 inactivation.

Effects of teriparatide on lung function and pain relief in women with multiple osteoporotic vertebral compression fractures.

BACKGROUND: Osteoporosis is predominantly a condition of the elderly. In this study, we evaluated the effects of teriparatide on lung function and pain relief in elderly women with multiple osteoporotic vertebral compression fractures. METHODS: A total of 37 patients who received teriparatide treatment during the period January 2010 to December 2011 were enrolled. Dual-energy X-ray absorptiometry scans were used to measure bone mineral density (BMD) and lung function was measured using a MasterScreen Body Jaeger spirometer. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values were recorded. The Oswestry Disability Index (ODI) and the Visual Analog Scale (VAS) for pain were used to evaluate physical health and pain intensity, respectively, at baseline and after 6 months of teriparatide treatment. RESULTS: Mean BMD at the lumbar spine increased from 0.716 g/cm(2) at baseline to 0.829 g/cm(2) after 6 months of treatment. In addition, both mean FVC and FEV1 values after 6 months of treatment were significantly higher than baseline values (99.01% and 100.06% vs. 87.62% and 90.62%, respectively). Teriparatide treatment also resulted in a significant reduction in self-reported pain intensity and a significant improvement in physical health as measured by VAS and ODI scores, respectively. CONCLUSIONS: In addition to increasing BMD, teriparatide treatment improves the lung function and results in diminished pain intensity in women with multiple osteoporotic vertebral compression fractures.

Inhibitory effects of scutellarein on proliferation of human lung cancer A549 cells through ERK and NFκB mediated by the EGFR pathway.

High expression levels of cyclooxygenase-2 (COX-2) contribute a strong proliferative ability to human lung cancer cells, and this function is link to the epidermal growth factor receptor (EGFR) pathway, which was mediated by extracellular-signal-regulated kinase (ERK) and nuclear factor kappa B (NFκB). In this study, scutellarein, a flavonoid compound, was screened for proliferation inhibition at different concentrations (0, 5, 25 and 50 µM) at 24 h or 48 h in human lung cancer cell line A549. Results showed that A549 cell proliferation was inhibited by 50 µM scutellarein treatment in 24 h and 48 h of treatment. The expression levels of phosphorylated EGFR, phosphorylated ERK, phosphorylated NFκB and COX-2 were reduced in a dose-dependent manner after 24 h scutellarein treatments at different concentrations. Further, ERK inhibitor U0126 and NFκB inhibitor MG132 also inhibited A549 cell proliferation similar to 50 κM scutellarein treatment from 24 h to 48 h. The experimental results showed that scutellarein could inhibit proliferation of the human lung cancer cell line A549 through ERK and NFκB mediated by the EGFR pathway.

Metastasis tumor-associated protein-2 knockdown suppresses the proliferation and invasion of human glioma cells in vitro and in vivo.

Metastasis tumor-associated protein 2 (MTA2) is a member of the MTA family that is closely associated with tumor progression and metastasis. However, the role of MTA2 in glioma cells remains unclear. The expression of MTA2 was measured using immunohistochemistry and western blotting in the human brain tumor tissue array and human glioma cell lines. The impact of MTA2 knockdown on GBM8401 and Hs683 cell growth was evaluated by MTT assay and flow cytometry. Cell migration and invasion were analyzed by cell-migration assay and Matrigel invasion assay. In addition, we used subcutaneous tumor models to study the effect of MTA2 on the growth of glioma cells in vivo. We found that MTA2 protein and mRNA expression are higher in GBM8401 and Hs683 cells than in other glioma cells (M059 J, M059 K and U-87 MG), and glioma tumor tissue correlated significantly with tumor grade (P < 0.001). Knockdown of MTA2 expression significantly inhibited cell growth, cell migration and invasion, and induced G0/G1 phase arrest in human GBM8401 and Hs683 cells in vitro. Moreover, in vivo studies using subcutaneous xenografts in mice models indicate that MTA2 knockdown significantly inhibited tumorigenicity. These results indicate that MTA2 plays an important oncogenic role in the development and progression of gliomas.