Iwona Bednarz−Misa

Wroclaw Medical University

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Małgorzata Krzystek‐Korpacka

Wroclaw Medical University

Andrzej Gamian

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy

Katarzyna Neubauer

Wroclaw Medical University

Wojciech Witkiewicz

Łukasiewicz Research Network – PORT Polish Center for Technology Development

ŁL

Łukasz Lewandowski

Wroclaw Medical University

Marek Zawadzki

St. Anna Hospital

Jadwiga Pietkiewicz

Wroclaw Medical University

Magdalena Mierzchała-Pasierb

Wroclaw Medical University

Mariusz G. Fleszar

Wroclaw Medical University

Julita Kulbacka

Wroclaw Medical University

Cooperative Institutions

National Institute of Standards and Technology

219

Université de Lorraine

219

Wroclaw Medical University

187

University of Wrocław

107

Wroclaw University of Environmental and Life Sciences

Wrocław University of Science and Technology

Polish Academy of Sciences

Niepubliczna Wyższa Szkoła Medyczna

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy

AGH University of Krakow

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Interleukin (IL)-7 Signaling in the Tumor Microenvironment

Advances in experimental medicine and biology (2021)

Iwona Bednarz−Misa Mariusz A. Bromke Małgorzata Krzystek‐Korpacka

10.1007/978-3-030-55617-4_2

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Citations (11)

Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro

Oxidative Medicine and Cellular Longevity (2020)

Marta Szandruk-Bender Maria Rutkowska Anna Merwid‐Ląd Benita Wiatrak Adam Szeląg

Background and Aims. Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods. Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results. Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions. CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.

Sulfasalazine

10.1155/2020/7697851

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Citations (23)

Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay

Advances in Clinical and Experimental Medicine (2019)

Małgorzata Krzystek‐Korpacka Krzysztof Kędzior Leszek Masłowski Magdalena Mierzchała-Pasierb Iwona Bednarz−Misa

Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies.The aim of this article is to evaluate the effects of wound etiology on a panel of circulating cytokines in patients with non-healing wounds of the lower extremities.This prospective case-control study involved 104 individuals: healthy elderly people (n = 46) and patients with diabetes and/or cardiovascular disease (n = 58; among them 38 with chronic wounds of venous, ischemic or neurotrophic etiology). Selected serum cytokines - i.e. IL-1β, IL-4, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-BB - were measured using the Luminex platform.Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, MCP-1 and G-CSF while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and GM-CSF. Among diseased elderly people, having wounds was associated with increased levels of IL-1β, IL-4, IL-6, IL-8, FGF-2, MIP-1α, PDGF-BB, and VEGF-A. Interleukin 1β elevation was a sole independent predictor of chronic wounds with an odds ratio (OR) of 6.3. Cytokines in healthy seniors were loosely interrelated, while the levels of cytokines in diseased patients with wounds displayed a tight pattern of association. When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and VEGF-A was disrupted in neurotrophic wounds.The results presented herein may improve our understanding of the pathomechanisms which lead to chronic wounds and of the effects they exert on a systemic level, as well as providing potential targets for more effective therapies.

Etiology

Proinflammatory cytokine

10.17219/acem/103845

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Citations (12)

Advances in Clinical and Experimental Medicine (2023)

Agnieszka Bronowicka-Szydełko Łukasz Lewandowski Maciej Rabczyński Małgorzata Trocha Edwin Kuźnik

We are delighted to welcome you to the 5 th International Wroclaw Scientific Meetings (IWSM), a gathering that brings together researchers from around the world.This year, the Scientific Meetings are being organized by dedicated students from the Faculty of Pharmacy and the Faculty of Medicine.These students are actively engaged in various groups, including the Group of Cancer Cell Biology, the Group of Biomedical and Environmental Analyses, the Group of Flow Cytometry and Biomedical Research, the Cardiac Perfusion Laboratory, and the Group of Toxicology.Our conference, the 5 th International Wroclaw Scientific Meetings, is specially dedicated to young scientists.Furthermore, this edition of IWSM is dedicated to the memory of Prof. Jolanta Saczko (1964-2023), an esteemed initiator of Scientific Meetings, who made significant contributions to the field of experimental anticancer therapies.Prof. Saczko was not only a pioneer but also an inspiring mentor to countless young scientists.In keeping with tradition, this conference aims to facilitate the exchange of scientific knowledge among young researchers and science enthusiasts from various centers in Poland and abroad.This multidisciplinary conference covers a wide array of topics, including cell biology, drug interactions in both cancer and normal cells, cell-drug interactions, cellular responses to oxidative stress, and cellular engineering, including computer modeling.Throughout the conference, young scientists will have the invaluable opportunity to present their research findings and engage in discussions with experienced and esteemed researchers in the world of science, who have graciously accepted our invitation to participate in this year's event.This year's plenary lectures will be delivered by world-renowned scientists from both Poland and abroad.In addition to these lectures, practical workshops on flow cytometry, quantum dots, electroporation, and cellular impedance will be organized, providing hands-on learning experiences for attendees.We extend a warm invitation to all of you to participate in these enriching sessions and discussions.We sincerely hope that this conference will be a platform for fruitful exchanges and foster valuable connections among attendees.Moreover, it brings us immense joy to witness the growing interest of young science enthusiasts from Poland and other international centers in our conference.We wish all conference participants engaging discussions and memorable moments in Wrocław.

