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We report the case of a 55-year-old man with multi-symptomatic transverse myelitis after vaccination against coronavirus disease 2019 (COVID-19). The patient was diagnosed based on the course of the disease and the results of imaging and laboratory tests. We excluded other most probable causes of the disease. The quick start of diagnosis allowed for early treatment with intravenous steroids and then plasmapheresis and the implementation of modern rehabilitation methods using biofeedback platforms, among others, and an exoskeleton. The patient returned to work, but the rehabilitation process continues to this day due to persistent symptoms that impair the patient's quality of life.

The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis and in vitro studies assessing cancer cell phenotypes, and we searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and immune system. Moreover, we observed that ZNF643 positively influences cell cycle, migration, and invasion. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes.

Despite the ongoing progress in diagnosis and treatments, cancer remains a threat to more than one-third of the human population. The emerging data indicate that many Krüppel-associated box zinc finger proteins (KRAB-ZNF) belonging to a large gene family may be involved in carcinogenesis. Our previous study identified Zinc Finger Protein 714 (ZNF714), a KRAB-ZNF gene of unknown function, as being commonly overexpressed in many tumors, pointing to its hypothetical oncogenic role. Here, we harnessed The Cancer Genome Atlas (TCGA)-centered databases and performed functional studies with transcriptomic and methylomic profiling to explore ZNF714 function in cancer. Our pan-cancer analyses confirmed frequent ZNF714 overexpression in multiple tumors, possibly due to regional amplification, promoter hypomethylation, and Nuclear Transcription Factor Y Subunit Beta (NFYB) signaling. We also showed that ZNF714 expression correlates with tumor immunosuppressive features. The in vitro studies indicated that ZNF714 expression positively associates with proliferation, migration, and invasion. The transcriptomic analysis of ZNF714 knocked-down cells demonstrated deregulation of cell adhesion, migration, proliferation, apoptosis, and differentiation. Importantly, we provided evidence that ZNF714 negatively regulates the expression of several known TSGs indirectly via promoter methylation. However, as ZNF714 did not show nuclear localization in our research model, the regulatory mechanisms exerted by ZNF714 require further investigation. In conclusion, our results reveal, for the first time, that ZNF714 may support pro-oncogenic features in lung cancer cells.

In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development.

Wharton's jelly (WJ) contains mesenchymal stem cells (MSCs) exhibiting broad immunomodulatory properties and differentiation capacity, which makes them a promising tool for cellular therapies. Although the osteogenic, chondrogenic and adipogenic differentiation is a gold standard for proper identification of MSCs, it is important to elucidate the exact molecular mechanisms governing these processes to develop safe and efficient cellular therapies. Umbilical cords were collected from healthy, full-term deliveries, for subsequent MSCs (WJ-MSCs) isolation. WJ-MSCs were cultivated in vitro for osteogenic, chondrogenic, adipogenic and neurogenic differentiation. The RNA samples were isolated and the transcript levels were evaluated using NovaSeq platform, which led to the identification of differentially expressed genes. Expression of H19 and SLPI was enhanced in adipocytes, chondrocytes and osteoblasts, and NPPB was decreased in all analyzed groups compared to the control. KISS1 was down-regulated in adipocytes, chondrocytes, and neural-like cells compared to the control. The most of identified genes were already implicated in differentiation of MSCs; however, some genes ( PROK1 , OCA2 ) have not yet been associated with initiating final cell fate. The current results indicate that both osteo- and adipo-induced WJ-MSCs share many similarities regarding the most overexpressed genes, while the neuro-induced WJ-MSCs are quite distinctive from the other three groups. Overall, this study provides an insight into the transcriptomic changes occurring during the differentiation of WJ-MSCs and enables the identification of novel markers involved in this process, which may serve as a reference for further research exploring the role of these genes in physiology of WJ-MSCs and in regenerative medicine.

