Search

Introduction: There is a significant increase in the number of children and adolescents diagnosed with autism spectrum disorder (ASD). The principle of collaboration with parents is one of the basic elements of comprehensive support provided to both children with ASD and their families. Research Aim: The aim of the research was a multi-faceted approach to the level of satisfaction of parents of children with ASD with the professional support and a search for personal traits and dispositions related to the level and various aspects of parents’ satisfaction with collaboration with specialists supporting their children and families. Method: The research was carried out in a group of 204 parents of children with ASD. The following measures were used: Family-Professional Partnership Scale (FPPS), Enabling Practices Scale (EPS), Ten Item Personality Inventory (TIPI) – TIPI-PL; Psychological Entitlement Scale (PES), and Gratitude Questionnaire (GQ-6). Results: The obtained results show an above-average satisfaction of parents with the support they receive. Significant predictors of the satisfaction of surveyed parents with the specialist support were the following personal characteristics and dispositions: gratitude, agreeableness, conscientiousness and openness. Conclusions: The results enable an initial assessment of satisfaction with formal support among parents of children with ASD. They also indicate selected personal dispositions related to a high level of satisfaction with the support received.

Abstract Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

Despite ongoing research in the field of breast cancer, the morbidity rates indicate that the disease remains a significant challenge. While patients with primary tumors have relatively high survival rates, these chances significantly decrease once metastasis begins. Thus, exploring alternative approaches, such as targeting proteins overexpressed in malignancies, remains significant. Filamin A (FLNa), an actin-binding protein (ABP), is involved in various cellular processes, including cell migration, adhesion, proliferation, and DNA repair. Overexpression of the protein was confirmed in samples from patients with numerous oncological diseases such as prostate, lung, gastric, colorectal, and pancreatic cancer, as well as breast cancer. Although most researchers concur on its role in promoting breast cancer progression and aggressiveness, discrepancies exist among studies. Moreover, the precise mechanisms through which FLNa affects cell migration, invasion, and even cancer progression remain unclear, highlighting the need for further research. To evaluate FLNa’s potential as a therapeutic target, we have summarized its roles in breast cancer.

Selection of the proper media is one of the teacher's duties in teaching. It must be followed by several aspects, one of which is teacher's ability in digital literacy to keep up with the developments of today's all-digital era. The study aimed to examine the effects of digital literacy levels on the selection of learning media for social science teachers. In the study, correlational quantitative method was used, with data collection applying questionnaires and document studies. The participants of the study were 22 social science teachers from 11 junior high schools selected via total sampling method. The obtained data were analyzed using simple linear regression. The results revealed that there was a significant effect between digital literacy on the selection of social science teacher learning media. The result of the regression equation is Y = 0.553 + 0.119X. Meanwhile, the result of hypothesis testing from the T-Test and F-Test showed that Ho was rejected and Ha was accepted.

Objectives: The purpose of this study was to determine the correlation between microscopic degeneration in the long head of the biceps tendon (LHBT) and the apoptotic process. Methods: This study included 26 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHBT with or without concomitant rotator cuff tears (RCTs). Histological examination of the specimens under a light microscope was conducted after staining with hematoxylin, eosin, and the Alcian blue. Histopathological changes were assessed using the original Bonar score and the modified Bonar score and then correlated with the expression of the subsequent apoptosis markers: activated caspase-3 (casp3), tumor protein p53 (p53), and B-cell lymphoma 2 (BCL-2). Results: The mean original Bonar score was 8.65 (range 5–11), while the modified Bonar score was 7.61. There was no correlation between the original Bonar score and the age of the patients, but a positive correlation was found between the modified Bonar score and the age of the patients (p = 0.0022). There was no correlation between the age of patients and the expression indexes of BCL-2 and casp3. However, the expression of the p53 index showed a positive correlation with patient aging (p = 0.0441). Furthermore, there was no correlation observed between the expression of apoptotic indexes and both the original and modified Bonar scale. Conclusions: In LHB tendinopathy, the expression of apoptosis does not seem to directly correlate with the extent of degeneration, particularly in the late stages of tendinopathy. However, the transformations observed in collagen and ground substance were significantly associated with age, as well as tendinous tissue degeneration quantified according to modified Bonar score. The age of patients was also linked with the expression of the p53 index, as an increased apoptosis in the studied population.

Abstract Targeting peptides or presequences are N-terminal extensions of proteins that encode information about their cellular localization. They include signal peptides (SP), which target proteins to the endoplasmic reticulum, and transit peptides (TP) directing proteins to the organelles of endosymbiotic origin: chloroplasts and mitochondria. TPs were hypothesized to have evolved from antimicrobial peptides (AMPs), which are responsible for the host defence against microorganisms, including bacteria, fungi and viruses. In this study, we performed comprehensive bioinformatic analyses of amino acid motifs of targeting peptides and AMPs using a curated set of experimentally verified proteins. We identified motifs frequently occurring in each type of presequence showing specific patterns associated with their amino acid composition, and investigated their position within the presequence. We also compared motif patterns among different taxonomic groups and identified taxon-specific features, providing some evolutionary insights. Considering the functional relevance and many practical applications of targeting peptides and AMPs, we believe that our analyses will prove useful for their design, and better understanding of protein import mechanism and presequence evolution.

