Fucoxanthin,a Marine-Derived Carotenoid from Brown Seaweeds and Microalgae: A Promising Bioactive Compound for Cancer Therapy

Fucoxanthin is a well-known carotenoid of the xanthophyll family, mainly produced by marine organisms such as the macroalgae of the fucus genus or microalgae such as Phaeodactylum tricornutum. Fucoxanthin has antioxidant and anti-inflammatory properties but also several anticancer effects. Fucoxanthin induces cell growth arrest, apoptosis, and/or autophagy in several cancer cell lines as well as in animal models of cancer. Fucoxanthin treatment leads to the inhibition of metastasis-related migration, invasion, epithelial–mesenchymal transition, and angiogenesis. Fucoxanthin also affects the DNA repair pathways, which could be involved in the resistance phenotype of tumor cells. Moreover, combined treatments of fucoxanthin, or its metabolite fucoxanthinol, with usual anticancer treatments can support conventional therapeutic strategies by reducing drug resistance. This review focuses on the current knowledge of fucoxanthin with its potential anticancer properties, showing that fucoxanthin could be a promising compound for cancer therapy by acting on most of the classical hallmarks of tumor cells.     

Repurposing the Pummerer Rearrangement: Determination of Methionine Sulfoxides in Peptides

The reversible oxidation of methionine residues in proteins has emerged as a biologically important post-translational modification. However, detection and quantitation of methionine sulfoxide in proteins is difficult. Our aim is to develop a method for specifically derivatizing methionine sulfoxide residues. We report a Pummerer rearrangement of methionine sulfoxide treated sequentially with trimethylsilyl chloride and then 2-mercaptoimidazole or pyridine-2-thiol to produce a dithioacetal product. This derivative is stable to standard mass spectrometry conditions, and its formation identified oxidized methionine residues. The scope and requirements of dithioacetal formation are reported for methionine sulfoxide and model substrates. The reaction intermediates have been investigated by computational techniques and by ¹³C NMR spectroscopy. These provide evidence for an α-chlorinated intermediate. The derivatization allows for detection and quantitation of methionine sulfoxide in proteins by mass spectrometry and potentially by immunochemical methods.     

Cyp1 Inhibition Prevents Doxorubicin-Induced Cardiomyopathy in a Zebrafish Heart-Failure Model

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.     

A Step toward Molecular Evolution of RNA: Ribose Binds to Prebiotic Fatty Acid Membranes,and Nucleosides Bind Better than Individual Bases Do

A major challenge in understanding how biological cells arose on the early Earth is explaining how RNA and membranes originally colocalized. We propose that the building blocks of RNA (nucleobases and ribose) bound to self-assembled prebiotic membranes. We have previously demonstrated that the bases bind to membranes composed of a prebiotic fatty acid, but evidence for the binding of sugars has remained a technical challenge. Here, we used pulsed-field gradient NMR spectroscopy to demonstrate that ribose and other sugars bind to membranes of decanoic acid. Moreover, the binding of some bases is strongly enhanced when they are linked to ribose to form a nucleoside or – with the addition of phosphate – a nucleotide. This enhanced binding could have played a role in the molecular evolution leading to the production of RNA.     

Dietary fat and breast cancer mortality: A systematic review and meta-analysis

Background: The influence of dietary fat upon breast cancer mortality remains largely understudied despite extensive investigation into its influence upon breast cancer risk. Objective: To conduct meta-analyses of studies to clarify the association between dietary fat and breast cancer mortality. Design: MEDLINE and EMBASE were searched for relevant articles published up to March 2012. Risk of all-cause or breast-cancer-specific death was evaluated by combining multivariable adjusted estimates comparing highest versus lowest categories of intake; and per 20 g increase in intake of total and/or saturated fat (g/day) using random-effects meta-analyses. Results: Fifteen prospective cohort studies investigating total fat and/or saturated fat intake (g/day) and breast cancer mortality were included. There was no difference in risk of breast-cancer-specific death (n = 6; HR = 1.14; 95% CI: 0.86, 1.52; p = 0.34) or all-cause death (n = 4; HR = 1.73; 95% CI: 0.82, 3.66; p = 0.15) for women in the highest versus lowest category of total fat intake. Breast-cancer-specific death (n = 4; HR = 1.51; 95% CI: 1.09, 2.09; p < 0.01) was higher for women in the highest versus lowest category of saturated fat intake. Conclusions: These meta-analyses have shown that saturated fat intake negatively impacts upon breast cancer survival.     

Effect of boiling and roasting on the fermentation of soybeans into dawadawa (soy-dawadawa)

Soybeans which had initially been dehulled by either boiling (boiled/dehulled) or roasting (roasted/dehulled) before peeling, were cooked and fermented into dawadawa, a traditional food condiment. The micropopulation, enzymatic activities, proximate composition, amino acid, and aroma profiles of the two types of soybean dawadawa were evaluated during fermentation. Only minor differences were found in the microbial profiles of the two types of soy-dawadawa. Although boiled/dehulled soy-dawadawa initially had lower microbial counts, it recorded higher counts at the advanced stages of fermentation. Proteolytic and amylolytic Bacillus species including Bacillus subtilis, Bacillus pumilus, Bacillus licheniformis, Bacillus cereus, and Bacillus firmus dominated the micropopulation of the two types of soy-dawadawa with Bacillus subtilis accounting for about 50% of the Bacillus species in all samples. Lactic acid bacteria and yeasts occurred in low numbers in the two types of soy-dawadawa. The proximate composition of the two types of soy-dawadawa were similar, and their contents of moisture and protein increased whilst fat and ash decreased during fermentation. Both types of fermenting soy-dawadawa recorded similar levels of alpha-amylase activity, but boiled/dehulled soy-dawadawa showed slightly higher protease activity. The levels of isoleucine, leucine, lysine, phenylalanine, arginine and proline increased significantly with fermentation time in both types of soy-dawadawa. With respect to differences in their aroma profiles, hexanodecanol, octadecyl acetate, 1,2-dimethyl benzene, tetradecene, (E)-5-eicosene, cyclohexadecane, and hexacosane were found only in the roasted/dehulled samples, whilst 1,2-ethanediol, ethyl acetate, dimethyl disulfide, cyclotetradecane, decene, indole , 2 butyl-octenal, acetophenone, and toluene were found only in the boiled/dehulled samples. A market focus group showed preference for roasted/dehulled soy-dawadawa over boiled/dehulled soy-dawadawa. Apart from the volatile aroma compounds, the biochemical and microbiological profiles of the two types of soy-dawadawa showed only minor differences and were also similar to the profiles reported for African locust bean dawadawa.     

Depressive symptoms in early marriage: Predictions from relationship confidence and negative marital interaction.

The authors proposed a model of depressive symptoms in early marriage in which relationship confidence, defined as perceived couple-level efficacy to manage conflicts and maintain a healthy relationship, mediates the effect of negative marital interactions on depressive symptoms. The model was tested in a sample of 139 couples assessed prior to marriage and 1 year later. As predicted, relationship confidence demonstrated simple negative associations with negative marital interaction and depressive symptoms for all participants. Longitudinal path analyses supported the mediational model for women only. In women but not men, negative marital interaction indirectly had an impact on depressive symptoms through the mediator of relationship confidence. Findings suggest that relationship confidence may be important to understanding links between marital distress and depressive symptoms, especially in women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)