Publications by authors named "Jacek Bogucki"

41 Publications

How Do Polish Students Manage Emotional Distress during the COVID-19 Lockdown? A Web-Based Cross-Sectional Study.

J Clin Med 2021 Oct 26;10(21). Epub 2021 Oct 26.

Chair and I Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, 20-439 Lublin, Poland.

Choices regarding coping strategies during the COVID-19 pandemic outbreak may imply the development as well as the severity of emotional disorders. The aim of this web-based cross-sectional study was to: (1) assess the coping strategies for stress in a population of Polish students and (2) evaluate the impact of those strategies on the severity of depression, stress, and anxiety symptoms during the COVID-19 lockdown. To evaluate emotional distress, we used the DASS-21 scale and coping strategies Brief-COPE Inventory. The study included 2172 respondents (73% female, 27% male) with a mean age of 22.1 ± 2.2. Students more frequently chose stress coping strategies belonging to the 'approach' coping strategies (M = 29.60 ± 6.89) compared to 'avoidant' coping strategies (M = 22.82 ± 5.78). The intensification of distress in women caused a turn to religion ( = 0.001), while men used substances ( < 0.001) and a sense of humor ( < 0.001). Medical students coped best with emotional distress, which is very encouraging for their future profession. The highest level of DASS total score was associated with the usage of avoidant coping strategies, prior use of psychiatric or psychological support, and loneliness. Planning interventions to prevent emotional disorders in students requires the identification of factors contributing to increased emotional distress.
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http://dx.doi.org/10.3390/jcm10214964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584627PMC
October 2021

Eye Tracking-An Innovative Tool in Medical Parasitology.

J Clin Med 2021 Jul 4;10(13). Epub 2021 Jul 4.

Chair and Department of Biology and Genetics, Medical University of Lublin, 20-093 Lublin, Poland.

The innovative Eye Movement Modelling Examples (EMMEs) method can be used in medicine as an educational training tool for the assessment and verification of students and professionals. Our work was intended to analyse the possibility of using eye tracking tools to verify the skills and training of people engaged in laboratory medicine on the example of parasitological diagnostics. Professionally active laboratory diagnosticians working in a multi-profile laboratory (non-parasitological) ( = 16), laboratory diagnosticians no longer working in this profession ( = 10), and medical analyst students ( = 56), participated in the study. The studied group analysed microscopic images of parasitological preparations made with the cellSens Dimension Software (Olympus) system. Eye activity parameters were obtained using a stationary, video-based eye tracker Tobii TX300 which has a 3-ms temporal resolution. Eye movement activity parameters were analysed along with time parameters. The results of our studies have shown that the eye tracking method is a valuable tool for the analysis of parasitological preparations. Detailed quantitative and qualitative analysis confirmed that the EMMEs method may facilitate learning of the correct microscopic image scanning path. The analysis of the results of our studies allows us to conclude that the EMMEs method may be a valuable tool in the preparation of teaching materials in virtual microscopy. These teaching materials generated with the use of eye tracking, prepared by experienced professionals in the field of laboratory medicine, can be used during various training, simulations and courses in medical parasitology and contribute to the verification of education results, professional skills, and elimination of errors in parasitological diagnostics.
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http://dx.doi.org/10.3390/jcm10132989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268455PMC
July 2021

Psychological consequences of hospital isolation during the COVID-19 pandemic - research on the sample of polish firefighting academy students.

Curr Psychol 2021 Jun 28:1-10. Epub 2021 Jun 28.

Department of Human Sciences, University of Economics and Innovation in Lublin, 4, Projektowa St., 20-209 Lublin, Poland.

Currently, a very important thread of research on COVID-19 is to determine the dimension of the psychopathological emotional reactions induced by the COVID-19 pandemic. A non-experimental online research project was designed to determine the predictors of the severity of psychopathological symptoms, such as depression and PTSD symptoms, and the nature of the feedback mechanism between them in groups of men, remaining in hospital isolation due to infection and at-home isolation during the COVID-19 epidemic. The presence of symptoms of depression, post-traumatic stress disorder (PTSD) and a sense of threat due to the pandemic were assessed using the following screening tests: IES-R by Weiss and Marmar, PHQ-9 by Spitzer et al., and a self-constructed sliding scale for assessing COVID-19 anxiety. The study was carried out on a group of 57 firefighting cadets, hospitalized in a COVID-19 isolation room (M = 23.01), staying in isolation due to SARS-CoV-2 virus infection and a control group of 57 healthy men (M = 41.38) staying at home during quarantine and national lockdown. COVID-19 pandemic causes many psychopathological reactions. The predictive models revealed that the predictors of symptoms of PTSD in isolated patients included depression and the experienced sense of COVID-19 threat resulting from the disease, while in the control group the symptoms of depression were the only predictor of PTSD. PTSD experiences are usually associated with depression. It may also be a form of the re-experiencing process or the effect of high affectivity, indirectly confirmed by the participation of hyperarousal in the feedback loop. Our findings highlight the importance of mental health aspects in patients treated during the COVID-19 pandemic. The COVID-19 pandemic requires social distancing, quarantine and isolation, which may cause psychopathological symptoms not only in affected people, but also in the general population. Moreover, the need for greater psychological support can be emphasized for both: the sick and the general population.
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http://dx.doi.org/10.1007/s12144-021-01982-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238034PMC
June 2021

Alzheimer's Disease Associated and Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.

