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Background and objectives: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1–2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1–2.5 and hyperuricemia among male traffic officers. Methods: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1–2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1–2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1–2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. Results: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 μg/m3 increment in PM1, PM2.5, and PM1–2.5 were 1.67 (95% CI:1.30–2.36), 1.49 (95% CI: 1.27–1.75), and 2.18 (95% CI: 1.58–3.02), respectively. The SUA concentrations increased by 12.23 μmol/L (95% CI: 5.91–18.56), 6.93 μmol/L (95% CI: 3.02–10.84), and 8.72 μmol/L (95% CI: 0.76–16.68) per 10 μg/m3 increase in PM1, PM2.5, and PM1–2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1–2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1–2.5 with SUA levels were stronger in non-drinkers. Conclusion: Long-term PM1, PM2.5, and PM1–2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.

Exogenous toxicants (e.g. arsenic, cigarette smoke), trigger oxidative stress, and initiate the pathogenesis of many human diseases. Induction of nuclear factor E2-related factor 2 (Nrf2) counteracts exogenous toxicant-induced oxidative insults. Using a high-throughput screen, we firstly identified a citrus polymethoxyflavone, (2S)-5,6,7,3′,4′-pentamethoxyflavanone (PMF), to be an Nrf2 activator, and an investigation targeting Nrf2 pathway was performed. Our study indicated that: (i) PMF activated Nrf2 and its downstream genes, NQO1 and γ-GCS, and enhanced the stabilization of Nrf2 through inhibiting Nrf2 ubiquitination. (ii) Inhibition of PI3K, p38 MAPK, PKC and PERK by specific kinase inhibitors suppressed PMF-induced activation of Nrf2. (iii) PMF conferred Nrf2-dependent protection against sodium arsenite- and cigarette smoke extract- induced cytotoxicity in lung epithelial cells. Collectively, our data demonstrate that PMF is a novel Nrf2 activator with potential prevention against oxidative insults. The diverse pharmacological functions of citrus polymethoxyflavone might be related to their ability of activating Nrf2 pathway.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, β-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3â², 4, 4â²-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 proteinâprotein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue. Keywords: Cinnamomum chartophyllum, Nrf2 activator, Arsenic, Oxidative insult

Background/purpose: The signaling mechanisms for Porphyromonas gingivalis lipopolysaccharide (PgLPS)-induced inflammation in human dental pulp cells are not fully clarified. This in vitro study aimed to evaluate the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in PgLPS-induced pulpal inflammation. Methods: Human dental pulp cells (HDPCs) were challenged with PgLPS with or without pretreatment and coincubation with a PI3K/Akt inhibitor (LY294002). The gene or protein levels of PI3K, Akt, interleukin (IL)-6, IL-8, alkaline phosphatase (ALP), osteocalcin and osteonectin were analyzed by reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and immunofluorescent staining. In addition, an enzyme-linked immunosorbent assay was used to analyze IL-6 and IL-8 levels in culture medium. Results: In response to 5 μg/ml PgLPS, IL-6, IL-8, and PI3K, but not Akt mRNA expression of HDPCs, was upregulated. IL-6, IL-8, PI3K, and p-Akt protein levels were stimulated by 10–50 μg/ml of PgLPS in HDPCs. PgLPS also induced IL-6 and IL-8 secretion at concentrations higher than 5 μg/ml. Pretreatment and co-incubation by LY294002 attenuated PgLPS-induced IL-6 and IL-8 mRNA expression in HDPCs. The mRNA expression of ALP, but not osteocalcin and osteonectin, was inhibited by higher concentrations of PgLPS in HDPCs. Conclusion: P. gingivalis contributes to pulpal inflammation in HDPCs by dysregulating PI3K/Akt signaling pathway to stimulate IL-6 and IL-8 mRNA/protein expression and secretion. These results are useful for understanding the pulpal inflammation and possible biomarkers of inflamed pulp diagnosis and treatment.

Motion of point defects is a fundamental process that governs microstructure and properties of materials. Here, we examine the near-surface and grain boundary cavity swelling depth profiles in neutron- and ion-irradiated simple metals (Cu, Ni, and Fe-Cr) and investigate diffusional broadening of implanted Ni ions in Fe-Cr alloys. Vacancy migration energies and radiation-enhanced diffusion were experimentally estimated. Cavity denuded zone widths near planar sinks are shown to be dependent on temperature, damage rate, balance of point defects and sinks, and vacancy migration energies. An enhanced cavity swelling zone adjacent to the void-denuded zone was observed in specimens with low to moderate sink strength and interpreted as evidence of 1D gliding interstitial clusters. Radiation-enhanced diffusional broadening of implanted Ni ions (at 400–550 °C) in Fe and Fe-Cr was up to 250 nm toward the surface, which leads to a much broader near-peak-damage region where cavity swelling is suppressed. Diffusional broadening of implanted ions is calculated to be similarly pronounced for self-ion irradiations, particularly near the peak and higher swelling temperature regimes. Adequately high ion energies (∼8–15 MeV) are recommended for ion-irradiation studies to provide a sufficiently broad midrange safe analysis region with minimized surface and injected ion effects.

The level of chromium plays an essential role in irradiation tolerance of Fe-Cr ferritic alloys. However, conflicting results have been reported regarding the dependence of cavity swelling under irradiation on Cr level and temperature. Here, we have performed a comprehensive set of simultaneous dual-ion (Ni + He) irradiations to high dose (∼30 displacements per atom, dpa) at 400–550 °C on a series of ultra-high purity Fe and Fe-Cr binary alloys (3–14 wt.%Cr). Helium co-implantation rates of 0.1 and 10 appm He/dpa were selected to examine He synergistic effects relevant for fission and fusion reactor conditions, respectively. Cavities were observed in all irradiated samples by transmission electron microscopy. The results show that higher He implantation rate causes a shift in the swelling peak to higher temperatures in both Fe and Fe-Cr alloys. When assuming smaller cavities as biased sinks, the non-monotonic nature of the cavity swelling behavior is related to the ratio of biased to unbiased point defect sink strengths. Cr-enriched precipitates were observed in Fe-14Cr irradiated at 400 °C by atom probe tomography. Our analysis suggests the formation of Cr-enriched precipitates could suppress cavity swelling for Fe-Cr alloys with Cr content above 10 wt%.

Hypericum perforatum L., which includes a wide range of bioactive substances and is sold as a functional food formulation, has been used as an alternative to estrogen replacement treatment to relieve menopausal syndromes. However, methods to track HPL mechanisms and link them to metabolism disorder regulation during menopause periods have been lacking. To investigate HPL function in endocrine-related metabolic recognition, we applied both global and targeted metabolomic methods on ovariectomised rat serum and urine metabolites for treatment-specific metabolic profiling and to explore biomarkers and deduce their mechanisms via 1H-NMR and HPLC–MS/MS techniques. Results from the comparison of metabolite levels of rats that underwent an ovariectomy (OVX) before and after the administration of different doses of HPL showed that HPL can reverse the disordered changes induced in multiple biomarkers by menopausal syndromes. Through screening, identification, and quantification of the differential regulatory metabolites, 23 metabolites involved in 4 major metabolic pathways, including the arginine, taurine, pyruvate and tryptophan metabolic pathways, were highlighted as important for explaining the mechanisms of HPL. These pathways may be applicable for explanations of other menopausal syndrome symptoms, such as depression and hot flashes, and the effects of other herbs rich in flavonoids with menopause remission potential.