RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells.

The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.

MYO1F regulates antifungal immunity by regulating acetylation of microtubules.

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9 Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow-derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

Fluidic Spatial-Confinement Scaffold Affords a Multicomponent DNA Reaction with Improved Efficiency and Accelerated Kinetics.

Enzyme-free nucleic acid amplification reactions with the capability of signal catalytic amplification have been widely used in biosensors. However, these multicomponent, multistep nucleic acid amplification systems often suffer from low reaction efficiency and kinetics. Herein, inspired by the natural cell membrane system, we utilized the red blood cell membrane as a fluidic spatial-confinement scaffold to construct a novel accelerated reaction platform. By simply modifying with cholesterol, DNA components can be efficiently integrated into the red blood cell membrane through hydrophobic interactions, which greatly increases the local concentration of DNA strands. Moreover, the fluidity of the erythrocyte membrane improves the collision efficiency of DNA components in the amplification system. Based on the increased local concentration and improved collision efficiency, the fluidic spatial-confinement scaffold significantly improved the reaction efficiency and kinetics. Taking catalytic hairpin assembly (CHA) as a model reaction, an RBC-CHA probe based on the erythrocyte membrane platform enables a more sensitive detection of miR-21 with a sensitivity that is 2 orders of magnitude higher than the free CHA probe and a fast reaction rate (about 3.3-fold). The proposed strategy provides a new idea for the construction of a novel spatial-confinement accelerated DNA reaction platform.

PtSnBi Nanoplates Enable Photoacoustic Imaging-Guided Highly Efficient Photothermal Tumor Ablation.

The development of photothermal agents (PTAs) with robust photostability and high photothermal conversion efficiency is of great importance for cancer photothermal therapy. Herein, a novel PTA was created using two-dimensional intermetallic PtSnBi nanoplates (NPs), which demonstrated excellent photostability and biocompatibility with a high photothermal conversion efficiency of ∼61 % after PEGylation. More importantly, PtSnBi NPs could be employed as photoacoustic imaging contrast agents for tumor visualization due to their strong absorbance in the NIR range. In addition, both in vitro and in vivo experiments confirmed that PtSnBi NPs had a good photothermal efficacy under NIR laser irradiation. Therefore, the remarkable therapeutic characteristics of PtSnBi NPs make them a most promising candidate for cancer theranostics.

Cutting Edge: EPHB2 Is a Coreceptor for Fungal Recognition and Phosphorylation of Syk in the Dectin-1 Signaling Pathway.

Invasive fungal infections have become a leading cause of death among immunocompromised patients, leading to around 1.5 million deaths per year globally. The molecular mechanisms by which hosts defend themselves against fungal infection remain largely unclear, which impedes the development of antifungal drugs and other treatment options. In this article, we show that the tyrosine kinase receptor EPH receptor B2 (EPHB2), together with dectin-1, recognizes ß-glucan and activates downstream signaling pathways. Mechanistically, we found that EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation after dectin-1 ligand stimulation, whereas dectin-1 is critical for the recruitment of Syk. Ephb2-deficient mice are susceptible to Candida albicans-induced fungemia model, which also supports the role of EPHB2 in antifungal immunity. Overall, we provide evidence that EPHB2 is a coreceptor for the recognition of dectin-1 ligands and plays an essential role in antifungal immunity by phosphorylating Syk.

Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases.

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.

Detecting lesion-specific ischemia in patients with coronary artery disease with computed tomography fractional flow reserve measured at different sites.

