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51.
Teresa Glomb Benita Wiatrak Katarzyna Gbczak Tomasz Gbarowski Dorota Bodetko aneta Czynikowska Piotr
witek 《International journal of molecular sciences》2020,21(23)
Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases. 相似文献
52.
Mariusz Mital Kosma Szutkowski Karolina Bossak-Ahmad Piotr Skrobecki Simon C. Drew Jarosaw Poznaski Igor Zhukov Tomasz Frczyk Wojciech Bal 《International journal of molecular sciences》2020,21(23)
The A peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer’s Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in A and A model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage. Structural characterization of Cu(II)A complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-A complex as a model. To avoid a kinetic trapping of Pd(II) in an inappropriate transient structure, we designed an appropriate pH-dependent synthetic procedure for ATCUN Pd(II)A, controlled by CD, fluorescence and ESI-MS. Its assignments and structure at pH 6.5 were obtained by TOCSY, NOESY, ROESY, H-C HSQC and H-N HSQC NMR experiments, for natural abundance C and N isotopes, aided by corresponding experiments for Pd(II)-Phe-Arg-His. The square-planar Pd(II)-ATCUN coordination was confirmed, with the rest of the peptide mostly unstructured. The diffusion rates of A, Pd(II)-A and their mixture determined using PGSE-NMR experiment suggested that the Pd(II) complex forms a supramolecular assembly with the apopeptide. These results confirm that Pd(II) substitution enables NMR studies of structural aspects of Cu(II)-A complexes. 相似文献
53.
Aleksandra Czumaj Sylwia Szrok-Jurga Areta Hebanowska Jacek Turyn Julian Swierczynski Tomasz Sledzinski Ewa Stelmanska 《International journal of molecular sciences》2020,21(23)
The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia. 相似文献
54.
Julian Zacharjasz Anna M. Mleczko Pawe Bkowski Tomasz Piontek Kamilla Bkowska-ywicka 《International journal of molecular sciences》2021,22(11)
Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis. 相似文献
55.
Tomasz Wokowicz Katarzyna Zacharczuk Rafa Gierczyski Magdalena Nowakowska Katarzyna Piekarska 《International journal of molecular sciences》2021,22(17)
Background: Salmonella Kentucky belongs to zoonotic serotypes that demonstrate that the high antimicrobial resistance and multidrug resistance (including fluoroquinolones) is an emerging problem. To the best of our knowledge, clinical S. Kentucky strains isolated in Poland remain undescribed. Methods: Eighteen clinical S. Kentucky strains collected in the years 2018–2019 in Poland were investigated. All the strains were tested for susceptibility to 11 antimicrobials using the disc diffusion and E-test methods. Whole genome sequences were analysed for antimicrobial resistance genes, mutations, the presence and structure of SGI1-K (Salmonella Genomic Island and the genetic relationship of the isolates. Results: Sixteen of 18 isolates (88.9%) were assigned as ST198 and were found to be high-level resistant to ampicillin (>256 mg/L) and quinolones (nalidixic acid MIC ≥ 1024 mg/L, ciprofloxacin MIC range 6–16 mg/L). All the 16 strains revealed three mutations in QRDR of GyrA and ParC. The substitutions of Ser83 → Phe and Asp87 → Tyr of the GyrA subunit and Ser80→Ile of the ParC subunit were the most common. One S. Kentucky isolate had qnrS1 in addition to the QRDR mutations. Five of the ST198 strains, grouped in cluster A, had multiple resistant determinants like blaTEM1-B, aac(6′)-Iaa, sul1 or tetA, mostly in SGI1 K. Seven strains, grouped in cluster B, had shorter SGI1-K with deletions of many regions and with few resistance genes detected. Conclusion: The results of this study demonstrated that a significant part of S. Kentucky isolates from humans in Poland belonged to ST198 and were high-level resistant to ampicillin and quinolones. 相似文献
56.
