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Biology subjects

Ceylan, H.

Publications and source records attributed to Ceylan, H..

6 recordsLinked to original sources

Extended normothermic machine perfusion preserves viability and tissue integrity of ex vivo human intestine segments

Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the integrated vascular, immune, and metabolic complexity of the intestine. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37{degrees}C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

bioengineering↗

CARTiBASE: an interactive knowledge base for CAR sequence retrieval and similarity analysis

SummaryChimeric Antigen Receptors (CARs) are modular synthetic constructs that have transformed cellular immunotherapy, enabling targeted recognition and killing of malignant cells. Their clinical success has driven an explosive growth in new receptor designs, but these sequences are dispersed across heterogeneous sources such as publications, patents and supplementary files. This fragmentation and inconsistency limits comparative analysis, reproducibility and the reuse of existing constructs. To address this, we curated and standardized more than 10,000 CAR sequences into a single, harmonized resource. CARTiBASE is a web-based platform that provides standardized annotation, interactive browsing and fast similarity search across this curated collection. This unique database was leveraged to analyse the diversity in current CAR constructs within the public domain, revealing common design trends and lineages, as well as highlighting potential avenues for future CAR development. Availability and ImplementationCARTiBASE is freely available for non-commercial use at https://www.cartibase.org, without mandatory registration. The web server is implemented with a Python/Flask API backend and a Vue-based frontend and supports all major browsers. Users can search and filter thousands of CARs, inspect domain boundaries across signal peptide, antigen-binding domain, hinge, transmembrane, co-stimulatory and intracellular signaling regions, compare constructs and download sequences as FASTA files for downstream use.

immunology↗

SquiDBase: a community resource of raw nanopore data from microbes

Experimental data-driven research relies on raw data, which consist of unprocessed experimental outputs, whereas derived data are transformed through a number of processing steps to reveal specific insights. Such processing, however, can potentially introduce biases or information loss, compromising transparency and reproducibility. In nucleic acid sequencing, nucleotide sequences stored in the FASTQ format are widely shared, but FASTQ files are generated from platform-specific raw data outputs, which vary depending on the sequencing platform used. The raw data produced by Oxford Nanopore Technologies (ONT) sequencing devices contain valuable biological information and are also useful to improve data processing methods, which includes basecaller optimisation and modification detection. Increasing attention goes to exploring these raw signals to develop algorithms that could improve ONT device portability and enhance target enrichment efficiency through adaptive sampling. Despite these benefits, the storage and sharing of raw nanopore data remain limited due to technical constraints and the lack of appropriate, standardised and centralised infrastructure. To address this challenge, we developed SquiDBase (https://squidbase.org), a dedicated repository to collect raw microbial nanopore sequencing data. To maximise the utility of SquiDBase from its inception, we built SquiDPipe, a Nextflow pipeline for the automated removal of human or unwanted reads from raw nanopore data. Additionally, we sequenced 24 clinically relevant viruses and incorporated them into SquiDBase, significantly expanding the diversity of publicly available reference datasets. By offering a centralised, open-access raw data collection platform, SquiDBase facilitates data sharing, enhances reproducibility, and supports the development and benchmarking of novel computational tools, reinforcing open science in nanopore sequencing research.

bioinformatics↗

Fluoroscopic-Guided Magnetic Soft Millirobot for Atraumatic Endovascular Drug Delivery

Atraumatic and precise drug delivery to arteries and veins remains an unmet need in interventional medicine, with significant implications for managing vascular diseases and long-term patient outcomes. Conventional endovascular methods, such as drug-coated balloons and drug-eluting stents, often damage vessel endothelium and compromise wall integrity, leading to reduced therapeutic efficacy and severe complications including restenosis and thrombosis. To address these limitations, we introduce EndoBot, an untethered soft millirobot designed for atraumatic vessel navigation and localized drug delivery under physiological blood flow. EndoBot achieves this through magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling, exerting low radial pressure (< 1 kPa) to preserve endothelial integrity. We validated its performance in phantom vessels, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava under fluoroscopic guidance using a human-scale magnetic manipulation platform. Despite dynamic vessel contractions and compressions along non-uniform cross-sections, mechanically adaptive locomotion strategy ensures safe navigation and protects the inner endothelial lining. EndoBot is deployable and retrievable via clinical vascular sheaths and remains stable even under supra-physiological blood flow conditions (> 155 cm/s). Extensive blood compatibility tests demonstrated minimal hemolysis (<0.01%), low platelet activation on the robot surface, and no increased coagulation tendency. For drug delivery, a hydrophobic transfer coating enables EndoBot to gently deposit a stable, flow-resistant drug layer onto the vessel wall without fragmentation. This novel platform enables safer and more effective targeted endovascular drug delivery, paving the way for transformative approaches to address early-stage vascular pathologies and deliver more effective preventive interventions.

bioengineering↗

RPRD Proteins Control Transcription in Human Cells

The regulation of transcription is an essential process that allows the cell to respond to various internal and external signals. RNA Polymerase II (Pol II) activity is controlled by a number of factors which bind to the C-terminal domain (CTD) of its largest subunit, RPB1, and stimulate or suppress RNA synthesis. Here, we demonstrate that CTD-interacting proteins, RPRD2, RPRD1B and RPRD1A act as negative regulators of transcription and their levels inversely correlate with the accumulation of nascent and newly transcribed RNA in human cells. We show that the RPRD proteins form mutually exclusive complexes with Pol II to coordinate their roles in transcriptional control. Our data indicate that RPRD2 exerts the most substantial impact on transcription and has the potential to alter key biological processes including the cellular stress response and cell growth.

molecular biology↗

3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

Miniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 m length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.

bioengineering↗