Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines

We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC50 in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least equivalent pro-apoptotic effect than curcumin. The analysis of molecular mechanisms of action of the curcumin derivatives under study has highlighted that they decreased NF-κB transcriptional factor activity, and consequently the expression of some NF-κB targets. Our data confirmed once again that curcumin may represent a very good lead compound to design analogues with higher antitumor capacities and able to overcome drug resistance with respect to conventional ones, even in tumors difficult to treat as TNBC

The status of Orobanche crenata in Sicily and preliminary observations on Orobanche crenata susceptibility in Vicia faba

Since more than 10 years we are recording Orobanche crenata populations variations and testing traditional remedies to assess their applicability in a low impact agriculture that may be applied also in developing countries. Starting from the observation that often in C Sicily dense fields of Broadbean show lower Broomrape infestation, we did some preliminary observations on Orobanche crenata susceptibility in Vicia faba var. faba and Vicia faba var. equina with different agricultural techniques. First results show a higher resistance of the latter sowed at higher densities

Essential oil of Cyphostemma juttae (Vitaceae): chemical composition and antitumor mechanism in triple negative breast cancer cells

The genus Cyphostemma (Planch.) Alston (Vitaceae) includes about 150 species distrib- uted in eastern and southern Africa and Madagascar. Some species are used in traditional medicine and their biological activities, including antiproliferative effects against cancer cell lines, have been demonstrated. To date no investigations on Cyphostemma essential oils have been carried out. Essential oils, which play important roles in plant defenses have been demonstrated to be active in the treatment of several human diseases and to enhance bioavability of other drugs. The aim of this paper was to identify the chemical composition of the essential oil of the leaves of Cyphostemma juttae (Dinter & Gilg) Desc. and to verify some biological activities on two triple negative breast cancer cell lines (MDA-MB-231, SUM 149), characterized by the over-expression of the transcription factor NF-κB. In the essential oil, obtained by hydrodistillation and analysed by gas chromatography-mass spectrometry, 39 compounds were detected and with phytol (30%) dominating the chemical composition. C. juttae essential oil reduced cell growth and showed a pro-oxidant activity in both cell lines. Moreover, C. juttae essential oil caused a substantial decrease of NF-κB activation and consequently a significant reduction of some NF-κB target genes. The present study shows for the first time the cytotoxic properties of C. juttae essential oil and highlight its avail- ability to interfere with NF-κB pathway, suggesting a potential therapeutic use in triple nega- tive breast cancers (TNBCs) of this essential oil

Indeterminate Thyroid Nodules: From Cytology to Molecular Testing

Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients’ management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS-like (NRAS, HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAFV600E-like (including BRAFV600E mutation and RET and BRAF fusions). The purpose of this review is to discuss the latest molecular findings in the context of indeterminate thyroid nodules, highlighting the role of molecular tests in patients’ management

Epigenetic changes and nuclear factor-\u3baB activation, but not microRNA-224, downregulate Raf-1 kinase inhibitor protein in triple\u2011negative breast cancer SUM 159 cells

Raf-1 kinase inhibitor protein (RKIP) is a tumor suppressor and metastasis inhibitor, which enhances drug\u2011induced apoptosis of cancer cells. Downregulation of RKIP may be significant in the biology of highly aggressive and drug\u2011resistant tumors, for example triple\u2011negative breast cancers (TNBCs). Potential causes for the low levels of RKIP expressed by SUM 159 TNBC cells were investigated in the present study. Bisulphite modification, methylation specific\u2011polymerase chain reaction (PCR) and a TransAM NF-\u3baB assay were performed and the results suggested that various mechanisms, including methylation of the gene promoter, histone deacetylation and nuclear factor\u2011\u3baB (NF\u2011\u3baB) activation, but not targeting by microRNA\u2011224 (miR/miRNA\u2011224), as determined by transfection of pre\u2011miR\u2011224 miRNA precursor or anti\u2011miR\u2011224 miRNA inhibitor, may downregulate RKIP in these cells. Furthermore, reverse transcription\u2011quantitative PCR, western blotting,3\u2011(4,5\u2011dimethylthiazol\u20112\u2011yl)\u20115\u2011(3\u2011carboxymethoxyphenyl)\u20112\u2011(4\u2011sulphophenyl)\u20112H\u2011tetrazolium cell growth assay and flow cytometry revealed that in SUM 159 cells, the demethylating agent 5\u2011aza\u20112'\u2011deoxycytidine (5\u2011AZA), the histone deacetylase inhibitor trichostatin A (TSA) and the NF\u2011\u3baB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) enhanced RKIP expression and resulted in significant cell growth inhibition and induction of apoptosis. 5\u2011AZA and TSA mainly produced additive antitumor effects, while the combination of DHMEQ and TSA exhibited significant synergy in cell growth inhibition and induction of apoptosis assays. Increasing evidence that aberrant activation of NF\u2011\u3baB signaling is a frequent characteristic of TNBC highlights the fact that this transcription factor may be a useful target for treatment of such tumors. In addition to DHMEQ, proteasome inhibitors may also represent valuable therapeutic resources in this context. Notably, proteasome inhibitors, in addition to the inhibition of NF\u2011\u3baB activation, may also restore RKIP levels by inhibiting proteasome degradation of the ubiquitinated protein. The current results contribute to the understanding of the molecular mechanisms of RKIP downregulation in TNBC and suggest possible novel therapeutic approaches for the treatment of these types of cancer

