The oncogenic role of HIF-1α/miR-182-5p/ZFP36L1 signaling pathway in nasopharyngeal carcinoma.

BACKGROUND: Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC. RESULTS: Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3' un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). CONCLUSIONS: Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.

Thermoneutral housing temperature regulates T-regulatory cell function and inhibits ovabumin-induced asthma development in mice.

The change in ambient temperature is one of the risk factors for the aggravation of bronchial asthma (BA). Yet, whether the ambient temperature influences the immune functions associated with allergic asthma remains unknown. In this study, we treated asthmatic mice with standard temperature (ST, 20 °C) or thermoneutral temperature (TT, 30 °C). The results showed that the airway inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR) were significantly reduced in the mice treated with TT as compared with the mice treated with ST. The imbalance of Th1/Th2 response in the lung was improved following housing the mice at TT. In addition, the pulmonary Treg cells were increased in asthmatic mice after TT treatment. The temperature stress (29 °C and 41 °C) drove naïve CD4T cells towards Th2 cells. Our data demonstrate that the change of ambient temperature was a risk factor to aggravate experimental asthma.

High nasal resistance may be a result rather than a cause of obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) show high nasal resistance (NR). The present study tested the hypothesis that nasal obstruction in OSA patients could be caused by pharyngeal narrow. The aim of this study was to investigate the effect of uvulopalatopharyngoplasty (UPPP) on NR in patients with OSA. Rhinomanometry was performed and the Mallampati score was recorded during wakefulness in a sitting position before and after UPPP for 33 patients with OSA. Thirty-three healthy volunteers were used as a control group. The NR in patients with OSA (0.37 ± 0.22 Pa/cm(3)/s) was significantly higher than that of the normal controls (0.19 ± 0.04 Pa/cm(3)/s) (p < 0.01). The NR decreased from 0.37 ± 0.22 to 0.20 ± 0.05 Pa/cm(3)/s (p < 0.01) after UPPP with the Mallampati score decreased from 3.00 ± 0.56 to 1.52 ± 0.57 (p < 0.01). However, NR values after UPPP were still higher than those of the control group, but there was no significant difference between those two groups (p = 0.34). The present study showed that the high NR may not be completely attributable to nasal anatomic obstruction, but may result from pharyngeal narrow in OSA. High NR may be a result of OSA rather than a cause.

Synchrotron-based chemical nano-tomography of microbial cell-mineral aggregates in their natural, hydrated state.

Chemical nano-tomography of microbial cells in their natural, hydrated state provides direct evidence of metabolic and chemical processes. Cells of the nitrate-reducing Acidovorax sp. strain BoFeN1 were cultured in the presence of ferrous iron. Bacterial reduction of nitrate causes precipitation of Fe(III)-(oxyhydr)oxides in the periplasm and in direct vicinity of the cells. Nanoliter aliquots of cell-suspension were injected into custom-designed sample holders wherein polyimide membranes collapse around the cells by capillary forces. The immobilized, hydrated cells were analyzed by synchrotron-based scanning transmission X-ray microscopy in combination with angle-scan tomography. This approach provides three-dimensional (3D) maps of the chemical species in the sample by employing their intrinsic near-edge X-ray absorption properties. The cells were scanned through the focus of a monochromatic soft X-ray beam at different, chemically specific X-ray energies to acquire projection images of their corresponding X-ray absorbance. Based on these images, chemical composition maps were then calculated. Acquiring projections at different tilt angles allowed for 3D reconstruction of the chemical composition. Our approach allows for 3D chemical mapping of hydrated samples and thus provides direct evidence for the localization of metabolic and chemical processes in situ.

Low prevalence of hypersensitivity to nonsteroidal anti-inflammatory drugs in Chinese patients with chronic rhinosinusitis.

The exact prevalence of hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) remains unclear in patients with chronic rhinosinusitis (CRS) because many of these patients routinely avoid the use of NSAIDs. Since the diagnosis of aspirin hypersensitivity is based mainly on history, the aspirin challenge protocol is seldom used clinically in China. The objective of this study is to investigate the prevalence of NSAID hypersensitivity in Chinese patients diagnosed with CRS. In a unique cohort study, consecutive CRS patients received intramuscular diclofenac sodium injection or diclofenac sodium sustained-release tablets to relieve intraoperative and postoperative pain following nasal surgery. In addition, data on NSAID hypersensitivity in large-sample series of CRS patients were collected by searching relevant literature published in Chinese to determine the prevalence of NSAID hypersensitivity in Chinese patients with CRS. A total of 244 consecutive CRS patients were included in this study. Three (1.34%) patients experienced a severe asthmatic attack after intramuscular diclofenac sodium injection and were diagnosed with NSAID hypersensitivity. Despite the use of different methods to diagnose NSAID hypersensitivity, the prevalence of NSAID hypersensitivity in Chinese CRS patients was between 0.28 and 1.46%. The prevalence of NSAID hypersensitivity in Chinese patients with CRS is low, which is a distinct clinical characteristic of Chinese CRS patients. Despite the apparently low prevalence of the condition in this population, a large number of patients in China are affected by this disorder, which should not be overlooked or regarded with an indifferent attitude in medical research and clinical practices.

Micro- and nano-environments of C sequestration in soil: a multi-elemental STXM-NEXAFS assessment of black C and organomineral associations.

