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Abstract Sleep deprivation (DS) is the forced elimination of sleep. While brain-derived neurotrophic factor (BDNF) has been extensively studied in the context of in mood changes following DS, the role of other neurotrophins remains elusive. This study explores the impact of DS on BDNF, glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) at mRNA and protein level, considering their potential links to mood disturbances. The study involved 81 participants subjected to polysomnography (PSG) and DS. Blood samples, mood assessments, and actigraphy data were collected twice, after PSG and DS. NT mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured. Participants were divided into Responders and Non-Responders based on mood improvement after DS. DS reduced BDNF mRNA expression in all participants, with no change in serum BDNF protein. GDNF protein decreased in Non-Responders, while Responders exhibited reduced GDNF mRNA. NT3 protein increased in both groups, while NT3 mRNA decreased in Respondents. NT4 protein rose universally post-DS, but NT4 mRNA remained unchanged. Physical activity (PA) negatively correlated with mRNA expression of BDNF, GDNF, and NT3 post-DS. The study’s short DS duration and exclusion of immature NT forms limit comprehensive insights. GDNF, together with NT3, might play an important role in mood response to DS. PA during DS seems to impair the mRNA expression of NTs in leukocytes. Future studies on the subject of sleep deprivation might consider investigating the relationship between BDNF and NT4 in the context of their apparent redundancy.

Background: Tourette syndrome is a developmental neuropsychiatric disorder. Its etiology is complex and elusive, although an important role of genetic factors has been established. The aim of the present study was to identify the genomic basis of Tourette syndrome in a group of families with affected members in 2 or 3 generations. Methods: Whole-genome sequencing was performed followed by co-segregation and bioinformatic analyses. Identified variants were used to select candidate genes, which were then subjected to gene ontology and pathway enrichment analysis. Results: The study group included 17 families comprising 80 patients with Tourette syndrome and 44 healthy family members. Co-segregation analysis and subsequent prioritization of variants pinpointed 37 rare and possibly pathogenic variants shared among affected individuals within a single family. Three such variants, in the ALDH2, DLD and ALDH1B1 genes, could influence oxidoreductase activity in the brain. Two variants, in SLC17A8 and BSN genes, were involved in sensory processing of sound by inner hair cells of the cochlea. Enrichment analysis of genes whose rare variants were present in all patients from at least 2 families identified significant gene sets implicated in cell-cell adhesion, cell junction assembly and organization, processing of sound, synapse assembly, and synaptic signalling processes. Limitations: We did not examine intergenic variants, but they still could influence clinical phenotype. Conclusion: Our results provide a further argument for a role of adhesion molecules and synaptic transmission in neuropsychiatric diseases. Moreover, an involvement of processes related to oxidative stress response and sound-sensing in the pathology of Tourette syndrome seems likely., Introduction Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal/phonic tics persisting for longer than a year. The clinical phenotype of Tourette syndrome belongs to the spectrum of [...]

Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications. [ABSTRACT FROM AUTHOR]

Indroduction: Cryptoglandular perianal fistula represents a prevalent benign anorectal condition, primarily addressed through surgical interventions, occasionally posing considerable therapeutic challenges. The associated decline in patient quality of life underscores the significance of effective management. However, the lack of a fully understood pathogenesis complicates the treatment approach. Recent research has proposed the involvement of adipose fat tissue in the inflammatory response and pathogenesis of cryptoglandular anal fistula. Aim: The study aims to characterize the role of adipose fat tissue in the pathogenesis of cryptoglandular anal fistula, with a specific focus on understanding the potential involvement of proinflammatory cytokines in the development of chronic inflammation. Materials and methods: This study involved the characterization of serum levels of inflammatory cytokines and adipose tissue hormones. A total of 35 samples from both simple and complex cryptoglandular perianal fistula cases were collected during surgical procedures. Results: Serum levels of leptin, resistin, IL-1β, and IL-8 were significantly elevated in patients operated on due to complex cryptoglandular perianal fistula when compared to patients with simple fistula. Adiponectin was significantly lowered in samples from complex perianal fistula in comparison to simple fistula. Conclusions: Complex perianal cryptoglandular fistula has a reduced level of anti-inflammatory adipokines i.e. adiponectin, and an increased level of proinflammatory resistin, leptin, IL-1β, and IL-8. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) is one of the most deadly cancers on a global scale. Diagnosis of CRC is challenging and it is often detected at a late stage. Identification of relevant biomarkers could lead to the development of effective diagnostic methods for CRC. Areas covered: We reviewed the literature on lipid (including exosomal) biomarkers that have the potential to become common, minimally invasive and effective diagnostic tools for CRC. We showed that differences in lipid levels (single compounds and entire panels) make it possible to classify patients into diseased or healthy groups, determine the stage of CRC, as well as accompanying inflammation and immune reactions associated with tumorigenesis. We also discussed exosomes which are important components of the tumor microenvironment that influence tumor progression and for which only a small number of studies were conducted so far in this area. Expert opinion: A rapid development in the field of lipid-based biomarkers, including exosomal lipid biomarkers, is expected as growing evidence shows their potential application and good accuracy. However, one of the major issues that needs to be addressed within this topic is to translate findings into a noninvasive and versatile diagnostic test robustly validated in clinical conditions. [ABSTRACT FROM AUTHOR]

