659 research outputs found
Purification, Cloning, Characterization and Essential Amino Acid Residues Analysis of a New iota-Carrageenase from Cellulophaga sp QY3
ι-Carrageenases belong to family 82 of glycoside hydrolases that degrade sulfated galactans in the red algae known as ι-carrageenans. The catalytic mechanism and some substrate-binding residues of family GH82 have been studied but the substrate recognition and binding mechanism of this family have not been fully elucidated. We report here the purification, cloning and characterization of a new ι-carrageenase CgiA_Ce from the marine bacterium Cellulophaga sp. QY3. CgiA_Ce was the most thermostable carrageenase described so far. It was most active at 50°C and pH 7.0 and retained more than 70% of the original activity after incubation at 50°C for 1 h at pH 7.0 or at pH 5.0–10.6 for 24 h. CgiA_Ce was an endo-type ι-carrageenase; it cleaved ι-carrageenan yielding neo-ι-carrabiose and neo-ι-carratetraose as the main end products, and neo-ι-carrahexaose was the minimum substrate. Sequence analysis and structure modeling showed that CgiA_Ce is indeed a new member of family GH82. Moreover, sequence analysis of ι-carrageenases revealed that the amino acid residues at subsites −1 and +1 were more conserved than those at other subsites. Site-directed mutagenesis followed by kinetic analysis identified three strictly conserved residues at subsites −1 and +1 of ι-carrageenases, G228, Y229 and R254 in CgiA_Ce, which played important roles for substrate binding. Furthermore, our results suggested that Y229 and R254 in CgiA_Ce interacted specifically with the sulfate groups of the sugar moieties located at subsites −1 and +1, shedding light on the mechanism of ι-carrageenan recognition in the family GH82
Comparing quality of life and treatment satisfaction between patients on warfarin and direct oral anticoagulants : a cross-sectional study
Introduction and aim: Patient quality of life (QOL) while on long-term oral anticoagulant therapy has been receiving greater attention in recent years due to the increase in life expectancy brought about by advances in medical care. This study aimed to compare the QOL, treatment satisfaction, hospitalization and bleeding rate in patients on long-term warfarin versus direct oral anticoagulants (DOAC). Methods: This was a cross-sectional study of patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) on long-term anticoagulant therapy attending the cardiology clinic and anticoagulation clinic of the University Malaya Medical Centre from July 1, 2016, to June 30, 2018. Patient QOL was assessed by using the Short Form 12
Health Survey (SF12), while treatment satisfaction was assessed by using the Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2).
Results: A total of 208 patients were recruited; 52.4% received warfarin and 47.6% received DOAC. There was no significant difference in QOL between warfarin and DOAC based on SF12 (physical QOL, P=0.083; mental QOL, P=0.665). Nevertheless, patients in the DOAC
group were significantly more satisfied with their treatment compared to the warfarin group based on PACT-Q2 (P=0.004). The hospitalisation rate was significantly higher in the warfarin group than the DOAC group (15.6% versus 3.0%, P=0.002). Clinically relevant minor bleeds and severe bleeding events were non-significantly higher in the warfarin group than the DOAC group (66.7% versus 40.0%, P=0.069).
Conclusion: Compared to warfarin, treatment of NVAF and VTE with DOAC showed comparable QOL, higher treatment satisfaction, lesser hospitalization, and a non-significant trend toward fewer bleeding episodes
Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro
Background/Aims: Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L., and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Methods: Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Results: Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP+ multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Conclusions: Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro
Burnout, anxiety and depression in healthcare workers during the early COVID-19 period in Singapore
acceptedVersionPeer reviewe
Mannitol cannot reduce the mortality on acute severe traumatic brain injury (TBI) patients: a meta–analyses and systematic review
Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy
Sustained proliferation in cancer: mechanisms and novel therapeutic targets
Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression
Measurement of proton electromagnetic form factors in in the energy region 2.00-3.08 GeV
The process of is studied at 22 center-of-mass
energy points () from 2.00 to 3.08 GeV, exploiting 688.5~pb of
data collected with the BESIII detector operating at the BEPCII collider. The
Born cross section~() of is
measured with the energy-scan technique and it is found to be consistent with
previously published data, but with much improved accuracy. In addition, the
electromagnetic form-factor ratio () and the value of the
effective (), electric () and magnetic () form
factors are measured by studying the helicity angle of the proton at 16
center-of-mass energy points. and are determined with
high accuracy, providing uncertainties comparable to data in the space-like
region, and is measured for the first time. We reach unprecedented
accuracy, and precision results in the time-like region provide information to
improve our understanding of the proton inner structure and to test theoretical
models which depend on non-perturbative Quantum Chromodynamics
Observation of in
Using a sample of events recorded with
the BESIII detector at the symmetric electron positron collider BEPCII, we
report the observation of the decay of the charmonium state
into a pair of mesons in the process
. The branching fraction is measured for the first
time to be , where the first uncertainty is
statistical, the second systematic and the third is from the uncertainty of
. The mass and width of the are
determined as MeV/ and
MeV.Comment: 13 pages, 6 figure
Observation and study of the decay
We report the observation and study of the decay
using events
collected with the BESIII detector. Its branching fraction, including all
possible intermediate states, is measured to be
. We also report evidence for a structure,
denoted as , in the mass spectrum in the GeV/
region. Using two decay modes of the meson ( and
), a simultaneous fit to the mass spectra is
performed. Assuming the quantum numbers of the to be , its
significance is found to be 4.4, with a mass and width of MeV/ and MeV, respectively, and a
product branching fraction
. Alternatively, assuming , the
significance is 3.8, with a mass and width of MeV/ and MeV, respectively, and a product
branching fraction
. The angular distribution of
is studied and the two assumptions of the
cannot be clearly distinguished due to the limited statistics. In all
measurements the first uncertainties are statistical and the second systematic.Comment: 10 pages, 6 figures and 4 table
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