OBJECTIVES: Whether a stenosis can cause hemodynamic lesion-specific ischemia is critical for the treatment decision in patients with coronary artery disease (CAD). Based on coronary computed tomography angiography (CCTA), CT fractional flow reserve (FFRCT) can be used to assess lesion-specific ischemia. The selection of an appropriate site along the coronary artery tree is vital for measuring FFRCT. However the optimal site to measure FFRCT for a target stenosis remains to be adequately determined. The purpose of this study was to determine the optimal site to measure FFRCT for a target lesion in detecting lesion-specific ischemia in CAD patients by evaluating the performance of FFRCT measured at different sites distal to the target lesion in detecting lesion-specific ischemia with FFR measured with invasive coronary angiography (ICA) as reference standard. METHODS: In this single-center retrospective cohort study, a total of 401 patients suspected of having CAD underwent invasive ICA and FFR between March 2017 and December 2021 were identified. 52 patients having both CCTA and invasive FFR within 90 days were enrolled. Patients with vessels 30%-90% diameter stenosis as determined by ICA were referred to invasive FFR evaluation, which was performed 2-3 cm distal to the stenosis under the condition of hyperemia. For each vessel with 30%-90% diameter stenosis, if only one stenosis was present, this stenosis was selected as the target lesion; if serial stenoses were present, the stenosis most distal to the vessel end was chosen as the target lesion. FFRCT was measured at four sites: 1 cm, 2 cm, and 3 cm distal to the lower border of the target lesion (FFRCT-1 cm, FFRCT-2 cm, FFRCT-3 cm), and the lowest FFRCT at the distal vessel tip (FFRCT-lowest). The normality of quantitative data was assessed using the Shapiro-Wilk test. Pearson's correlation analysis and Bland-Altman plots were used for assessing the correlation and difference between invasive FFR and FFRCT. Correlation coefficients derived from Chi-suqare test were used to assess the correlation between invasive FFR and the cominbaiton of FFRCT measred at four sites. The performances of significant obstruction stenosis (diameter stenosis ≥ 50%) at CCTA and FFRCT measured at the four sites and their combinations in diagnosing lesion-specific ischemia were evaluated by receiver-operating characteristic (ROC) curves using invasive FFR as the reference standard. The areas under ROC curves (AUCs) of CCTA and FFRCT were compared by the DeLong test. RESULTS: A total of 72 coronary arteries in 52 patients were included for analysis. Twenty-five vessels (34.7%) had lesion-specific ischemia detected by invasive FFR and 47 vesseles (65.3%) had no lesion-spefifice ischemia. Good correlation was found between invasive FFR and FFRCT-2 cm and FFRCT-3 cm (r = 0.80, 95% CI, 0.70 to 0.87, p < 0.001; r = 0.82, 95% CI, 0.72 to 0.88, p < 0.001). Moderate correlation was found between invasive FFR and FFRCT-1 cm and FFRCT-lowest (r = 0.77, 95% CI, 0.65 to 0.85, p < 0.001; r = 0.78, 95% CI, 0.67 to 0.86, p < 0.001). FFRCT-1 cm + FFRCT-2 cm, FFRCT-2 cm + FFRCT-3 cm, FFRCT-3 cm + FFRCT-lowest, FFRCT-1 cm + FFRCT-2 cm + FFRCT-3 cm, and FFRCT-2 cm + FFRCT-3 cm + FFRCT-lowest were correatled with invasive FFR (r = 0.722; 0.722; 0.701; 0.722; and 0.722, respectively; p < 0.001 for all). Bland-Altman plots revealed a mild difference between invasive FFR and the four FFRCT (invasive FFR vs. FFRCT-1 cm, mean difference -0.0158, 95% limits of agreement: -0.1475 to 0.1159; invasive FFR vs. FFRCT-2 cm, mean difference 0.0001, 95% limits of agreement: -0.1222 to 0.1220; invasive FFR vs. FFRCT-3 cm, mean difference 0.0117, 95% limits of agreement: -0.1085 to 0.1318; and invasive FFR vs. FFRCT-lowest, mean difference 0.0343, 95% limits of agreement: -0.1033 to 0.1720). AUCs of CCTA, FFRCT-1 cm, FFRCT-2 cm, FFRCT-3 cm, and FFRCT-lowest in detecting lesion-specific ischemia were 0.578, 0.768, 0.857, 0.856 and 0.770, respectively. All FFRCT had a higher AUC than CCTA (all p < 0.05), FFRCT-2 cm achieved the highest AUC at 0.857. The AUCs of FFRCT-2 cm and FFRCT-3 cm were comparable (p > 0.05). The AUCs were similar between FFRCT-1 cm + FFRCT-2 cm, FFRCT-3 cm + FFRCT-lowest and FFRCT-2 cm alone (AUC = 0.857, 0.857, 0.857, respectively; p > 0.05 for all). The AUCs of FFRCT-2 cm + FFRCT-3 cm, FFRCT-1 cm + FFRCT-2 cm + FFRCT-3 cm, FFRCT-and 2 cm + FFRCT-3 cm + FFRCT-lowest (0.871, 0.871, 0.872, respectively) were slightly higher than that of FFRCT-2 cm alone (0.857), but without significnacne differences (p > 0.05 for all). CONCLUSIONS: FFRCT measured at 2 cm distal to the lower border of the target lesion is the optimal measurement site for identifying lesion-specific ischemia in patients with CAD.

