The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

Comparison of Vitamin D3 Supplementation Doses of 1,000, 2,000, 4,000 and 8,000 IU in Young Healthy Individuals.

Background/aim: Low levels of vitamin D are a widespread global issue. This study aimed to determine the optimal vitamin D3 supplementation dose for healthy young adults by comparing the effectiveness of gradually increasing cholecalciferol doses over two years.

Patients And Methods: Thirty-five volunteers participated in a two-season pilot study conducted from October to April to avoid sunlight-induced vitamin D3 synthesis.

Identification and characterization of the functional tetrameric UDP-glucose pyrophosphorylase from .

In all kingdoms of life, the enzyme uridine diphosphate-glucose pyrophosphorylase (UGP) occupies a central role in metabolism, as its reaction product uridine diphosphate-glucose (UDP-Glc) is involved in various crucial cellular processes. Pathogens, including fungi, parasites, and bacteria, depend on UGP for the synthesis of virulence factors; in particular, various bacterial species utilize UDP-Glc and its derivatives for the synthesis of lipopolysaccharides, capsular polysaccharides, and biofilm exopolysaccharides. UGPs have, therefore, gained attention as anti-bacterial drug target candidates, prompting us to study their structure-function relationships to provide a basis for the rational development of specific inhibitors.

Pharmacogenetics of dabigatran and apixaban in association with gastrointestinal bleeding.

Objectives: To determine whether selected single nucleotide polymorphisms (SNPs) of genes encoding proteins responsible for the activation, transport, or metabolism of dabigatran and apixaban might be associated with a risk of gastrointestinal bleeding in a cohort of adult patients treated with these drugs. No previous study has focused specifically on the association with gastrointestinal bleeding.

Materials And Methods: Ninety-one patients treated with dabigatran or apixaban were genotyped for selected polymorphisms.

Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells.

The commonly altered glycosylation of tumor cells is a hallmark of tumor progression and metastasis formation. One prominent example is the interaction of sialylated glycans at the tumor cell surface with endothelial (E)-selectin as an early event of an adhesion cascade that enables extravasation of circulating tumor cells (CTCs) into distant tissues. In a previous study, we identified GCNT3 (mucin-type core2/ core4 β1,6-N-acetylglucosaminyltransferase) highly over-expressed in gastrointestinal adenocarcinoma cells that facilitate the canonical E-selectin ligands sialyl-Lewis A and X (sLeA/X) for E-selectin binding and endothelial adhesion.

Neurobiological and Anti-Inflammatory Effects of a Deep Diaphragmatic Breathing Technique Based on Neofunctional Psychotherapy: A Pilot RCT.

We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty-four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention.

Downregulation of the keratins CK13 and CK14 does not significantly affect cell viability of human urinary bladder carcinoma cells.

Introduction: Bladder cancer is the ninth most common tumour entity worldwide. Aberrant expression of different keratins has been described in bladder cancer, which is used for diagnostic purposes, but it can also have prognostic value. However, not all keratins have been analysed in bladder cancer, and whether keratins are important for cell viability of bladder cancer tumour cells is not yet known.

Interleukin-11 receptor is an alternative α-receptor for interleukin-6 and the chimeric cytokine IC7.

The cytokine interleukin 6 (IL-6) signals via the IL-6 α-receptor (IL-6Rα or IL-6R) in complex with the gp130 β-receptor. Cell type restricted expression of the IL-6R limits the action of IL-6 mainly to hepatocytes and some immune cells. Here, we show that IL-6 also binds to the IL-11 α receptor (IL-11Rα or IL-11R) and induces signaling via IL-11R:gp130 complexes, albeit with a lower affinity compared to IL-11.

Cerebrospinal Fluid Neurofilaments Light-Chain Differentiate Patients Affected by Alzheimer's Disease with Different Rate of Progression (RoP): A Preliminary Study.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia. One major challenge for clinicians is accurately assessing the rate of disease progression (RoP) early in the diagnostic process, which is crucial for patient management and clinical trial stratification. This study evaluated the role of cerebrospinal fluid biomarkers-Aβ42, t-Tau, pTau, Neurogranin (Ng), and Neurofilament light-chain (NF-L)-in predicting RoP at the time of AD diagnosis.

Interleukin-2 receptor α (IL-2Rα/CD25) shedding is differentially regulated by N- and O-glycosylation.

The cytokine interleukin-2 (IL-2) is a critical regulator of immune responses, with an especially well-characterized role in regulating T-cell homeostasis. IL-2 signaling involves three distinct receptor subunits: the IL-2Rα (CD25), IL-2Rβ, and IL-2Rγ. The intracellular transduction of IL-2-induced signals is strictly dependent on IL-2Rβ and IL-2Rγ, while the IL-2Rα is not directly involved in signaling.

The role of interleukin-6 classic and trans-signaling and interleukin-11 classic signaling in gastric cancer cells.

Introduction: The cytokine interleukin-11 (IL-11) binds on its target cells to a membrane-bound IL-11R, which results in homodimerization of the signal-transducing β-receptor gp130. Recent studies have uncovered a pro- inflammatory role in several diseases, including different tumor entities, and mouse models have revealed a crucial role of the IL-11/IL-11R axis in gastric cancer. However, studies regarding human gastric cancer are sparse, and whether the results obtained in mouse models also hold true in the human situation is little investigated.

Therapy concepts in type 1 diabetes mellitus treatment: disease modifying versus curative approaches.

For many autoimmune diseases, including type 1 diabetes mellitus (T1DM), efforts have been made to modify the disease process through pharmacotherapy. The ultimate goal must be to develop therapies with curative potential by achieving an organ without signs of parenchymal cell destruction and without signs of immune cell infiltration. In the case of the pancreas, this means regenerated and well-preserved beta cells in the islets without activated infiltrating immune cells.

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa.

Background: Luspatercept, an inhibitor of the transforming growth factor beta (TGF-β) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic.

Methods: By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55-95) were treated with luspatercept ± ESA at two Charles University hematology centers in Prague and Hradec Králové.

The metalloproteinase ADAM10 sheds angiotensin-converting enzyme (ACE) from the pulmonary endothelium as a soluble, functionally active convertase.

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the regulation of blood pressure and fluid balance, with angiotensin-converting enzyme (ACE) being a key transmembrane enzyme that converts angiotensin I to angiotensin II. Hence, ACE activity is an important drug target in cardiovascular pathologies such as hypertension. Our study demonstrates that human pulmonary microvascular endothelial cells (HPMECs) are an important source of proteolytically released ACE.

ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi.

Glycosylation is one of the most structurally and functionally diverse co- and post-translational modifications in a cell. Addition and removal of glycans, especially to proteins and lipids, characterize this process which has important implications in several biological processes. In mammals, the repeated enzymatic addition of a sialic acid unit to underlying sialic acids (Sia) by polysialyltransferases, including ST8Sia2, leads to the formation of a sugar polymer called polysialic acid (polySia).

Comparison of a Fully Automated Platform and an Established ELISA for the Quantification of Neurofilament Light Chain in Patients With Cognitive Decline.

Background: Enzyme-linked immunosorbent assay (ELISA) is the most-used method for neurofilament light chain (NfL) quantification in cerebrospinal fluid (CSF). Recently, fully automated immunoassays for NfL measurement in CSF and blood have allowed high reproducibility among laboratories, making NfLs suitable for routine use in clinical practice. In this study, we compared the Uman Diagnostics NF-light ELISA with the fully automated platform Lumipulse.

Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.

Background: Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood.