Ralf Weiskirchen

University Hospital RWTH Aachen · Institute of Molecular Pathobiochemistry, Experimental Gene Therapy, and Clinical Chemistry

Estrogen receptor alpha (ERα) is widely expressed in reproductive organs, but also in non-reproductive tissues of females and males. There is evidence that lipocalin 2 (LCN2), which has diverse immunological and metabolic functions, is regulated by ERα in adipose tissue. However, in many other tissues, the impact of ERα on LCN2 expression has not b...

Vitamin A is a micronutrient important for vision, cell growth, reproduction and immunity. Both deficiency and excess consuming of vitamin A cause severe health consequences. Although discovered as the first lipophilic vitamin already more than a century ago and the definition of precise biological roles of vitamin A in the setting of health and di...

Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been impli...

The cellular (centralized) communication network (CCN) factor protein family contains six small secreted cysteine-rich proteins sharing high structural similarity. These matricellular proteins have vital biological functions in cell adhesion, migration, cell cycle progression, and control of production and degradation of extracellular matrix. Howev...

Perilipin 5 (PLIN5) is a lipid droplet coat protein that is highly expressed in oxidative tissues such as those of muscles, the heart and the liver. PLIN5 expression is regulated by a family of peroxisome proliferator-activated receptors (PPARs) and modulated by the cellular lipid status. So far, research has focused on the role of PLIN5 in the con...

Mast cells (MCs) are immune cells of the myeloid lineage distributed in tissues throughout the body. Phenotypically, they are a heterogeneous group characterized by different protease repertoires stored in secretory granules and differential presence of receptors. To adequately address aspects of MC biology either primary MCs isolated from human or...

Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lympho...

The cultivation of cells in a favorable artificial environment has become a versatile tool in cellular and molecular biology. Cultured primary cells and continuous cell lines are indispensable in investigations of basic, biomedical, and translation research. However, despite their important role, cell lines are frequently misidentified or contamina...

Purpose of Review This review evaluates cow milk’s impact on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer (BCa) pathogenesis. Recent Findings Recent prospective cohort studies support the association between cow’s milk consumption and th...

Multidrug resistance (MDR) reduces the efficacy of chemotherapy. Besides inducing the expression of drug efflux pumps, chemotherapy treatment alters the composition of the tumor microenvironment (TME), thereby potentially limiting tumor-directed drug delivery. To study the impact of MDR signaling in cancer cells on TME remodeling and nanomedicine d...

Wilson disease (WD) is a rare, inherited metabolic disorder manifested with varying clinical presentations including hepatic, neurological, psychiatric, and ophthalmological features, often in combination. Causative mutations in the ATP7B gene result in copper accumulation in hepatocytes and/or neurons, but clinical diagnosis remains challenging. D...

During decades of cancer research, different disciplines have made important contributions to the development of our knowledge about cancer. Identification of complex problems not being solved using a single discipline has directed scientists toward interdisciplinary approaches. Cancer is a complex problem that, regardless of great advances in diff...

Mast cells (MCs) are immune cells of the myeloid lineage distributed in tissues throughout the body. Phenotypically, they are a heterogeneous group characterized by different protease repertoires stored in secretory granules and differential presence of receptors. To adequately address aspects of MC biology either primary MCs isolated from human or...

Sepsis is a major health burden with insufficiently understood mechanisms of inflammation and immune paralysis, leading to a life-threatening critical illness. The secreted frizzled related protein 5 (SFRP5) acts as an anti-inflammatory adipokine by antagonizing the Wnt5a pathway. The aim of this study was to elucidate the role of SFRP5 in critical...

The estrogen receptor beta (ERβ) is physiologically essential for reproductive biology and is implicated in various diseases. However, despite more than 20 years of intensive research on ERβ, there are still uncertainties about its distribution in tissues and cellular expression. Several studies show contrasts between mRNA and protein levels, and t...

Clusterin is a multifunctional protein that is recognized to mediate cellular stress response associated with organ failure, systemic inflammation, and metabolic alterations. The aim of this study was to determine the value of clusterin as a clinical biomarker in critical ill patients with or without sepsis. We analyzed clusterin plasma concentrati...

TNBC represents the most aggressive breast cancer subtype. Although cancer stem cells (CSCs) are a minor fraction of all cancer cells, they are highly cancerous when compared to their non-stem counterparts, playing a major role in tumor recurrence and metastasis. Angiogenic stimuli and the tumor environment response are vital factors in cancer meta...

Introduction Over the past two decades, understanding of hepatic macrophage biology has provided astounding details of their role in the progression and regression of liver diseases. The hepatic macrophages constitute resident macrophages, Kupffer cells, and circulating bone marrow monocyte-derived macrophages, which play a diverse role in liver in...

