Dynamic stratified porosity computation from canopy interaction simulation between airflow and leaves.

The main goal of wind-driven spraying is to use assisted airflow to disrupt the structure of branches and leaves and broaden the air delivery channel, so as to achieve uniform droplet deposition in the middle and lower parts of the canopy. Due to the complex branch and leaf structure inside the canopy, there is currently no effective method to express the dynamic changes of canopy porosity and the law of airflow attenuation under assisted airflow. In this study, based on the two-way fluid-structure interaction numerical simulation method, the relating between the assisted airflow and the structural parameters of the cotton canopy is analyzed, and a new method for predicting and simulating the dynamic porosity of the canopy is proposed. Firstly, a two-way fluid-structure interaction model based on Lattice Boltzmann (LB) solver and Finite Element (FE) solver is developed to simulate the deformation motion of cotton leaves and the spatial distribution of airflow field, and the correctness of the numerical simulation is verified based on indoor measurement data. Secondly, the post-processing method of Computational Fluid Dynamics (CFD) is used to obtain images of leaves at different canopy positions under assisted airflow, and the porosity changes are calculated and analyzed by image processing. The research results show that under different initial wind speeds (5 m·s-1, 10 m·s-1, 15 m·s-1), the maximum normalized mean absolute error (NMAE) between the simulated values and the measured values is 13.99%, 20.72% and 16.08%, respectively. The coefficient of determination (R2) for linear fitting between simulated values and measured values is 0.9221. These validation results indicate the effectiveness of the numerical simulation method. The validated CFD model is applied to predict leaf deformation and porosity changes within the canopy under various wind loads and times. The application results have well revealed the interaction between crop leaves and airflow, and will be beneficial to make a better understanding of the effect of assisted airflow on droplet deposition.

Autocrine S100B in astrocytes promotes VEGF-dependent inflammation and oxidative stress and causes impaired neuroprotection.

Minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains not fully understood. In the present study, we investigated the effect and mechanism of S100B, a predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. We discovered that S100B expressions and autocrine were significantly increased in MHE rat brains and MHE rat brain-derived astrocytes. Furthermore, S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress in MHE astrocytes. MHE astrocytes supported impairment of neuronal survival and growth in a co-culture system. To sum up, a comprehensive understanding of the role of S100B-overexpressed MHE astrocyte in MHE pathogenesis may provide insights into the etiology of MHE.

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology.

Paclitaxel is an herbal active ingredient used in clinical practice that shows anti-tumor effects. However, its biological activity, mechanism, and cancer cell-killing effects remain unknown. Information on the chemical gene interactions of paclitaxel was obtained from the Comparative Toxicogenomics Database, SwishTargetPrediction, Binding DB, and TargetNet databases. Gene expression data were obtained from the GSE4290 dataset. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses were performed. Gene set enrichment analysis was performed to evaluate disease pathway activation; weighted gene co-expression network analysis with diff analysis was used to identify disease-associated genes, analyze differential genes, and identify drug targets via protein-protein interactions. The Molecular Complex Detection (MCODE) analysis of critical subgroup networks was conducted to identify essential genes affected by paclitaxel, assess crucial cluster gene expression differences in glioma versus standard samples, and perform receiver operator characteristic mapping. To evaluate the pharmacological targets and signaling pathways of paclitaxel in glioblastoma, the single-cell GSE148196 dataset was acquired from the Gene Expression Omnibus database and preprocessed using Seurat software. Based on the single-cell RNA-sequencing dataset, 24 cell clusters were identified, along with marker genes for the two different cell types in each cluster. Correlation analysis revealed that the mechanism of paclitaxel treatment involves effects on neurons. Paclitaxel may affect glioblastoma by improving glucose metabolism and processes involved in modulating immune function in the body.

Construction and validation of a glioblastoma prognostic model based on immune-related genes.

Background: Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose: Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods: Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB). Results: Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB. Conclusion: Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