The untargeted approach to mass spectrometry-based metabolomics has a wide potential to investigate health and disease states, identify new biomarkers for diseases, and elucidate metabolic pathways. All this holds great promise for many applications in biological and chemical research. However, the complexity of instrumental parameters on advanced hybrid mass spectrometers can make the optimization of the analytical method immensely challenging. Here, we report a strategy to optimize the selected settings of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for untargeted metabolomics studies of human plasma, as a sample matrix. Specifically, we evaluated the effects of the reconstitution solvent in the sample preparation procedure, the injection volume employed, and different mass spectrometry-related operating parameters including mass range, the number of data-dependent fragmentation scans, collision energy mode, duration of dynamic exclusion time, and mass resolution settings on the metabolomics data quality and output. This study highlights key instrumental variables influencing the detection of metabolites along with suggested settings for the IQ-X tribrid system and proposes a new methodological framework to ensure increased metabolome coverage.

Heart failure remains a major cause of death worldwide. There is a need to establish new management options as current treatment is frequently suboptimal. Clinical approaches based on autologous stem cell transplant is potentially a good alternative. The heart was long considered an organ unable to regenerate and renew. However, several reports imply that it may possess modest intrinsic regenerative potential. To allow for detailed characterization of cell cultures, whole transcriptome profiling was performed after 0, 7, 15, and 30 days of in vitro cell cultures (IVC) from the right atrial appendage and right atrial wall utilizing microarray technology. In total, 4239 differentially expressed genes (DEGs) with ratio > abs |2| and adjusted p -value ≤ 0.05 for the right atrial wall and 4662 DEGs for the right atrial appendage were identified. It was shown that a subset of DEGs, which have demonstrated some regulation of expression levels with the duration of the cell culture, were enriched in the following GO BP (Gene Ontology Biological Process) terms: "stem cell population maintenance" and "stem cell proliferation". The results were validated by RT-qPCR. The establishment and detailed characterization of in vitro culture of myocardial cells may be important for future applications of these cells in heart regeneration processes.

Despite the rising public awareness of the risk factors and the possible prevention of melanoma development, it remains challenging in terms of diagnosis and treatment. To improve the clinical situation of patients, it would be especially beneficial to develop prognostic methods for the effective and continuous assessment of the disease course. The solution could lie in the selection of effective biomarkers derived from the tumor microenvironment, increasing the effectiveness of melanoma prognoses and monitoring. Hence, in this study, we evaluated the number of circulating melanoma cells (CMCs) in representative blood samples of melanoma patients vs. healthy controls, as well as the proportion of particular cytotoxic T cells in the total lymphocyte and leukocyte population as a reflection of immune resistance. The results were correlated with the clinical parameters of the patients to examine the potential value of CMC quantification and lymphoid cell phenotyping in melanoma diagnostics, prognostics, and treatment outcome monitoring. The CMC numbers were significantly higher in melanoma patients than in healthy controls. However, an analysis of the correlations between the baseline CMC counts and the clinical parameters found no significant results. In turn, we found significant differences between the groups in the percentage of various profiles of CD8+ cytotoxic T lymphocytes characterized by TIGIT and TIM-3 differential expression. Importantly, the CMC number correlated with CD8+TIGIT+ and CD8+TIGIT+TIM-3- cytotoxic T cell counts in the melanoma patient group. Considering the above, the combination of CMCs and the immunological status of the patient, as defined by the prevalence of selected immune cell types, seems to be a promising approach in melanoma diagnostics and prognostics.

Breast cancer is one of the most frequently observed malignancies worldwide and represents a heterogeneous group of cancers. For this reason, it is crucial to properly diagnose every single case so a specific and efficient therapy can be adjusted. One of the most critical diagnostic parameters evaluated in cancer tissue is the status of the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). Interestingly, the expression of the indicated receptors may be used in a personalized therapy approach. Importantly, the promising role of phytochemicals in the modulation of pathways controlled by ER and EGFR was also demonstrated in several types of cancer. One such biologically active compound is oleanolic acid, but due to poor water solubility and cell membrane permeability that limits its use, alternative derivative compounds were developed. These are HIMOXOL and Br-HIMOLID, which were demonstrated to be capable of inducing apoptosis and autophagy or diminishing the migratory and invasive potential of breast cancer cells in vitro. In our study, we revealed that proliferation, cell cycle, apoptosis, autophagy, and also the migratory potential of HIMOXOL and Br-HIMOLID in breast cancer cells are mediated by ER (MCF7) and EGFR (MDA-MB-231) receptors. These observations make the studied compounds interesting in the context of anticancer strategies.

