The Regenerative Potential of Donkey and Human Milk on the Redox-Sensitive and Proliferative Signaling Pathways of Skin Fibroblasts.

The influence of milk bioactive peptides on skin regenerative potential and rejuvenation is very often limited because of allergic reactions. The current study is aimed at exploring the influence of donkey colostrum and mature milk, human colostrum and mature milk, and ß-casein and ß-casomorphine-7, on the growth and inflammatory response of the culture of cultured skin fibroblasts exposed to these conditions for twenty-four hours. Their effects on the growth-regulatory kinases and redox-sensitive, proinflammatory transcriptional factor NF-κB were detected by using specific primary antibodies against NF-κB p65, Akt-1, phospho-Akt-1, Erk-1, phospho-Erk-1, JNK, phospho-JNK, phospho-STAT-1, and CD26, while logarithmic integrated fluorescence intensity patterns were recorded by flow cytometry. The downregulation of NF-κB p65 was observed after the exposure of skin fibroblasts to donkey milk and human colostrum, while ß-casein and ß-casomorphine-7 exerted the opposite effect, which suggests that noncasein bioactive peptides of donkey and human milk may be responsible for anti-inflammatory properties. The exposure to all milk species examined and ß-casein leads to the activation of growth-regulatory kinases (Akt1/2/3 kinase, Erk kinase, JNK kinase, and Stat-1 kinase), especially for the p-Erk pathway, which suggests that essential amino acids of casein may be responsible for Erk-induced cell cycle activation and proliferation. The opposite effect was observed when cells were exposed to ß-casomorphine-7, which may affect the skin fibroblast survival and their proliferative and regenerative potential. Donkey milk did not significantly change the CD26 antigen expression. In conclusion, our results suggest that among cell signaling molecules, the most sensitive but nonspecific downstream effector is p-Erk kinase, which may point to donkey milk usefulness in wound healing, regenerative, and aesthetic dermatology. The noncasein bioactive peptides of donkey milk may be responsible for the anti-inflammatory property of donkey milk and colostrum, which may indicate the usefulness in the treatment of inflammatory skin diseases.

A common approach for ranking of microbiological and chemical hazards in foods based on risk assessment - useful but is it possible?

This article compares and contrasts microbial and chemical risk assessment methodologies in order to evaluate the potential for a common framework for ranking of risk of chemical and microbiological hazards, and developments needed for such a framework. An overview of microbial (MRA) and chemical (CRA) risk assessment is presented and important differences are highlighted. Two microbiological and two chemical hazard-food combinations were ranked based on both a margin of exposure and a risk assessment approach. The comparisons illustrated that it is possible to rank chemical and microbiological hazard-food combinations with traditional approaches from each domain and indicated that the rank order but not the absolute measures is similar using either approach. Including severity in the assessment using DALY reduced differences between hazards and affected the outcome more than which approach was used. Ranking frameworks should include assessment of uncertainty as an integral part of the ranking, and be based on assessment of risk, not safety, and expressed in a common health metric such as disease burden. Necessary simplifications to address data gaps can involve the use of default scenarios. Challenges include comparisons of case-based vs. non-case-based health-endpoints, e.g. biomarker concentration, and integration of the severity of health effects into ranking.

Risk ranking of chemical and microbiological hazards in food.

Risk ranking is a versatile tool used to prioritise activities performed by public health regulatory bodies. It also allows efficient communication between all stakeholders in the process of risk analysis. However, risk ranking methods are still not optimal. Because of the different approaches employed in the risk assessment of microbiological agents and chemicals, it is difficult to rank them together using the same metrics. In our work, we first discuss differences and commonalities between chemical and microbiological risk assessment to provide a starting point for consideration of a common risk ranking platform. In the second part, we perform risk ranking of contaminants and regulated chemicals using the recently developed Risk Thermometer tool. In this approach, chemicals are not ranked solely on the basis of the margin of exposure between a reference value and the exposure, but also by considering the severity of the critical health effects used. The results show that ranking using both methods provides different results from the use of either method alone. Overall, specific chemical groups (i.e. heavy metals, pesticides, etc.) do not generally rank higher or lower, but individual compounds are scattered in the rankings from low to high. Risk ranking methods demand further development to gain wide acceptability and recognition.

Crosstalk between possible cytostatic and antiinflammatory potential of ketoprofen in the treatment of culture of colon and cervix cancer cell lines.

OBJECTIVES: The aim of this study was to test the cytostatic potential of ketoprofen in the in vitro treatment of cells derived from colon and cervix cancer. BACKGROUND: NF-κB and cyclooxygenase can have a role in different stages of the development and progression of cancer. In recent years, special attention has been paid to the possible cytostatic potential of nonsteroidal anti-inflammatory drugs. There are no published data on the use of ketoprofen in pharmacotherapy of the colon and cervical carcinoma. METHODS: We examined the effect of ketoprofen alone or in combination with cisplatin and 5-fluorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. Measurement of the level of NF-κB was also performed in the cells of both cell lines. RESULTS: The results of present study have shown that at least one of the mechanisms of antiproliferating and/or cytostatic effects of different concentrations of ketoprofen on Caco-2 and HeLa cells could include the transcription factor NF-κB. CONCLUSIONS: Since this transcription factor is controlled by the altered expression of COX-2, the inhibition of this enzyme by ketoprofen may represent a significant step in synergistic cascade of the therapy and prevention of colon and cervical cancer (Tab. 4, Ref. 31).

Novel metabolic roles of L-arginine in body energy metabolism and possible clinical applications.

Although the body can synthesize L-arginine, exogenous supplementation may be sometimes necessary, especially in particular conditions which results in depleted endogenous source. Among diseases and states when exogenous supplementation may be necessary are: burns, severe wounds, infections, insufficient circulation, intensive physical activity or sterility. In recent time, the attention was paid to the use of L-arginine supplementation by athletes during intensive sport activity, to enhance tissue growth and general performance, to potentiate the ergogenic potential and muscle tolerance to high intensive work and gas exchange threshold, to decrease ammonia liberation and recovery performance period and to improve wound healing. High-intensity exercise produces transient hyperammoniemia, presumably due to AMP catabolism. Catabolic pathways of AMP may involve its deamination or dephosphorylation, mainly in order to compensate fall in adenylate enrgy charge (AEC), due to AMP rise. The enzymes of purine metabolism have been documented to be particularly sensitive to the effect of dietary L-arginine supplementation. L-arginine supplementation leads to redirection of AMP deamination on account of increased AMP dephosphorylation and subsequent adenosine production and may increase ATP regeneration via activation of AMP kinase (AMPK) pathway. The central role of AMPK in regulating cellular ATP regeneration, makes this enzyme as a central control point in energy homeostasis. The effects of L-arginine supplementation on energy expenditure were successful independently of age or previous disease, in young sport active, elderly, older population and patients with angina pectoris.

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines.

OBJECTIVES: The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the influence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. BACKGROUND: In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. METHODS: We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fluorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. RESULTS: At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. CONCLUSION: The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31).