Biology subjects

Vasilyev, V.

Publications and source records attributed to Vasilyev, V..

4 recordsLinked to original sources

bioRxiv2026

A robust negative association between estimated tumour circadian clock function and survival in early stage breast cancer

Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of chronic conditions including cardio-metabolic diseases and cancer. For the latter, they also suggest that chronotherapy offers the potential to refine current treatments and improve the development of future anti-cancer medicines. Therefore, there is a need for tools to measure the functional state of the tumoural circadian clock in patients. We have previously developed a model-led machine-learning algorithm called TimeTeller which has the potential to provide such a tool. Here we demonstrate its potential for clinical relevance by a study of 1286 breast cancer patients in which we characterise the nature of the circadian clock disruption in their tumours and demonstrate a strong nonlinear association between 10-year survival and TimeTellers tumoural clock disfunction score {Theta}. We find that good tumour clock function is antagonistic to survival.

cancer biology↗

bioRxiv2025

Cationic antimicrobial copolymers reveal immunomodulatory properties in LPS stimulated macrophages in vitro

Antimicrobial polymers, which have emerged as a promising alternative to antibiotics in the fight against antimicrobial resistance, are based on the design of cationic host defence peptides (CHDPs). Being a part of the mammalian innate immune system, CHDPs possess both antimicrobial and immunoregulatory effects to manage bacterial infections. However, the immunomodulatory effects of antimicrobial polymers remain largely unexplored. Within this work, a library of 15 copolymers were synthesised by reversible addition-fragmentation chain transfer (RAFT) polymerisation and their abilities to modulate pro-inflammatory pathways in LPS-activated murine and human macrophages were investigated. We found that two diblock copolymers with cationic units copolymerised with either apolar or hydrophilic comonomers appeared to have anti-inflammatory activity through suppression of the activation of the NF-{kappa}B signalling pathway, scavenging of reactive oxygen species and reduced production of the pro-inflammatory cytokine IL-6. Furthermore, the cationic-apolar copolymer exhibits significant antimicrobial activity against P. aeruginosa. Thus, this promising copolymer holds potential as a dual-action therapeutic, effectively combating bacterial infections while curbing prolonged inflammation and thereby preventing sepsis at the site of infection.

microbiology↗

bioRxiv2024

Preclinical testing of RRx-001 in mouse models of experimental endometriosis reveals promising therapeutic impacts

Endometriosis is a chronic inflammatory condition characterised by the presence of ectopic endometrial-like tissue (lesions), reduced fertility and chronic pain. Impacting both the health and psycho-social functioning of millions of women worldwide, there is an urgent need for innovative non-hormonal, non-invasive treatments for the disorder. Both peritoneal and lesion-resident macrophages have been strongly implicated in the pathogenesis of endometriosis; key roles include promotion of lesion growth, neuroangiogenesis and nerve sensitization. With such a central role in the disease, macrophages represent a novel therapeutic target. In the current preclinical study, we sought to repurpose the macrophage targeting anti-cancer drug RRx-001 for the treatment of endometriosis. We utilised mouse models of induced endometriosis to demonstrate that RRx-001 induces regression of endometriosis lesions and attenuates pain-like behaviours, without negatively impacting fertility. Targeted depletion of peritoneal cavity macrophages significantly impairs lesion reduction, demonstrating their critical role in mediating the anti-endometriosis impact of RRx-001. Using single nuclei multiomics, we identified a modification of macrophage subpopulations in the peritoneal cavity, specifically reduced acquisition of a pro-disease phenotype and an accumulation of a pro-resolving phenotype. These observations signify the potential of RRx-001 as a novel therapeutic for endometriosis management.

immunology↗

bioRxiv2023

TimeTeller: a tool to probe the circadian clock as a multigene dynamical system

AO_SCPLOWBSTRACTC_SCPLOWRecent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart diseases. Therefore, there is a need for tools to measure the functional state of the molecular circadian clock and its downstream targets in patients. Moreover, the clock is a multi-dimensional stochastic oscillator and there are few tools for analysing it as a system. In this paper we consider the methodology behind Time-Teller, a machine learning tool that analyses the clock as a system and aims to estimate circadian clock function from a single transcriptome by modelling the multi-dimensional state of the clock. We demonstrate its potential for clock systems assessment by applying it to mouse, baboon and human microarray and RNA-seq data and show how to visualise and quantify the global structure of the clock, quantitatively stratify individual transcriptomic samples by clock dysfunction and globally compare clocks across individuals, conditions and tissues thus highlighting its potential relevance for advancing circadian medicine.

systems biology↗