Black C is an essential component of the terrestrial C pool and its formation is often credited as a CO(2) sink by transferring the fast-cycling C from the atmosphere-biosphere system into slower cycling C in the geosphere. This study is the first multi-element K- (C, N, Ca, Fe, Al and Si) soft-X-ray STXM-NEXAFS investigation conducted at a submicron-scale spatial resolution specifically targeting black C and its interaction with the mineral and non-black C organic matter in the organomineral assemblage. The STXM-NEXAFS micrographs and spectra demonstrated that pyrogenic C was dominated by quinoide, aromatic, phenol, ketone, alcohol, carboxylic and hydroxylated- and ether-linked C species. There was also evidence for the presence of pyridinic, pyridonic, pyrrolic, amine and nitril N functionalities. The non-black C organic matter contained amino acids, amino sugars, nucleic acids and polysaccharides known to exhibit negatively charged carboxylic, phenolic, enolic, thiolate and phosphate functionalities highly reactive towards metal ions and black C. The metal-rich mineral matrix was composed of phyllosilicate clay minerals, Fe and Al hydroxypolycations, oxides, hydroxides and oxyhydroxide that can attract and bind organic biopolymers. STXM-NEXAFS provided evidence for interactive association between pyrogenic C, non-black C organic matter and the mineral oxide and oxyhydroxide communities in the organomineral interface. These intimate associations occurred through a "two-way" direct linkage between black C and the mineral or non-black C organic matter or via a "three-way" indirect association where non-black C organic matter could serve as a molecular cross-linking agent binding black C with the mineral matrix or vice versa where inorganic oxides, hydroxides and polycations could act as a bridge to bind black C with non-black C organic matter. The binding and sequestration of black C in the investigated micro- and nano-C repository environments seem to be the combined action of physical entrapment in seemingly terminal biotic exclusion zone through the action of metal oxides and organic matter induced microaggregation and through molecular-level association ranging from ligand exchange, polyvalent cation bridging to weak hydrophobic interactions including van der Waals and H-bonding.

[Microbial profile and antibiotic susceptibility of chronic rhinosinusitis].

OBJECTIVE: To investigate distribution and drug-susceptibility of bacteria in patients with chronic rhinosinusitis. METHOD: The purulent discharges or mucous membrane lesions were collected from the sinus of 51 patients with chronic rhinosinusitis receiving sinus surgery. The clinical specimens were incubated and the drug susceptibility was analyzed. RESULT: Of 51 specimens, 41 (80.39%) showed positive results in bacteria culture. The antibiotic susceptibility was as follows: vancomycin-100%, moxifloxacin-100%, levofloxacin-92.31%, rifampin-90.91%, ciprofloxacin-81.58%, SMZ-TMP-67.65%, azithromycin-47.62%, clarithromycin-45.00%, ampicillin sodium and sulbactam sodium-35.90%, cefatriaxone-39.39%, cefuroxime sodium-30.43%, penicillin-8.33%. CONCLUSION: There are bacteria infections in most of chronic rhinosinusitis. The fluoroquinolones should be preferred in sinus surgery.

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection.

BACKGROUND: There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects. METHODS: Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220). RESULTS: Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 +/- 0.04). CONCLUSIONS: A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.

Novel plasma phospholipid biomarkers of autism: mitochondrial dysfunction as a putative causative mechanism.

Autism is a neurological disorder that manifests as noticeable behavioral and developmental abnormalities predominantly in males between the ages of 2 and 10. Although the genetics, biochemistry and neuropathology of this disease have been extensively studied, underlying causal factors to this disease have remained elusive. Using a longitudinal trial design in which three plasma samples were collected from 15 autistic and 12 non-autistic age-matched controls over the course of 1 year, universal and unambiguous alterations in lipid metabolism were observed. Biomarkers of fatty acid elongation and desaturation (poly-unsaturated long chain fatty acids (PUFA) and/or saturated very long chain fatty acids (VLCFA)-containing ethanolamine phospholipids) were statistically elevated in all autistic subjects. In all 8 of the affected/non-affected sibling pairs, the affected sibling had higher levels of these biomarkers than the unaffected sibling. Exposure of neurons, astrocytes and hepatocytes in vitro to elevated extracellular glutamate levels resulted in lipid biomarker changes indistinguishable from those observed in autistic subjects. Glutamate stress also resulted in in vitro decreased levels of reduced glutathione (GSH), methionine and cysteine, in a similar way to the decreases we observed in autism plasma. Impaired mitochondrial fatty acid oxidation, elevated plasma VLCFAs, and glutamate toxicity as putative causal factors in the biochemistry, neuropathology, and gender bias in autism are discussed.

Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia.

Although dementia of the Alzheimer's type (DAT) is the most common form of dementia, the severity of dementia is only weakly correlated with DAT pathology. In contrast, postmortem measurements of cholinergic function and membrane ethanolamine plasmalogen (PlsEtn) content in the cortex and hippocampus correlate with the severity of dementia in DAT. Currently, the largest risk factor for DAT is age. Because the synthesis of PlsEtn occurs via a single nonredundant peroxisomal pathway that has been shown to decrease with age and PlsEtn is decreased in the DAT brain, we investigated potential relationships between serum PlsEtn levels, dementia severity, and DAT pathology. In total, serum PlsEtn levels were measured in five independent population collections comprising >400 clinically demented and >350 nondemented subjects. Circulating PlsEtn levels were observed to be significantly decreased in serum from clinically and pathologically diagnosed DAT subjects at all stages of dementia, and the severity of this decrease correlated with the severity of dementia. Furthermore, a linear regression model predicted that serum PlsEtn levels decrease years before clinical symptoms. The putative roles that PlsEtn biochemistry play in the etiology of cholinergic degeneration, amyloid accumulation, and dementia are discussed.