We measured the fundamental financial knowledge and the level of using basic financial offers by persons with Asperger syndrome. It was pilot study. The method of diagnostic survey was used. The questionnaire used in the study was authorship, developed on the basis of S&P Global FinLit Survey, conducted by World Bank Development Research Group and GFLEC. The purposive sampling was used for this aim. 32 persons aged 16-22 with Asperger syndrome took part in the study. The results show that respondents are able to use theoretical knowledge acquired in the process of education and know the mechanism of simple and compound interest. Unfortunately, they have a significantly lower level of knowledge than an average citizen in the field of less standard issues, and reveal problems in practical use of the mentioned knowledge. It is recommended to expand the financial education and introduction of special programs for persons with communication disorders.

Abstract Due to their complex history, plastids possess proteins encoded in the nuclear and plastid genome. Moreover, these proteins localize to various subplastid compartments. Since protein localization is associated with its function, prediction of subplastid localization is one of the most important steps in plastid protein annotation, providing insight into their potential function. Therefore, we create a novel manually curated data set of plastid proteins and build an ensemble model for prediction of protein subplastid localization. Moreover, we discuss problems associated with the task, e.g. data set sizes and homology reduction. PlastoGram classifies proteins as nuclear- or plastid-encoded and predicts their localization considering: envelope, stroma, thylakoid membrane or thylakoid lumen; for the latter, the import pathway is also predicted. We also provide an additional function to differentiate nuclear-encoded inner and outer membrane proteins. PlastoGram is available as a web server at https://biogenies.info/PlastoGram and as an R package at https://github.com/BioGenies/PlastoGram . The code used for described analyses is available at https://github.com/BioGenies/PlastoGram-analysis .

Background and Objectives: The objective of this retrospective study was to investigate the association between acetabulum fractures; the mechanism of injury; and variables such as BMI, duration of hospital stay, blood loss, and surgery time. By exploring these factors, we aim to enhance our understanding of them and their impact on the healing process and the subsequent management of pelvic fractures. Materials and Methods: This study included 67 of 136 consecutive patients who were admitted for pelvic ring fracture surgery between 2017 and 2022. The data were collected prospectively at a single trauma center. The inclusion criteria were acetabulum fractures and indications for operative treatment. The exclusion criteria were non-operative treatment for acetabular and pelvic ring fractures, fractures requiring primary total hip arthroplasty (THA), and periprosthetic acetabular fractures. Upon admission, all patients underwent evaluation using X-ray and computed tomography (CT) scans of the pelvis. Results: The present study found no statistically significant differences between the examined groups of patients with pelvic fractures in terms of BMI, surgery duration, length of hospital stay, and blood transfusion. However, two notable findings approached statistical significance. Firstly, patients who experienced a fall from height while sustaining a pelvic fracture required a higher number of blood transfusions (2.3 units) than those with other mechanisms of injury which was close to achieving statistical significance (p = 0.07). Secondly, patients undergoing posterior wall stabilization required a significantly lower number of blood transfusions than those with other specific pelvic injuries (0.33 units per patient), approaching statistical significance (p = 0.056). Conclusions: The findings indicated that factors such as BMI, time of surgery, blood loss, and the duration of hospital stay were not directly correlated with the morphology of acetabular fractures, the presence of additional trauma, or the mechanism of injury. However, in the studied group, the patients whose mechanism of trauma involved falling from height had an increased number of blood transfusions compared to other groups. Moreover, the patients who had surgery due to posterior wall acetabulum fracture had decreased blood transfusions compared to those with other Judet and Letournel types of fractures. Additionally, they had the shortest duration of surgery.

Background and Objectives: The negative effects of smoking on the musculoskeletal system were presented by many authors, although the relationship between smoking and osteoarthritis remains unclear. The aim of this paper was to investigate the negative effects of smoking on meniscal tissue in osteoarthritic knees by microscopic examination, by adapting the Bonar scoring system and its modifications. Materials and Methods: The study involved 34 patients with varus knees, from whom 65 samples of knee menisci were obtained. The mean age in the studied group was 65.385 years. The smoking status of the patients concluded that there were 13 smokers and 21 nonsmokers. Results: Among smokers, the mean classical Bonar score was 8.42 and the mean modified Bonar score was 6.65, while nonsmokers were characterized by scores of 8.51 and 7.35, respectively. There was a statistically significant negative correlation between the number of cigarettes and the collagen in the medial meniscus (p = 0.0197). Moreover, in the medial meniscus, the modified Bonar score correlated negatively with the number of cigarettes (p = 0.0180). Similarly, such a correlation was observed between the number of cigarettes and the modified Bonar score in the lateral meniscus (p = 0.04571). Furthermore, no correlation was identified between the number of cigarettes and the classical Bonar score in the lateral meniscus. There was a statistically significant difference in the collagen variable value between the smokers and nonsmokers groups (p = 0.04525). Conclusions: The microscopic investigation showed no differences in the menisci of smokers and nonsmokers, except for the collagen, which was more organized in smokers. Moreover, the modified Bonar score was correlated negatively with the number of cigarettes, which supports the role of neovascularization in meniscus pathology under the influence of tobacco smoking.