A Multielement Prognostic Nomogram Based on a Peripheral Blood Test, Conventional MRI and Clinical Factors for Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most malignant types of tumors in the central nervous system, and the 5-year survival remains low. Several studies have shown that preoperative peripheral blood tests and preoperative conventional Magnetic Resonance Imaging (MRI) examinations affect the prognosis of GBM patients. Therefore, it is necessary to construct a risk score based on a preoperative peripheral blood test and conventional MRI and develop a multielement prognostic nomogram for GBM. METHODS: This study retrospectively analyzed 131 GBM patients. Determination of the association between peripheral blood test variables and conventional MRI variables and prognosis was performed by univariate Cox regression. The nomogram model, which was internally validated using a cohort of 56 GBM patients, was constructed by multivariate Cox regression. RNA sequencing data from Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA datasets were used to determine peripheral blood test-related genes based on GBM prognosis. RESULTS: The constructed risk score included the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), albumin/fibrinogen (AFR), platelet/lymphocyte ratio (PLR), and center point-to-ventricle distance (CPVD). A final nomogram was developed using factors associated with prognosis, including age, sex, the extent of tumor resection, IDH mutation status, radiotherapy status, chemotherapy status, and risk. The Area Under Curve (AUC) values of the receiver operating characteristic curve (ROC) curve were 0.876 (12-month ROC), 0.834 (24-month ROC) and 0.803 (36-month ROC) in the training set and 0.906 (12-month ROC), 0.800 (18-month ROC) and 0.776 (24-month ROC) in the validation set. In addition, vascular endothelial growth factor A (VEGFA) was closely associated with NLR and LMR and identified as the most central negative gene related to the immune microenvironment and influencing immune activities. CONCLUSION: The risk score was established as an independent predictor of GBM prognosis, and the nomogram model exhibit appropriate predictive power. In addition, VEGFA is the key peripheral blood test-related gene that is significantly associated with poor prognosis.

ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway.

ACT001, derived from traditional herbal medicine, is a novel compound with effective anticancer activity in clinical trials. However, little is known regarding its role in pituitary adenomas. Here, we demonstrated that ACT001 suppressed cell proliferation and induced cell death of pituitary tumor cells in vitro and in vivo. ACT001 was also effective in suppressing the growth of different subtypes of human pituitary adenomas. The cytotoxic mechanism ACT001 employed was mainly related to autophagic cell death (ACD), indicated by autophagosome formation and LC3-II accumulation. In addition, ACT001-mediated inhibitory effect decreased when either ATG7 was downregulated or cells were cotreated with autophagy inhibitor 3-methyladenine (3-MA). RNA-seq analysis showed that mitogen-activated protein kinase (MAPK) pathway was a putative target of ACT001. Specifically, ACT001 treatment promoted the phosphorylation of JNK and P38 by binding to mitogen-activated protein kinase kinase 4 (MEK4). Our study indicated that ACT001-induced ACD of pituitary tumor cells via activating JNK and P38 phosphorylation by binding with MEK4, and it might be a novel and effective anticancer drug for pituitary adenomas.

Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1.

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

Surgery and Medical Treatment in Microprolactinoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Dopamine agonists (DAs) are recommended as the first-line treatment for prolactinomas; however, tumour recurrence after drug withdrawal remains a clinical problem. Recent studies have reported high remission rates via surgery in microprolactinomas. The aim of this systematic review and meta-analysis was to compare the clinical result of DA treatment with surgery as initial therapy in patients with treatment-naive microprolactinoma. METHODS: A comprehensive literature search for studies and reports regarding microprolactinoma patients treated with DAs and/or surgery published between January 1970 and November 2020 was conducted using four electronic databases (PubMed, Embase, Google Scholar, and the Cochrane Library). Clinical treatment outcome was evaluated by the biochemical remission of serum prolactin level to normal after treatment. The I 2 statistic was used to quantify heterogeneity. Pooled data were analysed according to a random effect model. RESULTS: Eighteen studies with 661 patients were included for analysis. The DA treatment group achieved a higher remission rate at ≥12 months follow-up (96% vs. 86%; P=0.019). Surgery showed a higher remission rate than the DA treatment group after the treatment withdrawal (78% vs. 44%; P=0.003). Patients with preoperative prolactin level of ≤200 ng/mL had a higher remission rate than patients with preoperative prolactin level of >200 ng/mL (92% vs. 40%; P=0.029). CONCLUSION: Surgery showed a high remission rate in treatment-naive microprolactinoma patients after treatment withdrawal and may be an alternative first-line treatment strategy in addition to DAs, particularly in patients with a preoperative prolactin level of ≤200 ng/mL.

Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas.

Cabergoline (CAB) is the first choice for treatment of prolactinoma and the most common subtype of pituitary adenoma. However, drug resistance and lack of effectiveness in other pituitary tumor types remain clinical challenges to this treatment. Brusatol (BT) is known to inhibit cell growth and promote apoptosis in a variety of cancer cells. In our present studies, we investigate the effects of BT on pituitary tumor cell proliferation in vitro and in vivo. BT treatment resulted in an increase in Annexin V-expressing cells and promoted the expression of apoptosis-related proteins in rat and human pituitary tumor cells. Investigation of the mechanism underlying this effect revealed that BT increased the production of reactive oxygen species (ROS) and inhibited the phosphorylation of 4EBP1 and S6K1. Furthermore, treatment with a combination of BT and CAB resulted in greater antitumor effects than either treatment alone in nude mice and pituitary tumor cells. Collectively, our results suggest that the BT-induced ROS accumulation and inhibition of mTORC1 signaling pathway leads to inhibition of tumor growth. Combined use of CAB and BT may increase the clinical effectiveness of treatment for human pituitary adenomas.

