A Machine Learning Approach to Gene Expression in Hypertrophic Cardiomyopathy.

BACKGROUND/OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a common heart disorder characterized by the thickening of the heart muscle, particularly in the left ventricle, which increases the risk of cardiac complications. This study aims to analyze the expression of apoptosis-regulating genes (CASP8, CASP9, CASP3, BAX, and BCL2) in blood samples from HCM patients, to better understand their potential as biomarkers for disease progression. METHODS: Quantitative real-time PCR (qPCR) was used to evaluate gene expression in blood samples from 93 HCM patients. The correlation between apoptosis-regulating genes was conducted and clinical parameters were integrated for feature importance and clustering analysis. RESULTS: Most patients exhibited significant downregulation of CASP8, CASP9, and CASP3. In contrast, BAX expression was elevated in 71 out of 93 patients, while BCL2 was increased in 55 out of 93 patients. Correlation analysis revealed weak negative correlations between the BAX/BCL2 ratio and CASP gene expression. CONCLUSIONS: These findings suggest that reduced expression of apoptotic genes may indicate a protective cellular mechanism, which could serve as a biomarker for disease progression. Further studies are needed to investigate the potential for therapeutic modulation of these pathways to improve patient outcomes.

Electrospun Gelatin Scaffolds with Incorporated Antibiotics for Skin Wound Healing.

Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this study, five gelatin combination solutions were prepared and successfully electrospun using an electrospinning technique. After careful screening, the optimal concentration of the most promising combination was selected for further investigation. The obtained scaffolds were crosslinked with 25% glutaraldehyde vapor and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The incorporation of antibiotic agents such as ciprofloxacin hydrochloride and gentamicin sulfate into gelatin membranes improved the already existing antibacterial properties of antibiotic-free gelatin scaffolds against Pseudomonas aeruginosa and Staphylococcus aureus. Also, the outcomes from the in vivo model study revealed that skin regeneration was significantly accelerated with gelatin/ciprofloxacin scaffold treatment. Moreover, the gelatin nanofibers were found to strongly promote the neoangiogenic process in the in vivo chick embryo chorioallantoic membrane assay. Finally, the combination of gelatin's extracellular matrix and antibacterial agents in the scaffold suggests its potential for effective wound-healing treatments, emphasizing the importance of gelatin scaffolds in tissue engineering.

Enhancing Bioactivity of N,N,N-Chelating Rhodium(III) Complexes with Ionic Liquids: Toward Targeted Cancer Therapy.

This study investigates the potential of using ionic liquids as cosolvents to enhance the solubility and activity of poorly soluble rhodium(III) complexes, particularly those with diene, pyridine derivatives, and camphor-derived bis-pyrazolylpyridine ligands, in relation to 5'-GMP, CT-DNA, and HSA as well as their biological activity. Findings indicate that ionic liquids significantly increase the substitution activity of these complexes toward 5'-GMP while only marginally affecting DNA/HSA binding affinities with molecular docking, further confirming the experimental results. Lipophilicity assessments indicated good lipophilicity. Notably, cytotoxicity studies show that Rh2 is selectively effective against HeLa cancer cells, with IL1 and IL10 modulating the cytotoxic effects. Redox evaluations indicate that rhodium complexes induce oxidative stress in cancerous cells while maintaining redox balance in noncancerous cells. By elucidating the role of ionic liquids in modulating these effects, the study proposes a promising avenue for augmenting the efficacy and selectivity of cancer treatments, thus opening new horizons in cancer therapeutics.

Machine Learning Model for Prediction of Development of Cancer Stem Cell Subpopulation in Tumurs Subjected to Polystyrene Nanoparticles.

Cancer stem cells (CSCs) play a key role in tumor progression, as they are often responsible for drug resistance and metastasis. Environmental pollution with polystyrene has a negative impact on human health. We investigated the effect of polystyrene nanoparticles (PSNPs) on cancer cell stemness using flow cytometric analysis of CD24, CD44, ABCG2, ALDH1 and their combinations. This study uses simultaneous in vitro cell lines and an in silico machine learning (ML) model to predict the progression of cancer stem cell (CSC) subpopulations in colon (HCT-116) and breast (MDA-MB-231) cancer cells. Our findings indicate a significant increase in cancer stemness induced by PSNPs. Exposure to polystyrene nanoparticles stimulated the development of less differentiated subpopulations of cells within the tumor, a marker of increased tumor aggressiveness. The experimental results were further used to train an ML model that accurately predicts the development of CSC markers. Machine learning, especially genetic algorithms, may be useful in predicting the development of cancer stem cells over time.

AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing.

Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment.

Modeling 5-FU-Induced Chemotherapy Selection of a Drug-Resistant Cancer Stem Cell Subpopulation.

(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)-genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.

Bioactivities and Medicinal Value of the Fruiting Body Extracts of Laetiporus sulphureus and Meripilus giganteus Polypore Mushrooms (Agaricomycetes).

In the present investigation methanol and acetone extracts of basidiocarps of mushrooms Laetiporus sulphureus and Meripilus giganteus were evaluated for their antimicrobial, cytotoxic and antioxidant/prooxidant effects. The antimicrobial potential was determined by the microdilution method against ten microorganisms. Cytotoxic effects were evaluated by MTT test, while changes of the redox status parameters (superoxide anion radical, nitrites and reduced glutathione) were determined spectrophotometrically on a human colorectal cancer cell line and human health fibroblasts cells. The results were measured 24 and 72 h after the treatment. Tested extracts exhibited moderate antimicrobial activity with MIC values from 0.004 to 20 mg/mL. The maximum antimicrobial activity was found in the methanol extracts of the M. giganteus against Bacillus subtilis, which was better than positive control. The acetone extract of M. giganteus with IC5072h = 13.36 µg/mL showed significant cytotoxic effect with strong cell selectivity (selectivity index = 37.42) against cancer human colorectal cancer cells. The tested extracts, especially M. giganteus acetone extract, induced an increase in oxidative stress parameters in tested cell lines, but significantly heightened it in human colorectal cancer cells. The obtained results suggest that these extracts, especially M. giganteus acetone extract, can be proposed as a novel source of nutraceuticals and pharmaceuticals.

Novel N-pyrocatechoyl and N-pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity.

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress-associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N-pyrocatechoyl and N-pyrogalloyl hydrazones (N-PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N-PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT-116 cells and healthy fibroblasts MRC-5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone-type hybrids encouraged investigations on G+ and G- bacterial strains, which revealed the antibacterial potency of several N-PYRs. These findings highlighted the N-PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.

Evaluation of Novel Dendrimer-Gold Complex Nanoparticles for Theranostic Application in Oncology.

AIM: Despite some successful examples of therapeutic nanoparticles reaching clinical stages, there is still a significant need for novel formulations in order to improve the selectivity and efficacy of cancer treatment. METHODS: The authors developed two novel dendrimer-gold (Au) complex-based nanoparticles using two different synthesis routes: complexation method (formulation A) and precipitation method (formulation B). Using a biomimetic cancer-on-a-chip model, the authors evaluated the possible cytotoxicity and internalization by colorectal cancer cells of dendrimer-Au complex-based nanoparticles. RESULTS: The results showed promising capabilities of these nanoparticles for selectively targeting cancer cells and delivering drugs, particularly for the formulation A nanoparticles. CONCLUSION: This work highlights the potential of dendrimer-Au complex-based nanoparticles as a new strategy to improve the targeting of anticancer drugs.

Correction: Qamar et al. Treatment of Peripheral Artery Disease Using Injectable Biomaterials and Drug-Coated Balloons: Safety and Efficacy Perspective. Pharmaceutics 2023, 15, 1813.

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Effects of direct pulp capping with recombinant human erythropoietin and/or mineral trioxide aggregate on inflamed rat dental pulp.

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Its all about IFN-λ4: Protective role of IFNL4 polymorphism against COVID-19-related pneumonia in females.

Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females.

Treatment of Peripheral Artery Disease Using Injectable Biomaterials and Drug-Coated Balloons: Safety and Efficacy Perspective.

