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Article ; Online: CTCF shapes chromatin structure and gene expression in health and disease.

Dehingia, Bondita / Milewska, Małgorzata / Janowski, Marcin / Pękowska, Aleksandra

2022 Volume 23, Issue 9, Page(s) e55146

Abstract: CCCTC-binding factor (CTCF) is an eleven zinc finger (ZF), multivalent transcriptional regulator, that recognizes numerous motifs thanks to the deployment of distinct combinations of its ZFs. The great majority of the ~50,000 genomic locations bound by ... ...

Abstract	CCCTC-binding factor (CTCF) is an eleven zinc finger (ZF), multivalent transcriptional regulator, that recognizes numerous motifs thanks to the deployment of distinct combinations of its ZFs. The great majority of the ~50,000 genomic locations bound by the CTCF protein in a given cell type is intergenic, and a fraction of these sites overlaps with transcriptional enhancers. Furthermore, a proportion of the regions bound by CTCF intersect genes and promoters. This suggests multiple ways in which CTCF may impact gene expression. At promoters, CTCF can directly affect transcription. At more distal sites, CTCF may orchestrate interactions between regulatory elements and help separate eu- and heterochromatic areas in the genome, exerting a chromatin barrier function. In this review, we outline how CTCF contributes to the regulation of the three-dimensional structure of chromatin and the formation of chromatin domains. We discuss how CTCF binding and architectural functions are regulated. We examine the literature implicating CTCF in controlling gene expression in development and disease both by acting as an insulator and a factor facilitating regulatory elements to efficiently interact with each other in the nuclear space.
MeSH term(s)	Binding Sites ; CCCTC-Binding Factor/genetics ; CCCTC-Binding Factor/metabolism ; Chromatin/genetics ; Enhancer Elements, Genetic ; Gene Expression ; Promoter Regions, Genetic ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
Chemical Substances	CCCTC-Binding Factor ; Chromatin ; Repressor Proteins
Language	English
Publishing date	2022-08-22
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202255146
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Article ; Online: Curcumin-Poly(sodium 4-styrenesulfonate) Conjugates as Potent Zika Virus Entry Inhibitors.

Obłoza, Magdalena / Milewska, Aleksandra / Botwina, Paweł / Szczepański, Artur / Medaj, Aneta / Bonarek, Piotr / Szczubiałka, Krzysztof / Pyrć, Krzysztof / Nowakowska, Maria

ACS applied materials & interfaces

2024 Volume 16, Issue 5, Page(s) 5426–5437

Abstract: Curcumin, a natural product with recognized antiviral properties, is limited in its application largely due to its poor solubility. This study presents the synthesis of water-soluble curcumin-poly(sodium 4-styrenesulfonate) (Cur- ... ...

Abstract	Curcumin, a natural product with recognized antiviral properties, is limited in its application largely due to its poor solubility. This study presents the synthesis of water-soluble curcumin-poly(sodium 4-styrenesulfonate) (Cur-PSSNa
MeSH term(s)	Humans ; Curcumin/pharmacology ; Zika Virus ; Virus Internalization ; Zika Virus Infection/drug therapy ; Solubility ; Water
Chemical Substances	Curcumin (IT942ZTH98) ; Water (059QF0KO0R)
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c13893
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Article ; Online: Targeted Delivery of Cisplatin by Gold Nanoparticles: The Influence of Nanocarrier Surface Modification Type on the Efficiency of Drug Binding Examined by CE-ICP-MS/MS.

Wróblewska, Anna M / Milewska, Aleksandra / Drozd, Marcin / Matczuk, Magdalena

International journal of molecular sciences

2022 Volume 23, Issue 4

Abstract: Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, ... ...

