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.

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.

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.

Factors affecting rehabilitation of infants with Central Coordination Disorders during a three-month-long observation.

BACKGROUND: Central coordination disorders (CCD) encompass various abnormalities observed in infants but early therapy may have an impact on their condition. The aim was to seek factors that may affect the early results of therapy of infants with CCD. METHODS: We analyzed the outcomes of a three-month period of rehabilitation of infants living with CCD. Children were treated at Non-public Specialist Healthcare Institution Medi-Reh in Kalisz in the period from 1 Jan 2014 to 31 Nov 2019. In our retrospective study results of three-month therapy of infants, aged 1 to 6 months, with CCD were analysed regards to the effectiveness and the potential impact of different factors. Therapy and assessment of children were conducted with the use of the Vojta method, which was performed during the first visit (WW) and the follow-up visit (after 3 months- 1WK). The analysis of the influence of various factors on the effect of therapy included: mother's age at the time of delivery, duration of breastfeeding, child APGAR, gestational age in which the child was born, sex of the child, birth weight, age of the child at WW, type of delivery, craniosacral therapy as an additive treatment. RESULTS: Based on the examination results from 66 medical records it was demonstrated that after active period of the therapy, improvement was observed in 54 (81.81%) (p=0.48) children (condition during WW versus 1WK among the group). The sole factor impacting improvement after 3 months was the age of the child at WW, when the child started therapy. This factor significantly (p=0.002) increased the chance of achieving improvement - by 3.2 times (OR= 3,2; CI= 95). No statistically significant differences were shown for the other studied factors. CONCLUSIONS: Prompt implementation of rehabilitation in children with CCD provides a better chance of improving their motor function. The rehabilitation should be started as soon as possible after the diagnosis is constituted.

MVP Expression Facilitates Tumor Cell Proliferation and Migration Supporting the Metastasis of Colorectal Cancer Cells.

Cancer cells show significant dysregulation of genes expression, which may favor their survival in the tumor environment. In this study, the cellular vault's components MVP (major vault protein), TEP1 (telomerase-associated protein 1) and vPARP (vault poly(ADP-ribose) polymerase) were transiently or completely inhibited in U2OS cells (human bone osteosarcoma epithelial cells) to evaluate their impact on the cell proliferative and migratory capacity as well as on the development of their resistance to the drug vinorelbine. Comparative analysis of MVP protein expression level in normal colon tissue, primary colorectal tumor, and metastasis showed that the expression of this protein does not increase significantly in the primary tumor, but its expression increases in metastatic cells. Further comparative molecular analysis using the whole transcriptome microarrays for MVP-positive and MVP-negative cells showed that MVP is involved in regulating proliferation and migration of cancer cells. MVP may facilitate metastasis of colon cancer due to its impact on cell migration. Moreover, two vault proteins, MVP and TEP1, contribute the resistance to vinorelbine, while vPARP does not.

Prevalence and Antibiotic Resistance of Campylobacter spp. in Urban and Rural Black-Headed Gulls Chroicocephalus ridibundus.

We investigate the role of black-headed gulls (Chroicocephalus ridibundus), an omnivorous species that is among the most likely wild bird candidates for transmission of zoonotic agents, as a potential reservoir of Campylobacter spp. Colonies with different anthropogenic pressures were studied to examine differences in exposure to sources of Campylobacter between rural and urban birds. We recorded Campylobacter spp. in 4.87% of adult black-headed gulls and 2.22% of their chicks after analysing 1036 cloacal swabs collected over two breeding seasons in three colonies in northern Poland. Campylobacter jejuni was found most frequently (85.72%), and Campylobacter lari and Campylobacter coli were much scarcer. Prevalence of Campylobacter did not differ significantly between black-headed gulls breeding in urban (4.27%) and rural (3.80%) habitats. Almost all isolates from chicks and adults were susceptible to azithromycin (97.62%) and erythromycin (95.24%), but fewer to tetracycline (50.00%) and ciprofloxacin (47.62%). Campylobacter prevalence was unrelated to the date of sampling. Our study indicates that black-headed gulls are carriers of resistant to antibiotics Campylobacter and they can contaminate natural waterbodies with their faeces, which poses a threat to human and farm animal health.

Drug resistance evaluation in novel 3D in vitro model.

Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to changes in the expression of many drug resistance genes as well as expression of extracellular matrix proteins and cell density in the tumor. We developed a simple two-dimensional and three-dimensional model of drug sensitive A2780 and resistant to cisplatin and paclitaxel variants of ovarian cancer cell line. Using MTT assay, we compared drug resistance in two-dimensional and three-dimensional cell culture conditions. Real-time polymerase chain reaction analysis was used to compare the expression of drug resistance genes. The expression of proteins in spheroids was determined by immunohistochemistry. We observed a moderate increase in cisplatin resistance and a significant increase in paclitaxel resistance between two-dimensional and three-dimensional cell culture conditions. Our findings show that changes in the expression of drug resistance genes may play a crucial role in the drug resistance of cancer cells in traditional cell culture. On the other hand, the drug resistance in spheroids may result from different mechanisms such as cell density in the spheroid, extracellular matrix proteins expression and drug capacity to diffuse into the spheroid.

Campylobacter in wintering great tits Parus major in Poland.

Domestic and wild mammals, domestic birds and particularly wild birds are considered to be reservoirs of many species of Enterobacteriaceae, and also important human enteric pathogens, e.g., the bacteria of the genus Campylobacter that occur in their digestive tracts. These species may be vectors of antimicrobial resistance dissemination in the environment, because they may have contact with an environment contaminated with antibiotics. Bird feeders have been suggested as potential dispersal centres between wild wintering birds whose feeding is supported by humans. Therefore, we checked for the presence of Campylobacter bacteria among great tits Parus major, the most common bird species on bird feeders in Poland. Samples (n = 787 cloacal swabs) were collected in urban and rural areas of Poland. Bacterial species were identified using multiplex PCR, and 23 (2.9%) positive tests for Campylobacter spp. were found; in ten samples, C. jejuni was detected. The odds ratio of Campylobacter infection in rural birds was over 2.5 times higher than urban birds. Ten samples with C. jejuni were tested for antibiotic resistance, and all were sensitive to azithromycin, erythromycin and gentamycin, while six isolates were resistant to tetracycline, and five were resistant to ciprofloxacin. Four Campylobacter isolates were resistant to both these antibiotics.

Prevalence, Virulence, and Antimicrobial Resistance of Campylobacter spp. in Raw Milk, Beef, and Pork Meat in Northern Poland.

The purpose of this study was to determine whether raw milk, unpasteurized dairy products, pork, and beef available for sale in the Kujawsko-Pomorskie and Wielkopolska regions in Poland are contaminated with Campylobacter spp. bacteria and may be a potential source of infection. For isolated strains, antibiotic susceptibility and the presence of genes responsible for virulence were examined. Material for research included 1058 food samples collected between 2014 and 2018 with 454 samples of raw milk and unpasteurized dairy products (milk from vending machines, milk from owners of dairy cows, cheese, milk cream) and 604 samples of raw meat (pork, beef). The results indicated that 9.3% of the samples were positive for Campylobacter spp., and Campylobacter jejuni was predominant in this study. Campylobacter bacteria was not found in milk collected from vending machines, as well as cheese and milk cream samples. Campylobacter was noted in 12.7% of beef samples, 11.8% of raw milk purchased from individual suppliers, and 10.9% of pork samples. Resistance to erythromycin (2.0%), azithromycin (3.1%), gentamicin (4.1%), tetracycline (65.3%), and ciprofloxacin (71.4%) was determined using the disc diffusion method. Furthermore, the prevalence of racR, sodB, csrA, virB11, cdtB, iam, and wlaN genes were examined using the PCR method. The sodB, csrA, and cdtB genes exhibited the highest detection rate, but none of the genes were identified in 100% of the isolates. Statistically significant differences between the presence of virulence marker genes, including for iam, racR, and csrA markers, were noted among different sources of the isolates. Differences in the distribution of iam, wlaN, and virB11 were also shown between C. jejuni and C. coli strains. As a result of the analysis, it has been concluded that unpasteurized milk, beef, and pork could be a sources of Campylobacter pathogens. Moreover, this study revealed virulent properties of Campylobacter isolated from such food products and high resistance rates to fluoroquinolones, which may represent difficulties in campylobacteriosis treatment.

Mutual Expression of ALDH1A1, LOX, and Collagens in Ovarian Cancer Cell Lines as Combined CSCs- and ECM-Related Models of Drug Resistance Development.

A major contributor leading to treatment failure of ovarian cancer patients is the drug resistance of cancer cell. CSCs- (cancer stem cells) and ECM (extracellular matrix)-related models of drug resistance are described as independently occurring in cancer cells. Lysyl oxidase (LOX) is another extracellular protein involved in collagen cross-linking and remodeling of extracellular matrix and has been correlated with tumor progression. The expression of LOX, COL1A2, COL3A1, and ALDH1A1 was performed in sensitive (A2780, W1) and resistant to paclitaxel (PAC) (A2780PR1 and W1PR2) and topotecan (TOP) (W1TR) cell lines at the mRNA (real-time PCR analysis) and protein level (Western blot and immunofluorescence analysis). The ALDH1A1 activity was measured with the ALDEFLUOR test and flow cytometry analysis. The protein expression in ovarian cancer tissues was determined by immunohistochemistry. We observed an increased expression of LOX and collagens in PAC and TOP resistant cell lines. Subpopulations of ALDH1A1 positive and negative cells were also noted for examined cell lines. Additionally, the coexpression of LOX with ALDH1A1 and COL1A2 with ALDH1A1 was observed. The expression of LOX, collagens, and ALDH1A1 was also detected in ovarian cancer lesions. In our study LOX, ALDH1A1 and collagens were found to be coordinately expressed by cells resistant to PAC (LOX, ALDH1A1, and COL1A2) or to TOP (LOX and ALDH1A1). This represents the study where molecules related with CSCs (ALDH1A1) and ECM (LOX, collagens) models of drug resistance are described as occurring simultaneously in ovarian cancer cells treated with PAC and TOP.

Differential expression of mucin 1 and mucin 2 in colorectal cancer.

AIM: To determine tissue expression (mRNA, protein) of two types of mucins [mucin 1 (MUC1) and mucin 2 (MUC2)] in patients with colorectal cancer (CRC). METHODS: Expression of membrane-bound mucin (MUC1) and secretory mucin (MUC2) in CRC (mRNA, protein) were analyzed in tissue material including fragments of tumors obtained from CRC patients (n = 34), and fragments of normal colorectal tissue from the same patients (control). The analysis was conducted using real-time quantitative polymerase chain reaction (RT-qPCR) (transcripts), immunohistochemistry (IHC) (apomucins), and the modern approach for morphometric analysis of IHC reaction (HSV filter software). Results on tissue expression of both mucins (mRNA, protein) were compared to histological alterations in colorectal cancer samples and correlated with selected clinical data in the patients. The statistical analysis was conducted using Statistica PL v. 12.0 software. RESULTS: Significantly higher expression of the MUC1 mRNA in the CRC, compared with the control and the borderline correlation of mRNA expression with MUC1 protein levels in colorectal samples was observed. The expression of apomucins concerned cell membranes (MUC1) and cytoplasm (MUC2) and occurred both in control tissues and in most cancerous samples. There were no significant relationships between MUC1 (mRNA, protein) and the clinicopathological data of patients. MUC2 protein expression was significantly lower as compared to the control, while MUC2 mRNA expression was comparable in both groups. The MUC1/MUC2 ratio was significantly higher in CRC tissues than in the control. The higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Negative correlations have been obtained between MUC2 and the Ki-67 antigen, as well as between MUC2 and p53 protein expressions in CRC. CONCLUSION: A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 is a factor of poor prognosis in CRC patients. MUC2 tissue expression allows to differentiate mucinous and nonmucinous CRC subtypes.

The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines.

The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. MGP mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.

[The rehabilitation of a child with a sotos syndrome. case report].

OBJECTIVE: Introduction: Sotos syndrome is a rare genetic disease characterized by various physical and mental development disorders. The article proposes and discusses the developmental changes of a child with cerebral gigantism after 8 months improvement according to the proposed scheme. PATIENTS AND METHODS: Material and methods: A six-months-old girl with Sotos syndrome was referred for rehabilitation due to a delay in development. After the neurokinesiological examination, the physiotherapy with use of the Vojta method was started, which after 5 months was supplemented with cranio-sacral and speech therapy. The effects of treatment were evaluated after 5 and 8 months using the Vojty method and 2 developmental profiles according to the Munich Functional Developmental Diagnostics. RESULTS: Results: At the beginning of the therapy, in the neurokinesiological examination was found: 6 abnormal postural positions with asymmetry, spontaneous motor activity at the level below 3 months of age, abnormal primitive reflexes. After 8 months of therapy, 4 abnormal postural positions without asymmetry, spontaneous motor activity at the level of 7.5 months of age, primitive reflexes appropriate to age were found in a neurokinesiological examination. In addition, the child's development was rated the highest in terms of social functions - at 10 months of age, while the age of perception, sitting, crawling, walking and speech function respectively on: 8,7,6,5 and 4 months of age. CONCLUSION: Conclusions: The proposed improvement procedure has contributed to the improvement of the quality of motor patterns and cognitive activation of the child.