Endometriosis is a gynecological condition where endometrium-like tissue grows outside the uterus, posing challenges in understanding and treatment. This article delves into the deep cellular and molecular processes underlying endometriosis, with a focus on the crucial roles played by cyclins and cytoskeletal proteins in its pathogenesis, particularly in the context of Epithelial–Mesenchymal Transition (EMT). The investigation begins by examining the activities of cyclins, elucidating their diverse biological roles such as cell cycle control, proliferation, evasion of apoptosis, and angiogenesis among ectopic endometrial cells. A comprehensive analysis of cytoskeletal proteins follows, emphasizing their fundamental biological roles and their specific significance to endometriotic cell features. This review sheds light on the interconnected pathways through which cyclins and cytoskeletal proteins converge, contributing to the genesis and progression of endometriosis. Understanding these molecular complexities not only provides insight into the underlying causes of the disease but also holds promise for the development of specific therapeutic approaches, ushering in a new era in the management of this devastating disorder.

Background: The substances present in cigarette smoke have a negative impact on cellular integrity and metabolism, can reduce blood flow to tissues, and can disrupt collagen synthesis. Ultimately this can lead to cell death, which clinically may result in impaired tendon healing and the onset of chronic tendinopathy. Within the shoulder, the exact association between the extent of apoptosis in the long head of the biceps (LHB) tendon and harmful factors like cigarette smoke remains unclear. Objectives: The purpose of this study was to investigate the connection between smoking, the degree of apoptosis in LHB tendinopathy, and the long-term outcomes of surgical treatment. Design: Observational, retrospective study. Methods: This study included 22 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHB tendinopathy with or without concomitant rotator cuff tears (RCT). The intra-articular LHB tendon remnants were histologically examined by measuring the level of expression of apoptotic cell markers such as BCL2, cleaved caspase 3, and p53. Pre- and postoperative clinical outcomes were analyzed by collecting patient report outcome measures such as the American Shoulder and Elbow Surgeons (ASES) score and the Visual Analogue Scale (VAS) for pain. Results: The smokers group had a mean pack-year history of 13.12 (SD = 9.94), mean number of cigarettes per day of 14.77 (SD = 4.64), and a mean smoking duration of 16.38 (SD = 10.1) years. Among the smoking indexes, the number of cigarettes per day showed a positive correlation with Snyder classification (p = 0.0459, rho = 0.3682). Non-smokers and smokers did not show a statistically significant difference in the expression indexes of BCL2, cleaved caspase 3, or p53 (p = 0.4216, p = 0.5449, p = 0.5613, respectively). However, the cleaved caspase 3 expression index showed a negative correlation with the severity of rotator cuff lesions in the total population (p = 0.0193, rho = −0.4651). Conclusions: While apoptotic processes in the LHB tendon were observed, no significant association was found between tobacco smoking, the extent of apoptosis, and clinical outcomes. However, the expression of the apoptotic marker cleaved caspase 3 correlated with the severity of rotator cuff pathology. Furthermore, active smoker status was associated with worse clinical outcomes in terms of pain following LHB tenodesis or tenotomy.

Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.

Melatonin (N-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor N-acetylserotonin (NAS) are only poorly understood. Herein, we treated human epidermal keratinocytes with UVB and assessed the protective effect of the studied substances in terms of the maintenance of mitochondrial function or their radical scavenging capacity. Our results show that UVB caused the significant elevation of catalase (CAT) and superoxide dismutase (Mn-SOD), the dissipation of mitochondrial transmembrane potential (mtΔΨ), a reduction in ATP synthesis, and the enhanced release of cytochrome c into cytosol, leading subsequently to UVB-mediated activation of the caspases and apoptosis (appearance of sub-G1 population). Our findings, combined with data reported so far, indicate the counteracting and beneficial actions of melatonin and its molecular derivatives against these deleterious changes within mitochondria. Therefore, they define a path to the development of novel strategies delaying mitochondrial aging and promoting the well-being of human skin.

Summary: The main aim of this study was to determine social support in the perception of mothers of children with autism spectrum disorders who experience their husband's economic migration. An important goal was also to show the differences in between the perceived social support in among mothers of children with autism spectrum disorders who experience their husband's migration, and those whose husbands do not go abroad for work. The research involved 94 mothers raising children with autism spectrum disorders, 46 women whose husbands migrate (A) and 48 women who do not experience their husbands' migration (B). The sample selection was deliberate. The Polish adaptation by E. Szlachta of the ISEL questionnaire (The Interpersonal Support Evaluation List) was used to achieve the goals, as accompanied by a self-made questionnaire. Analysis of the data on perceived social support showed statistically significant differences in the studied groups both in the overall result and across all scales. The results indicate that while mothers of children with autism spectrum disorders whose husbands go abroad are in a better financial situation, the absence and lack of active participation and support of the husband in caring for the child makes them feel there is less social support (scale of cognitive support, belonging, self-esteem), and they cope with problems much worse than women whose husbands do not go abroad. The results are statistically significant

Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking.