10.17219/acem/2023-5iwsm-abstractbook

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Oversecretion and Overexpression of Nicotinamide Phosphoribosyltransferase/Pre-B Colony-Enhancing Factor/Visfatin in Inflammatory Bowel Disease Reflects the Disease Activity, Severity of Inflammatory Response and Hypoxia

International Journal of Molecular Sciences (2019)

Katarzyna Neubauer Iwona Bednarz−Misa Ewa Wałecka-Zacharska Jarosław Wierzbicki Anil Agrawal

Nicotinamide phosphoribosyltransferase's (Nampt) association with inflammatory bowel disease (IBD) is unclear. The study was aimed at unraveling Nampt's clinical and diagnostic relevance. The serum concentration (Luminex-xMAP® technology) was measured in 113 patients with Crohn's disease (CD), 127 with ulcerative colitis (UC) and 60 non-IBD controls: 40 healthy individuals and 20 with irritable bowel syndrome (IBS). The leukocyte (44 CD/37 UC/19 IBS) and bowel expression (186 samples) was also evaluated (RT-qPCR). All were referred to IBD phenotype, activity, treatment, and inflammatory/nutritional/angiogenic/hypoxia indices. Serum-Nampt and leukocyte-

Nicotinamide phosphoribosyltransferase

Hypoxia

10.3390/ijms20010166

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Citations (35)

Serum availability affects expression of common house-keeping genes in colon adenocarcinoma cell lines: implications for quantitative real-time PCR studies

Cytotechnology (2016)

Małgorzata Krzystek‐Korpacka Katarzyna Hotowy Elżbieta Czapińska Magdalena Podkowik Jacek Bania

Careful selection of housekeeping genes (HKG) is prerequisite to yield sound qPCR results. HKG expression varies in response to hypoxia but the effect of manipulations of serum availability, a common experimental procedure, remains unknown. Also, no data on HKG expression stability across colon adenocarcinoma lines that would aid selection of normalizers suitable for studies involving several lines are available. Thus, we evaluated the effect of serum availability on the expression of commonly used HKG (ACTB, B2M, GAPDH, GUSB, HPRT1, IPO8, MRPL19, PGK1, PPIA, RPLP0, RPS23, SDHA, TBP, UBC, and YWHAZ) in seven colon adenocarcinoma cell lines (Caco-2, DLD-1, HCT116, HT29, Lovo, SW480, and SW620). Sets of stably expressed line-specific and pan-line HKG were validated against absolutely quantified CDKN1A, TP53, and MDK transcripts. Both serum availability and line type affected HKG expression. UBC was fourfold down-regulated and HPRT1 1.75-fold up-regulated in re-fed HT29 cultures. Line-to-line variability in HKG expression was more pronounced than that caused by altering serum availability and could be found even between isogenic cell lines. PPIA, RPLP0, YWHAZ, and IPO8 were repeatedly highly ranked while ACTB, B2M, UBC, and PGK1 were ranked poorly. Normalization against PPIA/RPLP0/SDHA was found optimal for studies involving various colon adenocarcinoma cell lines subjected to manipulations of serum availability. We found HKG expression to vary, more pronouncedly by line type than growth conditions with significant differences also between isogenic cell lines. Although using line-specific normalizers remains optimal, a set of pan-line HKG that yields good estimation of relative expression of target genes was proposed.

SDHA

Housekeeping gene

Reference Genes

Colorectal adenocarcinoma

10.1007/s10616-016-9971-4

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Citations (17)

Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility

Cancers (2020)

Iwona Bednarz−Misa Dorota Diakowska Izabela Szczuka Paulina Fortuna Agnieszka Kubiak