Myeloid-derived suppressor cells (MDSC) are a subset of immature myeloid cells with suppressive activity well described in the context of cancer. They inhibit anti-tumour immunity, promote metastasis formation and can lead to immune therapy resistance. In a retrospective study, blood probes of 46 advanced melanoma patients were analysed before the first administration of anti-PD-1 immunotherapy and in the third month of treatment for MDSC, immature monocytic (ImMC), monocytic MDSC (MoMDSC) and granulocytic MDSC (GrMDSC) by multi-channel flow cytometry. Cell frequencies were correlated with response to immunotherapy, progression-free survival (PFS) and lactate dehydrogenase (LDH) serum level. Responders to anti-PD-1 therapy had higher MoMDSC levels (4.1 ± 1.2%) compared to non-responders (3.0 ± 1.2%) ( p = 0.0333) before the first administration of anti-PD-1. No significant changes in MDSCs frequencies were observed in the groups of patients before and in the third month of therapy. The cut-off values of MDSCs, MoMDSCs, GrMDSCs and ImMCs for favourable 2- and 3-year PFS were established. Elevated LDH level is a negative prognostic factor of response to the treatment and is related to an elevated ratio of GrMDSCs and ImMCs level compared to patients' LDH level below the cut-off. Our data may provide a new perspective for more careful consideration of MDSCs, and specially MoMDSCs, as a tool for monitoring the immune status of melanoma patients. Changes in MDSC levels may have a potential prognostic value, however a correlation with other parameters must be established.

The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy, and ten healthy subjects were recruited. The response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis and the metataxonomics of the microbiota. In the responders, the Bacteroidota to Firmicutes ratio was higher, and the richness was decreased. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas the non-responders’ gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption as well as gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota along with diet were found to be associated with the response to the therapy in the population of melanoma patients.

Traditionally, sustainable development has been seen as a combination of three pillars: economic, social and environmental development. In recent years, another one has been added to these three pillars, namely culture, as being indispensable in achieving sustainable development. This study proposes an integrated approach for the identification and classification of safety culture factors in the company in a sustainability context. The research design was based on the assumption that safety culture is part of organizational culture that should support the development of corporate sustainability. Firstly, the identification of the safety culture factors (SCFs) based on the literature review was presented. Then, the ISM method was used to identify the interaction between SCFs and to develop the hierarchical structure of these factors. In the next step, ISM was integrated with the MICMAC method to cluster the factors based on driving power and dependence power into four categories. Finally, safety culture factors with high driving power were rated using the fuzzy TOPSIS method from the sustainability dimension perspective. This approach was used in an automotive industry company to improve and develop the company's practices aimed at implementing a sustainable development strategy. A sensitivity analysis was also carried out to monitor the robustness of the approach.

The interest in stem cell research continuously increased over the last decades, becoming one of the most important trends in the 21st century medicine. Stem cell-based therapies have a potential to become a solution for a range of currently untreatable diseases, such as spinal cord injuries, type I diabetes, Parkinson's disease, heart disease, stroke, and osteoarthritis. Hence, this study, based on canine material, aims to investigate the molecular basis of adipose-derived stem cell (ASC) differentiation into chondrocytes, to serve as a transcriptomic reference for further research aiming to introduce ASC into treatment of bone and cartilage related diseases, such as osteoarthritis in veterinary medicine. Adipose tissue samples were harvested from a canine specimen subjected to a routine ovariohysterecromy procedure at an associated veterinary clinic. The material was treated for ASC isolation and chondrogenic differentiation. RNA samples were isolated at day 1 of culture, day 30 of culture in unsupplemented culture media, and day 30 of culture in chondrogenic differentiation media. The resulting RNA was analyzed using RNAseq assays, with the results validated by RT-qPCR. Between differentiated chondrocytes, early and late cultures, most up- and down-regulated genes in each comparison were selected for further analysis., there are several genes (e.g., MMP12 , MPEG1 , CHI3L1 , and CD36 ) that could be identified as new markers of chondrogenesis and the influence of long-term culture conditions on ASCs. The results of the study prove the usefulness of the in vitro culture model, providing further molecular insight into the processes associated with ASC culture and differentiation. Furthermore, the knowledge obtained could be used as a molecular reference for future in vivo and clinical studies.