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental psychiatric disorder with complex and elusive etiology with a significant role of genetic factors. The aim of this study was to identify structural variants that could be associated with familial GTS. The study group comprised 17 multiplex families with 80 patients. Structural variants were identified from whole-genome sequencing data and followed by co-segregation and bioinformatic analyses. The localization of these variants was used to select candidate genes and create gene sets, which were subsequently processed in gene ontology and pathway enrichment analysis. Seventy putative pathogenic variants shared among affected individuals within one family but not present in the control group were identified. Only four private or rare deletions were exonic in LDLRAD4, B2M, USH2A, and ZNF765 genes. Notably, the USH2A gene is involved in cochlear development and sensory perception of sound, a process that was associated previously with familial GTS. In addition, two rare variants and three not present in the control group were co-segregating with the disease in two families, and uncommon insertions in GOLM1 and DISC1 were co-segregating in three families each. Enrichment analysis showed that identified structural variants affected synaptic vesicle endocytosis, cell leading-edge organization, and signaling for neurite outgrowth. The results further support the involvement of the regulation of neurotransmission, neuronal migration, and sound-sensing in GTS. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder affecting 9–23% of the world's population, with a higher prevalence among women. IBS is a complex disorder influenced by psychosocial, physiological, and genetic factors, exacerbated by stress. Research confirms that the most common subtype of IBS is IBS-C. Therefore, new therapies are being developed to speed up bowel movement and reduce constipation, with drugs such as linaclotide, plecanatide, lubiprostone, or tegaserod available to reduce IBS-C symptoms. In addition, patients' condition is improved by foods rich in fiber and low in FODMAP and the use of biotics. The topic is of great importance due to the growing number of patients suffering from IBS-C and its significant impact on quality of life. Current clinical trials of new therapeutic options are not too successful, and it seems that one of the plausible treatment options could be the multi-drug cocktail with some, or perhaps even all its ingredients emerging from drug re-purposing. Another important path that needs to be explored further in IBS-C patients is the adjustment of dietary habits and/or introduction of dietary or nutritional intervention. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) represents the third most diagnosed cancer worldwide, with 1.9 million new cases reported annually. Notwithstanding the progress made in the field of therapeutic modalities and the advent of early diagnosis, CRC continues to represent the second most common cause of cancer-related mortality. The interactions between cancer cells and enteric nervous system (ENS) neurons are of great importance for the prevention and/or progression of CRC. Dietary factors play an important role in regulating both processes. The consumption of foods rich in polyphenols, omega-3 fatty acids, and the use of probiotics has been shown to promote proper ENS function, which in turn has been demonstrated to indirectly inhibit the development or progression of CRC. Conversely, a diet comprising a high proportion of saturated fats and refined sugars can induce oxidative stress and inflammation, which exacerbates the disease. Nutritional education and dietary modifications can reduce the incidence of new cases of CRC and improve prognosis. Further research into the potential anti- or pro-cancer effects of food substances is recommended. [ABSTRACT FROM AUTHOR]