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127 result(s) for "Zawadzka, Katarzyna"
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The Synergistic Effect of Triterpenoids and Flavonoids—New Approaches for Treating Bacterial Infections?
Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.
Zinc(II) Complexes with Amino Acids for Potential Use in Dermatology: Synthesis, Crystal Structures, and Antibacterial Activity
The multifunctional profile of Zn2+ has influenced its great popularity in various pharmaceutical, food, and cosmetic products. Despite the use of different inorganic and organic zinc derivatives, the search for new zinc-containing compounds with a safer skin profile still remains an open issue. The present paper describes the synthesis, structural characterization, and antibacterial activity of zinc(II) complexes with proteinogenic amino acids as potential candidates for dermatological treatments. The obtained complexes are of the general formula [Zn(AA)2], where AA represents an amino acid (L-Glu, Gly, L-His, L-Pro, L-Met, and L-Trp). Their synthesis was designed in such a way that the final bis(aminoacidate) zinc(II) complexes did not contain any counter-ions such as Cl−, NO3−, or SO42− that can cause some skin irritations. The chemical structure and composition of the compounds were identified by 1H NMR spectroscopy and elemental analysis, and four were also characterized by single-crystal X-ray diffraction. The Hirshfeld surface analysis for the Zn2+ metallic center helped to determine its coordination number and geometry for each complex. Finally, the antibacterial properties of the complexes were determined with respect to three Gram-positive strains, viz. Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Streptococcus pyogenes ATCC 19615, and two Gram-negative bacteria, viz. Escherichia coli ATCC 25992 and Pseudomonas aeruginosa ATCC 27853, and were compared with the activity of zinc 2-pirrolidone 5-carboxylate (ZnPCA), commonly applied in dermatology. It was found that the Zn(II) complexes with methionine and glycine exhibited a higher antibacterial activity than the tested standard, and the antimicrobial properties of complex with Trp were satisfactory. The results of the antimicrobial activity examination allow us to postulate that the obtained zinc complexes might become new active substances for use in dermatological products.
Silver Nanoparticles at Low Concentrations Embedded in ECM Promote Endothelial Monolayer Formation and Cell Migration
Several scientific studies have reported the opposing effects of silver nanoparticles (AgNPs) on angiogenesis, ranging from proangiogenic to anti-angiogenic. The widespread use of AgNPs in biomedical applications and the variability of their effects depending on concentration and exposure conditions highlight the need for further research into their impact on vascularization and endothelial cell behavior. This study aimed to investigate the potential influence of AgNPs on human umbilical vein endothelial cells (HUVECs) using a model incorporating a thin layer of an extracellular matrix (ECM). To this end, cytotoxicity was assessed, and endogenous nitric oxide and superoxide levels were measured. Additionally, the effects of AgNPs on HUVEC confluence and migration were evaluated. The expression levels of 43 proteins involved in angiogenesis were also analyzed. The results revealed that ECM enriched with AgNPs at a concentration of 0.5 mg/L enhanced cell coverage, promoted migration, and supported monolayer formation without inducing cytotoxicity.
Effect of Quinoline on the Phospholipid Profile of Curvularia lunata and Its Microbial Detoxification
Quinoline is an N-heterocyclic compound commonly found in wastewater, especially that derived from coal processing, chemical, and pharmaceutical industries. In the present study, the microscopic fungus Curvularia lunata IM 4417, which is known to degrade various xenobiotics, was used. The aim of the research was to study the elimination of quinoline and its influence on fungal phospholipids, which are considered to be excellent indicators of environmental monitoring. Quinoline biodegradation products and phospholipid contents were analyzed using gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry. C. lunata IM 4417 degraded quinoline, which led to the formation of conjugates of glucose with hydroxylated derivatives of the compound. Toxicity tests (Artoxkit M and Microtox assay) indicated that the elimination of lower concentrations of quinoline was efficient and led to a reduction in sample toxicity. The presence of quinoline also significantly affected the profile of fatty acids and phospholipids. The addition of quinoline to a culture of C. lunata IM 4417 caused an increase in the content of phosphatidylcholine (PC) and a decrease in the amount of phosphatidylethanolamine (PE), two major structural lipids. Additionally, decreases in the contents of phosphatidylinositol (PI) and phosphatidylserine (PS), which are responsible for tolerance to toxic substances, cell viability, and signal transduction, were noted. Thus, it can be concluded that the presence of quinoline modifies the membrane composition, and this change may be an important indicator of the presence of N-heterocyclic compounds or other toxins in the environment.
