Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, ...APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ
= 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ
= 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.
The graph shows the action of zeolite on the NAA heavy water. Display omitted
Square 1 - zeolite with sodium promotes ion exchange of calcium and magnesium present in water hard. ► Square 2 - water ...free of calcium and magnesium captured by zeolite. ► Square 3 - calcium and magnesium present in hard water withheld in the sites of adsorption.
Zeolite 4A (LTA) has been successfully synthesized by a hydrothermal method, where kaolin was used as silica and alumina source. The synthesized zeolite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), laser granulometry, and FTIR spectroscopy. XRD data from the Rietveld refinement method confirmed only one crystallographic phase. Zeolite A morphology was observed by SEM analysis, and it showed well-defined crystals with slightly different sizes but with the same cubic shape. Particle size distribution of the crystals was confirmed by laser granulometry, whereas FTIR spectroscopy revealed significant structural differences between the starting material and the final zeolite product used as water softener.
The mononuclear zinc(II) complex
-ZnL
(H
O)
(
; L = 4-(pyridin-3-ylcarbamoyl)benzoate) was synthesized and characterized. By soaking crystals of
in a mixture of DMF-H
O solution containing a slight ...excess of Cu(NO
)
× 3H
O a transmetalation reaction occurred affording the related copper(II) complex
-CuL
(H
O)
(
). The structures of the compounds were authenticated by single crystal X-ray diffraction revealing, apart from a change in the isomerism, an alteration in the relative orientation of the chelating carboxylate groups and of the pyridine moieties. H-bond interactions stabilize both geometries and expand them into two-dimensional (2D) networks. The transmetalation was confirmed by SEM-EDS analysis. Moreover, the thermodynamic feasibility of the transmetalation is demonstrated by density-functional theory (DFT) studies. The catalytic activities of
and
for the oxidation of styrene and for the nitroaldol (Henry) C-C coupling reaction were investigated. The copper(II) compound
acts as heterogeneous catalyst for the microwave-assisted oxidation of styrene with aqueous hydrogen peroxide, yielding selectively (>99%) benzaldehyde up to 66% of conversion and with a turnover frequency (TOF) of 132 h
. The zinc(II) complex
is the most active catalyst (up to 87% yield) towards the nitroaldol (Henry) coupling reaction between benzaldehyde and nitro-methane or -ethane to afford the corresponding β-nitro alcohols. The reaction of benzaldehyde with nitroethane in the presence of
produced 2-nitro-1-phenylpropanol in the
and the
diastereoisomeric forms, with a considerable higher selectivity towards the former (66:34).
The severe forms and worsened outcomes of COVID-19 (coronavirus disease 19) are closely associated with hypertension and cardiovascular disease. Endothelial cells express Angiotensin-Converting ...Enzyme 2 (ACE2), which is the entrance door for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The hallmarks of severe illness caused by SARS-CoV-2 infection are increased levels of IL-6, C-reactive protein, D-dimer, ferritin, neutrophilia and lymphopenia, pulmonary intravascular coagulopathy and microthrombi of alveolar capillaries. The endothelial glycocalyx, a proteoglycan- and glycoprotein-rich layer covering the luminal side of endothelial cells, contributes to vascular homeostasis. It regulates vascular tonus and permeability, prevents thrombosis, and modulates leukocyte adhesion and inflammatory response. We hypothesized that cytokine production and reactive oxygen species (ROS) generation associated with COVID-19 leads to glycocalyx degradation. A cohort of 20 hospitalized patients with a confirmed COVID-19 diagnosis and healthy subjects were enrolled in this study. Mechanisms associated with glycocalyx degradation in COVID-19 were investigated. Increased plasma concentrations of IL-6 and IL1-β, as well as increased lipid peroxidation and glycocalyx components were detected in plasma from COVID-19 patients compared to plasma from healthy subjects. Plasma from COVID-19 patients induced glycocalyx shedding in cultured human umbilical vein endothelial cells (HUVECs) and disrupted redox balance. Treatment of HUVECs with low molecular weight heparin inhibited the glycocalyx perturbation. In conclusion, plasma from COVID-19 patients promotes glycocalyx shedding and redox imbalance in endothelial cells, and heparin treatment potentially inhibits glycocalyx disruption.