The possibility of injectable biomaterials being used in the therapy of peripheral artery disease (PAD) is investigated in this article. We conducted a thorough review of the literature on the use and efficacy of biomaterials (BMs) and drug-coated balloons (DCBs). These BMs included hydrogels, collagen scaffolds, and nanoparticles. These BMs could be used alone or in combination with growth factors, stem cells, or gene therapy. The treatment of peripheral artery disease with DCBs is increasingly common in the field of interventional angiology. Studies have been carried out to examine the effectiveness of paclitaxel-coated balloons such as PaccocathTM in lowering the frequency with which further revascularization operations are required. PCB angioplasty and angioplasty without paclitaxel did not significantly vary in terms of mortality, according to the findings of a recent meta-analysis that included the results of four randomized controlled studies. On the other hand, age was found to be a factor that predicted mortality. There was a correlation between the routine utilization of scoring balloon angioplasty along with DCBs and improved clinical outcomes in de novo lesions. In both preclinical and clinical testing, the SelutionTM DCB has demonstrated efficacy and safety, but further research is required to determine whether or not it is effective and safe over the long term. In addition, we reviewed the difficulties involved in bringing injectable BMs-based medicines to clinical trials, including the approval processes required by regulatory bodies. Injectable BMs have a significant amount of therapeutic promise for PAD, which highlights the need for more research and clinical studies to be conducted in this field. In conclusion, this research focuses on the potential of injectable BMs and DCBs in the treatment of PAD as well as the hurdles that must be overcome in order to translate these treatments into clinical trials. In this particular field, there is a demand for further research as well as clinical trials.

Combined Biological and Numerical Modeling Approach for Better Understanding of the Cancer Viability and Apoptosis.

Nowadays, biomedicine is a multidisciplinary science that requires a very broad approach to the study and analysis of various phenomena essential for a better understanding of human health. This study deals with the use of numerical simulations to better understand the processes of cancer viability and apoptosis in treatment with commercial chemotherapeutics. Starting from many experiments examining cell viability in real-time, determining the type of cell death and genetic factors that control these processes, a lot of numerical results were obtained. These in vitro test results were used to create a numerical model that gives us a new angle of observation of the proposed problem. Model systems of colon and breast cancer cell lines (HCT-116 and MDA-MB-231), as well as a healthy lung fibroblast cell line (MRC-5), were treated with commercial chemotherapeutics in this study. The results indicate a decrease in viability and the appearance of predominantly late apoptosis in the treatment, a strong correlation between parameters. A mathematical model was created and employed for a better understanding of investigated processes. Such an approach is capable of accurately simulating the behavior of cancer cells and reliably predicting the growth of these cells.

The effects of traumatic experiences during transit and pushback on the mental health of refugees, asylum seekers, and migrants.

Background: There are 26 million people recognised as refugees worldwide. Many of them spent a prolonged period of time in transit - time after they leave their country of origin and before they reach the receiving country. Transit brings numerous protection and mental health risks refugees are exposed to.Objective: The aim of this study was to assess the stressful and traumatic experiences refugees are exposed to during transit, with a special focus on the experience of pushback - the denial of access to the territory to foreign nationals and forcible return to countries of origin or neighbouring countries without an assessment of their rights to international protection, as well as the impact of these experiences on refugees' mental health and well-being.Method: 201 refugees currently residing in Serbia completed the Stressful and Traumatic Experiences in Transit questionnaire - short version (SET-SF), questionnaire for assessing stressful and traumatic experiences during pushback (SET-SF PB), Refugee Health Screener (RHS-15), and Well-being index (WHO-5).Results: The results showed that refugees experience a large number of stressful and traumatic events (M = 10.27, SD = 4.85). In addition, half of the participants experience severe symptoms of depression (50.7%), while about a third of the participants experience severe symptoms of anxiety (37.8%) and post-traumatic stress disorder (PTSD) (32.3%). Refugees who experienced pushback showed overall higher levels of depression, anxiety, and PTSD. Traumatic experiences during transit and pushback were positively related to the severity of depression, anxiety, and PTSD. In addition, traumatic experiences during pushback showed an incremental contribution in predicting refugees' mental health difficulties over and above traumatic experiences in transit.Conclusions: This study provides valuable insights into the multiple risks refugees are exposed to and emphasise the need for the provision of adequate protection and support.

