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排序方式: 共有2244条查询结果,搜索用时 15 毫秒
1.
Matteo Di Giosia Alice Soldà Markus Seeger Andrea Cantelli Fabio Arnesano Maria I. Nardella Vincenzo Mangini Francesco Valle Marco Montalti Francesco Zerbetto Stefania Rapino Matteo Calvaresi Vasilis Ntziachristos 《Advanced functional materials》2021,31(20):2101527
Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV-visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications. 相似文献
2.
Celia Nieto Milena A. Vega Eva M. Martín del Valle 《International journal of molecular sciences》2021,22(6)
Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe3+ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe3+ was adsorbed in PDA NPs at pH values close to which Fe(OH)3 begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe3+. Otherwise, it was demonstrated that Fe3+ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca2+ content, and that when Fe3+ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe3+ and doxorubicin may constitute a good approach to target breast tumors. 相似文献
3.
A case of traumatic extracranial vertebral arterial dissection leading to vertebrobasilar thrombosis and respiratory compromise requiring mechanical ventilation was managed with intraarterial thrombolysis and stenting of the vertebral intimal dissection. In contrast to similar, previously reported cases, this critically ill patient made a full recovery, returning to his job as a secondary school teacher. 相似文献
4.
Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes
R Hanecak V Brown-Driver MC Fox RF Azad S Furusako C Nozaki C Ford H Sasmor KP Anderson 《Canadian Metallurgical Quarterly》1996,70(8):5203-5212
Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV. 相似文献
5.
OL Lopez RP Brenner JT Becker RF Ulrich F Boller ST DeKosky 《Canadian Metallurgical Quarterly》1997,48(6):1521-1525
We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival. 相似文献
6.
G Armengol M Tarkkanen M Virolainen A Forus J Valle T B?hling S Asko-Seljavaara C Blomqvist I Elomaa E Karaharju AH Kivioja MA Siimes E Tukiainen MR Caballín O Myklebost S Knuutila 《Canadian Metallurgical Quarterly》1997,75(10):1403-1409
Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q. 相似文献
7.
TW Mittag A Tormay C Severin T Taniguchi PY Lee RF Wang SM Podos 《Canadian Metallurgical Quarterly》1993,34(3):606-612
PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics. 相似文献
8.
9.
RF Speck K Wehrly EJ Platt RE Atchison IF Charo D Kabat B Chesebro MA Goldsmith 《Canadian Metallurgical Quarterly》1997,71(9):7136-7139
The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo. 相似文献
10.
Cytomegalovirus (CMV) is the leading cause of congenital viral infection in the United States. To prevent damaging congenital CMV infections, it is necessary to have accurate population estimates of prevalence and to identify maternal factors associated with an elevated risk of congenital infection in the newborn. From 1980 through 1990, 17,163 offspring of predominantly low-income nonwhite women who delivered at a public hospital and 9892 newborns of predominantly mid- to upper-income white women who delivered at a private hospital were screened for congenital CMV infection. Women < 20 years old (adjusted prevalence odds ratio [POR], 4.8; 95% confidence interval [CI], 2.6-8.9) at the public hospital and all nonwhite women (adjusted POR, 1.6; 95% CI, 1.1-2.2) had an increased risk of delivering an infected newborn. Newborns of adolescent women in both populations had the highest prevalence of clinically apparent infection. Offspring of nonwhite low-income adolescents are at greatest risk for congenital CMV infection and more damaging sequelae. 相似文献