Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.

Some chemotherapy drugs modulate the formation of stress granules (SGs), which are RNA-containing cytoplasmic foci contributing to stress response pathways. How SGs mechanistically contribute to pro-survival or pro-apoptotic functions must be better defined. The chemotherapy drug lomustine promotes SG formation by activating the stress-sensing eIF2α kinase HRI (encoded by the EIF2AK1 gene). Here, we applied a DNA microarray-based transcriptome analysis to determine the genes modulated by lomustine-induced stress and suggest roles for SGs in this process. We found that the expression of the pro-apoptotic EGR1 gene was specifically regulated in cells upon lomustine treatment. The appearance of EGR1-encoding mRNA in SGs correlated with a decrease in EGR1 mRNA translation. Specifically, EGR1 mRNA was sequestered to SGs upon lomustine treatment, probably preventing its ribosome translation and consequently limiting the degree of apoptosis. Our data support the model where SGs can selectively sequester specific mRNAs in a stress-specific manner, modulate their availability for translation, and thus determine the fate of a stressed cell.

From physiological complexity to data interactions-A case study of recordings from exercise monitoring.

The popularity of nonlinear analysis has been growing simultaneously with the technology of effort monitoring. Therefore, considering the simple methods of physiological data collection and the approaches from the information domain, we proposed integrating univariate and bivariate analysis for the rest and effort comparison. Two sessions separated by an intensive training program were studied. Nine subjects participated in the first session (S1) and seven in the second session (S2). The protocol included baseline (BAS), exercise, and recovery phase. During all phases, electrocardiogram (ECG) was recorded. For the analysis, we selected corresponding data lengths of BAS and exercise usually lasting less than 5 min. We found the utility of the differences between original data and their surrogates for sample entropy Sdiff and Kullback-Leibler divergence KLDdiff. Sdiff of heart rate variability was negative in BAS and exercise but its sensitivity for phases discrimination was not satisfactory. We studied the bivariate analysis of RR intervals and corresponding QT peaks by Interlayer Mutual Information (IMI) and average edge overlap (AVO) markers. While the IMI parameter decreases in exercise conditions, AVO increased in effort compared to BAS. These findings conclude that researchers should consider a bivariate analysis of extracted RR intervals and corresponding QT datasets, when only ECG is recorded during tests.

The response and resistance to drugs in ovarian cancer cell lines in 2D monolayers and 3D spheroids.

Ovarian cancer is the most common type of gynecologic cancer. One of the leading causes of high mortality is chemoresistance, developed primarily or during treatment. Different mechanisms of drug resistance appear at the cellular and cancer tissue organization levels. We examined the differences in response to the cytotoxic drugs CIS, MTX, DOX, VIN, PAC, and TOP using 2D (two-dimensional) and 3D (three-dimensional) culture methods. We tested the drug-sensitive ovarian cancer cell line W1 and established resistant cell lines to appropriate cytotoxic drugs. The following qualitative and quantitative methods were used to assess: 1) morphology - inverted microscope and hematoxylin & eosin staining; 2) viability - MTT assay; 3) gene expression - a quantitative polymerase chain reaction; 4) identification of proteins - immunohistochemistry, and immunofluorescence. Our results indicate that the drug-sensitive and drug-resistant cells cultured in 3D conditions exhibit stronger resistance than the cells cultured in 2D conditions. A traditional 2D model shows that drug resistance of cancer cells is caused mainly by changes in the expression of genes encoding ATP-binding cassette transporter proteins, components of the extracellular matrix, "new" established genes related to drug resistance in ovarian cancer cell lines, and universal marker of cancer stem cells. Whereas in a 3D model, the drug resistance in spheroids can be related to other mechanisms such as the structure of the spheroid (dense or loose), the cell type (necrotic, quiescent, proliferating cells), drug concentrations or drug diffusion into the dense cellular/ECM structure.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

Genetic relatedness, virulence, and drug susceptibility of Campylobacter isolated from water and wild birds.