The immune system, unlike other systems, must be flexible and able to “adapt” to fully cope with lurking dangers. The transition from intracorporeal balance to homeostasis disruption is associated with activation of inflammatory signaling pathways, which causes modulation of the immunology response. Chemotactic cytokines, signaling molecules, and extracellular vesicles act as critical mediators of inflammation and participate in intercellular communication, conditioning the immune system’s proper response. Among the well-known cytokines allowing for the development and proper functioning of the immune system by mediating cell survival and cell-death-inducing signaling, the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) are noteworthy. The high bloodstream concentration of those pleiotropic cytokines can be characterized by anti- and pro-inflammatory activity, considering the powerful anti-inflammatory and anti-oxidative stress capabilities of TGF-β known from the literature. Together with the chemokines, the immune system response is also influenced by biologically active chemicals, such as melatonin. The enhanced cellular communication shows the relationship between the TGF-β signaling pathway and the extracellular vesicles (EVs) secreted under the influence of melatonin. This review outlines the findings on melatonin activity on TGF-β-dependent inflammatory response regulation in cell-to-cell communication leading to secretion of the different EV populations.

The broad spectrum of disorders of the long head of the biceps (LHBT) can be divided into 3 main categories: inflammatory reactions, degenerative conditions, and instability. More than 90% of patients with LHB tendinopathy have an additional shoulder pathology. Thus, a detailed radiological and histopathological evaluation is crucial for a complete and accurate diagnosis. The pathology of the LHBT starts from its ultrastructure with the alterations of both tenocytes and extracellular matrix. Furthermore, this is reflected in the light microscopy investigation, with marginal inflammatory response. The ultrasonography is useful in the detection of LHBT instability, hypoechogenic areas, increased tendon diameter, and dynamic examination of the tendon. A standard non-contrast magnetic resonance imaging (MRI) of the shoulder is a useful tool in the diagnostics of advance tendinopathy; however, it is essentially limited in the detection of partial tears. Based on current knowledge, ultrasound and MRI diagnostics modalities should be simultaneously used in the examination of LHBT disorders.

Abstract This study developed a new procedure of urinary bladder transplantation on a rat model (n = 40). Heterotopic urinary bladder transplantation (n = 10) in the right groin vessels was performed. Direct urinary bladder examination, microangiography, histological analysis, and India ink injection were performed to evaluate the proposed method's functionality. Observation time was four weeks. One week after the procedure, the graft survival rate was 80%, two urinary bladders were lost due to anastomosis failure. The rest of the grafts survived two weeks without any complications. Lack of transitional epithelium or smooth muscle layer loss and lack of inflammatory process development were observed. This study was performed in order to obtain the necessary knowledge about urinary bladder transplantation. The proposed technique offers a new approach to the existing orthotropic models.

Amyloids and antimicrobial peptides (AMPs) have many similarities, e.g., both kill microorganisms by destroying their membranes, form aggregates, and modulate the innate immune system. Given these similarities and the fact that the antimicrobial properties of short amyloids have not yet been investigated, we chose a group of potentially antimicrobial short amyloids to verify their impact on bacterial and eukaryotic cells. We used AmpGram, a best-performing AMP classification model, and selected ten amyloids with the highest AMP probability for our experimental research. Our results indicate that four tested amyloids: VQIVCK, VCIVYK, KCWCFT, and GGYLLG, formed aggregates under the conditions routinely used to evaluate peptide antimicrobial properties, but none of the tested amyloids exhibited antimicrobial or cytotoxic properties. Accordingly, they should be included in the negative datasets to train the next-generation AMP prediction models, based on experimentally confirmed AMP and non-AMP sequences. In the article, we also emphasize the importance of reporting non-AMPs, given that only a handful of such sequences have been officially confirmed.

Adrian Krajewski, Maciej Gagat, Klaudia Mikołajczyk, Magdalena Izdebska, Agnieszka Żuryń, Alina Grzanka Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, PolandCorrespondence: Maciej Gagat Tel +48 52 585 37 25Fax +48 52 585 37 34Email mgagat@cm.umk.plBackground: Cyclins are well-known cell cycle regulators. The activation of cyclin-dependent kinases by cyclins allows orchestration of the complicated cell cycle machinery and drives the cell from the G1 phase to the end of the mitotic phase. In recent years, it has become evident that cyclins are involved in processes beyond the cell cycle. Cyclin F does not activate CDKs but forms part of the Skp1-Cul1-F-box (SCF) complex where it is responsible for protein target recognition and subsequent degradation in a proteasome-dependent manner.Results: Here, we report that the downregulation of cyclin F in the A-375 melanoma cell line increases cell viability and colony formation in a cell cycle independent manner. Lower levels of cyclin F do not appear to affect the cell cycle, based on flow cytometry measuring BrdU incorporation and propidium iodide staining. By means of immunofluorescence staining and Western blot analysis, we observed changes in cell morphology-related markers which suggested ongoing epithelial-mesenchymal transition (EMT) in response to cyclin F downregulation. Increases in vimentin and N-cadherin protein levels, decreases in levels of epithelial markers such as ZO-1, along with changes in morphology to a spindle-like shape with the appearance of actin stress fibers, are all hallmarks of EMT. These changes are associated with increased invasive and migratory potential, based on 2D migration assays. Moreover, we observe an increase in RhoABC, talin and paxillin levels, the proteins involved in controlling cell signaling and motility. Lastly, upon knocking down cyclin F expression, we observed a decrease in thrombospondin-1 expression, suggesting a role of cyclin F in angiogenesis.Conclusion: Cyclin F depletion induces proliferation and EMT processes in the A-375 melanoma model.Keywords: cyclin F, melanoma, invasiveness, proliferation, cancer

