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1.
Ewa Bczyska Katarzyna Karolina Pels Subhadip Basu Jakub Wodarczyk Baej Ruszczycki 《International journal of molecular sciences》2021,22(8)
Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance. 相似文献
2.
Agnieszka Rybarczyk-Kasiuchnicz Rodryg Ramlau Katarzyna Stencel 《International journal of molecular sciences》2021,22(2)
Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases. 相似文献
3.
Ewelina Bik Lukasz Mateuszuk Jagoda Orleanska Malgorzata Baranska Stefan Chlopicki Katarzyna Majzner 《International journal of molecular sciences》2021,22(5)
Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ on human microvascular endothelial cells (HMEC-1). HMEC-1 cells after CQ exposure were measured using a combined methodology based on label-free Raman and fluorescence imaging. Raman spectroscopy was applied to characterize subtle chemical changes in lipid contents and their distribution in the cells, while the fluorescence staining (LipidTox, LysoTracker and LC3) was used as a reference method. The results showed that CQ was not toxic to endothelial cells and did not result in the endothelial inflammation at concentrations of 1–30 µM. Notwithstanding, it yielded an increased intensity of LipidTox, LysoTracker, and LC3 staining, suggesting changes in the content of neutral lipids, lysosomotropism, and autophagy inhibition, respectively. The CQ-induced endothelial response was associated with lipid accumulation and was characterized by Raman spectroscopy. CQ-induced autophagosome accumulation in the endothelium is featured by a pronounced alteration in the lipid profile, but not in the endothelial inflammation. Raman-based assessment of CQ-induced biochemical changes offers a better understanding of the autophagy mechanism in the endothelial cells. 相似文献
4.
Ewa Maria Kratz Katarzyna Sokiewicz Adriana Kubis-Kubiak Agnieszka Piwowar 《International journal of molecular sciences》2021,22(2)
Sirtuins (SIRTs), enzymes from the family of NAD+-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results. 相似文献
5.
Rita Głowacka Agata Górska Magdalena Wirkowska-Wojdyła Rafał Wołosiak Ewa Majewska Dorota Derewiaka 《International Journal of Food Science & Technology》2019,54(11):3008-3014
The content of bioactive compounds in spent coffee grounds (SGC) was studied. SGC were obtained from Coffea arabica beans of different roasting degrees (light and dark) and different geographical origins (Nicaragua, Columbia and Mexico) processed using four brewing methods (mocha, filtered, drip and infusion). The highest caffeine and chlorogenic acid contents were determined in filtered spent coffee extracts. All extracts of light roasted spent coffee grounds showed lower browning index levels in comparison to that from dark roasted spent coffee grounds. Generally, the highest content of total polyphenolic compounds and highest antioxidant capacity were determined in extracts prepared in drip. In conclusion, the results obtained in this study indicate that the spent coffee grounds produced of domestic levels, especially those obtained from filter coffeemaker, could be considered as a good source of natural antioxidants. 相似文献
6.
Katarzyna Świrk Paulina Summa Dominik Wierzbicki Monika Motak Patrick Da Costa 《International Journal of Hydrogen Energy》2021,46(34):17776-17783
A series of V-promoted hydrotalcite-derived nickel catalysts (1.0, 2.0, and 4.0 wt%) were tested in CO2 methanation. Ni–I–V2.0 with 2.0 wt% vanadium loading showed the highest catalytic activity, achieving 74.7% of CO2 conversion and 100% of CH4 selectivity at 300 °C. XRD and XANES analyses showed that the smallest Ni0 particles in Ni–I–V2.0 were consistent with the improved textural features observed for this catalyst. Moreover, CO2-TPD revealed the highest sum of weak and medium basic sites in Ni–I–V2.0 that can positively influence catalytic behavior. For the studied catalysts, a clear correlation was demonstrated between the catalytic activity and specific surface area, as well as the basic properties. 相似文献
7.
