Secondary caries and micro-cracks are the main limiting factors for dentin bond durability. The objectives of this study were to develop a self-healing adhesive containing dimethylaminohexadecyl ...methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and investigate the effects of water-aging for 12 months on self-healing, dentin bonding, and antibacterial properties for the first time.
Microcapsules were synthesized with poly (urea-formaldehyde) (PUF) shells containing triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT). The adhesive contained 7.5% microcapsules, 10% DMAHDM, and 20% NACP (all mass). Specimens were water-aged at 37 °C for 1 day to 12 months. Dentin bond strength was measured using extracted human teeth. A single-edge-V-notched-beam (SEVNB) method was used to measure fracture toughness KIC and self-healing efficiency. A dental plaque microcosm biofilm model was used with human saliva as inoculum.
The microcapsules + DMAHDM + NACP group showed no decline in dentin bond strength after water-aging for 12 months, which was significantly higher than that of other groups without DMAHDM (p < 0.05). A self-healing efficiency of 67% recovery in KIC was obtained even after 12 months of water immersion, indicating that the self-healing ability was not lost in water-aging (p > 0.1). The bacteria-killing ability of this adhesive did not decline from 1 day to 12 months (p > 0.1), with biofilm CFU reduction by 3–4 orders of magnitude after the resin was water-aged for 12 months, compared to control resin.
This novel adhesive with triple merits of self-healing, antibacterial and remineralization functions showed an excellent long-term durability in water-aging for 12 months. This multifunctional adhesive has the potential for dental applications to heal cracks, inhibit bacteria, provide ions for remineralization, and increase the restoration longevity.
•Quercetin and other flavonols do not activate rat, mouse or human VDR.•Quercetin does not induce human VDR target genes in Caco-2 and LS180 cells.•These chemicals do not create molecular ...interactions crucial for VDR activation.
It has been reported that quercetin is an activator of rat vitamin D receptor (rVDR). However, the conclusion was based on experiments performed without all the appropriate control groups, raising the possibility of a false-positive finding. Furthermore, distinct differences exist in the chemical structures of quercetin and 1α,25-dihydroxyvitamin D3, which is a prototypic agonist of VDR. Therefore, we investigated systematically whether quercetin and other flavonols are agonists of rVDR, mouse VDR (mVDR), or human VDR (hVDR). Quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin did not activate rVDR, mVDR, or hVDR in HEK-293 and HepG2 cells transfected with the corresponding receptor expression plasmid and either the secreted phosphoprotein 1 (Spp1) or cytochrome P450 24A1 (CYP24A1) reporter plasmid, when compared to the respective empty vector control group transfected with one or the other reporter plasmid and treated with one of the flavonols. Control analysis indicated that lithocholic acid and 1α,25-dihydroxyvitamin D3, but not rifampicin, activated rVDR, mVDR, and hVDR. As shown in transfected HEK293 and HepG2 cells, the flavonols did not influence hVDR ligand binding domain transactivation, steroid receptor coactivator-1 recruitment, or hVDR target gene expression (transient receptor potential cation channel 6 and CYP24A1) in hVDR-expressing Caco-2 or LS180 cells. The cumulative data from the cell-based experiments were corroborated by results obtained from molecular docking analysis. In conclusion, quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin are not agonists of rVDR, mVDR, or hVDR, as judged by cell-based and in silico evidence.
Valproic acid (2-n-propylpentanoic acid; VPA) has several therapeutic indications, but it is used primarily as an anticonvulsant. VPA is a relatively safe drug, but its use is associated with ...idiosyncratic hepatotoxicity, which in some cases may lead to fatality. The underlying mechanism responsible for the hepatotoxicity is still not well understood, but various hypotheses have been proposed, including oxidative stress. This article discusses the experimental evidence on the effect of VPA on the various indices of oxidative stress and on the potential role of oxidative stress in VPA-associated hepatotoxicity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There is concern that, with prolonged survival, patients with human immunodeficiency virus (HIV) infection may be at risk for cardiovascular and cerebrovascular disease due to HIV infection itself ...and to the effects of antiretroviral drugs. This retrospective study, involving a large population of veterans, dispels this concern.