Selective In Situ Analysis of Mature microRNAs in Extracellular Vesicles Using a DNA Cage-Based Thermophoretic Assay.

Mature microRNAs (miRNAs) in extracellular vesicles (EVs) are involved in different stages of cancer progression, yet it remains challenging to precisely detect mature miRNAs in EVs due to the presence of interfering RNAs (such as longer precursor miRNAs, pre-miRNAs) and the low abundance of tumor-associated miRNAs. By leveraging the size-selective ability of DNA cages and polyethylene glycol (PEG)-enhanced thermophoretic accumulation of EVs, we devised a DNA cage-based thermophoretic assay for highly sensitive, selective, and in situ detection of mature miRNAs in EVs with a low limit of detection (LoD) of 2.05 fM. Our assay can profile EV mature miRNAs directly in serum samples without the interference of pre-miRNAs and the need for ultracentrifugation. A clinical study showed that EV miR-21 or miR-155 had an overall accuracy of 90 % for discrimination between breast cancer patients and healthy donors, which outperformed conventional molecular probes detecting both mature miRNAs and pre-miRNAs. We envision that our assay can advance EV miRNA-based diagnosis of cancer.

Metal-Organic Frameworks Featuring 18-Connected Nonanuclear Rare-Earth Oxygen Clusters and Cavities for Efficient C2H2/CO2 Separation.

Two rare-earth (RE) metal-organic frameworks (MOFs) formulated as {(Me2NH2)2[RE9(µ3-OH)8(µ2-OH)3(DCPB)6(H2O)3]}n (RE = Y3+ and Tb3+; termed JXNU-10) built from a triangular 3,5-di(4'-carboxylphenyl)benzoic acid (DCPB3-) ligand are presented. JXNU-10 features the rarely observed 18-connected nonanuclear [RE9(µ3-OH)8(µ2-OH)3] clusters, one-dimensional-nanosized tubular channels, and trigonal-bipyramidal cavities. The presence of the high-nuclear RE-oxo clusters and the robust coordination bonds between the highly charged RE ions and the hard base of the carboxylate/hydroxyl oxygen atoms yielded the water-resistant JXNU-10 materials. JXNU-10 exhibits highly selective sorption of C2H2 over CO2 and highly efficient separation of a C2H2 and CO2 mixture. The carboxylate oxygen atoms and the rich π systems of the organic ligands on the pore walls are the desirable binding sites for a C2H2 molecule with acidic hydrogen atoms and an alkyne group, facilitating the excellent efficiency of JXNU-10 for C2H2/CO2 separation demonstrated by breakthrough experiments.

Quantitative dynamic contrast-enhanced MR imaging can be used to predict the pathologic stages of oral tongue squamous cell carcinoma.

BACKGROUND: To investigate whether quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters can be used to predict the pathologic stages of oral tongue squamous cell carcinoma (OTSCC). METHODS: For this prospective study, DCE-MRI was performed in participants with OTSCC from May 2016 to June 2017. The pharmacokinetic parameters, including Ktrans, Kep, Ve, and Vp, were derived from DCE-MRI by utilizing a two-compartment extended Tofts model and a three-dimensional volume of interest. The postoperative pathologic stage was determined in each patient based on the 8th AJCC cancer staging manual. The quantitative DCE-MRI parameters were compared between stage I-II and stage III-IV lesions. Logistic regression analysis was used to determine independent predictors of tumor stages, followed by receiver operating characteristic (ROC) analysis to evaluate the predictive performance. RESULTS: The mean Ktrans, Kep and Vp values were significantly lower in stage III-IV lesions compared with stage I-II lesions (p = 0.013, 0.005 and 0.011, respectively). Kep was an independent predictor for the advanced stages as determined by univariate and multivariate logistic analysis. ROC analysis showed that Kep had the highest predictive capability, with a sensitivity of 64.3%, a specificity of 82.6%, a positive predictive value of 81.8%, a negative predictive value of 65.5%, and an accuracy of 72.5%. CONCLUSION: The quantitative DCE-MRI parameter Kep can be used as a biomarker for predicting pathologic stages of OTSCC.