Numerous cardiovascular diseases (CVD) eventually lead to severe myocardial dysfunction, which is the most common cause of death worldwide. A better understanding of underlying molecular mechanisms of cardiovascular pathologies seems to be crucial to develop effective therapeutic options. Therefore, a worthwhile endeavor is a detailed molecular characterization of cells extracted from the myocardium. A transcriptomic profile of atrial cardiomyocytes during long-term primary cell culture revealed the expression patterns depending on the duration of the culture and the heart segment of origin (right atrial appendage and right atrium). Differentially expressed genes (DEGs) were classified as involved in ontological groups such as: "cellular component assembly", "cellular component organization", "cellular component biogenesis", and "cytoskeleton organization". Transcriptomic profiling allowed us to indicate the increased expression of COL5A2 , COL8A1 , and COL12A1 , encoding different collagen subunits, pivotal in cardiac extracellular matrix (ECM) structure. Conversely, genes important for cellular architecture, such as ABLIM1 , TMOD1 , XIRP1 , and PHACTR1 , were downregulated during in vitro culture. The culture conditions may create a favorable environment for reconstruction of the ECM structures, whereas they may be suboptimal for expression of some pivotal transcripts responsible for the formation of intracellular structures.

This article presents a comparative analysis of bacterial cellulose membranes synthesized by several strains of the Komagataeibacter genus in terms of their specific physical, physico-chemical, and mechanical properties. Herein, the aim was to choose the most suitable microorganisms producing cellulosic materials with the greatest potential for the fabrication of bio-inspired nanocomposites. The selection was based on three main steps, starting from the evaluation of BNC biosynthetic efficiency with and without the addition of ethanol, followed by the assessment of mechanical breaking strength, and the physical parameters (compactness, structural integrity, appearance, and thickness) of the obtained biological materials. Ultimately, based on the performed screening procedure, three efficiently growing strains ( K. hansenii H3 (6Et), K. rhaeticus K4 (8Et), and Komagataeibacter sp. isolated from balsamic vinegar (12Et)) were chosen for further modifications, enabling additional cellulose functionalization. Here, supplementation of the growth medium with five representative polymeric compounds (citrus/apple pectin, wheat starch, polyvinyl alcohol, polyethylene glycol) led to significant changes in BNC properties, especially dye loading abilities, mechanical strength, and water adsorption/retention capacities. The resulting nanocomposites can be potentially useful in various fields of medicine and industry, and in the future, they may become a practical and cost-effective competitor against commercial biomaterials currently available on the market.

Platinum electrodes were modified with polymers of the (±)- trans -N,N'-bis(salicylidene)-1,2-cyclohexanediaminenickel(II) ([Ni(salcn)]) and (±)- trans -N,N'-bis(3,3'- tert -Bu-salicylidene)-1,2-cyclohexanediaminenickel(II) ([Ni(salcn(Bu))]) complexes to study their electrocatalytic and electroanalytical properties. Poly [Ni(salcn)] and poly [Ni(salcn(Bu))]) modified electrodes catalyze the oxidation of catechol, aspartic acid and NO 2 - . In the case of poly [Ni(salcn)] modified electrodes, the electrocatalysis process depends on the electroactive surface coverage. The films with low electroactive surface coverage are only a barrier in the path of the reducer to the electrode surface. The films with more electroactive surface coverage ensure both electrocatalysis inside the film and oxidation of the reducer directly on the electrode surface. In the films with the most electroactive surface coverage, electrocatalysis occurs only at the polymer-solution interface. The analysis was based on cyclic voltammetry, EQCM (electrochemical quartz crystal microbalance) and rotating disc electrode method.

