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BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis.METHODS: We investi
Objective of this study was to assess platelet response to clopidogrel and its association with certain single nucleotide polymorphisms (SNPs) of the P2RY12 gene. Several studies have shown that patients with poor in vitro response to clopidogrel have worse outcomes after coronary interventions. Pharmacological response to clopidogrel is mediated by the P2Y12 platelet receptor, therefore, SNPs of
Altered folate levels may play an important role in colon carcinogenesis. The aim of this study was to investigate the association of polymorphisms in key folate-metabolizing genes with susceptibility to sporadic colon cancer. Six common polymorphisms (two in MTHFR and one each in MTR, MTRR, RFC1, and DHFR genes) were genotyped in 300 healthy subjects and 300 colon cancer patients from Croatia. Ob
Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain. Recent epidemiological and clinical data suggest intrauterine infection/inflammation as the most common cause of preterm delivery and neonatal complications, including CP. Cyclooxygenases are key enzymes in the conversion of arachidonic acid to prostaglandins. The COX family consists of tw
Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investi
Hormone-producing cells in the pancreas and intestine regulate whole-body metabolism and are dysregulated in obesity and diabetes. A deeper understanding of endocrine lineage formation (endocrinogenesis) in these organs is essential to elucidate the healthy state and disease trajectories. Here, we performed cross-species (mouse and human) and cross-system (in vivo and in vitro) comparisons of panc
Islets of Langerhans are highly structured mini-organs containing hormone-producing cells of the pancreas that regulate glucose metabolism. Studies of endocrine cell differentiation and clustering into immature proto-islets, as well as remodeling into mature islets, are beginning to clarify the critical timepoints and mechanisms governing islet formation across species. In this review, we compare
Primary human pancreatic ductal organoids (HPDO) have emerged as a model to study pancreas biology and model disease like pancreatitis and pancreatic cancer. Yet, donor material availability, genetic variability and a lack of extensive benchmarking to healthy and disease pancreas limits the range of applications. To address this gap, we established porcine pancreatic ductal organoids (PPDO) as a s
DNA origami-based nanotechnology is a versatile tool for exploring fundamental biological questions and holds significant promise for future biomedical applications. Here, we leverage the optical transparency of the embryonic zebrafish to analyze live embryos injected intravenously with fluorescently labeled wireframe DNA origami nanosheets. Our approach integrated long-term, high-resolution imagi
Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insig
Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of β-cell loss. Using lineage tra
Getting mature and functional stem cell-derived, insulin-producing β cells is an important step for disease modeling, drug screening, and cell replacement therapy. In this issue, Hua et al.1 used single-cell multiomics analysis coupled with chemical screening to identify a crucial role for ceramides in generating mature stem cell-derived β cells.
Insulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer and neurodegenerative disorders. IRs have been reported to form nanoclusters at the cell membrane in several cell types, even in the absence of insulin binding. Here we exploit the nanoscale spatial organization of the I
Building a blastema from the stump is a key step of salamander limb regeneration. Stump-derived cells temporarily suspend their identity as they contribute to the blastema by a process generally referred to as dedifferentiation. Here, we provide evidence for a mechanism that involves an active inhibition of protein synthesis during blastema formation and growth. Relieving this inhibition results i
INTRODUCTION: Inconsistent results have been reported on the association between folic acid use in pregnancy and risk of GDM. The aim of this study was to estimate the association between folic acid use and GDM in two population-based Nordic cohorts.MATERIAL AND METHODS: Two cohort studies were conducted using data from the national population registers in Norway (2005-2018, n = 791,709) and Swede
Regenerating pancreatic β-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of β-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetic
BACKGROUND: Experimental animal studies suggest a novel role for the folate receptor 1 in β-cell differentiation in the pancreas, with potential implications for glycemic control. We tested the hypothesis of a protective association between prenatal folic acid use and neonatal diabetes or hyperglycemia and type 1 diabetes in an observational cohort study using data from the national population hea
Diabetes can be caused by an insufficiency in β-cell mass. Here, we performed a genetic screen in a zebrafish model of β-cell loss to identify pathways promoting β-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated β-cell differentiation in zebrafish. Treatment with folinic acid also stimulated β-cell differentiation in cultur
