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111.
Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies
Damian Bartuzi Ewa Kdzierska Agnieszka A. Kaczor Helmut Schmidhammer Dariusz Matosiuk 《International journal of molecular sciences》2020,21(22)
Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator. 相似文献
112.
Barbara Stypińska Agnieszka Paradowska-Gorycka 《International journal of molecular sciences》2015,16(10):24194-24218
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with varied course and symptoms. Its etiology is very complex and not clearly understood. There is growing evidence of the important role of cytokines in SLE pathogenesis, as well as their utility as biomarkers and targets in new therapies. Other potential new SLE biomarkers are microRNAs. Recently, over one hundred different microRNAs have been demonstrated to have a significant impact on the immune system. Various alterations in these microRNAs, associated with disease pathogenesis, have been described. They influence the signaling pathways and functions of immune response cells. Here, we aim to review the emerging new data on SLE etiology and pathogenesis. 相似文献
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115.
Marzena Danowska-Oziewicz Agnieszka Narwojsz Anna Draszanowska Natalia Marat 《International Journal of Food Science & Technology》2020,55(1):127-135
Broccoli and green asparagus were cooked using boiling water, steam, microwave oven and combi oven with overheated steam and combination of hot air with overheated steam (only broccoli). Vegetables were analysed for chlorophylls a and b, carotenoids, total polyphenols, antioxidant activity, colour parameters and sensory properties. Cooking in the combi oven with overheated steam was an effective method to achieve the highest levels of polyphenols and antioxidant activity, but it negatively influenced the contents of chlorophylls in both vegetables and carotenoids in asparagus. Boiling and cooking in the combi oven with overheated steam or hot air and steam ensured the best and comparable sensory properties of broccoli. Asparagus showed a lower susceptibility to heat treatments than broccoli as none of the treatments applied caused significant differences in colour redness and yellowness, polyphenol content and sensory properties of this vegetable. 相似文献
116.
Dobrakowski Adam Gabriel Mykowiecka Agnieszka Marciniak Małgorzata Jaworski Wojciech Biecek Przemysław 《Journal of Intelligent Information Systems》2021,57(3):447-465
Journal of Intelligent Information Systems - Medical free-text records store a lot of useful information that can be exploited in developing computer-supported medicine. However, extracting the... 相似文献
117.
Sylwia Chudy Agnieszka Makowska Micha Pitek Mirosawa Krzywdziska‐Bartkowiak 《International Journal of Dairy Technology》2019,72(1):82-88
The aim of the study was to obtain and describe crispy snacks purely made of cheese (also referred to as ‘pure’ cheese snacks) using microwave vacuum drying technology. An acid‐set ripened cheese (Harzer cheese) was tested as the raw material. Cutting, hot air drying and microwave vacuum drying were applied in the technology process. This paper investigates the impact of these processes on the physical properties of the puffs; it also includes sensory evaluation of the resulting product. The cheese pieces expanded by ca. 1000% of their original size with a sharp decrease in the bulk density of the puffed samples. Water activity, hardness and brittleness of the cheese puffs were 0.35, 1511.17 g and 3.20 mm, respectively. The CIE LAB coordinates (in spin position), L*, a* and b*, were 82.81, 1.51 and 20.54, respectively. This paper shows that a new form of dairy product can be produced using microwave technology. 相似文献
118.
