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  1. Article ; Online: Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

    Alvarez-Martinez, Marisol / Cox, Luke S / Pearson, Claire F / Branchett, William J / Chakravarty, Probir / Wu, Xuemei / Slawinski, Hubert / Al-Dibouni, Alaa / Samelis, Vasileios A / Gabryšová, Leona / Priestnall, Simon L / Suárez-Bonnet, Alejandro / Mikolajczak, Anna / Briscoe, James / Powrie, Fiona / O'Garra, Anne

    Nature immunology

    2024  Volume 25, Issue 5, Page(s) 886–901

    Abstract: Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified ... ...

    Abstract Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4
    MeSH term(s) Animals ; Positive Regulatory Domain I-Binding Factor 1/genetics ; Positive Regulatory Domain I-Binding Factor 1/metabolism ; Mice ; Proto-Oncogene Proteins c-maf/genetics ; Colitis/immunology ; Colitis/genetics ; Mice, Knockout ; Humans ; Helicobacter hepaticus/immunology ; Helicobacter Infections/immunology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Intestinal Mucosa/microbiology ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/genetics ; Gene Expression Regulation ; Disease Models, Animal
    Chemical Substances Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-) ; Proto-Oncogene Proteins c-maf ; Prdm1 protein, mouse ; Maf protein, mouse
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-024-01814-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Deep Learning Enables Spatial Mapping of the Mosaic Microenvironment of Myeloma Bone Marrow Trephine Biopsies.

    Hagos, Yeman Brhane / Lecat, Catherine S Y / Patel, Dominic / Mikolajczak, Anna / Castillo, Simon P / Lyon, Emma J / Foster, Kane / Tran, Thien-An / Lee, Lydia S H / Rodriguez-Justo, Manuel / Yong, Kwee L / Yuan, Yinyin

    Cancer research

    2023  Volume 84, Issue 3, Page(s) 493–508

    Abstract: Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphologic, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse ... ...

    Abstract Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphologic, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an AUC of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and posttreatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of patients with multiple myeloma, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and regulatory T cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of patients with multiple myeloma. In summary, deep learning-based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques.
    Significance: Spatial analysis of bone marrow trephine biopsies using histology, deep learning, and tailored algorithms reveals the bone marrow architectural heterogeneity and evolution during myeloma progression and treatment.
    MeSH term(s) Humans ; Bone Marrow/pathology ; Multiple Myeloma/pathology ; Deep Learning ; Monoclonal Gammopathy of Undetermined Significance/pathology ; Biopsy ; Tumor Microenvironment
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-22-2654
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction.

    Mikolajczak, Anna / Sallam, Nada A / Singh, Radha D / Scheidl, Taylor B / Walsh, Emma J / Larion, Sebastian / Huang, Carol / Thompson, Jennifer A

    American journal of physiology. Endocrinology and metabolism

    2021  Volume 321, Issue 5, Page(s) E581–E591

    Abstract: This study determined if a perturbation in in utero adipogenesis leading to later life adipose tissue (AT) dysfunction underlies programming of cardiometabolic risk in offspring born to dams with metabolic dysfunction. Female mice heterozygous for the ... ...

    Abstract This study determined if a perturbation in in utero adipogenesis leading to later life adipose tissue (AT) dysfunction underlies programming of cardiometabolic risk in offspring born to dams with metabolic dysfunction. Female mice heterozygous for the leptin receptor deficiency (Het
    MeSH term(s) Adipocytes/ultrastructure ; Adipogenesis ; Adipose Tissue/embryology ; Adipose Tissue/growth & development ; Adipose Tissue/metabolism ; Animals ; Cardiometabolic Risk Factors ; Cell Size ; Diet, High-Fat ; Female ; Fructose/pharmacology ; Hyperlipidemias/genetics ; Insulin/blood ; Lipidomics ; Male ; Metabolic Diseases/metabolism ; Metabolic Diseases/pathology ; Mice ; Pregnancy ; Receptors, Leptin/genetics ; Stem Cells ; Triglycerides/blood
    Chemical Substances Insulin ; Receptors, Leptin ; Triglycerides ; Fructose (30237-26-4)
    Language English
    Publishing date 2021-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603841-4
    ISSN 1522-1555 ; 0193-1849
    ISSN (online) 1522-1555
    ISSN 0193-1849
    DOI 10.1152/ajpendo.00229.2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The relationship between concentrations of magnesium and oxidized low density lipoprotein and the activity of platelet activating factor acetylhydrolase in the serum of patients with type 1 diabetes.

