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Article ; Online: IRAK-M deficiency promotes the development of type 1 diabetes in NOD mice.

Tan, Qiyuan / Majewska-Szczepanik, Monika / Zhang, Xiaojun / Szczepanik, Marian / Zhou, Zhiguang / Wong, F Susan / Wen, Li

Diabetes

2014 Volume 63, Issue 8, Page(s) 2761–2775

Abstract: ... M (IRAK-M) can effectively inhibit the MyD88 downstream signals in Toll-like receptor pathways ... while lack of IRAK-M is known to be associated with autoimmunity. Our study showed that IRAK-M-deficient ... IRAK-M(-/-)) nonobese diabetic (NOD) mice displayed early onset and rapid progression of T1DM ...

Abstract	Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease characterized by progressive destruction of insulin-secreting pancreatic β-cells. Both T-cell-mediated adaptive responses as well as innate immune processes are involved in pathogenesis. Interleukin-1 receptor-associated kinase M (IRAK-M) can effectively inhibit the MyD88 downstream signals in Toll-like receptor pathways, while lack of IRAK-M is known to be associated with autoimmunity. Our study showed that IRAK-M-deficient (IRAK-M(-/-)) nonobese diabetic (NOD) mice displayed early onset and rapid progression of T1DM with impaired glucose tolerance, more severe insulitis, and increased serum anti-insulin autoantibodies. Mechanistic studies showed that the enhanced activation and antigen-presenting function of IRAK-M(-/-) antigen-presenting cells from IRAK-M(-/-) mice were responsible for the rapid progression of disease. Moreover, IRAK-M(-/-) dendritic cells induced enhanced activation of diabetogenic T cells in vitro and the rapid onset of T1DM in vivo in immunodeficient NOD mice when cotransferred with diabetogenic T cells. This study illustrates how the modulation of innate immune pathways through IRAK-M influences the development of autoimmune diabetes.
MeSH term(s)	Animals ; Autoantibodies ; CD4-Positive T-Lymphocytes ; Cytokines/genetics ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/metabolism ; Gene Expression Regulation ; Insulin/immunology ; Interleukin-1 Receptor-Associated Kinases/genetics ; Interleukin-1 Receptor-Associated Kinases/metabolism ; Lymphocyte Activation/physiology ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mice, Transgenic
Chemical Substances	Autoantibodies ; Cytokines ; Insulin ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1) ; Irak3 protein, mouse (EC 2.7.11.1)
Language	English
Publishing date	2014-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db13-1504
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Article ; Online: Migraine and the microbiota. Can probiotics be beneficial in its prevention? - a narrative review.

Kiecka, Aneta / Szczepanik, Marian

Pharmacological reports : PR

2024 Volume 76, Issue 2, Page(s) 251–262

Abstract: Migraine is a recurrent disease of the central nervous system that affects an increasing number of people worldwide causing a continuous increase in the costs of treatment. The mechanisms underlying migraine are still unclear but recent reports show that ...

Abstract	Migraine is a recurrent disease of the central nervous system that affects an increasing number of people worldwide causing a continuous increase in the costs of treatment. The mechanisms underlying migraine are still unclear but recent reports show that people with migraine may have an altered composition of the intestinal microbiota. It is well established that the gut-brain axis is involved in many neurological diseases, and probiotic supplementation may be an interesting treatment option for these conditions. This review collects data on the gastrointestinal and oral microbiota in people suffering from migraine and the use of probiotics as a novel therapeutic approach in its treatment.
MeSH term(s)	Humans ; Migraine Disorders/drug therapy ; Migraine Disorders/prevention & control ; Central Nervous System ; Gastrointestinal Microbiome/physiology ; Nervous System Diseases ; Probiotics/therapeutic use
Language	English
Publishing date	2024-03-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2186248-5
ISSN	2299-5684 ; 1734-1140
ISSN (online)	2299-5684
ISSN	1734-1140
DOI	10.1007/s43440-024-00584-7
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Article ; Online: Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics.

Kiecka, Aneta / Szczepanik, Marian

Pharmacological reports : PR

2023 Volume 75, Issue 4, Page(s) 791–804

Abstract: Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison ...