Katarzyna Chamera Ewa Trojan Katarzyna Kotarska Magdalena Szuster-Guszczak Natalia Bryniarska Kinga Tylek Agnieszka Basta-Kaim 《International journal of molecular sciences》2021,22(4)
Multiple lines of evidence support the pathogenic role of maternal immune activation (MIA) in the occurrence of the schizophrenia-like disturbances in offspring. While in the brain the homeostatic role of neuron-microglia protein systems is well documented, the participation of the CX3CL1-CX3CR1 and CD200-CD200R dyads in the adverse impact of MIA often goes under-recognized. Therefore, in the present study, we examined the effect of MIA induced by polyinosinic:polycytidylic acid (Poly I:C) on the CX3CL1-CX3CR1 and CD200-CD200R axes, microglial trajectory (MhcII, Cd40, iNos, Il-1β, Tnf-α, Il-6, Arg1, Igf-1, Tgf-β and Il-4), and schizophrenia-like behaviour in adult male offspring of Sprague-Dawley rats. Additionally, according to the “two-hit” hypothesis of schizophrenia, we evaluated the influence of acute challenge with Poly I:C in adult prenatally MIA-exposed animals on the above parameters. In the present study, MIA evoked by Poly I:C injection in the late period of gestation led to the appearance of schizophrenia-like disturbances in adult offspring. Our results revealed the deficits manifested as a diminished number of aggressive interactions, presence of depressive-like episodes, and increase of exploratory activity, as well as a dichotomy in the sensorimotor gating in the prepulse inhibition (PPI) test expressed as two behavioural phenotypes (MIAPPI-low and MIAPPI-high). Furthermore, in the offspring rats subjected to a prenatal challenge (i.e., MIA) we noticed the lack of modulation of behavioural changes after the additional acute immune stimulus (Poly I:C) in adulthood. The important finding reported in this article is that MIA affects the expression and levels of the neuron-microglia proteins in the frontal cortex and hippocampus of adult offspring. We found that the changes in the CX3CL1-CX3CR1 axis could affect microglial trajectory, including decreased hippocampal mRNA level of MhcII and elevated cortical expression of Igf-1 in the MIAPPI-high animals and/or could cause the up-regulation of an inflammatory response (Il-6, Tnf-α, iNos) after the “second hit” in both examined brain regions and, at least in part, might differentiate behavioural disturbances in adult offspring. Consequently, the future effort to identify the biological background of these interactions in the Poly I:C-induced MIA model in Sprague-Dawley rats is desirable to unequivocally clarify this issue. 相似文献
119.
Justyna Popi Agnieszka Gunia-Krzyak Karolina Soczyska Paulina Koczurkiewicz-Adamczyk Kamil Piska Katarzyna Wjcik-Pszczoa Dorota elaszczyk Anna Krupa Pawe mudzki Henryk Marona Elbieta Pkala 《International journal of molecular sciences》2021,22(1)
Excessive UV exposure contributes to several pathological conditions like skin burns, erythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorption, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPFin vitro of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at concentrations up to 50 µM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Additionally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application. 相似文献
120.
Sandra Gromolak Agnieszka Krawczenko Agnieszka Antoczyk Krzysztof Buczak Zdzisaw Kiebowicz Aleksandra Klimczak 《International journal of molecular sciences》2020,21(24)
Cell-based therapies using mesenchymal stem cells (MSCs) are a promising tool in bone tissue engineering. Bone regeneration with MSCs involves a series of molecular processes leading to the activation of the osteoinductive cascade supported by bioactive factors, including fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2). In this study, we examined the biological characteristics and osteogenic differentiation potential of sheep bone marrow MSCs (BM-MSCs) treated with 20 ng/mL of FGF-2 and 100 ng/mL BMP-2 in vitro. The biological properties of osteogenic-induced BM-MSCs were investigated by assessing their morphology, proliferation, phenotype, and cytokine secretory profile. The osteogenic differentiation was characterized by Alizarin Red S staining, immunofluorescent staining of osteocalcin and collagen type I, and expression levels of genetic markers of osteogenesis. The results demonstrated that BM-MSCs treated with FGF-2 and BMP-2 maintained their primary MSC properties and improved their osteogenic differentiation capacity, as confirmed by increased expression of osteocalcin and collagen type I and upregulation of osteogenic-related gene markers BMP-2, Runx2, osterix, collagen type I, osteocalcin, and osteopontin. Furthermore, sheep BM-MSCs produced a variety of bioactive factors involved in osteogenesis, and supplementation of the culture medium with FGF-2 and BMP-2 affected the secretome profile of the cells. The results suggest that sheep osteogenic-induced BM-MSCs may be used as a cellular therapy to study bone repair in the preclinical large animal model. 相似文献