AutoDock Vina (Vina) achieved a very high docking‐success rate, p^, but give a rather low correlation coefficient, R, for binding affinity with respect to experiments. This low correlation can be an ...obstacle for ranking of ligand‐binding affinity, which is the main objective of docking simulations. In this context, we evaluated the dependence of Vina R coefficient upon its empirical parameters. R is affected more by changing the gauss2 and rotation than other terms. The docking‐success rate p^ is sensitive to the alterations of the gauss1, gauss2, repulsion, and hydrogen bond parameters. Based on our benchmarks, the parameter set1 has been suggested to be the most optimal. The testing study over 800 complexes indicated that the modified Vina provided higher correlation with experiment Rset1=0.556±0.025 compared with RDefault=0.493±0.028 obtained by the original Vina and RVina1.2=0.503±0.029 by Vina version 1.2. Besides, the modified Vina can be also applied more widely, giving R≥0.500 for 32/48 targets, compared with the default package, giving R≥0.500 for 31/48 targets. In addition, validation calculations for 1036 complexes obtained from version 2019 of PDBbind refined structures showed that the set1 of parameters gave higher correlation coefficient (Rset1=0.617±0.017) than the default package (RDefault=0.543±0.020) and Vina version 1.2 (RVina1.2=0.540±0.020). The version of Vina with set1 of parameters can be downloaded at https://github.com/sontungngo/mvina. The outcomes would enhance the ranking of ligand‐binding affinity using Autodock Vina.
A new set of empirical parameters of AutoDock Vina was proposed. The accuracy of affinity prediction was significantly increased from RDefault=0.493±0.028 to Rset1=0.556±0.025 over 800 testing complexes. Over 1036 validating complexes, the proposed parameter formed Rset1=0.617±0.017, which is rigidly larger than the default package (RDefault=0.543±0.020) and Vina version 1.2 (RVina1.2=0.540±0.020).
Interventions are needed to improve stroke literacy among recent stroke survivors. We developed an educational video for patients hospitalized with acute ischemic stroke (AIS) and intracerebral ...hemorrhage (ICH).
A 5-minute stroke education video was shown to our AIS and ICH patients admitted from March to June 2015. Demographics and a 5-minute protocol Montreal Cognitive Assessment were also collected. Questions related to stroke knowledge, self-efficacy, and patient satisfaction were answered before, immediately after, and 30 days after the video.
Among 250 screened, 102 patients consented, and 93 completed the video intervention. There was a significant difference between pre-video median knowledge score of 6 (IQR 4-7) and the post-video score of 7 (IQR 6-8; p<0.001) and between pre-video and the 30 day score of 7 (IQR 5-8; p = 0.04). There was a significant difference between the proportion of patients who were very certain in recognizing symptoms of a stroke pre- and post-video, which was maintained at 30-days (35.5% vs. 53.5%, p = 0.01; 35.5% vs. 54.4%, p = 0.02). The proportion who were "very satisfied" with their education post-video (74.2%) was significantly higher than pre-video (49.5%, p<0.01), and this was maintained at 30 days (75.4%, p<0.01). There was no association between MoCA scores and stroke knowledge acquisition or retention. There was no association between stroke knowledge acquisition and rates of home blood pressure monitoring or primary care provider follow-up.
