Biology subjects

Sarmiento, J.

Publications and source records attributed to Sarmiento, J..

3 recordsLinked to original sources

bioRxiv2025

EVALUATION OF STAINING FOR FIBRONECTIN ISOFORMS IN LIVER DISEASES

Fibronectin is an ubiquitous extracellular matrix protein, that is produced by the hepatocytes contributing to circulating fibronectin, and by the hepatic stellate cells contributing to fibrotic bundles. Fibronectin is required for the accumulation of collagen type I, the main fibrotic collagen in liver disease. It is presumed that cellular fibronectins including EDA-containing, EDB-containing and oncofetal fibronectin are the ones localized to the fibrotic bundles, since these isoforms are increased in the presence of fibrosis and cirrhosis in patients with liver disease. The aim of this work was therefore to evaluate the distribution of the various isoforms and determine whether they are detected in the hepatocytes too or whether they are indeed limited in their expression to fibrotic bundles. Total fibronectin was detected in hepatocytes particularly in healthy liver tissue. In advanced disease, fibronectin staining seemed diminished. All three isoforms, EDA-, EDB-, and oFN were detected in hepatocytes or the fibrotic bundles, with EDB being the most abundant. Interestingly, the isoforms did not fully account for all of fibronectin. Staining patterns confirmed that the three isoforms are not limited to the fibrotic bundles, but are also found in the hepatocytes. This contradicts the common notion that cellular fibronectins precipitate and are localized in the matrix, and explains why they can be measured in the circulation. Finally, there is some convergence between the presence of the isoforms in the fibrotic bundles and the elevation of their levels in the blood stream at least in chronic hepatitis C and cholestatic liver disease. This is in line with a high degree of complexity of fibronectin distribution and effects.

cell biology↗

bioRxiv2022

Retrotransposons facilitates tissue specific horizontal Transfer of circulating tumor DNA

A variety of organisms have been shown to have altered physiology or developed pathology due to gene transfer, but mammals have never been shown to do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal gene transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ctDNA enters the host cell, it migrates to the nucleus and integrates into the cells genome, thereby transferring its genetic information. We determine that retrotransposons of the ERVL, SINE, and LINE families are necessary for cell targeting and the integration of ctDNA into host DNA. Using chemically synthesized retrotransposons, we found that AluSp and MER11C reproduced multiple myelomas (MM) ctDNAs cell targeting and integration into MM cells. We also discovered that ctDNA might, as a result of HGT, influence the treatment response of multiple myeloma and pancreatic cancer models. Overall, this is the first study to show that retrotransposon-directed HGT can promote genetic material transfer in cancer. There is, however, a broader impact of our findings than just cancer since cell-free DNA has also been found in physiological and other pathological conditions as well. Furthermore, with the discovery of transposons-mediated tissue-specific targeting, a new avenue for the delivery of genes and therapies will emerge.

cancer biology↗

bioRxiv2020

Tamoxifen reduces inflammatory infiltration of neutrophils in the airways.

ABSTRACTTamoxifen is a drug of choice for treatment of breast cancer but it has also been reported to bear anti-inflammatory activity. Previously, we have observed that tamoxifen treatment successfully reduced inflammation in horses affected by equine asthma syndrome. More notorious, tamoxifen was effective at reducing the infiltration of neutrophils in the inflamed airways by a mechanism that increases efferocytosis, allowing the resolution of inflammation. Due to the emerging increase in patients with chronic inflammatory lung diseases, there is an urgent need for therapies that help reduce airway inflammation. Thus we tested the effect of tamoxifen on airway neutrophil infiltration by using three different mouse models for acute and chronic inflammation of the lung. We found that the drug was able to produce a significant reduction in neutrophils in all scenarios. Ussing chamber experiments demonstrated that tamoxifen has no effect on fluid secretion and absorption, discarding a possible reduction in mucociliary clearance due to the known ion-channel blocking effects of tamoxifen. Since this drug has been largely used in human medicine, tamoxifen might be a “low hanging fruit” for a novel anti-inflammatory therapy for airway diseases characterized by neutrophilic inflammation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology↗