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排序方式: 共有897条查询结果,搜索用时 312 毫秒
191.
《Contact lens & anterior eye》2019,42(3):253-257
Lactoferrin (LF), an iron-binding protein with antioxidant activity, is significantly reduced in the lacrimal film of patients affected by keratoconus (KC) compared to healthy subjects, and this is supposed to be the cause for tear iron increase and consequent iron deposition and oxygen free radical accumulation in the cornea. We decided to study if LF-loaded contact lenses (LF-CLs) could exert antioxidant activity on epithelial cells incubated in tears collected from two patients affected by keratoconus (KC1 and KC2). Moreover through this model we indirectly estimated iron concentration in the tears of healthy and KC subjects.Reflex tears were collected during the first 2 min of light or onion-induced lacrimation and stored at −20 °C. After incubation in tears for 18 h, mortality of epithelial cells was investigated by trypan blue exclusion test. Successively, LF-CLs were deposed on cells incubated in KC1 tears. For the indirect determination of iron content, cells were incubated with LF 1.2 mg/mL and different FeSO4 concentrations, and for the estimation of iron from the patient’s tears, cells were incubated with free serum medium and healthy tears (1:1) and different FeSO4 concentrations.Epithelial cells incubated with reflex tears of KC patients showed increased mortality (27.7 ± 3.9%, p = 0.0003, for KC1 and 17.6 ± 0.95%, p = 0.014, for KC2) compared to epithelial cells maintained in control healthy tears (8.6 ± 1.2%). This difference in mortality was correlated with tear iron concentration, which was estimated at 4.58 μg/mL for the healthy subjects, at 56.28 μg/mL for KC1, and at 8.7 μg/mL for KC2 patient. Application of LF-CLs counteracted KC tear cytotoxicity restoring viability obtained in the presence of control tears.Therapeutic contact lenses obtained by LF loading can reduce oxidative stress induced by patients’ tears and might represent an efficient device to arrest the progression of keratoconus. 相似文献
192.
Yanhui Xu Prof. Wen Shi Hongyu Li Prof. Xiaohua Li Prof. Huimin Ma 《ChemMedChem》2019,14(11):1079-1085
Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane-borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol-containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si-Dox@HA nanoparticles with the ability to target CD44-overexpressing cancer cells. The Si-Dox@HA nanoparticles exhibited H2O2-responsive release of about 80 % Dox and displayed seven-fold selectivity for killing cancer cells over normal cells, relative to Dox and Si-Dox nanoparticles. Moreover, these Si-Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44-overexpressing cancer cells. 相似文献
193.
Adhan Pilon Prof. Julia Lorenzo Sergi Rodriguez-Calado Dr. Pedro Adão Prof. Ana M. Martins Dr. Andreia Valente Dr. Luis G. Alves 《ChemMedChem》2019,14(7):770-778
New cyclam derivatives (HOCH2CH2CH2)2(PhCH2)2Cyclam and (HOCH2CH2CH2)2( PhCH2)2Cyclam, as well as their CuII and FeIII complexes, were synthesized and characterized and their stability in cellular media was assessed. The cytotoxic effect of all compounds was examined on human cervical cancer (HeLa) cells, revealing strong anticancer activity. After 24 h, only complexes with the (HOCH2CH2CH2)2( PhCH2)2Cyclam ligand are cytotoxic, whereas after incubation for 72 h all compounds show significant antiproliferative effects. Notably, compounds containing PhCH2 pendant arms on the cyclam ring revealed the most activity, with cytotoxicity values up to 12 times higher than those of cisplatin. All metal complexes seem to induce cell death through the formation of reactive oxygen species. 相似文献
194.
Dr. Satoshi Mizuta Mohammed S. O. Tagod Dr. Masashi Iwasaki Prof. Yoichi Nakamura Dr. Hiroaki Senju Prof. Hiroshi Mukae Prof. Craig T. Morita Prof. Yoshimasa Tanaka 《ChemMedChem》2019,14(4):462-468
Immune checkpoint blockade using anti-PD-1/PD-L1 or anti-CTLA-4 monoclonal antibodies (mAbs) has revolutionized cancer treatment. However, many types of cancer do not respond and for those that do, only a minority of patients achieve durable remissions. Therefore, oncoimmunologists are working to develop adoptive cell therapies for non-hematopoietic tumors by harnessing immune effector cells such as αβ T cells and γδ T cells. In contrast to conventional αβ T cells that recognize peptides in the context of MHC class I or II molecules, γδ T cells expressing Vγ2Vδ2 T cell receptors (also termed Vγ9Vδ2) are stimulated by isoprenoid metabolites (phosphoantigens) such as isopentenyl diphosphate in a butyrophilin-3A1-dependent manner. Vγ2Vδ2 T cells kill almost all types of tumor cells that have been treated with bisphosphonates. In this study, we synthesized a series of fluorine-containing bisphosphonates based on current drugs and found that they stimulated Vγ2Vδ2 T cell killing of tumor cells. A fluorine-containing prodrug analogue of zoledronate where phosphonate moieties were masked with pivaloyloxymethyl groups markedly enhanced Vγ2Vδ2 T-cell-mediated cytotoxicity, and also promoted the expansion of peripheral blood Vγ2Vδ2 T cells. These results demonstrate that a prodrug of a fluorine-containing zoledronate analogue can sensitize tumor cells for killing as well as expand Vγ2Vδ2 T cells for adoptive cell therapy. 相似文献
195.
