Demonstration of HNE-related Aldehyde Formation via Lipoxygenase-catalyzed Synthesis of a <i>bis</i>-Allylic Dihydroperoxide Intermediate

One of the proposed pathways to the synthesis of 4-hydroxy-nonenal (HNE) and related aldehydes entails formation of an intermediate bis-allylic fatty acid dihydroperoxide. As a first direct demonstration of such a pathway and proof of principle, herein we show that 8<i>R</i>-lipoxygenase (8<i>R</i>-LOX) catalyzes the enzymatic production of the HNE-like product (11-oxo-8-hydroperoxy-undeca-5,9-dienoic acid) via synthesis of 8,11-dihydroperoxy-eicosa-5,9,12,14-tetraenoic acid intermediate. Incubation of arachidonic acid with 8<i>R</i>-LOX formed initially 8<i>R</i>-hydroperoxy-eicosatetraenoic acid (8<i>R</i>-HPETE), which was further converted to a mixture of products including a prominent HPNE-like enone. A new bis-allylic dihydroperoxide was trapped when the incubation was repeated on ice. Reincubation of this intermediate with 8<i>R</i>-LOX successfully demonstrated its conversion to the enone products, and this reaction was greatly accelerated by coincubation with NDGA, a reductant of the LOX iron. These findings identify a plausible mechanism that could contribute to the production of 4-hydroxy-alkenals <i>in vivo</i>

Begg’s funnel plot of publication bias testing for OS in lung cancer.

<p>Begg’s funnel plot of publication bias testing for OS in lung cancer.</p

Clinical utility of the modified Glasgow prognostic score in lung cancer: A meta-analysis

<div><p>Objective</p><p>To perform a meta-analysis of prospective and retrospective studies exploring the association of the modified Glasgow prognostic score (mGPS) with overall survival (OS) in patients with lung cancer.</p><p>Methods</p><p>Relevant studies were identified by searching the Cochrane Library, Web of Science, Embase and PubMed until April 16, 2017. We combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the correlation between mGPS and OS in patients with lung cancer.</p><p>Results</p><p>Eleven studies involving 5817 participants from several countries were included in the meta-analysis. In a pooled analysis of all studies, elevated mGPS predicted poorer OS (HR = 1.77; 95% CI: 1.35–2.31; P<0.05). Subgroup analyses stratified by mGPS showed that mGPS of 1 or 2 and mGPS≥1 were predictive of poorer OS and that the HR for mGPS of 2 (HR = 5.82; 95% CI: 1.85–18.22; P = 0.003) was significantly greater than that for mGPS of 1 (HR = 1.74; 95% CI: 1.24–2.45; P = 0.001) and mGPS≥1 (HR = 1.42; 95% CI: 1.14–1.76; P = 0.002). Among patients undergoing surgery, elevated mGPS had a non-significant correlation with reduced OS (HR = 2.48; 95% CI: 0.90–6.85; P = 0.079), whereas the correlation was significant for patients receiving chemotherapy or other palliative treatment (HR = 1.74; 95% CI: 1.31–2.30; P<0.05).</p><p>Conclusions</p><p>Our findings indicate that mGPS may have prognostic value in lung cancer, as we detected a significant association between elevated mGPS and poorer OS. The association between mGPS and poorer OS was non-significant among patients undergoing surgery, which may be attributable to lower tumor load. However, further studies are warranted to draw firm conclusions.</p></div

Begg’s funnel plot of publication bias testing for OS in lung cancer.

<p>Begg’s funnel plot of publication bias testing for OS in lung cancer.</p

Sensitivity analysis of the relationship between mGPS and OS in lung cancer.

<p>Sensitivity analysis of the relationship between mGPS and OS in lung cancer.</p

Forest plot of the association between mGPS and OS in patients with lung cancer.

<p>Forest plot of the association between mGPS and OS in patients with lung cancer.</p

Structural Transformation of Guanine Coordination Motifs in Water Induced by Metal Ions and Temperature

The transformation effects of metal ions and temperature on the DNA base guanine (G) metal–organic coordination motifs in water have been investigated by scanning tunneling microcopy (STM). The G molecules form an ordered hydrogen-bonded structure at the water–highly oriented pyrolytic graphite interface. The STM observations reveal that the canonical G/9H form can be transformed into the G/(3H,7H) tautomer by increasing the temperature of the G solution to 38.6 °C. Moreover, metal ions bind with G molecules to form G₄Fe₁³⁺, G₃Fe₃²⁺, and the heterochiral intermixed G₄Na₁⁺ metal–organic networks after the introduction of alkali-metal ions in cellular environment

Forest plot of the association between mGPS and OS in patients with lung cancer stratified by pathology, ethnicity, treatment and study design.

<p>Forest plot of the association between mGPS and OS in patients with lung cancer stratified by pathology, ethnicity, treatment and study design.</p

Characteristics of all included studies.

<p>Characteristics of all included studies.</p

Flow chart of study selection.

<p>Flow chart of study selection.</p