Chronic rhinitis and stress: the possible culprits of midfacial segment pain.

BACKGROUND: Bilateral symmetrical pain in the midfacial region without evidence of sinonasal disease is termed midfacial segment pain (MSP), about which little is known. The present study explored the prevalence of facial pain and the risk factors for MSP. METHODS: We analysed cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES). Those who reported facial pain or pressure lasting at least three months with no evidence of a sinonasal disease on nasal endoscopy were considered to have MSP. The participants were categorised according to the presence of facial pain and chronic rhinosinusitis. Basic demographic data and medical conditions, including hypertension, diabetes mellitus, and dyslipidemia, were compared between subject groups. We also evaluated psychological stress, depressive episodes, and suicidal thoughts, as well as physician-diagnosed nasal diseases, including chronic rhinitis and symptomatic nasal septal deviation. Univariate and multivariate logistic regression analyses were performed to determine risk factors for MSP. RESULTS: Of 31,999 participants, the prevalence of facial pain was 0.59%. A total of 58 (0.18%) respondents had MSP, of whom 40 (73.5%) were female. On univariate analysis, female sex, chronic rhinitis, and psychological stress were more prevalent in the subjects with MSP than the control subjects. However, in the multivariate analysis, only chronic rhinitis and psychological stress remained significant, while the female sex exhibited only marginal significance. CONCLUSION: Chronic rhinitis and psychological stress may be significant risk factors for MSP.

Increased risk of cardiovascular diseases in patients with chronic rhinosinusitis: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases and is characterized by sinonasal inflammation that lasts longer than 12 weeks. Whether the effect of chronic inflammation caused by CRS on cardiovascular diseases (CVDs) is similar to its effect on other inflammatory disorders has not been thoroughly evaluated. We aimed to demonstrate whether CRS patients have a higher prevalence of CVDs, including stroke and ischemic heart disease (IHD). METHODOLOGY: We compared the prevalence of various comorbidities between CRS and control participants through a case-control cohort study from 2002 to 2015 that included 514,866 participants. CRS (n=6,552) and control (n=26,208) participants who were over 40 years old were selected by matching age, sex, income, and area of residence at a 1:4 ratio. RESULTS: A stratified Cox proportional hazards model was utilized to assess the hazard ratio (HR) of CRS for stroke and IHD. The HRs for stroke and IHD were significantly increased in CRS patients compared to controls after adjusting for obesity, alcohol consumption, smoking, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, hemoglobin, and Charlson Comorbidity Index (CCI) scores. The HR of stroke was significantly higher in the absence of nasal polyps than in the presence of nasal polyps. The HR of IHD was significantly increased in the CRS group regardless of the presence of nasal polyps. CONCLUSIONS: This study showed that CRS participants had a significantly higher prevalence of stroke and IHD.

Does serum vitamin D level affect the association between cardiovascular health and cognition? Results of the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) study.

BACKGROUND AND PURPOSE: Few studies have assessed the role of vitamin D in the association between cardiovascular risk factors and cognitive function. Here, the aim was to investigate the association between cardiovascular health (CVH) and cognitive function according to vitamin D level in a middle-aged Korean population. METHODS: This cross-sectional study included 840 men and 1811 women (mean age 57.2 years) from the Cardiovascular and Metabolic Diseases Etiology Research Center study baseline enrolment (2013-2018). Life's Simple 7 tools from the American Heart Association were used to assess CVH. Cognitive function was evaluated using the Mini-Mental State Estimation for Dementia Screening (MMSE-DS), and the serum 25-hydroxyvitamin D level was measured. RESULTS: In the adjusted generalized linear regression models, no significant association between a high Life's Simple 7 score (4-7 metric at optimal level) and MMSE-DS score (ß = 0.01, P = 0.93) was found. Amongst men with a high vitamin D level, the high Life's Simple 7 score group showed a significantly higher MMSE-DS score (ß = 0.48, P = 0.03). However, amongst men in the low vitamin D group, the association was opposite with no statistical significance (ß = -0.23, P = 0.08). In women, the results were similar, but both strata according to vitamin D level showed no statistical significance. CONCLUSIONS: Our findings suggest that vitamin D is an effect modifier in the association between CVH and cognition, especially in men.

Mental health states and influencing factors of risky and problem drinking in South Korean female adolescents.