    Wegner, Małgorzata / Araszkiewicz, Aleksandra / Zozulińska-Ziółkiewicz, Dorota / Wierusz-Wysocka, Bogna / Pioruńska-Mikołajczak, Anna / Pioruńska-Stolzmann, Maria

    Magnesium research

    2010  Volume 23, Issue 2, Page(s) 97–104

    Abstract: The study was aimed at comparing the concentration of metabolic parameters, the serum concentration of oxidized low density lipoproteins (oxLDL) and the activity of platelet activating factor acetylhydrolase (PAF-AH) in the relation to the serum ... ...

    Abstract The study was aimed at comparing the concentration of metabolic parameters, the serum concentration of oxidized low density lipoproteins (oxLDL) and the activity of platelet activating factor acetylhydrolase (PAF-AH) in the relation to the serum concentration of magnesium (Mg) in patients with type 1 diabetes (DM1). DM1 patients (n=78) were divided into 2 groups: patients with low serum Mg concentration (<0.7 mmol/L, group 1, n=34) and patients with reference levels of Mg (>or=0.7 mmol/L, group 2, n=44). A control group (n=24) of healthy subjects was also recruited. Our results showed that DM1 patients had lower serum Mg concentrations than the control group. It was found that parameters of poor metabolic control and lipid profile are not related to the serum Mg concentration in DM1 patients. However, both the Mg concentration and the PAF-AH activity are independently related to the serum oxLDL concentration. In group 1 the oxLDL concentration and the PAF-AH activity were higher than in group 2, and the control group. Two groups of DM1 patients did not show any differences with regard to the metabolic control. Therefore, the oxidative modification of LDL and the higher activity of PAF-AH are related with the low Mg status; however, no relation has been observed between these parameters and the poor metabolic control in DM1 patients.
    MeSH term(s) 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood ; Adult ; Case-Control Studies ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/enzymology ; Female ; Humans ; Lipoproteins, LDL/blood ; Magnesium/blood ; Magnesium Deficiency/blood ; Magnesium Deficiency/complications ; Male ; Reference Standards
    Chemical Substances Lipoproteins, LDL ; oxidized low density lipoprotein ; 1-Alkyl-2-acetylglycerophosphocholine Esterase (EC 3.1.1.47) ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2010-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1036384-1
    ISSN 1952-4021 ; 0953-1424
    ISSN (online) 1952-4021
    ISSN 0953-1424
    DOI 10.1684/mrh.2010.0207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Acamprosate involvement in triacylglycerol hydrolysis and transacylation with cholesterol in chronically ethanol-drinking rats.

    Piorunska-Mikolajczak, Anna / Piorunska-Stolzmann, Maria / Mikolajczak, Przemyslaw / Okulicz-Kozaryn, Irena / Kaminska, Ewa

    Journal of basic and clinical physiology and pharmacology

    2005  Volume 15, Issue 3-4, Page(s) 153–173

    Abstract: Acamprosate (AC) is used as a drug for treating alcoholism. We evaluated the effect of AC on serum triacylglycerol hydrolysis (GEH, glycerol ester hydrolysis), triacylglycerol transacylation with cholesterol (GECAT, glycerol ester:cholesterol ... ...

    Abstract Acamprosate (AC) is used as a drug for treating alcoholism. We evaluated the effect of AC on serum triacylglycerol hydrolysis (GEH, glycerol ester hydrolysis), triacylglycerol transacylation with cholesterol (GECAT, glycerol ester:cholesterol acyltransferase), and acylcholesterol hydrolysis (Cease, cholesterol ester hydrolysis) in an experimental model of alcoholism. Ethanol-preferring (PRF), non-preferring (NPF), and control (CR) male Wistar rats were treated with AC (500 mg/kg, p.o.) for 21 consecutive days. The beneficial effect of AC on lipid parameters of PRF rats included decreased triacylglycerol, total cholesterol, and LDL-cholesterol, and increased HDL-cholesterol levels. Acamprosate-compensated changes associated with ethanol consumption were observed. Acamprosate treatment decreased GECAT and increased Cease control rats, but increased GECAT and decreased CEase in PRF animals. In all groups of rats, AC treatment did not influence GEH. In conclusion, our results suggest that AC can influence triacylglycerol metabolism by its action on the balance between hydrolysis and transacylation in rats.
    MeSH term(s) Acamprosate ; Acylation/drug effects ; Alcohol Deterrents/pharmacology ; Alcohol Deterrents/therapeutic use ; Alcohol Drinking/blood ; Alcohol Drinking/prevention & control ; Animals ; Cholesterol/blood ; Ethanol/administration & dosage ; Hydrolysis/drug effects ; Male ; Rats ; Rats, Wistar ; Sterol O-Acyltransferase/blood ; Taurine/analogs & derivatives ; Taurine/pharmacology ; Taurine/therapeutic use ; Triglycerides/blood
    Chemical Substances Alcohol Deterrents ; Triglycerides ; Taurine (1EQV5MLY3D) ; Ethanol (3K9958V90M) ; Cholesterol (97C5T2UQ7J) ; Sterol O-Acyltransferase (EC 2.3.1.26) ; Acamprosate (N4K14YGM3J)
    Language English
    Publishing date 2005-03-31
    Publishing country Germany
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071737-7
    ISSN 2191-0286 ; 0792-6855 ; 0334-1534
    ISSN (online) 2191-0286
    ISSN 0792-6855 ; 0334-1534
    DOI 10.1515/jbcpp.2004.15.3-4.153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The evaluation of IL-12 concentration, PAF-AH, and PLA(2) activity in patients with type 1 diabetes treated with intensive insulin therapy.

    Wegner, Małgorzata / Araszkiewicz, Aleksandra / Pioruńska-Mikołajczak, Anna / Zozulińska-Ziółkiewicz, Dorota / Wierusz-Wysocka, Bogna / Pioruńska-Stolzmann, Maria

    Clinical biochemistry

    2009  Volume 42, Issue 16-17, Page(s) 1621–1627

    Abstract: Objectives: The aim of the study was to evaluate the concentration of interleukin 12 (IL-12), the activity of phospholipase A(2) (PLA(2)), and platelet-activating factor acetylhydrolase (PAF-AH) in type 1 diabetes (DM1) patients treated with intensive ... ...

    Abstract Objectives: The aim of the study was to evaluate the concentration of interleukin 12 (IL-12), the activity of phospholipase A(2) (PLA(2)), and platelet-activating factor acetylhydrolase (PAF-AH) in type 1 diabetes (DM1) patients treated with intensive insulin therapy.
    Design and methods: Studied parameters were measured in 81 patients, who were subdivided according to the HbA(1)c value, hsCRP concentration, and presence or absence of late complications.
    Results: PAF-AH activity was higher in the DM1 patients versus the control group (P=0.042). IL-12 concentration was the highest in subgroup with > or =3 mg/L hsCRP (P<0.05). Negative correlations were found for the IL-12 and age of patients and for apo A-I in the subgroup with poor metabolic control. In addition, positive correlation for hsCRP and PAF-AH activity in the subgroup with > or =3 mg/L CRP (P<0.05) was also found.
    Conclusions: PAF-AH and IL-12 appear to be implicated in the development of a chronic inflammation in DM1. In addition, our results emphasize a protective role of apo A-I against an increase in IL-12 production.
    MeSH term(s) 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood ; Adult ; Case-Control Studies ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/enzymology ; Diabetes Mellitus, Type 1/metabolism ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; Interleukin-12/blood ; Male ; Phospholipases A2/blood
    Chemical Substances Hypoglycemic Agents ; Insulin ; Interleukin-12 (187348-17-0) ; Phospholipases A2 (EC 3.1.1.4) ; 1-Alkyl-2-acetylglycerophosphocholine Esterase (EC 3.1.1.47)
    Language English
    Publishing date 2009-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390372-2
    ISSN 1873-2933 ; 0009-9120
    ISSN (online) 1873-2933
    ISSN 0009-9120
    DOI 10.1016/j.clinbiochem.2009.07.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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