Agata Binienda

Background: Deprivation of sleep (DS) might affect mood and cognitive abilities, including psychomotor functions (PF). Molecular mechanisms underlying these effects remain unclear, though studies suggest that the circadian rhythm plays a role. Methods: Seventy participants underwent polysomnography (PSG) and DS. PF was evaluated using Bimanual Eye–Hand Coordination Test (BEHCT). Mood, PF, and clock gene expression (Circadian Locomotor Output Cycles Kaput (CLOCK), Brain and Muscle ARNT-Like 1 (BMAL1), Period Circadian Regulator 1 (PER1), Cryptochrome Circadian Regulator 1 (CRY1), Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1), and Neuronal PAS Domain Protein 2 (NPAS2)) were analyzed post-PSG and post-DS. Mood changes after DS classified participants as responders (RE) or non-responders (NR). Results: In NRs, but not REs, the BEHCT error count positively correlated with the expression of BMAL1, CRY1, PER1, NR1D1 (R = 0.60, p = 0.002; R = 0.49, p = 0.018; R = 0.57, p = 0.023; and R = 0.53, p = 0.011, respectively), with PER1 explaining its variability in 57.8% (b = 0.174, R² = 0.578, F = 20.144, and p < 0.001). Conclusions: Obtained results suggest that altered clock gene expression may contribute to individual differences in mood and PF following DS.

Deprivation of sleep (DS) is linked to increased risk of immune-mediated diseases. Toll-like receptors (TLR7, TLR9) and BANK1 are key B-cell signaling components that may contribute to their pathogenesis. Seventy-six adults underwent polysomnography (PSG) followed by DS. Venous blood was collected after PSG and DS. Mood was evaluated before and after each stage using Montgomery–Åsberg Depression Rating Scale. Participants were classified as Responders (REs) or Non-Responders (NRs) based on mood changes post-DS. Gene mRNA expression of TLR7, TLR9, and BANK1 in peripheral blood mononuclear cells was analyzed by qRT-PCR. DS reduced TLR7 expression in the entire study group and within NRs, REs, and male and female subgroups (all p < 0.001). During analysis of covariance, women exhibited higher TLR7 expression than men post-DS (p = 0.022), independent of age and body mass index (BMI). At baseline, women exhibited lower expression of TLR9 (p = 0.009, independent of age and BMI), which was abolished after DS (p = 0.570). BANK1 expression increased post-DS in the entire study group and in NRs (p = 0.021), but not REs (p = 0.329). DS modulates B-cell-related immune signaling, with reduced TLR7 and increased BANK1 expression in a sex- and mood-dependent manner.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, characterized by debilitating motor and non-motor symptoms. Its complex pathogenesis involves dopaminergic neuron degeneration, α-synuclein aggregation, neuroinflammation, oxidative stress, and mitochondrial dysfunction. Current symptomatic treatments offer limited symptom improvement, highlighting the urgent need for new strategies, including lifestyle modifications. The ketogenic diet (KD), a dietary approach that shifts the body’s primary energy source from glucose to ketone bodies (KBs) like β-hydroxybutyrate (β-HB), has demonstrated significant therapeutic potential. This review explores KD as a promising, multifaceted intervention for PD. The potential beneficial impact of KD on PD stems from several key mechanisms. β-HB exhibits potent anti-inflammatory properties, reducing pro-inflammatory cytokines and microglial activation by inhibiting pathways such as NF-κB and NLRP3 inflammasome. The diet also improves mitochondrial function by enhancing electron transport chain activity and increasing ATP synthesis, which is crucial given the mitochondrial deficits observed in PD. Furthermore, KBs directly alleviate oxidative stress through enhanced antioxidant defenses. KD offers neuroprotection for dopaminergic neurons, provides an alternative fuel source to the brain, and optimizes cerebral glucose metabolism. It also boosts levels of essential neurotrophic factors, including brain-derived neurotrophic factor (BDNF). Beyond direct neurological effects, KD may enhance levodopa efficacy by improving its bioavailability and appears to play a crucial role in modulating gut microbiota dysbiosis, a frequently observed and potentially contributing factor in PD. While further research is essential, the comprehensive effects of KD on PD-related pathophysiology position it as a promising non-pharmacological strategy.

Background: Cyclic vomiting syndrome (CVS) is a disorder characterized by sudden, recurrent episodes of severe nausea and vomiting. The pathophysiology of CVS is not known but genetic factors that regulate emetic neurocircuitry have been proposed. The aim of this study was to investigate whether different variations in genes encoding serotonin receptors (HTRs) are associated with susceptibility to CVS and/or CVS symptoms.Methods: This case–control study included 70 patients with CVS:16 male and 54 female, and 2504 healthy controls from the 1000 Genomes Project database. Single‐nucleotide polymorphisms (SNPs) in genes encoding serotonin receptors (HTR1B, HTR1D, HTR3B and HTR3C) and correlations between SNPs and the symptoms of CVS were determined.Key Results: Our study discovered that patients with GG, AA and GG genotypes of HTR1B/D rs6296, rs6298 and rs6300, respectively, as well as the CC genotype of HTR3B rs176744 are associated with an increased risk (p < 0.001), whereas allele C in rs3788987 (HTR3B, p < 0.01) and allele A in rs6766410 (HTR3C, p < 0.05) were associated with a decreased risk of CVS. In addition, statistical analysis indicated that CVS patients with GA or AA genotypes of HTR1D rs676643 gene have a seven‐fold increase in risk of depression compared to patients with GG genotype (p < 0.01).Conclusions and Inferences: Our study revealed for the first time that variations in 5‐HTR genes may contribute to CVS susceptibility and CVS‐related symptoms.

