According to WHO statistics, breast cancer (BC) disease represents about 2.3 million diagnosed and 685,000 deaths globally. Regarding histological classification of BC, the Estrogen (ER) and ...Progesterone (PR) receptors negative-expression cancer, named Triple-Negative BC (TNBC), represents the most aggressive type of this disease, making it a challenge for drug discovery. In this context, our research group, applying a well-established Virtual Screening (VS) protocol, in addition to docking and molecular dynamics simulations studies, yielded two ligands identified as 6 and 37 which were chemically synthesized and evaluated on MCF-7 and MDA-MB-231 cancer cell lines. Strikingly, 37 assayed on MDA-MB-231 (a TNBC cell model) depicted an outstanding value of 18.66 μM much lower than 65.67 μM yielded by Gossypol Bcl-2 inhibitor whose main disadvantage is to produce multiple toxic effects. Highlighted above, enforce the premise of the computational tools to find new therapeutic options against the most aggressive forms of breast cancer, as the results herein showed.
Objectives. To determine the outcome predictors of in-hospital mortality in acute total occlusion of the left main coronary artery (ATOLMA) patients referred to emergent angioplasty and to describe ...the clinical presentation and the long-term outcome of these patients. Background. ATOLMA is an uncommon angiographic finding that usually leads to a catastrophic presentation. Limited and inconsistent data have been previously reported regarding true ATOLMA, yet comprehensive knowledge remains scarce. Methods. This is a multicenter retrospective cohort that includes patients presenting with myocardial infarction due to a confirmed ATOLMA who underwent emergency percutaneous coronary intervention (PCI). Results. In the period of the study, 7930 emergent PCI were performed in the five participating centers, and 46 of them had a true ATOLMA (0.58%). At admission, cardiogenic shock was present in 89% of patients, and cardiopulmonary resuscitation was required in 67.4%. All the patients had right dominance. Angiographic success was achieved in 80.4% of the procedures, 13 patients (28.2%) died during the catheterization, and the in-hospital mortality rate was 58.6% (27/46). At one-year and at the final follow-up, 18 patients (39%) were alive, including four cases successfully transplanted. Multivariate analysis showed that postprocedural TIMI flow was the only independent predictor of in-hospital mortality (OR 0.23, (95% CI 0.1–0.36), p<0.001). Conclusions. Our study confirms that the clinical presentation of ATOLMA is catastrophic, presenting a high in-hospital mortality rate; nevertheless, primary angioplasty in this setting is feasible. Postprocedural TIMI flow resulted as the only independent predictor of in-hospital mortality. In-hospital survivors presented an encouraging outcome. ATOLMA and left dominance could be incompatible with life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bioactive compounds from medicinal plants have applications in the development of functional foods. However, since they are unstable, encapsulation is used as a conservation alternative. This work ...aimed to assess the bioactive properties (antioxidant and hypoglycemic) of different extracts, including the infusion, as well as their spray-dried microencapsulates from
leaves. A factorial design was proposed to determine the best extraction conditions, based on ABTS and DPPH inhibition. Maltodextrin (MD), arabic gum (AG), and a 1:1 blend (MD:AG) were used as encapsulating agents. Moreover, characterization through physicochemical properties, gas chromatography/mass spectrometry (GC-MS) and scanning electron microscopy (SEM) of the best two powders based on the bioactive properties were analyzed. The results showed that the combination of stirring, water, and 5 min provided the highest inhibition to ABTS and DPPH (35.64 ± 1.25 mg Trolox/g d.s. and 2.77 ± 0.01 g Trolox/g d.s., respectively). Spray drying decreased the antioxidant activity of the extract while preserving it in the infusion. The encapsulated infusion with MD:AG had the highest hypoglycemic activity as it presented the lowest glycemic index (GI = 47). According to the results, the microencapsulates could potentially be added in foods to enhance nutritional quality and prevent/treat ailments.
We present a long-term assessment of precipitation trends in Southwestern Europe (1850-2018) using data from multiple sources, including observations, gridded datasets and global climate model ...experiments. Contrary to previous investigations based on shorter records, we demonstrate, using new long-term, quality controlled precipitation series, the lack of statistically significant long-term decreasing trends in precipitation for the region. Rather, significant trends were mostly found for shorter periods, highlighting the prevalence of interdecadal and interannual variability at these time-scales. Global climate model outputs from three CMIP experiments are evaluated for periods concurrent with observations. Both the CMIP3 and CMIP5 ensembles show precipitation decline, with only CMIP6 showing agreement with long term trends in observations. However, for both CMIP3 and CMIP5 large interannual and internal variability among ensemble members makes it difficult to identify a trend that is statistically different from observations. Across both observations and models, our results make it difficult to associate any declining trends in precipitation in Southwestern Europe to anthropogenic forcing at this stage.