This study aimed to explore the prognostic value of SATB1, SMAD3, and TLR2 expression in non–small-cell lung carcinoma patients with clinical stages I-II. To investigate, we evaluated immunohistochemical staining to each of these markers using tissue sections from 69 patients from our cohort and gene expression data for The Cancer Genome Atlas (TCGA) cohort. We found that, in our cohort, high expression levels of nuclear SATB1 n and SMAD3 were independent prognostic markers for better overall survival (OS) in NSCLC patients. Interestingly, expression of cytoplasmic SATB1 c exhibited a significant but inverse association with survival rate, and it was an independent predictor of unfavorable prognosis. Likewise, TLR2 was a negative outcome biomarker for NSCLC even when adjusting for covariates. Importantly, stratification of NSCLCs with respect to combined expression of the three biomarkers allowed us to identify subgroups of patients with the greatest difference in duration of survival. Specifically, expression profile of SATB1 n-high /SMAD3 high /TLR2 low was associated with the best OS, and it was superior to each single protein alone in predicting patient prognosis. Furthermore, based on the TCGA dataset, we found that overexpression of SATB1 mRNA was significantly associated with better OS, whereas high mRNA levels of SMAD3 and TLR2 with poor OS. In conclusion, the present study identified a set of proteins that may play a significant role in predicting prognosis of NSCLC patients with clinical stages I-II.

Extracellular vesicles (EVs) serve as central mediators in communication between tumor and non-tumor cells. These interactions are largely dependent on the function of the endothelial barrier and the set of receptors present on its surface, as endothelial cells (ECs) are a plenteous source of EVs. The molecular basis for EV secretion and action in the tumor microenvironment (TME) has not been fully elucidated to date. Emerging evidence suggests a prominent role of inflammatory pathways in promoting tumor progression and metastasis. Although transforming growth factor β (TGF-β) is a cytokine with strong immunomodulatory and protective activity in benign and early-stage cancer cells, it plays a pro-tumorigenic role in advanced cancer cells, which is known as the “TGF-β paradox”. Thus, the aim of this review is to describe the correlation between EV release, TGF-β-dependent inflammation, and dysregulation of downstream TGF-β signaling in the context of cancer development.

Tumor necrosis factor α (TNFα) is one of the most important proinflammatory cytokines, which affects many processes associated with the growth and characteristics of endothelial, smooth muscle, and immune system cells. However, there is no correlation between most in vivo and in vitro studies on its role in endothelial cell proliferation and migration. In this study, we examined the effect of recombinant human (rh) TNFα produced in HEK293 cells on primary human coronary artery endothelial cells (pHCAECs) in the context of F-actin organization and such processes as migration and adhesion. Furthermore, we evaluated the possibility of the inhibition of the endothelial inflammatory response by the CRISPR-based regulation of TPM1 gene expression. We showed that TNFα-induced activation of pHCAECs was related to the reorganization of the actin cytoskeleton into parallel-arranged stress fibers running along the longer axis of pHCAECs. It allowed for the directed and parallel motion of the cells during coordinated migration. This change in F-actin organization promoted strong but discontinuous cell–cell contacts involved in signalization between migrating cells. Moreover, this form of intercellular connections together with locally increased adhesion was related to the formation of migrasomes and further migracytosis. Stabilization of the actin cytoskeleton through the CRISPR-based activation of endogenous expression of TPM1 resulted in the inhibition of the inflammatory response of pHCAECs following treatment with rh TNFα and stabilization of cell–cell junctions through reduced cleavage of vascular endothelial cadherin (VE-cadherin) and maintenance of the stable levels of α- and β-catenins. We also showed that CRISPR-based activation of TPM1 reduced inflammatory activation, proliferation, and migration of primary human coronary artery smooth muscle cells. Therefore, products of the TPM1 gene may be a potential therapeutic target for the treatment of proinflammatory vascular disorders.

The importance of savings in providing the financial well-being of an individual (a household) is unquestionable. Spending less money than one earns and saving for the future is a valuable rule and a good habit enabling one control personal finances. However, in real life circumstances, it does not always prove to be easy — people are often unable to gather incomes and/or rationally save. Conscious saving requires proper financial knowledge and skills, which are focused on making conscious and rational financial decisions and lead to effective financial behaviour, including in the field of saving. The quality of financial behaviour is determined by numerous factors, the special importance among which is attributed to incomes and the level of own knowledge and financial skills as well as individual traits of particular financial consumers are essential. The aim of this article is to study the level of basic financial knowledge and skills as well as fundamental behaviour in the field of saving among young people with Autism spectrum and Asperger syndrome.