Tropomyosin (Tpm) is an actin-binding coiled-coil protein. In muscle, it regulates contractions in a troponin/Ca 2+ -dependent manner and controls the thin filament lengths at the pointed end. Due to its size and periodic structure, it is difficult to observe small local structural changes in the coiled coil caused by disease-related mutations. In this study, we designed 97-residue peptides, Tpm1.1 64-154 and Tpm3.12 65-155 , focusing on the actin-binding period 3 of two muscle isoforms. Using these peptides, we evaluated the effects of cardiomyopathy mutations: I92T and V95A in Tpm1.1, and congenital myopathy mutations R91P and R91C in Tpm3.12. We introduced a cysteine at the N-terminus of each fragment to promote the formation of the coiled-coil structure by disulfide bonds. Dimerization of the designed peptides was confirmed by gel electrophoresis in the presence and absence of dithiothreitol. Using circular dichroism, we showed that all mutations decreased coiled coil stability, with Tpm3.12 65-155 R91P and Tpm1.1 64-154 I92T having the most drastic effects. Our experiments also indicated that adding the N-terminal cysteine increased coiled coil stability demonstrating that our design can serve as an effective tool in studying the coiled-coil fragments of various proteins.

Higher stress reactivity during adolescence is a vulnerability marker of exposure to various environmental stressors. This study aimed to investigate the association between a high level of perceived stress experienced by adolescents and stressful stimuli induced from school environment, peer, and parental relationships. The data used were from a cross-sectional, observational study conducted in a stratified sample of 1846 adolescents (13-18 years) in the Wielkopolska province, Poland. Data were collected through self-administered questionnaires and anthropometric measurements. Perceived stress was assessed using the Perceived Stress Scale (PSS-10). The association of a high level of perceived stress with school-induced exposures was determined using multivariate logistic regression after adjusting for gender, age, height and weight status and interpersonal relationships (STATISTICA 13.1). It was found that girls were over three times more likely than boys to experience a high level of perceived stress. Moreover, girls appeared to be more vulnerable than boys to school-related stressors and weight status, while boys to stressors that can arise from interpersonal relationships. School environment was the only predictor factor of high perceived stress level with a large effect size in both boys (OR = 4.45; 95% CI: 3.11-6.36) and girls (OR = 6.22; 95% CI: 4.18-7.59). Given the findings of the present study, preventive programs are critical to mitigate the effect of stress from school on adolescents' health and well-being.

Approximately 20-30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes' derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin β1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.

The population of satellite cells (mSCs) is highly diversified. The cells comprising it differ in their ability to regenerate their own population and differentiate, as well as in the properties they exhibit. The heterogeneity of this group of cells is evidenced by multiple differentiating markers that enable their recognition, classification, labeling, and characterization. One of the main tasks of satellite cells is skeletal muscle regeneration. Myofibers are often damaged during vigorous exercise in people who participate in sports activities. The number of satellite cells and the speed of the regeneration processes that depend on them affect the time structure of an athlete's training. This process depends on inflammatory cells. The multitude of reactions and pathways that occur during the regeneration process results in the participation and control of many factors that are activated and secreted during muscle fiber damage and at different stages of its regeneration. However, not all of them are well understood yet. This paper presents the current state of knowledge on satellite cell-dependent skeletal muscle regeneration. Studies describing the effects of various forms of exercise and age on this process were reviewed.

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells' application in regenerative medicine.

Photobiomodulation (PBM), also called low-level laser treatment (LLLT), has been considered a promising tool in periodontal treatment due to its anti-inflammatory and wound healing properties. However, photobiomodulation's effectiveness depends on a combination of parameters, such as energy density, the duration and frequency of the irradiation sessions, and wavelength, which has been shown to play a key role in laser-tissue interaction. The objective of the study was to compare the in vitro effects of two different wavelengths-635 nm and 808 nm-on the human primary gingival fibroblasts in terms of viability, oxidative stress, inflammation markers, and specific gene expression during the four treatment sessions at power and energy density widely used in dental practice (100 mW, 4 J/cm 2 ). PBM with both 635 and 808 nm at 4 J/cm 2 increased the cell number, modulated extracellular oxidative stress and inflammation markers and decreased the susceptibility of human primary gingival fibroblasts to apoptosis through the downregulation of apoptotic-related genes ( P53 , CASP9 , BAX ). Moreover, modulation of mesenchymal markers expression ( CD90 , CD105 ) can reflect the possible changes in the differentiation status of irradiated fibroblasts. The most pronounced results were observed following the third irradiation session. They should be considered for the possible optimization of existing low-level laser irradiation protocols used in periodontal therapies.