An educational video was associated with improved stroke knowledge, self-efficacy in recognizing stroke symptoms, and satisfaction with education in hospitalized stroke patients, which was maintained at 30 days after discharge.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tetramethrin (Tm) is a commonly used pesticide that has been reported to exert estrogen-antagonistic effects selectively on female rats. The present study was undertaken to assess the protective role ...of lobaric acid (La) on estrous cycle in Tm-treated female Wistar rats. Female rats were exposed to Tm (50 mg/kg b.w/day) only or in combination with La at low (50 mg/kg b.w/day) or high (100 mg/kg b.w/day) dose for 30 days. The results showed that Tm altered the estrous cycle of female rats by decreasing the levels of luteinizing hormone, follicular-stimulating hormone, progesterone, estrone, and estradiol while increasing testosterone level. The morphology of vaginal smears of Tm-treated female rats showed the presence of abnormal cells and/or structures at different phases of estrus cycle. Strikingly, in (Tm + La)-treated rats, all the observed adverse effects of Tm on the hormonal parameters, cell morphology, and the length of each phase of estrous cycle were significantly diminished in a dose-dependent manner. The docking results showed that La competes with Tm for Gonadotropin-Releasing Hormone (GnRH) receptor, thereby reducing the toxicity of Tm but did not cancel the response of GnRH receptor completely. In conclusion, our results designated that La could be used as a potential candidate in the management of insecticide-induced alterations of the reproductive cycle of rodents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nanobubbles have been widely studied for their use in water treatments. Conventional methods for producing nanobubbles require significantly high levels of electric power. A system that involves ...inducing an alternative magnetic field (AMF) in flowing water has been developed, which has relatively low power requirements compared to other methods. Experimental results are presented that indicate nanobubbles are generated by this AMF system. These results include ζ potential measurements in deionized water, light scattering observations, and nanoparticle tracking analysis (NTA) measurements of object size and relative scattering intensity for water containing 5 × 10–4 M CaCO3. The NTA results also suggest the formation of nanobubble–nanoparticle clusters. Finally, an earlier work is reviewed which demonstrated that this AMF treatment led to the removal of tubercles on the inner walls of pipe samples. This prior result is discussed in light of the present evidence of nanobubble formation and a hypothesis is proposed based on the dissolution of CaCO3 as a result of nanobubble–nanoparticle clustering.
Natural metabolites with their specific bioactivities are being considered as a potential source of materials for pharmacological studies. In this study, we successfully isolated and identified five ...known clerodane diterpenes, namely 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (1), 16-hydroxy-cleroda-3,13-dien-15-oic acid (2), 16-hydroxy-cleroda-4(18),13-dien-16,15-olide (3), 3α,16α-dihydroxy-cleroda-4(18),13(14)Z-dien-15,16-olide (4), and 16α-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (5) from the methanolic extract of seeds of Polyalthia longifolia. Initially, all the isolated metabolites were investigated for COX-1, COX-2, and 5-LOX inhibitory activities using the standard inhibitory kits. Of which, compounds 3, 4, and 5 exhibited to be potent COX-1, COX-2, and 5-LOX inhibitors with the IC
values similar or lower to those of the reference drugs. To understand the underlying mechanism, these compounds were subjected to molecular docking on COX-1, COX-2, and 5-LOX proteins. Interestingly, the in silico study results were in high accordance with in vitro studies where compounds 3, 4, and 5 hits assumed interactions and binding pattern comparable to that of reference drugs (indomethacin and diclofenac), as a co-crystallized ligand explaining their remarkable dual (COX/LOX) inhibitor actions. Taken together, our findings demonstrated that compounds 3, 4, and 5 functioned as dual inhibitors of COX/5-LOX and can contribute to the development of novel, more effective anti-inflammatory drugs with minimal side-effects.
Purpose
Our previous rodent study demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. The ...pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Topical tacrolimus has been shown to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating one contributor to necrosis. The purpose of this study was to investigate the vascular and histological differences between these 2 groups to identify the etiology of our research findings.
Methods
A 3 × 10-cm cranially based dorsal skin flap was raised and reinset on 22 Sprague Dawley rats. They were randomized to receive 0.2 g of either topical petroleum jelly or topical 0.1% tacrolimus ointment daily to the flaps. The rats were killed 7 days postoperatively. Two blinded reviewers marked the total flap area as well as areas of viable tissue, reversible ischemia, and necrotic tissue. Full-thickness biopsies of each area were taken from 2 randomly chosen animals in each group. Paraffin-embedded tissue was sectioned to generate hematoxylin and eosin–stained slides. Representative images of each area of the flap were taken less than 40× magnification using light microscopy. Arteries, veins, and lymphatics in the dermal layer were quantified under blinded conditions by a trained pathologist and calculated per cross-sectional area using Fiji software.
Results
The average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm
2
, respectively. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (
P
= 0.015). In the control cohort, average total number of vessels was 12.5, 6, and 0, in the areas of viable tissue, reversible ischemia, and necrosis, respectively. In the tacrolimus cohort, average total number of vessels increased was 20, 11.5, and 5.4, in the areas of viable tissue, reversible ischemia, and necrosis, respectively.
Conclusions
On a histological level, topical tacrolimus is correlated with increased vascular growth in areas most susceptible for ischemic damage as compared with topical control. Future work is needed to investigate vascular biomarkers and increase the power of our study.
