The cuproptosis-related signature predicts the prognosis and immune microenvironments of primary diffuse gliomas: a comprehensive analysis.

BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

Analysis of prognostic biomarker models of TXNIP/NLRP3/IL1B inflammasome pathway in patients with acute myeloid leukemia.

Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.

Utility of protein-protein binding surfaces composed of anti-parallel alpha-helices and beta-sheets selected by phage display.

Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded 4-helix bundle, the CC4 domain from reversion-inducing Cysteine-rich Protein with Kazal Motifs and (ii) a concave beta-sheet surface and two adjacent loops in the human FN3 domain, the scaffold for the widely used monobody platform. Using M13 phage display and next generation sequencing, we observe that, in both systems, libraries of ∼30 million variants contain binding proteins with affinities in the low µM range for baits corresponding to the extracellular domains of multiple mammalian proteins. CC4- and FN3-based binding proteins were fused to the N- and/or C-termini of Fc domains and used for immunostaining of transfected cells. Additionally, FN3-based binding proteins were inserted into VP1 of AAV to direct AAV infection to cells expressing a defined surface receptor. Finally, FN3-based binding proteins were inserted into the Pvc13 tail fiber protein of an extracellular contractile injection system particle to direct protein cargo delivery to cells expressing a defined surface receptor. These experiments support the utility of CC4 helices B and C and of FN3 beta-strands C, D, and F together with adjacent loops CD and FG as surfaces for engineering general purpose protein-binding reagents.

Lactate drives CD38 signaling to promote Epithelial-Mesenchymal Transition through Snail induction in non-small cell lung cancer cells.

CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

Prognostic nomogram models for predicting survival probability in elderly glioblastoma patients.

PURPOSE: To investigate the prognostic factors of survival and develop a predictive nomogram model for elderly GBM patients. METHODS: Elderly patients (> = 65 years) with histologically diagnosed GBM were extracted from the SEER database. Survival analysis of overall survival (OS) was performed by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used to determine independent prognostic factors and these factors were used to further construct the nomogram model. RESULTS: A total of 9068 elderly GBM patients (5122 males and 3946 females) were included, with a median age of 72 years (65-96 years). All patients were divided randomly into the training group (n = 6044) and the validation group (n = 3024) by a ratio of 2:1. Cox regression analyses on OS showed eight independent prognostic factors (race, age, tumor side, tumor size, metastasis, surgery, radiotherapy, and chemotherapy) in the training cohort. Also, seven variables (except for race) were identified on CSS in the training group. By comprising these variables, the nomogram models on OS and CSS for predicting the 6-month, 1-year, and 2-year survival probability were constructed and exhibited moderate consistency, respectively. Then, they could be validated well in the validation cohort and by C-index, time-dependent ROC curve, calibration plot, and DCA curve. CONCLUSIONS: Nomogram models on OS and CSS could provide an applicable tool to predict the survival probability and provide clinical references regarding treatment strategies and prognosis.

Structure of WNT inhibitor adenomatosis polyposis coli down-regulated 1 (APCDD1), a cell-surface lipid-binding protein.

Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues, APCDD1 transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed ß-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.

The Association of Homocysteine and Diabetic Retinopathy in Homocysteine Cycle in Chinese Patients With Type 2 Diabetes.

Objective: This study aimed to explore the relationship between homocysteine (Hcy) and diabetic retinopathy (DR) and the impacts of the Hcy pathway on this relationship against this background. Methods: This study retrieved 1979 patients with type 2 diabetes (T2D) from the First Affiliated Hospital of Liaoning Medical University in Jinzhou, Liaoning Province, China. Multiple logistic regression was used to analyze the effects of Hcy cycle on the relationship between Hcy and DR. Spearman's rank correlation analysis was used to analyze the correlation between risk factors related to DR progression and Hcy. Finally, the results of logistic regression were supplemented by mediation analysis. Results: We found there was a negative correlation between low concentration of Hcy and DR (OR : 0.83, 95%CI: 0.69-1). After stratifying all patients by cysteine (Cys) or Methionine (Met), this relationship remained significant only in low concentration of Cys (OR: 0.75, 95%CI: 0.61-0.94). Through the RCS curve, we found that the effect of Hcy on DR presents a U-shaped curve relationship. Mediating effect in Met and Hcy cycles was also significant [Total effect c (OR: 0.968, 95%CI: 0.938-0.998), Direct effect path c' (OR: 0.969, 95%CI: 0.940-0.999), Path a (OR: 1.047, 95%CI: 1.004-1.091), Path b (OR: 0.964, 95%CI: 0.932-0.998)]. Conclusions: The relationship between Hcy and DR presents a U-shaped curve and the homocysteine cycle pathway has an impact on it. And too low concentration of Hcy indicates a lack of other substances, such as vitamins. It is suggested that the progression of DR is the result of a combination of many risk factors. Further prospective studies are needed to determine the role of Hcy in the pathogenesis of DR.

Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats.

The aim of the study was to investigate the inhibitory effect of hydroxysaff yellow A (HSYA) on diabetic retinopathy (DR). For this, a total of 27 rats were randomly divided into normal control, model, and HSYA groups. The body weight, blood glucose, and blood-retinal barrier damage of the rats were observed and compared. The pathological change of retinal tissue were measured using H&E staining. The apoptosis of retinal tissue ganglion cells was detected by TUNEL. The interleukin (IL)-1ß and tumor necrosis fator (TNF)-α levels were detected using enzyme-linked immunosorbent assay. The level of malondialdehyde (MDA) was detected using thiobarbituric acid method. Superoxide dismutase levels were detected using xanthine oxidase method; Nrf2 and total HO-1 protein expressions were detected using western blot assay; Bcl-2 and P53 protein expression was measured using immunohistochemical staining. The body weight and retinal damage of the HYSA group were significantly improved (p < 0.01, respectively). The apoptosis index of the HYSA group was lower than the model group (p < 0.001). The IL-1ß, TNF-α, and MDA levels of the HYSA group were significantly improved in comparison with those of the model group (p < 0.01, respectively). The Nrf-2, HO-1, Bcl-2, and P53 protein expression of HYSA group was significantly improved (p < 0.001, respectively). In conclusion, HYSA can effectively alleviate the apoptosis of retinal ganglion cells in type 2 diabetic rats and improve the progression of DR.

KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status.

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.

Noninvasive evaluation of intracranial pressure in patients with traumatic brain injury by transcranial Doppler ultrasound.

INTRODUCTION: The purpose of this study was to investigate the relationship between pulsatility index (PI) or optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in patients with traumatic brain injury (TBI), and the ability of ONSD and ICP to predict intracranial hypertension. METHODS: A total of 68 patients with TBI were included in this retrospective study. After receiving surgery treatment, they underwent transcranial Doppler ultrasound (TCD). The statistical correlation between PI or ONSD and ICP 1 week after surgery was analyzed. Furthermore, the areas under the curve (AUCs) of ONSD or PI or a combination of them were calculated to predict intracranial hypertension. RESULTS: There was a correlation between ONSD and ICP. This correlation still remained at ONSD ≥ 5 mm. Furthermore, there was a strong correlation between PI and ICP. There was a moderate correlation between ICP and PI on days 3, 4, and 5 after surgery (r = 0.508, p < .001), and a strong correlation on days 6 and 7 after surgery (r = 0.645, p < .001). Moreover, for predicting intracranial hypertension with PI ≥ 1.2 mm or ONSD ≥ 5 mm or a combination of them, the AUC was 0.729, 0.900, and 0.943, respectively (p < .001). CONCLUSIONS: The correlation between ONSD or PI and invasive ICP was different with different levels of ICP in different periods in patients with TBI after surgery. When ONSD ≥ 5 mm and PI ≥ 1.2, it could predict elevated ICP more accurately.

CircPTK2 (hsa_circ_0003221) Contributes to Laryngeal Squamous Cell Carcinoma by the miR-1278/YAP1 Axis.