Immunosuppressive interleukins (IL)-4 and 13 may directly promote cancer but neither their status nor role in gastrointestinal tract is clarified. We aim at quantifying ILs and their receptors in paired normal-tumor samples (n = 49/51) and sera (n = 263), using immunoassays and RTqPCR, and screening for their effect on colonic cancer cells. Both ILs were elevated locally at protein level in all cancers but only IL13 transcripts in colon were upregulated. Interleukin and their receptor expression reflected cancer pathology to varying degrees, with the association frequently inverse and manifested in non-cancerous tissue. Positive correlation with cancer-promoting genes BCL2, BCLxL, HIF1A, VEGFA, ACTA2, CCL2, PTGS2, and CDKN1A, but not Ki67, was demonstrated, particularly for ILs’ receptors. Circulating IL-4 was elevated in all, while IL-13 only in colorectal or esophageal cancers, reflecting their advancement. IL4Ra and IL13Ra1 transcripts were downregulated by hypoxia and, in Caco-2, also by IL-4. Interleukin stimulation slightly improved colonic cancer cell viability, weakly upregulating BCL2 and Ki67 in HCT116 and HT-29. It affected cell motility more markedly and was consistently accompanied by upregulation of claudin-2. Gastrointestinal tract cancers are associated with IL-4 and IL-13 upregulation, which may facilitate cancer growth. Targeting both interleukins as an antineoplastic strategy warrants further investigation.

Interleukin 8

10.3390/cancers12061463

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Citations (19)

Atherogenic Plasma Index or Non-High-Density Lipoproteins as Markers Best Reflecting Age-Related High Concentrations of Small Dense Low-Density Lipoproteins

International Journal of Molecular Sciences (2022)

Sylwia Płaczkowska Katarzyna Sołkiewicz Iwona Bednarz−Misa Ewa Maria Kratz

The study aimed to assess the strength of the relationships between small dense low-density lipoproteins (sdLDL) and other parameters describing metabolic disorders and determine which of the lipid profile parameters can be used as markers of increased sdLDL concentration. The proposed model of sdLDL (examined by heparin−magnesium precipitation method) as a function of lipid parameters and atherogenic plasma indexes non-high-dense lipoproteins (non-HDL) and total cholesterol to high-dense lipoprotein ratio (TC/HDL), Atherogenic plasma index (API) is based on data from 485 participants divided into two age groups, <35≥ years. In multiple linear regression, sdLDL concentration was associated with the concentration of non-HDL-C (p = 0.043) and API value (p < 0.001) in participants <35 years, and with non-HDL-C (p < 0.001) and triglycerides (p = 0.020) concentration ≥35 years. The presence of abnormal values of API in participants <35 years and non-HDL-C in participants ≥35 years is a significant factor increasing the chances of the highest sdLDL (≥1.03 mmol/L) corresponding to Q4 in people without metabolic disorders. Different lipid parameters and atherogenicity indexes are associated with a high concentration of sdLDL depending on the age group. Abnormal API <35 years and non-HDL ≥35 years are associated with the highest sdLDL values and may be an indication for further specialist diagnosis of cardiovascular disease risk factors.

Lipid Profile

High-density lipoprotein

10.3390/ijms23095089

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Citations (15)

Transcriptional and Metabolomic Analysis of L-Arginine/Nitric Oxide Pathway in Inflammatory Bowel Disease and Its Association with Local Inflammatory and Angiogenic Response: Preliminary Findings

International Journal of Molecular Sciences (2020)

Małgorzata Krzystek‐Korpacka Mariusz G. Fleszar Iwona Bednarz−Misa Łukasz Lewandowski Izabela Szczuka

L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.

Asymmetric dimethylarginine

10.3390/ijms21051641

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Citations (32)

Visfatin in juvenile obesity – the effect of obesity intervention and sex

European Journal of Clinical Investigation (2011)

Małgorzata Krzystek‐Korpacka Eliza Patryn Iwona Bednarz−Misa Katarzyna Hotowy Anna Noczyńska

Eur J Clin Invest 2011; 41 (12): 1284–1291 Abstract Background The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re‐established as previously used tests occurred to be nonspecific. Objective To evaluate visfatin association with a metabolic profile of 88 overweight/obese and 26 lean children/adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity ± metformin). Design A case–control and cohort study. Results Visfatin was higher in obese than lean and overweight individuals (2·07 vs. 1·53 and 1·47 ng mL −1 , P = 0·034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin ( r = 0·40, P = 0·009) and thiols ( r = −0·36, P = 0·009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference ( r = 0·36, P = 0·036), BMI% ( r = 0·38, P = 0·025), whole body insulin sensitivity index ( r = −0·36, P = 0·036), IL‐6 ( r = 0·38, P = 0·024) and thiobarbituric acid reactive substances (TBARS) ( r = 0·52, P = 0·001), of which IL‐6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1·43 vs. 1·83 ng mL −1 , P = 0·033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. ΔVisfatin correlated exclusively with baseline visfatin ( r = 0·612, P < 0·0001), which explained 38% in data variability. Conclusions Central obesity combined with HI/IR contributes to visfatin elevation. Visfatin association with metabolic/biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfatin.

TBARS

Hyperinsulinemia

10.1111/j.1365-2362.2011.02538.x

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Citations (22)