In a large population there was no increase in the rate of cardiovascular disease.
Widespread use of potent combination antiretroviral therapy dramatically improves survival among patients infected with the human immunodeficiency virus (HIV) but introduces questions about long-term management.
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HIV-associated abnormalities of lipid and insulin metabolism have been recognized, and there is an increasing prevalence of fat redistribution, frank diabetes, and hyperlipidemia.
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There are reports of premature cardiovascular and cerebrovascular disease and of endothelial dysfunction, possibly linked to both effects of the drugs and HIV infection itself.
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These reports have aroused concern about highly active antiretroviral therapy.
We used anonymous data bases of the Department of Veterans Affairs (VA) to construct . . .
Background and Purpose
Rilpivirine and etravirine are second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) indicated for the treatment of HIV/AIDS. The constitutive androstane ...receptor (CAR) regulates the expression of genes involved in various biological processes, including the transport and biotransformation of drugs. We investigated the effect of rilpivirine and etravirine on the activity of the wild‐type human CAR (hCAR‐WT) and its hCAR‐SV23 and hCAR‐SV24 splice variants, and compared it with first‐generation NNRTIs (efavirenz, nevirapine, and delavirdine).
Experimental Approach
Receptor activation, ligand‐binding domain (LBD) transactivation, and co‐activator recruitment were investigated in transiently transfected, NNRTI‐treated HepG2 cells. Nuclear translocation of green fluorescent protein‐tagged hCAR‐WT and CYP2B6 gene expression were assessed in NNRTI‐treated human hepatocytes.
Key Results
Rilpivirine and etravirine activated hCAR‐WT, but not hCAR‐SV23 or hCAR‐SV24, and without transactivating the LBD or recruiting steroid receptor coactivators SRC‐1, SRC‐2, or SRC‐3. Among the first‐generation NNRTIs investigated, only efavirenz activated hCAR‐WT, hCAR‐SV23, and hCAR‐SV24, but none of them transactivated the LBD of these receptors or substantively recruited SRC‐1, SRC‐2, or SRC‐3. Rilpivirine, etravirine, and efavirenz triggered nuclear translocation of hCAR‐WT and increased hCAR target gene (CYP2B6) expression.
Conclusion and Implications
NNRTIs activate hCAR‐WT, hCAR‐SV23, and hCAR‐SV24 in a drug‐specific and isoform‐selective manner. The activation occurs by a mechanism that does not appear to involve binding to the LBD or recruitment of SRC‐1, SRC‐2, or SRC‐3.
Acyl glucuronides are reactive electrophilic metabolites implicated in the toxicity of carboxylic acid drugs. Valproyl 1-O-β-acyl glucuronide (VPA-G), which is a major metabolite of valproic acid ...(VPA), has been linked to the development of oxidative stress in VPA-treated rats. However, relatively little is known about the toxicity of in situ generated VPA-G and its contribution to VPA hepatotoxicity. Therefore, we investigated the effects of modulating the in situ formation of VPA-G on lactate dehydrogenase (LDH) release (a marker of necrosis), BODIPY 558/568 C12 accumulation (a marker of steatosis), and cellular glutathione (GSH) content in VPA-treated sandwich-cultured rat hepatocytes. VPA increased LDH release and BODIPY 558/568 C12 accumulation, whereas it had little or no effect on total GSH content. Among the various uridine 5'-diphospho-glucuronosyltransferase inducers evaluated, β-naphthoflavone produced the greatest increase in VPA-G formation. This was accompanied by an attenuation of the increase in BODIPY 558/568 C12 accumulation, but did not affect the change in LDH release or total GSH content in VPA-treated hepatocytes. Inhibition of in situ formation of VPA-G by borneol was not accompanied by substantive changes in the effects of VPA on any of the toxicity markers. In a comparative study, in situ generated diclofenac glucuronide was not toxic to rat hepatocytes, as assessed using the same chemical modulators, thereby demonstrating the utility of the sandwich-cultured rat hepatocyte model. Overall, in situ generated VPA-G was not toxic to sandwich-cultured rat hepatocytes, suggesting that VPA glucuronidation per se is not expected to be a contributing mechanism for VPA hepatotoxicity.
