•Hyaluronan nanoparticles (HA-DEX-DOX) for delivering dexamethasone and doxorubicin.•HA-DEX-DOX suppress thromboinflammation and platelet aggregation triggered by DOX.•HA-DEX-DOX polarize M2 ...macrophages to a pro-inflammatory M1 phenotype.•DEX could intensify or suppress cytotoxicity of DOX in human cancers.
Anti-inflammatory drugs such as dexamethasone (DEX) are commonly administered to cancer patients along with anticancer drugs, however, the effect of DEX on human cancers is poorly understood. In this article, we have tailored self-assembled nanoparticles derived from hyaluronic acid (HA) wherein, anti-inflammatory DEX was used as a hydrophobic moiety for inducing amphiphilicity. The HA-DEX micelles were subsequently loaded with chemotherapeutic agent, doxorubicin (DOX) (HA-DEX-DOX) and was utilized to deliver drug cargo to human cancer cells expressing different levels of CD44 receptors. We found that DEX suppressed the cytotoxicity of DOX in HCT116, while it synergistically enhanced cytotoxicity in MCF-7 cells. When we tested DOX and HA-DEX-DOX in an ex-vivo human whole blood, we found activation of complement and the coagulation cascade in one group of donors. Encapsulation of DOX within the nanoparticle core eliminated such deleterious side-effects. The HA-DEX-DOX also polarized bone-marrow-derived anti-inflammatory M2 macrophages, to pro-inflammatory M1 phenotype with the upregulation of the cytokines TNF-α, iNOS and IL-1β.
The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100
mg/kg bw, administered intraperitoneally 30
min prior to 9.5
Gy whole-body γ-irradiation was studied ...in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50
mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100
mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50
mg/kg bw) in mice irradiated with 15
Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50
mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM 50 and 100
mg/kg bw at all monitored post-irradiation intervals. There was no protection at a dose less than 25
mg/kg bw.
The smaller dimension devices and larger scales of integration are demanding constant reduction of the macroscopic and microscopic defects in the manufacturing of silicon integrated circuits. ...Increasing capital investment in manufacturing is forcing us toward processes and equipment that are effective not only in reduction of the cost of ownership but can also increase the effectiveness of equipment of current as well as future applications. Rapid thermal processing (RTP) based on incoherent light as the source of energy is playing an important role in the manufacturing of 300 nm and larger diameter wafers. The dominance of ultraviolet and vacuum ultraviolet photons in RTP results in rapid photothermal processing (RPP). The results presented in this paper show that the materials and devices processed by RPP are better than those processed by other thermal processes. This paper discusses the manufacturing science, operating principles of RPP and experimental results supporting its role in future process integration.
Abstract
Background
Vedolizumab (VDZ) is a monoclonal antibody designed to inhibit α4β7 integrin and result in gut-selective anti-inflammatory activity. Randomised control trials have shown VDZ to be ...safe and effective in treating patients with ulcerative colitis (UC). However, real-world data describing the outcome of VDZ therapy in routine clinical practice are limited. We aimed to evaluate the safety and efficacy of VDZ in routine clinical practice.
Methods
A multicentre, retrospective study across seven Irish academic hospitals in the INITIATIVE Network was conducted. N = 68 eligible UC patients were identified with n = 39 having at least 6 months of follow-up included in the final study cohort. Demographics and disease characteristics were collected at baseline, and 3 and 6 months following VDZ initiation. VDZ was administered as per standard protocol. Primary endpoints were 3-month clinical response and 6-month steroid-free remission. Clinical response was defined as a decrease from baseline in clinical Mayo subscore of ≥3 points, with ongoing receipt of VDZ. Clinical remission was defined as a clinical Mayo subscore of ≤1, the absence of corticosteroid use and continuing receipt of VDZ. Secondary endpoints were baseline variables associated with VDZ induction outcome and rates of adverse events.
Results
Thirty-nine patients were included in the final study cohort. Baseline characteristics included (median range): age 44 17–79; gender 58% male; 61% extensive and 39% left-sided colitis; median clinical Mayo subscore at initiation 6 2–9; CRP 8mg/l 0.8–85mg/l) and median albumin 37g/l (20–47g/l). At VDZ initiation proportions receiving 5-aminosalicylates; thiopurines and systemic corticosteroids were 67%, 48%, and 50%, respectively. 24%, 35%, and 41% had been exposed to no, 1 and 2 anti-TNF agents, respectively. Three-month clinical response and 6-month steroid-free clinical remission rates were 47% and 46% respectively. Comparing anti-TNF naïve and exposed individuals; 3 months response rates was similar (40% vs. 48% respectively, p = 0.73); however, there was a trend toward increased 6 months steroid-free remission rates (75% vs. 35%, respectively, p = 0.10). Regression analysis demonstrated no baseline clinical or biochemical variable to be associated with 3-month clinical response or 6-month steroid-free remission. The rate of adverse events was 6.1%, none requiring hospitalisation.
Conclusions
These data support the efficacy and safety of VDZ as an induction and maintenance agent in UC. Consistent with published literature the long-term outcome of VDZ therapy appears improved in anti-TNF naïve cohorts.
In this work, the roles of vacuum ultraviolet (VUV) photons in improving the gap fill properties of a low dielectric constant (K) material (Teflon amorphous fluoropolymer, K=1.93) deposited by direct ...liquid injection assisted rapid photothermal chemical vapor deposition technique are discussed. A qualitative explanation is presented wherein it is proposed that high-energy photons provide photoexcitation of the species involved in the deposition of Teflon AF/sup TM/, thereby lowering the activation energy and migrational enthalpy required for surface diffusion leading to a higher molecular mobility on the patterned surface.
We report evidence for the simultaneous production of J/ψ and Υ mesons in 8.1 fb$^{-1}$of data collected at $\sqrt{s}$ = 1.96 TeV by the D0 experiment at the Fermilab $p\bar{p}$ Tevatron Collider. ...Events with these characteristics are expected to be produced predominantly by gluon-gluon interactions. In this analysis, we extract the effective cross section characterizing the initial parton spatial distribution, σ$_{eff}$=2.2±0.7(stat)±0.9(syst) mb.
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