1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis

Background: 1-methylnicotinamide (1-MNA), an endogenous metabolite of nicotinamide, has recently gained interest due to its anti-inflammatory and anti-thrombotic activities linked to the COX-2/PGI2 pathway. Given the previously reported anti-metastatic activity of prostacyclin (PGI2), we aimed to assess the effects of 1-MNA and its structurally related analog, 1,4-dimethylpyridine (1,4-DMP), in the prevention of cancer metastasis. Methods: All the studies on the anti-tumor and anti-metastatic activity of 1-MNA and 1,4-DMP were conducted using the model of murine mammary gland cancer (4T1) transplanted either orthotopically or intravenously into female BALB/c mouse. Additionally, the effect of the investigated molecules on cancer cell-induced angiogenesis was estimated using the matrigel plug assay utilizing 4T1 cells as a source of pro-angiogenic factors. Results: Neither 1-MNA nor 1,4-DMP, when given in a monotherapy of metastatic cancer, influenced the growth of 4T1 primary tumors transplanted orthotopically; however, both compounds tended to inhibit 4T1 metastases formation in lungs of mice that were orthotopically or intravenously inoculated with 4T1 or 4T1-luc2-tdTomato cells, respectively. Additionally, while 1-MNA enhanced tumor vasculature formation and markedly increased PGI2 generation, 1,4-DMP did not have such an effect. The anti-metastatic activity of 1-MNA and 1,4-DMP was further confirmed when both agents were applied with a cytostatic drug in a combined treatment of 4T1 murine mammary gland cancer what resulted in up to 80 % diminution of lung metastases formation. Conclusions: The results of the studies presented below indicate that 1-MNA and its structural analog 1,4-DMP prevent metastasis and might be beneficially implemented into the treatment of metastatic breast cancer to ensure a comprehensive strategy of metastasis control

Global forecasting of thermal health hazards: the skill of probabilistic predictions of the Universal Thermal Climate Index (UTCI)

Although over a hundred thermal indices can be used for assessing thermal health hazards, many ignore the human heat budget, physiology and clothing. The Universal Thermal Climate Index (UTCI) addresses these shortcomings by using an advanced thermo-physiological model. This paper assesses the potential of using the UTCI for forecasting thermal health hazards. Traditionally, such hazard forecasting has had two further limitations: it has been narrowly focused on a particular region or nation and has relied on the use of single ‘deterministic’ forecasts. Here, the UTCI is computed on a global scale,which is essential for international health-hazard warnings and disaster preparedness, and it is provided as a probabilistic forecast. It is shown that probabilistic UTCI forecasts are superior in skill to deterministic forecasts and that despite global variations, the UTCI forecast is skilful for lead times up to 10 days. The paper also demonstrates the utility of probabilistic UTCI forecasts on the example of the 2010 heat wave in Russia

Genomic and Epigenomic Responses to Chronic Stress Involve miRNA-Mediated Programming

Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function

Application of lactic acid bacteria to produce probiotic vegetable juice

Celem pracy było zaprojektowanie i wytworzenie probiotycznego soku warzywnego o właściwej jakości mikrobiologicznej i sensorycznej. Użyto pięciu potencjalnie probiotycznych szczepów bakterii z gatunku Lactobacillus, tj. Lb. plantarum, Lb. rhamnosus (2 szczepy), Lb. brevis i Lb. pentosus do przeprowadzenia kontrolowanej fermentacji soku z kapusty oraz soku z kapusty z dodatkiem soku jabłkowego. W ocenie sensorycznej najwyżej oceniono sok fermentowany szczepem Lb. plantarum K1. Przez cały okres przechowywania liczba komórek bakterii utrzymywała się na poziomie 8,76 ÷ 9,17 log jtk/cm³. W zależności od temperatury przechowywania wartość pH soków stopniowo zmniejszała się z 4,17 do poziomu 3,61 ÷ 3,34. Po 16 dniach składowania nastąpiło obniżenie ogólnej jakości sensorycznej soków przechowywanych w temp. 4 i 8 ºC, co mogło być spowodowane znacznym stopniem ich zakwaszenia. W sokach przechowywanych w temp. 15 ºC po 8 dniach zaobserwowano obniżenie jakości ogólnej do poziomu poniżej 5 j.u. Potwierdzono możliwość zastosowania szczepu Lb. plantarum K1 do otrzymania fermentowanego soku z kapusty z dodatkiem soku jabłkowego o zadowalającej jakości sensorycznej, zawierającego odpowiednio dużą (10⁸ jtk/cm³) liczbę komórek bakterii.The objective of the research study was to design and produce a probiotic vegetable juice of a proper microbiological and sensory quality. Five potentially probiotic bacterial strains were used, i.e.: Lactobacillus plantarum,, Lb. rhamnosus (two strains), Lb. brevis, and Lb. pentosus to perform a controlled fermentation of cabbage juice and cabbage juice with apple juice added. The sensory assessed juice that was fermented using an Lb. plantarum K1 strain was rated the highest. During the entire storage, the count of lactic acid bacteria was at the same level, which ranged from 8.76 to 9.17 log jtk/cm³. Depending on the storage temperature, the pH value decreased gradually from 4.17 to a level of 3.61 ÷ 3.34. After a 16 day period of storage, the overall sensory quality of juices stored at 4 and 8 ºC declined; this could probably be caused by a considerable degree of their acidity. In the juices stored at 15 ºC, after the 8th day of storage, a reduction below a level of 5 j.u. was reported in the overall sensory quality. It was confirmed that there was a possibility of using the Lb. plantarum K1 strain to produce a fermented cabbage juice with apple juice added; such fermented juice would have an acceptable sensory quality and would contain a sufficient count (10⁸ cfu/cm³) of lactic acid bacteria