The article discusses the issue of educational, professional and family aspirations among young adults with Asperger syndrome. The research is focused on families, where one of parents migrates to enhance economic status of family. There are substantial additional costs in families with member affected with Asperger's syndrome. It brings great impact on the family’s financial situation and many families with such problem experience financial hardships. In addition, in many countries there are unsatisfactory institutional financial support for these families. The migration of one of parent brings additional income, which can fill the financial deficit. On the other hand migration of one of parents influences the emotional situation in family. This study contributes a more detailed understanding of how the migration of one of parents influences the educational, professional and family aspirations among young adults with Asperger syndrome.

Maciej Gagat,1 Marta Hałas-Wiśniewska,1 Wioletta Zielińska,1 Magdalena Izdebska,1 Dariusz Grzanka,2 Alina Grzanka1 1Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland; 2Department of Clinical Pathomorphology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland Purpose: The aim of the study was to evaluate the effect of piperlongumine (2 and 4 µM) on endothelial EA.hy926 and lung adenocarcinoma A549 cells with regulated expression of profilin-1 (PFN1). Material and methods: The cytotoxicity of alkaloid was evaluated by MTT assay, while cell death was assessed using double staining with annexin V and propidium iodide. Subsequently, the level of PFN1 1) upregulation in EA.hy926 endothelial cells and 2) downregulation in A549 lung adenocarcinoma cells. The next step was the analysis of the effect of PFN1 manipulation on cytoskeletal proteins. Results: The results showed that piperlongumine may inhibit proliferation of EA.hy926 and A549 cell lines and also induce cell death in a dose-dependent manner. Furthermore, endothelial cells with PFN1 overexpression showed lower sensitivity to alkaloid and strengthening of cell–cell interactions. In the case of A549 cells, loss of PFN1 expression resulted in a lower percentage of early apoptotic cells, reorganization of F-actin and vimentin network, and reduction of migratory potential. Conclusion: We suggest that upregulation of PFN1 in endothelial cell line may stabilize the cell junctions. In turn, PFN1 downregulation in A549 cells probably suppresses cell migration and sensitizes cells to anticancer agents. Keywords: profilin-1, piperlongumine, lung cancer, endothelial cell, F-actin, lung adeno­carcinoma

Abstract Background The tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model. Methods ADSCs isolated from a superficial abdominal Camper’s fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation. Results Sixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells. Conclusions The data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.

Aim: The purpose of this study was to investigate whether there is an association between smoking, the extent of the degeneration process in the biceps tendinopathy, including cells and extracellular matrix (ECM) alterations, and long-term surgical results. Methods: This study comprised 40 consecutive patients admitted for shoulder arthroscopy due to symptomatic biceps tendinopathy and classified into three groups based on smoking status: active smokers, former smokers, and non-smokers. According to the classical Bonar score criteria, the histopathologic evaluation of the harvested intra-articular portion of the tendon was done. The follow-up examination was based on the American Shoulder and Elbow Surgeons Score (ASES). Results: A cohort of 32 patients was enrolled in the final follow-up examination; mean 37.56 months. Histopathological evaluation according to the classical Bonar score revealed degeneration of the tendinous tissue in each group but there was no correlation between the extent of degeneration, smoking indexes and the ASES. After revision of Bonar scale within the vascularity criterion, we found a correlation between the extent of degeneration of tendinous tissue, smoking data, ASES score, and the severity of rotator cuff injury. Conclusion: In this paper, we indicate the ambiguous role of the neovascularization in the biceps tendinopathy, and it was used for modification of the classical Bonar score. Consequently, recalculated, modified Bonar score was correlated positively with smoking indexes and functional outcomes. Furthermore, the morphological alterations of rotator cuff tendons also correlated positively with the extent of biceps tendon degeneration, measured according to the modified scoring system.

Aims: The purpose of this study was to investigate whether smoking is associated with neovascularization in the tendinopathy of the long head of the biceps tendon (LHBT). Methods: The study included 40 consecutive patients who underwent arthroscopic biceps tenotomy/tenodesis due to chronic biceps tendinopathy and divided into three groups: (1) non-smokers, (2) former smokers, (3) smokers. LHBT tissue samples were stained with H&E, Alcian blue and Trichrome staining. Immunohistochemical examination was performed using anti-CD31 and anti-CD34. The neovessel density score (NDS) was scored by Bonar criteria. Results: The mean period of smoking was 15.50 years with an average number of 24 cigarettes/day in the former smokers and 21.69 years with an average number of 15 cigarettes/day in the active smokers. The mean NDS was 2.23/3 in non-smokers, whereas it was 1.60/3 in former smokers and 1.31/3 in active smokers. The mean American Shoulder and Elbow Surgeons score equaled 46 in never smoked patients, 43.60 in former smokers, and 41.46 in active smokers. In the patients with smoking history, the disorganized tendinous tissue islands were avascular and composed of compact acidic polysaccharides and mucopolysaccharides. We observed negative correlation between the NDS and the smoking indexes, including cigarettes per day ( p = 0.0150), smoking years ( p = 0.0140), pack-years ( p = 0.0088). Conclusion: In conclusion, the present study revealed that smoking impairs the vascularization of the biceps tendon in chronic tendinopathy. Clinically, we observed a negative correlation between smoking and neovascularization. Furthermore, there was no correlation between neovascularization and functional preoperative status.