Laryngeal cancer accounts for 20% of all head and neck malignancies. Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer and is characterized by squamous differentiation, a high mortality rate, and poor prognosis. Accumulating studies have indicated that circular RNAs (circRNAs) are critical regulators in many cancers. CircPTK2 exerts an important regulatory role in several cancers. In this study, we aimed to elucidate the function of circPTK2 (hsa_circ_0003221) in LSCC. Through a series of investigations, we discovered that circPTK2 was significantly upregulated in LSCC tissues cells. Functionally, cell counting kit-8 (CCK-8) and flow cytometry analyses revealed that knockdown of circPTK2 suppressed LSCC cell viability and the cell cycle while promoting cell apoptosis. Notably, silencing circPTK2 inhibited tumor growth in vivo. Mechanistically, circPTK2 functioned as a molecular sponge of miR-1278 to upregulate YAP1 expression in LSCC cells. Moreover, YAP1 knockdown inhibited malignant phenotypes of LSCC cells. The rescue experiments showed that YAP1 overexpression reversed the effects of circPTK2 on LSCC cells. Therefore, we concluded that circPTK2 facilitates LSCC progression through the miR-1278/YAP1 axis.

Ultrasound-homogenization-assisted extraction of polyphenols from coconut mesocarp: Optimization study.

Coconut pericarp (shell fiber (mesocarp) and shell (endocarp)), the main by-product of coconut production, is often discarded and causing serious environmental pollution. To make better use of coconut pericarp, the extraction process of polyphenols from coconut mesocarp (CM) carefully studied by screening seven solvent systems, optimizing the assisted ultrasonic process by response surface methodology, and comparing the four processes of Ultrasound-Assisted Extraction (UAE), Homogenization-Assisted Extraction (HAE), Homogenization-Ultrasound-Assisted Extraction (HUAE), and Ultrasound-Homogenization-Assisted Extraction (UHAE). The UAE and HAE are considered to be the main methods for efficient extraction of natural active ingredients. The former effectively destroys the cell wall structure and promotes the intermolecular diffusion based on the cavitation, thermal and mechanical effect of ultrasonic, while the latter breaks the material based on strong shear force between the rotor and stator. Their combinations (HUAE and UHAE) enhance the damage to the cell wall of raw materials and improve the extraction efficiency by the synergistic effect. The results showed that using 60% acetone (V : V) as extraction solvent, solid-liquid ratio of 1:5 g mL-1, ultrasonic temperature of 80 â„ƒ, ultrasonic time of 80 min, ultrasonic power of 225 W, and then homogenizing at 10,000 rpm for 10 min, the total flavonoid content of CM reached the maximum value of 551.99 ± 12.69 mg Rutin g-1 dry weight (dw), while the total phenolic content reached the maximum value of 289.48 ± 4.41 mg GAE g-1 dw at 10,000 rpm for 5 min, which may be related to the oxidative degradation of polyphenols caused by the increase of polyphenol oxidase with the extension of homogenization time. This study provides a technical guarantee for the further utilization of phenolic substances in CM.

Risk Factors and Neurologic Outcomes in Patients with Traumatic Brain Injury and Coagulopathy Within 72 h After Surgery.

OBJECTIVE: The purpose of this study was to explore the effect of coagulopathy in patients with traumatic brain injury (TBI) during the early postoperative period. METHODS: The baseline characteristics, intraoperative management, and follow-up data of 462 patients with TBI between January 2015 and June 2019 were collected and retrospectively analyzed by multivariate logistic regression. Coagulopathy was defined as activated partial thromboplastin time > 40 s, international normalized ratio > 1.4, or platelet counts < 100×109/L. RESULTS: Multivariate logistic regression analysis revealed that the Glasgow Coma Scale (GCS) on admission, Injury Severity Score (ISS) on admission, pupil mydriasis, duration of surgery, intraoperative blood loss, and intraoperative crystalloid resuscitation were independent risk factors for patients who developed coagulopathy after surgery. There were statistical differences in mortality (p = 0.049), the Glasgow Outcome Scale-Extended (GCS-E; p = 0.024), and the modified Rankin Scale (p = 0.043) between the patients with and without coagulopathy 1 week after surgery. Coagulopathy within 72 h after surgery revealed the higher mortality at 1 week (66.7%), 3 months (71.4%), and 6 months (76.2%). Coagulopathy within 72 h after surgery in patients with a TBI predicted worse disease progression and unfavorable neurologic outcomes. CONCLUSION: Taking practical and reasonable measures to manage these risk factors may protect patients with TBI from postoperative coagulopathy.

Evaluation of the quality and readability of online information about breast cancer in China.

