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71.
Sara Silva Kaido Kurrikoff Ülo Langel Antnio J. Almeida Nuno Vale 《International journal of molecular sciences》2022,23(15)
Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. 相似文献
72.
73.
Joo C. C. Ferreira Sara Granja Ana F. Almeida Ftima Baltazar M. Sameiro T. Gonalves Ana Preto Maria Joo Sousa 《International journal of molecular sciences》2023,24(1)
Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC. 相似文献
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Ferracin LM Fier CB Vieira ML Monteiro-Vitorello CB Varani Ade M Rossi MM Müller-Santos M Taniwaki MH Thie Iamanaka B Fungaro MH 《International journal of food microbiology》2012,155(3):137-145
In silico comparison of 34 putative pks genes in Aspergillus niger strain CBS 513.88 versus A. niger strain ATCC 1015 genome revealed significant nucleotide identity (>95% covering a minimum of 99% of the gene sequence) for 31 of these genes (approximately 91%). A. niger CBS 513.88 harbors three putative pks genes (An01g01130, An11g05940, and An15g07920), for which nucleotide identity was not found in A. niger ATCC 1015. To compare the results of the in silico analysis with the in vivo situation, experimental data were obtained for a large number of A. niger strains obtained from different substrates and geographical regions. Three putative pks genes that were found to be variable between the two A. niger strains using bioinformatics tools were in fact strain-specific genes based on experimental data. The PCR amplification signals for the An01g01130, An11g05940, and An15g07920 pks genes were detected in only 97%, 71%, and 26% of the strains, respectively. Southern blot analyses confirmed the PCR data. Because one of the strain-specific pks genes (An15g07920) is located in a putative ochratoxin cluster, we focused our investigation on that region. We assessed the ochratoxin production capability of the 119 A. niger strains and found a positive association between the presence of this pks gene and the capability of the respective strain to produce ochratoxin. 相似文献
76.
Ana I.R.N.A. Barros Fernando M. Nunes Berta Gonçalves Richard N. Bennett Ana Paula Silva 《Food chemistry》2011
In this work the total vitamin C contents (ascorbic acid + dehydroascorbic acid) and antioxidant activity of raw and cooked chestnuts was evaluated. The vitamin C contents of raw chestnuts varied significantly between the different cultivars (cv) studied and it varied from 400 mg/kg dry weight (cv Lada) to 693 mg/kg dry weight (cv Martaínha). The different cultivars behave differently during the cooking process concerning the loss of vitamin C. A significant decrease in the vitamin C content of the chestnuts was observed, 25–54% for the boiling process and 2–77% for the roasting process. Boiled and roasted chestnuts can be good sources of vitamin C since it may represent 22.4%, 16.2%, 26.8% and 19.4%, respectively, of the recommended dietary intake for an adult man and woman. The cooking process significantly changed the antioxidant activity of the chestnuts. A difference was observed between the cultivars during the cooking processes, concerning the antioxidant activity. For the raw chestnuts the variation in vitamin C content of the chestnuts explains 99% of the antioxidant activity variation but for the roasted and boiled chestnuts this percentage significantly decreases to 51% and 88%, respectively. Although a high antioxidant activity is still present in the cooked chestnuts, the cause for this antioxidant activity is less dependent on the vitamin C content of the chestnuts, probably due to the conversion of ascorbic acid to dehydroascorbic acid. The increase in gallic acid during the cooking process, presumably transferred from the peels to the fruit, also contributes to the high antioxidant activity observed for the cooked chestnuts. 相似文献
77.
Phenol‐enriched olive oils modify paraoxonase‐related variables: A randomized,crossover, controlled trial 下载免费PDF全文
78.
Sara Lombardo Gaetano Pandino Giovanni Mauromicale Matthias Knödler Reinhold Carle Andreas Schieber 《Food chemistry》2010
Globe artichoke is an ancient herbaceous plant native to the Mediterranean Basin. The edible part of the plant (head) is particularly rich in polyphenols, whose therapeutic properties are well documented. A field experiment was conducted in Sicily (south Italy) to examine the influence of genotype and harvest time on the polyphenol content and profile of different head parts. The concentrations of 19 phenolic compounds were determined by HPLC-DAD-ESI/MSn analysis. It was observed that individual phenolic substances were preferentially accumulated in specific head parts and genotypes. Apigenin 7-O-glucuronide was found to be the major flavonoid, with 6298 mg kg−1 DM in ‘Romanesco clone C3’ receptacle, whereas chlorogenic acid represented the main caffeoylquinic acid, reaching 14841 mg kg−1 DM in the inner bracts of ‘Violetto di Sicilia’. Our findings prove also the influence of climatic conditions on the phenolic profile and thus suggest giving specific consideration to harvest time. 相似文献
79.
Sara Garcinuo Francisco Javier Gil-Etayo Esther Mancebo Marta Lpez-Nevado Antonio Lalueza Raquel Díaz-Simn Daniel Enrique Pleguezuelo Manuel Serrano Oscar Cabrera-Marante Luis M. Allende Estela Paz-Artal Antonio Serrano 《International journal of molecular sciences》2022,23(12)
NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution. 相似文献
80.