Micha Abendrot Elbieta Puciennik Aleksandra Felczak Katarzyna Zawadzka Ewelina Pitczak Piotr Nowaczyk Urszula Kalinowska-Lis 《International journal of molecular sciences》2021,22(4)
Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc–amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability. 相似文献
196.
Marcin Cielak Mariola Napirkowska Julia Ka
mierczak-Baraska Karolina Krlewska-Goliska Anna Hawry Iwona Wybraska Barbara Nawrot 《International journal of molecular sciences》2021,22(9)
Based on previously identified dicarboximides with significant anticancer and immunomodulatory activities, a series of 26 new derivatives were designed and synthesized by the Diels–Alder reaction between appropriate diene and maleimide or hydroxymaleimide moieties. The resulting imides were functionalized with alkanolamine or alkylamine side chains and subsequently converted to their hydrochlorides. The structures of the obtained compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was evaluated in human leukemia (K562, MOLT4), cervical cancer (HeLa), and normal endothelial cells (HUVEC). The majority of derivatives exhibited high to moderate cytotoxicity and induced apoptosis in K562 cells. Microarray gene profiling demonstrated upregulation of proapoptotic genes involved in receptor-mediated and mitochondrial cell death pathways as well as antiapoptotic genes involved in NF-kB signaling. Selected dicarboximides activated JNK and p38 kinases in leukemia cells, suggesting that MAPKs may be involved in the regulation of apoptosis. The tested dicarboximides bind to DNA as assessed by a plasmid DNA cleavage protection assay. The selected dicarboximides offer new scaffolds for further development as anticancer drugs. 相似文献
197.
Chang-Youh Tsai Song-Chou Hsieh Chih-Wei Liu Cheng-Shiun Lu Cheng-Han Wu Hsien-Tzung Liao Ming-Han Chen Ko-Jen Li Chieh-Yu Shen Yu-Min Kuo Chia-Li Yu 《International journal of molecular sciences》2021,22(6)
Polymorphonuclear neutrophils (PMNs) are traditionally regarded as professional phagocytic and acute inflammatory cells that engulf the microbial pathogens. However, accumulating data have suggested that PMNs are multi-potential cells exhibiting many important biological functions in addition to phagocytosis. These newly found novel activities of PMN include production of different kinds of cytokines/chemokines/growth factors, release of neutrophil extracellular traps (NET)/ectosomes/exosomes and trogocytosis (membrane exchange) with neighboring cells for modulating innate, and adaptive immune responses. Besides, PMNs exhibit potential heterogeneity and plasticity in involving antibody-dependent cellular cytotoxicity (ADCC), cancer immunity, autoimmunity, inflammatory rheumatic diseases, and cardiovascular diseases. Interestingly, PMNs may also play a role in ameliorating inflammatory reaction and wound healing by a subset of PMN myeloid-derived suppressor cells (PMN-MDSC). Furthermore, PMNs can interact with other non-immune cells including platelets, epithelial and endothelial cells to link hemostasis, mucosal inflammation, and atherogenesis. The release of low-density granulocytes (LDG) from bone marrow initiates systemic autoimmune reaction in systemic lupus erythematosus (SLE). In clinical application, identification of certain PMN phenotypes may become prognostic factors for severe traumatic patients. In the present review, we will discuss these newly discovered biological and pathobiological functions of the PMNs. 相似文献
198.
199.
Orapa Suwannapan Kwanruedee Wachirattanapongmetee Supawan Thawornchinsombut Somporn Katekaew 《International Journal of Food Science & Technology》2020,55(6):2441-2450
Rice bran protein hydrolysate (<50 kDa RBPH) from Thai jasmine variety demonstrating a high Angiotensin I converting enzyme (ACE) inhibitory activity was purified and characterised. ACE inhibitory peptides were obtained from a two-step purification process: gel filtration and preparative reverse-phase high-performance chromatography (RP-HPLC) and then identified by mass spectrometer hybrid quadrupole-time-of-flight. A novel peptide GSGYF in the RBPH was firstly identified and found to have a partial sequence homology of Oryza sativa Japonica Group. This sequence was further synthesised to exhibit as good an inhibition potency with IC50 value of 2.11 µg mL−1 as Captopril (1.15 µg mL−1). The cytotoxicity test revealed that this RBPH is non-toxic against Vero cells. In addition, the <50 kDa RBPH was resistant to in vitro digestion by pepsin and trypsin. These findings suggest that the RBPH containing ACE inhibitory peptides is likely to be safer and healthier than synthetic drugs and can be an effective food supplement for lowering blood pressure. 相似文献
200.