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排序方式: 共有1103条查询结果,搜索用时 15 毫秒
991.
Pawe Bryniarski Katarzyna Nazimek Janusz Marcinkiewicz 《International journal of molecular sciences》2021,22(21)
Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy. 相似文献
992.
Edyta Adamska-Patruno Witold Bauer Dorota Bielska Joanna Fiedorczuk Monika Moroz Urszula Krasowska Przemyslaw Czajkowski Marta Wielogorska Katarzyna Maliszewska Sylwia Puckowska Lukasz Szczerbinski Danuta Lipinska Maria Gorska Adam Kretowski 《International journal of molecular sciences》2021,22(21)
The melanocortin-4 receptor (MC4R) gene harbours one of the strongest susceptibility loci for obesity and obesity-related metabolic consequences. We analysed whether dietary factors may attenuate the associations between MC4R genotypes and obesity and metabolic parameters. In 819 participants genotyped for common MC4R polymorphisms (rs17782313, rs12970134, rs633265, and rs135034), the anthropometric measurements, body fat content and distribution (visceral and subcutaneous adipose tissue, VAT and SAT, respectively), and blood glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides concentrations, and daily macronutrient intake were assessed. ANOVA or Kruskal–Wallis tests were used, and multivariate linear regression models were developed. We observed that the CC genotype carriers (rs17782313) presented higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations when they were stratified to the upper quantiles of protein intake. An increase in energy derived from proteins was associated with higher BMI (Est. 5.74, R2 = 0.12), body fat content (Est. 8.44, R2 = 0.82), VAT (Est. 32.59, R2 = 0.06), and VAT/SAT ratio (Est. 0.96, R2 = 0.05). The AA genotype carriers (rs12970134) presented higher BMI, body fat, SAT and VAT, fasting blood glucose, triglycerides and total cholesterol concentrations. An increase in energy derived from proteins by AA carriers was associated with higher VAT (Est.19.95, R2 = 0.06) and VAT/SAT ratio (Est. 0.64, R2 = 0.05). Our findings suggest that associations of the common MC4R SNPs with obesity and its metabolic complications may be dependent on the daily dietary intake, which may open new areas for developing personalised diets for preventing and treating obesity and obesity-related comorbidities. 相似文献
993.
Katarzyna Z. Kuter ukasz Olech Urszula Gowacka Martyna Paleczna 《International journal of molecular sciences》2021,22(14)
The benefits of a ketogenic diet in childhood epilepsy steered up hope for neuroprotective effects of hyperketonemia in Parkinson’s disease (PD). There are multiple theoretical reasons but very little actual experimental proof or clinical trials. We examined the long-term effects of the ketogenic diet in an animal model of early PD. A progressive, selective dopaminergic medium size lesion was induced by 6-OHDA injection into the medial forebrain bundle. Animals were kept on the stringent ketogenic diet (1% carbohydrates, 8% protein, 70% fat) for 3 weeks prior and 4 weeks after the brain operation. Locomotor activity, neuron count, dopaminergic terminal density, dopamine level, and turnover were analyzed at three time-points post-lesion, up to 4 weeks after the operation. Energy metabolism parameters (glycogen, mitochondrial complex I and IV, lactate, beta-hydroxybutyrate, glucose) were analyzed in the brain and liver or plasma. Protein expression of enzymes essential for gluconeogenesis (PEPCK, G6PC) and glucose utilization (GCK) was analyzed in the liver. Despite long-term hyperketonemia pre- and post-lesion, the ketogenic diet did not protect against 6-OHDA-induced dopaminergic neuron lesions. The ketogenic diet only tended to improve locomotor activity and normalize DA turnover in the striatum. Rats fed 7 weeks in total with a restrictive ketogenic diet maintained normoglycemia, and neither gluconeogenesis nor glycogenolysis in the liver was responsible for this effect. Therefore, potentially, the ketogenic diet could be therapeutically helpful to support the late compensatory mechanisms active via glial cells but does not necessarily act against the oxidative stress-induced parkinsonian neurodegeneration itself. A word of caution is required as the stringent ketogenic diet itself also carries the risk of unwanted side effects, so it is important to study the long-term effects of such treatments. More detailed metabolic long-term studies using unified diet parameters are required, and human vs. animal differences should be taken under consideration. 相似文献
994.
