The Unusual Mechanical Evolution of Biodegradable Double Hydrogen Bonding Strengthened Hydrogels in Response to pH Change

Conventionally, biodegradable hydrogels end up with quick disintegration and consequently fail to bear external loading after degradation. Here, a biocleavable high‐strength hydrogel prepared by copolymerization of 2‐vinyl‐4,6‐diamino‐1,3,5‐triazine (alkali active H‐bonding monomer), 3‐acrylamidophenylboronic acid (acid active H‐bonding monomer), oligo(ethylene glycol) methacrylate, and crosslinker N,N′‐bis(acryloyl)cystamine is reported. The hydrogel is shown to be degraded after the disulfide bonds in the chemical crosslinkers are broken down in a reducible medium. Remarkably, the degraded hydrogel evolves into supramolecular network, which is strengthened by diaminotriazine–diaminotriazine and phenylboronic acid–phenylboronic acid dual H‐bonded physical crosslinks despite the loss of chemical crosslinking. It is demonstrated that over a broad pH range, the degraded hydrogels are able to retain macroscopic integrity and withstand high external loading due to the existence of at least one kind of hydrogen bonding crosslinking. This biodegradable double hydrogen bonding strengthened hydrogel may push forward the research on a new type of high‐strength hydrogels.

     

Hydrogen‐Bonding Effects for the C–ON Bond Homolysis and Reformation Reactions of Alkoxyamines

N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐O‐(2‐carboxyprop‐2‐yl) hydroxylamine (BlocBuilder MA) is, among the commercially available alkoxyamines, one of the most efficient for nitroxide‐mediated polymerization (NMP). However, recent results have shown that it does not perform well for the NMP of isoprene. The occurrence of intramolecular hydrogen bonding (IHB) between the carboxylic function and the diethoxyphosphoryl group has been proposed as the reason for its low efficiency. In this article, the presence of this IHB is confirmed using IR, ³¹P NMR, ³¹P‐¹H HOESY, and DFT calculation results. The solvent effect on this IHB and consequently on k_d values is also investigated. However, combining kinetic analysis and rate measurements in various solvents, the influence of this IHB on the C? ON bond homolysis and reformation in alkoxyamine is shown to be very weak.

     

Adriamycin stimulates proliferation of human lymphoblastic leukaemic cells via a mechanism of hydrogen peroxide (H2O2) production

It is becoming clear that adriamycin cytotoxicity may be mediated by semiquinone-free radicals derived from the drug itself and reactive oxygen species (ROS). Recent evidence supports the concept that low concentrations of ROS are able to stimulate cell proliferation, and, based on the observation that subtoxic concentrations of adriamycin can also induce cell proliferation, we hypothesize that low concentrations of adriamycin stimulate cell proliferation by a ROS generation mechanism. We have employed spin-trapping and electron spin resonance (ESR) spectroscopy to investigate the nature of the adriamycin-generated ROS. The spin trap 3,5-dibromo-4-nitrosobenzenesulphonate (DBNBS), which is oxidized in the presence of H₂O₂ and peroxidase enzymes, was used to produce a characteristic three-line spectrum, and it was found that an identical spectrum was produced by human lymphoblastic leukaemic cells (CCRF-CEM cells) after exposure to adriamycin. We tested our hypothesis further by exposing CCRF-CEM cells to subtoxic concentrations of adriamycin (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and low concentrations of H₂O₂ (10⁻⁸, 10⁻⁹ and 10⁻¹⁰  M ) and subsequently monitored cell proliferation. We found that low concentrations of both adriamycin and H₂O₂ significantly stimulate CCRF-CEM cell proliferation. We therefore conclude that subtoxic concentrations of adriamycin are likely to induce cell proliferation via an H₂O₂ mediated mechanism.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

枸杞黄酮对H2O2损伤的血管内皮细胞NO及NOS作用的研究

目的：研究枸杞黄酮对过氧化氢(H 2 O2)损伤的血管内皮细胞一氧化氮(NO)及一氧化氮合酶(NOS)作用。方法以人脐静脉内皮细胞(HUVEC)为研究对象,建立 H 2 O2诱导 HUVEC 的氧化损伤模型。实验分为正常对照组、H 2 O2组、维生素C(VitC)组、枸杞黄酮低、中、高浓度组(枸杞黄酮100 mg/L、200 mg/L 和400 mg/L 预处理)。用 MTT 法观察枸杞黄酮对 H 2 O2损伤的血管内皮细胞活性的影响,观察枸杞黄酮类化合物对氧化应激损伤细胞过氧化物丙二醛(MDA)、人总一氧化氮合成酶(TNOS)、诱导型一氧化氮合成酶(iNOS)、及 NO 的作用。结果(1)MTT 结果表明 H 2 O2损伤后内皮细胞生长抑制率(IR)为38.8%;枸杞黄酮低、中、高浓度组 IR 分别为34.0%、30.7%、25.5%,与 H 2 O2组比较差异有统计学意义(P <0.01);(2)与正常对照组相比较,H 2 O2组细胞 NO 活性降低,而 TNOS、iNOS、MDA 生成增加。与 H 2 O2组相比较,枸杞黄酮低、中、高浓度组中NO、TNOS、iNOS、MDA 的变化则相反,与枸杞黄酮呈剂量依赖性(P <0.01)。结论枸杞黄酮对 H 2 O2所致人血管内皮细胞损伤有保护作用,且保护效果与枸杞黄酮呈一定相关性。     

