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991.
Joanna Depciuch Justyna Miszczyk Alexey Maximenko Piotr M. Zielinski Kamila Rawoj Agnieszka Panek Pawel Olko Magdalena Parlinska-Wojtan 《International journal of molecular sciences》2020,21(23)
Herein, we propose newly designed and synthesized gold nanopeanuts (Au NPes) as supports for cisplatin (cPt) immobilization, dedicated to combined glioblastoma nano-chemo-radiotherapy. Au NPes offer a large active surface, which can be used for drugs immobilization. Transmission electron microscopy (TEM) revealed that the size of the synthesized Au NPes along the longitudinal axis is ~60 nm, while along the transverse axis ~20 nm. Raman, thermogravimetric analysis (TGA) and differential scanning calorimetry (DCS) measurements showed, that the created nanosystem is stable up to a temperature of 110 °C. MTT assay revealed, that the highest cell mortality was observed for cell lines subjected to nano-chemo-radiotherapy (20–55%). Hence, Au NPes with immobilized cPt (cPt@AuNPes) are a promising nanosystem to improve the therapeutic efficiency of combined nano-chemo-radiotherapy. 相似文献
992.
Katarzyna Kaawaj Adrianna Sawiska-Brych Magdalena Mizerska-Kowalska Aleksandra urek Agnieszka Bojarska-Junak Martyna Kandefer-Szersze Barbara Zdzisiska 《International journal of molecular sciences》2020,21(24)
Osteosarcoma (OS) is the most common type of primary bone tumor. Currently, there are limited treatment options for metastatic OS. Alpha-ketoglutarate (AKG), i.e., a multifunctional intermediate of the Krebs cycle, is one of the central metabolic regulators of tumor fate and plays an important role in cancerogenesis and tumor progression. There is growing evidence suggesting that AKG may represent a novel adjuvant therapeutic opportunity in anti-cancer therapy. The present study was intended to check whether supplementation of Saos-2 and HOS osteosarcoma cell lines (harboring a TP53 mutation) with exogenous AKG exerted an anti-cancer effect. The results revealed that AKG inhibited the proliferation of both OS cell lines in a concentration-dependent manner. As evidenced by flow cytometry, AKG blocked cell cycle progression at the G1 stage in both cell lines, which was accompanied by a decreased level of cyclin D1 in HOS and increased expression of p21Waf1/Cip1 protein in Saos-2 cells (evaluated with the ELISA method). Moreover, AKG induced apoptotic cell death and caspase-3 activation in both OS cell lines (determined by cytometric analysis). Both the immunoblotting and cytometric analysis revealed that the AKG-induced apoptosis proceeded predominantly through activation of an intrinsic caspase 9-dependent apoptotic pathway and an increased Bax/Bcl-2 ratio. The apoptotic process in the AKG-treated cells was mediated via c-Jun N-terminal protein kinase (JNK) activation, as the specific inhibitor of this kinase partially rescued the cells from apoptotic death. In addition, the AKG treatment led to reduced activation of extracellular signal-regulated kinase (ERK1/2) and significant inhibition of cell migration and invasion in vitro concomitantly with decreased production of pro-metastatic transforming growth factor β (TGF-β) and pro-angiogenic vascular endothelial growth factor (VEGF) in both OS cell lines suggesting the anti-metastatic potential of this compound. In conclusion, we showed the anti-osteosarcoma potential of AKG and provided a rationale for a further study of the possible application of AKG in OS therapy. 相似文献
993.