Assessment of Cardiac Lead Perforation: Comparison Among Chest Radiography, Transthoracic Echocardiography and Electrocardiography-gated Contrast-enhanced Cardiac CT.

OBJECTIVES: Cardiac lead perforation is a rare but potentially life-threatening event. The purpose of this study was to investigate the diagnostic performances of chest radiography, transthoracic echocardiography (TTE) and electrocardiography (ECG)-gated contrast-enhanced cardiac CT in the assessment of cardiac lead perforation. METHODS: This retrospective study was approved by the ethics review board of Sun Yat-Sen Memorial Hospital at Sun Yat-Sen University (Guangzhou, China), and the need to obtain informed consent was waived. Between May 2010 and Oct 2017, 52 patients were clinically suspected to have a cardiac lead perforation and received chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT. Among them, 13 patients were identified as having cardiac lead perforation. The diagnostic performances of these three modalities were evaluated by receiver-operating characteristic (ROC) curves using a composite reference standard of surgical and electrophysiological results and clinical follow-up. The areas under ROCs (AUROCs) were compared with the McNemar test. RESULTS: The accuracies of chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT imaging for the diagnosis of cardiac lead perforation were 73.1%, 82.7% and 98.1%, respectively. ECG-gated contrast-enhanced cardiac CT had a higher AUROC than chest radiography (p < 0.001) and TTE (p < 0.001). CONCLUSIONS: ECG-gated contrast-enhanced cardiac CT is superior to both chest radiography and TTE imaging for the assessment of cardiac lead perforation. KEY POINTS: • ECG-gated contrast-enhanced cardiac CT has an accuracy of 98.1% in the diagnosis of cardiac lead perforation. • The AUROC of ECG-gated contrast-enhanced cardiac CT is higher than those of chest radiography and TTE imaging. • ECG-gated contrast-enhanced cardiac CT imaging has better diagnostic performance than both chest radiography and TTE imaging for the assessment of cardiac lead perforation.

The Prognostic Role of Expression of Nectin-4 in Esophageal Cancer.

BACKGROUND Nectin-4 is overexpressed in several human malignant tumors. This study aimed to investigate the expression of Nectin-4 in esophageal cancer tissues compared with adjacent normal esophageal tissue and its association with clinicopathological parameters and prognosis. MATERIAL AND METHODS Nectin-4 expression in esophageal cancer tissues was compared with adjacent normal esophageal tissue from 94 patients using immunohistochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The chi-squared (χ²) test and Fisher's exact test compared categorical variables. The log-rank test and Kaplan-Meier survival analysis assessed the relationship between Nectin-4 expression and overall survival (OS). Univariate and multivariate Cox proportional risk models compared Nectin-4 expression, patient prognosis, and clinicopathological parameters. RESULTS Nectin-4 expression was significantly increased in esophageal cancer tissue compared with normal tissue (P<0.001), tumor size ≥4.5 cm, and tumor invasion in T3/T4 compared with T1/T2 stage. Kaplan-Meier survival analysis showed that the OS of patients with increased Nectin-4 expression was significantly reduced compared with patients with low levels of Nectin-4 expression. Patient prognosis in men was less than women, tumor diameter ≥4.5 cm, lymph node involvement, and depth of invasion were associated with poor prognosis. Independent prognostic factors were Nectin-4 expression, lymph node involvement, and depth of invasion. CONCLUSIONS In patients with esophageal cancer, the expression levels of Nectin-4, lymph node involvement, and depth of tumor invasion were independent prognostic factors. Further studies should be performed to evaluate the diagnostic and prognostic roles of Nectin-4 and its potential role as a therapeutic target.

SUZ12 is a novel putative oncogene promoting tumorigenesis in head and neck squamous cell carcinoma.

