Fluorinated chalcones are organic compounds with diverse biological activities and are of interest for drug development due to their improved properties, such as lipophilicity, bioavailability, and ...metabolic stability. Therefore, the correlation between structure and properties is fundamental to discover the potential use on pharmaceutical and technological applications. In this sense, we synthesized and characterized a novel fluorinated chalcone (E)-1-(4-fluorophenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (FCH), and compared its supramolecular arrangement and topological analysis with a chalcone (E)-1-(4-hydroxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (HCH). The molecular electrostatic potential, QTAIM, and frontier molecular orbitals of both chalcones were investigated using the M06-2X/6-311++G(d,p) level of theory. Our findings show that the FCH exhibits a herringbone packing with intermolecular interactions of C–H⋯F and C–H⋯π, while the HCH assumes a staircase packing coordinated by O–H⋯O and π⋯π intermolecular interactions. Furthermore, the electrostatic potential analysis shows that FCH is susceptible to electrophilic attack, while HCH is susceptible to nucleophilic attack. Finally, the structural basis analysis for both chalcones indicated that FCH has a higher lipophilicity than HCH due to the stronger hydrogen bond of HCH with water.
To describe onset features, classification and treatment of juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre registry.
Inclusion criteria were onset age lower than 18 ...years and a diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician. Bohan & Peter (1975) criteria categorisation was established by a scoring algorithm to define JDM and JPM based on clinical protocol data.
Of the 189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not fit the criteria; 6.9% had features of chronic arthritis and connective tissue disease overlap. Diagnosis classification agreement occurred in 66.1%. Median onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash 83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result. Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was done in 66 cases with all parameters assessed and only aldolase resulted significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4, p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%.
Evaluation of predefined criteria set for a valid diagnosis indicated aldolase as the most important parameter associated with definite JDM category. In practice, prednisone-methotrexate combination was the most indicated treatment.
The title compound, C(19)H(20)O(5), was synthesized by reaction of 4-meth-oxy-acetophenone and 3,4,5-trimeth-oxy-benzaldehyde. The aromatic rings form a dihedral angle of 36.39 (7)°. Two ...intramolecular C-H⋯O hydrogen bonds occur. The crystal packing features weak C-H⋯O inter-actions.
Since 2005, the blazar 3C 454.3 has shown remarkable flaring activity at all frequencies, and during the last four years it has exhibited more than one Delta *g-ray flare per year, becoming the most ...active Delta *g-ray blazar in the sky. We present for the first time the multi-wavelength AGILE, Swift, INTEGRAL, and GASP-WEBT data collected in order to explain the extraordinary Delta *g-ray flare of 3C 454.3 which occurred in 2010 November. On 2010 November 20 (MJD 55520), 3C 454.3 reached a peak flux (E >100 MeV) of Fp Delta *g = (6.8 ? 1.0) X 10--5 photons cm--2 s--1 on a timescale of about 12 hr, more than a factor of six higher than the flux of the brightest steady Delta *g-ray source, the Vela pulsar, and more than a factor of three brighter than its previous super-flare on 2009 December 2-3. The multi-wavelength data make possible a thorough study of the present event: the comparison with the previous outbursts indicates a close similarity to the one that occurred in 2009. By comparing the broadband emission before, during, and after the Delta *g-ray flare, we find that the radio, optical, and X-ray emission varies within a factor of 2-3, whereas the Delta *g-ray flux by a factor of 10. This remarkable behavior is modeled by an external Compton component driven by a substantial local enhancement of soft seed photons.
Dental cementum (DC) covers the tooth root and has important functions in tooth attachment and position. DC can be lost to disease, and regeneration is currently unpredictable due to limited ...understanding of DC formation. This study used a model of experimentally-induced apposition (EIA) in mice to identify proteins associated with new DC formation. Mandibular first molars were induced to super-erupt for 6 and 21days after extracting opposing maxillary molars. Decalcified and formalin-fixed paraffin-embedded mandible sections were prepared for laser capture microdissection. Microdissected protein extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and the data submitted to repeated measure ANOVA test (RM-ANOVA, alpha=5%). A total of 519 proteins were identified, with 97 (18.6%) proteins found exclusively in EIA sites and 50 (9.6%) proteins exclusively expressed in control sites. Fifty six (10.7%) proteins were differentially regulated by RM-ANOVA (p<0.05), with 24 regulated by the exclusive effect of EIA (12 proteins) or the interaction between EIA and time (12 proteins), including serpin 1a, procollagen C-endopeptidase enhancer, tenascin X (TNX), and asporin (ASPN). In conclusion, proteomic analysis demonstrated significantly altered protein profile in DC under EIA, providing new insights on DC biology and potential candidates for tissue engineering applications.
Dental cementum (DC) is a mineralized tissue that covers the tooth root surface and has important functions in tooth attachment and position. DC and other periodontal tissues can be lost to disease, and regeneration is currently unpredictable due to lack of understanding of DC formation. This study used a model of experimentally-induced apposition (EIA) in mice to promote new cementum formation, followed by laser capture microdissection (LCM) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomic analysis. This approach identified proteins associated with new cementum formation that may be targets for promoting cementum regeneration.
