Liver disease is a leading cause of death worldwide with increasing morbidity and mortality and limited therapeutic options. The only curative treatment for end-stage liver disease is liver transplantation, restricted by the shortage of available organs, graft rejection and failure. One of the most common causes of graft loss after liver transplantation is biliary damage. There is an urgent clinical need for treatments that could prevent or repair bile ducts, increasing the availability of organs for transplantation and reducing the ever-increasing demand for organ transplantation.
Regenerative biology could address this pressing need by using cells or artificial tissue grown in the lab to regenerate or replace damaged ducts, and the Sampaziotis lab has shown proof-of-principle for the feasibility of this approach. The lab developed a method to grow primary biliary epithelial cells (cholangiocytes) as organoids, which resemble their native counterparts and maintain genetic stability in culture. These characteristics make cholangiocyte organoids a valuable tool for investigating the molecular and cellular events involved in liver regeneration, as well as for cell-based therapy and tissue engineering. The group transplanted cholangiocyte organoids in human livers perfused ex-situ and repaired damaged bile ducts. These results show great promise for the application of regenerative biology in hepatobiliary disorders; however, some challenges remain prior to tangible clinical translation of this technology.
Key words: liver regeneration, cholangiocytes; organoids
Acknowledgements: Our research is supported by the UK Research and Innovation (UKRI) Future Leaders Fellowship, Wellcome Trust, Evelyn Trust, Clare Hall Ivan D Jankovic Scholarship, and Trinity Henry-Barlow Scholarship.
Introduction: Plastic films, containers, and fibers are almost ubiquitous, making our life better, easier, and safer. However, the uncontrollable disposal of plastic waste has raised global concern. Plastic pollution is not a recent issue; it originated decades ago with the advent of industrial plastic production. While recycling, incineration, and other methods exist for managing plastic waste, unfortunately, landfilling remains the most prevalent "solution" adopted by many countries.
In response to the pressing issue of plastic pollution, a new scientific field has emerged, dedicated to employing innovative green methodologies inspired by nature's mechanisms. This approach centers around the discovery and identification of microorganisms with the ability to harness the carbon derived from plastic waste for their growth and survival. In the context of this research, we aim to accomplish two main objectives: isolating enzymes expressed by diverse microbial strains and exploring the potential of well-known hydrolytic enzymes in breaking down synthetic and biosourced polymers.
Methods: To optimize and improve biodegradation yields, our approach combines enzymatic and microbial plastic degradation with polymer treatment techniques. These techniques are designed to modify the structure of polymers, making them more accessible for hydrolysis and assimilation by microorganisms. After polymer hydrolysis, our concept emphasizes the recovery and utilization of the released compounds, which can be further converted into valuable bio-products through fermentation.
Results: Number of new enzymes, microorganisms and microbial communities has been isolated and characterized with the potential to degrade both single and mixed plastic substrates.
Conclusion: By adopting this multidisciplinary approach, we aim to establish a sustainable pathway for the efficient management of plastic waste. Through the transformation of polymers into high-added value products such as bioplastics, biopigments and biosurfactants, we contribute to a circular economy plan and mitigate the environmental impact associated with plastic waste.
Acknowledgements: This study was supported by the EC within Horizon 2020 program - BioICEP project (Agreement no. 870292) and Horizon Europe program - EcoPlastiC project (Agreement no. 101046758).
Introduction: Patients with hematological malignancies have an increased risk of thrombotic complications, ranging from 3-5% in patients with lymphoma and acute myeloid leukemia (AML). The presented study observed the onset of thrombus formation to predict risk factors for thrombosis in lymphoid and myeloid malignancies. Methods: Coagulation factors, inflammatory signaling pathways and adhesion molecules have been observed in patients with Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and AML. Their mononuclear cells (MNC) trans-endothelial migration through human microvascular endothelial cells (HMEC-1) monolayer is observed by Boyden chamber. Results: Thrombin was in positive correlation with tumor necrosis factor alpha (TNF-α) in HL, while with P-selectin (p<0.001), tumor growth factor-beta (TGF-β) and factor VIII (p<0.05) in DLBCL and AML. Trans-endothelial migration of MNC was increased by TNF-α (p<0.001) in DLBCL regardless of previous thrombosis. Regarding coagulation, factor VIII was increased in HL and AML (p<0.05), while tissue factor in non-Hodgkin lymphomas (DLBCL and FL, p<0.05). Tissue factor was in positive correlation with adhesion molecule P-selectin and factor VIII (p<0.05). P-selectin was increased in non-Hodgkin lymphomas (p<0.0001), while TGF-β only in FL (p<0.001). Fibrinolytic activity was decreased in plasma of patients with HL, DLBCL, and FL (p<0.05), but largely in AML (p<0.01) as measured by tissue-type plasminogen activator. Inflammatory NF-κB signaling has been activated in HL and DLBCL, while p38 signaling only in HL. Conclusion: Coagulation factors and inflammation are increased in hematological malignancies along with the interaction of the endothelium and circulating cells that predispose to thrombus formation.
Aging is a universal process associated with impaired functioning, leading to increased morbidity and mortality rate. Various hallmarks of aging were defined, with epigenetic alterations among them. It is well-known that DNA methylation (DNAm) changes correlate with age, in general, leading to global hypomethylation, but also local hypermethylation of cytosine in the CpG-rich regions. Genome-wide studies revealed a high number of age-dependent DNAm positions, and various mathematical models, using, mostly, selected age-dependent DNAm markers, were created for DNAm-based age prediction. Those models, used for „epigenetic age“ estimation, were named „epigenetic clocks“.
The purpose of the „epigenetic clock“ depends on the selection of age-related DNAm markers. „Biological epigenetic cloks“ developed for the estimation of „biological age“ compare the difference between calculated „epigenetic age“ and real „chronological age“, actually measuring alterations in functionally important DNA methylation patterns resulting in acceleration or deceleration of aging. On the other hand, the aim of the „forensic epigenetic clock“ is to predict the „chronological age“ with maximal accuracy, so age-dependent DNAm markers are selected to be the least sensitive to genetic and environmental factors, but associated with the age itself.
Forensic analyses are generally constrained with low quality and quantity, and often the unknown origin of available biological material, mixtures of different cell types and tissues, and material of individuals of varying age and gender, pointing out the factors that should be considered when creating „forensic epigenetic clock“, both for marker selection and methodology used, which makes its creation rather challenging.
A circadian clock is an internalized timing system that synchronizes all physiological processes with the 24-hour changes in the environment. As physiological activities occur at specific times, circadian rhythm disturbances can harm overall health, with testicular function being particularly vulnerable. The increasing prevalence of lifestyles that disrupt circadian rhythms, coupled with the rise in male idiopathic infertility, highlights the need for a comprehensive understanding of the impact of circadian rhythm disruption on fertility regulation.
Recently, our animal model studies have provided insights into the consequences of circadian disturbances on testicular function. These disturbances lead to desynchronization between the central brain circadian pacemaker and peripheral clocks within the reproductive axis including testicular somatic and germ cells, impacting hormonal signaling pathways and impairing Leydig cell steroidogenesis. This results in reduced testosterone production and compromised testosterone-dependent functions, including spermatogenesis. Moreover, circadian disruptions negatively affect spermatozoa motility and impair the acrosome reaction.
The underlying mechanisms connecting circadian clock disruption to testicular dysfunction involve dysregulation in the expression of key clock genes and genes involved in steroidogenesis, mitochondrial network control, and biogenesis. These changes disrupt energetic homeostasis in testosterone-producing Leydig cells and germ cells, contributing to testicular function deterioration and ultimately compromising male fertility.
However, there are still numerous gaps in understanding the mechanisms through which the circadian system impacts testicular physiology. The need to expand knowledge in this area is particularly urgent, given the ever-evolving work schedules and lifestyle choices individuals face.