Tumor stem-like cells isolated from MMQ cells resist to dopamine agonist treatment.

Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.

Lipidomic analysis and diagnosis of glioblastoma multiforme with rapid evaporative ionization mass spectrometry.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in the central nervous system. GBM patients have a very low 5-year survival rate and most of them died within 1 year. Conventional histopathological examination for GBM diagnosis is complicated and time-consuming, which always blocks the development of more precise and effective treatments in resection operation. Rapid evaporative ionization mass spectrometry (REIMS) is a MS technique in clinical medicine research, which combines the common diathermy device with MS to acquire the lipid profiles of tissue specimens for lipidomic analysis and real-time tumor diagnosis. In this study, the REIMS method employing bipolar forceps was optimized and validated for high-throughput lipidomics and diagnosis of GBM for the first time. Total 42 lipid metabolites were tentatively identified and 12 out of 13 lipid biomarkers showed higher intensities in GBM, which were consistent with previous studies. After this, a statistic model was built with the lipidomic data for the diagnosis of GBM tumor in real-time. The diagnostic accuracy (94.74%), sensitivity (95.38%), and specificity (93.33%) were evaluated with histopathology validated brain tissue specimens that were not used in the training set. The proposed REIMS method for the lipidomic-analysis and diagnosis of GBM tumor provides a new direction for MS-based lipidomics and precision medicine and might be used to guide surgeons to precisely resect the GBM tissue and keep the normal brain tissue in operation.

Ubiquitination of p21 by E3 Ligase TRIM21 Promotes the Proliferation of Human Neuroblastoma Cells.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, which shows great clinical and biomolecule heterogeneity. Currently, surgery is still the main method of neuroblastoma treatment and specific therapeutic drugs are lacking, so useful targets are urgently needed. TRIM21 is a RING-type E3 ligase that its overexpression promotes the progression of human glioma, while whose effects on neuroblastoma have not been illustrated. Firstly, the shRNAs targeting TRIM21 were designed and found that the ablation of TRIM21 inhibits the proliferation of human neuroblastoma cells. Then the molecular mechanism study indicated that TRIM21 interacts with, and mediates p21 degradation by ubiquitination modification. Further study demonstrates that TRIM21 regulates the proliferation of neuroblastoma cells in a p21-dependent manner. These results suggest that TRIM21 might be a potential therapeutic target for neuroblastoma.

Ciclopirox and bortezomib synergistically inhibits glioblastoma multiforme growth via simultaneously enhancing JNK/p38 MAPK and NF-κB signaling.

Ciclopirox (CPX) is an antifungal drug that has recently been reported to act as a potential anticancer drug. However, the effects and underlying molecular mechanisms of CPX on glioblastoma multiforme (GBM) remain unknown. Bortezomib (BTZ) is the first proteasome inhibitor-based anticancer drug approved to treat multiple myeloma and mantle cell lymphoma, as BTZ exhibits toxic effects on diverse tumor cells. Herein, we show that CPX displays strong anti-tumorigenic activity on GBM. Mechanistically, CPX inhibits GBM cellular migration and invasion by reducing N-Cadherin, MMP9 and Snail expression. Further analysis revealed that CPX suppresses the expression of several key subunits of mitochondrial enzyme complex, thus leading to the disruption of mitochondrial oxidative phosphorylation (OXPHOS) in GBM cells. In combination with BTZ, CPX promotes apoptosis in GBM cells through the induction of reactive oxygen species (ROS)-mediated c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling. Moreover, CPX and BTZ synergistically activates nuclear factor kappa B (NF-κB) signaling and induces cellular senescence. Our findings suggest that a combination of CPX and BTZ may serve as a novel therapeutic strategy to enhance the anticancer activity of CPX against GBM.

In Vivo Regenerable Cerium Oxide Nanozyme-Loaded pH/H2O2-Responsive Nanovesicle for Tumor-Targeted Photothermal and Photodynamic Therapies.