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•Microdissection of FFPE tissues followed by LC-MS/MS was used successfully for proteomic analysis of dental cementum.•We identified 24 proteins in cementum regulated by experimentally-induced apposition.•We produced evidence for cementocyte activity during new cementum formation.
TAT (a 13‐mer derived from the HIV‐1 Tat protein)‐linked cell‐permeable peptides deliver plasma membrane impermeable cargos into the cell. We investigated the effect of a TAT‐linked intracellular ...third loop of the endothelin‐1 type B receptor on endothelin‐1 activation of ERK. The effect of this peptide on ERK activation was determined in ETB receptor cDNA‐transfected Chinese hamster ovary cells and in ETA‐ and ETB‐expressing human pulmonary artery smooth muscle cells obtained from a normal and a bone morphogenetic protein‐2 receptor, exon 1–8 deletion subject, with pulmonary hypertension. In the Chinese hamster ovary cells the peptide, at optimum 10 μm concentration, suppressed endothelin‐1 activation. In the normal human pulmonary artery smooth muscle cells, the peptide marginally enhanced endothelin‐1 activation of ERK. However, it markedly enhanced the endothelin‐1 activation of ERK in the bone morphogenetic protein‐2 receptor human pulmonary artery smooth muscle cells. While the effective concentration for endothelin‐1 activation of ERK remained unchanged in the bone morphogenetic protein‐2 receptor human pulmonary artery smooth muscle cells, the number of ETB receptors declined by 2/3. These data point to the intracellular third loop peptide as having variable receptor interactive effects with both signal repressive and enhancing capabilities. Peptides that can alter endothelin‐1 signal capabilities are potentially important in the study and treatment of pulmonary hypertension.
A peptide consisting of the cell‐permeable peptide, TAT, linked to the intracellular third loop of the endothelin‐1 (ET‐1) type B receptor (ETB) was synthesized and investigated for its ability to modulate ETB receptor activity. In CHO cells transfected with the human ETB receptor, the peptide suppressed ET‐1 activation. In the normal human pulmonary artery smooth muscle cells (hPASMCs), the peptide enhanced ERK activation by ET‐1 slightly but it markedly enhanced the ET‐1 activation of ERK in the BMP2R mutant hPASMCs.
A produção de ceramida ocorre em todo o corpo e desempenha um papel importante na manutenção da fisiologia normal. No entanto, os níveis de ceramidas são alterados em estados de doença, ...principalmente durante o desenvolvimento de diabetes e dislipidemia. A produção de ceramidas também está associada à instabilidade das placas ateroscleróticas. Estudos recentes revelam que pacientes com doença arterial coronariana instável apresentam níveis plasmáticos aumentados de ceramidas (principalmente C16, C18 e C24:1). Atualmente, são consideradas biomarcadores emergentes nas doenças cardiovasculares, sendo utilizadas na predição de instabilidade da placa aterosclerótica e eventos cardiovasculares adversos de forma independente aos fatores de risco tradicionais. Com o objetivo de descrever e discutir o papel das ceramidas na estratificação das doenças cardiovasculares, o desenvolvimento desta revisão narrativa contextualiza a importância desse biomarcador no cenário atual da cardiologia.
The Esophagectomy Complications Consensus Group (ECCG) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA) have set standards in reporting outcomes after oesophagectomy. Reporting outcomes from ...selected high-volume centres or centralized national cancer programmes may not, however, be reflective of the true global prevalence of complications. This study aimed to compare complication rates after oesophagectomy from these existing sources with those of an unselected international cohort from the Oesophago-Gastric Anastomosis Audit (OGAA).
The OGAA was a prospective multicentre cohort study coordinated by the West Midlands Research Collaborative, and included patients undergoing oesophagectomy for oesophageal cancer between April and December 2018, with 90 days of follow-up.
The OGAA study included 2247 oesophagectomies across 137 hospitals in 41 countries. Comparisons with the ECCG and DUCA found differences in baseline demographics between the three cohorts, including age, ASA grade, and rates of chronic pulmonary disease. The OGAA had the lowest rates of neoadjuvant treatment (OGAA 75.1 per cent, ECCG 78.9 per cent, DUCA 93.5 per cent; P < 0.001). DUCA exhibited the highest rates of minimally invasive surgery (OGAA 57.2 per cent, ECCG 47.9 per cent, DUCA 85.8 per cent; P < 0.001). Overall complication rates were similar in the three cohorts (OGAA 63.6 per cent, ECCG 59.0 per cent, DUCA 62.2 per cent), with no statistically significant difference in Clavien-Dindo grades (P = 0.752). However, a significant difference in 30-day mortality was observed, with DUCA reporting the lowest rate (OGAA 3.2 per cent, ECCG 2.4 per cent, DUCA 1.7 per cent; P = 0.013).
Despite differences in rates of co-morbidities, oncological treatment strategies, and access to minimal-access surgery, overall complication rates were similar in the three cohorts.
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