Downregulation of TAZ elicits a mitochondrial redox imbalance and ferroptosis in lung epithelial cells exposed to diesel exhaust particles.

Mitochondrial dysfunction was reported to be involved in the development of lung diseases including chronic obstructive pulmonary disease (COPD). However, molecular regulation underlying metabolic disorders in the airway epithelia exposed to air pollution remains unclear. In the present study, lung bronchial epithelial BEAS-2B and alveolar epithelial A549 cells were treated with diesel exhaust particles (DEPs), the primary representative of ambient particle matter. This treatment elicited cell death accompanied by induction of lipid reactive oxygen species (ROS) production and ferroptosis. Lipidomics analyses revealed that DEPs increased glycerophospholipid contents. Accordingly, DEPs upregulated expression of the electron transport chain (ETC) complex and induced mitochondrial ROS production. Mechanistically, DEP exposure downregulated the Hippo transducer transcriptional co-activator with PDZ-binding motif (TAZ), which was further identified to be crucial for the ferroptosis-associated antioxidant system, including glutathione peroxidase 4 (GPX4), the glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione-disulfide reductase (GSR). Moreover, immunohistochemistry confirmed downregulation of GPX4 and upregulation of lipid peroxidation in the bronchial epithelium of COPD patients and Sprague-Dawley rats exposed to air pollution. Finally, proteomics analyses confirmed alterations of ETC-related proteins in bronchoalveolar lavage from COPD patients compared to healthy subjects. Together, our study discovered that involvement of mitochondrial redox dysregulation plays a vital role in pulmonary epithelial cell destruction after exposure to air pollution.

Occurrence, distribution and risk assessment of suspected endocrine-disrupting chemicals in surface water and suspended particulate matter of Yangtze River (Nanjing section).

The occurrence and distribution of eight selected endocrine-disrupting chemicals were investigated in samples of surface water and suspended particulate matter (SPM) in Nanjing section of Yangtze River over a year (the flow period, the wet period and the dry period). All target compounds were detected at least once in surface water with 4-tert-butylphenol (4-TBP), nonyphenol (NP) and bisphenol A (BPA) as the dominant compounds, with concentrations in the range of 225-1121ng/L, 1.4-858ng/L and 1.7-563ng/L, respectively. Except for December, all selected compounds for the other sampling times were not found in all sampling points. NP (mean concentration 69.8µg/g) and BPA (mean concentration 51.8µg/g) were also the dominant estrogens in SPM. In addition, the highest total compounds concentrations were found in December in both phases, which could be due to the low flow conditions and temperature during this season. Meanwhile, a significant positive correlation was found between the total compounds concentrations in the water phase and those in SPM phase. Risk assessment based on the calculated risk quotients (RQ) showed that low and moderate risk for the aquatic environment from presence of the target compounds at all sampling points with exception of 4-TBP and NP which might pose a high risk to aquatic organisms.

[Association of 8-hydroxyguanine glycosidase OGG1 Ser326Cys polymorphism with male infertility].

OBJECTIVE: To explore the association of 8-hydroxyguanine glycosidase OGG1 Ser326Cys polymorphism with semen quality and the risk of male infertility. METHODS: This case-control study included 620 idiopathic infertile patients and 385 normal fertile controls. We determined their genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and analyzed their semen quality by computer-aided semen analysis (CASA). RESULTS: The individuals with OGG1 326 Cys/Cys showed significantly lower sperm motility and concentration ([52.1 +/- 26.7]% and (3.75 +/- 0.91) x 10(6)/ml, ln transformed value) than the Ser/Ser carriers ([59.0 +/- 21.8] % and (4.12 +/- 0.88) x 10(6)/ml, ln transformed value) (P < 0.05). The risk of male infertility increased 69% in the OGG1 326Cys allele carriers as compared with the Ser carriers (OR = 1.69, 95% CI: 1.24 -2.31). CONCLUSION: OGG1 326 Ser/Cys polymorphism might contribute to the risk of male infertility in the southern Chinese population.

[Bulky DNA adducts in human sperm correlate with semen parameters and sperm apoptosis].

OBJECTIVE: To explore the correlation of sperm polycyclic aromatic hydrocarbons (PAH)-DNA adducts with semen quality and sperm apoptosis. METHODS: We collected semen samples from 433 infertile Chinese men, detected sperm PAH-DNA adducts using immunofluorescence staining and flow cytometry, and determined the rate of sperm apoptosis by TUNEL. RESULTS: Multiple linear regression analysis showed that the level of sperm PAH-DNA adducts was correlated negatively with sperm concentration (beta = -0.632), total sperm count (beta = -0.830) and sperm motility (beta = -9.647), but positively with the rate of sperm apoptosis (beta = 0.130). CONCLUSION: Sperm PAH-DNA adducts are evidently correlated with semen quality and sperm apoptosis, and play an important role in the evaluation of male productivity.

Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer.