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•Endothelial cells are a crucial interface between blood and tissues, maintaining vascular homeostasis•SARS-CoV-2 infection threatens endothelial function by increasing cytokines and ROS, thus shedding the endothelial glycocalyx•Plasma from COVID-19 patients disrupts the glycocalyx, which is prevented by heparin/LMWH
Adhesive bonding has become more efficient in the last few decades due to the adhesives developments, granting higher strength and ductility. On the other hand, natural fibre composites have recently ...gained interest due to the low cost and density. It is therefore essential to predict the fracture behavior of joints between these materials, to assess the feasibility of joining or repairing with adhesives. In this work, the tensile fracture toughness (Gnc) of adhesive joints between natural fibre composites is studied, by bonding with a ductile adhesive and co-curing. Conventional methods to obtain Gnc are used for the co-cured specimens, while for the adhesive within the bonded joint, the J-integral is considered. For the J-integral calculation, an optical measurement method is developed for the evaluation of the crack tip opening and adherends rotation at the crack tip during the test, supported by a Matlab sub-routine for the automated extraction of these quantities. As output of this work, an optical method that allows an easier and quicker extraction of the parameters to obtain Gnc than the available methods is proposed (by the J-integral technique), and the fracture behaviour in tension of bonded and co-cured joints in jute-reinforced natural fibre composites is also provided for the subsequent strength prediction. Additionally, for the adhesively-bonded joints, the tensile cohesive law of the adhesive is derived by the direct method.
A number of novel, water-stable redox-active cobalt complexes of the C-functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH(2), CH(2)OCH(2)Py or CH(2)OSO(2)Me) are reported ...along with their effects on DNA. The compounds were isolated as air-stable solids and fully characterized by IR and FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential electrolysis, elemental analysis and, in a number of cases, also by single-crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell lines. This viability loss is correlated with an increase of tumour cell lines apoptosis. Reactivity studies with biomolecules, such as reducing agents, H(2)O(2), plasmid DNA and UV-visible titrations were also performed to provide tentative insights into the mode of action of the complexes. Incubation of Co(II) complexes with pDNA induced double strand breaks, without requiring the presence of any activator. This pDNA cleavage appears to be mediated by O-centred radical species.
Lap joints are used extensively in the manufacture of cars. In order to determine the effect of using a structural adhesive instead of spot-welding, a detailed series of tests and finite element ...analyses were conducted using a range of loadings. The adhesive was a toughened epoxy and the adherend was mild steel typical of that used in the manufacture of car bodyshells. The lap joints were tested in tension (which creates shear across the bondline), four-point loading (pure bending) and three-point loading (bending plus shear). Various parameters were investigated such as the overlap length, the bondline thickness and the spew fillet. The major finding is that three-point bending and tension loading are very similar in the way in which they affect the adhesive while the four-point bend test does not cause failure because the steel yields before the joint fails. A failure criterion has been proposed based on the tensile load and bending moment applied to the joint.
Self-healing in asphalt mixtures is a property that can be enhanced by external heating, which causes a thermal expansion that increases the flow of bitumen with reduced viscosity through the cracks. ...Therefore, this study aims to evaluate the effects of microwave heating on the self-healing performance of three asphalt mixtures: (1) conventional, (2) with steel wool fibers (SWF), and (3) with steel slag aggregates (SSA) and SWF. After evaluating the microwave heating capacity of the three asphalt mixtures with a thermographic camera, their self-healing performance was determined with fracture or fatigue tests and microwave heating recovery cycles. The results demonstrated that the mixtures with SSA and SWF promoted higher heating temperatures and presented the best self-healing capacity during the semicircular bending test and heating cycles, with significant strength recovery after a total fracture. In contrast, the mixtures without SSA presented inferior fracture results. Both the conventional mixture and that containing SSA and SWF presented high healing indexes after the four-point bending fatigue test and heating cycles, with a fatigue life recovery of around 150% after applying two healing cycles. Therefore, the conclusion is that SSA greatly influences the self-healing performance of asphalt mixtures after microwave radiation heating.
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In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the ...final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03μM. The 8c derivative showed the highest potency against cruzain (IC50=2.4μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb=−7.39kcal·mol−1) indicates interaction (via dipole–dipole) between the hybridized sulfur sp3 atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.
Asthma is a chronic inflammatory disease of the airways related to epithelial damage, bronchial hyperresponsiveness to contractile agents, tissue remodeling, and luminal narrowing. Currently, there ...are many data about the pathophysiology of asthma; however, a new aspect has emerged related to the influence of reactive oxygen and nitrogen species (ROS and RNS) on the origin of this disease. Several studies have shown that an imbalance between the production of ROS and RNS and the antioxidant enzymatic and nonenzymatic systems plays an important role in the pathogenesis of this disease. Considering this aspect, this study is aimed at gathering data from the scientific literature on the role of oxidative distress in the development of inflammatory airway and lung diseases, especially bronchial asthma. For that, articles related to these themes were selected from scientific databases, including human and animal studies. The main findings of this work showed that the respiratory system works as a highly propitious place for the formation of ROS and RNS, especially superoxide anion, hydrogen peroxide, and peroxynitrite, and the epithelial damage is reflected in an important loss of antioxidant defenses that, in turn, culminates in an imbalance and formation of inflammatory and contractile mediators, such as isoprostanes, changes in the activity of protein kinases, and activation of cell proliferation signalling pathways, such as the MAP kinase pathway. Thus, the oxidative imbalance appears as a promising path for future investigations as a therapeutic target for the treatment of asthmatic patients, especially those resistant to currently available therapies.
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