Ewa Rokosik Aleksander Siger Magdalena Rudziska Przemysaw Siejak Krzysztof Dwiecki 《European Journal of Lipid Science and Technology》2020,122(2)
This study describes the formation of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) association colloids (reverse micelles) in rapeseed oil and interactions of sinapic and ferulic acids with these structures. Furthermore, the process of oil autoxidation in the presence of DOPC is characterized and the antioxidant efficiency of phenolic acids in the oil containing reverse micelles is determined. Formation of DOPC reverse micelles above the phospholipid critical micelle concentration (51.13 µmol kg–1) is observed. The fluorescence probe emission parameters confirm the interactions of sinapic and ferulic acids with reverse micelles and changes of their structure (reduced rigidity) as a result of phenolic acid incorporation. In the analyzed rapeseed oil, an evident prooxidative effect of DOPC reverse micelles is found, as their presence accelerates decomposition of hydroperoxides to hexanal. The antioxidant effect of sinapic acid is strongly influenced by the presence of DOPC reverse micelles. Ferulic acid shows a concentration‐dependent antioxidant effect in relation to the formation of hexanal. Practical Applications: Understanding the influence of sinapic and ferulic acids on the structure of association colloids and rapeseed oil autoxidation in the presence of reverse micelles should facilitate extension of shelf life and reduce oil quality deterioration during storage. This knowledge may also be used to optimize industrial oil refining to provide the desired amount of amphiphilic minor components and native antioxidants. Thus, developed refining using mild conditions or even minimizing the degree of refining is attractive in view of greater retention of health‐promoting compounds in vegetable oil, reduction of processing costs, and increased sustainability of the oil‐refining process. 相似文献
994.
Genipin is an important monoterpene iridoid compound isolated from Gardenia jasminoides J.Ellis fruits and from Genipa americana fruits, or genipap. It is a precursor of a blue pigment which may be attractive alternative to existing food dyes and it possesses various potential therapeutic properties such as anti-cancer, anti-diabetic and hepatoprotective activity. Biomedical studies also show that genipin may act as a neuroprotective drug. This review describes new aspects of the bioactivity of genipin against various diseases, as well as its toxicity and industrial applications, and presents its potential mechanism of action. 相似文献
995.
Agata Gurba Przemysaw Taciak Mariusz Sacharczuk Izabela Mynarczuk-Biay Magdalena Bujalska-Zadrony Jakub Fichna 《International journal of molecular sciences》2022,23(2)
Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described. 相似文献
996.
Magdalena Wsierska Anna Kloska Diego L. Medina Joanna Jakbkiewicz-Banecka Magdalena Gabig-Cimiska Marta Radziska Marta Moskot Marcelina Malinowska 《International journal of molecular sciences》2022,23(3)
Flavonoids are investigated as therapeutics for mucopolysaccharidosis, a metabolic disorder with impaired glycosaminoglycan degradation. Here we determined the effects of genistein and kaempferol, used alone or in combination, on cellular response and gene expression in a mucopolysaccharidosis type I model. We assessed the cell cycle, viability, proliferation, subcellular localization of the translocation factor EB (TFEB), number and distribution of lysosomes, and glycosaminoglycan synthesis after exposure to flavonoids. Global gene expression was analysed using DNA microarray and quantitative PCR. The type and degree of flavonoid interaction were determined based on the combination and dose reduction indexes. The combination of both flavonoids synergistically inhibits glycosaminoglycan synthesis, modulates TFEB localization, lysosomal number, and distribution. Genistein and kaempferol in a 1:1 ratio regulate the expression of 52% of glycosaminoglycan metabolism genes. Flavonoids show synergy, additivity, or slight antagonism in all analysed parameters, and the type of interaction depends on the concentration and component ratios. With the simultaneous use of genistein and kaempferol in a ratio of 4:1, even a 10-fold reduction in the concentration of kaempferol is possible. Flavonoid mixtures, used as the treatment of mucopolysaccharidosis, are effective in reducing glycosaminoglycan production and storage and show a slight cytotoxic effect compared to single-flavonoid usage. 相似文献
997.