在非水介质中用表面引发接枝聚合法制备接枝微粒PHEMA-SiO2及其对槲皮素的氢键吸附性能

首先,将偶联剂γ-巯丙基三甲氧基硅烷(MPMS)上的巯基(-SH)键合在微米级硅胶(SiO₂)微粒表面,得到了改性微粒MPMS-SiO₂。在非水溶剂N,N-二甲基甲酰胺(DMF)中,使溶液中的过氧化苯甲酰(BPO)与改性微粒MPMS-SiO₂表面的巯基构成表面引发体系(-SH/BPO),于非水介质中在硅胶微粒表面实现了甲基丙烯酸羟乙酯(HEMA)的接枝聚合,成功制备出接枝微粒PHEMA-SiO₂,接枝度高达28 g/100 g。采用红外光谱(FT-IR)、热重分析(TG)及扫描电子显微镜(SEM)等手段对PHEMA-SiO₂进行了表征,研究了主要因素对HEMA表面引发接枝聚合的影响规律。在此基础上探索研究了PHEMA-SiO₂对槲皮素(Quercetin)的氢键吸附作用。研究结果表明:-SH/BPO引发体系可以顺利地引发HEMA在非水介质中的接枝聚合,适宜的温度为65℃,适宜的BPO用量为单体质量的1.0%。PHEMA-SiO₂与槲皮素分子之间会产生多位点普通氢键与π型氢键两种氢键相互作用,使PHEMA-SiO₂对槲皮素具有强吸附能力。溶剂分子对槲皮素的竞争吸附以及温度的升高均可使槲皮素在极性溶剂或质子性溶剂中吸附容量下降。     

Protective Effect of Total Phenolic Compounds from Inula helenium on Hydrogen Peroxide-induced Oxidative Stress in SH-SY5Y Cells

Inula helenium has been reported to contain a large amount of phenolic compounds, which have shown promise in scavenging free radicals and prevention of neurodegenerative diseases. This study is to investigate the neuroprotective effects of total phenolic compounds from I. helenium on hydrogen peroxide-induced oxidative damage in human SH-SY5Y cells. Antioxidant capacity of total phenolic compounds was determined by radical scavenging activity, the level of intracellular reactive oxygen species and superoxide dismutase activity. The cytotoxicity of total phenolic compounds was determined using a cell counting kit-8 assay. The effect of total phenolic compounds on cell apoptosis due to hydrogen peroxide-induced oxidative damage was detected by Hoechst 33258 and Annexin-V/PI staining using fluorescence microscope and flow cytometry, respectively. Mitochondrial function was evaluated using the mitochondrial membrane potential and mitochondrial ATP synthesis by JC-1 dye and high performance liquid chromatography, respectively. It was shown that hydrogen peroxide significantly induced the loss of cell viability, increment of apoptosis, formation of reactive oxygen species, reduction of superoxide dismutase activity, decrease in mitochondrial membrane potential and a decrease in adenosine triphosphate production. On the other hand, total phenolic compounds dose-dependently reversed these effects. This study suggests that total phenolic compounds exert neuroprotective effects against hydrogen peroxide-induced oxidative damage via blocking reactive oxygen species production and improving mitochondrial function. The potential of total phenolic compounds and its neuroprotective mechanisms in attenuating hydrogen peroxide-induced oxidative stress-related cytotoxicity is worth further exploration.     

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells

Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH₂Cl₂) were investigated against cytotoxic and genotoxic effects of H₂O₂ in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15–250?μg ml^?1), defatted fraction (15–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and toxic concentration of H₂O₂ (200?µM) at 37?°C for 2?h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25–250?μg ml^?1), defatted fraction (25–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and H₂O₂ (25?µM) at 4?°C for 20?min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC₅₀ values of TME, defatted fraction and CH₂Cl₂ fraction against DNA damage were determined as 48, 138 and 8?μg ml^?1, respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.     

Site selective syntheses of [3H]omeprazole using hydrogen isotope exchange chemistry

Omeprazole (Prilosec®) is a selective and irreversible proton pump inhibitor used to treat various medical conditions related to the production of excess stomach acids. It functions by suppressing secretion of those acids. Radiolabeled compounds are commonly employed in the drug discovery and development process to support efforts including library screening, target identification, receptor binding, assay development and validation and safety assessment. Herein, we describe synthetic approaches to the controlled and selective labeling of omeprazole with tritium via hydrogen isotope exchange chemistry. The chemistry may also be used to prepare tritium labeled esomeprazole (Nexium®), the active pure (S)‐enantiomer of omeprazole.