9 research outputs found
Additional file 1 of Does the use of different scaffolds have an impact on the therapeutic efficacy of regenerative endodontic procedures? A systematic evaluation and meta-analysis
Additional file 1. Appendix Table 1. Search strategy used for each database
Steering On-Surface Supramolecular Nanostructures by <i>tert</i>-Butyl Group
Molecular
self-assembly is an efficient approach to fabricate supramolecular
nanostructures on well-defined surfaces. The nanostructures can be
regulated through functionalizing the molecular precursors with different
functional groups. Here, from an interplay of high-resolution scanning
tunneling microscopy imaging and density functional theory calculations,
we have at the atomic scale investigated the influence of <i>tert</i>-butyl groups on the on-surface self-assembled behaviors
of the organic molecules where intermolecular interactions mainly
originate from relatively weak van der Waals interactions. Our results
demonstrate that the <i>tert</i>-butyl groups can not only
affect the adsorption geometry but also change the self-assembled
properties of organic molecules on surfaces due to the enhanced intermolecular
interactions
Investigation on the Linker Length of Synthetic Zwitterionic Polypeptides for Improved Nonfouling Surfaces
Zwitterionic
polymers are outstanding nonfouling materials widely used for surface
modification. However, works that systematically evaluate the structure–activity
relationship of the side chain linker effect with related antifouling
abilities are sparse. Here, we generate a series of well-defined zwitterionic
polypeptides bearing oligoethylene glycol (EG) linkers in the side
chain (PÂ(CB-EG<sub><i>x</i></sub>Glu), <i>x</i> = 1–3) and anchor them on gold surfaces via the grafting-to
approach to compare their antifouling performances. The surface properties
are characterized by X-ray photoelectron spectroscopy (XPS), circular
dichroism spectroscopy (CD), variable angle spectroscopic ellipsometry
(VASE), static water contact angle (SCA), and atomic force microscopy
(AFM). By use of quartz crystal microbalance with dissipation (QCM-D),
confocal microscopy, and scanning electron microscope, our results
convincingly demonstrate the excellent antifouling performance of
all zwitterionic polypeptides. Importantly, the surface coated with
PÂ(CB-EG<sub>3</sub>Glu), the one with the longest EG linker, exhibits
the best resistance to single protein (below the detection limit of
QCM) and blood serum (∼96–98% reduction) adsorption,
which largely outperforms those of the PEG positive control and the
two PÂ(CB-EG<sub><i>x</i></sub>Glu) analogues with shorter
EG<sub><i>x</i></sub> linkers. The same PÂ(CB-EG<sub>3</sub>Glu) surface also gives the highest degree of prevention of cell/platelet/bacterial
attachment (∼99% reduction) among all samples tested. Together,
our study highlights the linker effect to the nonfouling performance
of zwitterionic polypeptides, and the results strongly support PÂ(CB-EG<sub>3</sub>Glu) as a robust nonfouling material for numerous applications
Atomic-Scale Investigation on the Facilitation and Inhibition of Guanine Tautomerization at Au(111) Surface
Nucleobase tautomerization might induce mismatch of base pairing. Metals, involved in many important biophysical processes, have been theoretically proven to be capable of affecting tautomeric equilibria and stabilities of different nucleobase tautomers. However, direct real-space evidence on demonstrating different nucleobase tautomers and further revealing the effect of metals on their tautomerization at surfaces has not been reported to date. From the interplay of high-resolution STM imaging and DFT calculations, we show for the first time that tautomerization of guanine from G/9H to G/7H is facilitated on Au(111) by heating, whereas such tautomerization process is effectively inhibited by introducing Ni atoms due to its preferential coordination at the N7 site of G/9H. These findings may help to elucidate possible influence of metals on nucleobase tautomerization and provide from a molecular level some theoretical basis on metal-based drug design
The expression of β-ENaC was significantly reduced in the placenta of preeclampsia patients.
