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BACKGROUND: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. OBJECTIVES: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. METHODS: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. RESULTS: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. CONCLUSIONS: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. http://dx.doi.org/10.1289/EHP360, Introduction Cadmium, a ubiquitous environmental compound, is present in soils, sediments, air, and water. Cadmium exposure affects human populations worldwide. In addition to cigarette smoke, contamination of the food chain [...]

Research reveals that under low denaturant concentrations, the four-helix bundle protein exhibits partially unfolded intemediates that are more stable than those of fully unfolded forms. Data indicate that the four-helix bundle protein shows an apparent two-state folding kinetics with partially unfolded forms forming after the rate-limiting step.

BACKGROUND: Benzo[a]pyrene (B[a]P) is a common environmental and foodborne pollutant. Although the carcinogenicity of high-dose B[a]P has been extensively reported, the effects of long-term B[a]P exposure at lower environmental doses on cancer development are less understood. OBJECTIVES: We investigated the impact of B[a]P on human hepatocellular carcinoma (HCC) progression at various levels of exposure and identified a potential intervention target. METHODS: We used a model based on human HCC cells exposed to various concentrations of B[a]P (i.e., 0.01, 1, or 100 nM) for 1 month to examine the effects of B[a]P on cell growth, migration, invasion, and angiogenicity. A bioluminescent murine model was established to assess tumor metastasis in vivo. RESULTS: Chronic B[a]P exposure did not alter HCC cell growth but promoted cell migration and invasion both in vitro and in vivo. There was an negative association between B[a]P exposure and the survival of tumor-bearing mice. In addition, B[a]P-treated HCC cells recruited vascular endothelial cells and promoted tumor angiogenesis, possibly through elevating vascular endothelial growth factor secretion. Furthermore, the NF-κB pathway may be an adverse outcome pathway associated with the cumulative effects of B[a]P on HCC metastasis. CONCLUSIONS: These findings a) indicate that B[a]P has effects on HCC progression; b) identify a possible adverse outcome pathway; and c) contribute to a better understanding of the adverse effects of chronic exposure of B[a]P to human health. http://dx.doi.org/10.1289/ehp.1408524, Introduction Benzo[@]pyrene (B[a]P), a prototypical and well characterized member of the polycyclic aromatic hydrocarbon (PAH) family (Phillips 1983; Srivastava et al. 2000), is a procarcinogen formed in the process of [...]

Benzo( a )pyrene (B[ a ]P) is a common environmental and foodborne pollutant which has been identified as a Group I carcinogen. Although the carcinogenicity of B[ a ]P has been illustrated, its comprehensive influence on metabolism and further relevance in adverse health outcomes are not well understood. To investigate the global metabolic effects of long-term B[ a ]P exposure at environmental dosage, we utilized the human SMMC-7721 cell-based B[ a ]P exposure models to perform a metabolomics study and network analysis. A total of 316 biochemicals were identified and 104 metabolites were found to be significantly altered. Bioinformatics analysis showed that the amino acid, carbohydrate, and lipid metabolism pathways and the nucleotide metabolism pathway were influenced by prolonged B[ a ]P exposure. Notably, the metabolic effects of B[ a ]P varied with different dosages. In addition, B[ a ]P exposure caused a decline in the glycolysis process but enhanced the glycolytic capability of SMMC-7721 cells in vitro . These findings establish the overall B[ a ]P-induced metabolic network, characterize the metabolic effects of chronic and environmental B[ a ]P exposure on human-relevant cells, and enhance the understanding of the adverse outcome pathway frame of B[ a ]P.

Context: Circulating levels of 25-hydroxyvitamin D [25(OH)D] may affect the prognosis of cancer patients; however, the epidemiological results are not consistent., Objective: To perform a meta-analysis of all published studies to assess the associations of circulating 25(OH)D levels measured at or near the time of diagnosis and outcomes for cancer patients., Data Sources: Searches of the PubMed and MEDLINE databases were performed and updated to December 2013., Study Selection: Studies reporting an association between circulating 25(OH)D levels at or near the time of diagnosis and outcomes for the patients were included., Data Extraction: Data extraction was performed independently by two authors, and conflicts were resolved by a third investigator., Data Synthesis: Included in the meta-analysis were 25 studies with 17 332 cases. Significant associations between circulating 25(OH)D levels at or near the time of diagnosis and the outcomes for cancer patients were found. The pooled hazard ratio for the highest vs the lowest quartile of circulating 25(OH)D levels was 0.55 (95% confidence interval [CI] = 0.33-0.91) for overall survival of colorectal cancer patients, 0.63 (95% CI = 0.51-0.77) for breast cancer patients, and 0.48 (95% CI = 0.36-0.64) for lymphoma patients. Higher 25(OH)D levels were significantly associated with reduced cancer-specific mortality for patients with colorectal cancer (P = .005) and lymphoma (P < .001) and improved disease-free survival for patients with breast cancer (P < .001) or lymphoma (P < .05). A 10-nmol/L increment in circulating 25(OH)D levels conferred a hazard ratio of 0.96 (95% CI = 0.95-0.97) for overall survival of the cancer patients., Conclusions: The results indicate that cancer patients with higher circulating 25(OH)D levels at or near the time of diagnosis have better outcomes.