There is a high prevalence of traumatic experiences refugees face during transit and pushback, a high prevalence of mental health problems, and impaired psychological well-being in refugees.Traumatic experiences contribute to mental health problems.Urgent measures are needed.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome.

Coronavirus Disease 2019 (COVID-19) has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 single nucleotide polymorphisms (SNPs), namely rs12980275, rs8099917, rs12979860, and rs368234815. 21.9% and 65.0% of hospitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased Charlson Comorbidity Index (CCI), N/L, and lactate dehydrogenase (LDH) level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19.

Impact of the COVID-19 Pandemic on the Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: A Single Center Experience from a Developing Country.

Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.

Coping with Secondary Traumatic Stress.

Exposure to the traumatic experiences of others can lead to secondary traumatization (STS), a condition comprising trauma-related symptoms. There is a lack of evidence on efficient ways to mitigate STS among professionals working with refugees, who are secondarily exposed to traumatic content. This study examines the latent structure of coping mechanisms and explores the predictive power of coping strategies for STS in a sample of professionals working with refugees. A total of 288 participants (age: M = 34.01, SD = 10.03; 57.3% female) working with refugees completed the COPE Inventory and Secondary Traumatic Stress Scale. Factor analysis of the COPE Inventory showed that coping mechanisms are grouped around four interrelated factors-Problem-focused, Socially supported emotion-focused, Avoidant, and Passive coping-which accounted for 46.7% of the variance. The regression model showed that Avoidant coping positively predicts negative alterations in cognition, mood, and reactivity (NACMR) and intrusions, and Passive coping was positively associated with NACMR and avoidance. Problem-focused coping was related to lower NACMR and avoidance, while Socially supported emotion-focused coping was not associated with any of the STS symptoms. In total, coping factors accounted for 10.8%, 6.3%, and 4.3% of the variance of NACMR, intrusions, and avoidance, respectively. The study provides a foundation for programs to mitigate STS among professionals working with refugees.

Numerical modelling of WNT/ß-catenin signal pathway in characterization of EMT of colorectal carcinoma cell lines after treatment with Pt(IV) complexes.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is at the top of the most common cancer types in the world, with significant mortality rates among both men and women. Deregulation of Wnt/ß-catenin pathway and cell-cell junctions' components, acquisition of invasive phenotype, epithelial-mesenchymal transition (EMT) and invasion are important for development and progression of colorectal cancer. Numerical simulation presents method for estimation of the Wnt pathway via its individual components in cells, thus providing information about EMT, migratory and invasive potential. By using this numerical model, the effectiveness of treatment in EMT suppression can be assessed. Furthermore, the model can be adapted to ``every'' cell type, application time or duration of treatment can be also modified. METHODS: We characterized colorectal cancer (CRC) cell lines (HCT-116, SW-480) from the aspect of EMT, via markers ß-catenin and E-cadherin using numerical modeling. To confirm the numerical model, cells were treated with sublethal concentrations of platinum(IV) complexes and their ligands. We confirmed ß-catenin regulated expression of mesenchymal markers: N-cadherin, Vimentin and MMP-9, and decreased E-cadherin expression. Treatment-induced changes were determined in the protein expression of tested markers and results showed cell-specific responses. Molecular docking was performed to investigate exact effects of treatments on E-cadherin and ß-catenin in cell-cell junctions and individually in tested cells. RESULTS: The application of the numerical model via ß-catenin and E-cadherin (experimentally measured), is largely valid for the categorization of EMT progression in cells. This numerical modeling better characterizes cells with single cell migration, higher expression of mesenchymal markers, and advanced mesenchymal phenotype like HCT-116 cell line. The model was validated for the treatments and results show HCT-116 cells as more sensitive to applied compounds, among which ligands were more potent in reducing migration and invasiveness. Anti-migratory/invasive effects were due to increased E-cadherin, cytoplasmic ß-catenin expression and suppressed mesenchymal markers. In silico methods showed higher affinity of tested chemicals towards free ß-catenin, which is the key for regulation of migratory/invasive potential. CONCLUSIONS: Our study shows that, no matter individual properties of cell lines and EMT degree, de novo formation of intercellular junctions stands in the basis of anti-migratory/invasive process.