Overvoltage transients occur after any type of switching activity in a power network, such as breaker operation, fault occurrence/clearance and rapid load change. This distortion of voltage is transformed to the secondary circuit of a voltage transformer. The maximum values of such impulses may many times exceed the rated value of its secondary voltage. This can lead to malfunction of measuring or protection devices connected to the secondary circuit of a voltage transformer and even their damage. The paper presents the application of determined values of ratio error at harmonics of the inductive voltage of the transformer to predict the value of transformed slow-front transient overvoltage to their secondary circuits. This will help to prevent malfunction of measuring or protection devices connected to the secondary side of the voltage transformer and increase their safety of operation. The inductive voltage transformer equivalent circuit for transformation of higher frequency components of distorted voltage must be extended with internal capacitances of windings. This is caused by the fact that the resonance phenomenon of the slow-front transient overvoltage results from leakage inductance and capacitance of primary winding, not from the magnetic core. Therefore, this behaviour is independent from the value of the applied voltage.

The methylated resveratrol analogue 3'-hydroxy-3,4,5,4'-tetramethoxystilbene (DMU-214) has been revealed to exert the anti-cancer activity by a block of the cell cycle at the G2/M phase, apoptosis induction, and metastasis inhibition. These biological events may be involved in crosstalk with the epidermal growth factor receptor (EGFR), which belongs to the ErbB family of receptor tyrosine kinases. Several cancer therapeutic approaches employ small molecules capable of inhibiting tyrosine kinases (e.g., gefitinib). According to more recent reports, combining gefitinib with chemotherapeutics, such as cisplatin, seems to be more effective than monotherapy. The present study aimed to assess the molecular mechanism of the potential anti-proliferative activity of individual and combined treatments with DMU-214 and gefitinib in SCC-25 and CAL-27 human tongue cancer cell lines. We showed for the first time the anti-cancer effects of DMU-214, gefitinib, and their combination in tongue cancer cells triggered via cell cycle arrest, apoptosis induction, and inhibition of the EGFR signaling pathway. The anti-proliferative effects of DMU-214 and gefitinib are also suggested to be related to the EGFR and EGFRP (phosphorylated epidermal growth factor receptor) expression status since we found significantly weaker cytotoxic activity of the compounds tested in SCC-25 cells, which overexpressed EGFR and EGFRP proteins.

In this study, we aimed to determine the effect of long-term exposure to artificial urine on the physical properties of CoCrMo alloy with biodegradable heparin-releasing polymeric coatings. Variants of polymer coatings of poly(L,L-lactide-ɛ-caprolactone) (P(L,L-L/CL)) and poly(D,L-lactide-ɛ-caprolactone) (P(D,L-L/CL)) constituting the base for heparin-releasing (HEP) polyvinyl alcohol (PVA) coatings were analyzed. The coatings were applied by the dip-coating method. Heparin was used to counteract the incrustation process in the artificial urine. The study included tests of wettability, resistance to pitting and crevice corrosion, determination of the mass density of metal ions penetrating into the artificial urine, and the kinetics of heparin release. In addition, microscopic observations of surface roughness and adhesion to the metal substrate were performed. Electrolytically polished CoCrMo samples (as a reference level) and samples with polymer coatings were used for the tests. The tests were conducted on samples in the initial state and after 30, 60, and 90 days of exposure to artificial urine. The analysis of the test results shows that the polymer coatings contribute by improving the resistance of the metal substrate to pitting and crevice corrosion in the initial state and reducing (as compared with the metal substrate) the mass density of metal ion release into the artificial urine. Moreover, the PVA + HEP coating, regardless of the base polymer coatings used, contributes to a reduction in the incrustation process in the first 30 days of exposure to the artificial urine.

