2,667 research outputs found
Screening of the activity of quercetin-biapigenin and their poly(ε-caprolactone)-loaded nanoparticles in HepG2 cells
Hypericum perforatum extracts have been used for their antidepressive effects. A selected fraction (HP) containing quercetin and biapigenin proved to be neuroprotective. Liver is the organ primary responsible for compound metabolization and extremely susceptibility to toxic effects. This study aims to determine the hepatotoxic/protective activity of HP and HP PCL-loaded nanoparticles.info:eu-repo/semantics/publishedVersio
Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia
<p>Abstract</p> <p>Background</p> <p>Recent studies suggest an important role for neurotransmitters as modulators of inflammation. Neuroinflammatory mediators such as cytokines and molecules of the arachidonic acid pathway are generated and released by microglia. The monoamine norepinephrine reduces the production of cytokines by activated microglia <it>in vitro</it>. However, little is known about the effects of norepinephrine on prostanoid synthesis. In the present study, we investigate the role of norepinephrine on cyclooxygenase- (COX-)2 expression/synthesis and prostaglandin (PG)E<sub>2 </sub>production in rat primary microglia.</p> <p>Results</p> <p>Interestingly, norepinephrine increased COX-2 mRNA, but not protein expression. Norepinephrine strongly enhanced COX-2 expression and PGE<sub>2 </sub>production induced by lipopolysaccharide (LPS). This effect is likely to be mediated by β-adrenoreceptors, since β-, but not α-adrenoreceptor agonists produced similar results. Furthermore, β-adrenoreceptor antagonists blocked the enhancement of COX-2 levels induced by norepinephrine and β-adrenoreceptor agonists.</p> <p>Conclusions</p> <p>Considering that PGE<sub>2 </sub>displays different roles in neuroinflammatory and neurodegenerative disorders, norepinephrine may play an important function in the modulation of these processes in pathophysiological conditions.</p
Inv21p12q22del21q22 and intellectual disability
Chromosomal rearrangements are common in humans. Pericentric inversions are among the most frequent aberrations (1-2%). Most inversions are balanced and do not cause problems in carriers unless one of the breakpoints disrupts important functional genes, has near submicroscopic copy number variants or hosts "cryptic" complex chromosomal rearrangements. Pericentric inversions can lead to imbalance in offspring. Less than 3% of Down syndrome patients have duplication as a result of parental pericentric inversion of chromosome 21. We report a family with an apparently balanced pericentric inversion of chromosome 21. The proband, a 23-year-old female was referred for prenatal diagnosis at 16weeks gestation because of increased nuchal translucency. She has a familial history of Down's syndrome and moderate intellectual disability, a personal history of four spontaneous abortions and learning difficulties. Peripheral blood and amniotic fluid samples were collected to perform proband's and fetus' cytogenetic analyses. Additionally, another six family members were evaluated and cytogenetic analysis was performed. Complementary FISH and MLPA studies were carried out. An apparent balanced chromosome 21 pericentric inversion was observed in four family members, two revealed a recombinant chromosome 21 with partial trisomy, and one a full trisomy 21 with an inverted chromosome 21. Array CGH analysis was performed in the mother and the brother's proband. MLPA and aCGH studies identified a deletion of about 1.7Mb on the long arm of inverted chromosome 21q22.11. We believe the cause of the intellectual disability/learning difficulties observed in the members with the inversion is related to this deletion. The recombinant chromosome 21 has a partial trisomy including the DSCR with no deletion. The risk for carriers of having a child with multiple malformations/intellectual disability is about 30% depending on whether and how this rearrangement interferes with meiosis
Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2
BACKGROUND: The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). METHODS: Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability. RESULTS: In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population. CONCLUSIONS: Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD. TRIAL REGISTRATION NUMBERS: PATENT-1 (NCT00810693), PATENT-2 (NCT00863681)
Molecular Recognition Force Spectroscopy for Probing Cell Targeted Nanoparticles In Vitro
In the development and design of cell targeted nanoparticle-based systems the density of targeting
moieties plays a fundamental role in allowing maximal cell-specific interaction. Here, we describe the
use of molecular recognition force spectroscopy as a valuable tool for the characterization and
optimization of targeted nanoparticles toward attaining cell-specific interaction. By tailoring the
density of targeting moieties at the nanoparticle surface, one can correlate the unbinding event
probability between nanoparticles tethered to an atomic force microscopy tip and cells to the
nanoparticle vectoring capacity. This novel approach allows for a rapid and cost-effective design of
targeted nanomedicines reducing the need for long and tedious in vitro tests.The authors would like to acknowledge the Bioimaging Platform (i3S-INEB) for the support with
atomic force microscopy. This work was financed by projects NORTE-01-0145-FEDER-000008 and
NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme
(NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional
Development Fund (ERDF) and FEDER - Fundo Europeu de Desenvolvimento Regional funds through
the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI),
Portugal 2020; and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in
the framework of the projects UID/BIM/04293/ 2013, PTDC/CTM-NAN/115124/2009, and PTDC/CTMNAN/3547/2014. C.P. Gomes acknowledge FCT for her PhD scholarship SFRH/BD/79930/2011
Fracturing ranked surfaces
Discretized landscapes can be mapped onto ranked surfaces, where every
element (site or bond) has a unique rank associated with its corresponding
relative height. By sequentially allocating these elements according to their
ranks and systematically preventing the occupation of bridges, namely elements
that, if occupied, would provide global connectivity, we disclose that bridges
hide a new tricritical point at an occupation fraction , where
is the percolation threshold of random percolation. For any value of in the
interval , our results show that the set of bridges has a
fractal dimension in two dimensions. In the limit , a self-similar fracture is revealed as a singly connected line
that divides the system in two domains. We then unveil how several seemingly
unrelated physical models tumble into the same universality class and also
present results for higher dimensions
Holographic Superconductors with Power-Maxwell field
With the Sturm-Liouville analytical and numerical methods, we investigate the
behaviors of the holographic superconductors by introducing a complex charged
scalar field coupled with a Power-Maxwell field in the background of
-dimensional Schwarzschild AdS black hole. We note that the Power-Maxwell
field takes the special asymptotical solution near boundary which is different
from all known cases. We find that the larger power parameter for the
Power-Maxwell field makes it harder for the scalar hair to be condensated. We
also find that, for different , the critical exponent of the system is still
1/2, which seems to be an universal property for various nonlinear
electrodynamics if the scalar field takes the form of this paper.Comment: 14 pages, 1 figure, and 2 table
The Noncommutative Harmonic Oscillator based in Simplectic Representation of Galilei Group
In this work we study symplectic unitary representations for the Galilei
group. As a consequence the Schr\"odinger equation is derived in phase space.
The formalism is based on the non-commutative structure of the star-product,
and using the group theory approach as a guide a physical consistent theory in
phase space is constructed. The state is described by a quasi-probability
amplitude that is in association with the Wigner function. The 3D harmonic
oscillator and the noncommutative oscillator are studied in phase space as an
application, and the Wigner function associated to both cases are determined.Comment: 7 pages,no figure
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