The influence of soybean extract on the expression level of selected drug transporters, transcription factors and cytochrome P450 genes encoding phase I drug-metabolizing enzymes

Objective: Soybean phytoestrogens, such as genistein and daidzein, reduce climacteric symptoms and the risk of certain chronic diseases such as cancer and cardiovascular diseases. Despite their widespread use in functional foods and dietary supplements, there is very little data available on their safety and herb-drug interactions, especially with antineoplastic agents. Hence, the aim of our study was to assess the effects of soybean extracts on the expression level of CYP genes and their transcriptional factors. We also investigated the effect of soybean on the mRNA level of transporters, such as P-glycoprotein (MDR1) and multidrug resistance-associated proteins (MRP1, MRP2). Materials and methods: Wistar rats were fed a standardized soybean extract (100 mg/kg, p.o.). cDNA was synthesized from total RNA isolated from different tissues (liver and intestinal epithelium) using reverse transcription. Gene expression level was analyzed by RT-PCR method. Results: We demonstrated a significant increase of CYP1A1 mRNA level (by 89%, p=0.002 and 125%, p=0.004) as compared with the control group. An increase of AHR and CAR expression after 10 days was also observed (by 60%, p0.05, respectively). Additionally, an inductive effect for CYP2D1 by 22% (p=0.008), Mdr1a by 267% (

Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters

There are a number of compounds that can modify the activity of ATP-binding cassette (ABC) and solute carrier (SLC) transporters in the blood-brain barrier (BBB). The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A, quercetin) substances showed a selective inhibitory effect. Moreover, extract from roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes except for mrp2. Extract from aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance against pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

Effect of Epilobium angustifolium and Serenoa repens extracts on regulation of non-genomic signaling pathway of kinases

Objectives: Changes of kinase activity of non-genomic cellular signaling pathway may influence the effectiveness of pharmacotherapy in case of hormone-dependent tumors. Our study investigated a possible interaction at the molecular level between an aqueous herbal extract of Epilobium angustifolium as well as a lipid-sterolic fruit extract of Serenoa repens and synthetic drugs used in the treatment of hormone-dependent cancers. Material and methods: E. angustifolium and Serenoa repens extracts were orally administered to testosteroneinduced rats for 21 days. Changes of RafA/Mapk3/Mapk1 mRNA levels were analyzed by real-time quantitative PCR using target specific primers. Results: The level of RafA mRNA slightly increased in rats receiving Epilobium angustifolium (p=0.076) and Serenoa repens (p=0.016) extracts. Administration of these extracts resulted in significantly elevated Mapk1 and Mapk3 transcripts in the investigated animals (

State business: gender, sex and marriage in Tajikistan

This article examines the relation of the state to masculinity and sexuality by way of an exploration of the sexual problems of a young man and his wife in Tajikistan at the end of the Soviet era. It suggests that the regime’s inattention to this kind of issue was bound up with the importance to the state of projecting appropriate versions of masculinity. It further posits the idea that the continued refusal of the independent Tajik state to offer appropriate treatments for sexual dysfunction is consistent with the image of modernity President Rahmon wishes to present to the world. The article shows that as masculinity discursively occupies the superior gender position, with men expected to dominate, the state is itself impotent to respond when they are, in fact, unable to do so in sexual practice. However, the myth of male dominance persists to the point that it may prevent women from seeing beyond their subordination and finding mutually beneficial solutions in their familial and sexual relationships

Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers

Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microscopy) and chemical (nanoscale secondary ion mass spectrometry) imaging on the same samples, we show that pores formed by antimicrobial peptides in supported lipid bilayers are not necessarily limited to a particular diameter, nor they are transient, but can expand laterally at the nano-to-micrometer scale to the point of complete membrane disintegration. The results offer a mechanistic basis for membrane poration as a generic physicochemical process of cooperative and continuous peptide recruitment in the available phospholipid matrix

Diagnosis of melanoma localized in ulcer associated with diabetic foot syndrome — case report

Difficult-to-heal wounds, which include ulcers in diabetic foot syndrome (DFS), are characterized by long healing times, sometimes leading to sepsis and the need for amputation. The often months-long persistence of the ulceration creates conditions for uncontrolled proliferation of granulation tissue, which is a component of the wound, also in the direction of neoplastic lesions. The co-occurrence of such a condition with hyperglycemia can increase the risk of cancer development within the ulcer. This article presents the case of a 71-year-old man in whom a histopathological examination of a wound specimen was performed due to a lack of progress in the healing process. The patient was diagnosed with melanoma and was referred urgently to a referral centre, where a toe resection and sentinel node biopsy were performed. In addition, the article presents a diagnostic pathway that applies to patients with suspected proliferative disease in the wound associated with DFS

Advancing the use of passive sampling in risk assessment and management of contaminated sediments: Results of an international passive sampling inter-laboratory comparison

This work presents the results of an international interlaboratory comparison on ex situ passive sampling in sediments. The main objectives were to map the state of the science in passively sampling sediments, identify sources of variability, provide recommendations and practical guidance for standardized passive sampling, and advance the use of passive sampling in regulatory decision making by increasing confidence in the use of the technique. The study was performed by a consortium of 11 laboratories and included experiments with 14 passive sampling formats on 3 sediments for 25 target chemicals (PAHs and PCBs). The resulting overall interlaboratory variability was large (a factor of ∼10), but standardization of methods halved this variability. The remaining variability was primarily due to factors not related to passive sampling itself, i.e., sediment heterogeneity and analytical chemistry. Excluding the latter source of variability, by performing all analyses in one laboratory, showed that passive sampling results can have a high precision and a very low intermethod variability

Vermiculite bio-barriers for Cu and Zn remediation: an eco-friendly approach for freshwater and sediments protection

The increase in heavy metal contamination in freshwater systems causes serious environmental problems in most industrialized countries, and the effort to find ecofriendly techniques for reducing water and sediment contamination is fundamental for environmental protection. Permeable barriers made of natural clays can be used as low-cost and eco-friendly materials for adsorbing heavy metals from water solution and thus reducing the sediment contamination. This study discusses the application of permeable barriers made of vermiculite clay for heavy metals remediation at the interface between water and sediments and investigates the possibility to increase their efficiency by loading the vermiculite surface with a microbial biofilm of Pseudomonas putida, which is well known to be a heavy metal accumulator. Some batch assays were performed to verify the uptake capacity of two systems and their adsorption kinetics, and the results indicated that the vermiculite bio-barrier system had a higher removal capacity than the vermiculite barrier (?34.4 and 22.8 % for Cu and Zn, respectively). Moreover, the presence of P. putida biofilm strongly contributed to fasten the kinetics of metals adsorption onto vermiculite sheets. In open-system conditions, the presence of a vermiculite barrier at the interface between water and sediment could reduce the sediment contamination up to 20 and 23 % for Cu and Zn, respectively, highlighting the efficiency of these eco-friendly materials for environmental applications. Nevertheless, the contribution of microbial biofilm in open-system setup should be optimized, and some important considerations about biofilm attachment in a continuous-flow system have been discussed.This work has been produced thanks to the collaboration of Dip.SA (University of Bologna) and IBB (University of Minho). A particular acknowledgment is due to Dr. E. Rosales. The work was partially financed by the FCT Strategic Project Pest-OE/EQB/LA0023 and the Project ‘‘BioEnv—Biotechnology and Bioengineering for a sustainable world,’’ co-funded by the Programa Operacional Regional do Norte (ON.2–O Novo Norte), QREN, FEDER