OBJECTIVES: Alcohol is one of the most used and abused psychoactive substances by adolescents. We investigated influencing factors of risky and problem drinking in Korean female adolescents. STUDY DESIGN: The study design used is a cross-sectional modeling. METHODS: We used data from the 13th Korean Youth Risk Behavior Web-based Survey (KYRBS) conducted in 2017. KYRBS data were obtained from a stratified, multistage, clustered sample. Risky drinking was binge drinking and problem drinking was drinking with several conflicts association with alcohol consumption. RESULTS: Among 62,276 participants, the rates of current, risky, and problem drinking among all participants were 16.1%, 8.3%, and 6.1%, respectively. Although all of these rates were higher in males, risky and problem drinking rates among current female drinkers were higher than those of males (55.4 vs 48.5%, 38.9 vs 37.2%, respectively). Problem drinking was most strongly associated with risky drinking (adjusted odds ratio: 17.53 [95% confidence interval: 14.63-21.00]), similarly, risky drinking was most strongly associated with problem drinking in female current drinkers (17.76 [14.84-21.27]). Current smoking was the second strongest risk factor for risky and problem drinking in females (5.22 [3.92-6.95] and 2.93 [2.21-3.89], respectively). CONCLUSION: Many female adolescents in Korea drink alcohol in an unhealthy manner. The female risky and problem drinking rates among current drinkers were higher than those of males. Risky drinking and problem drinking was most significant influencing factor among females, reciprocally. Public education on abstinence in female adolescents is warranted.

Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa.

BACKGROUND: Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. OBJECTIVES: To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment. METHODS: Influenza A virus mRNA, viral titres and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection. RESULTS: Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN-ß and IFN-λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titres in IAV-infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV-infected AR mouse. CONCLUSION: Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.

Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis.

Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk.

Percentage of the population at high risk of osteoporotic fracture in South Korea: analysis of the 2010 Fifth Korean National Health and Nutrition Examination survey data.

UNLABELLED: Osteoporosis and high-risk osteopenia (high-risk of osteoporotic fractures) are highly prevalent in South Korean postmenopausal women and men aged 50 years and over. INTRODUCTION: This study determined the percentages of the population at high risk of osteoporotic fractures according to the World Health Organization (WHO) criteria and the Fracture Risk Assessment (FRAX) model. METHODS: Data collected from the 2010 Fifth Korean National Health and Nutrition Examination Survey, a cross-sectional survey of the general South Korean general population, were analyzed. The percentages of the population with high-risk osteopenia according to the US National Osteoporosis Foundation (NOF) and Japanese treatment guidelines were subsequently determined and compared. RESULTS: Based on the WHO criteria and FRAX model, 37.7% of the menopausal women and 12.7% of the men aged 50 years and older are at high risk of osteoporotic fracture. According to the Japanese and NOF guidelines, 10.9 (10.6% of men and 11.2% of women) and 10.7% (10.6% of men and 10.9% of women), respectively, of the study population with osteopenia are at high risk of fracture. By age group, 49.3% of Korean women aged 55 years and older, 67.7% of Korean women aged 65 years and older, and 33.5% of Korean men aged 75 years and older are at high risk. CONCLUSION: As a very large percentage of the South Korean postmenopausal population has osteoporosis or high-risk osteopenia, greater effort at identifying and treating this population should be expended to prevent osteoporotic fracture.

Bilateral asymmetrical multiple renal arteries associated with the left testicular artery.

We found 3 right and 2 left renal arteries with asymmetrical origins in a 61-year-old Korean male cadaver, whose cause of death was 'laryngeal carcinoma'. According to a previous classification, the first and second right renal arteries correspond to the early division and other renal arteries - to the extra renal arteries, except the first left renal artery as a typical renal artery. The third right renal artery ran anterior to the inferior vena cava to the inferior pole of the kidney. The first and second left renal arteries were associated with the inferior suprarenal artery and the testicular artery, respectively. The bilateral asymmetry in the number of renal arteries can be explained by the embryological development, degeneration and persistence of the renal artery in the process of ascending of kidneys.

Association of transforming growth factor-beta 1 gene polymorphism with genetic susceptibility to ossification of the posterior longitudinal ligament in Korean patients.