Katarzyna Szkudelska Marzanna Deniziak Maciej Sassek Ignacy Szkudelski Wojciech Noskowiak Tomasz Szkudelski 《International journal of molecular sciences》2021,22(5)
Resveratrol is a biologically active diphenolic compound exerting multiple beneficial effects in the organism, including anti-diabetic properties. This action is, however, not fully elucidated. In the present study, we examined effects of resveratrol on some parameters related to insulin signaling, and also on diabetes-associated dysregulation in Goto-Kakizaki (GK) rats with congenital type 2 diabetes. Resveratrol was given at the dose of 20 mg/kg b.w. for 10 weeks. It was shown that the expression and phosphorylation levels of insulin receptor in the skeletal muscle of GK rats were significantly decreased, compared with control animals. However, these changes were totally prevented by resveratrol. Liver expression of the insulin receptor was also reduced, but in this case, resveratrol was ineffective. Resveratrol was also demonstrated to significantly influence parameters of insulin binding (dissociation constant and binding capacity) in the skeletal muscle and liver. Moreover, it was shown that the expression levels of proteins related to intracellular glucose transport (GLUT4 and TUG) in adipose tissue of GK rats were significantly decreased. However, treatment with resveratrol completely abolished these changes. Resveratrol was found to induce normalization of TUG expression in the skeletal muscle. Blood levels of insulin and GIP were elevated, whereas proinsulin and GLP-1 diminished in GK rats. However, concentrations of these hormones were not affected by resveratrol. These results indicate that resveratrol partially ameliorates diabetes-associated dysregulation in GK rats. The most relevant finding covers the normalization of the insulin receptor expression in the skeletal muscle and also GLUT4 and TUG in adipose tissue. 相似文献
8.
Katarzyna Tokarczyk-Dorociak Jan K. Kazak Haładyj Anna Szymon Szewrański Małgorzata Świąder 《影响评估与项目评价》2019,37(3-4):279-291
The paper presents the results of an evaluation of the effectiveness of SEA obtained as a result of a survey with the participation of stakeholders. In Poland, several hundred SEAs are conducted annually at the local and regional levels and several at the national level. Although the survey demonstrated that SEA is evaluated as effective or quite effective, the respondents pointed to several irregularities in the non-procedural dimension of effectiveness. The main ones in terms of substantive effectiveness are that SEA is rarely used to help develop plans/programmes and procedures are highly politicised. Moreover, low effectiveness in terms of variant assessment and cumulative impacts and nearly non-existent monitoring of the actual effects of implementing plans/programmes influence substantive effectiveness significantly. The respondents pointed to the problem resulting from the fact that plan-makers are unwilling to take into account the SEA recommended changes. They also emphasised that there are certain attempts to put pressure on SEA consultants to make the conclusions less stringent. Respondents indicate that in Poland the costs associated with conducting SEA often outweigh the profits. The research shows that the society is properly informed about SEA, but public involvement is still low. 相似文献
9.
Ryszard Żywica Monika Modzelewska-Kapituła Katarzyna Tkacz 《International Journal of Food Properties》2018,21(1):1386-1394
The aim of the present study was to determine mathematical relationships between pH changes in beef 24 h post-slaughter and changes in the intensity of electrical current flowing through bull and heifer carcasses during high-voltage electrical stimulation. The electrical stimulation was applied 40 min postmortem for 120 s. The pH values of m. longissimus thoracis et lumborum were analyzed in the function of electrical current intensity changes and its change during electrical stimulation. Mathematical linear correlations of the y = ax ± b type were demonstrated between pH values at 2, 6, and 24 h postmortem and the initial (Ii) and ultimate (Iu) electrical current intensity values, the difference between them and the initial pH values determined before electrical stimulation. High multiple correlation coefficients (R2 = 0.416, α ≤ 0.001) between Iu and pH values 24 h post-slaughter enabled concluding that there is a possibility to predict a pH value of stimulated carcass with high accuracy, and thus also beef quality, based merely on the ultimate electrical current intensity values. 相似文献
10.
A hybrid fluidized-bed bioreactor for water purification was proposed and analyzed. It is a novel type of bioreactor characterized by hitherto unknown stationary and dynamic features. Steady-state characteristics of this hybrid bioreactor with external liquid circulation are presented. A quantitative analysis of steady-state properties of the bioreactor was performed with the aid of an original mathematical model developed for a double-substrate aerobic microbiological process. A steady-state analysis of aerobic processes characterized by different oxygen demand was performed. The effect of essential parameters was evaluated, including carbonaceous substrate concentration in the feed stream to the apparatus, aeration intensity, total residence time of a liquid in the bioreactor, and height of the bed of fine carrier particles. 相似文献