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This study explores structure–reactivity relationships for the degradation of emerging perfluoroalkyl ether carboxylic acid (PFECA) pollutants with ultraviolet-generated hydrated electrons (eaq –). The rate and extent of PFECA degradation depend on both the branching extent and the chain length of oxygen-segregated fluoroalkyl moieties. Kinetic measurements, theoretical calculations, and transformation product analyses provide a comprehensive understanding of the PFECA degradation mechanisms and pathways. In comparison to traditional full-carbon-chain perfluorocarboxylic acids, the distinct degradation behavior of PFECAs is attributed to their ether structures. The ether oxygen atoms increase the bond dissociation energy of the C–F bonds on the adjacent −CF2– moieties. This impact reduces the formation of H/F-exchanged polyfluorinated products that are recalcitrant to reductive defluorination. Instead, the cleavage of ether C–O bonds generates unstable perfluoroalcohols and thus promotes deep defluorination of short fluoroalkyl moieties. In comparison to linear PFECAs, branched PFECAs have a higher tendency of H/F exchange on the tertiary carbon and thus lower percentages of defluorination. These findings provide mechanistic insights for an improved design and efficient degradation of fluorochemicals.

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Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the mechanism underlying the progression from cirrhosis to HCC remains unclear. Herein we report the concurrent increase of liver progenitor cells (LPCs) and transforming growth factor‐β (TGF‐β) in diethylnitrosamine (DEN)‐induced rat hepatocarcinogenesis and cirrhotic livers of HCC patients. Using several experimental approaches, including 2‐acetylaminofluorene/partial hepatectomy (2‐AAF/PHx) and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐elicited murine liver regeneration, we found that activation of LPCs in the absence of TGF‐β induction was insufficient to trigger hepatocarcinogenesis. Moreover, a small fraction of LPCs was detected to coexpress tumor initiating cell (T‐IC) markers during rat hepatocarcinogenesis and in human HCCs, and TGF‐β levels were positively correlated with T‐IC marker expression, which indicates a role of TGF‐β in T‐IC generation. Rat pluripotent LPC‐like WB‐F344 cells were exposed to low doses of TGF‐β for 18 weeks imitating the enhanced TGF‐β expression in cirrhotic liver. Interestingly, long‐term treatment of TGF‐β on WB‐F344 cells impaired their LPC potential but granted them T‐IC properties including expression of T‐IC markers, increased self‐renewal capacity, stronger chemoresistance, and tumorigenicity in NOD‐SCID mice. Hyperactivation of Akt but not Notch, signal transducer and activator of transcription 3 (STAT3), or mammalian target of rapamycin (mTOR) was detected in TGF‐β‐treated WB‐F344 cells. Introduction of the dominant‐negative mutant of Akt significantly attenuated T‐IC properties of those transformed WB‐F344 cells, indicating Akt was required in TGF‐β‐mediated‐generation of hepatic T‐ICs. We further demonstrate that TGF‐β‐induced Akt activation and LPC transformation was mediated by microRNA‐216a‐modulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppression. Conclusion: Hepatoma‐initiating cells may derive from hepatic progenitor cells exposed to chronic and constant TGF‐β stimulation in cirrhotic liver, and pharmaceutical inhibition of microRNA‐216a/PTEN/Akt signaling could be a novel strategy for HCC prevention and therapy targeting hepatic T‐ICs. (HEPATOLOGY 2012;56:2255–2267)

Colorectal cancer (CRC) is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States. Considering the risk factors of CRC, dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality. The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. As the most common types of microbes used as probiotics, lactic acid bacteria (LAB) are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism. LAB have been successfully used in managing diarrhea, food allergies, and inflammatory bowel disease. LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways. In this review, we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis, antioxidant DNA damages, immune responses, and epigenetics. The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.

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ObjectiveWe investigated the relationship between diabetes and telomere length by meta-analysis.MethodsWe searched five popular databases for articles published between 1990 and 2015 using “diabetes” and “telomere” as search terms. Data were processed with RevMan5, and random- or fixed-effects meta-analysis was applied. The effects of geographical region, diabetes type, body mass index (BMI), age and sex were examined. Funnel plots were applied to evaluate publication bias.ResultsSeventeen articles were obtained from 571 references. We identified a significant association between telomere length and diabetes mellitus (standardized mean difference [SMD]: −3.41; 95% confidence interval [CI]: −4.01, −2.80; heterogeneity, I2 = 99%) by comparing 5575 patients with diabetes and 6349 healthy individuals. The pooled SMD by geographic region indicated a significant association between shortened telomere length and diabetes mellitus (SMD: −3.41; 95% CI: −4.01, −2.80; heterogeneity, I2 = 99%). In addition, telomere length was significantly associated with age (SMD: −3.41; 95% CI: −4.01, −2.80), diabetes type (SMD: −3.41; 95% CI: −4.01, −2.80), BMI (SMD: −1.61; 95% CI: −1.98, −1.23) and sex (SMD: −4.94; 95% CI: −9.47, −0.40).ConclusionsThe study demonstrated a close relationship between diabetes mellitus and telomere length, which was influenced by region, age, diabetes type, BMI and sex.

Our data indicate that antibody profiling is a promising approach that could achieve high diagnostic accuracy for non-small cell lung cancer.