Changes in the IGF-1 and TNF-α synthesis pathways before and after three-month reduction diet with low glicemic index in women with PCOS

Objectives: An increase in IGF-I and TNF-α may be a cardioprotective effect. To examine the relationships between IGF-I and TNF-α and test the anthropometric and biochemical parameters before and after a low-glycemic index reduction diet using a correlation matrix. Material and methods: Twenty-two women diagnosed with PCOS according to Rotterdam’s criteria were eligible for this study, which analysed the results before and after a three months dietary intervention. Body composition measurements were determined by bioimpedance and performed twice, along with the labelling of lipid, carbohydrate and hormonal profiles. IGF-I and TNF-α were also determined in the serum. Results: Before dietary intervention, a significant correlation was observed. A correlation was also noted between the increase in TNF-α and DHEA-SO4, FSH, glucose level and total cholesterol. The increase in IGF-I was not related to anth­ropometric measurements: however, its concentration was observed to be related to the level of SHBG and HDL. After dietary intervention, the correlation between TNF-α and muscle mass percentage was confirmed, as was the correlation between WHR and fasting blood glucose levels. A significant negative correlation was observed between extracellular water, provided in litres, and SHBG level. Conclusions: One important role of IGF-I in PCOS pathogenesis is the stimulation of increased synthesis of SHBG and HDL. The increased level of IGF-I after the reduction diet had a cardioprotective effect. TNF-α inhibits FSH synthesis, preventing the growth of numerous follicles. Its synthesis is also related to DHEA-SO4. After three-month reduction diet does not significantly reduce TNF-α

The effects of 1,4-dimethylpyridine in metastatic prostate cancer in mice

BACKGROUND: We previously showed that 1-methylnicotinamide (1-MNA) and its analog 1,4-dimethylpyridine (1,4-DMP) could inhibit the formation of lung metastases and enhance the efficacy of cyclophosphamide-based chemotherapy in the model of spontaneously metastasizing 4T1 mouse mammary gland tumors. In the present study, we aimed to investigate whether the previously observed activity of pyridine compounds pertains also to the prevention and the treatment of metastatic prostate tumors, in a combined chemotherapy with docetaxel. METHODS: Cancer-preventing activity of 1,4-DMP was studied in the model of prostate tumors spontaneously arising in C57BL/6-Tg (TRAMP)8247Ng/J (TRAMP) mice. The efficacy of the combined chemotherapy, comprising simultaneous use of 1,4-DMP and docetaxel, was evaluated in the orthotopic mouse model of human PC-3M-luc2 prostate cancer. The toxicity of the applied treatment was also determined. RESULTS: The development of prostate tumors in TRAMP mice remained unaffected after administration of 1,4-DMP. Similarly, no effect of 1,4-DMP was found on the growth of orthotopically transplanted PC-3M-luc2 tumors. However, when 1,4-DMP was administered along with docetaxel, it enhanced the anticancer activity of the chemotherapy. As a result, in PC-3M-luc2-bearing mice statistically significant inhibition of the tumor growth and lower metastases incidence were observed. The decreased metastatic yield is probably related to the diminished platelet activity observed in mice treated with combined therapeutic regimen. Finally, the combined treatment exhibited lowered side effects accompanying docetaxel administration. CONCLUSIONS: Results presented herein confirm previously published data on the anticancer activity of pyridine compounds and demonstrate that 1,4-DMP may be beneficially implemented into chemotherapy utilizing various cytotoxic agents, directed against multiple metastatic tumor types. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3161-4) contains supplementary material, which is available to authorized users

Results of the first European Source Apportionment intercomparison for Receptor and Chemical Transport Models

In this study, the performance of the source apportionment model applications were evaluated by comparing the model results provided by 44 participants adopting a methodology based on performance indicators: z-scores and RMSEu, with pre-established acceptability criteria. Involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), provided a unique opportunity to cross-validate them. In addition, comparing the modelled source chemical profiles, with those measured directly at the source contributed to corroborate the chemical profile of the tested model results. The most used RM was EPA- PMF5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) and more difficulties are observed with SCE time series (72% of RMSEu accepted). Industry resulted the most problematic source for RMs due to the high variability among participants. Also the results obtained with CTMs were quite comparable to their ensemble reference using all models for the overall average (>92% of successful z-scores) while the comparability of the time series is more problematic (between 58% and 77% of the candidates’ RMSEu are accepted). In the CTM models a gap was observed between the sum of source contributions and the gravimetric PM10 mass likely due to PM underestimation in the base case. Interestingly, when only the tagged species CTM results were used in the reference, the differences between the two CTM approaches (brute force and tagged species) were evident. In this case the percentage of candidates passing the z-score and RMSEu tests were only 50% and 86%, respectively. CTMs showed good comparability with RMs for the overall dataset (83% of the z-scores accepted), more differences were observed when dealing with the time series of the single source categories. In this case the share of successful RMSEu was in the range 25% - 34%.JRC.C.5-Air and Climat