Biology subjects

Szekely, G.

Publications and source records attributed to Szekely, G..

3 recordsLinked to original sources

bioRxiv2025

Lymphocyte damage in four differently treated prostate radiotherapy cohort

Data comparing the biological dose of radiotherapy techniques in the same patient group are scarce. Furthermore, the assessment of lymphocyte damage caused by radiotherapy can be of importance as immunotherapies are used more frequently. By applying the chromosome aberration technique, over five years prospective comparison of the biological impact of four different types of treatments for low- and intermediate-risk prostate cancer was performed (at 3, 6, 9, 12, 24, 36, 48, and 60 months, 195 patients): conventional LINAC (linear accelerator) (70-78 Gy), CyberKnife (40-37.5 Gy) teletherapy, low-dose rate brachytherapy (LDR; 145 Gy) and high-dose rate brachytherapy (HDR; 19-21 Gy). Multivariate regression analyses were performed to analyze the predictive potential of chromosome aberrations for side effects. The median follow-up was 60 months. We found that teletherapy techniques (conventional LINAC and CyberKnife therapy) caused 1.7-3.2-fold more chromosomal aberrations than brachytherapy did. At three months, 4.6-12.7% of the lymphocytes were damaged. Five years after treatment, the total aberration values of conventional LINAC and LDR brachytherapy patients were still significantly greater than those before therapy (p=0.035 for LINAC and p=0.029 for LDR BT). We found that significant regression models suggest total aberrations or aberrant cell frequency might predict side effects in addition to biological effective dose (BED) and irradiated volume (V100%) (p=0.005 for model including total aberrations, p=0.003 for aberrant cell frequency). We reported a lower biological dose and fewer side effects in brachytherapy patients. We also demonstrated that long-term lymphocyte damage was dependent on the type of radiotherapy. Novelty and impactWe analyzed radiation dose of the immune cells after four types of radiotherapy for five years. The damage of the lymphocytes can be of significance, if patients receive immunotherapy after radiotherapy in the future. We demonstrated chromosome aberrations were still present in lymphocytes years after the radiation. We found that there can be threefold difference in lymphocyte damage between therapy types. We also showed capacity of chromosome aberration technique to predict side effects.

cancer biology↗

bioRxiv2023

A green alternative to fragrant agarwood sesquiterpenoid production

Certain endangered Thymelaeaceous trees are major sources of the fragrant and highly valued resinous agarwood, comprised of hundreds of oxygenated sesquiterpenoids (STPs). Despite growing pressure on natural agarwood sources, the chemical complexity of STPs severely limits synthetic production. Here, we catalogued the chemical diversity in 58 agarwood samples by two-dimensional gas chromatography-mass spectrometry and partially recreated complex STP mixtures through synthetic biology. We improved STP yields in the unicellular alga Chlamydomonas reinhardtii by combinatorial engineering to biosynthesise nine macrocyclic STP backbones found in agarwood. A bioprocess following green-chemistry principles was developed that exploits milking of STPs without cell lysis, solvent-solvent STP extraction, solvent-STP nanofiltration, and bulk STP oxy-functionalisation to obtain terpene mixtures like those of agarwood. This process occurs with total solvent recycling and enables continuous production. Our synthetic-biology approach offers a sustainable alternative to harvesting agarwood trees to obtain mixtures of complex, fragrant, oxygenated STPs.

synthetic biology↗

bioRxiv2022

Continuous extraction and concentration of secreted metabolites from engineered microbes using membrane technology

Microalgal cultivation in photobioreactors and membrane separations are both considered sustainable processes. Here we explore their synergistic combination to extract and concentrate a heterologous sesquiterpenoid produced by engineered green algal cells. A hydrophobic hollow-fiber membrane contactor was used to allow interaction of culture broth and cells with a dodecane solvent phase to accumulate algal produced patchoulol. Subsequent continuous membrane extraction of patchoulol from dodecane enabled product concentration in a methanol stream as well as dodecane recovery for its reuse. A structure-based prediction using machine learning was used to model a process whereby 100% patchoulol recovery from dodecane could be achieved with solvent-resistant nanofiltration membranes. Solvent consumption, E-factor, and economic sustainability were assessed and compared with existing patchoulol production processes. Our extraction and product purification process offers six- and two-orders of magnitude lower solvent consumption compared to synthetic production and thermal-based separation, respectively. Our proposed methodology is transferable to other microbial systems for the isolation of high-value isoprenoid and hydrocarbon products.

bioengineering↗