Mariusz Popek Bartosz Bobula Karolina Orze-Gajowik Magdalena Zieliska 《International journal of molecular sciences》2022,23(3)
Decreased platelet count represents a feature of acute liver failure (ALF) pathogenesis. Platelets are the reservoir of transforming growth factor 1 (TGF-β1), a multipotent cytokine involved in the maintenance of, i.a., central nervous system homeostasis. Here, we analyzed the effect of a decrease in TGF-β1 active form on synaptic proteins levels, and brain electrophysiology, in mice after intraperitoneal (ip) administration of TGF-β1 antibody (anti-TGF-β1; 1 mg/mL). Next, we correlated it with a thrombocytopenia-induced TGF-β1 decrease, documented in an azoxymethane-induced (AOM; 100 mM ip) model of ALF, and clarified the impact of TGF-β1 decrease on blood–brain barrier functionality. The increase of both synaptophysin and synaptotagmin in the cytosolic fraction, and its reduction in a membrane fraction, were confirmed in the AOM mice brains. Both proteins’ decrease in analyzed fractions occurred in anti-TGF-β1 mice. In turn, an increase in postsynaptic (NR1 subunit of N-methyl-D-aspartate receptor, postsynaptic density protein 95, gephyrin) proteins in the AOM brain cortex, but a selective compensatory increase of NR1 subunit in anti-TGF-β mice, was observed. The alterations of synaptic proteins levels were not translated on electrophysiological parameters in the anti-TGF-β1 model. The results suggest the impairment of synaptic vesicles docking to the postsynaptic membrane in the AOM model. Nevertheless, changes in synaptic protein level in the anti-TGF-β1 mice do not affect neurotransmission and may not contribute to neurologic deficits in AOM mice. 相似文献
998.
Jacek Sikorski Magdalena Matczuk Agnieszka Kamiska Joanna Kruszewska Maciej Trzaskowski Andrei R. Timerbaev Maciej Jarosz 《International journal of molecular sciences》2022,23(3)
Progress toward translating superparamagnetic iron oxide nanoparticles (SPIONs) with specific diagnostic and therapeutic properties for clinical applications depends on developing and implementing appropriate methodologies that would allow in-depth characterizations of their behavior in a real biological environment. Herein, we report a versatile approach for studying interactions between SPIONs and proteins using single-particle inductively coupled plasma tandem mass spectrometry. By monitoring the changes in the size distribution upon exposure to human serum, the formation of stable protein corona is revealed, accompanied by particle disaggregation. 相似文献
999.
1000.
Hanna Kozowska Barbara Malinowska Marta Baranowska-Kuczko Magdalena Kusaczuk Miosz Nesterowicz Mirosaw Kozowski Christa E. Müller Katarzyna Kie-Kononowicz Eberhard Schlicker 《International journal of molecular sciences》2022,23(3)
GPR18 receptor protein was detected in the heart and vasculature and appears to play a functional role in the cardiovascular system. We investigated the effects of the new GPR18 agonists PSB-MZ-1415 and PSB-MZ-1440 and the new GPR18 antagonist PSB-CB-27 on isolated human pulmonary arteries (hPAs) and compared their effects with the previously proposed, but unconfirmed, GPR18 ligands NAGly, Abn-CBD (agonists) and O-1918 (antagonist). GPR18 expression in hPAs was shown at the mRNA level. PSB-MZ-1415, PSB-MZ-1440, NAGly and Abn-CBD fully relaxed endothelium-intact hPAs precontracted with the thromboxane A2 analog U46619. PSB-CB-27 shifted the concentration-response curves (CRCs) of PSB-MZ-1415, PSB-MZ-1440, NAGly and Abn-CBD to the right; O-1918 caused rightward shifts of the CRCs of PSB-MZ-1415 and NAGly. Endothelium removal diminished the potency and the maximum effect of PSB-MZ-1415. The potency of PSB-MZ-1415 or NAGly was reduced in male patients, smokers and patients with hypercholesterolemia. In conclusion, the novel GPR18 agonists, PSB-MZ-1415 and PSB-MZ-1440, relax hPAs and the effect is inhibited by the new GPR18 antagonist PSB-CB-27. GPR18, which appears to exhibit lower activity in hPAs from male, smoking or hypercholesterolemic patients, may become a new target for the treatment of pulmonary arterial hypertension. 相似文献