Introduction: This study aimed to identify the characteristics of Campylobacter isolated from wild birds (Black-headed gulls Chroicocephalus ridibundus and Great tits Parus major) and collect surface water samples (from rivers, ponds, ornamental lakes, freshwater beaches). Research material included 33 Campylobacter isolates. All the strains were isolated by different monitoring and surveillance plans. Methods: The prevalence of selected genes (flaA, cadF, iam, cdtB, wlaN, sodB, tet0) encoding virulence factors and resistance among Campylobacter spp. was assessed by the PCR method. The genetic similarities of isolates were determined by Pulsed-Field Gel Electrophoresis (PFGE). The susceptibility of Campylobacter isolates to clinically important antimicrobials: erythromycin, tetracycline, and ciprofloxacin, previously assessed by E-test, was presented in the form of drug susceptibility profiles depending on the origin of the isolates. Results: The cadF, flaA, cdtB, and sodB genes exhibited the highest detection rate. Statistically significant differences between the presence of wlaN virulence genes were noted among different species of the isolates. No genetically identical isolates were found. The most numerous antibiotic susceptibility profile included strains susceptible to all antibiotics studied (profile A-33.3%). The second most common were the tetracycline - and ciprofloxacin-resistant (profile B-27.2%), and tetracycline-resistant profile (C-24.2%) respectively. Discussion: The study revealed the virulent properties of Campylobacter isolated from water samples, and wild birds, and high resistance rates to tetracycline, and fluoroquinolones. The lack of genetic relatedness among strains isolated from water, and birds may indicate other sources of surface water contamination with Campylobacter bacteria than birds. The presence of Campylobacter spp. in wild birds could also have other environmental origins.

Effect of Radiant Catalytic Ionization and Ozonation on Salmonella spp. on Eggshells.

Three Salmonella enterica strains were used in the study (serovars: S. enteritidis, S. typhimurim and S. virchow). This study evaluated the efficacy of radiant catalytic ionization (RCI) and ozonation against Salmonella spp. on eggshell (expressed as log CFU/egg). The egg surface was contaminated three different bacterial suspension (103 CFU/mL, 105 CFU/mL and 108 CFU/mL) with or without poultry manure. Experiments were conducted at 4 °C and 20 °C in three different time period: 30 min, 60 min and 120 min. Treatment with RCI reduced Salmonella numbers from 0.26 log CFU/egg in bacterial suspension 108 CFU/mL, 4 °C and 20 °C, with manure for 30 min to level decrease in bacteria number below the detection limit (BDL) in bacterial suspension 105 CFU/mL, 20 °C, with or without manure for 120 min. The populations of Salmonella spp. on eggs treated by ozonizer ranged from 0.20 log CFU/egg in bacteria suspension 108 CFU/mL, 20 °C, with manure for 30 min to 2.73 log CFU/egg in bacterial suspension 105 CFU/mL, 20 °C, with manure for 120 min. In all treatment conditions contamination with poultry manure decrease effectiveness the RCI and ozonation. In summary, RCI technology shows similar effectiveness to the ozonation, but it is safer for poultry plant workers and consumers.

The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System-A Systematic Review.

Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut-brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut-brain axis based on selected diseases, i.e., Alzheimer's disease, Parkinson's disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut-brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota-gut-brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome.

Two Faces of Fermented Foods-The Benefits and Threats of Its Consumption.

