Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in Live Cells and In Vivo.

Superoxide anion radical (O2(•-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(•-) detecting strategy involving O2(•-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(•-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(•-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(•-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(•-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(•-) in health and disease.

Association of leptin gene -2548 G/A polymorphism with obesity: a meta-analysis.

BACKGROUND: A common single-nucleotide polymorphism identified in the 5'-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis. METHODS: Medline, Embase and ISI Web of Science databases were searched to identify relevant studies. Meta-analysis of the total and subgroup populations was conducted using allelic, additive, dominant and recessive models, and odds ratios and their 95% confidence intervals were calculated in a fixed-effect model if no heterogeneity (evaluated as I(2) statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by ethnicity. Meta-regression and the HETRED analysis were used to explore the potential sources of between-study heterogeneity. Egger's test and influence analysis were conducted to evaluate the publication bias and study power, respectively. RESULTS: The final selection enrolled 9 studies, including 2,988 subjects (1,372 obese subjects and 1,616 controls). No significant association was identified between the LEP -2548 G/A polymorphism and obesity for all genetic models in the overall population and Caucasians. We found a significant association with allelic, additive and dominant models for subjects of mixed race from South America. Notwithstanding, this significance should be treated cautiously for it is based on a rather small sample (788 involved subjects). CONCLUSIONS: In total, the combined analysis of data from current and published studies suggested that the LEP -2548 G/A polymorphism does not contribute to the development of obesity, despite the fact that a significant association exists in a small subgroup from South America. Further studies are needed to elucidate the relationship. .

HKOCl-3: a fluorescent hypochlorous acid probe for live-cell and in vivo imaging and quantitative application in flow cytometry and a 96-well microplate assay.

Ultra-selective and ultra-sensitive probes for hypochlorous acid (HOCl), one of the most poorly understood reactive oxygen species (ROS), are urgently needed to unravel the HOCl functions in important biological processes such as development and innate immunity. Based on a selective oxidative O-dearylation reaction of 2,6-dichlorophenol toward HOCl over other reactive oxygen species, we have developed a novel fluorescent probe HKOCl-3 for HOCl detection with ultra-selectivity, ultra-sensitivity and a rapid turn-on response. The functional robustness of HKOCl-3 for endogenous HOCl detection and imaging has been thoroughly scrutinized in multiple types of phagocytes and in vivo imaging of live intact zebrafish embryos. Furthermore, HKOCl-3 has been successfully applied to the detection of endogenous HOCl by a 96-well microplate assay and flow cytometry. Therefore, HKOCl-3 holds great promise as a versatile molecular tool that enables innovative investigation of HOCl biology and ROS-related diseases in multiple detection modalities.

Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer.

AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer. METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients. RESULTS: The positive likelihood ratios of TSGF, CA242 and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17, respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0% and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9. CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking. There is very important correlation between the three markers and the pancreatic cancer.