In this study, nanoparticles of five photocatalytic systems based on pure zinc oxide and with rare earths ions M-ZnO (M = La3+, Ce3+, Pr3+ or Nd3+) calcined at 500 °C or 700 °C were synthesized and ...investigated as potential photocatalysts for the removal of dyes. The addition of rare earth ions causes a decrease in the bandgap of ZnO; therefore, it can be well used to improve the photocatalytic properties. The photocatalytic activity of the synthesized nanoparticles was evaluated by the degradation of Rhodamine B in the presence of H2O2 under ultraviolet illumination. The results indicate that all the synthesized nanoparticles show good dye degradation efficiency. The highest degradation efficiency was 97.72% for the Ce-ZnO sample calcined at 500 °C and was achieved in 90 min with an excellent constant of the dye degradation rate k = 0.0363 min−1 following a first-order kinetic mechanism. The presence of oxychlorides as secondary phases inhibits the rate of the photocatalytic reaction.
Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, ...histopathological and immunohistochemical findings in livers of squirrel monkeys (
spp.) infected with the YFV. Viremia occurred 1-30 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-γ and TNF-α, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease.
Histidine-proline-rich glycoprotein (HPRG) is an abundant multidomain plasma protein evolutionarily related to high-molecular-weight kininogen. The cleaved form of high-molecular-weight kininogen has ...recently been demonstrated to exhibit antiangiogenic activities in vitro (J. C. Zhang et al., FASEB J., 14: 2589-2600, 2000), mediated primarily through domain 5. HPRG contains a histidine-proline-rich (H/P) domain with sequence and functional similarities to HKa-D5. We hypothesized that HPRG may also have antiangiogenic properties, localized within its H/P domain. The H/P domain is highly conserved among species, and because rabbit H/P domain is more resistant to internal proteolytic cleavage than the human domain, the rabbit HPRG (rbHPRG) was primarily used to assess the antiangiogenic activity of HPRG. Rabbit HPRG inhibited human umbilical vein endothelial cell (HUVEC) tube formation stimulated by fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor on a Matrigel surface as well as cell proliferation of FGF-2 stimulated HUVECs. The antiangiogenic activity of rbHPRG was localized to the H/P domain by use of proteolytic fragments of rbHPRG and was further confirmed and characterized in two in vivo models of angiogenesis: the chorioallantoic membrane of the chick assay and the mouse Matrigel plug assay. Caspase-3 activation was observed in HUVECs stimulated with FGF-2 in the presence of rbHPRG, suggesting that apoptosis of activated endothelial cells may be one of the mechanisms underlying its antiangiogenic activity. Finally, the H/P domain of rbHPRG reduced tumor cell number when tumor cells were co-inoculated in the Matrigel plug assay. In conclusion, the H/P domain within HPRG induces the apoptosis of activated endothelial cells leading to potent antiangiogenic effects.
The main limitation of the six-minute walk test (6-MWT) is that not all pulmonary function testing facilities have an indoor flat, 30-m-long corridor. Therefore, this study aimed 1) to evaluate the ...correlation and agreement of the distances walked in 30-m- vs. 15-m-long corridors by subjects with chronic lung diseases (CLD group) and 2) to compare the levels of oxygen saturation (nSpO2), blood pressure (BP), heart rate recovery at minute one post-exercise (HRR1), and Borg scale scores for dyspnea and fatigue between the two distances walked.
A prospective, cross-sectional study was conducted at the National Institute of Respiratory Diseases in Mexico City. Subjects with chronic lung diseases and healthy adults were invited to participate. The distance of the 6-MWT was randomly assigned based on whether the first test was in the 15-m or 30-m corridor.
Ninety individuals were included; the correlation in meters walked between the two corridors was r = 0.96 in CLD; the 95% limits of agreement for the 6-MWT ranged from −73 to +37 m. Most subjects walked further in the 30-m corridor (82%); however, the percent predicted values for the CLD group were 3.5% lower for the 15-m corridor than the 30-m corridor. Only 10.5% of the subjects with CLD would have been falsely classified as having a normal 6-MWT (false negative). No significant differences in the nSpO2, Borg scale, BP or HRR1 were found between the two 6-MWT corridor lengths.
The 6-MWT can be performed using a 15-m corridor in subjects with CLD, and the results for the distance walked, HRR1, nSpO2, and Borg scale scores are similar to between the 15-m and 30-m corridors.
Conformationally altered proteins and protein fragments derived from the extracellular matrix and hemostatic system may function as naturally occurring angiogenesis inhibitors. One example of such a ...protein is cleaved high molecular weight kininogen (HKa). HKa inhibits angiogenesis by inducing apoptosis of proliferating endothelial cells, effects mediated largely by HKa domain 5. However, the mechanisms underlying the antiangiogenic activity of HKa have not been characterized, and its binding site on proliferating endothelial cells has not been defined. Here, we report that the induction of endothelial cell apoptosis by HKa, as well as the antiangiogenic activity of HKa in the chick chorioallantoic membrane, was inhibited completely by antitropomyosin monoclonal antibody TM-311. TM-311 also blocked the high-affinity Zn2+-dependent binding of HKa to both purified tropomyosin and proliferating endothelial cells. Confocal microscopic analysis of endothelial cells stained with monoclonal antibody TM-311, as well as biotin labeling of cell surface proteins on intact endothelial cells, revealed that tropomyosin exposure was enhanced on the surface of proliferating cells. These studies demonstrate that the antiangiogenic effects of HKa depend on high-affinity binding to endothelial cell tropomyosin.