Ossification of the posterior longitudinal ligaments (OPLL) has been considered to be associated with abnormalities of bone metabolism, and transforming growth factor-ß1 (TGF-ß1) has been demonstrated to affect the bone remodeling process. We investigated two SNPs of the TGF-ß1 promoter (-509C>T; rs1800469) and exon 1 (869T>C; rs1982073) in 298 Koreans (98 patients with OPLL and 200 control subjects). The promoter SNP -509C>T was determined by PCR and RFLP, and the TaqMan probe assay was used to determine 869T>C polymorphism genotypes. The subjects were divided into OPLL continuous group (continuous type plus mixed type) and OPLL segmental group (segmental and localized type). We also separately analyzed this association according to gender difference. There was no significant difference in genotype distributions of -509C>T and 869T>C polymorphisms of the TGF-ß1 gene between OPLL patients and controls. A combined analysis of TGF-ß1 -509C>T and 869T>C polymorphisms showed no significant association with OPLL, and a subgroup analysis did not show any significant correlation between the SNP -509C>T or SNP 869T>C and OPLL subgroups. Stratification by gender demonstrated no significant effect. We conclude that promoter region (-509C>T) and exon 1 (869T>C) polymorphisms are not associated with OPLL in the Korean population.

Association between VEGF and eNOS gene polymorphisms and lumbar disc degeneration in a young Korean population.

Disturbances in blood flow to intervertebral discs (IVD) play an important role in IVD degeneration. Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) are extremely important angiogenic factors for vasodilation and neovascularization. We investigated the relationship between single nucleotide polymorphisms (SNPs) of the VEGF and eNOS genes and genetic susceptibility to lumbar IVD degeneration in a young adult Korean population. Two hundred and forty-one participants (aged 18 to 30 years), with or without low back pain, were selected for the study. Magnetic resonance imaging was made of the lumbar spine in all participants. The patient group (N = 102) had low back pain clinically and lumbar IVD degeneration radiographically. The control group (N = 139) included subjects with and without low back pain; all were negative radiographically for lumbar IVD degeneration. Using PCR-RFLP analysis, we analyzed VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) and eNOS (-786T>C, 4a4b and 894G>T) SNPs. We made combined analyses of the genes and performed haplotype analyses. There were no significant differences in the genotype distribution of polymorphisms of VEGF and eNOS genes among patients and controls. However, the frequency of VEGF -2578CA +AA/-634CC combined genotypes was significantly higher in patients when compared with controls [odds ratio (OR) = 21.00; 95% confidence interval (CI) = 2.590- 170.240]. The frequencies of the -2578A/-1154A/-634C/936C (OR = 3.831; 95%CI = 1.068-13.742), -2578A/-1154A/-634C (OR = 3.356; 95%CI = 1.198-9.400), and -2578A/-634C/936C (OR = 10.820; 95%CI = 2.811-41.656) haplotypes were also significantly higher in patients than in controls. We conclude that the combined genotype VEGF -2578CA+AA/-634CC is a possible risk factor for IVD degeneration and the VEGF -2578A/-1154A/-634C/936C haplotype may increase the risk for development of IVD degeneration. Furthermore, the VEGF -634C allele appears to be associated with susceptibility to IVD degeneration.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients.

BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Xylitol production from a mutant strain of Candida tropicalis.

AIMS: To characterize the kinetics of growth, sugar uptake and xylitol production in batch and fed-batch cultures for a xylitol assimilation-deficient strain of Candida tropicalis isolated via chemical mutagenesis. METHODS AND RESULTS: Chemical mutagenesis using nitrosoguanidine led to the isolation of the xylitol-assimilation deficient strain C. tropicalis SS2. Shake-flask fermentations with this mutant showed a sixfold higher xylitol yield than the parent strain in medium containing 25 g l⁻¹ glucose and 25 g l⁻¹ xylose. With 20 g l⁻¹ glycerol, replacing glucose for cell growth, and various concentrations of xylose, the studies indicated that the mutant strain resulted in xylitol yields from xylose close to theoretical. Under fully aerobic conditions, fed-batch fermentation with repeated addition of glycerol and xylose resulted in 3.3 g l⁻¹ h⁻¹ xylitol volumetric productivity with the final concentration of 220 g l⁻¹ and overall yield of 0.93 g g⁻¹ xylitol. CONCLUSIONS: The xylitol assimilation-deficient mutant isolated in this study showed the potential for high xylitol yield and volumetric productivity under aerobic conditions. In the evaluation of glycerol as an alternative low-cost nonfermentable carbon source, high biomass and xylitol yields under aerobic conditions were achieved; however, the increase in initial xylose concentrations resulted in a reduction in biomass yield based on glycerol consumption. This may be a consequence of the role of an active transport system in the yeast requiring increasing energy for xylose uptake and possible xylitol secretion, with little or no energy available from xylose metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: The study confirms the advantage of using a xylitol assimilation-deficient yeast under aerobic conditions for xylitol production with glycerol as a primary carbon source. It illustrates the potential of using the xylose stream in a biomass-based bio-refinery for the production of xylitol with further cost reductions resulting from using glycerol for yeast growth and energy production.