Perinatal asphyxia is mainly a brain disease leading to the development of neurodegeneration, in which a number of peripheral lesions have been identified; however, little is known about the expression of key genes involved in amyloid production by peripheral cells, such as lymphocytes, during the development of hypoxic-ischemic encephalopathy. We analyzed the gene expression of the , , and and by RT-PCR in the lymphocytes of post-asphyxia and control neonates. In all examined periods after asphyxia, decreased expression of the genes of the , and was noted in lymphocytes. Conversely, expression of and genes decreased on days 1-7 and 8-14 but increased after survival for more than 15 days. We believe that the expression of genes in lymphocytes could be a potential biomarker to determine the severity of the post-asphyxia neurodegeneration or to identify the underlying factors for brain neurodegeneration and get information about the time they occurred. This appears to be the first worldwide data on the role of the and genes associated with Alzheimer's disease in the dysregulation of neonatal lymphocytes after perinatal asphyxia.
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http://dx.doi.org/10.3390/ijms22105140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152038PMC
May 2021

The Outbreak of SARS-CoV-2 Pandemic and the Well-Being of Polish Students: The Risk Factors of the Emotional Distress during COVID-19 Lockdown.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Chair and I Department of Psychiatry, Psychotherapy, and Early Intervention, Medical University of Lublin, 20-439 Lublin, Poland.

The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on both physical and mental health. The aim of this cross-sectional study was to (1) evaluate depression, anxiety, and stress levels among students from Polish universities during the first weeks of the COVID-19 pandemic and (2) assess the risk factors of the higher intensity of emotional distress. We conducted an online survey using the Depression, Anxiety, and Stress Scale-21 (DASS-21) to assess well-being. The study included 2172 respondents (73% female, 27% male) with a mean age of 22.1 ± 2.2. Moderate to extremely severe scores of depression, anxiety, and stress were reported by 43.4%, 27.3%, and 41.0% of the respondents, respectively. Higher scores of DASS-21 were related to female sex (odds ratio (OR) = 3.01), studying sciences (OR = 2.04), co-residence with the roommates (OR = 1.25), suffering from a mental disorder (OR = 5.88), loneliness (OR = 293.30), the usage of psychiatric support before pandemic (OR = 8.06), poor economic situation (OR = 13.49), and the lower scores were found for being currently employed (OR = 0.4). This study highlights an urgent need for (1) crisis-oriented psychological and psychiatric support for students during the outbreak of the COVID-19 pandemic and (2) preparing appropriate psychological interventions to improve the mental health of students for a possible similar situation in the future.
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http://dx.doi.org/10.3390/jcm10050944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957694PMC
March 2021

Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens.

Int J Mol Sci 2021 Mar 21;22(6). Epub 2021 Mar 21.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Several human tissues are investigated in studies of molecular biomarkers associated with diseases development. Special attention is focused on the blood and its components due to combining abundant information about systemic responses to pathological processes as well as high accessibility. In the current study, transcriptome profiles of peripheral blood mononuclear cells (PBMCs) were used to compare differentially expressed genes between patients with lower extremities arterial disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD). Gene expression patterns were generated using the Ion S5XL next-generation sequencing platform and were analyzed using DESeq2 and UVE-PLS methods implemented in R programming software. In direct pairwise analysis, 21, 58 and 10 differentially expressed genes were selected from the comparison of LEAD vs. AAA, LEAD vs. CVD and AAA vs. CVD patient groups, respectively. Relationships between expression of dysregulated genes and age, body mass index, creatinine levels, hypertension and medication were identified using Spearman rank correlation test and two-sided Mann-Whitney U test. The functional analysis, performed using DAVID website tool, provides potential implications of selected genes in pathological processes underlying diseases studied. Presented research provides new insight into differences of pathogenesis in LEAD, AAA and CVD, and selected genes could be considered as potential candidates for biomarkers useful in diagnosis and differentiation of studied diseases.
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http://dx.doi.org/10.3390/ijms22063200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004090PMC
March 2021

The Family Genes Expression in Patients with Triple Negative Breast Cancer.

Int J Mol Sci 2021 Feb 12;22(4). Epub 2021 Feb 12.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

The (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.
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http://dx.doi.org/10.3390/ijms22041820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918547PMC
February 2021

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer-A Preliminary Study.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Chair and Department of Biology and Genetics, Medical University of Lublin, 20-093 Lublin, Poland.

