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

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

Microcephaly and macrocephaly. A study on anthropometric and clinical data from 308 subjects

Head circumference is the auxological parameter that most correlates with developmental anomalies in childhood. Head circumference (HC) two standard deviations (SD) below or above the mean defines microcephaly and macrocephaly, respectively. The aim of this retrospective study was to explore anthropometric parameters and clinical characteristics among subjects with abnormalities in HC who had been referred for developmental assessment. One hundred and sixty four subjects with microcephaly and 144 subjects with macrocephaly were enrolled from birth to 18 months of age. Head circumference at birth and the association with variables related to maternal health status, gestational age, growth pattern, brain imaging and clinical characteristics were analyzed. In some cases, an etiological diagnosis was made. In the two considered conditions, we found different anthropometric and clinical associations, some of which were statistically significant, with implications for ongoing neurodevelopmental surveillance

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

Effects of vessel traffic on relative abundance and behaviour of cetaceans : the case of the bottlenose dolphins in the Archipelago de La Maddalena, north-western Mediterranean sea

Acknowledgements This study was part of the Tursiops Project of the Dolphin Research Centre of Caprera, La Maddalena. Financial and logistical support was provided by the Centro Turistico Studentesco (CTS) and by the National Park of the Archipelago de La Maddalena. We thank the Natural Reserve of Bocche di Bonifacio for the support provided during data collection. The authors thank the numerous volunteers of the Caprera Dolphin Research Centre and especially Marco Ferraro, Mirko Ugo, Angela Pira and Maurizio Piras whose assistance during field observation and skills as a boat driver were invaluable.Peer reviewedPostprin

Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children

Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying "organic" causes of chronic diarrhea in consecutive adults and children

The First 1000 Days of Life: How Changes in the Microbiota Can Influence Food Allergy Onset in Children

Background: Allergic disease, including food allergies (FA)s, has been identified as a major global disease. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility”, during which several factors can predispose children to FA development. Changes in the composition of the gut microbiota from pregnancy to infancy may play a pivotal role in this regard: some bacterial genera, such as Lactobacillus and Bifidobacterium, seem to be protective against FA development. On the contrary, Clostridium and Staphylococcus appear to be unprotective. Methods: We conducted research on the most recent literature (2013–2023) using the PubMed and Scopus databases. We included original papers, clinical trials, meta-analyses, and reviews in English. Case reports, series, and letters were excluded. Results: During pregnancy, the maternal diet can play a fundamental role in influencing the gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species via human milk oligosaccharides (HMOs), which play a prebiotic role. Moreover, complementary feeding can modify the gut microbiota’s composition. Conclusions: The first two years of life are a critical period, during which several factors can increase the risk of FA development in genetically predisposed children

Antioxidant Therapy in Neonatal Hypoxic Ischemic Encephalopathy: Adjuvant or Future Alternative to Therapeutic Hypothermia?

Background: Oxidative stress-related diseases in newborns arise from pro-oxidant/antioxidant imbalance in both term and preterm neonates. Pro-oxidant/antioxidant imbalance has shown to be present in different pathological conditions such as hypoxic ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA). Methods and Results: We performed a narrative review according to the most recent available literature (2012-2024), using Scopus and PubMed as electronic databases. Many observational and experimental studies in vitro and in vivo have evaluated the effectiveness of antioxidant therapies such as melatonin, erythropoietin (EPO), allopurinol, N-acetylcisteine (NAS), and nitric oxide synthase (NOS) inhibitors in these diseases. Perinatal asphyxia is one of the most important causes of mortality and morbidity in term and near-term newborns. Therapeutic hypothermia (TH) is the gold standard treatment for neonates with moderate-severe perinatal asphyxia, resulting in a reduction in the mortality and neurodevelopmental disability rates. Conclusions: According to the most recent literature and clinical trials, melatonin, allopurinol, NAS, NOS inhibitors, magnesium sulfate, and stem cells stand out as promising as both adjuvants and future probable alternatives to TH in the treatment of HIE

“Calcium-Phosphorus-Magnesium Axis” and the Metabolic Issue of Newborns Undergoing Parenteral Nutrition: Is It Time to Change Our Perspectives?

Background: In recent years, progress in the field of care has made prematurity an increasingly frequent phenomenon. The premature newborn, due to incompetence, is often subjected to parenteral nutrition (PN) for prolonged periods, and there may be several complications associated with it, first and foremost metabolic complications. Methods: In particular, the aim of this study was to evaluate how specific risk factors and/or auxological parameters influenced plasma variations in calcium, phosphorus, and magnesium levels. This is because, although little analyzed in the past, these electrolytes are essential for limiting the onset of unfavorable outcomes in neonatal age. This retrospective observational study was conducted by accessing the site intranet of the University Hospital "P. Giaccone" of Palermo, recruiting all newborns with PN necessities (106 in a total of 191), admitted to NICU in the period between 1 January 2020 and 1 January 2023. Infants undergoing PN through a central venous catheter (CVC), who remained in situ for a period >= 72 h, admitted to the NICU for the first time, were included. Infants with congenital malformations and/or deceased and/or transferred and/or without CVC or with CVC who remained in situ for a period < 72 h were excluded. We thus obtained 35 newborns in 2020, 33 newborns in 2021, and 38 newborns in 2022. Results: Hypophosphatemia was associated with a lower weight percentile (average 34.8 degrees C vs. 50.8 degrees C; p = 0.02) and a longer duration of PN (average 34.6 days vs. 17.3 days; p = 0.002). Newborns with hypercalcemia had, on average, lower gestational age (average 31.6 weeks vs. 35.7 weeks; p = 0.049) and weight at birth (average 1586 g vs. 2520 g; p = 0.038). Newborns with hypermagnesemia had, on average, higher weight and length (average weight percentile 62.1 degrees C vs. 42.7 degrees C; p = 0.038; average length percentile 66.7 degrees C vs. 44.4 degrees C; p = 0.003). Among the risk factors, cesarean section and undergoing surgery most influence the serum trend of the analyzed electrolytes. Conclusions: Although our results are partial and preliminary and have not always reached statistical significance, it is clear that dyselectrolytemias, in the context of metabolic complications PN-related, must be re-evaluated and carefully examined by the clinician. Prospective and controlled trials are needed to confirm our data, i.e., that the "calcium-phosphorus-magnesium axis" no longer plays only the niche role that was previously believed