Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ‐tocopherol on N‐methyl‐N‐nitrosourea (MNU)‐induced epithelial dysplasia in the rat ventral prostate (VP). Thirty‐two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ‐tocopherol (CT+γT): healthy control animals without intervention fed a γ‐tocopherol‐enriched diet (20 mg/kg); N‐methyl‐N‐nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ‐tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ‐tocopherol‐enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase‐2 (Cox‐2), glutathione‐S‐transferase‐pi (GST‐pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase‐9 (MMP‐9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST‐pi and Cox‐2 immunoexpression and pro‐MMP‐9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ‐tocopherol‐enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST‐pi and Cox‐2 immunoexpression. The gelatinolytic activity of pro‐MMP‐9 returned to the levels observed for the CT group. These results suggest that γ‐tocopherol acts as a protective agent against MNU‐induced prostatic disorders in the rat ventral prostate. 相似文献
Poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) (poly(NIPAAm‐co‐NIPMAAm)) is synthesized as an attractive thermo‐responsive copolymer by an original procedure. Due to the similar structure of the two co‐monomers, the poly(NIPAAm‐co‐NIPMAAm) copolymer displays a very sharp phase transition, under physiological conditions (phosphate buffer solution at pH = 7.4). The copolymer, showing the 51/49 co‐monomer NIPAAm/NIPMAAm molar ratio, displays a lower critical solution temperature (LCST) close to that of the human body temperature (36.8 °C). The poly(NIPAAm‐co‐NIPMAAm) microgels obtained at the 51:49 co‐monomer ratio displays a volume phase transition temperature (VPTT) slightly smaller than LCST. The deswelling rate of the microgels is very high (k = 0.019 s?1), the shrinkage occurring almost instantaneously, whereas the swelling rate is slightly lower (k = 0.0077 s?1). The microgels are loaded with the model drug dexamethasone and the drug release is investigated at different temperatures, below and above the VPTT. Under thermal cycling operation between 32 and 38 °C, the pulsatile release of dexamethasone is observed.
N‐vinylcaprolactam (NVCL) is modified via alkylation at the α‐position. The α‐substituents are ethyl (3‐ethyl‐1‐vinylcaprolactam), dodecyl (3‐dodecyl‐1‐vinylcaprolactam), octadecyl (3‐octadecyl‐1‐vinylcaprolactam), 1‐propanol (3‐(3‐hydroxy‐propyl)‐1‐vinylcaprolactam), and PEG3 bromide (3‐PEG3‐bromide‐1‐vinylcaprolactam). These monomers are homo‐ and copolymerized with N‐(4‐methylphenyl)maleimide by the free radical mechanism. The structures of the obtained polymers are characterized by means of 1H NMR and IR spectroscopy, gel permeation chromatography (GPC), and by use of differential scanning calorimetry (DSC) (Tg).
A series of polymerizations of 3,6‐dibromo‐9‐(2‐ethylhexyl)carbazole was carried out in different monomer concentrations using standard Yamamoto reaction conditions. It was found that the molecular weight of the resulting poly(N‐(2‐ethylhexyl)carbazol‐3,6‐diyl) strongly depends on the monomer concentration in the reaction mixture. Matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) measurements confirmed the formation of low‐molar‐mass cyclic oligomers of the 3,6‐disubstituted carbazole. In this paper we describe, for the first time, the formation of large amounts of a cyclic tetramer and of higher macrocycles in the synthesis of poly(N‐alkyl‐3,6‐carbazoles) by the Yamamoto method. This seems to be a limiting factor in the synthesis of high molecular weight poly(N‐alkyl‐3,6‐carbazole)s. The optical, thermal, and electrochemical properties of poly(N‐(2‐ethylhexyl)carbazol‐3,6‐diyl) have been investigated. Poly(N‐(2‐ethylhexyl)carbazol‐3,6‐diyl) is thermally stable, with 5% weight loss at 460 °C in nitrogen. The polymer exhibits a weak blue fluorescence with a maximum at 425 nm. Poly(N‐(2‐ethylhexyl)carbazol‐3,6‐diyl) is electrochemically stable, its highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels are ?5.0 and ?1.6 eV, respectively.
A kind of γ‐(cyclodextrin) (γ‐CD)‐based polyrotaxane (PR) is synthesized via an aqueous click reaction between propargylamine‐substituted β‐CD and polypseudorotaxanes (PPRs) self‐assembled from azido‐endcapped PNIPAAm‐b‐Pluronic F68‐b‐PNIPAAm with a varying amount of γ‐CD. The evolution of the self assembly, dependent on the preparation process, is observable by X‐ray diffraction (XRD) and DSC analyses. The γ‐CD is able to be included and preferably entrapped on the PNIPAAm blocks, showing a unique loose‐fit aggregate structure after the click reaction. Most γ‐CDs gradually slip over to the middle PPG block of Pluronic F68, giving rise to a characteristic channel‐type crystal structure in the dialysis process. In addition, the lower critical solution temperature (LCST) is sharply enhanced due to the coverage of the remaining γ‐CDs hindering the thermally responsive aggregation of the PNIPAAm blocks.