We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable information for predicting metastasis and recurrence in breast cancer. The objective of this study was to investigate the significance of detecting survivin-expressing CCC on the clinical outcomes of patients with non-small cell lung cancer (NSCLC). Peripheral blood samples collected from 143 NSCLC patients and 177 healthy volunteers were quantitatively evaluated using a technique developed in our laboratory that detected reverse transcription-polymerase chain reaction (RT-PCR) products based on a hybridisation-enzyme linked immunosorbant essay (ELISA), which we called RT-PCR ELISA. The presence of survivin-expressing CCC was detected in 63 cancer patients (44.1%) and was significantly associated with pathological T classification, nodal status, and disease stages (all P<0.001). During a follow-up period of 36 months, patients who had positive survivin expressions at the time of the initial assay test had a higher relapse rate and shorter survival time when compared to those who had negative survivin expressions (all P<0.001). Through multivariate analysis, the detection of survivin-expressing CCC was found to be an independent predictor for cancer recurrence (HR=43.5; 95% CI=2.67-70.9; P=0.008) and survival (HR=1.35; 95% CI=1.02-4.31; P=0.049). Thus, detection of survivin-expressing CCC could be used in the prediction of disease recurrence as well as in the prognosis of NSCLC.

The change in circulating tumor cells before and during concurrent chemoradiotherapy is associated with survival in patients with locally advanced head and neck cancer.

BACKGROUND: This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the outcomes in patients with head and neck squamous cell carcinoma. METHODS: CTCs were detected using a negative selection strategy and flow cytometry protocol. RESULTS: We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2-4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression-free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses. CONCLUSION: In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.

Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse.

BACKGROUND: We previously demonstrated that the detection of circulating cancer cells (CCCs) expressing survivin mRNA could provide valuable information for predicting metastasis and recurrence in breast cancer. The objective of this study was to investigate whether or not the detection of survivin expression in the peripheral blood could also have significant effects on the clinical outcomes of patients with gastric and colorectal cancer. METHODS: Survivin-expressing CCCs in peripheral blood samples obtained from 55 gastric cancer patients, 86 colorectal cancer patients, and 87 healthy volunteers were quantitatively examined by using a RT-PCR ELISA. Its clinical significance was statistically evaluated. RESULTS: The CCCs in the peripheral blood samples were detected in 45.4% and 44.0% of gastric and colorectal cancer patients, respectively. The presence of survivin-expressing CCCs was found to be significantly associated with the degree of tumor penetration, nodal status, and disease stages for both types of cancers. During a follow-up period of 36 months, patients who had a positive detection at the time of the initial assay test had a higher relapse rate than those who had a negative detection. As well, survivin-expressing CCCs were statistically shown to be a significant and independent predictor for cancer recurrence. The detection of survivin-expressing CCCs was also demonstrated to be more accurate in terms of predicting recurrence than traditional detection methods such as plasma carcinoembryonic antigen (CEA) measurements. CONCLUSION: The detection of CCCs expressing survivin mRNA could be used to accurately identify gastric and colorectal cancer patients with high risks of relapse.

Occurrence, spatial distribution, and ecological risks of typical hydroxylated polybrominated diphenyl ethers in surface sediments from a large freshwater lake of China.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been frequently observed in marine aquatic environments; however, little information is available on the occurrence of these compounds in freshwater aquatic environments, including freshwater lakes. In this study, we investigated the occurrence and spatial distribution of typical OH-PBDEs, including 2'-OH-BDE-68, 3-OH-BDE-47, 5-OH-BDE-47, and 6-OH-BDE-47 in surface sediments of Taihu Lake. 3-OH-BDE-47 was the predominant congener, followed by 5-OH-BDE-47, 2'-OH-BDE-68, and 6-OH-BDE-47. Distributions of these compounds are drastically different between sampling site which may be a result of differences in nearby point sources, such as the discharge of industrial wastewater and e-waste leachate. The positive correlation between ∑OH-PBDEs and total organic carbon (TOC) was moderate (r = 0.485, p < 0.05), and site S3 and S15 were excluded due to point source pollution, suggesting that OH-PBDEs concentrations were controlled by sediment TOC content, as well as other factors. The pairwise correlations between the concentrations of these compounds suggest that these compounds may have similar input sources and environmental behavior. The target compounds in the sediments of Lake Taihu pose low risks to aquatic organisms. Results show that OH-PBDEs in Lake Taihu are largely dependent on pollution sources. Because of bioaccumulation and subsequent harmful effects on aquatic organisms, the concentrations of OH-PBDEs in freshwater ecosystems are of environmental concern.

Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance.

We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable information for predicting recurrence in patients with breast, lung, gastric and colorectal carcinoma. The purpose of this study is to investigate whether the detection of survivin-expressing CCC in the peripheral blood is also useful for predicting recurrence in patients with esophageal squamous cell carcinoma (ESCC). Blood samples obtained from 108 ESCC patients and 75 healthy volunteers were quantitatively investigated by a technique that detected reverse transcription-polymerase chain reaction products based on a hybridization-enzyme linked immunosorbent essay. Not all of the patients were available for the follow-up study. Only 48 patients who were treated with similar adjuvant therapy regimens were available and followed-up for 33 months after the initial assay test. Survivin-expressing CCC were detected in 51 (47.2%) patients. The presence of survivin-expressing CCC was found to be significantly associated with depth of invasion, vascular invasion, nodal status, and disease stages (P = 0.032, 0.019, 0.018, and 0.001, respectively). During the follow-up period, patients who had positive survivin expressions had a higher relapse rate and a shorter survival time than those who had negative survivin expressions (P = 0.002 and 0.016, respectively). Examination of survivin-expressing CCC could provide valuable information in the prediction of haematogenous recurrence as well as in the prognosis of ESCC.