Comparative evaluations of cellulosic raw materials for second generation bioethanol production.

AIMS: To evaluate sugar recoveries and fermentabilities of eight lignocellulosic raw materials following mild acid pretreatment and enzyme hydrolysis using a recombinant strain of Zymomonas mobilis. METHODS AND RESULTS: Dilute acid pretreatment (2% H(2) SO(4) ) with 10% (w/v) substrate loading was performed at 134°C for 60 min followed by enzyme hydrolysis at 60°C. The results demonstrated that hydrolysis of herbaceous raw materials resulted in higher sugar recoveries (up to 60-75%) than the woody sources (<50%). Fermentation studies with recombinant Z. mobilis ZM4 (pZB5) demonstrated that final ethanol concentrations and yields were also higher for the herbaceous hydrolysates. Significant reduction in growth rates and specific rates of sugar uptake and ethanol production occurred for all hydrolysates, with the greatest reductions evident for woody hydrolysates. Further studies on optimization of enzyme hydrolysis established that higher sugar recoveries were achieved at 50°C compared to 60°C following acid pretreatment. CONCLUSIONS: Of the various raw materials evaluated, the highest ethanol yields and productivities were achieved with wheat straw and sugarcane bagasse hydrolysates. Sorghum straw, sugarcane tops and Arundo donax hydrolysates were similar in their characteristics, while fermentation of woody hydrolysates (oil mallee, pine and eucalyptus) resulted in relatively low ethanol concentrations and productivities. The concentrations of a range of inhibitory compounds likely to have influence the fermentation kinetics were determined in the various hydrolysates. SIGNIFICANCE AND IMPACT OF THE STUDY: The study focuses on lignocellulosic materials available for second generation ethanol fermentations designed to use renewable agricultural/forestry biomass rather than food-based resources. From the results, it is evident that relatively good sugar and ethanol yields can be achieved from some herbaceous raw materials (e.g. sugarcane bagasse and sorghum straw), while much lower yields were obtained from woody biomass.

The Role of MRI in Diagnosing Neurovascular Compression of the Cochlear Nerve Resulting in Typewriter Tinnitus.

BACKGROUND AND PURPOSE: Typewriter tinnitus, a symptom characterized by paroxysmal attacks of staccato sounds, has been thought to be caused by neurovascular compression of the cochlear nerve, but the correlation between radiologic evidence of neurovascular compression of the cochlear nerve and symptom presentation has not been thoroughly investigated. The purpose of this study was to examine whether radiologic evidence of neurovascular compression of the cochlear nerve is pathognomonic in typewriter tinnitus. MATERIALS AND METHODS: Fifteen carbamazepine-responding patients with typewriter tinnitus and 8 control subjects were evaluated with a 3D T2-weighted volume isotropic turbo spin-echo acquisition sequence. Groups 1 (16 symptomatic sides), 2 (14 asymptomatic sides), and 3 (16 control sides) were compared with regard to the anatomic relation between the vascular loop and the internal auditory canal and the presence of neurovascular compression of the cochlear nerve with/without angulation/indentation. RESULTS: The anatomic location of the vascular loop was not significantly different among the 3 groups (all, P > .05). Meanwhile, neurovascular compression of the cochlear nerve on MR imaging was significantly higher in group 1 than in group 3 (P = .032). However, considerable false-positive (no symptoms with neurovascular compression of the cochlear nerve on MR imaging) and false-negative (typewriter tinnitus without demonstrable neurovascular compression of the cochlear nerve) findings were also observed. CONCLUSIONS: Neurovascular compression of the cochlear nerve was more frequently detected on the symptomatic side of patients with typewriter tinnitus compared with the asymptomatic side of these patients or on both sides of control subjects on MR imaging. However, considering false-positive and false-negative findings, meticulous history-taking and the response to the initial carbamazepine trial should be regarded as more reliable diagnostic clues than radiologic evidence of neurovascular compression of the cochlear nerve.

A simulation study on angular and micro pattern effects in GEM detectors.

A useful approach for the enhancement of thermal neutrons detection has been reported here. This technique, based on the angular and micro pattern effects, has been developed and applied to the boron-coated ((10)B) Gas Electron multiplier (GEM) detector. In the angular effect case, as a general rule, the detector device is turned at an angle which improves the device response per unit area of the detector. While for the latter case, a regular pattern in the form of micrometer deep grooves is fabricated onto the converter coating, consequently it enhances the capture probability of the detector. For the current study, both of these techniques using a (10)B-coated GEM detector have been simulated for low energy neutrons. For the evaluation of detector response thermal neutrons in the energy ranges from 25meV to 100meV were transported onto the detector surface. For this work, FLUKA MC code has been utilized. The output in both cases has been estimated as a function of incident thermal neutron energies. By employing both techniques, the angle and the micro pattern dependent efficiencies for (10)B-coated GEM detectors are presented, which indicate an improved efficiency response of the device. We anticipate that by using these modifications can lead a further forward step in the development and improvement of thermal neutron detection technology.

Thermal neutron response of a boron-coated GEM detector via GEANT4 Monte Carlo code.

In this work, we report the design configuration and the performance of the hybrid Gas Electron Multiplier (GEM) detector. In order to make the detector sensitive to thermal neutrons, the forward electrode of the GEM has been coated with the enriched boron-10 material, which works as a neutron converter. A total of 5×5cm2 configuration of GEM has been used for thermal neutron studies. The response of the detector has been estimated via using GEANT4 MC code with two different physics lists. Using the QGSP_BIC_HP physics list, the neutron detection efficiency was determined to be about 3%, while with QGSP_BERT_HP physics list the efficiency was around 2.5%, at the incident thermal neutron energies of 25meV. The higher response of the detector proves that GEM-coated with boron converter improves the efficiency for thermal neutrons detection.

The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in glioma stem cells.

Glioblastomas (GBMs) maintain their cellular heterogeneity with glioma stem cells (GSCs) producing a variety of tumor cell types. Here we interrogated the oncogenic roles of Lim domain only 2 (LMO2) in GBM and GSCs in mice and human. High expression of LMO2 was found in human patient-derived GSCs compared with the differentiated progeny cells. LMO2 is required for GSC proliferation both in vitro and in vivo, as shRNA-mediated LMO2 silencing attenuated tumor growth derived from human GSCs. Further, LMO2 is sufficient to induce stem cell characteristics (stemness) in mouse premalignant astrocytes, as forced LMO2 expression facilitated in vitro and in vivo growth of astrocytes derived from Ink4a/Arf null mice and acquisition of GSC phenotypes. A subset of mouse and human GSCs converted into vascular endothelial-like tumor cells both in vitro and in vivo, which phenotype was attenuated by LMO2 silencing and promoted by LMO2 overexpression. Mechanistically, the action of LMO2 for induction of glioma stemness is mediated by transcriptional regulation of Jagged1 resulting in activation of the Notch pathway, whereas LMO2 directly occupies the promoter regions of the VE-cadherin gene for a gain of endothelial cellular phenotype. Subsequently, selective ablation of human GSC-derived VE-cadherin-expressing cells attenuated vascular formation in mouse intracranial tumors, thereby significantly prolonging mouse survival. Clinically, LMO2 expression was elevated in GBM tissues and inversely correlated with prognosis of GBM patients. Taken together, our findings describe novel dual roles of LMO2 to induce tumorigenesis and angiogenesis, and provide potential therapeutic targets in GBMs.

2-amino-3-methylimidazo[4,5-f]quinoline-mediated immunosuppression involves inhibition of protein kinase C in murine splenocytes.

The effects of the food-borne mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), on the proliferation of murine spleen cells was examined. A significant and dose-related suppression of the proliferative response to concanavalin A (Con A) was observed by the treatment of IQ. IQ also decreased markedly the level of proliferative response induced by PMA and ionomycin and the IL-2 secretion by T cells. Treatment of PMA resulted in the recovery of IQ-induced suppression of IL-2 production, but the addition of ionomycin (Io) had no effect. IQ decreased PKC activity in both the membrane fraction and the cytosol fraction and inhibited the phosphorylation of MARCKS protein. These results suggest that the suppression of spleen cell proliferation induced by IQ might be associated with the inhibition of PKC activity and the subsequent IL-2 secretion of T cells.