Joanna Krasowska Katarzyna Pierzchaa Agnieszka Bzowska Lszl Forr Andrzej Sienkiewicz Beata Wielgus-Kutrowska 《International journal of molecular sciences》2021,22(16)
Under stress conditions, elevated levels of cellular reactive oxygen species (ROS) may impair crucial cellular structures. To counteract the resulting oxidative damage, living cells are equipped with several defense mechanisms, including photoprotective functions of specific proteins. Here, we discuss the plausible ROS scavenging mechanisms by the enhanced green fluorescent protein, EGFP. To check if this protein could fulfill a photoprotective function, we employed electron spin resonance (ESR) in combination with spin-trapping. Two organic photosensitizers, rose bengal and methylene blue, as well as an inorganic photocatalyst, nano-TiO2, were used to photogenerate ROS. Spin-traps, TMP-OH and DMPO, and a nitroxide radical, TEMPOL, served as molecular targets for ROS. Our results show that EGFP quenches various forms of ROS, including superoxide radicals and singlet oxygen. Compared to the three proteins PNP, papain, and BSA, EGFP revealed high ROS quenching ability, which suggests its photoprotective role in living systems. Damage to the EGFP chromophore was also observed under strong photo-oxidative conditions. This study contributes to the discussion on the protective function of fluorescent proteins homologous to the green fluorescent protein (GFP). It also draws attention to the possible interactions of GFP-like proteins with ROS in systems where such proteins are used as biological markers. 相似文献
995.
Wojciech Bocian Beata Naumczuk Magdalena Urbanowicz Jerzy Sitkowski Anna Bierczyska-Krzysik Elbieta Bednarek Katarzyna Wiktorska Magorzata Milczarek Lech Kozerski 《International journal of molecular sciences》2021,22(14)
The compounds 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (2) and 7-ethyl-9-(N-morpholino)methyl-10-hydroxycamptothecin (3) are potential topoisomerase I poisons. Moreover, they were shown to have favorable anti-neoplastic effects on several tumor cell lines. Due to these properties, the compounds are being considered for advancement to the preclinical development stage. To gain better insights into the molecular mechanism with the biological target, here, we conducted an investigation into their interactions with model nicked DNA (1) using different techniques. In this work, we observed the complexity of the mechanism of action of the compounds 2 and 3, in addition to their decomposition products: compound 4 and SN38. Using DOSY experiments, evidence of the formation of strongly bonded molecular complexes of SN38 derivatives with DNA duplexes was provided. The molecular modeling based on cross-peaks from the NOESY spectrum also allowed us to assign the geometry of a molecular complex of DNA with compound 2. Confirmation of the alkylation reaction of both compounds was obtained using MALDI–MS. Additionally, in the case of 3, alkylation was confirmed in the recording of cross-peaks in the 1H/13C HSQC spectrum of 13C-enriched compound 3. In this work, we showed that the studied compounds—parent compounds 2 and 3, and their potential metabolite 4 and SN38—interact inside the nick of 1, either forming the molecular complex or alkylating the DNA nitrogen bases. In order to confirm the influence of the studied compounds on the topoisomerase I relaxation activity of supercoiled DNA, the test was performed based upon the measurement of the fluorescence of DNA stain which can differentiate between supercoiled and relaxed DNA. The presented results confirmed that studied SN38 derivatives effectively block DNA relaxation mediated by Topo I, which means that they stop the machinery of Topo I activity. 相似文献
996.
Katarzyna Szewczyk Wioleta Pietrzak Katarzyna Klimek Magorzata Miazga-Karska Agnieszka Firlej Marek Flisiski Anna Grzywa-Celiska 《International journal of molecular sciences》2021,22(12)
Skin aging is a natural, unavoidable, and complex process caused by oxidative stress. As a consequence, it leads to an increase in the activation of extracellular matrix disruption enzymes and DNA damage. The search for natural sources that inhibit these mechanisms can be a good approach to prevent skin aging. The purpose of our study was to evaluate the composition of flavonoids and phenolic acids in the extracts obtained from the flowers, roots, and leaves of Eutrema japonicum cultivated in Poland. Then, the resultant extracts were subjected to an assessment of antioxidant, anti-collagenase, anti-elastase, anti-hyaluronidase, antibacterial, and cytotoxic properties. It was demonstrated that the extract from the flowers had the highest content of flavonoid glycosides (17.15 mg/g DE). This extract showed the greatest antioxidant, anti-collagenase, anti-elastase, and anti-hyaluronidase activities compared to the other samples. Importantly, the collagenase inhibitory activity of this extract (93.34% ± 0.77%) was better than that of positive control epigallocatechin gallate (88.49% ± 0.45%). An undeniable advantage of this extract was also to possess moderate antibacterial properties and no cytotoxicity towards normal human skin fibroblasts. Our results suggest that extracts from E. japonicum flowers may be considered as a promising antiaging compound for applications in cosmetic formulations. 相似文献
997.