There is an urgent need to seek new molecular biomarkers helpful in diagnosing and treating breast cancer. In this elaboration, we performed a molecular analysis of mutations and expression of genes within the PI3K/Akt/mTOR pathway in patients with ductal breast cancer of various malignancy levels. We recognized significant correlations between the expression levels of the studied genes. We also performed a bioinformatics analysis of the data available on the international database TCGA and compared them with our own research. Studies on mutations and expression of genes were conducted using High-Resolution Melt PCR (HRM-PCR), Allele-Specific-quantitative PCR (ASP-qPCR), Real-Time PCR molecular methods in a group of women with ductal breast cancer. Bioinformatics analysis was carried out using web source Ualcan and bc-GenExMiner. In the studied group of women, it was observed that the prevalence of mutations in the studied and genes was 29.63%. It was stated that the average expression level of the , , genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the and genes in the studied group was higher in comparison to the control group. It was also indicated that in the group of patients with mutations in the area of the and genes, the gene expression level is statistically significantly lower than in the group without mutations. According to our knowledge, we demonstrate, for the first time, that there is a very strong positive correlation between the levels of and gene expression in the case of patients with mutations and without mutations.
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http://dx.doi.org/10.3390/ijms22042061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922286PMC
February 2021

Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa-Exploratory Study.

Nutrients 2021 Jan 24;13(2). Epub 2021 Jan 24.

Laboratory of Cellular and Molecular Pharmacology, Chair and Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland.

The link between the kynurenine pathway and immunomodulatory molecules-fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)-in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases () were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered. The expression of the gene encoding , but not of genes encoding and (measured in blood mononuclear cells), was higher in patients with AN. In AN, fractalkine positively correlated with TRP, while sICAM-1 was negatively associated with 3-OH-KYN and positively linked with the ratio KYN/3-OH-KYN. Furthermore, TRP and fractalkine were negatively associated with the body mass index (BMI) in AN. Expression of , and did not correlate with fractalkine, sICAM-1 or BMI, either in AN or control. Increased fractalkine may be an independent factor associated with the restrictive type of AN. Excessive physical activity probably underlies increased expression of observed among enrolled patients. Further, longitudinal studies on a larger cohort of patients should be aimed to clarify the contribution of fractalkine and to the pathogenesis of AN.
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http://dx.doi.org/10.3390/nu13020339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910978PMC
January 2021

Influence of the Treatment Used in Inflammatory Bowel Disease on the Protease Activities.

Int J Gen Med 2020 23;13:1633-1642. Epub 2020 Dec 23.

Subdepartment of General and Molecular Genetics, Institute of Biological Basis of Animal Production, University of Life Sciences in Lublin, Lublin 20-950, Poland.

Introduction: There is growing evidence that intestinal proteases have a role in the pathogenesis of gastrointestinal inflammatory diseases. Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has an additional source of proteases represented by infiltrated and activated inflammatory cells. The aim of our study was to determine proteolytic system activity in patients with CD and UC. We limited the number of proteases tested by determining proteases active in acidic, neutral and alkaline pH.

Materials And Methods: The study included 40 patients with IBD - 20 CD patients and 20 UC patients. The control group consisted of 20 healthy subjects. Among the 20 CD patients, 17 were treated with aminosalicylates, 14 with azathioprine, and 4 with corticosteroids, while 8 patients were undergoing biological treatment. Among the 20 UC patients, 19 were treated with aminosalicylates, 8 with azathioprine, and 3 with corticosteroids. The total protein concentration was assayed by the Lowry method. The optimal pH was assayed in pH from 2.2 to 12.8, separated by 0.2 intervals. Proteolytic activities were determined against different substrates (gelatine, haemoglobin, ovalbumin, albumin, cytochrome C, and casein), and haemoglobin was the optimal substrate. Protease activities were determined according to Anson method. Determination of the activities of natural inhibitors of acidic, neutral and alkaline proteases is based on the Lee and Lin method.

Results: Decreases were observed in the activities of acid proteases (pH 5), alkaline proteases (pH 7), and neutral proteases (pH 7.6 and 8.6) in the groups of CD patients in remission in comparison with the active phase. In the group of patients with biologically treated CD patients, acid protease activity (pH 5.0) was lower than in CD patients not receiving biological treatment. Activities of neutral (pH 7.0) and alkaline (pH 7.6 and 8.6) proteases in the plasma of patients with UC in remission were lower in comparison to the active phase. Activities of acid (pH 5.0) and alkaline (8.6) protease inhibitors were higher in CD patients in the active phase in comparison to remission. In UC patients with exacerbation of the disease, the activity of alkaline (pH 8.6) protease inhibitors was increased compared to remission.

Conclusion: 1. Our research may suggest that the immunomodulatory treatment used in IBD, aimed at reducing the level of leukocytes and reduction of inflammation, may contribute to a reduction in protease activity. 2. The decrease of protease activities in patients with CD and UC in remission may be a marker suggesting the patients' response to the treatment.
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http://dx.doi.org/10.2147/IJGM.S267036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767739PMC
December 2020

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm.

J Clin Med 2020 Jun 24;9(6). Epub 2020 Jun 24.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.
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http://dx.doi.org/10.3390/jcm9061974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355415PMC
June 2020

Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease.

J Clin Med 2020 Apr 25;9(5). Epub 2020 Apr 25.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.
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http://dx.doi.org/10.3390/jcm9051251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287878PMC
April 2020

The effects of interior design on wellness - Eye tracking analysis in determining emotional experience of architectural space. A survey on a group of volunteers from the Lublin Region, Eastern Poland.