Abstract	Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.
MeSH term(s)	Humans ; Proton Pump Inhibitors/adverse effects ; Clostridioides difficile ; Dysbiosis/chemically induced ; Gastroesophageal Reflux/chemically induced ; Gastroesophageal Reflux/drug therapy ; Probiotics/therapeutic use ; Immunity ; Immunomodulation
Chemical Substances	Proton Pump Inhibitors
Language	English
Publishing date	2023-05-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2186248-5
ISSN	2299-5684 ; 1734-1140
ISSN (online)	2299-5684
ISSN	1734-1140
DOI	10.1007/s43440-023-00489-x
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Article ; Online: Natural killer cell-mediated contact dermatitis-like reaction induced by treatment with TLR3 ligand poly(I:C).

Majewska-Szczepanik, Monika / Kowalczyk, Paulina / Askenase, Philip W / Szczepanik, Marian

Contact dermatitis

2023 Volume 89, Issue 4, Page(s) 230–240

Abstract: Introduction: Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long-lasting T-cell-mediated ... ...

Abstract	Introduction: Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long-lasting T-cell-mediated responses. In addition, TLR3 modulates the contact hypersensitivity reaction. Objective: This study aimed to determine whether poly(I:C) injection can induce NK-mediated hapten reactivity in mice. Methods: Mice were treated with poly(I:C), and their response to dinitrofluorobenzene hapten was measured by assessing ear swelling and serum interferon gamma (IFN-γ) production. Adoptive cell transfer and cell sorting were used to investigate the mechanism of the reaction, and the phenotype of poly(I:C)-activated liver NK cells was determined by flow cytometry analysis. Results: The results showed that poly(I:C) administration increased ear swelling, serum IFN-γ levels and the response to hapten in both immunocompetent and T- and B-cell-deficient mice. Only liver poly(I:C)-activated DX5(+) NK cells were able to transfer reactivity to hapten into a naive recipient. Induction of liver NK cells after poly(I:C) administration was TLR3/TRIF- and IFN-γ-dependent, interleukin 12-independent, and not modulated by MyD88. Conclusion: This study provides new insights into how poly(I:C) stimulates NK-mediated reactivity to hapten and suggests that liver NK cells may modulate the immune response to non-pathogenic factors during viral infection.
MeSH term(s)	Mice ; Animals ; Toll-Like Receptor 3/agonists ; Toll-Like Receptor 3/genetics ; Ligands ; Dermatitis, Allergic Contact/etiology ; Killer Cells, Natural ; Poly I-C/adverse effects ; Interferon-gamma ; Mice, Inbred C57BL
Chemical Substances	Toll-Like Receptor 3 ; Ligands ; Poly I-C (O84C90HH2L) ; Interferon-gamma (82115-62-6) ; TLR3 protein, mouse
Language	English
Publishing date	2023-07-18
Publishing country	England
Document type	Journal Article
ZDB-ID	193121-0
ISSN	1600-0536 ; 0105-1873
ISSN (online)	1600-0536
ISSN	0105-1873
DOI	10.1111/cod.14380
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Zs.A 1116: Show issues

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Article ; Online: Epicutaneous immunization with TNP-Ig antigen induces CD11c

Majewska-Szczepanik, Monika / Strzępa, Anna / Marcińska, Katarzyna / Szczepanik, Marian

International immunopharmacology

2023 Volume 119, Page(s) 110281

Abstract: The contact hypersensitivity response (CHS) is a mouse model of allergic contact dermatitis in humans. The reaction is classified as type IV hypersensitivity and underlies many autoimmune disorders. Experiments employing the CHS model in wild-type mice ... ...

Abstract	The contact hypersensitivity response (CHS) is a mouse model of allergic contact dermatitis in humans. The reaction is classified as type IV hypersensitivity and underlies many autoimmune disorders. Experiments employing the CHS model in wild-type mice showed that the protein antigen applied to the skin in the form of a gauze patch one week before the induction of Th1-dependent CHS was an effective strategy to reduce the inflammatory response in the skin. The approach of epicutaneous (EC) immunization also effectively suppressed the inflammatory response in various mouse models of autoimmune diseases. To evaluate the potential of EC immunization to suppress T cell-dependent immune response in humans, we used HLA-DR4 tg mice, which express the human DRB1*0401 allele and lack all endogenous mouse MHC class II genes. Our data show that EC immunization with TNP-conjugated protein antigen followed by induction of CHS to trinitrochlorobenzene (TNCB), effectively suppressed the CHS response as described by ear swelling, MPO activity in ear extracts, and the number of TCRβ
MeSH term(s)	Mice ; Humans ; Animals ; Mice, Transgenic ; HLA-DR4 Antigen/genetics ; Interleukin-10 ; Immunization ; Antigens ; Dermatitis, Allergic Contact/therapy ; Dendritic Cells
Chemical Substances	HLA-DR4 Antigen ; Interleukin-10 (130068-27-8) ; Antigens
Language	English
Publishing date	2023-05-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110281
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Article ; Online: The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis.

