85 results match your criteria: "Institute of General Pharmacology and Toxicology[Affiliation]"

Lymphomas in 3D and 4D spaces.

Hum Pathol

November 2024

Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address:

Article Synopsis
  • - The lymph node is structured into dynamic compartments like T and B zones, which enhance both innate and adaptive immune responses and have led to new insights across various biological and medical fields.
  • - The review emphasizes advanced 3D and 4D imaging techniques to study human lymph nodes, highlighting the insights gained from these methods compared to traditional 2D tissue analysis, particularly in understanding immune interactions and lymphoma behavior.
  • - Findings show that T cells move faster than B cells and reticulum cells within reactive lymphoid tissue, with variations in cell contact times potentially aiding in lymphoma classification; 4D technology can also play a key role in testing new cancer therapies.
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Background And Purpose: Endocannabinoids are lipid mediators, which elicit complex biological effects that extend beyond the central nervous system. Tissue concentrations of endocannabinoids increase in atherosclerosis, and for the endocannabinoid N-arachidonoyl-ethanolamine (anandamide, AEA), this has been linked to an anti-inflammatory function. In this study, we set out to determine the anti-inflammatory mechanism of action of AEA, specifically focusing on vascular smooth muscle cells.

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Since the available treatments are not highly effective to combat cancer, therefore, the alternative strategies are unavoidable. Photodynamic therapy (PDT) is one of the emerging approaches which is target specific and minimally invasive. This study explores the successful development of Poly (D,L-lactide-co-glycolide) (PLGA) coated mesoporous silica nanoparticles (MSNs) and their augmented effects achieved by integrating curcumin (Cur) and cetyltrimethylammonium bromide (CTAB) in the polymeric layer and silica's pores, respectively.

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Atypical sphingosine-1-phosphate metabolites-biological implications of alkyl chain length.

Pflugers Arch

December 2024

Institute of General Pharmacology and Toxicology, Pharmazentrum Frankfurt, Goethe University, Frankfurt am Main, 60596, Frankfurt, Germany.

Sphingosine-1-phosphate (S1P) is a bioactive lipid signaling molecule with pleiotropic implications by both auto- and paracrine signaling. Signaling occurs by engaging five G protein-coupled receptors (S1P) or intracellular pathways. While the extensively studied S1P with a chain length of 18 carbon atoms (d18:1 S1P) affects lymphocyte trafficking, immune cell survival and inflammatory responses, the biological implication of atypical S1Ps such as d16:1 or d20:1 remains elusive.

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The present study aims to evaluate the effect of ink on insulin resistance in PCOS-induced mice. Treatment with sepia ink in dehydroepiandrosterone (DHEA)-induced PCOS mice at various doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg body weight mitigated the insulin resistance in the study groups with decreased concentration of testosterone and increased concentrations of estrogen and progesterone compared to the PCOS group tested by ELISA. The histopathological analysis and restoration of glucose analysis showed a significant reduction in treatment groups.

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Ex vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors.

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Targeting cathepsin C ameliorates murine acetaminophen-induced liver injury.

Theranostics

June 2024

pharmazentrum frankfurt/ZAFES, Institute of General Pharmacology and Toxicology, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany.

Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3'mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication.

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Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood.

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID-19 Syndrome (PCS). A fraction of the PCS patients develop the full clinical picture of ME/CFS.

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The purpose of this study was to produce hyaluronic acid customized nanoparticles with chitosan for the delivery of chebulinic acid (CLA) to enhance its anticancer potential against breast cancer. A significant portion of CLA was encapsulated (89.72 ± 4.

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The SARS-CoV-2 pandemic has affected nations globally leading to illness, death, and economic downturn. Why disease severity, ranging from no symptoms to the requirement for extracorporeal membrane oxygenation, varies between patients is still incompletely understood. Consequently, we aimed at understanding the impact of genetic factors on disease severity in infection with SARS-CoV-2.