Telomerase is known to contribute to telomere maintenance and to provide cancer cell immortality. However, numerous reports are showing that the function of the enzyme goes far beyond chromosome ends. The study aimed to explore how telomerase downregulation in MCF7 and MDA-MB-231 breast cancer cells affects their ability to survive. Consequently, sensitivity to drug resistance, proliferation, and adhesion were assessed. The lentiviral-mediated human telomerase reverse transcriptase (hTERT) downregulation efficiency was performed at gene expression and protein level using qPCR and Western blot, respectively. Telomerase activity was evaluated using the Telomeric Repeat Amplification Protocol (TRAP) assay. The study revealed that hTERT downregulation led to an increased sensitivity of breast cancer cells to doxorubicin which was demonstrated in MTT and clonogenic assays. During a long-term doubling time assessment, a decreased population doubling level was observed. Interestingly, it did not dramatically affect cell cycle distribution. hTERT downregulation was accompanied by an alteration in β1-integrin- and by focal adhesion kinase (FAK)-driven pathways together with the reduction of target proteins phosphorylation, i.e., paxillin and c-Src. Additionally, autophagy activation was observed in MDA-MB-231 cells manifested by alternations in Atg5, Beclin 1, LC3II/I ratio, and p62. These results provide new evidence supporting the possible therapeutic potential of telomerase downregulation leading to induction of autophagy and cancer cells elimination.

The influence of irradiation should be considered in fatigue reliability analyses of reactor structures under irradiation conditions. In this study, the effects of irradiation hardening and irradiation embrittlement on fatigue performance parameters were quantified and a fatigue life prediction model was developed. Based on this model, which takes into account the cumulative effect of a neutron dose, the total fatigue damage was calculated according to Miner's linear cumulative damage law, and the reliability analysis was carried out using the Monte Carlo simulation method. The case results show that the fatigue life acquired by taking into account the cumulative effect of irradiation was reduced by 24.3% compared with that acquired without considering the irradiation effect. Irradiation led to the increase of the fatigue life at low strains and its decrease at high strains, which is in accordance with the findings of an irradiation fatigue test. The rate of increase in the fatigue life decreased gradually with the increase of the neutron dose. The irradiation performance parameters had a small influence on fatigue reliability, while the fatigue strength coefficient and the elastic modulus had a great influence on the fatigue reliability. Compared with the current method, which uses a high safety factor to determine design parameters, a fatigue reliability analysis method taking into account the cumulative effect of irradiation could be more accurate in the reliability analysis and life prediction of reactor structures.

The aim of this review is to provide an overview of recent findings related to bacterial cellulose application in bio-packaging industry. This constantly growing sector fulfils a major role by the maintenance of product safety and quality, protection against environmental impacts that affect the shelf life. Conventional petroleum-based plastic packaging are still rarely recyclable and have a number of harmful environmental effects. Herein, we discuss the most recent studies on potential good alternative to plastic packaging-bacterial nanocellulose (BNC), known as an ecological, safe, biodegradable, and chemically pure biopolymer. The limitations of this bio-based packaging material, including relatively poor mechanical properties or lack of antimicrobial and antioxidant activity, can be successfully overcome by its modification with a wide variety of bioactive and reinforcing compounds. BNC active and intelligent food packaging offer a new and innovative approach to extend the shelf life and maintain, improve, or monitor product quality and safety. Incorporation of different agents BNC matrices allows to obtain e.g., antioxidant-releasing films, moisture absorbers, antimicrobial membranes or pH, freshness and damage indicators, humidity, and other biosensors. However, further development and implementation of this kind of bio-packaging will highly depend on the final performance and cost-effectiveness for the industry and consumers.

Self-calibration of a designed wideband inductive current transformer (CT) was carried out in the ampere-turns condition. This method does not require a reference transducer. The values of current and phase errors at the harmonics of frequencies from 100 Hz to 5 kHz were determined for the distorted primary current of the rated main frequency equal to 50 Hz. These results were verified based on the comparison of values measured between two CTs and calculated as the difference between values obtained from their calibration. Moreover, from vectorial diagrams drawn for transformation of the higher harmonics, the source of the change in the values of current and phase errors with frequency is explained. Furthermore, the method for calculation of the values of the corresponding harmonics of the current associated with the active power losses in the core and the magnetization current is presented.

The inhibition of the corrosion of metal implants is still a challenge. This study aimed to increase the corrosion resistance of Ti6Al7Nb alloy implants through surface modification, including grinding, sandblasting, and anodic oxidation followed by the deposition of a polymer coating. The aim of the work was to determine the influence of biodegradable polymer coatings on the physico-chemical properties of a Ti6Al7Nb alloy used for short-term implants. Biodegradable coatings prepared from poly(glycolide-caprolactone) (P(GCap)), poly(glycolide ε-caprolactone-lactide) (P(GCapL)), and poly(lactide-glycolide) (PLGA) were applied in the studies. The dip-coating method with three cycles of dipping was applied. Corrosion resistance was assessed on the basis of potentiodynamic studies. The studies were carried out on samples after 30, 60, and 90 days of exposure to Ringer's solution. Surface topography, wettability, and cytotoxicity studies were also carried out. The degradation process of the base material was evaluated on the basis of the mass density of the metal ions released to the solution. The results indicated the influence of the coating type on corrosion resistance. In addition, a beneficial effect of the polymer coating on the reduction of the density of the released metal ions was found, as compared to the samples without polymer coatings. The obtained results provide basic knowledge for the development of polymer coatings enriched with an active substance. The presence of ciprofloxacin in the coating did not reduce the corrosion resistance of the metal substrate. Moreover, the cytotoxicity test using the extract dilution method demonstrated that the implants' coatings are promising for further in vitro and in vivo studies.

The aim of the present study was to evaluate advanced glycation end products (AGEs) and soluble form of receptor RAGE (sRAGE) concentrations as well as the AGEs/sRAGE ratio in mild (MH) and resistant (RH) hypertensive patients in comparison with normotensive individuals. We also evaluated the association between AGEs, sRAGE as well as AGEs/sRAGE ratio and circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs). The MH group consisted of 30 patients, whereas 30 patients were classified for the RH group. The control group (C) included 25 normotensive volunteers. AGEs and sRAGE were measured using enzyme-linked-immunosorbent assay (ELISA). The multicolor flow cytometry was used for analysis of CECs and CEPCs. Significantly higher levels of AGEs in RH cohort were observed as compared to C cohort. Furthermore, significantly lower sRAGE levels as well as a higher AGEs/sRAGE ratio were observed between MH and RH cohorts. Significant correlations were found in the MH cohort for sRAGE and CECs, and CEPCs. The elevation of AGEs levels suggests that oxidative modification of proteins occurs in hypertension pathogenesis. The decrease in sRAGE levels and elevation of the AGEs/sRAGE ratio in MH and RH groups may suggest that hypertensive patients are less protected against the side effects of AGEs as a consequence of an insufficient competitive role of sRAGE against the AGEs-RAGE axis. Finally, it may be concluded that the level of AGEs may be an independent predictor of the condition and function of the endothelium. Furthermore, sRAGE may be classified as a potential biomarker of inflammation and endothelium dysfunction.

Human telomeres were one of the first discovered and characterized sequences forming quadruplex structures. Association of these structures with oncogenic and tumor suppressor proteins suggests their important role in cancer development and therapy efficacy. Since cationic porphyrin TMPyP4 is known as G-quadruplex stabilizer and telomerase inhibitor, the aim of the study was to analyze the anticancer properties of this compound in two different human breast-cancer MCF7 and MDA-MB-231 cell lines. The cytotoxicity of TMPyP4 alone or in combination with doxorubicin was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) and clonogenic assays, and the cell-cycle alterations were analyzed by flow cytometry. Telomerase expression and activity were evaluated using qPCR and telomeric repeat amplification protocol (TRAP) assays, respectively. The contribution of G-quadruplex inhibitor to protein pathways engaged in cell survival, DNA repair, adhesion, and migration was performed using immunodetection. Scratch assay and functional assessment of migration and cell adhesion were also performed. Consequently, it was revealed that in the short term, TMPyP4 neither revealed cytotoxic effect nor sensitized MCF7 and MDA-MB-231 to doxorubicin, but altered breast-cancer cell adhesion and migration. It suggests that TMPyP4 might substantially contribute to a significant decrease in cancer cell dissemination and, consequently, cancer cell survival reduction. Importantly, this effect might not be associated with telomeres or telomerase.