Genetic associations between gene polymorphisms on 3p25 and oral squamous cell carcinoma.

OBJECTIVES: To evaluate the association of SYN2, PPARG, RAF1, TIMP4, and IQSEC1 polymorphisms in 3p25 with oral squamous cell carcinoma (OSCC) in the Chinese Han population. SUBJECTS AND METHODS: Genomic DNA was extracted from 494 subjects with or without OSCC. Basic information on the subjects, clinical data, and prognoses were collected. Fifteen candidate single nucleotide polymorphisms (SNPs) were selected and genotyped. The statistical analyses included descriptive statistics, logistic regression, survival, and functional annotation was performed. RESULTS: IQSEC1-rs2686742 correlated with OSCC occurrence. In addition, RAF1-rs1051208, PPARG-rs10865710, PPARG-rs3856806, IQSEC1-rs2686742, PPARG-rs1175544, IQSEC1-rs9211, and IQSEC1-rs2600322 were significantly associated with the clinical characteristics of patients with OSCC. The log-rank test showed that IQSEC1-rs2600322 may play an important role in the survival of patients with OSCC. The Cox regression analysis suggested that PPARG-rs10865710, PPARG-rs7649970, IQSEC1-rs9211, IQSEC1-rs2600322, and IQSEC1-rs12487715 influenced survival outcomes. The functional annotation indicated that the transcript levels of IQSEC1 were upregulated in head and neck squamous cell carcinoma tissues, whereas PPARG gene transcription was downregulated. CONCLUSIONS: IQSEC1-rs2686742 may be closely associated with OSCC onset. Multiple SNPs in IQSEC1 and PPARG genes correlated with the clinical characteristics of OSCC, among which PPARG-rs10865710, IQSEC1-rs9211, and IQSEC1-rs2600322 were associated with cancer prognosis.

Development and Validation of a Tunable Diode Laser Absorption Spectroscopy System for Hot Gas Flow and Small-Scale Flame Measurement.

TDLAS (tunable diode laser absorption spectroscopy) is an important gas analysis method that can be employed to obtain characteristic parameters non-invasively by the infrared absorption spectra of tracer molecules such as CH4, H2O and O2. In this study, a portable H2O-based TDLAS system with a dual optical path was developed with the aim of assessing the combustion characteristics of flammable gases. Firstly, a calculation method of gas characteristics including temperature and velocity combining absorption spectra and a HITRAN database was provided. Secondly, to calibrate and validate this TDLAS system precisely, a pressure vessel and a shock tube were introduced innovatively to generate static or steady flow fields with preset constant temperatures, pressures, or velocities. Static tests within environment pressures up to 2 MPa and steady flow field tests with temperatures up to 1600 K and flow velocities up to 950 m/s were performed for verification. It was proved that this system can provide an accurate values for high temperature and velocity gas flows. Finally, an experimental investigation of CH4/air flames was conducted to test the effectiveness of the system when applied to small diffusion flames. This TDLAS system gave satisfactory flame temperature and velocity data owing to the dual optical path design and high frequency scanning, which compensated for scale effects and pulsation of the flame. This work demonstrates a valuable new approach to thermal hazard analysis in specific environments.

Binding of fluphenazine with human serum albumin in the presence of rutin and quercetin: An evaluation of food-drug interaction by spectroscopic techniques.

The interactions between human serum albumin (HSA) and fluphenazine (FPZ) in the presence or absence of rutin or quercetin were studied by fluorescence, absorption and circular dichroism (CD) spectroscopy and molecular modeling. The results showed that the fluorescence quenching mechanism was static quenching by the formation of an HSA-FPZ complex. Entropy change (ΔS0 ) and enthalpy change (ΔH0 ) values were 68.42 J/(mol⋅K) and -4.637 kJ/mol, respectively, which indicated that hydrophobic interactions and hydrogen bonds played major roles in the acting forces. The interaction process was spontaneous because the Gibbs free energy change (ΔG0 ) values were negative. The results of competitive experiments demonstrated that FPZ was mainly located within HSA site I (sub-domain IIA). Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters and competition experiments. Competitive binding to HSA between flavonoids and FPZ decreased the association constants and increased the binding distances of FPZ binding to HSA. The results of absorption, synchronous fluorescence, three-dimensional fluorescence, and CD spectra showed that the binding of FPZ to HSA caused conformational changes in HSA and simultaneous effects of FPZ and flavonoids induced further HSA conformational changes.

Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis.

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.

BACKGROUND: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. METHODS: Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. RESULTS: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. CONCLUSIONS: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

Contribution of gene polymorphisms on 3p25 to salivary gland carcinoma, ameloblastoma, and odontogenic keratocyst in the Chinese Han population.

OBJECTIVE: This study aimed to investigate the contribution of gene polymorphisms in 3p25 to salivary gland carcinoma (SGC), ameloblastoma (AM), and odontogenic keratocyst (OKC) in the Chinese Han population. STUDY DESIGN: Sixteen tag-single nucleotide polymorphisms (SNPs) within 5 genes (SYN2, TIMP4, PPARG, RAF1, and IQSEC1) in 3p25 were genotyped in 411 individuals with or without SGC, AM, and OKC. Genotype, clinical phenotype, and bioinformatics analyses were performed to evaluate the function of candidate SNPs. RESULTS: SYN2-rs3773364, TIMP4-rs3755724, PPARG-rs10865710, and PPARG-rs1175544 were related to decreased SGC susceptibility, whereas IQSEC1-rs2600322 and IQSEC1-rs2686742 decreased and increased AM risk, respectively. Stratification analysis revealed that the significance of the identified SNPs was stronger in females or individuals younger than 46 years in SGC. PPARG-rs10865710 and PPARG-rs1175544 were associated with lower lymph node metastasis. SYN2-rs3773364 and PPARG-rs1175544 were associated with favorable SGC patient survival. Functional assessments linked PPARG-rs1175544 to PPARG expression regulation. Linkage disequilibrium analysis revealed a haplotype (SYN2-rs3773364-A, TIMP4-rs3817004-A, and TIMP4-rs3755724-C) associated with decreased susceptibility to SGC. Generalized multifactor dimensionality reduction analysis indicated the gene-gene interactions among IQSEC1, TIMP4, and PPARG in SGC, AM, and OKC progression. CONCLUSIONS: These variants play important roles in the progression of SGC, AM, and OKC in the Chinese Han population and may be considered biomarkers for early diagnosis and prognosis prediction.

A Synthesis of Viral Contribution to Marine Nitrogen Cycling.

Nitrogen is an essential component of major cellular macromolecules, such as DNA and proteins. Its bioavailability has a fundamental influence on the primary production of both terrestrial and oceanic ecosystems. Diverse marine microbes consume nitrogen, while only a limited taxon could replenish it, leaving nitrogen one of the most deficient nutrients in the ocean. A variety of microbes are involved in complex biogeochemical transformations of nitrogen compounds, and their ecological functions might be regulated by viruses in different manners. First and foremost, viruses drive marine nitrogen flow via host cell lysis, releasing abundant organic nitrogen into the surrounding environment. Secondly, viruses can also participate in the marine nitrogen cycle by expressing auxiliary metabolic genes (AMGs) to modulate host nitrogen metabolic pathways, such as nitrification, denitrification, anammox, and nitrogen transmembrane transport. Additionally, viruses also serve as a considerable reservoir of nitrogen element. The efficient turnover of viruses fundamentally promotes nitrogen flow in the oceans. In this review, we summarize viral contributions in the marine nitrogen cycling in different aspects and discuss challenges and issues based on recent discoveries of novel viruses involved in different processes of nitrogen biotransformation.

Correlation Between Brain 18F-AV45 and 18F-FDG PET Distribution Characteristics and Cognitive Function in Patients with Mild and Moderate Alzheimer's Disease.

