Strategies to improve management of patients with native valve endocarditis (NVE) are needed because of persistently high morbidity and mortality. We sought to assess the impact of an operative ...protocol of multidisciplinary approach on the outcome of patients with NVE. A formal policy for the care of infective endocarditis was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. The initial multidisciplinary evaluation was performed within 12 hours of admission. Whenever conditions associated with impending hemodynamic impairment, high-risk for systemic embolization, or unsuccessful medical therapy were found, patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever the above high-risk conditions had developed. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients were more numerous (190 vs 102), older (mean age 59.1 vs 54.2, p = 0.01), and had more co-morbidities (mean Charlson index 3.01 vs 2.31, p = 0.02). The pattern of infection did not change in terms of valve infected or paravalvular complications. In the second period, fewer patients had culture-negative NVE (8% vs 21%, p = 0.01) and worsened renal function (37% vs 58%, p = 0.001). A significant reduction in overall in-hospital mortality (28% to 13%, p = 0.02), mortality for surgery during the active phase (47% to 13%, p ≤0.001), and 3-year mortality (34% vs 16%, p = 0.0007) was observed. In conclusion, formalized, collaborative management led to significant improvement in NVE-related mortality, notwithstanding the less favorable patients' baseline characteristics.
Growing attention to environmental protection leads food industries to adopt a model of “circular economy” applying safe and sustainable technologies to recover, recycle and valorize by-products. ...Therefore, by-products become raw material for other industries. Tomato processing industry produces significant amounts of by-products, consisting of skins and seeds. Tomato skin is very rich in lycopene, and from its seeds, high nutritional oil can be extracted. Alternative use of the two fractions not only could cut disposal costs but also allow one to extract bioactive compounds and an oil with a high nutritional value. This review focused on the recent advance in extraction of lycopene, whose beneficial effects on health are widely recognized.
Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcription factor, is an essential marker ...correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation by directly binding to a highly conserved N-Myc region. As a result, elevated levels of N-Myc are observed. During recent years, it has been demonstrated that some ATP competitive inhibitors of AURKA also cause essential conformational changes in the structure of the activation loop of the kinase that prevents N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complexes with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results identify PHA-680626 as an amphosteric inhibitor both in vitro and in MYCN overexpressing cell lines, thus expanding the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex and confirming that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.
Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in drug targets. Despite the fast speed of new chemotherapeutic agent design, the increasing ...prevalence of this phenomenon requires further research and treatment development. Recently, we reported a new aminopyrimidine compound-namely RDS 344-as a potential innovative anticancer agent.
Herein, we report the design, synthesis, and anti-proliferative activity of new aminopyrimidine derivatives structurally related to RDS 3442 obtained by carrying out substitutions at position 6 of the pyrimidine core and/or on the 2-aniline ring of our hit. The ability to inhibit cell proliferation was evaluated on different types of tumors, glioblastoma, triple-negative breast cancer, oral squamous cell carcinomas and colon cancer plus on human dermal fibroblasts chosen as control of normal cells.
The most interesting compound was the
-benzyl counterpart of RDS 3442, namely
, that induced a significant decrease in cell viability in all the tested tumor cell lines, with EC
s ranging from 4 and 8 μM, 4-13 times more active of hit.
These data suggest a potential role for this class of molecules as promising tool for new approaches in treating cancers of different histotype.
The resinous exudate produced by
(Nees) Engl. is commonly known as true myrrh and has been used since antiquity for several medicinal applications. Hundreds of metabolites have been identified in the ...volatile component of myrrh so far, mainly sesquiterpenes. Although several efforts have been devoted to identifying these sesquiterpenes, the phytochemical analyses have been performed by gas-chromatography/mass spectrometry (GC-MS) where the high temperature employed can promote degradation of the components. In this work, we report the extraction of
by supercritical CO
, an extraction method known for the mild extraction conditions that allow avoiding undesired chemical reactions during the process. In addition, the analyses of myrrh oil and of its metabolites were performed by HPLC and GC-MS. Moreover, we evaluated the antiviral activity against influenza A virus of the myrrh extracts, that was possible to appreciate after the addition of vitamin E acetate (α-tocopheryl acetate) to the extract. Further, the single main bioactive components of the oil of
commercially available were tested. Interestingly, we found that both furanodienone and curzerene affect viral replication by acting on different steps of the virus life cycle.
