Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.

The structure of primary afferent nerve terminals profoundly influences their function. While the complex vagal airway nerve terminals (stretch receptors, cough receptors and neuroepithelial bodies) were thoroughly characterized, much less is known about the structure of airway nerves that do not form distinct complex terminals (often termed free nerve fibers). We selectively induced expression of GFP in vagal afferent nerves in the mouse by transfection with AAV-GFP virus vector and visualized nerve terminals in the trachea by whole organ confocal imaging. Based on structural characteristics we identified four types of vagal afferent nerve fiber terminals in the trachea. Importantly, we found that distinct compartments of tracheal tissue are innervated by distinct nerve fiber terminal types in a non-overlapping manner. Thus, separate terminal types innervate tracheal epithelium vs. anterolateral tracheal wall containing cartilaginous rings and ligaments vs. dorsal wall containing smooth muscle. Our results will aid the study of structure-function relationships in vagal airway afferent nerves and regulation of respiratory reflexes.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic neurons, and at the cellular level by the formation of Lewy bodies in the central nervous system (CNS). However, the onset of the disease is believed to be localized to peripheral organs, particularly the gastrointestinal tract (GIT) and the olfactory bulb sooner before neuropathological changes occur in the CNS. Patients already in the pre-motor stage of PD suffer from various digestive problems and/or due to significant changes in the composition of the intestinal microbiome in this early stage of the disease. Detailed analyses of patient biopsies and autopsies as well as animal models of neuropathological changes characteristic of PD provided important information on the pathology or treatment of PD symptoms. However, presently is not clarified (i) the specific tissue in the GIT where the pathological processes associated with PD is initiated; (ii) the mechanism by which these processes are disseminated to the CNS or other tissues within the GIT; and (iii) which neuropathological changes could also serve as a reliable diagnostic marker of the premotor stages of PD, or (iv) which type of GIT tissue would be the most appropriate choice for routine examination of patient biopsies.

The primary pathogenesis associated with Parkinson’s disease (PD) occurs in peripheral tissues several years before the onset of typical motor symptoms. Early and reliable diagnosis of PD could provide new treatment options for PD patients and improve their quality of life. At present, however, diagnosis relies mainly on clinical symptoms, and definitive diagnosis is still based on postmortem pathological confirmation of dopaminergic neuronal degeneration. In addition, the similarity of the clinical, cognitive, and neuropathological features of PD with other neurodegenerative diseases calls for new biomarkers, suitable for differential diagnosis. Alpha-synuclein (α-Syn) is a potential PD biomarker, due to its close connection with the pathogenesis of the disease. Here we summarize the currently available information on the possible use of α-Syn as a biomarker of early stages of PD in gastrointestinal (GI) tissues, highlight its potential to distinguish PD and other neurodegenerative diseases, and suggest alternative methods (primarily developed for other tissue analysis) that could improve α-Syn detection procedures or diagnostic methods in general.

The main role of research in medicine is to provide relevant knowledge which, after successful translation to clinical practice, improves the quality of healthcare. The sex bias which is still present in the majority of research disciplines prefers male subjects despite legislation changes in the US grant agencies and European research programme Horizon 2020. Male subjects (cells, animals) still dominate in preclinical research and it has detrimental consequences for women’s health and the quality of science. Opposite bias exists for data obtained mainly in animal models utilizing female subjects (e.g. research in multiple sclerosis, osteoporosis) with skewed outcomes for men affected by these diseases. Either way, scientists are producing results which compromise half of the population. Assumptions that females as cohorts are more variable and another assumption that the oestrous cycle should be tracked in case the females are enrolled in preclinical studies were proven wrong. Variability of male versus female cohorts are comparable and do not only stem from hormonal levels. The widespread prevalence of sex differences in human diseases ultimately requires detailed experiments performed on both sexes, unless the studies are specifically addressing reproduction or sex-related behaviors.