Photodynamic therapy (PDT) and photothermal therapies (PTTs) are both promising strategies for effective tumor therapy. However, the absence of O2 at tumor sites hinders the sustained response of photosensitizers. Here, we develop a recycled cerium oxide (CeO2) catalase nanozyme-loaded hyaluronic acid nanovesicle to address the hypoxic tumor microenvironments and targeted delivery of the photosensitizers [indocyanine green (ICG)] to tumors. A polysaccharide complex effectively modifies the surface of a polyethylenimine phenylboronic acid nanostructure to achieve the CeO2 nanozyme-loading nanovesicles that exhibit both tumor-targeted enhancement and an improved hypoxic microenvironment. Also, the hydrogen peroxide responsiveness and acid-sensitive cleavage of phenylboronic acid specifically disintegrate the ICG/nanozyme coloaded nanovesicles in the tumor microenvironment. The in vitro synergistic tests and tumor suppression rate tests indicated that the cerium oxide nanozyme significantly improves the outcomes of PDT via cerium-element valence state recycling and hypoxia improvement, thus enhancing the tumor suppression efficiency. This pH/H2O2-responsive nanozyme/ICG codelivery system provides a good carrier model for improving the tumor microenvironment and increasing the efficiency of tumor-targeted PTT and PDT therapies.

A Quantified Risk-Scoring System for the Recurrence of Meningiomas: Results From a Retrospective Study of 392 Patients.

Aim: This study aimed to identify the independent risk factors of recurrence in patients undergoing primary resection of meningioma and construct a scoring system for the prediction of the risk of postoperative recurrence. Materials and Methods: The clinical data of 591 patients who underwent primary surgical resection for meningioma at the First Affiliated Hospital of Wenzhou Medical University between November 2010 and December 2016 were retrospectively reviewed. The clinical, radiological, and pathological characteristics were evaluated, and the independent risk factors for recurrence were identified via receiver operating characteristic (ROC) curve and logistic analyses. A scoring system that included these independent risk factors was used to construct a risk-predicting model that was evaluated via a ROC curve analysis. The recurrences of different subgroups were observed by Kaplan-Meier's curves. Results: The clinical data of 392 patients with meningioma were used to construct the scoring system. The logistic analysis showed that sex (OR = 2.793, 95% CI = 1.076-7.249, P = 0.035), heterogeneous tumor enhancement (OR = 4.452, 95% CI = 1.714-11.559, P = 0.002), brain invasion (OR = 2.650, 95% CI = 1.043-6.733, P = 0.041), Simpson's removal grade (OR = 5.139, 95% CI = 1.355-19.489, P = 0.016), and pathological grade (OR = 3.282, 95% CI = 1.123-9.595, P = 0.030) were independent risk factors for recurrence. A scoring system was developed and used to divide the patients into the following four subgroups: subgroup 1 with scores of 0-75 (n = 249), subgroup 2 with scores of 76-154 (n = 88), subgroup 3 with scores of 155-215 (n = 46), and subgroup 4 with scores of 216-275 (n = 9). The incidences of recurrence in each subgroup were as follows: subgroup 1, 1.2%; subgroup 2, 5.7%; subgroup 3, 26.1%; and subgroup 4, 66.7% (P < 0.001). The scoring system reliably predicted the postoperative recurrence of meningioma with a high area under the ROC curve. Conclusions: Our scoring system is a simple and reliable instrument for identifying meningioma patients at risk of postoperative recurrence and could help in optimizing individualized clinical treatment.

ß-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion.

PD-L1 up-regulation in cancer contributes to immune evasion by tumor cells. Here, we show that Wnt ligand and activated EGFR induce the binding of the ß-catenin/TCF/LEF complex to the CD274 gene promoter region to induce PD-L1 expression, in which AKT activation plays an important role. ß-Catenin depletion, AKT inhibition, or PTEN expression reduces PD-L1 expression in tumor cells, enhances activation and tumor infiltration of CD8+ T cells, and reduces tumor growth, accompanied by prolonged mouse survival. Combined treatment with a clinically available AKT inhibitor and an anti-PD-1 antibody overcomes tumor immune evasion and greatly inhibits tumor growth. In addition, AKT-mediated ß-catenin S552 phosphorylation and nuclear ß-catenin are positively correlated with PD-L1 expression and inversely correlated with the tumor infiltration of CD8+ T cells in human glioblastoma specimens, highlighting the clinical significance of ß-catenin activation in tumor immune evasion.

Immunohistochemical Profiles of Matrix Metalloproteinases and Vascular Endothelial Growth Factor Overexpression in the Antoni B Area of Vestibular Schwannomas.