Rosik, Jakub / Kulpa, Joanna / Szczepanik, Marcin / Pawlik, Andrzej

Cells

2024 Volume 13, Issue 7

Abstract: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their ... ...

Abstract	Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their pleiotropic nature has various effects on the further development of RA. This narrative review summarises the various roles of semaphorins in the pathology of RA and whether they could play a role in developing novel RA treatment options.
MeSH term(s)	Humans ; Semaphorins ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Inflammation ; Synovial Fluid
Chemical Substances	Semaphorins
Language	English
Publishing date	2024-04-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13070618
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Article ; Online: The potential action of SSRIs in the treatment of skin diseases including atopic dermatitis and slow-healing wounds.

Kiecka, Aneta / Szczepanik, Marian

Pharmacological reports : PR

2022 Volume 74, Issue 5, Page(s) 947–955

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are used to treat affective and anxiety disorders. Antidepressants have also been shown to have antimicrobial and immunomodulatory effects, which may affect the microbiota-intestinal-brain axis. Studies ... ...

Abstract	Selective serotonin reuptake inhibitors (SSRIs) are used to treat affective and anxiety disorders. Antidepressants have also been shown to have antimicrobial and immunomodulatory effects, which may affect the microbiota-intestinal-brain axis. Studies show that SSRIs have antimicrobial activity both in vivo and in vitro and influence bacteria by inhibiting biofilm, affecting efflux pumps, among others. A huge challenge today is the prevention and treatment of skin diseases, including atopic dermatitis (AD) and slow-healing wounds. Skin diseases including AD and non-healing wounds are serious medical problem. People suffering from these conditions feel constant discomfort, which also affects their psychological state. Research on new treatments for AD and slow-healing wounds is essential because current medications are not fully effective and have many side effects. Exploring new drug groups for AD and slow-healing wounds will allow for the creation of an alternative treatment for these diseases. SSRIs represent a hope for the treatment of skin diseases due to their immunomodulatory and antimicrobial properties.
MeSH term(s)	Humans ; Serotonin Uptake Inhibitors/pharmacology ; Serotonin Uptake Inhibitors/therapeutic use ; Dermatitis, Atopic/drug therapy ; Antidepressive Agents ; Anxiety
Chemical Substances	Serotonin Uptake Inhibitors ; Antidepressive Agents
Language	English
Publishing date	2022-10-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2186248-5
ISSN	2299-5684 ; 1734-1140
ISSN (online)	2299-5684
ISSN	1734-1140
DOI	10.1007/s43440-022-00423-7
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Article ; Online: Contact Hypersensitivity as a Murine Model of Allergic Contact Dermatitis.

Zemelka-Wiacek, Magdalena / Majewska-Szczepanik, Monika / Gajdanowicz, Pawel / Szczepanik, Marian

Journal of visualized experiments : JoVE

2022 , Issue 187

Abstract: Contact hypersensitivity (CHS) is an experimental model of allergic contact dermatitis (ACD) that can be studied in mice. This study aims to present an objective laboratory method that may help to study the CHS reaction in mice, which can be measured and ...

Abstract	Contact hypersensitivity (CHS) is an experimental model of allergic contact dermatitis (ACD) that can be studied in mice. This study aims to present an objective laboratory method that may help to study the CHS reaction in mice, which can be measured and quantified by various tests. To induce CHS, on day "0", mice were sensitized on a previously shaved spot by abdominal skin painting with the hapten 2,4,6-trinitrochlorobenzene (TNCB) in an acetone-ethanol mixture, whereas negative control mice were sham sensitized with vehicle alone-acetone-ethanol mixture. On day "4", the baseline ear thickness was measured with a micrometer prior to the elicitation of CHS (challenge) by painting both ears with diluted TNCB both in the test and control groups. After 24 h, the ear swelling was measured with a micrometer. CHS is an example of a T cell-mediated immune response that causes swelling in inflamed tissue, peaking 24 h after the skin challenge with the same hapten. An increase in ear edema correlated with augmented ear weight, myeloperoxidase (MPO) activity, pro-inflammatory cytokine concentration in the ear extracts, increased thickening of the edematous dermis in the histological examination, and ear vascular permeability. There was also an increase in the concentration of TNP-specific IgG1 antibodies in the sera of the test group when compared with the control mice. Additionally, CHS can be successfully transferred with the CHS-effector cells obtained from donors previously sensitized with TNCB. The CHS-effector cells were administered intravenously into naïve recipient mice, which were subsequently challenged with the same diluted hapten. Ear swelling was measured with a micrometer 24 h later.
MeSH term(s)	Mice ; Animals ; Picryl Chloride ; Peroxidase ; Disease Models, Animal ; Acetone ; Mice, Inbred BALB C ; Dermatitis, Allergic Contact/etiology ; Dermatitis, Allergic Contact/pathology ; Haptens ; Cytokines ; Immunoglobulin G ; Ethanol
Chemical Substances	Picryl Chloride (Z4ZG7O5SZ9) ; Peroxidase (EC 1.11.1.7) ; Acetone (1364PS73AF) ; Haptens ; Cytokines ; Immunoglobulin G ; Ethanol (3K9958V90M)
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64329
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Article: The Protective Effects of Astaxanthin (AST) in the Liver of Weaned Piglets.