Tendinopathy is a process of chaotic extracellular matrix remodeling followed by increased secretion of enzymes and mediators of inflammation. The histopathological assessment of tendinous tissue is crucial to formulate the diagnosis and establish the severity of tendon degeneration. Nevertheless, the microscopic analysis of tendinous tissue features is often challenging. In this review, we aimed to compare the most popular scales used in tendon pathology assessment and reevaluate the role of the neovascularization process. The following scores were evaluated: the Bonar score, the Movin score, the Astrom and Rausing Score, and the Soslowsky score. Moreover, the role of neovascularization in tendon degeneration was reassessed. The Bonar system is the most commonly used in tendon pathology. According to the literature, hematoxylin and eosin with additional Alcian Blue staining seems to provide satisfactory results. Furthermore, two observers experienced in musculoskeletal pathology are sufficient for tendinopathy microscopic evaluation. The control, due to similar and typical alterations in tendinous tissue, is not necessary. Neovascularization plays an ambiguous role in tendon disorders. The neovascularization process is crucial in the tendon healing process. On the other hand, it is also an important component of the degeneration of tendinous tissue when the regeneration is incomplete and insufficient. The microscopic analysis of tendinous tissue features is often challenging. The assessment of tendinous tissue using the Bonar system is the most universal. The neovascularization variable in tendinopathy scoring systems should be reconsidered due to discrepancies in studies.

Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) is a relatively recently identified coiled-coil domain containing protein and an important determinant of DNA fidelity by ensuring faithful mitosis. Hence, SPDL1 is suspected to underlie genomic (in-)stability in human cancers, yet its exact roles in these diseases remain largely underexplored. Given that genomic instability (GIN) is a crucial feature in colorectal cancer (CRC), we primarily asked whether the expression of this protein may account for differences in clinicopathological features and survival rates of CRC patients. Protein expression was evaluated by immunohistochemistry in the institutional tissue microarray (TMA), and gene expression by the analysis of publicly available datasets. To place the prognostic relevance in a predicted biological context, gene co-expression set around SPDL1 identified by public data mining was annotated and assessed for enrichment in gene ontology (GO) categories, BRITE hierarchies, and Reactome pathways. The comparison with adjacent normal tissue revealed a high expression of SPDL1 protein in a subset of tumor cases (48.84%), and these had better prognosis than the SPDL1-low expression counterpart even after adjustment for multiple confounders. SPDL1-high expression within tumors was associated with a median 56-month survival advantage, but not with any clinicopathological characteristics of our cohort. In the TCGA cohort, SPDL1 was overexpressed in tumor tissue and positively associated with improved survival, chromosome instability phenotype, and various GIN markers. In addition to the genes critically involved in the cell cycle and mitosis, a gene set co-expressed with SPDL1 contained checkpoint members of both chromosome segregation and DNA replication, as well as those associated with defective DNA repair, and retrograde vesicle-mediated transport. In conclusion, SPDL1 is an independent predictor of CRC patient survival in a possible connection with chromosomal instability.

Energy efficiency through energy saving is a key trend in the modern world. Analyses have been conducted by scientists in different fields on various target groups that influence sustainable energy consumption. The aim of the research presented in this article is to determine the association between parental attitudes and awareness of sustainable energy consumption in the perception of young people with ASD (13–17 years old). This was a pilot study. The diagnostic-survey method was used, along with The Scale of Parental Attitudes by M. Plopa and an authored survey questionnaire. Deliberate random sampling was applied. A statistical analysis showed a relationship between the acceptance attitude of both parents and the autonomy attitude of one parent—the father—and awareness of sustainable energy consumption among young people with Autistic Spectrum Disorder (ASD). In addition, a critical literature review confirmed the necessity of combining energy awareness and financial awareness, as each aspect, in terms of energy savings, reflects the financial situation of the household and influences the household budget. This is extremely important in the case of vulnerable groups such as households with a person with a disability (e.g., children with ASD). This research is interdisciplinary and covers important scientific fields such as pedagogy, psychology, and economics.

Homeostasis is a fundamental property of biological systems consisting of the ability to maintain a dynamic balance of the environment of biochemical processes. The action of endogenous and exogenous factors can lead to internal balance disorder, which results in the activation of the immune system and the development of inflammatory response. Inflammation determines the disturbances in the structure of the vessel wall, connected with the change in their diameter. These disorders consist of accumulation in the space between the endothelium and the muscle cells of low-density lipoproteins (LDL), resulting in the formation of fatty streaks narrowing the lumen and restricting the blood flow in the area behind the structure. The effect of inflammation may also be pathological dilatation of the vessel wall associated with the development of aneurysms. Described disease entities strongly correlate with the increased migration of immune cells. Recent scientific research indicates the secretion of specific vesicular structures during migration activated by the inflammation. The review focuses on the link between endothelial dysfunction and the inflammatory response and the impact of these processes on the development of disease entities potentially related to the secretion of extracellular vesicles (EVs).

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).