Naturally occurring splice variants of human constitutive androstane receptor (hCAR) exist, including hCAR-SV23 (insertion of amino acids SPTV), hCAR-SV24 (APYLT), and hCAR-SV25 (SPTV and APYLT). An ...extract of Ginkgo biloba was reported to activate hCAR-SV24 and the wild type (hCAR-WT). However, it is not known whether it selectively affects hCAR splice variants, how it activates hCAR isoforms, and which chemical is responsible for the effects of the extract. Therefore, we evaluated the impact of G. biloba extract on the functionality of hCAR-SV23, hCAR-SV24, hCAR-SV25, and hCAR-WT and compared it with that of phenobarbital, di-(2-ethylhexyl)phthalate (DEHP), 6-(4-chlorophenyl)imidazo2,1-b1,3thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), and 1,4-bis-2-(3,5-dichloropyridyloxy)benzene (TCPOBOP) in cell-based reporter gene assays. Among the hCAR splice variants investigated, only hCAR-SV23 was activated by G. biloba extract, and this required cotransfection of a retinoid X receptor α (RXRα) expression plasmid. The extract activated hCAR-SV23 to a lesser extent than hCAR-WT, but ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide were not responsible for the effects of the extract. CITCO activated hCAR-SV23, hCAR-SV24, and hCAR-WT. By comparison, phenobarbital activated hCAR-WT, whereas DEHP activated hCAR-SV23, hCAR-SV24 (with exogenous RXRα supplementation), and hCAR-WT. TCPOBOP did not affect the activity of any of the isoforms. G. biloba extract and phenobarbital did not bind or recruit coactivators to the ligand-binding domains of hCAR-WT and hCAR-SV23, whereas positive results were obtained with the controls (CITCO for hCAR-WT and DEHP for hCAR-SV23). In conclusion, G. biloba extract activates hCAR in an isoform-selective manner, and hCAR-SV23, hCAR-SV24, and hCAR-WT have overlapping, but distinct, sets of ligands.
IMPORTANCE: Smoking cessation interventions for hospitalized patients must continue after discharge to improve long-term tobacco abstinence. How health systems can best deliver postdischarge tobacco ...treatment is uncertain. OBJECTIVE: To determine if health system–based tobacco cessation treatment after hospital discharge produces more long-term tobacco abstinence than referral to a community-based quitline. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted September 2018 to November 2020 in 3 hospitals in Massachusetts, Pennsylvania, and Tennessee. Cigarette smokers admitted to a study hospital who received brief in-hospital tobacco treatment and wanted to quit smoking were recruited for participation and randomized for postdischarge treatment to health system–based Transitional Tobacco Care Management (TTCM) or electronic referral to a community-based quitline (QL). Both multicomponent interventions offered smoking cessation counseling and nicotine replacement therapy (NRT) for up to 3 months. Data were analyzed from February 1, 2021, to April 25, 2022. INTERVENTIONS: TTCM provided 8 weeks of NRT at discharge and 7 automated calls with a hospital-based counselor call-back option. The QL intervention sent referrals from the hospital electronic health record to the state quitline, which offered 5 counseling calls and an NRT sample. MAIN OUTCOMES AND MEASURES: The main outcome was biochemically verified past 7-day tobacco abstinence at 6 months. Self-reported point-prevalence and continuous tobacco abstinence and tobacco treatment utilization were assessed 1, 3, and 6 months after discharge. RESULTS: A total of 1409 participants (mean SD age, 51.7 12.6 years; 784 55.6% women; mean SD 16.4 10.6 cigarettes/day) were recruited, including 706 randomized to TTCM and 703 randomized to QL. Participants were comparable at baseline, including 216 Black participants (15.3%), 82 Hispanic participants (5.8%), and 1089 White participants (77.3%). At 1 and 3 months after discharge, more TTCM participants than QL participants used cessation counseling (1 