The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC patient cohorts. Moreover, SUZ12 protein was markedly up-regulated in primary HNSCC samples from our patient cohort as assessed by immunohistochemical staining and its overexpression significantly associated with cervical node metastasis and reduced overall and disease-free survival. In the 4-nitroquinoline 1-oxide (4NQO)-induced HNSCC mouse model, increased SUZ12 immunostaining was observed along with disease progression from epithelial hyperplasia to squamous cell carcinoma in tongue. Furthermore, shRNA-mediated SUZ12 knock-down significantly inhibited cell proliferation, migration and invasion in HNSCC cells, and resulted in compromised tumour growth in vivo. Collectively, our data reveal that SUZ12 might serve as a putative oncogene by promoting cell proliferation, migration and invasion, and also a novel biomarker with diagnostic and prognostic significance for HNSCC.

MR T2 value of the tibial nerve can be used as a potential non-invasive and quantitative biomarker for the diagnosis of diabetic peripheral neuropathy.

OBJECTIVE: To determine the role of quantitative tibial nerve T2 value in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: MR imaging and T2 mapping of the tibial nerve were performed in 22 diabetic patients with DPN, 20 diabetic patients without DPN and 20 healthy controls. Nerve T2 values were measured, and compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic ability of T2 value to identify DPN. RESULTS: Nerve T2 value was 55.06 ± 4.05 ms, 48.91 ± 3.06 ms and 45.61 ± 1.86 ms in patients with DPN, patients without DPN and controls, respectively. Patients with DPN had significantly higher nerve T2 values than patients without DPN (P < 0.001). Nerve T2 values in patients without DPN were higher than in controls (P < 0.001). ROC analysis showed that T2 values had a diagnostic sensitivity of 81.8 %, specificity of 89.2 % and area under the curve of 0.922 for identifying patients with DPN from patients without DPN plus controls when the cutoff point was 51.34 ms. CONCLUSION: T2 value of the tibial nerve can be used as an alternative, non-invasive quantitative parameter to assess DPN in diabetic patients. KEY POINTS: • Tibial nerves in patients with DPN showed T2 hyperintensity and enlargement. • Tibial nerves in patients with DPN had an increased T2 value. • T2 value might be used as a quantitative biomarker for DPN.

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma.

OBJECTIVE: Increased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). METHODS: The expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan. 2007 to Dec. 2013. The potential associations between SUZ12 abundance and multiple clinicopathological parameters were assessed by Chi square test. Moreover, the effect of SUZ12 expression on patients' survival was further estimated by Kaplan-Meier and Cox regression analyses. RESULTS: Our immunohistochemical staining data revealed aberrant overexpression of SUZ12 in a large subset of TSCC as compared to normal tongue mucosa. Elevated SUZ12 was found to be significantly associated with cervical nodes metastasis (P = 0.0325) and reduced overall as well as disease-free survival (Log-rank test, P = 0.0225, 0.0179, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of SUZ12 (low/high) as an important independent prognostic factor for patients' survival. CONCLUSIONS: Our data reveal that aberrant SUZ12 overexpression is associated with cervical nodes metastasis and reduced survival in TSCC. These findings suggest that SUZ12 might play critical roles during tongue tumorigenesis and serve as a novel biomarker with diagnostic and prognostic significance.

Inhibition of Hydrogen Peroxide-Induced Human Umbilical Vein Endothelial Cells Aging by Allicin Depends on Sirtuin1 Activation.

BACKGROUND The abnormal activity of Sirtuin 1 (Sirt1) is closely related to the aging of vascular endothelial cells. As a bioactive molecule, allicin has antioxidant, anti-inflammatory, and lipid-regulating mechanisms. However, few reports about the relationship of allicin and Sirt1 have been published. In this study, we aimed to elucidate the effect of allicin on Human Umbilical Vein Endothelial Cells (HUVECs) aging induced by hydrogen peroxide (H2O2) and the role of Sirt1 in this phenomenon. MATERIAL AND METHODS HUVEC were exposed to H2O2 to establish the aging model. The expression of protein and RNA were detected by Western blot and Reverse transcription-quantitative polymerase chain reaction. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability. Sirt1 enzyme activity assay was used to analyze enzymatic activity. Reactive oxygen species was detected by dichlorofluorescein diacetate (DCFH-DA). Cell aging was detected by Senescence ß-Galactosidase (SA-ß-gal) staining. RESULTS Results of this study revealed that pretreating HUVECs with 5 ng/mL allicin before exposure to H2O2 resulted in increased cell viability and reduced reactive oxygen species generation. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that H2O2 attenuated the phosphorylation and activation of Sirt1 and increased the expression of plasminogen activator inhibitor-1(PAI-1) protein. Moreover, H2O2 also promoted HUVEC aging. These effects were significantly alleviated by 5 ng/mL allicin co-treatment. Furthermore, the anti-aging effects of allicin were abolished by the Sirt1 inhibitor nicotinamide (NAM). CONCLUSIONS Overall, the results demonstrated that allicin protects HUVECs from H2O2-induced oxidative stress and aging via the activation of Sirt1.