Significance of HLA Haplotypes in Two Patients with Subacute Thyroiditis Triggered by mRNA-Based COVID-19 Vaccine
Subacute thyroiditis (SAT) can be triggered by several viral factors in genetically predisposed individuals. In the case of COVID-19, SAT can be induced by SARS-CoV-2 infection as well as COVID-19 vaccination. The aim of this study was to present two cases of SAT triggered by mRNA-based COVID-19 vaccines, with special attention paid to the possible significance of HLA-related SAT susceptibility. In our patients, a strong similarity of HLA profiles with regard not only to SAT high-risk alleles but also to other SAT-unrelated ones was observed. The rare phenomenon of SAT occurrence after COVID-19 vaccination can be HLA-dependent and related to a co-presence of HLA-B*35:03 and -C*04:01. Taking into account the similarity of HLA profiles in both our patients, the co-presence of other alleles, such as HLA-A*03:01, -DQA1:01, DQB1*05:01 as well as some of HLA-DRB1, can also play a role. This hypothesis is strongly consistent with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) being the postulated mechanism of this post-vaccine reaction, as ASIA-related immune reactions are directly associated with HLA-based genetic susceptibility. Further research is necessary to confirm these findings.
MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation
The Escherichia coli SMC complex, MukBEF, forms clusters of molecules that interact with the decatenase topisomerase IV and which are normally associated with the chromosome replication origin region ( ori ). Here we demonstrate an additional ATP-hydrolysis-dependent association of MukBEF with the replication termination region ( ter ). Consistent with this, MukBEF interacts with MatP, which binds matS sites in ter . MatP displaces wild-type MukBEF complexes from ter , thereby facilitating their association with ori , and limiting the availability of topoisomerase IV (TopoIV) at ter . Displacement of MukBEF is impaired when MukB ATP hydrolysis is compromised and when MatP is absent, leading to a stable association of ter and MukBEF. Impairing the TopoIV-MukBEF interaction delays sister ter segregation in cells lacking MatP. We propose that the interplay between MukBEF and MatP directs chromosome organization in relation to MukBEF clusters and associated topisomerase IV, thereby ensuring timely chromosome unlinking and segregation. MukBEF, the bacterial structural maintenance of chromosomes complex, is known to associate with origins of replication and topoisomerase IV. Here the authors show an association of MukBEF with MatP and replication termination regions, important for proper sister chromatid decatenation and segregation.
MukB ATPases are regulated independently by the N- and C-terminal domains of MukF kleisin
The Escherichia coli SMC complex, MukBEF, acts in chromosome segregation. MukBEF shares the distinctive architecture of other SMC complexes, with one prominent difference; unlike other kleisins, MukF forms dimers through its N-terminal domain. We show that a 4-helix bundle adjacent to the MukF dimerisation domain interacts functionally with the MukB coiled-coiled ‘neck’ adjacent to the ATPase head. We propose that this interaction leads to an asymmetric tripartite complex, as in other SMC complexes. Since MukF dimerisation is preserved during this interaction, MukF directs the formation of dimer of dimer MukBEF complexes, observed previously in vivo. The MukF N- and C-terminal domains stimulate MukB ATPase independently and additively. We demonstrate that impairment of the MukF interaction with MukB in vivo leads to ATP hydrolysis-dependent release of MukBEF complexes from chromosomes. Most DNA in a cell is arranged in structures called chromosomes. From bacteria to humans, chromosomes have to be compacted and highly organized to allow the cells to maintain and use their genetic information. In all organisms, large ring-shaped protein complexes play a crucial role in managing chromosomes. They transport and organize DNA thanks to reactions whose precise mechanism remains unknown. In bacteria, MukB and a type of kleisin called MukF are two examples of molecules involved in chromosome management. Two MukBs join at one end to form a hinge; at the other end, each MukB protein has a neck and a head. The two heads are linked by the kleisin to form a large protein ring, which can open to capture DNA. The MukB heads can trigger a biochemical reaction that creates the energy essential to trap and release DNA during DNA transport. Here, Zawadzka et al. study how the different components of the MukB-kleisin complex interact with each other to undergo the biochemical reactions that lead to DNA transport. The experiments show that the kleisin joins two MukB heads by attaching the base of one to the neck of the other, asymmetrically closing the ring. The separate interactions of different regions of the kleisin to the head and neck of MukB independently activate the two MukB heads, thereby controlling essential steps in the reactions with DNA. Two MukB-kleisin ring complexes are joined to each other because of a tight interaction between the two kleisin molecules. This leads Zawadzka et al. to suggest that DNA is sequentially grabbed and released from these two rings during DNA transport, similar to how a climbing rope is attached and released through carabiners. Cells cannot survive or be healthy without their chromosomes being accurately managed. It is still unclear how molecules such as MukBs and kleinsins drive this process. A better picture of their structure and interactions is an essential first step to understand these mechanisms.