OBJECTIVE: This study aimed at evaluating the quality and readability of online information about breast cancer written in Chinese. METHODS: An Internet search was conducted for "breast cancer" in Chinese using the Baidu search engine. Website quality was evaluated using the DISCERN instrument, and readability was evaluated using the Chinese Readability Index Explorer (CRIE). Higher DISCERN score indicated higher quality of websites, while higher CRIE score indicated lower readability of the content of the websites. We also investigated the effects of website producer category, and the associations of search engine ranking with DISCERN and CRIE scores. RESULTS: A total of 49 websites were included. The mean overall DISCERN score was 50.27 ± 4.14, and the mean CRIE score was 6.78 ± 0.16. Websites produced by non-profit organizations had the highest overall DISCERN scores, while those produced by private individuals had the lowest CRIE scores. Search engine ranking had no significant correlation with website quality or readability. CONCLUSIONS: The quality and readability of breast cancer websites in Chinese were not satisfactory, and they varied among different website producer categories. PRACTICE IMPLICATIONS: Website producers should seek to provide more accurate, comprehensive, and easy-to-understand information to better meet the needs of breast cancer patients. In addition, search engines should revise algorithms to promote websites with higher quality and accessibility.

Epidural Anesthesia With Low Concentration Ropivacaine and Sufentanil for Percutaneous Transforaminal Endoscopic Discectomy: A Randomized Controlled Trial.

Introduction: Percutaneous transforaminal endoscopic discectomy is a simple and effective treatment for lumbar intervertebral disc herniation, and local anesthesia is often applied in this kind of surgery in many developing countries, including China. However, many patients still feel excruciating pain under this condition. Epidural anesthesia with low-concentration ropivacaine has no impact on muscle strength, and patients might follow the surgeon well during operation. We hypothesize that epidural anesthesia is feasible for percutaneous transforaminal endoscopic discectomy. Methods: Two hundred patients with disc herniation who underwent percutaneous transforaminal endoscopic discectomy were randomized to receive either epidural anesthesia or local infiltration anesthesia. Primary outcome measures included the pain score, the cooperation degree, and patients' satisfaction. Mean arterial pressure and heart rate were also recorded. Results: Compared with the local anesthesia group, visual analog scale scores, mean arterial pressure, and heart rate were significantly lower in the epidural anesthesia group (P < 0.05), and patients' satisfaction was higher. There were no significant differences in the total operation time or blood loss between two groups. Conclusions: Epidural anesthesia with low-concentration ropivacaine and sufentanil is safe and effective for percutaneous transforaminal endoscopic discectomy. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR-IOR-17011768.

Cerebral venous sinus thrombosis following transsphenoidal surgery for craniopharyngioma: A case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare condition in patients with craniopharyngioma following transsphenoidal surgery. CASE SUMMARY: A 56-year-old man who underwent transsphenoidal surgery for craniopharyngioma 26 d ago presented gradual headache and cerebrospinal fluid leakage while vomiting 5 d post-discharge and required readmission to our department of neurosurgery. After admission, head imaging examination showed a hyperdense shadow in the superior sagittal sinus and right transverse sinus, edema at the bilateral parietal lobe, and hemorrhage at the left parietal lobe and right occipital lobe; the venous phase of cerebral angiography revealed CVST. The patient was treated immediately by intravenous thrombolysis, endovascular thrombolysis, and mechanical thrombectomy after the definite diagnosis. However, the neurological status of the patient continued to deteriorate and he died on the fourth day after readmission. CONCLUSION: For craniopharyngioma undergoing transsphenoidal surgery, it is vital to take an effective strategy to manage the postoperative complications, such as diabetes insipidus, severe electrolyte imbalance, and cerebrospinal fluid leakage. Additionally, the early differential diagnosis of CVST is essential when it develops clinical symptoms, especially in patients following transsphenoidal surgery with a high risk of CVST. Subsequently, the timely and effective treatment of the CVST is critical for preventing neurological deterioration.

Silver Nanoparticles on Nanoscale Silica Platelets (AgNP/NSP) and Nanoscale Silica Platelets (NSP) Inhibit the Development of Fusarium oxysporum f. sp. niveum.