Background and Objective: Milk exosomes (MEX) and their inherent microRNAs (miRs) were recently promoted as promising effectors and drug carrier systems for the treatment of various chronic human diseases. This review intends to provide a comprehensive view on the potential beneficial and adverse health effects of MEX miRs. Methods: English literat...

Many drug tests are carried out by means of hair analysis. The aim of the present study was to clarify if and to what extent it is possible to manipulate the results of hair analyses on tetrahydrocannabinol (THC) by using various commercially available everyday products and products advertised on the internet to be able to reduce the concentrations...

This study reports about a new ion chromatography method for the detection of chloride ions in sweat as an alternative to the gold standard of the chloridometer. Information about necessary materials, required preparations, reference ranges, advantages and disadvantages of this method is provided. We finally demonstrate that this method is useful t...

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)‐Cas technology possesses revolutionary potential to positively affect various domains of drug discovery. It has initiated a rise in the area of genetic engineering and its advantages range from classical science to translational medicine. These genome editing systems have given a new...

Hepatic stellate cells (HSCs) are also known as lipocytes, fat-storing cells, perisinusoidal cells, or Ito cells. These liver-specific mesenchymal cells represent about 5% to 8% of all liver cells, playing a key role in maintaining the microenvironment of the hepatic sinusoid. Upon chronic liver injury or in primary culture, these cells become acti...

Cover Illustration: Lipocalin 2 is a potential regulator of inflammation in the brain and possibly involved in Multiple Sclerosis (MS) lesion formation. The picture was taken from tissue obtained from an MS patient with progressive disease course. The maximum projection identifies intracellular Lipocalin 2 (green) within an activated astrocyte (GFA...

Primary hepatocytes are a major tool in biomedical research. However, obtaining high yields of variable hepatocytes is technically challenging. Most protocols rely on the two-step collagenase perfusion protocol introduced by Per Ottar Seglen in 1976. In this procedure, the liver is perfused in situ with a recirculating, constant volume of calcium-f...

Misidentification, cross-contamination and genetic drift of continuous animal cell lines are persistent problems in biomedical research, leading to erroneous results and inconsistent or invalidated studies. The establishment of immortalized hepatic stellate cell line Col-GFP HSC was reported in PLoS One in the year 2013. In the present study a mult...

In liver research, immortalized cell lines have assumed an important role in studying general physiological and pathological processes. However, misidentification and cross-contamination of cell lines is a widespread problem in biomedical sciences resulting in irreproducible results and false conclusions. Although the huge impact of working with wr...

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting t...

Background and Objective: The therapeutic arsenal in Wilson disease is limited, but effective. It focuses on copper depletion, although this has never been defined nor measured. Accordingly, disorder adapted long term dosing strategies are missing. Goal of the analysis was the elucidation of copper metabolism in Wilson disease to detect critical me...

Hepatic fibrosis is a common type of liver disease that is attracting increasing attention of basic scientists and clinicians worldwide [...]

Multiple sclerosis (MS) is a central nervous system disease characterized by both degenerative and inflammatory processes. Various mediators are involved in the interplay of degeneration and innate immunity on one hand and peripheral adaptive immunity on the other hand. The secreted protein lipocalin 2 (LCN2) is an inflammatory modulator in a varie...

Background: Phosphatidylcholine is an essential component of the intestinal mucus and serves as a protective shield against the ingress of bacteria from the stool. In the intestinal mucus of patients with ulcerative colitis, phosphatidylcholine is reduced by 70%, which makes the intestine susceptible to bacterial inflammation. Local application by...

Immortalized hepatic stellate cells (HSCs) established from mouse, rat, and humans are valuable in vitro models for the biomedical investigation of liver biology. These cell lines are homogenous, thereby providing consistent and reproducible results. They grow more robustly than primary HSCs and provide an unlimited supply of proteins or nucleic ac...

The murine cell line GRX has been introduced as an experimental tool to study aspects of hepatic stellate cell biology. It was established from livers of C3H/HeN mice that were infected with cercariae of Schistosoma mansoni. Although these cells display a myofibroblast phenotype, they can accumulate intracellular lipids and acquire a fat-storing li...

Apoptosis is an evolutionarily conserved sequential process of cell death to maintain a homeostatic balance between cell formation and cell death. It is a vital process for normal eukaryotic development as it contributes to the renewal of cells and tissues. Further, it plays a crucial role in the elimination of unnecessary cells through phagocytosi...

Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases...

Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of...

