Publications by authors named "Rayko Evstatiev"

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth.

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Background & Aims: Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism.

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Inflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA.

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Article Synopsis
  • Iron deficiency (ID) is widespread and linked not only to anemia but also to an increased risk of thrombosis, which could lead to further complications.
  • In a study using animal models, ID was shown to cause higher platelet counts and larger thrombus sizes, demonstrating a clear connection between ID and increased thrombotic tendency.
  • Iron replacement therapy effectively corrected the changes caused by ID, suggesting it could be a useful preventive measure for thrombotic diseases in patients with chronic illnesses predisposed to thrombosis.
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Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results.

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Article Synopsis
  • The study investigates how 5-ASA and AZTP, two treatments for inflammatory bowel disease (IBD), help restore the mucosal barrier that is often disrupted in IBD.
  • Both drugs improve epithelial barrier function by affecting cellular structures and proteins, particularly tight junctions, which are crucial for maintaining the intestinal lining.
  • While 5-ASA supports wound healing and alters cell cycle distribution in epithelial cells, AZTP has antiproliferative effects; both contribute to resolving barrier dysfunction but through different biological mechanisms.
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  • HuR is an RNA-binding protein linked to immune regulation and certain cancers, particularly colorectal cancer, by stabilizing mRNAs that promote tumor growth and inflammation.
  • The study found increased levels of HuR in colonic epithelial cells from patients with IBD, FAP, and colorectal cancer, while a small-molecule inhibitor of HuR, MS-444, worsened conditions in a model of IBD but reduced tumors in a FAP model.
  • These findings suggest that HuR plays a crucial role at different stages of colorectal cancer development, indicating potential for HuR inhibition as a preventive strategy for FAP, but caution is needed in patients with IBD.
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Iron deficiency, the most common nutritional deficiency worldwide, is often associated with reactive thrombocytosis. Although secondary thrombocytosis is commonly considered to be harmless, there is accumulating evidence that elevated platelet counts, especially in the setting of iron deficiency, can lead to an increased thromboembolic risk in both arterial and venous systems. Here we present the mechanisms of iron deficiency-induced thrombocytosis and summarize its clinical consequences especially in patients with inflammatory bowel diseases, chronic kidney disease or cancer.

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Iron deficiency and iron deficiency-associated anemia are common complications in cancer patients. Most iron deficient cancer patients present with functional iron deficiency (FID), a status with adequate storage iron, but insufficient iron supply for erythroblasts and other iron dependent tissues. FID is the consequence of the cancer-associated cytokine release, while in absolute iron deficiency iron stores are depleted resulting in similar but often more severe symptoms of insufficient iron supply.

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Article Synopsis
  • - PAK1 is an enzyme overexpressed in colorectal cancer and targeted by mesalamine, a drug used for ulcerative colitis that may help prevent cancer.
  • - Research on mice lacking PAK1 showed that this deletion led to a decrease in the number and burden of tumors but not in their size when comparing models of intestinal cancer.
  • - The study found that both PAK1 deletion and mesalamine treatment reduced tumor occurrence and disrupted critical cancer-promoting signaling pathways, suggesting PAK1 plays a role in the beginning stages of intestinal cancer development.
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P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot.

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Objective: Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2(loxP/loxP) Villin-Cre mouse model for Lynch syndrome.

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Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver.

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Background: Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been reported to possess anticarcinogenic properties.

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Background: Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population.

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Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background.

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Background & Aims: Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin.

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Background And Aims: Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia.

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Iron deficiency is a common condition increasingly diagnosed and treated by gastroenterologists. The most common presentation of iron deficiency is anaemia; however, it is a systemic disorder affecting multiple aspects of health in various organs. Iron is an essential element, with iron-containing proteins exerting a variety of vital functions, including oxygen transport, cellular respiration, intermediary metabolism, regulation of transcription and DNA repair.

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Background & Aims: Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA.

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Background: Individuals with ulcerative colitis are at high risk of developing colitis-associated cancer. 5-Aminosalicylate (5-ASA) protects from cancer by its antiinflammatory activity as well as by altering cell growth, inducing apoptosis, and reducing replication errors. So far neither 5-ASA's structural specificity nor its pharmacophore group have been identified.

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