<p>β-ENaC expression in placenta of preeclampsia was reduced in RNA and protein level. (A) right bar chart represent the statistics of the real time PCR result, while left figure is the representative gel result of the RT-PCR result of the placenta samples. 12P,14P,17P were patients numbers of severe preeclampsia while left were normal controls. (B) Representative result of the Western blot result; The right is the statistic result (*means p<0.05).</p
Immunohistochemistry staining of β-ENaC in placenta of normal pregnancy and preeclmpsia patients.
<p>The immunohistochemistry staining of β-ENaC in placenta tissue of full-term placenta of normal pregnancy(A-C). The signal was detected in placental villous trophoblast cells, especially in syncytiotrophoblast (arrow, A) with less staining in cytotrophoblast and the staining was seen in extravillous cytotrophoblastic cells (arrowhead, B). (D, E) are staining of β-ENaC in placenta tissue from the preeclampsia patients. Reduced expression was noticed in placenta of preeclampsia patients (N = 3). (F) is negative control of the IHC staining. Magnification: X400, scare bar = 20 µM.</p
Knowkdown of α-ENaC reduced the migration and invasion capability in HTR8/SVneo cells.
<p>(A) Western blot result shows that α-ENaC RNAi can dose-dependently reduce the expression of ENaC. (B) The representative pictures in cell wounding and migration assay. The pictures shows the migration of HTR8/SVneo cells in the martrigel surface after 32 hr of scrape in different groups. The dot line shows the initial start point where the cell began the migration process. The cell number between in dot lines were count. The right is the statistics of the cell migration ability. The data are expressed as means ± SEM, of the three measurements (*means p<0.05).</p
Knowkdown of α-ENaC reduced the invasion capability in HTR8/SVneo cells.
<p>(A) is the representative picture of cell invasion assay after 48 hr of invasion assay in the insert of 24 wells. Each group was repeated three times. (B) is the counting result of the cells number under microscope. The cells on the underside of the filters and the pores occupied were counted in 40 randomly selected non-overlapping fields of the membranes under a light microscope at x100 magnification. Student T test were used for comparison. (*meansP<0.05).</p
Macrocyclization of Interferon–Poly(α-amino acid) Conjugates Significantly Improves the Tumor Retention, Penetration, and Antitumor Efficacy
Cyclization and polymer conjugation
are two commonly used approaches
for enhancing the pharmacological properties of protein drugs. However,
cyclization of parental proteins often only affords a modest improvement
in biochemical or cell-based <i>in vitro</i> assays. Moreover,
very few studies have included a systematic pharmacological evaluation
of cyclized protein-based therapeutics in live animals. On the other
hand, polymer-conjugated proteins have longer circulation half-lives
but usually show poor tumor penetration and suboptimal pharmacodynamics
due to increased steric hindrance. We herein report the generation
of a head-to-tail interferon–polyÂ(α-amino
acid) macrocycle conjugate <i>circ</i>-PÂ(EG<sub>3</sub>Glu)<sub>20</sub>-IFN by combining the aforementioned two approaches. We then
compared the antitumor pharmacological activity of this macrocycle
conjugate against its linear counterparts, <i>N</i>-PÂ(EG<sub>3</sub>Glu)<sub>20</sub>-IFN, <i>C</i>-IFN-PÂ(EG<sub>3</sub>Glu)<sub>20</sub>, and <i>C</i>-IFN-PEG. Our results found <i>circ</i>-PÂ(EG<sub>3</sub>Glu)<sub>20</sub>-IFN to show considerably
greater stability, binding affinity, and <i>in vitro</i> antiproliferative activity toward OVCAR3 cells than the three linear
conjugates. More importantly, <i>circ</i>-PÂ(EG<sub>3</sub>Glu)<sub>20</sub>-IFN exhibited longer circulation half-life, remarkably
higher tumor retention, and deeper tumor penetration <i>in vivo</i>. As a result, administration of the macrocyclic conjugate could effectively
inhibit tumor progression and extend survival in mice bearing established
xenograft human OVCAR3 or SKOV3 tumors without causing severe paraneoplastic
syndromes. Taken together, our study provided until now the most relevant
experimental evidence in strong support of the <i>in vivo</i> benefit of macrocyclization of protein–polymer conjugates
and for its application in next-generation therapeutics