Summary: Hydrogels of NIPA and MBDA were synthesized by free‐radical crosslinking copolymerization with different monomer ratios and with two concentrations of the crosslinking agent. The aim of this work was to study the swelling behavior of these gels that are both temperature and pH sensitive. PNIPA hydrogels are typical examples of thermo‐shrinking hydrogels with a LCST, TC, around 31–34 °C. MBDA is a weakly ionizable monomer which imparts a pH sensitiveness to the copolymer hydrogels. The pH influence on the swelling behavior of the studied hydrogels was analyzed using deionized water and aqueous HCl and NaOH as swelling media. According to the results found in deionized water, the swelling processes of P(NIPA‐MBDA) hydrogels follow second‐order kinetics at 22 and 37 °C. The equilibrium water content, W∞, and the rate constant, K, increased at greater concentrations of MBDA and decreased as the crosslinking agent concentration increased. As the MBDA content in the hydrogel increased, the collapsing of the hydrogels at higher temperatures than the LCST became of less importance. The degree of swelling of pure PNIPA hydrogels was not influenced by the pH of the swelling medium. However, this influence increased as the MBDA content increased. This was due to the fact that at low pH most of the MBDA units are in the protonated (neutral) form and at high pH in the ionized one.
Swelling isotherms of hydrogels with different copolymer compositions and with 1.5 wt.‐% of BIS at 22 °C in deionized water. 相似文献
The c‐Jun N‐terminal kinase (JNK) signalling pathway appears to act as a critical intermediate in the regulation of lymphocyte activation and proliferation. The majority of studies on the importance of JNK are focused on its role in T helper responses, with very few reports addressing the mechanisms of JNK in governing CD8 T‐cell‐mediated immunity. By using a well‐defined mousepox model, we demonstrate that JNK is involved in CD8+ T‐cell‐mediated antiviral responses. Deficiency of either JNK1 or JNK2 impaired viral clearance, subsequently resulting in an increased susceptibility to ectromelia virus in resistant mice. The impairment of CD8 responses in JNK‐deficient mice was not directly due to an inhibition of effector T‐cell expansion, as both JNK1 and JNK2 had limited effect on the activation‐induced cell death of CD8+ T cells, and only JNK2‐deficient mice exhibited a significant change in CD8+ T‐cell proliferation after acute ectromelia virus infection. However, optimal activation of CD8+ T cells and their effector functions require signals from both JNK1 and JNK2. Our results suggest that the JNK pathway acts as a critical intermediate in antiviral immunity through regulation of the activation and effector function of CD8+ T cells rather than by altering their expansion. 相似文献
Stimuli‐responsive polymers in response to both low temperature and pH are of great potential for designing drug carriers to obtain a better therapeutic effect during cryotherapy of tumors. In this work, novel low‐temperature and pH dual‐responsive poly(N‐isopropylacrylamide‐co‐1H‐benzimidazolyl‐ethyl acrylate) (PNBM) linear copolymers are developed, which can undergo stretching/shrinking conformational transition at low temperature and mildly acidic conditions. The dual‐responsive properties of PNBM copolymers can be affected and regulated by the host–guest inclusion action between benzimidazole and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) molecules. The critical response temperature of the copolymers can be flexibly adjusted when the benzimidazole groups in copolymer chains are captured by HP‐β‐CD. And the PNBM copolymers present a pH‐responsive stretching‐to‐shrinking‐to‐stretching conformational transition in a narrow pH range in HP‐β‐CD solution. The results provide valuable guidance for designing and applying PNBM‐based smart materials in biomedical applications. 相似文献
Summary: Benzylamine, hexylamine and aniline‐initiated polymerizations of D ,L ‐phenylalanine and L ‐phenylalanine N‐carboxyanhydride (D ,L ‐Phe‐NCA and L ‐Phe‐NCA) were performed in various solvents. The isolated polypeptides were characterized by MALDI‐TOF mass spectroscopy. Exclusively linear polypeptides having one amide and one amino endgroup were found, when the polymerizations were conducted in a closed reaction vessel with dioxane or sulfolane as reaction media. Traces of water competed with aniline as initiator, when the reaction vessel was closed with a drying tube. In N,N‐dimethylformamide (DMF) formyl endgroups were formed at polymerization temperatures of 60 °C. In DMF and N‐methylpyrrolidone, cyclic oligo‐ and polypeptides were formed by a solvent‐induced polymerization initiated by zwitterions, which may compete with the primary amine‐initiated polymerizations.
