Publications by authors named "Katarzyna Kośla"

14 Publications

  • Page 1 of 1

Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM).

PeerJ 2021 14;9:e10604. Epub 2021 Jan 14.

Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.

Background: Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients.

Methods: Leukocytes were obtained from 135 pregnant women with ( = 98) or without ( = 37) GDM and, in turn, 3 months ( = 8) and 1 year ( = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport (), glycolytic pathway (), Wnt pathway (), and inflammatory response ().

Results: GDM patients displayed a significant downregulation of with simultaneous upregulation of which resulted in approximately six times reduction in ratio. As a consequence, induced genes () were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with ratio. The postpartum expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy.

Conclusions: The obtained results suggest a significant contribution of the gene to glucose metabolism in patients with gestational diabetes. Decreased expression in GDM compared to normal pregnancy, and in particular reduction of ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes.
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http://dx.doi.org/10.7717/peerj.10604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811782PMC
January 2021

Identification and accumulation of phenolic compounds in the leaves and bark of Salix alba (L.) and their biological potential.

Biomolecules 2020 09 29;10(10). Epub 2020 Sep 29.

Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź.

The study examines the phenolic compounds in hydromethanolic extracts of (L.) leaves and bark as well as their antioxidant activity and cytotoxic potential. UPLC-PDA-Q/TOF-MS analysis showed a total of 29 phenolic compounds in leaves and 34 in bark. Total phenolic compound content was 5575.96 mg/100 g of dry weight (DW) in leaves and 2330.31 mg/100 g DW in bark. The compounds were identified as derivatives of phenolic acids (seven in leaves and five in bark), flavanols and procyanidins (eight in leaves and 26 in bark) and flavonols (14 in leaves and three in bark). Both extracts exhibited strong antioxidant potential, assessed by radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), but the bark extract was even stronger than the ascorbic acid used as a standard. The cytotoxicity of both extracts was evaluated against human skin fibroblasts and human epidermal keratinocytes cell lines using the Presto Blue cell viability assay. The keratinocytes were more resistant to tested extracts than fibroblasts. The leaf and bark extracts at concentrations which exhibited antioxidant activity were also not toxic against the keratinocyte cell line. Thus, extracts, especially the leaf extract, offer promise as a nontoxic natural antioxidant, in cosmetic products or herbal medicines, and as a source of bioactive secondary metabolites.
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http://dx.doi.org/10.3390/biom10101391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600001PMC
September 2020

Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development.

Front Neurosci 2020 11;14:644. Epub 2020 Jun 11.

Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto "Giannina Gaslini", Genoa, Italy.

Mutations in the gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumor suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a -deficient human fetus from this family. A similar disorganization of cortical layers was identified in rats (carrying a homozygous truncating mutation which disrupts the active Wwox C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the gene in migrating neurons across different species.
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http://dx.doi.org/10.3389/fnins.2020.00644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300205PMC
June 2020

The Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells.

Front Cell Neurosci 2019 30;13:391. Epub 2019 Aug 30.

Department of Molecular Carcinogenesis, Medical University of Łódź, Łódź, Poland.

The brain is the most functionally organized structure of all organs. It manages behavior, perception and higher cognitive functions. The gene is non-classical tumor suppressor gene, which has been shown to have an impact on proliferation, apoptosis and migration processes. Moreover, genetic aberrations in induce severe neuropathological phenotypes in humans and rodents. The aim of the present study was to investigate in detail the impact of on human neural progenitor cell (hNPC) maintenance and how depletion of disturbs signaling pathways playing a pivotal role in neuronal differentiation and central nervous system (CNS) organogenesis. hNPC with a silenced gene exhibited lowered mitochondrial redox potential, enhanced adhesion to fibronectin and extracellular matrix protein mixture, downregulation of MMP2/9 expression and impaired 3D growth. Global transcriptome analysis using cap analysis of gene expression (CAGE) found that downregulation significantly changes the expression of multiple genes engaged in cytoskeleton organization, adhesion, cell signaling and chromatin remodeling. The massive changes in gene expression caused by silencing may strongly affect the differentiation and migration of neurons in organogenesis, brain injury, cancerogenesis or neurodifferentiation. gene appears to be an important regulator of neural tissue architecture and function.
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http://dx.doi.org/10.3389/fncel.2019.00391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730490PMC
August 2019

Effect of Accelerated Ageing on the Mechanical and Structural Properties of the Material System Used in Protectors.

Polymers (Basel) 2019 Jul 30;11(8). Epub 2019 Jul 30.

Institute of Polymer and Dye Technology, Lodz University of Technology, 12/16 Stefanowskiego Str., 90-924 Lodz, Poland.

Currently, there is a wide range of materials for motorcyclists available on the market that have a significant ability to absorb impact energy. Understanding the aging processes of materials is crucial for guaranteeing the long-term durability and safety of a new product. For this reason, the effect of accelerated aging on the mechanical and structural properties of the multifunctional materials used in commercial protectors was analyzed. The accelerated aging considered in this study simulated 3 years of use under real conditions. Then, DMTA and FT-IR research, as well as impact tests, were carried out on the commercially available protectors for motorcyclists, before and after the accelerated aging processes. Structural analysis using FT-IR showed no significant changes in the structure of the polymers used for producing the protectors. The DMA test results are consistent with those obtained from the impact study. Both methods showed that the samples maintain their protective properties, after accelerated aging. All of the examined protectors show that an increase in force is transferred through the sample, after the accelerated aging processes, but they still provide protection, according to the ISO standard.
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http://dx.doi.org/10.3390/polym11081263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723406PMC
July 2019

A Novel Set of WNT Pathway Effectors as a Predictive Marker of Uterine Corpus Endometrial Carcinoma-Study Based on Weighted Co-expression Matrices.

Front Oncol 2019 10;9:360. Epub 2019 May 10.

Department of Molecular Carcinogenesis, Medical University of Łódz, Łódz, Poland.

Uterine corpus endometrial carcinomas (UCEC) are clinically divided into two subgroups-endometrioid endometrial carcinoma (EEC) or non-endometrioid endometrial carcinoma (NEEC). The first group shows relatively better prognosis. However, the discrimination seems to be insufficient due to the fact that in the mildest EEC are patients with poor treatment response and bad prognosis. Our aim was to examine the molecular background of such phenomenon and whether gene expression patterns might be of importance for the clinic. We focused our analysis on WNT pathway target genes since it is one of the main regulators of endometrial proliferation and differentiation. analysis of TCGA data, including Weighted Co-expression Network Analysis, Principle Component Analysis, and Multiple Factor Analysis, allows to select 28 genes that serve as a predictive markers for UCEC patients. Our study revealed that there is a subgroup of the endometrioid cases that molecularly resembles mixed/serous groups. This may explain the reason for existence of subgroup of patients, that although clinically diagnosed with the mildest endometrioid UCEC type, yet present failure in treatment and aggressive course of the disease. Our study suggests that worse outcome in these patients may be based on a disruption of proper WNT signalling pathway resulting in deregulation of its effector genes. Moreover, we showed that mixed group consisting of tumours containing both endometrioid and serous types of cells, has serous expression profile of WNT targets. The proposed gene set allows to predict progression of the disease trough dividing patients into groups of low or high grade with 70.8% sensitivity and 88.6% specificity (AUC = 0.837) as well as could predict patient prognosis associated with UCEC subtype with 70.1% sensitivity and 86.2% specificity (AUC = 0.855). Relatively small number of implicated genes makes it highly applicable and possibly clinically simple and useful tool.
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http://dx.doi.org/10.3389/fonc.2019.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524344PMC
May 2019

Anatomical anomalies of the V3 segment of the vertebral artery in the Polish population.

Eur Spine J 2016 12 23;25(12):4164-4170. Epub 2016 Jun 23.

Department of Neurosurgery, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland.

Purpose: The aim of this study is to evaluate the incidence of the anatomical anomalies of the V3 segment of the vertebral artery in the Polish population. There is conflicting evidence on the incidence of these anomalies: Asian-based studies show high incidence of 10 %, whereas the North American study identifies these anomalies in less than 1 % of patients.

Methods: 1800 computed tomography angiographies (CTA) obtained at the Barlicki University Hospital in Lodz, Poland, were reviewed retrospectively.

Results: All the patients were Caucasians. There were 968 males and 832 females. The mean age of the patients was 58. CTAs were obtained for the following reasons: stroke 1312, trauma 25, vascular/aneurysm 216, and intracranial haemorrhage 247. Vertebral artery hypoplasia was present in 360 cases (20 %). Persistent intersegmental artery (type I anomaly) was not found in any study. Fenestration of the V3 vertebral artery (type II) was recognized in three angiograms (0.16 %). Vertebral artery ending up as posterior inferior cerebellar artery (type III anomaly) was seen in 11 patients (0.61 %).

Conclusions: Very low incidence of V3 segment anomalies does not justify in our opinion routine vascular imaging in patients undergoing posterior cervical instrumented procedures.
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http://dx.doi.org/10.1007/s00586-016-4675-1DOI Listing
December 2016

Reorganization of Language Areas in Patient with a Frontal Lobe Low Grade Glioma - fMRI Case Study.

Pol J Radiol 2015 4;80:290-5. Epub 2015 Jun 4.

Department of Radiology and Diagnostic Imaging, Medical University of Łódź, Łódź, Poland.

Background: Functional magnetic resonance (fMRI) studies results in case of an adult patient with low grade glioma (LGG) in dominant hemisphere suggest brain plasticity process with acquisition of language functions by the non-dominant hemisphere speech regions.

Case Report: A 36-years old right-handed woman was admitted to the Department of Neurosurgery for surgical treatment of brain tumor. An MRI examination revealed a pathological mass in the left frontal lobe, in close topographical relationship to the Broca's area. A left fronto-parietal craniotomy was performed, with an intraoperative awake language mapping procedure. A total resection of the pathological mass was achieved. The tumor was examined histologically as LGG. In the follow-up MRI exam 32 months after the operation a tumor recurrence was suggested. The fMRI exams performed preoperative and 3, 32 and 41 months after the operation showed changes in language regions activation patterns, with a progressive right-sided activation of Broca's and Wernicke's areas. Pre- and postoperative cognitive evaluation by a neuropsychologist did not detect any language impairment. We present a running process of reorganization of language areas in a patient after brain tumor resection, from strong left-sided to symmetrical lateralization.

Conclusions: 1. FMRI results in comparison with the psychological status of the patient proved contribution of functional reorganization to the preservation of language performance. 2. A slow growing LGG as well as the recurrence of the tumor near the left Broca's area might be the factors leading to reorganization of language-related areas by recruiting the right hemisphe.
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http://dx.doi.org/10.12659/PJR.893897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461046PMC
June 2015

WWOX modulates the gene expression profile in the T98G glioblastoma cell line rendering its phenotype less malignant.

Oncol Rep 2014 Oct 17;32(4):1362-8. Epub 2014 Jul 17.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, Poland.

The aim of the present study was to assess the influence of WWOX gene upregulation on the transcriptome and phenotype of the T98G glioblastoma cell line. The cells with high WWOX expression demonstrated a significantly different transcription profile for approximately 3,000 genes. The main cellular pathways affected were Wnt, TGFβ, Notch and Hedgehog. Moreover, the WWOX-transfected cells proliferated at less than half the rate, exhibited greatly lowered adhesion to ECM, increased apoptosis and impaired 3D culture formation. They also demonstrated an increased ability for crossing the basement membrane. Our results indicate that WWOX, apart from its tumor-suppressor function, appears to be a key regulator of the main cellular functions of the cell cycle and apoptosis. Furthermore, our results showed that WWOX may be involved in controlling metabolism, cytoskeletal structure and differentiation.
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http://dx.doi.org/10.3892/or.2014.3335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148378PMC
October 2014

Anomalous course and diameter of left-sided vertebral arteries--significance and predisposing factors in clinical practice.

Ann Anat 2014 Sep 4;196(5):360-4. Epub 2014 May 4.

Department of Radiology and Diagnostic Imaging, Medical University of Łódź, Barlicki University Hospital No.1, 90-153 Łódź, Poland. Electronic address:

Introduction: The purpose of this study was to determine whether any correlation exists between the level of entry of vertebral arteries (VAs) into the foramen transversarium (FT) and their anomalous course or diameter. To our knowledge there are no studies in the literature concerning the diameter of the vertebral artery (VA) as an impact factor on entrance level.

Material And Methods: Computed tomography angiography (CTA) images of the aortic arch (AA) and its branches, obtained at the Department of Radiology, Medical University of Łódź from May 2009 to April 2012, were reviewed and the entrance points into the FT were determined.

Results: Left vertebral arteries arising directly from the AA more often had an anomalous entrance point to the foramen transversarium and were more frequently hypoplastic. In addition, hypoplastic VAs entered the FT at an anomalous level more often than VAs with normal diameter.

Conclusion: The left vertebral arteries arising directly from the aortic arch are often more hypoplastic and often enter the foramen transversarium at a different level from the C6 vertebrae. In patients with hypoplastic VA detected on the basis of ultrasound Color Doppler examination, the presence of anomalies must be considered when planning surgical treatment.
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http://dx.doi.org/10.1016/j.aanat.2014.04.005DOI Listing
September 2014

Prenatal diagnosis of a vein of Galen aneurysmal malformation with MR imaging - report of two cases.

Pol J Radiol 2013 Oct 19;78(4):88-92. Epub 2013 Nov 19.

Department of Radiology and Diagnostic Imaging, Medical University of ŁódŸ, Barlicki University Hospital No. 1, ŁódŸ, Poland.

Background: Vein of Galen malformations (VGMs) are rare congenital defects of cerebral vessels. They are formed between the 6(th) and 11(th) week of gestation. The background of this defect involves presence of one or more arterovenous fistulas directing bloodflow toward a persistent, dilated, proximal part of median prosencephalic vein (MProsV). Ultrasound examination is a basic test for diagnosis of VGMs. It has now become possible to acquire images of diagnostic value using magnetic resonance (MR) techniques.

Case Report: This work presents two cases of vein of Galen aneurysms diagnosed prenatally with magnetic resonance imaging. In both patients fetal CNS malformations were diagnosed in ultrasound examinations. MR imaging of the fetal head was performed for further diagnostics.

Conclusions: Because of the ability to precisely determine the size of the ventricular system, presence of raised intraventricular pressure and topographic relationships between pathologically changed vessels and particular cerebral structures as well as the presence of ischemic areas MR examination is currently not only complementary to ultrasonography, but is becoming an independent examination method in the diagnostics of vein of Galen malformations.
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http://dx.doi.org/10.12659/PJR.889613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908515PMC
October 2013

The WWOX tumor suppressor gene in endometrial adenocarcinoma.

Int J Mol Med 2013 Dec 11;32(6):1458-64. Epub 2013 Oct 11.

Department of Molecular Cancerogenesis, Medical University of Lodz, PL 90-752 Lodz, Poland.

Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero-zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.
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http://dx.doi.org/10.3892/ijmm.2013.1526DOI Listing
December 2013

Functional rearrangement of language areas in patients with tumors of the central nervous system using functional magnetic resonance imaging.

Pol J Radiol 2012 Jul;77(3):39-45

Department of Radiology and Diagnostic Imaging, Medical University of Łódź, Barlicki University Hospital No.1, Łódź, Poland.

Background: The aim of this study was to determine the reorganization of the language areas in patients with tumors located near speech centers using functional magnetic resonance imaging (fMRI).

Material/methods: fMRI was performed prior to the surgical treatment of 11 right-handed patients with tumors located close to the Broca's or Wernicke's areas of the left hemisphere. The analysis included a record of the activity in four regions of interest (ROIs): Broca's and Wernicke's areas, and their anatomic homologues in the right hemisphere. For each patient a regional lateralization index was calculated separately for Broca's area versus its right-hemisphere homolog and Wernicke's area versus its right-hemisphere homolog. The results were correlated with the histopathological type of the tumor and its size.

Results: Our fMRI examinations showed activation of the Broca's area in the right hemisphere in 3/4 cases of low grade gliomas (LGG) localized in the left frontal lobe. In one case of the high grade glioma (HGG) only the left hemisphere Broca's area was activated (LI=1). Activation in Wernicke's area in both hemispheres was obtained irrespective of the size and histological type of the tumor. All tumors localized in the left temporal lobe were HGG. We obtained activation only in the right hemisphere Wernicke's area in 4/5 of the cases. In 4/5 of the cases activation in Broca's area was present- in 2 cases in the left hemisphere, in 1 case in the right hemisphere and in 1 case bilateral.

Conclusions: The presence of a neoplastic lesion in close topographic relationship to language areas induces their functional reorganization. fMRI is an useful method for determination of language areas localization in pre-operative planning. HGG tumors localized near Wernicke's area lead to transfer its function to the healthy hemisphere and/or to decreased activity in the affected hemisphere.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447432PMC
http://dx.doi.org/10.12659/pjr.883373DOI Listing
July 2012

Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme.

J Neurooncol 2011 Jan 10;101(2):207-13. Epub 2010 Jun 10.

Department of Molecular Cancerogenesis, Medical University of Lodz, Mazowiecka St 6/8, 92-215 Lodz, Poland.

Glioblastoma multiforme is the most common type of primary brain tumor in adults. WWOX is a tumor suppressor gene involved in carcinogenesis and cancer progression in many different neoplasms. Reduced WWOX expression is associated with more aggressive phenotype and poor patient outcome in several cancers. We investigated alternations of WWOX expression and its correlation with proliferation, apoptosis and signal trafficking in 67 glioblastoma multiforme specimens. Moreover, we examined the level of WWOX LOH and methylation status in WWOX promoter region. Our results suggest that loss of heterozygosity (relatively frequent in glioblastoma multiforme) along with promoter methylation may decrease the expression of this tumor suppressor gene. Our experiment revealed positive correlations between WWOX and Bcl2 and between WWOX and Ki67. We also confirmed that WWOX is positively correlated with ErbB4 signaling pathway in glioblastoma multiforme.
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http://dx.doi.org/10.1007/s11060-010-0254-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996532PMC
January 2011