Nanotechnology has attracted much attention recently because of its agricultural applications. In this study, we analyzed the ability of two potential nanomaterials (NMs), nanoscale silica platelets (NSP) and silver nanoparticles on nanoscale silica platelets (AgNP/NSP), to control Fusarium wilt [caused by Fusarium oxysporum f. sp. niveum (Fon)] disease in watermelon. Both AgNP/NSP and NSP significantly reduced Fon mycelial growth and spore viability. In addition, AgNP/NSP decreased the mycelium viability at concentrations of 150 and 200 ppm. Scanning and transmission electron microscopy showed significant morphological effects on Fon cells, such as increased roughness and interior hollowing after AgNP/NSP and NSP treatments. Further, fluorescence staining experiments showed that a concomitant increase in membrane permeability occurred after treatment with NMs. The biochemical effects of NM treatment included a significant reduction in secreted cellulase activity. Interestingly, the addition of cysteine as a reducing agent decreased effects of NSP on Fon spores, suggesting suppression of Fon spore development attributable to oxidative stress. Taken together, these results indicate that AgNP/NSP and NSP may potentially serve as nanofungicides for future control of Fusarium wilt and other fungal diseases.

Surgical Evacuation of Spontaneous Cerebellar Hemorrhage: Comparison of Safety and Efficacy of Suboccipital Craniotomy, Stereotactic Aspiration, and Thrombolysis and Endoscopic Surgery.

BACKGROUND: Current surgical therapies for spontaneous intracerebellar hemorrhage (SCH) include suboccipital craniotomy (SC), stereotactic aspiration and thrombolysis (SAT), and endoscopic surgery (ES). Evidence comparing the therapeutic effects of these 3 methods is scarce. The safety and efficacy of SC, SAT, and ES for SCH are still uncertain. METHODS: 75 patients with SCH who received SC, SAT, or ES were reviewed retrospectively. Baseline parameters before the operation, evacuation rate, perihematoma edema, postoperative complications, and cumulative case fatalities were collected. Also, 12 months after ictus, the long-term functional outcomes in patients with regard to fourth ventricle compression and age were judged, respectively, by the modified Rankin Scale (mRS). RESULTS: The SAT was less effective in evacuating hematoma than were SC and ES. The perihematoma edema on postoperative day 7 and surgical complications were highest in the SC group. The functional outcome represented by mRS was better in the SAT group than in the SC and ES groups for patients with fourth ventricle compression grade 1. For patients with fourth ventricle compression grades 2 and 3, the ES group achieved the best functional outcome. Patients older than 60 years benefited less from SC than from ES and SAT. CONCLUSIONS: SAT may be suitable for SCH patients with fourth ventricle compression grade 1, and ES may be suitable for SCH patients with fourth ventricle compression grades 2 and 3. Aged patients benefit less from SC than from SAT and ES.

The iron pro-chelator BHAPI attenuates glutamate-induced oxidative stress via Wnt-ß/catenin pathway in HT22 cells.

Disturbances in intracellular iron homeostasis are associated with brain damage under various neuropathological conditions. However, exposure of neuronal cells to classical iron chelators could interfere with physiological iron functions in the brain. Thus, iron pro-chelators represent a more advanced approach to exert strong free-iron binding capacity only under oxidative stress conditions. In the present study, we investigated the protective effects of an iron pro-chelator BHAPI [(E)-N'-(1-(2-((4- (4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene) isonicotino hydrazide] against glutamate-induced toxicity in neuronal HT22 cells. The results showed that BHAPI significantly increased cell viability, decreased lactate dehydrogenase (LDH) release, inhibited apoptotic cell death and reduced the activation of caspase-3 after glutamate treatment. This protection was accompanied by the preservation of mitochondrial function, as evidenced by reduced mitochondrial oxidative stress, attenuated lipid peroxidation and enhanced ATP generation. In addition, BHAPI promoted Wnt/ß-catenin signaling, which was related to destabilization of ß-catenin destruction complex. The Wnt/ß-catenin signaling inhibitor JW74, but not IWP2, partially prevented the protective effects of BHAPI. In conclusion, our data suggested that BHAPI acted as a neuroprotective agent against glutamate-induced toxicity, and this protection might be mediated by preservation of mitochondrial function and regulation of Wnt/ß-catenin pathway.