Copper is a trace element indispensable for life, but at the same time it is implicated in reactive oxygen species formation. Several inherited copper storage diseases are described of which Wilson disease (copper overload, mutations in ATP7B gene) and Menkes disease (copper deficiency, mutations in ATP7A gene) are the most prominent ones. After the discovery in 2002 of a novel gene product (i.e. COMMD1) involved in hepatic copper handling in Bedlington terriers, studies on the mechanism of action of COMMD1 revealed numerous non-copper related functions. Effects on hepatic copper handling are likely mediated via interactions with ATP7B. In addition, COMMD1 has many more interacting partners which guide their routing to either the plasma membrane or, often in an ubiquitination-dependent fashion, trigger their proteolysis via the S26 proteasome. By stimulating NF-κB ubiquitination, COMMD1 dampens an inflammatory reaction. Finally, targeting COMMD1 function can be a novel approach in the treatment of tumors.

Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. Among the most advanced pharmacologic candidates are resmetirom, a highly liver-selective thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) already approved for diabetes and obesity. Although both agents improve hepatic steatosis, their mechanisms of action, extra-hepatic benefits, and safety signatures diverge markedly. Resmetirom, which was approved by the Food and Drug Administration (FDA) in March 2024, acts hepatocentrically to accelerate β-oxidation, lower atherogenic lipoproteins, and deliver early signals necessary for fibrosis regression, all while largely avoiding systemic thyrotoxic effects. Semaglutide acts systemically by reducing caloric load through pronounced weight loss and glycemic control, producing the highest rates of histologic MASH resolution reported to date, albeit with less direct antifibrotic efficacy and characteristic gastrointestinal tolerability issues. This comparative perspective juxtaposes the two compounds with respect to molecular pharmacology, clinical efficacy, safety, and potential clinical positioning, and proposes that, because resmetirom primarily targets hepatic lipid disposal whereas semaglutide unloads systemic caloric pressure, their complementary actions could be harnessed sequentially or in combination to achieve broader, more durable disease modification across the heterogeneous spectrum of patients with MASH.

BACKGROUND: Reports of false laboratory findings due to a biotin supplementation have raised concerns about the safety of immunoassays. According to current research, biotin is known to cause interference in immunoassays. Since up to 70% of medical decisions are based on laboratory results and the significantly increased intake of biotin supplements in the recent years, the reliability of immunoassays is essential. METHODS: To evaluate this reliability two experiments were conducted. In the first experiment 59 interference suppressed immunoassays of the manufacturer Roche Diagnostics were examined regarding their sensitivity to a biotin interference. In the second experiment the pharmacokinetic of biotin was examined by supplementing volunteers with biotin. RESULTS: A combination of the results of both experiments suggests that a biotin interference in laboratory findings is probable. Contrary to the current state of research on sandwich immunoassays, falsely elevated test results occur more frequently than falsely low results. CONCLUSION: The interference suppressed immunoassays have shown in the experiment that they are susceptible to a biotin interference. Therefore, laboratory institutions, medical staff and patients must be aware of the possibility of a biotin interference. As a result, Roche Diagnostics may consider reviewing the interference suppression and their indications of the tests.

Background: Personalized medicine has revolutionized cancer treatment by utilizing genomic insights to tailor therapies based on individual molecular profiles. This approach enhances therapeutic efficacy, minimizes adverse effects, and addresses tumor heterogeneity through precision-targeted interventions. Methods: A scoping review was conducted through a comprehensive literature search in PubMed, using MeSH terms and keywords related to genomic profiling and targeted cancer therapies. Eligible studies included original research involving cancer patients who underwent genomic profiling and targeted therapies from January 1, 1950, to February 9, 2025. Results: Advances in next-generation sequencing (NGS) and bioinformatics have accelerated the identification of clinically relevant mutations-such as epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) and BRAF V600E in melanoma-enabling the development of effective targeted therapies. Emerging technologies like clustered regularly interspaced short palindromic repeats (CRISPR) gene editing and artificial intelligence (AI) are further refining treatment selection by enabling more precise and adaptive therapeutic strategies. Despite these innovations, challenges persist regarding data interpretation, equitable access, costs, regulatory frameworks, and integration into routine clinical workflows. Conclusions: Genomic profiling is central to the advancement of precision oncology. The convergence of genomics, gene editing, and AI is paving the way toward more personalized, efficient, and inclusive cancer care. Realizing the full potential of personalized medicine will require interdisciplinary collaboration, investment in infrastructure, and ethical oversight to ensure broad, equitable, and responsible implementation in clinical practice.

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 but are not limited to fluorochrome-conjugated antibodies, fluorescent expressing protein-, viability-, and DNA-binding dyes. Major developments in reagents, electronics, and software within the last 30 years have greatly expanded the ability to combine up to 50 antibodies in one single tube. However, these advances also harbor technical risks and interpretation issues in the identification of certain cell populations which will be summarized in this viewpoint article. It will further provide an overview of different potential applications of flow cytometry in research and its possibilities to be used in the clinic.

Background and Purpose Macrophage migration inhibitory factor (MIF) is an inflammatory and chemokine-like protein expressed in different diseases as well as solid tumours. CD74 - the cognate MIF receptor - was identified as an important target of MIF. We here analysed the role of MIF and CD74 in the progression of hepatocellular carcinoma (HCC) in vitro and in vivo using an experimental murine HCC model.

Introduction Leydig cells (LCs) are located in the interstitium of the testes and are characterized as steroid hormone-producing cells that are crucial for testicular function in maintaining spermatogenesis. Disruptions in their function, for instance due to genetic defects, endocrine disruptors, or age-related changes, often lead to hypogonadism and are among the main causes of male infertility. Therefore, reliable in vitro models are crucial for understanding the underlying signaling pathways, developing new therapeutic approaches and testing toxic substances that interfere with these processes. However, as primary LCs are naturally rare, require time-consuming isolation from animals and yield only small quantities, in theory, permanent LC lines offer a more practical and reproducible alternative. Methods We used non-tumorigenic TM3 cells and tumorigenic MLTC-1 cells, two commercially available LCs, and subjected them to a comprehensive molecular and genetic comparative analysis. Results and discussion Light microscopy and F-actin staining by Phalloidin revealed the typical polygonal LC shape of both cell lines growing in clusters with tight cell-cell contacts. Both cell lines contain endogenous lipid droplets (LDs) and synthesis was inducible with oleic acid. Transcriptomic analysis and RT-qPCR verified the expression of different steroidogenesis-associated LD genes including members of the PLIN family and lipolysis enzymes (e.g. Pnpla2 , Lipe , MgII ). In addition, we identified a comprehensive panel of steroidogenesis genes via RT-PCR, RT-qPCR and Western blot analysis in MLTC-1 cells, but these were not detectable in TM3 cells. In contrast to the originally described response to gonadotropins in TM3 cells, RNA sequencing revealed no Lhcgr expression and the cells are not responsive to stimulation with human chorionic gonadotropin (hCG). MLTC-1 cells are positive for Lhcgr and respond to hCG administration with strong StAR induction on the protein and mRNA level. Short tandem repeat (STR) profiling confirmed the authenticity of both cell lines used in our study. Taken together, comprehensive molecular characterization, which includes next generation sequencing (NGS)-based transcriptome analysis and STR profiling, is essential in confirming the validity of cell models and enhancing their significance in infertility research and endocrine toxicology.

The Factor VII-activating protease (FSAP) is a plasma serine protease that acts as an activator of factor VII, independently of tissue factor, promoting the coagulation cascade and it activates pro-urokinase in the fibrinolytic pathway. Two single nucleotide polymorphisms (SNPs) in the coding region of the FSAP gene that lead to amino acid substitutions within the serine protease domain are presently discussed to be involved in the formation of atherosclerosis leading to carotid stenosis, cardiovascular diseases, and thromboembolic disorders. The G534E polymorphism, also known as Marburg I, is a guanine to adenine substitution that is found in about 5% of the population and impairs the in vitro capacity to activate pro-urokinase while the biological effect of the second variant (E393Q), also known as the Marburg II, has not yet been identified. Based on the properties to impair the pro-urokinase activity and their association with the incidence and progression of carotid stenosis it is conceivable that genotyping of this allelic variants is potentially interesting for routine genotyping of risk patients. We here describe the development of a novel LightCycler-based methodology allowing simultaneous genotyping of both allelic variants. The different genotypes could be identified easily and clearly by the generation of characteristic fluorescence melting peaks. The outlined methodology will be helpful for routine genotyping of these FSAP variants.

Hintergrund: In den letzten Jahren hat die Proteomanalyse mehr und mehr an Bedeutung gewonnen. Die zweidimensionale (2D) Gelelektrophorese ist eine weit verbreitete Methode, um das Proteinmuster zweier Proben miteinander zu vergleichen (z.B. gesund vs. krank) und Unterschiede im Proteinmuster zu ermitteln. Bisher stellen Gel zu Gel Variationen und daraus resultierende Artefakte bei der Detektion von Expressionsunterschieden ein wesentliches Problem der 2D-Gelelektrophorese dar.