Emilia Szymańska Katarzyna Winnicka Piotr Wieczorek Pawe? Tomasz Sacha El?bieta Anna Tryniszewska 《International journal of molecular sciences》2014,15(10):17765-17777
The combination of an antifungal agent and drug carrier with adjunctive antimicrobial properties represents novel strategy of complex therapy in pharmaceutical technology. The goal of this study was to investigate the unmodified and ion cross-linked chitosan’s influence on anti-Candida activity of clotrimazole used as a model drug in hydrogels. It was particularly crucial to explore whether the chitosans’ structure modification by β-glycerophosphate altered its antifungal properties. Antifungal studies (performed by plate diffusion method according to CLSI reference protocol) revealed that hydrogels obtained with chitosan/β-glycerophosphate displayed lower anti-Candida effect, probably as a result of weakened polycationic properties of chitosan in the presence of ion cross-linker. Designed chitosan hydrogels with clotrimazole were found to be more efficient against tested Candida strains and showed more favorable drug release profile compared to commercially available product. These observations indicate that novel chitosan formulations may be considered as promising semi-solid delivery system of clotrimazole. 相似文献
57.
Design,Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents 下载免费PDF全文
Łukasz Janczewski Dr. Mateusz Psurski Dr. Marta Świtalska Dr. Anna Gajda Dr. Tomasz M. Goszczyński Prof. Dr. Józef Oleksyszyn Prof. Dr. Joanna Wietrzyk Prof. Dr. Tadeusz Gajda 《ChemMedChem》2018,13(1):105-115
A series of 21 novel, structurally diverse ω‐(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX‐5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell‐cycle arrest and apoptosis. Ethyl (6‐isothiocyanatohexyl)(phenyl)phosphinate ( 71 ) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide. 相似文献
58.
Tomasz Piechowiak Piotr Antos Radosław Józefczyk Patryk Kosowski Karol Skrobacz 《臭氧:科学与工程》2019,41(4):376-385
In the studies conducted, the impact of the innovative ozonation procedure on the microbial state and antioxidant potential of highbush blueberry (Vaccinum corymbosum L.) stored under cold storage conditions was assessed. Microbiological analysis was carried out to determine the total number of mesophilic aerobic bacteria and the total number of fungi during the storage experiment. In addition, changes in the flavonoid, anthocyanins, and vitamin C content and the total antioxidant capacity were monitored during the storage. The degree of fruit infection with gray mold and anthracnose was determined. It was found that daily ozonation of fruits with a dose of 15 ppm for 30 min, every 12 h, for 28 days effectively reduced the development of aerobic mesophilic bacteria and fungi. On the last day of storage, symptoms of the infection by gray mold were observed in 27.5% of the control fruit, while the absence of symptoms was observed in case of the ozonated fruit. On the other hand, ozone was ineffective in case of inhibiting the infection by anthracnose. Nevertheless, the ozonation process allowed maintaining a high antioxidant potential of the fruit and substantially reduced losses of flavonoids, anthocyanins, and vitamin C. The utilized procedure has proved to be effective, providing the possibility of extensive use of ozone as a factor allowing sustaining a high commercial and consumption value of the fruit over extended time. 相似文献
59.
Marcela Trybula Tomasz Gancarz Wladyslaw Gasior Alain Pasturel 《Metallurgical and Materials Transactions A》2014,45(12):5517-5530
Physicochemical properties like density, surface tension, and viscosity of liquid binary Al-Li and Li-Zn alloys have been measured using draining crucible method. The experimentally measured surface-tension values have been compared to theoretical results based either on the Butler model or the compound formation model assuming the existence of the most favored A 1 B 2 and A 2 B 3 clusters. Several models for viscosity calculation have been also applied and discussed in confrontation with measured data. Finally, the clustering effects in the liquid Al-Li and Li-Zn alloys have been examined using two microscopic functions, i.e., the concentration fluctuation function in the long-wavelength limit and the Warren-Cowley short-range order parameter. 相似文献
60.
Angelique A. Scharine Mary S. Binseel Timothy Mermagen Tomasz R. Letowski 《Ergonomics》2014,57(8):1222-1243
Helmets provide soldiers with ballistic and fragmentation protection but impair auditory spatial processing. Missed auditory information can be fatal for a soldier; therefore, helmet design requires compromise between protection and optimal acoustics. Twelve soldiers localised two sound signals presented from six azimuth angles and three levels of elevation presented at two intensity levels and with three background noises. Each participant completed the task while wearing no helmet and with two U.S. Army infantry helmets – the Personnel Armor System for Ground Troops (PASGT) helmet and the Advanced Combat Helmet (ACH). Results showed a significant effect of helmet type on the size of both azimuth and elevation error. The effects of level, background noise, azimuth and elevation were found to be significant. There was no effect of sound signal type. As hypothesised, localisation accuracy was greatest when soldiers did not wear helmet, followed by the ACH. Performance was worst with the PASGT helmet. 相似文献