Tomasz Oleszkiewicz Magdalena Klimek-Chodacka Micha Kruczek Kamila Godel-Jdrychowska Katarzyna Sala Anna Milewska-Hendel Maciej Zubko Ewa Kurczyska Yiping Qi Rafal Baranski 《International journal of molecular sciences》2021,22(12)
Recent data indicate that modifications to carotenoid biosynthesis pathway in plants alter the expression of genes affecting chemical composition of the cell wall. Phytoene synthase (PSY) is a rate limiting factor of carotenoid biosynthesis and it may exhibit species-specific and organ-specific roles determined by the presence of psy paralogous genes, the importance of which often remains unrevealed. Thus, the aim of this work was to elaborate the roles of two psy paralogs in a model system and to reveal biochemical changes in the cell wall of psy knockout mutants. For this purpose, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated (Cas9) proteins (CRISPR/Cas9) vectors were introduced to carotenoid-rich carrot (Daucus carota) callus cells in order to induce mutations in the psy1 and psy2 genes. Gene sequencing, expression analysis, and carotenoid content analysis revealed that the psy2 gene is critical for carotenoid biosynthesis in this model and its knockout blocks carotenogenesis. The psy2 knockout also decreased the expression of the psy1 paralog. Immunohistochemical staining of the psy2 mutant cells showed altered composition of arabinogalactan proteins, pectins, and extensins in the mutant cell walls. In particular, low-methylesterified pectins were abundantly present in the cell walls of carotenoid-rich callus in contrast to the carotenoid-free psy2 mutant. Transmission electron microscopy revealed altered plastid transition to amyloplasts instead of chromoplasts. The results demonstrate for the first time that the inhibited biosynthesis of carotenoids triggers the cell wall remodelling. 相似文献
998.
Sylwia Sudo Agnieszka Cios Magdalena Jastrzbska-Wisek Ewelina Honkisz-Orzechowska Barbara Mordyl Natalia Wilczyska-Zawal Grzegorz Sataa Katarzyna Kucwaj-Brysz Anna Partyka Gniewomir Latacz Agnieszka Olejarz-Maciej Anna Wesoowska Jadwiga Handzlik 《International journal of molecular sciences》2021,22(19)
Among the serotonin receptors, one of the most recently discovered 5-HT6 subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT6 receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT6 receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT6 receptor target. 相似文献
999.
Julia Borzyszkowska-Bukowska Justyna Grska Pawe Szczeblewski Tomasz Laskowski Iwona Gabriel Jakub Jurasz Katarzyna Kozowska-Tylingo Piotr Szweda Sawomir Milewski 《International journal of molecular sciences》2021,22(18)
Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans → all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling studies on interactions between original antibiotics and their photoisomers with ergosterol and cholesterol revealed some difference in free energy profiles of formation of binary antibiotic/sterol complexes in respective membrane environments. Moreover, different geometries of heptaene: sterol complexes and variations in polyene macrolide molecule alignment in cholesterol-and ergosterol-containing membranes were found. None of these effects are of the crucial importance for the observed improvement of selective toxicity of aromatic heptaene antifungals but each seems to provide a partial contribution. 相似文献
1000.
Kamila Rzd Ewa Paluszkiewicz Damian Neubauer Mateusz Olszewski Katarzyna Kozowska-Tylingo Wojciech Kamysz Iwona Gabriel 《International journal of molecular sciences》2021,22(24)
Acridine cell-penetrating peptide conjugates are an extremely important family of compounds in antitumor chemotherapy. These conjugates are not so widely analysed in antimicrobial therapy, although bioactive peptides could be used as nanocarriers to smuggle antimicrobial compounds. An octaarginine conjugate of an imidazoacridinone derivative (Compound 1-R8) synthetized by us exhibited high antifungal activity against reference and fluconazole-resistant clinical strains (MICs ≤ 4 μg mL−1). Our results clearly demonstrate the qualitative difference in accumulation of the mother compound and Compound 1-R8 conjugate into fungal cells. Only the latter was transported and accumulated effectively. Microscopic and flow cytometry analysis provide some evidence that the killing activity of Compound 1-R8 may be associated with a change in the permeability of the fungal cell membrane. The conjugate exhibited low cytotoxicity against human embryonic kidney (HEK-293) and human liver (HEPG2) cancer cell lines. Nevertheless, the selectivity index value of the conjugate for human pathogenic strains remained favourable and no hemolytic activity was observed. The inhibitory effect of the analysed compound on yeast topoisomerase II activity suggested its molecular target. In summary, conjugation with R8 effectively increased imidazoacridinone derivative ability to enter the fungal cell and achieve a concentration inside the cell that resulted in a high antifungal effect. 相似文献