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Haematopoietic stem cells (HSC) reside in the bone marrow microenvironment (BMM), where they respond to extracellular calcium [eCa] via the G-protein coupled calcium-sensing receptor (CaSR). Here we show that a calcium gradient exists in this BMM, and that [eCa] and response to [eCa] differ between leukaemias. CaSR influences the location of MLL-AF9 acute myeloid leukaemia (AML) cells within this niche and differentially impacts MLL-AF9 AML versus BCR-ABL1 leukaemias.

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment.

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Germinal centers (GCs) are some of the most important structures in the human immune system. As such, their cell types and functions have been thoroughly investigated. B cells, T cells, follicular dendritic cells (FDCs), and macrophages have widely been found to typically be aggregated in GCs.

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The application of photodynamic therapy has become more and more important in combating cancer. However, the high lipophilic nature of most photosensitizers limits their parenteral administration and leads to aggregation in the biological environment. To resolve this problem and deliver a photoactive form, the natural photosensitizer parietin (PTN) was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (PTN NPs) by emulsification diffusion method.

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Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration.

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Clonal T-cell proliferations occasionally occur in Kikuchi-Fujimoto disease.

Hum Pathol

August 2023

Frankfurt Institute for Advanced Studies, 60438 Frankfurt am Main, Germany; Institute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, D-60590 Frankfurt am Main, Germany.

Article Synopsis
  • - Kikuchi-Fujimoto disease (KFD) is a relatively harmless condition that mainly causes swollen lymph nodes in young women and can be mistaken for more serious diseases due to similar T-cell features.
  • - A recent study analyzed 88 KFD cases to see if clonal T-cell receptor (TCR) amplifications could be detected, finding clonal peaks in 18% of cases without significant differences in other clinical parameters.
  • - The findings suggest that while clonal TCR gamma results can occur in KFD, care must be taken not to misinterpret these as signs of a serious illness, like T-cell neoplasia.
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Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure.

Am J Physiol Cell Physiol

July 2023

Department of Internal Medicine B, Faculty of Medicine, University of Münster, Münster, Germany.

Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events.

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?

Medicina (Kaunas)

May 2023

Institute of General Pharmacology and Toxicology, University Hospital Frankfurt am Main, Goethe-University, Theodor-Stern Kai 7, D-60590 Frankfurt am Main, Germany.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood. We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease.

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Microglia, the resident immune cells of the central nervous system, play important roles in brain homeostasis as well as in neuroinflammation, neurodegeneration, neurovascular diseases, and traumatic brain injury. In this context, components of the endocannabinoid (eCB) system have been shown to shift microglia towards an anti-inflammatory activation state. Instead, much less is known about the functional role of the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) system in microglia biology.

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Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling.

Metabolites

March 2023

Institute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, Theodor-Stern Kai 7, D-60590 Frankfurt am Main, Germany.

Redox-active mediators are now appreciated as powerful molecules to regulate cellular dynamics such as viability, proliferation, migration, cell contraction, and relaxation, as well as gene expression under physiological and pathophysiological conditions. These molecules include the various reactive oxygen species (ROS), and the gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS). For each of these molecules, direct targets have been identified which transmit the signal from the cellular redox state to a cellular response.

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MicroRNAs (miRNAs) are small non coding RNAs responsible for posttranscriptional regulation of gene expression. Even though almost 2000 precursors have been described so far, additional miRNAs are still being discovered in normal as well as malignant cells. Alike protein coding genes, miRNAs may acquire oncogenic properties in consequence of altered expression or presence of gain or loss of function mutations.

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Holistic View on the Structure of Immune Response: Petri Net Model.

Biomedicines

February 2023

Molecular Bioinformatics, Institute of Computer Science, Goethe University Frankfurt, Robert-Mayer Str. 11-15, 60325 Frankfurt am Main, Germany.

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell-cell interactions or have to make assumptions about parameters. The broad variation of, e.

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A mass spectrometry-based lipidomic investigation of 30 patients with chronic hepatitis C virus (HCV) infection and 30 age- and sex-matched healthy blood donor controls was undertaken. The clustering and complete separation of these two groups was found by both unsupervised and supervised multivariate data analyses. Three patients who had spontaneously cleared the virus and three who were successfully treated with direct-acting antiviral drugs remained within the HCV-positive metabotype, suggesting that the metabolic effects of HCV may be longer-lived.

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