Prevalencia del enteroparasitismo en pacientes atendidos en el Laboratorio Quintanilla SRL., Trujillo (Perú): 2008-2012

Las prevalencias del parasitismo intestinal son reportadas en poblaciones infantiles o en entidades estatales, habiéndose analizado poco respecto de lo que sucede en entidades particulares, como laboratorios de análisis clínicos. En el presente informe se presentan los resultados de una investigación retrospectiva longitudinal que estuvo orientada a determinar la prevalencia del enteroparasitismo en pacientes atendidos en el Laboratorio Quintanilla SRL., Trujillo (Perú) en el periodo 2008-2012. Los datos obtenidos fueron obtenidos en la base de datos del laboratorio y agrupados según los años de estudio, sexo y edad. La mayor prevalencia se presentó para Blastocystis hominis en el año 2008 con 64,8%, Enterobius vermicularis en el año 2012 con 11,8%, Entamoeba coli en el año 2010 con 23,3%. El grupo etáreo de 0 a 15 años fue el más afectado puesto que se obtuvo una frecuencia de enteroparasitismo de 29,4%; el sexo masculino presento la mayor frecuencia de enteroparasitismo con 33,1%.Palabras clave: Prevalencia, Enteroparasitismo, Blastocystis hominis, Enterobius vermiculari

'He just gave up': an exploratory study into the perspectives of paid carers on supporting older people living in care homes with depression, self-harm, and suicide ideation and behaviours

This study explored the concept of ‘giving up’ from the perspective of care staff working in care homes, and their everyday communication and hidden knowledge concerning what they think about this taboo topic and the context it reflects. Moving to a care home is a major transition where cumulative losses can pose risks to mental health in later life. If not recognised, this vulnerability can lead to depression which extends to suicide ideation and behaviours in the form of self-harm and self-neglect. Care homes are a significant place of care until death, yet a discourse of silence means that self-harm and suicide is under-reported or not attended to with specialist expertise. The layperson’s concept of an older person ‘giving up’ on life is hardly discussed in the literature. This co-produced qualitative study used an inductive approach to explore this phenomenon through focus groups with 33 care staff across four care homes in South-East England. Findings paint a complex picture, highlighting tensions in providing the right support and creating spaces to respond to such challenging situations. ‘Giving up’ requires skilled detailed assessment to respond to risks alongside improved training and support for paid carers, to achieve a more holistic strategy which capitalises on significant relationships within a wider context

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing

Caratterizzazione e valutazione dell\u2019attivit\ue0 anti proliferativa di nuovi sistemi per il drug carrier Allosite-sali triazolici/cardanolo

Da precedenti studi \ue8 stato valutato che i nanotubi di allosite modificati con sali triazolici (f-HNT), sono dei promettenti sistemi carrier per molecole biologiche1. In questo lavoro si riportano i risultati ottenuti studiando gli f-HNT come carrier per il cardanolo, molecola con interessanti attivit\ue0 biologiche. L\u2019interazione fra il cardanolo e gli f-HNT \ue8 stata valutata tramite HPLC, spettroscopia FTIR, analisi termogravimentrica, misure di angolo di contatto e microscopia a scansione elettronica. Infine sono stati studiati sia il rilascio del cardanolo dal sistema che gli effetti citotossici del complesso f-HNT/Cardanolo verso linee cellulari di epatocarcinoma. I dati sperimentali ottenuti mostrano che l\u2019allosite risulta un promettente sistema atto al drug carrier