Abstract	Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle-cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold-drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface's processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH
MeSH term(s)	Antineoplastic Agents/chemistry ; Cisplatin/chemistry ; Drug Carriers/chemistry ; Dynamic Light Scattering/methods ; Electrophoresis, Capillary/methods ; Gold/chemistry ; Metal Nanoparticles/chemistry ; Nanoconjugates/chemistry ; Particle Size ; Tandem Mass Spectrometry/methods
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; Nanoconjugates ; Gold (7440-57-5) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23042324
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Article: Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.

Janowski, Marcin / Milewska, Małgorzata / Zare, Peyman / Pękowska, Aleksandra

Pharmaceuticals (Basel, Switzerland)

2021 Volume 14, Issue 8

Abstract: Neurological disorders (NDs) comprise a heterogeneous group of conditions that affect the function of the nervous system. Often incurable, NDs have profound and detrimental consequences on the affected individuals' lives. NDs have complex etiologies but ... ...

Abstract	Neurological disorders (NDs) comprise a heterogeneous group of conditions that affect the function of the nervous system. Often incurable, NDs have profound and detrimental consequences on the affected individuals' lives. NDs have complex etiologies but commonly feature altered gene expression and dysfunctions of the essential chromatin-modifying factors. Hence, compounds that target DNA and histone modification pathways, the so-called epidrugs, constitute promising tools to treat NDs. Yet, targeting the entire epigenome might reveal insufficient to modify a chosen gene expression or even unnecessary and detrimental to the patients' health. New technologies hold a promise to expand the clinical toolkit in the fight against NDs. (Epi)genome engineering using designer nucleases, including CRISPR-Cas9 and TALENs, can potentially help restore the correct gene expression patterns by targeting a defined gene or pathway, both genetically and epigenetically, with minimal off-target activity. Here, we review the implication of epigenetic machinery in NDs. We outline syndromes caused by mutations in chromatin-modifying enzymes and discuss the functional consequences of mutations in regulatory DNA in NDs. We review the approaches that allow modifying the (epi)genome, including tools based on TALENs and CRISPR-Cas9 technologies, and we highlight how these new strategies could potentially change clinical practices in the treatment of NDs.
Language	English
Publishing date	2021-08-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph14080765
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Article ; Online: Visualizing Coronavirus Entry into Cells.

Milewska, Aleksandra / Owczarek, Katarzyna / Szczepanski, Artur / Pyrc, Krzysztof

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2203, Page(s) 241–261

Abstract: Coronavirus entry encompasses the initial steps of infection, from virion attachment to genome release. Advances in fluorescent labeling of viral and cellular components and confocal imaging enable broad spectrum studies on this process. Here, we ... ...

Abstract	Coronavirus entry encompasses the initial steps of infection, from virion attachment to genome release. Advances in fluorescent labeling of viral and cellular components and confocal imaging enable broad spectrum studies on this process. Here, we describe methods for visualization of coronavirus entry into immortalized cell lines and 3D tissue culture models.
MeSH term(s)	Cell Line ; Coronavirus/isolation & purification ; Coronavirus/pathogenicity ; Coronavirus Nucleocapsid Proteins ; Culture Media/chemistry ; Endocytosis ; Host-Pathogen Interactions/physiology ; Humans ; Microscopy, Confocal/methods ; Nucleocapsid Proteins/metabolism ; Triiodobenzoic Acids/chemistry ; Virus Internalization
Chemical Substances	Coronavirus Nucleocapsid Proteins ; Culture Media ; Nucleocapsid Proteins ; Triiodobenzoic Acids ; iodixanol (HW8W27HTXX)
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0900-2_18
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Article ; Online: Targeted Delivery of Cisplatin by Gold Nanoparticles

Anna M. Wróblewska / Aleksandra Milewska / Marcin Drozd / Magdalena Matczuk

International Journal of Molecular Sciences, Vol 23, Iss 2324, p

The Influence of Nanocarrier Surface Modification Type on the Efficiency of Drug Binding Examined by CE-ICP-MS/MS

2022 Volume 2324

Abstract	Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle–cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold–drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface’s processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH 3 , and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability.
Keywords	cisplatin ; gold nanoparticles ; drug delivery ; targeted drug delivery systems ; nanoparticle surface modification ; nanocarrier surface functionalization ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue

Marcin Janowski / Małgorzata Milewska / Peyman Zare / Aleksandra Pękowska

Pharmaceuticals, Vol 14, Iss 765, p

2021 Volume 765

Abstract	Neurological disorders (NDs) comprise a heterogeneous group of conditions that affect the function of the nervous system. Often incurable, NDs have profound and detrimental consequences on the affected individuals’ lives. NDs have complex etiologies but commonly feature altered gene expression and dysfunctions of the essential chromatin-modifying factors. Hence, compounds that target DNA and histone modification pathways, the so-called epidrugs, constitute promising tools to treat NDs. Yet, targeting the entire epigenome might reveal insufficient to modify a chosen gene expression or even unnecessary and detrimental to the patients’ health. New technologies hold a promise to expand the clinical toolkit in the fight against NDs. (Epi)genome engineering using designer nucleases, including CRISPR-Cas9 and TALENs, can potentially help restore the correct gene expression patterns by targeting a defined gene or pathway, both genetically and epigenetically, with minimal off-target activity. Here, we review the implication of epigenetic machinery in NDs. We outline syndromes caused by mutations in chromatin-modifying enzymes and discuss the functional consequences of mutations in regulatory DNA in NDs. We review the approaches that allow modifying the (epi)genome, including tools based on TALENs and CRISPR-Cas9 technologies, and we highlight how these new strategies could potentially change clinical practices in the treatment of NDs.
Keywords	epigenetics ; transcriptional regulation ; cis-regulatory elements ; nervous system ; chromatin structure ; histone modifications ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Selected Organ and Endocrine Complications According to BMI and the Metabolic Category of Obesity: A Single Endocrine Center Study

Milewska, Ewa Malwina / Szczepanek-Parulska, Ewelina / Marciniak, Martyna / Krygier, Aleksandra / Dobrowolska, Agnieszka / Ruchala, Marek

Nutrients. 2022 Mar. 20, v. 14, no. 6

2022

Abstract: Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been ... ...

Abstract	Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been referred to a single endocrine center. The study aimed to assess the prevalence of selected organ and endocrine complications by subdividing the group, firstly according to body mass index (BMI) and secondly with regard to metabolic syndrome (MetS), pre-MetS and the metabolically healthy obesity (MHO) category. We have observed that in our groups, the prevalence of hyperlipidemia, hypertension, asthma, obstructive sleep apnea (OSA) depended on BMI category, whereas the incidence of hyperlipidemia, hypertension, OSA, hypothyroidism, non-alcoholic fatty liver disease, prediabetes, and type 2 diabetes was related to the metabolic category. We concluded that the distribution of particular organ and endocrine complications change significantly with increased BMI and with the shift from MHO to pre-MetS and MetS. Thus, to determine the risk of organ and endocrine complications more effectively, BMI and metabolic status should be assessed during the examination of patients with obesity.
Keywords	asthma ; body mass index ; fatty liver ; hyperlipidemia ; hypertension ; hypothyroidism ; metabolic syndrome ; noninsulin-dependent diabetes mellitus ; obesity ; risk ; sleep apnea
Language	English
Dates of publication	2022-0320
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14061307
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Selected Organ and Endocrine Complications According to BMI and the Metabolic Category of Obesity: A Single Endocrine Center Study.