Introduction: Free fatty acid receptors (FFARs) are G protein-coupled receptors that divide into 4 subtypes; FFAR2 and FFAR3 are activated by short-chain fatty acids, while FFAR1 and FFAR4 - by long-chain fatty acids. Recent studies show the potential involvement of FFARs in the pathophysiology of colorectal cancer (CRC). A decrease in FFAR2 and FFAR4 gene expression is observed in patients with CRC. The aim of our study was to evaluate the anti-cancer effect of FFAR2 and FFAR4 stimulation by selective synthetic agonists in in vitro and in vivo models of CRC. Materials and methods: FFAR2 agonist, 4-CMTB, and FFAR4 agonist, GSK137647 were used. Cell viability (CCD 841 CoN and SW-480) was determined after 48 h incubation with tested compounds using MTT assay. Real-time qPCR and Western Blot were used to identify changes in FFARs expression. Migration and invasion were characterized by commercially available tests. Colitis-associated CRC (CACRC) mouse model was induced by azoxymethane and dextran sodium sulfate. Results: 4-CMTB and GSK137647 significantly reduced cancer cell growth as well as migration and invasion capacities. Both synthetic compounds increased FFAR2 and FFAR4 expression in SW-480 cells. Neither 4-CMTB nor GSK137647 influenced the course of AOM/DSS-induced CACRC in mice, however, 4-CMTB elevated FFAR2 protein expression in mouse tissues. Conclusion: We presented that stimulation of FFAR2 and FFAR4 may inhibit CRC cell viability and migration and that the FFAR2 and FFAR4 expression decreased in CRC can be restored by treatment with respective agonists, indicating new promising pharmacological targets in CRC treatment.

Background: The molecular underpinnings of insufficient sleep remain underexplored, with disruptions in the neurotrophic signaling pathway emerging as a potential explanation. Neurotrophins (NTs), including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), neurotrophin 4 (NT4), and glial-cell-line-derived growth factor (GDNF), play crucial roles in nerve cell growth and repair. However, their associations with sleep patterns are poorly understood. This study aimed to investigate the relationship between the chosen neurotrophins and objective sleep parameters. Methods: The study involved 81 participants subjected to polysomnography (PSG). Blood samples were collected after PSG. The mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured using real-time quantitative reverse-transcription PCR (qRT-PCR) or enzyme-linked immunosorbent assay (ELISA) methods, respectively. Results: BDNF and NT3 proteins were negatively correlated with NREM events, while NT4 protein positively correlated with REM events. Electroencephalography power analysis revealed BDNF protein’s negative correlation with delta waves during rapid eye movement and non-rapid eye movement sleep. Conclusion: The study highlights associations between neurotrophins and sleep, emphasizing BDNF’s role in regulating NREM and REM sleep. The EEG power analysis implicated BDNF in delta wave modulation, shedding light on potential neurotrophic mechanisms underlying sleep effects on cognitive and mood processes.

The serotonergic pathway may impact the pathogenesis and the course of inflammatory bowel diseases (IBDs). The aim of this study was to investigate the relationship between 5-HT, the serotonin transporter (SERT), and the clinical course of the disease with the occurrence of sleep and mood disorders. Participants completed sleep questionnaires and the Beck Depression Inventory (BDI). Serum 5-HT, SERT protein expression, and mRNA levels were quantified. Additionally, patients treated with anti-TNF therapy were examined before and after treatment. In this study, 77 patients with IBD and 41 healthy controls (HCs) were enrolled and 24 of them were treated with anti-TNF therapy. Patients with IBD had higher 5-HT levels and SERT protein expression than the HCs, but not mRNA SERT levels (p = 0.015, p = 0.001, p = 0.069, respectively). Similar results were obtained for patients in the active state of the disease compared to the non-active state. There was a positive relationship between insomnia severity and SERT protein expression. BDI did not correlate with serotonin or SERT. After anti-TNF therapy, only 5-HT levels were decreased. 5-HT and SERT protein are overexpressed in active IBD and may represent a candidate for novel disease activity biomarkers. The correlation between the SERT protein level and the severity of insomnia symptoms might be among the underlying biochemical factors of sleep disturbances. Anti-TNF treatment might contribute to the reduction in 5-HT levels.

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.

Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. Methods: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO—an MOR agonist), 0.3 mg/kg BW (DPDPE—a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone—a non-selective OR antagonist, GLPG 0974—a FFAR2 antagonist, GSK 137647—a FFAR4 agonist and AH 7614—a FFAR4 antagonist) for 4 days. Results: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. Conclusions: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed.