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Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin-dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT-3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin-likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well. [ABSTRACT FROM AUTHOR]

Summary: Casein phosphopeptides (CPPs) are mineral‐binding bioactive peptides derived from enzymatic digestion of casein. They have been shown to increase iron bioavailability due to increasing iron solubility at the alkaline pH of the intestine. Thus, they are potentially applicable as an advantageous preparation for iron fortification of food. This study aimed to characterise a commercially available CPP and determines optimum experimental conditions for binding it with ferrous iron. The effect of three variables – pH (5–7.5), mass ratio of iron to CPP (MR) (0.04–0.16) and holding time (40–80 min) – on the CPP's iron content was investigated using the central composite design (CCD) in response surface methodology (RSM), and a quadratic model was developed. The optimisation in this survey was based on the maximum response. Among all the regression's terms, the main and quadratic effects of pH represented the most significant influences on the iron content (P‐value <0.05). The obtained optimum conditions were as follows: pH 6.5, MR 0.14 and holding time 72 min, resulting in binding 68.66 mg iron per gram of the CPP. The quantity of iron bound to the CPP depended considerably on the experimental conditions and proved the importance of optimisation. [ABSTRACT FROM AUTHOR]

Abstract: DNAzyme and aptamer conjugations have already been used for sensitive and accurate detection of several molecules. In this study, we tested the relationship between conjugation orientation of DNAzyme and aflatoxin B1 aptamer and their subsequent peroxidase activity. Circular dichroism (CD) spectroscopy and biochemical analysis were used here to differentiate between these two conjugation patterns. Results showed that DNAzyme–aptamer has more catalytic activity and efficiency than aptamer–DNAzyme. Thereby, DNAzyme–aptamer with its superior efficiency can be used for design and development of more sensitive aflatoxin B1 DNA based biosensors. [ABSTRACT FROM AUTHOR]

Voltage-dependent calcium channels are crucial targets for a wide range of clinically active pharmacological agents. From these agents, 1,4-dihydropyridines constitute a group of small organic compounds are based on a core pyridine structure which can both block and enhance calcium currents. They are considered specific for L-Type calcium channels; however, other channel types, and in particular certain T-Type channels, may show sensitivity to dihydropyridine compounds. In this study, we synthesized a novel group of bis-1,4-dihydropyridines using the procedure reported by Dagnino that involved the condensation of n-alkyl diacetoacetate ( n = 2–7) with methyl-3-aminocrotonate and nitrophenylaldehyde. The synthesis was run under two conditions: (i) reflux and (ii) microwave. Calcium channels antagonist activity were determined in vitro using guinea-pig ileum longitudinal smooth muscle assay. Synthesis of these compounds was confirmed with 1H-NMR, IR and mass spectrometry. Then IC50 of them are calculated and compared with Nifedipine. Finally, the result of this pharmacological assay was used in quantitative structure–activity relationship studies utilizing multiple linear regression analysis. Most of these compounds are less active compared with Nifedipine. Decrease in activity is the result of increase in steric hindrance. The quantitative structure–activity relationship study indicates that the activity is related to the electrostatic and topological parameters and the distance between two C5-esteric groups of 1,4-dihydropyridine rings. [ABSTRACT FROM AUTHOR]