Milewska, Ewa Malwina / Szczepanek-Parulska, Ewelina / Marciniak, Martyna / Krygier, Aleksandra / Dobrowolska, Agnieszka / Ruchala, Marek

Nutrients

2022 Volume 14, Issue 6

Abstract	Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been referred to a single endocrine center. The study aimed to assess the prevalence of selected organ and endocrine complications by subdividing the group, firstly according to body mass index (BMI) and secondly with regard to metabolic syndrome (MetS), pre-MetS and the metabolically healthy obesity (MHO) category. We have observed that in our groups, the prevalence of hyperlipidemia, hypertension, asthma, obstructive sleep apnea (OSA) depended on BMI category, whereas the incidence of hyperlipidemia, hypertension, OSA, hypothyroidism, non-alcoholic fatty liver disease, prediabetes, and type 2 diabetes was related to the metabolic category. We concluded that the distribution of particular organ and endocrine complications change significantly with increased BMI and with the shift from MHO to pre-MetS and MetS. Thus, to determine the risk of organ and endocrine complications more effectively, BMI and metabolic status should be assessed during the examination of patients with obesity.
MeSH term(s)	Body Mass Index ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Humans ; Metabolic Syndrome ; Obesity/complications ; Obesity/epidemiology ; Obesity, Metabolically Benign/complications
Language	English
Publishing date	2022-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14061307
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Article ; Online: Changes in the Concentrations of Proangiogenic Cytokines in Human Brain Glioma and Acute Lymphoblastic Leukemia.

Oldak, Lukasz / Zielinska, Zuzanna / Milewska, Patrycja / Chludzinska-Kasperuk, Sylwia / Latoch, Eryk / Konończuk, Katarzyna / Krawczuk-Rybak, Maryna / Starosz, Aleksandra / Grubczak, Kamil / Reszeć, Joanna / Gorodkiewicz, Ewa

International journal of molecular sciences

2024 Volume 25, Issue 5

Abstract: Acute lymphoblastic leukemia (ALL) and glioma are some of the most common malignancies, with ALL most often affecting children and glioma affecting adult men. Proangiogenic cytokines and growth factors play an important role in the development of both of ...

Abstract	Acute lymphoblastic leukemia (ALL) and glioma are some of the most common malignancies, with ALL most often affecting children and glioma affecting adult men. Proangiogenic cytokines and growth factors play an important role in the development of both of these tumors. Glioma is characterized by an extremely extensive network of blood vessels, which continues to expand mainly in the process of neoangiogenesis, the direct inducers of which are cytokines from the family of vascular endothelial growth factors, i.e., vascular endothelial growth factor (VEGF-A) and its receptor vascular endothelial growth factor receptor 2 (VEGF-R2), as well as a cytokine from the fibroblast growth factor family, fibroblast growth factor 2 (FGF-2 or bFGF). Growth factors are known primarily for their involvement in the progression and development of solid tumors, but there is evidence that local bone marrow angiogenesis and increased blood vessel density are also present in hematological malignancies, including leukemias. The aim of this study was to examine changes in the concentrations of VEGF-A, VEGF-R2, and FGF-2 (with a molecular weight of 17 kDa) in a group of patients divided into specific grades of malignancy (glioma) and a control group; changes of VEGF-A and FGF-2 concentrations in childhood acute lymphoblastic leukemia and a control group; and to determine correlations between the individual proteins as well as the influence of the patient's age, diet, and other conditions that may place the patient in the risk group. During the statistical analysis, significant differences in concentrations were found between the patient and control groups in samples from people with diagnosed glioma and from children with acute lymphoblastic leukemia, but in general, there are no significant differences in the concentrations of VEGF-A, VEGF-R2, and FGF-2 between different grades of glioma malignancy. Among individuals treated for glioma, there was no significant impact from the patient's gender and age, consumption of food from plastic packaging, frequency of eating vegetables and fruit, smoking of tobacco products, the intensity of physical exercise, or the general condition of the body (Karnofsky score) on the concentrations of the determined cytokines and receptor. The listed factors do not bring about an actual increase in the risk of developing brain glioma.
MeSH term(s)	Male ; Adult ; Child ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; Cytokines/metabolism ; Fibroblast Growth Factor 2/metabolism ; Vascular Endothelial Growth Factors/metabolism ; Glioma/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Brain/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A ; Cytokines ; Fibroblast Growth Factor 2 (103107-01-3) ; Vascular Endothelial Growth Factors
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25052586
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