We study the dynamics of three bodies located on a straight line for a given finite speed of gravity in the case where the masses of external bodies and their distances to the central body are ...identical. It is shown that the motion of these bodies is unstable and the escape velocity is higher than the corresponding velocity in the classical celestial mechanics.
Four compounds, luteolin (1), 6‐γ,γ‐dimethylallylquercetin 7‐O‐β‐D‐glucopyranoside (2), 6‐γ,γ‐dimethylallylkaempferol 7‐O‐β‐D‐glucopyranoside (3), and 6‐γ,γ‐dimethylallyldihydrokaempferol ...7‐O‐β‐D‐glucoside (4), were isolated for the first time from AcOEt extract of the O. integerrima flower. We then evaluated the antioxidant effects of AcOEt, butanol, and MeOH extracts and their effects on H2O2 against oxidative stress in HaCaT keratinocyte cell lines. Furthermore, 2,2‐diphenyl‐1‐picrylhydrazyl hydrate (DPPH⋅) radical scavenging activities of 1–4 were determined and their mechanisms of action on tyrosinase were predicted by in silico studies. The results revealed that the AcOEt extract and 1–3 exhibited good DPPH⋅ radical scavenging activity. Furthermore, this extract also had a significant protective effect against H2O2‐induced oxidative stress in HaCaT cells. In silico studies indicated that the activity of 1–3 may be due to tyrosinase inhibition with MM‐GBSA free binding energies of −78.9, −70.1, and −71.1 kcal mol−1, respectively, compared to 4 with an energy −56.9 kcal mol−1.
In the present study,
in silico
predictions and molecular docking were performed on five clerodane diterpenes
(1–5)
from
Polyalthia longifolia
seeds to evaluate their potential as xanthine oxidase ...(XO) inhibitors. The initial screening was conducted by target prediction using TargetNet web server application and only compounds
3
and
4
showed a potential interaction with XO. Compounds 3 and 4 were subsequently subjected to
in silico
analyses on XO protein structure (PDB: 1N5X) using Schrödinger Release 2020–3 followed by structural modeling & molecular simulation studies to confirm the initial prediction result and identify the binding mode of these compounds to the XO. Molecular docking results revealed that compounds 3 (-37.3 kcal/mol) and 4 (-32.0 kcal/mol) binds more stably to XO than the reference drug allopurinol (-27.0 kcal/mol). Interestingly, two residues Glu 802 and Thr 1010 were observed as the two main H-bond binding sites for both tested compounds and the allopurinol. The center scaffold of allopurinol was positioned by some π-π stacking with Phe 914 and Phe 1009, while that of compounds
3
and
4
were supported by many hydrophobic interactions mainly with Leu 648, Phe 649, Phe 1013, and Leu 1014. Additionally, the docking simulation predicted that the inhibitory effect of compounds
3
and
4
was mediated by creating H-bond with particularly Glu 802, which is a key amino acid for XO enzyme inhibition. Altogether,
in vitro
studies showed that compounds
3
and
4
had better inhibitory capacity against XO enzyme with IC
50
values significantly (
p
< 0.001) lower than that of allopurinol. In short, the present study identified cleroda-4(18),13-dien-15,16-olide as novel potential XO inhibitors, which can be potentially used for the treatment of gout.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A new xanthone derivative, aspidxanthone A (1), and three known compounds ((2S)‐1‐(β‐D‐galactopyranosyloxy)‐3‐(hexadecanoyloxy)propan‐2‐yl (9Z,12Z)‐octadeca‐9,12‐dienoate (2), ...(25S)‐spirostane‐1β,3α,5β‐triol (3), and asparenyldiol (4)) were isolated from the whole of the endemic species Aspidistra letreae in Vietnam. Their structures were elucidated by means of extensive spectroscopic analyses and comparison with published data. In this study, we report the isolation and structure elucidation of a new compound aspidxanthone A, antioxidant activities of the extract and isolates 1–4, and in silico molecular docking of aspidxanthone A. The ethyl acetate extract had good antioxidant activity with an IC50 value of 26.3 μg mL−1. Among the isolates, aspidxanthone A exhibited DPPH reduction activity with an IC50 value of 11.2 μM, which is in the same range as that of the positive control, ascorbic acid. The mechanism of action of aspidxanthone A on the tyrosinase and xanthine oxidase proteins have been clarified by in silico studies.
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