Szczepanik, Kinga / Oczkowicz, Maria / Dobrowolski, Piotr / Świątkiewicz, Małgorzata

Animals : an open access journal from MDPI

2023 Volume 13, Issue 20

Abstract: During the weaning period, piglets are exposed to high levels of stress, which often causes problems with the digestive system. This stress also promotes the production of free radicals, resulting in oxidative stress. Astaxanthin (AST) stands out as one ... ...

Abstract	During the weaning period, piglets are exposed to high levels of stress, which often causes problems with the digestive system. This stress also promotes the production of free radicals, resulting in oxidative stress. Astaxanthin (AST) stands out as one of the most potent antioxidants. Its resistance to light and heat makes it particularly valuable in compound feed production. This study was to determine the effect of AST impact on liver histology and gene expression in piglets. For our experiment, we used 16 weaned piglets of the PL breed, which we divided into two groups: Group I (control group with no AST supplementation) and Group II (supplemented with AST at 0.025 g/kg). Both feed mixtures were iso-proteins and iso-energetic, meeting the nutritional requirements of the piglets. The experiment lasted from day 35 to day 70 of the piglets' age, during which they had ad libitum access. The results indicate that the addition of AST prevents liver fibrosis due to reduced collagen deposition in the tissue. Analysis of gene expression supported these results. In the AST-supplemented group, we noted a decrease in
Language	English
Publishing date	2023-10-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13203268
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Article ; Online: Preparation and Characterization of Gelatin-Agarose and Gelatin-Starch Blends Using Alkaline Solvent.

Dzeikala, Oleksandra / Prochon, Miroslawa / Marzec, Anna / Szczepanik, Szymon

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Plastic waste is a serious problem in modern society. Every day, mankind produces tons of waste that must be disposed of or recycled. The most common types of plastic waste are disposable tableware, bags, packaging, bottles, and containers, and not all ... ...

Abstract	Plastic waste is a serious problem in modern society. Every day, mankind produces tons of waste that must be disposed of or recycled. The most common types of plastic waste are disposable tableware, bags, packaging, bottles, and containers, and not all are recycled. Therefore, there is a great interest in producing environmentally friendly disposable materials. In this study, modified gelatin blends using polysaccharides (e.g., agarose, starch) were produced to obtain a stable coating. Various techniques were used to characterize the obtained bioplastics, including FTIR spectroscopy (Fourier-transform infrared spectroscopy), TGA (thermogravimetric analysis)/DSC (differential scanning calorimetry), contact angle measurements, and surface energy characterization. We also investigated the influence of thermal and microbiological degradation on the properties of the biocomposite. The addition of agarose increased the hardness of the blend by 27% compared to the control sample without added polysaccharides. Increases were also observed in the surface energy (24%), softening point (15%), and glass transition temperature (14%) compared to the control sample. The addition of starch to the biopolymer increased the softening point by 15% and the glass transition temperature by 6%. After aging, both blends showed an increase in hardness of 26% and a decrease in tensile strength of 60%.
MeSH term(s)	Starch/metabolism ; Gelatin/chemistry ; Sepharose ; Solvents ; Polysaccharides ; Plastics ; Spectroscopy, Fourier Transform Infrared
Chemical Substances	Starch (9005-25-8) ; Gelatin (9000-70-8) ; Sepharose (9012-36-6) ; Solvents ; Polysaccharides ; Plastics
Language	English
Publishing date	2023-01-12
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/ijms24021473
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