Cholesterol-lowering action of a novel nutraceutical combination in uremic rats: Insights into the molecular mechanism in a hepatoma cell line

Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris®, containing MK-7, magnesium carbonate, and Sucrosomial® Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, i.e. control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial® Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; p < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (−18.9% in supplemental uremic vs. uremic diet; p < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (−38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients

The Management of Voluntary Abortion in Family Counselling Services. A Qualitative Study on the Role of Social Workers in Italy

Introduction. Elective abortion has always been considered taboo. The event can sometimes be experienced as traumatic, as the woman finds herself struggling against a range of emotions: fear, shame, ambivalence, and a sense of guilt. Multidisciplinary support is therefore fundamental to guide women during this complex phase, and social workers usually play a key role in the process. The present study aimed therefore to explore the experiences and perspectives of social workers who worked with women who decided to have abortions, focusing on the strongest and weakest aspects of their support process. Methodology. The study involved 10 social workers working in family counselling services in Italy. All of them were female, with a mean age of 47 years, and a mean of 16.7 years of experience in the field. The study followed a qualitative approach, based on semi-structured interviews that were studied following the principles of thematic analysis. Results. Three fundamental themes emerged from the data analysis: Limits of the family counselling procedures and organization; The emotional dimension of elective abortion; and The issue of conscientious objectors. Discussion. The study highlighted how family counselling services are facing a crisis due to the lack of resources, personnel, and projects allowing for women's proper sexual education and support. It also showed how the social worker's role, which is fundamental, has instead been reduced, especially regarding elective abortions. Moreover, there was a lack of social and sanitary contexts integration and professional training that would provide the operators with specific skills and make them feel prepared to address such delicate situations. Conclusions. The need has emerged for a new, multidisciplinary perspective on the issue of voluntary interruption of pregnancy and social workers play a major role. However, the support system still presents many shortcomings for the women in need of assistance. The present study offers innovative and practical suggestions to properly fill these gaps

Improved preparation and preservation of human keratoplasty lenticules

Purpose: To improve the preparation of lenticules from human cornea and to obtain their preservation without loss of viable keratocytes. Methods: The epithelium was manually removed after bathing the surface of the cornea with a solution of trypsin and EDTA. Lenticules were prepared by microkeratome resection and viable keratocytes were visualized by staining with thiazolyl blue (MTT). Results: The pretreatment with trypsin-EDTA allowed the removal of the epithelium without damage to the keratocytes and the stroma. When these lenticules were incubated in Optisol-GS for 7 days at 4\ub0C, they showed a limited thickness increase and a preservation of keratocyte viability. Conclusion: This procedure allows the preparation of lenticules with viable keratocytes that can be preserved in the cold for at least 1 week

Banking of Donor Tissues for Descemet Stripping Automated Endothelial Keratoplasty.

Purpose: The demands for precut lamellar grafts for Descemet stripping automated endothelial keratoplasty rose in our eye bank from 74 in 2007 to 408 in 2010. To meet this expanding requirement, we explored the possibility to preserve these preparations in organ culture. Methods: Organ cultured corneas, stored in a medium containing 6% dextran, were mounted on a Moria artificial anterior chamber, deprived of the epithelium and then cut with a microkeratome. The posterior lamella was protected by positioning the anterior stromal cap, trephined at a diameter of 8.5 mm and stored at 31[degrees]C in the medium containing dextran. The endothelium was examined with trypan blue and alizarin staining and tested for its glycolytic activity (conversion of glucose into lactate). Results: Incubation for a period of 1 week caused a small increase in the cell loss observed after trephination (from 6.2% to 10.6%). After 2 weeks, the decrease in endothelial cell density was 19.9% but the endothelial organization remained intact. The rate of glycolysis remained unchanged during the 2 weeks of preservation, with the majority of glucose uptake accounted for by lactate production. The thickness of the lenticules remained constant, ranging from 170 to 180 [mu]m during the preservation. Conclusions: The lamellar grafts for Descemet stripping automated endothelial keratoplasty may be stored in organ culture for 2 weeks without damaging the endothelium or increasing the overall thickness

Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis

Efficient foraging by plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism), and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although root electrotropism has been observed in a few species since the end of the 19th century, its molecular and physical mechanisms remain elusive, limiting its comparison with the more well-defined sensing pathways in plants. Here we provide a quantitative and molecular characterization of root electrotropism in the model system Arabidopsis (Arabidopsis thaliana), showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but instead requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals. Future studies involving more extensive molecular and quantitative characterization of root electrotropism would represent a step towards a better understanding of signal integration in plants and would also serve as an independent outgroup for comparative analysis of electroreception in animals and fungi

In vitro and in vivo anticancer activity of tridentate thiosemicarbazone copper complexes: Unravelling an unexplored pharmacological target

Certain metal complexes can have a great antitumor activity, as the use of cisplatin in therapy has been demonstrating for the past fifty years. Copper complexes, in particular, have attracted much attention as an example of anticancer compounds based on an endogenous metal. In this paper we present the synthesis and the activity of a series of copper(II) complexes with variously substituted salicylaldehyde thiosemicarbazone ligands. The in vitro activity of both ligands and copper complexes was assessed on a panel of cell lines (HCT-15, LoVo and LoVo oxaliplatin resistant colon carcinoma, A375 melanoma, BxPC3 and PSN1 pancreatic adenocarcinoma, BCPAP thyroid carcinoma, 2008 ovarian carcinoma, HEK293 non-transformed embryonic kidney), highlighting remarkable activity of the metal complexes, in some cases in the low nanomolar range. The copper(II) complexes were also screened, with good results, against 3D spheroids of colon (HCT-15) and pancreatic (PSN1) cancer cells. Detailed investigations on the mechanism of action of the copper(II) complexes are also reported: they are able to potently inhibit Protein Disulfide Isomerase, a copper-binding protein, that is recently emerging as a new therapeutic target for cancer treatment. Good preliminary results obtained in C57BL mice indicate that this series of metal-based compounds could be a very promising weapon in the fight against cancer