An
N
-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of
Trypanosoma cruzi
. However, their ...mechanism of action is not clear, although in
T. cruzi
it has been suggested that the enzyme cruzain is involved. The aim in this work was to obtain new
N
-propionyl-
N
′-benzeneacylhydrazone derivatives as potential anti-
T. cruzi
agents and elucidate their potential mechanism of action by a molecular docking analysis and effects on the expression of the cruzain gene. Compounds
9
and
12
were the most active agents against epimastigotes and compound
5
showed better activity than benznidazole in
T. cruzi
blood trypomastigotes. Additionally, compounds
9
and
12
significantly increase the expression of the cruzain gene. In summary, the in silico and in vitro data presented herein suggest that compound
9
is a cruzain inhibitor.
Graphic abstract
The use of artificial intelligence using convolutional neural networks in clinical practice is recent. Thus, a growing need exists to validate software performance in different tasks in different ...diseases.
To evaluate the performance of artificial intelligence software to determine metabolic tumor burden in the primary staging of rectal cancer.
A cross-sectional retrospective analysis was conducted on 51 histology-proven rectal cancer patients (35% females; mean age = 61 years) who underwent a staging 18F-FDG PET/CT. Whole-body metabolic tumor burden parameters (wbMTV and wbTLG) were quantified semi-automatically and through AI algorithm (Syngovia VB60; Siemens Healthineers Medical Solutions). The AI software's ability to correctly identify and classify the primary lesion, regional lymph nodes, and distant metastases was evaluated. In addition, the intraclass correlation coefficient (ICC) was applied to evaluate concordance between the AI-based software and the semiautomatic software in determining wbMTV and wbTLG. Values above 0.7 were considered to indicate substantial agreement. Resultados: The AI and semiautomatic tumor burden metrics correlated strongly for both wbMTV (ICC = 1.00; 95% CI = 0.94 - 0.99; P < 0.0000) and wbTLG (ICC = 1.00; 95% CI = 0.80 – 0.90; P < 0.0000). Additionally, the AI software's ability to correctly identify lesions compared to the documented staging was better for the identification of distant metastasis (78,57% of patients), mildly adequate to identify regional lymph nodes (50,00%) and had poor performance for identification of the primary lesion (5,76%). On the other hand, the time spent calculating these metrics was less by AI than by the semiautomatic method, especially in patients with advanced disease.
The determination of whole-body metabolic tumor burden on 18F-FDG PET/CT with artificial intelligence software is challenging because of the physiologic bowel activity. However, deep learning may have the ability to overcome these challenges and may therefore improve the primary staging of rectal cancer.
Objective
This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight‐loss success.
Methods
A ...human model, in which sixty‐five individuals with obesity underwent bariatric surgery, and a diet‐induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model.
Results
The levels of carboxyethyl‐lysine (CEL) and 2‐succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106 μmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes.
Conclusions
CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.
A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been implicated in angiogenesis and plays ...a significant role in tumor progression and metastasis. The presence and orientation of the phosphonate moiety (acting as a phosphate mimic) in these derivatives were critical for inhibitory activity. The most active compounds possessed a phosphonate group in an endo orientation. This was consistent with molecular modeling results that showed the endo isomer protein−ligand complex to be lower in energy than the exo complex.
Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been ...recently identified as an inhibitor of SOD1 that attenuates FGF-2- and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases (PTP) by oxidizing an essential cysteine residue in the active site. ATN-224-mediated inhibition of SOD1 in tumor and endothelial cells prevents the formation of sufficiently high levels of H₂O₂, resulting in the protection of PTPs from H₂O₂-mediated oxidation. This, in turn, leads to the inhibition of EGF-, IGF-1-, and FGF-2-mediated phosphorylation of ERK1/2. Pretreatment with exogenous H₂O₂ or with the phosphatase inhibitor vanadate abrogates the inhibition of ERK1/2 phosphorylation induced by ATN-224 or SOD1 siRNA treatments. Furthermore, ATN-224-mediated SOD1 inhibition causes the down-regulation of the PDGF receptor. SOD1 inhibition also increases the steady-state levels of superoxide, which induces protein oxidation in A431 cells but, surprisingly, does not oxidize phosphatases. Thus, SOD1 inhibition in A431 tumor cells results in both prooxidant effects caused by the increase in the levels of superoxide and antioxidant effects caused by lowering the levels of H₂O₂. These results identify SOD1 as a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth.
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