Nocodazole is an antineoplastic agent that exerts its effects by depolymerizing microtubules. Herein we report a structural analog of nocodazole, a (1H-pyrrol-1-yl)methyl-1H-benzoimidazole carbamate ...ester derivative, named RDS 60. We evaluated the antineoplastic properties of RDS 60 in two human head and neck squamous cell carcinoma (HNSCC) cell lines and we found that this compound significantly inhibited replication of both HNSCC cell lines without inducing any important cytotoxic effect on human dermal fibroblasts and human keratinocytes. The treatment of HNSCC cell lines with 1 μM RDS 60 for 24 h stopped development of normal bipolar mitotic spindles and, at the same time, blocked the cell cycle in G2/M phase together with cytoplasmic accumulation of cyclin B1. Consequently, treatment with 2 μM RDS 60 for 24 h induced the activation of apoptosis in both HNSCC cell lines. Additionally, RDS 60 was able to reverse the epithelial-mesenchymal transition and to inhibit cell migration and extracellular matrix infiltration of both HNSCC cell lines. The reported results demonstrate that this compound has a potent effect in blocking cell cycle, inducing apoptosis and inhibiting cell motility and stromal invasion of HNSCC cell lines. Therefore, the ability of RDS 60 to attenuate the malignancy of tumor cells suggests its potential role as an interesting and powerful tool for new approaches in treating HNSCC.
A critical aspect in the design of a marine reserve (MR) network is its spatial configuration (i.e., the number, size, and spacing of the individual reserves), particularly how these features ...influence the effect on fisheries. Here, we derived a size-based, spatially explicit, stochastic demographic model to explore how different spatial configurations of MR networks can affect abundance and commercial yield of the green abalone (Haliotis fulgens), taking as a reference case the abalone fishery of Isla Natividad in Baja California Sur (Mexico). Our analysis suggests that a network of MRs can have a positive effect on abalone population abundance and a slightly negative effect on fishery output with respect to traditional maximum sustainable yield (MSY; i.e., with no reserves). Simulations show that maximum catches achievable with MRs are, under the best configuration, ∼2%–14% lower than traditional MSY depending on the total fraction of the fishing grounds protected. In the case of overexploitation, long-term yields can increase following the implementation of MRs. In addition, in the presence of MRs, abundances and yields are much less sensitive to systematic errors in the enforcement of the optimal harvesting rate compared with situations in which MRs are not present. Given the limited dispersal ability of the species, the best outcomes in terms of fishery output would be achieved with very small reserves — around 100 m wide — so to maximize larval export in the fishable areas. Our results indicate appropriately designed MR networks are an effective strategy for meeting both conservation and economic goals under uncertainty. While the size of the existing reserves in Isla Natividad seems adequate to protect the abalone stock, smaller reserves could maximize fishery benefits, although this poses challenges for enforcement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant-based systems continue to play a pivotal role in healthcare, and their use has been extensively documented. Asphodelus L. is a genus comprising various herbaceous species, known by the trivial ...name Asphodelus. These plants have been known since antiquity for both food and therapeutic uses, especially for treating several diseases associated with inflammatory and infectious skin disorders. Phytochemical studies revealed the presence of different constituents, mainly anthraquinones, triterpenoids, phenolic acids, and flavonoids. Although extensive literature has been published on these constituents, a paucity of information has been reported regarding the carbohydrate composition, such as fructans and fructan-like derivatives. The extraction of water-soluble neutral polysaccharides is commonly performed using water extraction, at times assisted by microwaves and ultrasounds. Herein, we reported the investigation of the alkaline extraction of root-tubers of Asphodelus ramosus L., analyzing the water-soluble polysaccharides obtained by precipitation from the alkaline extract and its subsequent purification by chromatography. A polysaccharide was isolated by alkaline extraction; the HPTLC study to determine its composition showed fructose as the main monosaccharide. FT-IR analysis showed the presence of an inulin-type structure, and NMR analyses allowed us to conclude that A. ramosus roots contain polysaccharide with an inulin-type fructooligosaccharide with a degree of polymerization of 7–8.
Cannabis oils, namely concentrated cannabis extracts, are getting plenty of attention because of their therapeutic potential for treatment of patients with cancer, HIV, multiple sclerosis and several ...other pathologies. Here we propose the use of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) as alternative methods to the current protocols followed by pharmacists, the only authorized to manipulate standardized Cannabis. A third method, consisting of the use of Tween 20 as surfactant, was considered. Our best extraction methodology for commercial hemp extraction was applied to medicinal cannabis. Here we report the results obtained for 'Eletta campana', 'Carmagnola selezionata', Bediol
®
, FM2
®
and Bedrocan
®
.
PDF