The Beatles formed in Liverpool are one of the most famous music groups in the history of pop considered as the best‐selling artists in the category “band,” with the highest amount of claimed record sales. With their foremost pioneering activities in songwriting, artistic presentation, and recording, the band revolutionized many aspects of music in...

Background: Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various hepatoprotective compounds like, L-carnitine, are discussed...

Since the embedding of the principles of the 3Rs (Replacement, Reduction and Refinement) in national and international regulations on the use of animals, scientists have been challenged to find ways to reduce the number of animals in their research. Here, we present a digital platform, called ‘3R Backboard’, linked to a laboratory animal management...

The transporter protein lipocalin-2 (LCN2) also termed neutrophil-gelatinase-associated lipocalin (NGAL) has pleiotropic effects in tumorigenesis in various cancers. Since the precise role of LCN2 in prostate cancer (PCa) is poorly understood, we aimed to elucidate its functions in PCa in vitro. For this purpose, LCN2 was transiently suppressed or...

Organ fibrogenesis is characterized by a common pathophysiological final pathway independent of the underlying progressive disease of the respective organ. This makes it particularly suitable as a therapeutic target. The Transregional Collaborative Research Center "Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease" (referred to as...

The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was funded for 13 years (2009–2021) by the German Research Council (DFG). This consortium was hosted by the Medical Schools of the RWTH Aachen University and Bonn University in Germany. The SFB/TRR57 implem...

Abstract: Currently, there are few validated and standardized tests for drug screening in pregnant women. In these as-says, maternal and fetal tissues are taken for screening, including maternal and fetal blood, meconium, hair, urine, pieces of placental material, and umbilical cord. Screening methods use different techniques including enzyme-link...

This review analyzes the potential impact of milk-induced signal transduction on the pathogenesis of prostate cancer (PCa). Articles in PubMed until November 2021 reporting on milk intake and PCa were reviewed. Epidemiological studies identified commercial cow milk consumption as a potential risk factor of PCa. The potential impact of cow milk cons...

Programmed cell death protein 1 (PD-1)/PD-ligand (L)1, the immune checkpoint inhibitors have emerged as a promising strategy for the treatment of various diseases including chronic liver diseases (CLDs) such as hepatitis, liver injury and hepatocellular carcinoma (HCC). The role of PD-1/PD-L1 has been widely inspected in the treatment of viral hepa...

The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries. With the discovery of liver-specific pericytes-formerly called fat-storing cells, Ito-cells, lipocytes, and currently designated as hepatic stellate cells (HSC)-the insight into the cellular and molecular pathobiology of liver fibr...

Bis-choline-tetrathiomolybdate, introduced as WTX101 (now known as ALXN1840), is a first-in-class copper-protein-binding agent for oral therapy of Wilson’s disease. In contrast to other decoppering agents such as trientine or D-penicillamine it acts by forming a tripartite complex with copper and albumin, thereby detoxifying excess liver and blood...

Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity and metabolic syndrome by interfering with the composition of gut microbiota. Consequently, complete or hepa...

Spread of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a demanding challenge. This is of particular importance in schools and public areas of unavoidable access. New viral mutations may increase infectivity and require even better methods to identify areas of potential hazards. High-throughput SARS-CoV-2 testing and lega...

Chronic liver diseases (CLDs) caused by viral infections, alcohol/drug abuse, or metabolic disorders affect millions of people globally and have increased mortality owing to the lack of approved therapies. Lipoxygenases (LOXs) are a family of multifaceted enzymes that are responsible for the oxidation of polyunsaturated fatty acids (PUFAs) and are...

Flow cytometry is a laser-based technology generating a scattered and a fluorescent light signal that enables rapid analysis of the size and granularity of a particle or single cell. In addition, it offers the opportunity to phenotypically characterize and collect the cell with the use of a variety of fluorescent reagents. These reagents include bu...

Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and siz...

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a range of conditions caused by a build-up of fat in the liver. It is usually seen in people who are overweight or obese. Increasingly common around the world, this disease is the most common chronic liver disease in the United States, affecting about a quarter of the population. Rec...

Perilipin 2 (PLIN2) is a lipid droplet protein with various metabolic functions. However, studies investigating PLIN2 in the context of inflammation, especially in systemic and acute inflammation, are lacking. Hence, we assessed the relevance of serum PLIN2 in critically ill patients. We measured serum PLIN2 serum in 259 critically ill patients (16...

Lipocalin 2 (LCN2), an acute-phase protein produced during acute liver injury, plays an important role in the innate immune response against bacterial infection via iron scavenging. LCN2 further influences neutrophil development and physiology leading to increased inflammatory responses. We investigated the roles of LCN2 in chronic inflammation and...