Severe pulmonary edema following hyperbaric oxygen therapy for acute carbon monoxide poisoning: a case report and clinical experience.

PURPOSE: Pulmonary edema following hyperbaric oxygen (HBO2) therapy is a rare clinical phenomenon. This case report describes such a patient - a 56-year-old woman who suffered from severe pulmonary edema after HBO2 therapy for carbon monoxide (CO) poisoning. CASE: Patient experienced ecphysesis and dyspnea suddenly after HBO2 therapy (100% oxygen at 0.25 MPa, for 60 minutes with a five-minute air break and decompression at 0.01 MPa/minute). Post therapy her heart rate (HR), blood pressure (BP), respiratory rate (RR) and oxygen saturation (SO2) were 140 bpm, 60/40 mmHg, 38 bpm and 84%, respectively. Diagnoses of acute pulmonary edema and shock were made. Various treatments including antishock, tracheal intubation, mechanical ventilation for respiratory support, a diuretic, dexamethasone, asthma relief, and acidosis correction were administered. Pulmonary computed tomography (CT) indicated significant pulmonary edema. Due to active treatment, the patient showed gradual improvement. Pulmonary CT re-examination showed pulmonary edema markedly improved. At the two-year follow-up, the patient reported no abnormal mental or neurological symptoms. CONCLUSION: Acute pulmonary edema is rare but can lead to serious side effects of HBO2 therapy in patients with severe acute CO poisoning. This complication must be must considered when administering HBO2 therapy to patients with severe CO poisoning.

Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and accumulating evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. The aim of this work was to investigate the effect of treatment with hydrogen molecule on the development of disease in mutant SOD1 G93A transgenic mouse model of ALS. Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.

Predictive features of CT for risk stratifications in patients with primary gastrointestinal stromal tumour.

PURPOSE: To determine the predictive CT imaging features for risk stratifications in patients with primary gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: One hundred and twenty-nine patients with histologically confirmed primary GISTs (diameter >2 cm) were enrolled. CT imaging features were reviewed. Tumour risk stratifications were determined according to the 2008 NIH criteria where GISTs were classified into four categories according to the tumour size, location, mitosis count, and tumour rupture. The association between risk stratifications and CT features was analyzed using univariate analysis, followed by multinomial logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: CT imaging features including tumour margin, size, shape, tumour growth pattern, direct organ invasion, necrosis, enlarged vessels feeding or draining the mass (EVFDM), lymphadenopathy, and contrast enhancement pattern were associated with the risk stratifications, as determined by univariate analysis (P < 0.05). Only lesion size, growth pattern and EVFDM remained independent risk factors in multinomial logistic regression analysis (OR = 3.480-100.384). ROC curve analysis showed that the area under curve of the obtained multinomial logistic regression model was 0.806 (95 % CI: 0.727-0.885). CONCLUSION: CT features including lesion size, tumour growth pattern, and EVFDM were predictors of the risk stratifications for GIST. KEY POINTS: • CT features were of predictive value for risk stratification of GISTs. • Tumour size, growth patterns, and EVFDM were risk predictors of GISTs. • Large size, mixed growth pattern, or EVFDM indicated high risk GIST.

MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations.

OBJECTIVE: To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. METHODS: Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. RESULTS: Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 × 10-3 mm2/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. CONCLUSION: Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. KEY POINTS: • Cervical NECs show a tendency of lesion homogeneity and lymphadenopathy • Low ADC values are found in cervical NECs • MRI is an accurate imaging modality for the cervical NEC staging.