OBJECTIVE: To evaluate the clinical manifestations of cystic vestibular schwannomas (VSs), investigate the immunohistochemical profiles of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression in Antoni A and B areas, and speculate the pathogenesis of cystic formation and intratumoral hemorrhage. METHODS: Clinical features and outcomes of 24 cases of cystic VSs and 38 cases of solid VSs were retrospectively compared. Immunohistochemical studies were conducted to evaluate the characteristics of MMPs and VEGF in cystic and solid VSs. RESULTS: The tumor size was 38.92 ± 1.86 mm and 31.95 ± 1.74 mm in the cystic and solid VSs group, respectively (P = 0.011). Cystic VSs were rich in the Antoni B area. MMP-9 expression was low in the Antoni A and B areas. MMP-2 was moderately expressed. No significant difference in MMP-2 expression existed between the Antoni A and B areas (P > 0.05). VEGF and MMP-14 expression were moderate in the Antoni A area and intense in the Antoni B area, and the expression of both was significantly greater in the Antoni B area than in the Antoni A area (P < 0.001). CONCLUSIONS: MMP-14 and VEGF expression were significantly greater in the Antoni B area than in the Antoni A area. Upregulated MMP-14 may degrade loose collagen in the Antoni B area and contribute to cystic formation. MMP-14 can enhance VEGF activity, which may induce extravasation of a plasma ultrafiltrate, cystic expansion, and intratumoral hemorrhage. Therefore, MMP-14 inhibition may be a therapeutic strategy for treating cystic VSs.

Label-free discrimination of glioma brain tumors in different stages by surface enhanced Raman scattering.

According to the WHO classification criteria, the most common intracranial tumor gliomas can be divided into four grades based on their symptoms. Among them, Grade Ⅰ and Grade II are low-grade gliomas, and Grade III and Grade IV are high-grade gliomas. Because gliomas have a high lethal rate, they have received widespread attention in the medical field. Based on these circumstances, a rapid and facile surface enhanced Raman scattering (SERS) method using silver nano particle-decorated silver nanorod (AgNPs@AgNR) as substrates were developed for the discrimination of gliomas. Compared with SERS-active silver nanoparticles and silver nanorod substrates, the prepared AgNPs@AgNR substrates showed an outstanding SERS performance with an enhancement factor up to 1.37 × 109. Combined AgNPs@AgNR substrate with principal component analysis (PCA), we achieved rapid discrimination of healthy brain tissue and gliomas at different grades. The spectra obtained from the tissue illustrate prominently spectral differences which can be applied to identify whether it came from a healthy region or from a glioma. The most prominently difference between the SERS spectrum of healthy brain tissue and that of gliomas at different grades is the reduction in quotient of two characteristic peaks at 653 and 724 cm-1. Furthermore, healthy brain tissue and Grade II gliomas as low grade gliomas as well as Grade III and Grade IV as high-grade gliomas can be clearly distinguished by three-dimensional PCA. Preliminary results indicate that the SERS spectra based on AgNPs@AgNR substrates can be applied for a rapid identification owing to its simple preparation of specimen and high-speed spectral acquirement.

Regenerative Potential of Menstrual Blood-Derived Stem Cells and Platelet-Derived Growth Factor in Endometrial Injury.

BACKGROUND Endometrial regeneration is essential for normal endometrial function; however, it is unclear whether and how menstrual blood-derived stem cells (MenSCs) and platelet-derived growth factor (PGDF) are associated with this phenomenon. The present study explored this topic. MATERIAL AND METHODS EM-E6/E7/hTERT cells were divided into 5 groups: control group, NC group, PDGF group, MenSCs group, and PDGF+MenSCs group. The effects of MenSCs and PDGF on cell proliferation, invasion, and microvascular formation of endometrial epithelium were investigated by CCK-8, Transwell, and tube formation assays, respectively. Mouse endometrial injury models were established and mice were randomly divided into control, model, PDGF, MenSCs, and PDGF+MenSCs groups. Pathological change was examined with hematoxylin and eosin (H&E) staining. Microvessel formation of endometrial epithelium was estimated by detecting the expression of CD34 protein with immunohistochemical (IHC) staining. Western blot analysis was used to detect the activation of Akt and Bad proteins in endometrial tissue. RESULTS MenSCs, PDGF, and the combination treatments significantly promoted the proliferation, migration, and tube formation of endometrial epithelium compared to the control and NC group. The combination of MenSCs and PDGF remarkably promoted re-epithelialization and endometrial repair. IHC staining analysis showed significant increases in CD34 expression of the endometrial tissue following treatment with PDGF and MenSCs. The combination treatments also markedly enhanced the phosphorylation of Akt and Bad in endometrial tissue. CONCLUSIONS These results suggest that MenSCs and PDGF may be candidate substances for endometrial injury repair.

Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A.

BACKGROUND: Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM). METHODS: ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot. RESULTS: ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2. CONCLUSIONS: Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.