month: 245 participants 34.7% vs 154 participants 21.9%; 3 months: 248 participants 35.1% vs 123 participants 17.5%; P < .001) and pharmacotherapy (1 month: 455 participants 64.4% vs 324 participants 46.1%; 3 months: 367 participants 52.0% vs 264 participants 37.6%; P < .001). More TTCM than QL participants reported continuous abstinence for 3 months (RR, 1.30; 95% CI, 1.06-1.58) and point-prevalence abstinence at 1 month (RR, 1.22; 95% CI, 1.08-1.35) and 3 months (RR, 1.23; 95% CI, 1.09-1.37) but not at 6 months (RR, 1.14; 95% CI, 0.99-1.29). The primary outcome, biochemically verified point-prevalence abstinence at 6 months, was not statistically significantly different between groups (19.9% vs 16.9%; RR, 1.18; 95% CI, 0.92-1.50). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, biochemically verified tobacco abstinence rates were not significantly different between groups at the 6-month follow-up. However, the health system–based model was superior to the community-based quitline model throughout the 3 months of active treatment. A longer duration of postdischarge treatment may sustain the superiority of the health system–based model. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03603496.
Fluoride (F)-releasing restoratives typically are either weak mechanically or release only low levels of F ions. The objectives of this study were to: (1) develop a novel photo-cured nanocomposite ...with strong mechanical properties and high levels of sustained F ion release via a two-step “co-precipitation + spray-drying” technique to synthesize CaF2 nanoparticles (nCaF2); and (2) investigate the effect of spray-drying treatment after co-precipitation of nCaF2 on mechanical properties and F ion release of composite.
Two types of CaF2 particles were synthesized: A co-precipitation method yielded CaF2cp; “co-precipitation + spray-drying” yielded nCaF2cpsd. Composites were fabricated with fillers of: (1) 0% CaF2 + 70% glass; (2) 10% CaF2cp + 60% glass; (3) 15% CaF2cp + 55% glass; (4) 20% CaF2cp + 50% glass; (5) 10% nCaF2cpsd + 60% glass; (6) 15% nCaF2cpsd + 55% glass; and (7) 20% nCaF2cpsd + 50% glass. A commercial F-releasing nanocomposite served as control.
The nCaF2cpsd had much smaller particle size (median = 32 nm) and narrower distribution (22–57 nm) than CaF2cp (median = 5.25 μm, 162 nm–67 μm). The composite containing nCaF2cpsd had greater flowability, flexural strength, elastic modulus and hardness than CaF2cp composite and commercial control composite. At 84-day immersion in water, the nanocomposites containing 20% nCaF2cpsd had 65 times higher cumulative F release, and 77 times greater long-term F-release rate, than commercial control.
A novel two-step “co-precipitation + spray-drying” technique of synthesizing nCaF2 was developed. The photo-cured nanocomposite containing 20% nCaF2cpsd possessed strong mechanical properties and excellent long-term F-release ability, and hence is promising for dental restoration applications to inhibit secondary caries.
Bonding Changes in Compressed Superhard Graphite Mao, Wendy L.; Mao, Ho-kwang; Eng, Peter J. ...
Science (American Association for the Advancement of Science),
10/2003, Letnik:
302, Številka:
5644
Journal Article
Recenzirano
Compressed under ambient temperature, graphite undergoes a transition at ~17 gigapascals. The near K-edge spectroscopy of carbon using synchrotron x-ray inelastic scattering reveals that half of the ...π-bonds between graphite layers convert to σ-bonds, whereas the other half remain as π-bonds in the high-pressure form. The x-ray diffraction pattern of the high-pressure form is consistent with a distorted graphite structure in which bridging carbon atoms between graphite layers pair and form σ-bonds, whereas the nonbridging carbon atoms remain unpaired with π-bonds. The high-pressure form is superhard, capable of indenting cubic-diamond single crystals.
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