In underdeveloped and developing countries, due to poverty, fermentation is one of the most widely used preservation methods. It not only allows extending the shelf life of food, but also brings other benefits, including inhibiting the growth of pathogenic microorganisms, improving the organoleptic properties and product digestibility, and can be a valuable source of functional microorganisms. Today, there is a great interest in functional strains, which, in addition to typical probiotic strains, can participate in the treatment of numerous diseases, disorders of the digestive system, but also mental diseases, or stimulate our immune system. Hence, fermented foods and beverages are not only a part of the traditional diet, e.g., in Africa but also play a role in the nutrition of people around the world. The fermentation process for some products occurs spontaneously, without the use of well-defined starter cultures, under poorly controlled or uncontrolled conditions. Therefore, while this affordable technology has many advantages, it can also pose a potential health risk. The use of poor-quality ingredients, inadequate hygiene conditions in the manufacturing processes, the lack of standards for safety and hygiene controls lead to the failure food safety systems implementation, especially in low- and middle-income countries or for small-scale products (at household level, in villages and scale cottage industries). This can result in the presence of pathogenic microorganisms or their toxins in the food contributing to cases of illness or even outbreaks. Also, improper processing and storage, as by well as the conditions of sale affect the food safety. Foodborne diseases through the consumption of traditional fermented foods are not reported frequently, but this may be related, among other things, to a low percentage of people entering healthcare care or weaknesses in foodborne disease surveillance systems. In many parts of the world, especially in Africa and Asia, pathogens such as enterotoxigenic and enterohemorrhagic Escherichia coli, Shigella spp., Salmonella spp., enterotoxigenic Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus have been detected in fermented foods. Therefore, this review, in addition to the positive aspects, presents the potential risk associated with the consumption of this type of products.

Evaluation of the relationship between psoriasis, periodontitis, and markers of inflammation.

Introduction: Periodontal disease and psoriasis are chronic and multifactorial inflammatory conditions which share immunopathological mechanisms and risk factors. They often coexist and reflect each other as extensive research proved a correlation between the advancement of periodontitis and the severity of psoriasis. Aim: To assess the influence of the prevalence of psoriasis and periodontitis using the selected markers of inflammation, such as C-reactive protein (CRP), interleukin (IL) 1α (IL-1α) and IL-17. Material and methods: Test sample consisted of 30 psoriatic inpatients, subjected to dental examination and blood tests. 29 healthy individuals constituted the control group and underwent thorough clinical examination to rule out psoriasis. Results: Our results confirmed that all dental indices reflecting oral hygiene and periodontal health were significantly better in healthy controls than in patients with psoriasis. Further analysis revealed a statistically significant correlation between the levels of CRP, a few of the cytokines (IL-1, IL-17), and dental indices in psoriatic patients. Moreover, we found that patients with psoriasis visited the dentist less frequently than healthy participants. Conclusions: In order to fully establish the relationship between psoriasis, periodontitis and markers of inflammation, further research on larger sample sizes is needed. However, the results obtained point to the crucial role of diagnosing and treating periodontitis in preventing and mitigating psoriasis. Joint effort of physicians and dentists is necessary to ensure a comprehensive treatment of a psoriatic patient.

Assessment of time irreversibility in a time series using visibility graphs.

In this paper, we studied the time-domain irreversibility of time series, which is a fundamental property of systems in a nonequilibrium state. We analyzed a subgroup of the databases provided by University of Rochester, namely from the THEW Project. Our data consists of LQTS (Long QT Syndrome) patients and healthy persons. LQTS may be associated with an increased risk of sudden cardiac death (SCD), which is still a big clinical problem. ECG-based artificial intelligence methods can identify sudden cardiac death with a high accuracy. It follows that heart rate variability contains information about the possibility of SCD, which may be extracted, provided that appropriate methods are developed for this purpose. Our aim was to assess the complexity of both groups using visibility graph (VG) methods. Multivariate analysis of connection patterns of graphs built from time series was performed using multiplex visibility graph methods. For univariate time series, time irreversibility of the ECG interval QT of patients with LQTS was lower than for the healthy. However, we did not observe statistically significant difference in the comparison of RR intervals time series of the two groups studied. The connection patterns retrieved from multiplex VGs have more similarity with each other in the case of LQTS patients. This observation may be used to develop better methods for SCD risk stratification.