MALDI‐TOF mass spectrum of a poly(D ,L ‐phenylalanine) polymerized in NMP without addition of an initiator. 相似文献
According to recent models on visual attention, both the salience of signals (bottom‐up) and the intention to search for particular stimuli (top‐down) are determinants for attentional selection. We investigated these mechanisms by varying the top‐down set of participants that had to detect either luminance or orientation changes of two symmetrically located bars. Irrelevant changes impaired target detection when they were presented spatially separated to the relevant change. Initial attentional selection was represented in posterior N1 asymmetries and was determined by both the relative salience of orientation changes and a subsequent intentional bias towards relevant stimuli. Only when salient orientation changes interfered with luminance target selection in the N1 time window did an N2pc occur. Thus, the selection of relevant information proceeds in a network whose activation is induced by a dynamic interplay of bottom‐up and top‐down processes. 相似文献
Randomly methylated β‐cyclodextrin (me‐β‐CD) is used to include the hydrophobic monomer N‐(4‐methylphenyl)maleimide (MPM) ( 1 ) yielding the corresponding water‐soluble host‐guest structure 1a . Free‐radical copolymerization of 1a with N‐vinylpyrrolidone (NVP) ( 2 ) is performed and the reactivity ratios r1 and r2 are determined: 0.24 ± 0.03 (r2) and 1.10 ± 0.05 (r1a). This indicates a preferred incorporation of complexed maleimide into the copolymer chain. In contrast to that, the copolymerization of the uncomplexed monomers 1 and 2 is carried out using organic solvent (DMF/H2O) showing reactivity ratios corresponding to nearly alternating copolymerization (r2 = 0.09 ± 0.02; r1 = 0.34 ± 0.03).
Molecular‐recognition‐responsive characteristics of a novel poly(N‐isopropylacrylamide‐co‐benzo‐12‐crown‐4‐acrylamide) (PNB12C4) hydrogel have been investigated. In the prepared PNB12C4 hydrogel, benzo‐12‐crown‐4 (B12C4) groups act as guest molecules and γ‐cyclodextrin (γ‐CD)‐receptors, and poly(N‐isopropylacrylamide) (PNIPAM) networks act as phase‐transition actuators. The formation of stable γ‐CD/B12C4 complexes enhances the hydrophilicity of the PNB12C4 hydrogel networks, and induces positive shift of the volume phase transition temperature (VPTT) of PNB12C4 hydrogel. Moreover, the PNB12C4 hydrogel also shows thermoresponsive adsorption property selectively towards γ‐CD. The γ‐CD‐recognition sensitivity of PNB12C4 hydrogel can be dramatically improved by increasing γ‐CD concentration in solution or B12C4 content in PNB12C4 copolymer networks. The results in this study provide valuable information for developing crown ether‐based smart materials in various applications.
Four poly(N,N‐dimethylacrylamide)‐block‐poly(L ‐lysine) (PDMAM‐block‐PLL) hybrid diblock copolymers and two PLL homo‐polypeptides are prepared via ROP of ε‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride initiated by primary amino‐terminated PDMAM and n‐hexylamine respectively. The PLL blocks render the copolymers a multi‐responsive behavior in aqueous solution due to their conformational transitions from random coil to α‐helix with increasing pH, and from α‐helix to β‐sheet upon heating. The random coil‐to‐α‐helix transition is found to depend on the PLL length: the longer the peptide segment, the more readily the transition occurred. The same trend was observed for the α‐helix‐to‐β‐sheet transition, which was found to be inhibited for short polypeptides unless conjugated with the PDMAM block.
Functionalized temperature‐ and pH‐sensitive poly(N‐vinyl‐2‐caprolactam) (PVCL) polymers are prepared by copolymerizing monomers of N‐vinyl‐2‐caprolactam (VCL) and a VCL derivative, 3‐(tert‐butoxycarbonyl)‐N‐vinyl‐2‐caprolactam (TBVCL). Different molar compositions are studied, with the functional monomer at 9 and 14 mol%, respectively, (COOH‐PVCL9 and COOH‐PVCL14). Sharp, complete, and reversible phase transitions of the copolymers with little hysteresis are shown to be pH‐dependent, with cloud points ranging from 35 to 44 °C for COOH‐PVCL9, and 29 to 64 °C for COOH‐PVCL14, upon pH change from 2.0 to 7.4. Cytotoxicity assay demonstrates that the functionalized PVCL copolymers are biocompatible with NIH/3T3 up to 2 mg mL?1. Such new PVCL‐based water soluble copolymers with tunable properties could be useful in a variety of biomedical applications. 相似文献
Ring‐opening metathesis polymerization (ROMP) of N‐(1‐adamantyl)‐exo‐norbornene‐5,6‐dicarboximide (AdNDI) ( 3a ) and N‐cyclohexyl‐exo‐norbornene‐5,6‐dicarboximide (ChNDI) ( 3b ) was performed using well‐defined vinylidene ruthenium (II) catalysts Cl2(PR3)2RuCCH(t‐Bu) (R = Ph and Cy). The homopolymer of 3a showed a Tg of 271 °C while poly‐ChNDI of 3b had a Tg of 129 °C. Copolymers of these monomers with norbornene (NB) demonstrated significant Tg increases compared to unsubstituted poly‐NB. Analysis of copolymers of 3a and NB isolated at the initial stages of copolymerization showed that both monomers were incorporated randomly and displayed very similar reactivity.