Biology subjects

Dora, D.

Publications and source records attributed to Dora, D..

3 recordsLinked to original sources

bioRxiv2023

SCUBE-1 in The Diagnosis and Follow-Up Of Subclinical Atherosclerosis in The Experimental Diabetes Mellitus and Obesity Model

ABSCTRACTO_ST_ABSBACKGROUNDC_ST_ABSObesity and diabetes mellitus (DM) is a metabolic disease that is a global problem, the most crucial complication of which is atherosclerotic cardiovascular disease resulting from endothelial dysfunction and accompanying platelet hyperactivity. The presence of the SCUBE-1 protein has been observed within vascular endothelial cells and platelets, both recognized for their pivotal involvement in the arterial thrombosis mechanism. The objective of this research is to examine the utility of serum SCUBE-1 levels in diagnosing and monitoring subclinical atherosclerosis in experimentally induced DM and obese rats. METHODSThe study comprised a cohort of 28 male Sprague-Dawleyrats, which encompassed the following groups: the obese group subjected to a high-fat diet (HFD), the TII-DM group administered HFD in combination with a single dose of streptozocin (STZ), the TI-DM group treated solely with STZ, and the control group. Serum SCUBE1 was analyzed using the enzyme-linked immunosorbent assay method, and caspase-3 (Cas-3), interleukin-6 (IL-6), interferon-gamma (INF-gamma) and superoxide dismutase (SOD) expression in the liver and pancreas of rats were evaluated using immunohistochemical methods. RESULTSSerum SCUBE1 levels were significantly higher in the obese and DM groups than in the control group, but there was no significant difference among the obese, TI-DM and TII-DM groups. The study identified a significant relationship between serum SCUBE1 level and hepatic CAS3, IL-6 and SOD expression and pancreatic SOD expression. CONCULISONSCUBE1 can be used as a promising novel marker for the diagnosis and monitoring of subclinical atherosclerosis in individuals with obesity, TI-DM, and TII-DM

pathology↗

bioRxiv2021

TALPID3/KIAA0586 regulates multiple aspects of neuromuscular patterning during gastrointestinal development in animal models and human

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analysed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning

developmental biology↗

bioRxiv2020

Small Cell Lung Cancer Neuroendocrine Subtypes are Associated with Different Immune Microenvironment and Checkpoint Molecule Distribution

Small cell lung cancer (SCLC) has recently been sub-categorized into neuroendocrine (NE)- high and NE-low subtypes showing immune desert and immune oasis phenotypes, respectively. We aimed to characterize the immune cell localization and the microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on FFPE TMAs with antibodies against CD45, CD3, CD8 and immune checkpoints including poliovirus receptor (PVR) and Indoleamine 2,3-dioxygenase (IDO). According to our results, the stroma was significantly more infiltrated by immune cells both in primary tumors and LN metastases (vs tumor cell nests). Immune (CD45+) cell density was significantly higher in tumor nests (110.6 {+/-} 24.95 vs 42.74 {+/-} 10.30, cell/mm2, p= 0.0048), with increased CD8+ effector T cell infiltration (21.81 {+/-} 5.458 vs 3.16 {+/-} 1.36 cell/mm2, p < 0.001) in NE-low vs NE-high tumors. Furthermore, the expression of IDO was confirmed on stromal and endothelial cells, and it positively correlated (r= 0.755, p<0.01) with higher immune cell density both in primary tumors and LN metastases, regardless of the NE pattern. Expression of IDO in tumor nests was significantly higher in NE-low (vs NE-high) primary tumors. PVR expression was significantly higher in NE-low (vs NE-high) patients both in primary tumors) and LN metastases. To our knowledge, this is the first human study that demonstrates in situ that NE-low tumors are associated with increased immune cell infiltration compared to NE-high tumors. PVR and IDO are potential new targets in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.

cancer biology↗