Effects of diamond nanoparticle surface composition and the sp3/sp2 carbon ratio on tumor proangiogenic potential in vitro
The high proangiogenic potential of tumors is often associated with poor prognosis due to increased invasiveness and malignancy. Diamond nanoparticles (NDs) are considered a promising anti-tumor agent with anti-angiogenic properties; however, their activity is strictly connected with their physicochemical parameters and surface chemical composition. One of the main factors characterizing detonation NDs is the sp 2 surface carbon content, which can determine the character of nanoparticle–cell interaction. The primary objective of this study was to investigate the influence of different types of NDs on the proangiogenic potential of tumor cells distinguished by phenotype and invasiveness. NDs with a high sp 3 /sp 2 carbon ratio decreased the levels of crucial proangiogenic proteins secreted by T98G and HepG2 cells (IL-6, IL-8, ANG, TIMPs, and ANGPTs). Moreover, a lower sp 2 carbon content on the surface of NDs reduced oxidative stress in both mesenchymal T98G and epithelial HepG2 tumor cells and affected the NF-κB activation state in a cell-specific manner. Modified NDs, by affecting the tumor cell secretome composition, indirectly inhibited endothelial cell migration and tube formation, demonstrating high cell type specificity. Taken together, the results presented here indicate the significance of the surface parameters of NDs in the indirect regulation of cellular signaling and the microenvironment.
Clinical Manifestation of Subacute Thyroiditis Triggered by SARS-CoV-2 Infection Can Be HLA-Dependent
In the last two years, we have been struggling with the pandemic of SARS-CoV-2, the virus causing COVID-19. Several cases of subacute thyroiditis (SAT) have already been described as directly related to SARS-CoV-2 infection. The clinical course of SAT induced by SARS-CoV-2 can be entirely different from the classic SAT course, and one of the most important differences is a very rapid SAT onset observed in some patients, especially a phenomenon of the simultaneous presence of both diseases. The aim of this report is to compare HLA profile and clinical course of SAT in four patients, in whom SAT was considered as triggered by COVID-19, with special attention paid to the differences between a patient with rare simultaneous presence of SAT and COVID-19, and patients with longer time lag between the diseases. The unusual phenomenon of simultaneous occurrence of COVID-19 and SAT induced by SARS-CoV-2 infection can be HLA-dependent and related to the presence of homozygosity at HLA-B*35. Additionally, the clinical course of SAT triggered by COVID-19 can be HLA-related in regard to the risk of recurrence, and to a variety of other aspects, including severity of thyrotoxicosis.
Attitudes in Poland Towards the Legalization of Same-Sex Registered Partnerships in the Context of Political Preferences
BackgroundOver recent decades, the issue of same-sex civil unions has been discussed and then legally regulated in many European Union countries. In the case of Poland, this issue is still debated in the socio-political discourse.MethodsThe research presented in this article is aimed at analyzing the attitudes of Polish society towards legalization of same-sex registered partnerships. The study was nationwide and based on a quota sampling method (n = 2119). The data was collected in 2019.ResultsAn analysis of the collected data showed that the support for legalizing same-sex partnerships is not accepted by the majority of voters in Poland. However, there are differences between supporters of various political groups as well as between those who declare left-wing or right-wing views.ConclusionsFor opponents of equal rights for homosexuals and heterosexuals, a crucial issue is the objection to same-sex marriage. The voters of left-wing parties and people declaring left-wing political leanings were more likely to accept other forms of marriage, although for the majority of them, marriage can be only a union between a woman and a man.Policy ImplicationsThe resistance of the ruling party Law and Justice, a conservative one, against legalization of same-sex partnerships and making decisions aimed at LGBT community, for instance introducing “LGBT-free zones,” are one of the elements encouraging its electorate.