The essential oils (EOs) extracted by hydrodistillation (HYDRO) and steam distillation (SD) from Mexican Salvia officinalis L were analyzed for yield, chemical composition (GC-MS), particle ...morphology (SEM), antioxidant activity (ABTS), and antibacterial activity against Enterobacter agglomerans, Citrobacter freundii, Salmonella sp, E. coli, and Pseudomonas aeruginosa. The influence of the factors (method, quantity, and sample) was evaluated using a 23 full factorial design, Pareto chart, normal probability plot, main effects, and interaction plots in variance analysis on yield and antioxidant activity. The quantity, methods, sample, and the methods × sample and methods × quantity interactions were the most significant factors on yield (%). The sample, methods, and quantity × sample interaction were significant for antioxidant activity. EO yields were between 0.35 and 1.27 (% w/w), and the highest value was obtained by the HYDRO method using 50 g of whole sage leaves. The antioxidant activity values were in the range of 2.35 to 3.44 mg Trolox equivalent/g. Camphor, limonene, camphene, and caryophyllene were the main compounds identified. Micrographs of sage leaves showed relevant changes in the structure after extraction. The antibacterial activity was confirmed with the inhibition diameter and inhibition percentage of all bacteria, and P. aeruginosa was the most resistant bacteria. Finally, S. officinalis EO potentials can be considered an alternative natural preservative for the food and pharmaceutical industries.
Inflammation was detected in 9 of 13 patients with different phenotypes of dysferlin myopathy. Endomysial or perivascular infiltrates consisted of 11.1% +/- 6.6% CD8(+) cells, 40.6% +/- 22.8% CD4(+) ...cells, 36.7% +/- 23.7% macrophages, and no B cells. Major histocompatibility complex class I was not upregulated in normal muscle fibers. In young patients with sporadic proximal weakness, very high creatine kinase levels, necrotic fibers and inflammation in the muscle biopsy, a diagnosis of dysferlin myopathy should be considered.
The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and ...longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide
blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6
months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but,
the dosing regimens in humans should be different when administered at early age.
Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells.
In an effort to develop new therapeutic strategies ...against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA.
This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines.
In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies.
A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.
Display omitted
•Ni/H-MOR catalysts with low content (2 wt.%) reach high naphthalene hydroconversion.•Ni particles of small crystal size (∼10 Å) were obtained by ionic exchange and ...deposit-precipitation preparations.•Ni-DP catalysts led to an active catalyst with high selectivity trans-/cis decalin ratio.•Ni-IWI catalysts has large particles of Ni (∼100 Å), deactivates quickly and displayed a low trans-/cis- decalin ratio.•Ni-IE has deactivation by carbon deposition and reaches a high trans-/cis- decalin ratio.
Three Ni catalyst supported on mordenite zeolite with the same content of nickel, ∼2 wt.%, were prepared by incipient wetness impregnation (IWI), ionic exchange (IE), and deposition-precipitation (DP) methods. The catalysts were characterized by, X-ray diffraction (XRD), textural properties, temperature-programmed reduction (TPR), transmission electron microscopy (TEM) and scanning electron microscopy / energy-dispersive spectroscopy (SEM/EDS). For all the catalysts conversion and selectivity were studied in naphthalene hydrogenation without or with thiophene in the feedstock. Despite the low nickel content, the three preparations showed a high initial total naphthalene conversion up to 94%. The Ni-IWI catalyst exhibited high selectivity to tetralin and deactivated very fast. Ni-IE catalyst had good activity; however, it shows deactivation and the main products are related to acid reactions. The Ni-DP shows high hydrogenation activity and was the most active catalyst, it generated decalins, especially cis-decalin and at a long reaction time on stream, the catalyst remains active. TEM and TPR results suggest that this behavior is related to the crystal sizes which in turn is conected with the preparation method. In presence of thiophene, all the catalysts deactivate; but the Ni-DP deactivation was slower.
PDF