BACKGROUND: Florbetapir (AV45) and fluorodeoxyglucose (FDG) PET imaging are valuable techniques to detect the amyloid-ß (Aß) load and brain glucose metabolism in patients with Alzheimer's disease (AD). OBJECTIVE: The purpose of this study is to access the characteristics of Aß load and FDG metabolism in brain for further investigating their relationships with cognitive impairment in AD patients. METHODS: Twenty-seven patients with AD (average 70.6 years old, N = 13 male, N = 14 female) were enrolled in this study. These AD patients underwent the standard clinical assessment and received detailed imaging examinations of the nervous system by using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), 18F-AV45, and 18F-FDG PET scans. RESULTS: Of 27 AD patients, 22 patients (81.5%) showed significantly increases in Aß load and 26 patients (96.3%) had significantly reductions in FDG metabolism. The moderate AD patients had more brain areas of reduced FDG metabolism and more severe reductions in some regions compared to mild AD patients, with no differences in Aß load observed. Moreover, the range and degree of reduced FDG metabolism in several regions were positively correlated with the total score of MMSE or MOCA, whereas the range of Aß load did not. No correlation was found between the range of Aß load and the range of reduced FDG metabolism in this study. CONCLUSION: The reduction in FDG metabolisms captured by 18F-FDG imaging can be used as a potential biomarker for AD diagnosis in the future. 18F-AV45 imaging did not present valuable evidence for evaluating AD patient in this study.

Spectrum and dosing of urate-lowering drugs in a large cohort of chronic kidney disease patients and their effect on serum urate levels: a cross-sectional analysis from the German Chronic Kidney Disease study.

BACKGROUND: Despite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing. METHODS: We studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient's paper charts at the baseline visit, in which all currently used medications and their dosing were recorded. RESULTS: In this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m2 and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR <60 mL/min/1.73 m2 and 320 had an eGFR <45 mL/min/1.73 m2, 31.5% of the latter (n = 101) received a dose >150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32-49], 43 (34-52) and 42 (35-54) mL/min/1.73 m2, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis. CONCLUSIONS: The most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.

Genetics of serum urate concentrations and gout in a high-risk population, patients with chronic kidney disease.

We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients. Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined. Interactions of urate-associated variants with urate-altering medications and clinical characteristics of gout were evaluated. Genome-wide significant associations with serum urate and gout were identified for known loci at SLC2A9 and ABCG2, but not for novel loci. Effects of the 26 known SNPs were of similar magnitude in CKD patients compared to population-based individuals, except for SNPs at ABCG2 that showed greater effects in CKD. Gene-medication interactions were not significant when accounting for multiple testing. Associations with gout in specific joints were significant for SLC2A9 rs12498742 in wrists and midfoot joints. Known genetic variants in SLC2A9 and ABCG2 were associated with urate and gout in a CKD cohort, with effect sizes for ABCG2 significantly greater in CKD compared to the general population. CKD patients are at high risk of gout due to reduced kidney function, diuretics intake and genetic predisposition, making treatment to target challenging.

Spectroscopic investigation on the food components-drug interaction: the influence of flavonoids on the affinity of nifedipine to human serum albumin.

Nifedipine (NDP) is used extensively for the clinical treatment of a number of cardiovascular diseases. Herein, the interaction between human serum albumin (HSA) and NDP and the influence of flavonoids, rutin and baicalin, on their binding properties were investigated in vitro by means of fluorescence and absorption spectroscopy. The fluorescence of HSA was quenched remarkably by NDP and the quenching mechanism was considered as static quenching by forming a complex. The results of thermodynamic parameters indicate that both hydrogen bonds and hydrophobic interactions play the main role in the binding process and the binding process was spontaneous. The binding distance between the amino acid residue of HSA and NDP is 2.608 nm, which indicates that the energy transfer from HSA to NDP can occur with high probability. The decreased association constants and the increased binding distance of NDP binding to HSA in the presence of flavonoids were both due to their competitive binding to the site I of HSA. The results obtained from synchronous fluorescence and three-dimensional fluorescence spectra showed that the interaction between HSA and NDP caused the conformational changes of HSA and the synergism effects of NDP and flavonoids induced the further conformational changes of HSA.