Ann Agric Environ Med 2020 Mar 17;27(1):113-122. Epub 2019 Apr 17.

Deptartment of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick (NJ), USA.

Introduction And Objective: Using the concepts of Ulrich's theory of supportive design and Malkin's healing environment, an eye tracking experiment was designed in order to measure respondents' reactions while looking at visualisations of various interiors, with the aim of verifying whether certain parameters of an interior are related to emotional reactions in terms of positive stimulation, and the sense of security and comfort.

Material And Methods: 12 boards were designed, incorporating standard features of an interior, i.e. (1) proportions, (2) lighting, (3) colour scheme of a room, as well as (4) the colours and spatial arrangement of furnishings. Respondents' reactions were recorded with an eye tracker Tobii TX300 and supplemented by self-descriptions of emotional reactions.

Results: The results showed that the varying spatial and colour arrangements presented in the interior visualisations provoked different emotional responses, confirmed by pupil reaction parameters, as measured by the eye tracking device.

Conclusions: Architectural space can have a diverse emotional significance and impact on an individual's emotional state. This is an important conclusion from the point of view of optimising and creating the so-called supportive and healing environment. The results have implications for the interpretation of the pupil diameter as an index of emotional reactions to different architectural space visualisations. Testing the eye tracker as a method helpful in diagnosing the emotional reactions to features of the interior is justified, and can provide an effective tool for early diagnosis of the impact of architectural space on the well-being of individuals. It can also be a good form of testing the emotional significance of architectural designs before they are implemented.
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http://dx.doi.org/10.26444/aaem/106233DOI Listing
March 2020

Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease.

Front Genet 2019 22;10:1200. Epub 2019 Nov 22.

Department of Clinical Genetics, Chair of Medical Genetics, Medical University of Lublin, Lublin, Poland.

Atherosclerosis and its comorbidities are the major contributors to the global burden of death worldwide. Lower extremities arterial disease (LEAD) is a common manifestation of atherosclerotic disease of arteries of lower extremities. MicroRNAs belong to epigenetic factors that regulate gene expression and have not yet been extensively studied in LEAD. We aimed to indicate the most promising microRNA and gene expression signatures of LEAD, to identify interactions between microRNA and genes and to describe potential effect of modulated gene expression. High-throughput sequencing was employed to examine microRNAome and transcriptome of peripheral blood mononuclear cells of patients with LEAD, in relation to controls. Statistical significance of microRNAs and genes analysis results was evaluated using DESeq2 and uninformative variable elimination by partial least squares methods. Altered expression of 26 microRNAs (hsa-let-7f-1-3p, hsa-miR-34a-5p, -122-5p, -3591-3p, -34a-3p, -1261, -21-5p, -15a-5p, -548d-5p, -34b-5p, -424-3p, -548aa, -548t-3p, -4423-3p, -196a-5p, -330-3p, -766-3p, -30e-3p, -125b-5p, -1301-3p, -3184-5p, -423-3p, -339-3p, -138-5p, -99a-3p, and -6087) and 14 genes (, , , , , , , , , , , , , and ) were the most significantly differentially expressed in LEAD group compared to controls. Discriminative value of revealed microRNAs and genes were confirmed by receiver operating characteristic analysis. Dysregulations of 26 microRNAs and 14 genes were used to propose novel biomarkers of LEAD. Regulatory interactions between biomarker microRNAs and genes were studied using R multiMiR package. Functional analysis of genes modulated by proposed biomarker microRNAs was performed using DAVID 6.8 tools and revealed terms closely related to atherosclerosis and, interestingly, the processes involving nervous system. The study provides new insight into microRNA-dependent regulatory mechanisms involved in pathology of LEAD. Proposed microRNA and gene biomarkers of LEAD may provide new diagnostic and therapeutic opportunities.
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http://dx.doi.org/10.3389/fgene.2019.01200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892359PMC
November 2019

Expression of the Tau Protein and Amyloid Protein Precursor Processing Genes in the CA3 Area of the Hippocampus in the Ischemic Model of Alzheimer's Disease in the Rat.

Mol Neurobiol 2020 Feb 12;57(2):1281-1290. Epub 2019 Nov 12.

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.

Understanding the mechanisms underlying the selective susceptibility to ischemia of the CA3 region is very important to explain the neuropathology of memory loss after brain ischemia. We used a rat model to study changes in gene expression of the amyloid protein precursor and its cleaving enzymes and tau protein in the hippocampal CA3 sector, after transient 10-min global brain ischemia with survival times of 2, 7, and 30 days. The expression of the α-secretase gene was below control values at all times studied. But, the expression of the β-secretase gene was below the control values at 2-7 days after ischemia and the maximal increase in its expression was observed on day 30. Expression of the presenilin 1 gene was significantly elevated above the control values at 2-7 days after ischemia and decreased below the control values at day 30. Expression of the presenilin 2 gene showed an opposite trend to the expression of presenilin 1. Expression of the amyloid protein precursor gene after ischemia was at all times above the control values with a huge significant overexpression on day 7. Additionally, the expression of the tau protein gene was below the control values 2 days after ischemia, but the significant increase in its expression was observed on days 7-30. Data show that brain ischemia activates neuronal changes and death in the CA3 region of the hippocampus in a manner dependent on amyloid and tau protein, thus determining a new and important way to regulate the survival and/or death of ischemic neurons.
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http://dx.doi.org/10.1007/s12035-019-01799-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031177PMC
February 2020

Dysregulation of Autophagy, Mitophagy, and Apoptosis Genes in the CA3 Region of the Hippocampus in the Ischemic Model of Alzheimer's Disease in the Rat.

J Alzheimers Dis 2019 ;72(4):1279-1286

Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

There is currently no knowledge about the expression profile of the autophagy (BECN1), mitophagy (BNIP3), and apoptosis (CASP3) genes in the CA3 region of the hippocampus after cerebral ischemia. In addition, it is unknown whether genes for BECN1, BNIP3, and CASP3 have any effect on the neuronal death in the CA3 area of the hippocampus due to ischemia. In this study, for the first time, we present, by means of a quantitative PCR protocol with reverse transcriptase, the expression of BECN1 and CASP3 genes in the neuronal CA3 region of the hippocampus with the co-expression of the mitochondrial BNIP3 gene, which genes are associated with Alzheimer's disease, in the ischemic model of Alzheimer's disease in the rat. The present study showed that after ischemia, the CASP3 gene was significantly expressed within 7-30 days, the BECN1 gene was significantly overexpressed on the thirtieth day, and the BINP3 gene was lowered below control values during post-ischemic follow-up period. The caspase-dependent neuronal death in the CA3 region of the hippocampus after ischemia is not accompanied by overexpression of the BNIP3 gene. Our data may therefore suggest a new insight into the BNIP3 gene in the regulation of neuronal mitophagy in neurodegeneration in the CA3 region of the hippocampus after ischemia. This indicates no involvement of the BNIP3 gene along with the CASP3 gene in the CA3 region of the hippocampus in delayed neuronal death after brain ischemia.
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http://dx.doi.org/10.3233/JAD-190966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971835PMC
December 2020

Increased expression of kynurenine aminotransferases mRNA in lymphocytes of patients with inflammatory bowel disease.

Therap Adv Gastroenterol 2019 19;12:1756284819881304. Epub 2019 Oct 19.

Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Lubelskie, Poland.

Background: Complex interaction of genetic defects with environmental factors seems to play a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Accumulating data implicate a potential role of disturbed tryptophan metabolism in IBD. Kynurenic acid (KYNA), a derivative of tryptophan (TRP) along the kynurenine (KYN) pathway, displays cytoprotective and immunomodulating properties, whereas 3-OH-KYN is a cytotoxic compound, generating free radicals.

Methods: The expression of lymphocytic mRNA encoding enzymes synthesizing KYNA (KAT I-III) and serum levels of TRP and its metabolites were evaluated in 55 patients with IBD, during remission or relapse [27 patients with ulcerative colitis (UC) and 28 patients with Crohn's disease (CD)] and in 50 control individuals.

Results: The increased expression of KAT1 and KAT3 mRNA characterized the entire cohorts of patients with UC and CD, as well as relapse-remission subsets. Expression of KAT2 mRNA was enhanced in patients with UC and in patients with CD in remission. In the entire cohorts of UC or CD, TRP levels were lower, whereas KYN, KYNA and 3-OH-KYN were not altered. When analysed in subsets of patients with UC and CD (active phase-remission), KYNA level was significantly lower during remission than relapse, yet not control. Functionally, in the whole groups of patients with UC or CD, the TRP/KYN ratio has been lower than control, whereas KYN/KYNA and KYNA/3-OH-KYN ratios were not altered. The ratio KYN/3-OH-KYN increased approximately two-fold among all patients with CD; furthermore, patients with CD with relapse, manifested a significantly higher KYNA/3-OH-KYN ratio than patients in remission.

Conclusion: The presented data indicate that IBD is associated with an enhanced expression of genes encoding KYNA biosynthetic enzymes in lymphocytes; however, additional mechanisms appear to influence KYNA levels. Higher metabolic conversion of serum TRP in IBD seems to be followed by the functional shift of KYN pathway towards the arm producing KYNA during exacerbation. We propose that KYNA, possibly interaction with aryl hydrocarbon receptor or G-protein-coupled orphan receptor 35, may serve as a counter-regulatory mechanism, decreasing cytotoxicity and inflammation in IBD. Further longitudinal studies evaluating the individual dynamics of TRP and KYN pathway in patients with IBD, as well as the nature of precise mechanisms regulating KYNA synthesis, should be helpful in better understanding the processes underlying the observed changes.
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http://dx.doi.org/10.1177/1756284819881304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801885PMC
October 2019

Effect of Diosmin Administration in Patients with Chronic Venous Disorders on Selected Factors Affecting Angiogenesis.

Molecules 2019 Sep 12;24(18). Epub 2019 Sep 12.

Chair and Department of Biology and Genetics, Medical University of Lublin, W. Chodźki 4A, 20-093 Lublin, Poland.

Diosmin is a natural compound with a wide range of biological activity, e.g., it improves lymphatic drainage, supports microcirculation, and increases venous tone, and venous elasticity, hence, it is applied in the pharmacotherapy of chronic venous disorders (CVD). The aim of this study was to assess the correlation between diosmin administration (2 × 600 mg daily) in patients suffering from CVD and the levels of selected factors influencing angiogenesis, which are involved in CVD pathophysiology. Thirty-five CVD patients were examined. Levels of plasma tumor necrosis factor alpha (TNF alpha), vascular endothelial growth factor (VEGF-A and VEGF-C); angiostatin, interleukin 6 (IL-6), fibroblast growth factor 2 (FGF2); and plasminogen (PLG) were measured with an Elisa assay before and after three months of diosmin administration. The clinical symptoms of CVD were monitored using ultrasound images, echo Doppler assay, visual analogue scale (VAS), and measurement of the leg circumference. The average content of TNF alpha, VEGF-C, VEGF-A IL-6, and FGF2 decreased after the therapy with diosmin in a significant manner; with < 0.001, < 0.05, < 0.05, < 0.01, and < 0.01, respectively, and a significant ( < 0.05) increase in the plasma angiostatin level after the three-month treatment was found. A significant ( < 0.05) decrease in edema and the average leg circumference of the patients was observed after the therapy. Diosmin influences the angiogenic and inflammatory mechanisms involved in the pathophysiology of edema presented in patients with a different class of CVD.
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http://dx.doi.org/10.3390/molecules24183316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767141PMC
September 2019

The Effect of Furanocoumarin Derivatives on Induction of Apoptosis and Multidrug Resistance in Human Leukemic Cells.

Molecules 2019 May 12;24(9). Epub 2019 May 12.

Chair and Department of Biology and Genetics, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, 20-059 Lublin, Poland.

Background: The insensitivity of cancer cells to therapeutic agents is considered to be the main cause of failure of therapy and mortality of patients with cancer. A particularly important problem in these patients is the phenomenon of multidrug resistance, consisting of abnormal, elevated expression of transport proteins (ABC family). The aim of this research included determination of IC50 values of selected furanocoumarins in the presence and absence of mitoxantrone in leukemia cells and analysis of changes in apoptosis using anexinV/IP and Casp3/IP after 24 h exposure of cell lines to selected coumarins in the presence and absence of mitoxantrone in IC50 concentrations.

Methods: Research was conducted on 3 cell lines derived from the human hematopoietic system: HL-60, HL-60/MX1 and HL-60/MX2. After exposure to coumarin compounds, cells were subjected to cytometric analysis to determine the induction of apoptosis by two methods: the Annexin V test with propidium iodide and the PhiPhiLux-G1D2 reagent containing caspase 3 antibodies.

Results: All of the furanocoumarin derivatives studied were found to induce apoptosis in leukemia cell lines.

Conclusions: Our results clearly show that the furanocoumarin derivatives are therapeutic substances with antitumor activity inducing apoptosis in human leukemia cells with phenotypes of resistance.
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http://dx.doi.org/10.3390/molecules24091824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539621PMC
May 2019

Increased Aluminum Content in Certain Brain Structures is Correlated with Higher Silicon Concentration in Alcoholic Use Disorder.

Molecules 2019 May 3;24(9). Epub 2019 May 3.

Department of Environmental Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD).

Materials And Methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients ( = 31) and control ( = 32) post-mortem.

Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF.

Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
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http://dx.doi.org/10.3390/molecules24091721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539762PMC
May 2019

Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines.

Pharmacol Rep 2019 Apr 12;71(2):248-256. Epub 2018 Dec 12.

Chair and Department of Biology and Genetics, Medical University of Lublin, Lublin, Poland. Electronic address:

Background: Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.

Methods: Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA).

Results: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24 h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30 mM, while HL-60/MX2 was the most resistant with an IC50 value of 75 mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined.

Conclusion: We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued.
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http://dx.doi.org/10.1016/j.pharep.2018.12.003DOI Listing
April 2019

[Selected indicators of inflammation in patients hospitalized with various degrees of obesity and metabolic syndrome].

Pol Merkur Lekarski 2018 Sep;45(267):102-106

Department of Clinical Genetics, Medical University of Lublin, Poland.

In people with metabolic syndrome, obesity and diseases of the cardiovascular system are more often observed. At the basis of the pathogenesis of the metabolic syndrome, chronic inflammation plays a significant role. One of the markers of this process is C-reactive protein (CRP) - one of the indicators of the acute phase of inflammation. The role of other biochemical parameters in obesity has been less well understood.

Aim: The aim of the study is to assess the correlation of selected factors of inflammation in obese people and the relevant anthropometric parameters.

Materials And Methods: 263 patients participated in the study. In all subjects anthropometric measurements (body weight, waist/hip ratio and body mass index) were performed and selected biochemical parameters related to MS were determined. The obtained data were analyzed with the division into three degrees of obesity, taking into account gender and place of residence.

Results: The mean C-reactive protein (CRP) concentration was 5,32 ± 14 mg/dl; in women, the highest concentration in 2° of obesity (5mg/dL) and in men in 1-potency (8,41mg/dL). A statistically significant difference in the level of leukocytes between 1° and 3° of obesity in the study group was obtained (p = 0,02). In 3° of obesity in both sexes the highest concentration of monocytes was demonstrated. Positive correlations between leukocyte levels and individual parameters were demonstrated: triglyceride levels (r = 0,134); and the BMI value (r = 0,155); a waist (r = 0,147); and the level of PLT (r = 0,381) and RBC (r = 0,187).

Conclusions: The consequence of obesity is the continuous production of inflammatory factors causing destruction of the body's own tissues. In the present study, CRP values were shown to slightly exceed (p<0,05) above the accepted norm, while the remaining analyzed indicators were within diagnostic standards (in their upper ranges).
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September 2018

Influence of Diosmin Treatment on the Level of Oxidative Stress Markers in Patients with Chronic Venous Insufficiency.

Oxid Med Cell Longev 2018 28;2018:2561705. Epub 2018 Aug 28.

Chair and Department of Biology and Genetics, Medical University of Lublin, W. Chodźki 4A, 20-093 Lublin, Poland.

Oxidative stress plays an important role in the pathophysiology of many human disorders, while antioxidants prevent the development of various adverse symptoms. Diosmin is a natural flavonoid applied in vascular system disorders, especially in chronic venous insufficiency (CVI), and it plays a significant part in the alleviation of CVI symptoms. Due to antioxidant activity, it also has the ability to scavenge the oxygen free radicals and hence decreases the level of oxidative stress biomarkers, such as prostaglandins and their precursors-isoprostanes. In the study, the influence of diosmin treatment on the level of isoprostanes in plasma samples of patients suffering from CVI was examined. The qualitative analysis was performed using high-performance liquid chromatography with spectrometry detection (LC-MS). The statistically significant decrease of isoprostane content after 3 months of treatment was observed within the studied group; however, the most significant changes were observed in patients who smoke.
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http://dx.doi.org/10.1155/2018/2561705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136498PMC
November 2018

Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer's phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer's disease.

Pharmacol Rep 2018 Sep 16;70(5):881-884. Epub 2018 Mar 16.

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.

Background: Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer's disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.

Methods: We have investigated the relationship between hippocampal ischemia and Alzheimer's disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimer's disease tau protein gene expression during 2, 7 and 30 days post injury.

Results: We found the significant overexpression of tau protein gene on the 2nd day, but on day's 7 and 30 post-ischemia there a significant opposite tendency was observed.

Conclusion: The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimer's disease development.
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http://dx.doi.org/10.1016/j.pharep.2018.03.004DOI Listing
September 2018

Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer's phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer's disease.

Pharmacol Rep 2018 Oct 16;70(5):881-884. Epub 2018 Mar 16.

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland; Department of Physiopathology, Institute of Rural Health, Lublin, Poland. Electronic address:

Background: Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer's disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.

Methods: We have investigated the relationship between hippocampal ischemia and Alzheimer's disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimer's disease tau protein gene expression during 2, 7 and 30 days post injury.

Results: We found the significant overexpression of tau protein gene on the 2nd day, but on day's 7 and 30 post-ischemia there a significant opposite tendency was observed.

Conclusion: The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimer's disease development.
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http://dx.doi.org/10.1016/j.pharep.2018.03.004DOI Listing
October 2018

Modulation of Multidrug Resistance Gene Expression by Coumarin Derivatives in Human Leukemic Cells.

Oxid Med Cell Longev 2017 13;2017:5647281. Epub 2017 Dec 13.

Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.

The presence of multidrug resistance (MDR) in tumor cells is considered as the major cause of failure of cancer chemotherapy. The mechanism responsible for the phenomenon of multidrug resistance is explained, among others, as overexpression of membrane transporters primarily from the ABC family which actively remove cytostatics from the tumor cell. The effect of 20 coumarin derivatives on the cytotoxicity and expression of , , , and genes (encoding proteins responsible for multidrug resistance) in cancer cells was analyzed in the study. The aim of this research included determination of IC10 and IC50 values of selected coumarin derivatives in the presence and absence of mitoxantrone in leukemia cells and analysis of changes in the expression of genes involved in multidrug resistance: , , , and after 24-hour exposure of the investigated cell lines to selected coumarins in the presence and absence of mitoxantrone in IC10 and IC50 concentrations. The designed research was conducted on 5 cell lines derived from the human hematopoietic system: CCRF/CEM, CEM/C1, HL-60, HL-60/MX1, and HL-60/MX2. Cell lines CEM/C1, HL-60/MX1, and HL-60/MX2 exhibit a multidrug resistance phenotype.
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http://dx.doi.org/10.1155/2017/5647281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745744PMC
August 2018

Autophagy, mitophagy and apoptotic gene changes in the hippocampal CA1 area in a rat ischemic model of Alzheimer's disease.

Pharmacol Rep 2017 Dec 14;69(6):1289-1294. Epub 2017 Jul 14.

Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland. Electronic address:

Background: Postichemic brain injury correlates with poor prognosis since selectively vulnerable parts of brain are associated with apoptotic neuronal death. But autophagy has been recognized, as a probable survival mechanism following brain ischemia.

Methods: We have analyzed, by quantitative reverse-transcriptase PCR assay protocol, three genes: autophagy, mitophagy and caspase 3 for neuronal death response in ischemic hippocampal CA1 area.

Results: We have found that autophagy gene was not significantly modified at all time points after ischemia, whereas mitophagy and caspase 3 genes were upregulated at day 2 and decreased to basal values at days 7 and 30.

Conclusion: It may be inferred that mitophagy process markedly accompanies apoptosis during delayed neuronal death in hippocampal CA1 area following brain ischemia.
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http://dx.doi.org/10.1016/j.pharep.2017.07.015DOI Listing
December 2017

Dysregulation of Autophagy, Mitophagy, and Apoptotic Genes in the Medial Temporal Lobe Cortex in an Ischemic Model of Alzheimer's Disease.

J Alzheimers Dis 2016 07;54(1):113-21

Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Ischemic brain damage is a pathological incident that is often linked with medial temporal lobe cortex injury and finally its atrophy. Post-ischemic brain injury associates with poor prognosis since neurons of selectively vulnerable ischemic brain areas are disappearing by apoptotic program of neuronal death. Autophagy has been considered, after brain ischemia, as a guardian against neurodegeneration. Consequently, we have examined changes in autophagy (BECN 1), mitophagy (BNIP 3), and apoptotic (caspase 3) genes in the medial temporal lobe cortex with the use of quantitative reverse-transcriptase PCR following transient 10-min global brain ischemia in rats with survival 2, 7, and 30 days. The intense significant overexpression of BECN 1 gene was noted on the 2nd day, while on days 7-30 the expression of this gene was still upregulated. BNIP 3 gene was downregulated on the 2nd day, but on days 7-30 post-ischemia, there was a significant reverse tendency. Caspase 3 gene, associated with apoptotic neuronal death, was induced in the same way as BNIP 3 gene after brain ischemia. Thus, the demonstrated changes indicate that the considerable dysregulation of expression of BECN 1, BNIP 3, and caspase 3 genes may be connected with a response of neuronal cells in medial temporal lobe cortex to transient complete brain ischemia.
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http://dx.doi.org/10.3233/JAD-160387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008226PMC
July 2016

Discrepancy in Expression of β-Secretase and Amyloid-β Protein Precursor in Alzheimer-Related Genes in the Rat Medial Temporal Lobe Cortex Following Transient Global Brain Ischemia.

J Alzheimers Dis 2016 ;51(4):1023-31

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.

Brain ischemia may be causally related with Alzheimer's disease. Presumably, β-secretase and amyloid-β protein precursor gene expression changes may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both β-secretase and amyloid-β protein precursor genes in the medial temporal lobe cortex with the use of quantitative rtPCR analysis following 10-min global brain ischemia in rats with survival of 2, 7, and 30 days. The greatest significant overexpression of β-secretase gene was noted on the 2nd day, while on days 7-30 the expression of this gene was only modestly downregulated. Amyloid-β protein precursor gene was downregulated on the 2nd day, but on days 7-30 postischemia, there was a significant reverse tendency. Thus, the demonstrated alterations indicate that the considerable changes of expression of β-secretase and amyloid-β protein precursor genes may be connected with a response of neurons in medial temporal lobe cortex to transient global brain ischemia. Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology.
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http://dx.doi.org/10.3233/JAD-151102DOI Listing
December 2016

Alzheimer-associated presenilin 2 gene is dysregulated in rat medial temporal lobe cortex after complete brain ischemia due to cardiac arrest.

Pharmacol Rep 2016 Feb 20;68(1):155-61. Epub 2015 Aug 20.

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. Electronic address:

Background: Brain ischemia may be causally related with Alzheimer's disease. Probably, presenilin gene dysregulation may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both presenilin 1 and 2 genes in the medial temporal lobe cortex following 10-min global brain ischemia in rats.

Methods: Global brain ischemia was induced by cardiac arrest in female rats that were allowed to survive for 2, 7 and 30 days. The expression of presenilin genes was evaluated in the rat medial temporal lobe cortex with the use of quantitative RT-PCR analysis.

Results: Presenilin 1 gene expression tended to be downregulated from days 2 to 7 postischemia but at day 30, there was a reverse tendency. The greatest overexpression of presenilin 2 gene was noted at 2-nd day whilst on day 7, the expression of this gene was only modestly elevated. Eventually, at day 30 expression of presenilin 2 gene was modestly downregulated. Alterations of presenilin 2 gene expression between 2 and 7 days and between 2 and 30 days were statistically significant.

Conclusions: Thus, presented changes suggest that the significant dysregulation of presenilin 2 gene may be connected with a response of neuronal cells to transient global brain ischemia due to cardiac arrest. Finally, the ischemia-induced gene dysregulation may play a key role in the late onset of Alzheimer's-type dementia.
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http://dx.doi.org/10.1016/j.pharep.2015.08.002DOI Listing
February 2016
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