Neovascularization is a complex, multistep process that includes the activation of endothelial cells, degradation of the basement membrane surrounding the blood vessel, formation of tip cells, the sprouting, migration and proliferation of endothelial cells into the interstitial space, and then the generation of space in the matrix to allow for the formation of a new, proper lumen of a newly formed blood vessel. Abundant neovascularization can be found in tendinous tissue obtained from asymptomatic athletes or the meniscus early after the injury. The concept of neovascularization in musculoskeletal system disorders seems to be mainly associated with pain and poor clinical outcomes. On the one hand, this phenomenon allows for tissue regeneration, but on the other, it is present during the degeneration process in connective tissue. Establishing the current concept on neovascularization is also needed. A narrative review of the current literature was conducted using databases including Embase, PubMed and Cochrane. This review aims to investigate the exact role of the neovascularization process in tendon and meniscus lesions and its role as a potential target in clinics, specifically in platelet-rich plasma (PRP) therapy. The stabilization of the neovessels required to achieve the healed tissue, together with the standardization of the PRP injections, can offer an alternative future therapeutic approach for the treatment of tendinopathy and meniscal injuries.

Genomic instability (GIN) has an important contribution to the pathology of colorectal cancer (CRC). Therefore, we selected mitosis and cytokinesis kinesins, KIF11 and KIF14, as factors of potential clinical and functional value in CRC, as their aberrant expression has been suspected to underlie GIN. We examined the expression and the prognostic and biological significance of KIF11 and KIF14 in CRC via in-house immunohistochemistry on tissue microarrays, public mRNA expression datasets, as well as bioinformatics tools. We found that KIF11 and KIF14 expression, at both the protein and mRNA level, was markedly altered in cancer tissues compared to respective controls, which was reflected in the clinical outcome of CRC patients. Specifically, we provide the first evidence that KIF11 protein and mRNA, KIF14 mRNA, as well as both proteins together, can significantly discriminate between CRC patients with better and worse overall survival independently of other relevant clinical risk factors. The negative prognostic factors for OS were high KIF11 protein, high KIF11 protein + low KIF14 protein, low KIF11 mRNA and low KIF14 mRNA. Functional enrichment analysis revealed that the gene sets related to the cell cycle, DNA replication, DNA repair and recombination, among others, were positively associated with KIF11 or KIF14 expression in CRC tissues. In TCGA cohort, the positive correlations between several measures related to GIN and the expression of KIFs were also demonstrated. In conclusion, our results suggest that CRC patients can be stratified into distinct risk categories by biological and molecular determinants, such as KIF11 and KIF14 expression and, mechanistically, this is likely attributable to their role in maintaining genome integrity.

Background: The current standard of treatment of anterior cruciate ligament (ACL) is reconstruction (ACLR). This technique has some disadvantages: poor proprioception, donor site morbidity and the inability to restore joint kinematics. ACL repair could be an alternative treatment. The purpose of the study was to compare the stability and the function after ACL primary repair versus single-bundle ACLR. Methods: In a retrospective study, 12 patients underwent primary ACL repair with internal bracing, 15 patients underwent standard ACLR. Follow-up examinations were evaluated at up to 2 years postoperatively. One patient in the ACL repair group was lost to follow-up due to re-rupture. The absolute value of anterior tibial translation (ATT) and the side-to-side difference in the same patient (ΔATT) were evaluated using the GNRB arthrometer. The Lysholm knee scoring was obtained. Re-ruptures and other complications were recorded. Results: Anterior tibial translation (ATT) was significantly decreased in the ACL repair group compared with the ACLR group (5.31 mm vs. 7.18 mm, respectively; p = 0.0137). Arthrometric measurements demonstrated a mean side-to-side difference (ΔATT) 1.87 (range 0.2 to 4.9) mm significantly decreased compared to ACLR 3.36 (range 1.2–5.6 mm; p = 0.0107). The mean Lysholm score was 85.3 points in the ACL repair group and 89.9 in ACLR group. No significant differences between ACL repair and ACLR were found for the Lysholm score. There was no association between AP laxity and clinical outcomes. There were two complications in the internal bracing group: one patient had re-rupture and was treated by ACLR, another had limited extension and had arthroscopic debridement. Conclusions: Anterior tibial translation was significantly decreased after ACL repair. Additionally, the functional results after ACL repair with internal bracing were comparable with those after ACLR. It should be noted that the two complications occurred. The current study supports further development of ACL repair techniques.

The aim of the study was to determine the association between parental attitudes and saving energy in the perception of young people with autism spectrum (13–17 years old). The character of studies was pilot. The diagnostic survey method was used, along with The Scale of Parental Attitudes by M. Plopa and an authored survey questionnaire. Deliberate random sampling was applied. Statistical analysis showed that an attitude towards autonomy manifested by mothers, as well as an attitude of acceptance in mothers and fathers, turned out to be significant in adolescents with ASD showing a positive attitude towards energy saving, and these correlations were positive, strong and statistically significant. An overly protective attitude of mothers turned out to be significant in shaping a negative attitude towards energy saving among adolescents with ASD with a significant, positive moderate correlation. Regression analysis showed that the perception of the father’s parental attitude as accepting was a statistically significant predictor of a positive attitude towards energy saving, and that the perception of the mother’s parental attitude as demanding and overly protective was a statistically significant predictor of a negative attitude to energy saving. The achieved results acquire an additional aspect, i.e., a financial dimension in the household budget.

The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases.