Biology subjects

Tsymbalyuk, O.

Publications and source records attributed to Tsymbalyuk, O..

3 recordsLinked to original sources

bioRxiv2026

The Vagus Nerve conducts viable translocation of gut flora to the lungs that impacts interstitial lung disease severity in mice

Communication between gut microbiota and extraintestinal organs is increasingly recognized, yet elucidation of relevant translocation mechanism(s) remains enigmatic. Vagus neuroanatomy and reports of vagal protein transfer to extraintestinal organs suggest that this "superhighway" could translocate bacteria. Here we explore whether the vagus superhighway can translocate bacteria to extraintestinal organs. Gavage of green fluorescent protein-expressing Escherichia coli (GFP-E. coli) into germ-free (GF) or specific-pathogen free (SPF) C57BL/6 mice yielded high bacillary loads in the stomach and lungs, followed by the heart, stool and peripheral muscles, despite negative blood cultures. Notably, confocal microscopy and culture revealed GFP-E. coli within the vagus nerve within five minutes of gavage suggesting rapid translocation. Metagenomic analysis of stool, lung, heart, vagus nerve, and muscle from non-gavaged SPF mice demonstrated significant microbial overlap, supporting that bacterial translocation occurs despite the presence of endogenous microflora. Remarkably, subdiaphragmatic vagotomy performed prior to GFP-E. coli gavage resulted in marked reductions of bacterial transduction in the lungs and other extraintestinal organs, except muscle. Furthermore, vagotomy significantly reduced lung fibrosis in SPF mice following intranasal bleomycin administration. In lung cancer patients undergoing lobectomy, vagotomy inhibited postsurgical reductions in forced vital capacity. These findings identify the vagus nerve as a literal gut-lung axis, facilitating viable bacterial translocation and influencing lung severity.

microbiology↗

bioRxiv2025

Dose Escalation in Pentylenetetrazol Kindling Detects Differences in Chronic Seizure Susceptibility

ObjectivePentylenetetrazol (PTZ) kindling is a widely used model for inducing epileptogenesis and evaluating long-term seizure susceptibility differences among animals. This model is typically performed by chronic, repetitive exposures to a constant subconvulsive PTZ dose. However, the effectiveness of the commonly used subconvulsive dose (35mg/kg) varies among different animal groups and experimental conditions due to factors such as species, age, sex, and genetic background. The objective of this study was to characterize a novel model of kindling, the PTZ Dose Escalation (PTZ-DE) model, which assesses chronic seizure threshold with enhanced sensitivity by empirically determining the minimally effective dose to induce PTZ kindling for specific experimental conditions. MethodsThis study investigated the efficacy and validity of the PTZ-DE model by comparing its performance to the standard PTZ kindling approach across a series of conditions. First, the ability of the PTZ-DE model to produce the gradual increase in chronic seizure severity response characteristic of PTZ kindling was compared to the standard model across animal background characteristics (strain, sex). Next, the validity of this model was investigated by determining if the PTZ-DE model could replicate similar changes in chronic seizure susceptibility previously published using the standard approach after traumatic brain injury (TBI). Lastly, the PTZ-DE models efficacy to detect seizure differences was measured in a condition (glyburide treatment) in which alterations to chronic seizure susceptibility were not detected with standard kindling. ResultsThis study found that the PTZ-DE model corrects for background differences in PTZ susceptibility, replicates known differences in chronic seizure thresholds after TBI, and identifies new alterations in seizure threshold not detected with traditional kindling methods. SignificanceThe PTZ-DE model may prove to be a superior tool to standard PTZ kindling for discovering new pathological mechanisms of epileptogenesis and for developing targeted therapies for chronic seizure management, as evidenced by its ability to detect subtle differences in seizure susceptibility across various experimental conditions.

neuroscience↗

bioRxiv2021

Traumatic brain injury alters dendritic cell differentiation and distribution in lymphoid and non-lymphoid organs

Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary injury remain incompletely understood. In particular, the impact of TBI on the differentiation and maintenance of dendritic cells (DCs), remains completely unknown. Here, we report that DC-differentiation, maintenance and functions are altered at both early and late phases of TBI. Our studies identify that; 1. frequencies and absolute numbers of DCs in the spleen and BM are altered at both acute and late phases of TBI; 2. surface expression of key molecules involved in antigen presentation of DCs were affected both at early and late phases of TBI; 3. distribution and functions of tissue-specific DC subsets of both circulatory and lymphatic systems were imbalanced following TBI; 4. early differentiation program of DCs, especially the commitment of hematopoietic stem cells to common DC progenitors, were deregulated after TBI; and 5. intracellular ROS levels were reduced in DC progenitors and differentiated DCs at both early and late phases of TBI. Our data demonstrate, for the first time, that TBI affects the distribution pattern of DCs and induces an imbalance among DC subsets in both lymphoid and non-lymphoid organs. In addition, the current study demonstrates that TBI results in reduced levels of ROS in DCs at both early and late phases of TBI, which may explain altered DC differentiation paradigm following TBI. A deeper understanding on the molecular mechanisms that contribute to DC defects following TBI would be essential and beneficial in treating infections in patients with acute central nervous system (CNS) injuries.

immunology↗