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The Gastric pathogen Helicobacter pylori (HP) may influence the development of coronary heart disease (CHD). H. pylori induce reactive oxygen species (ROS), which transform cholesterol to 7-ketocholesterol (7-kCh), a CHD risk factor. Acetylsalicylic acid (ASA)—an Anti-aggregation drug used in CHD patients—may increase gastric bleeding and inflammation. We examined whether H. pylori driven ROS effects in the cell cultures of gastric epithelial cells (AGS) and vascular endothelial cells (HUVEC) progress in the milieu of 7-kCh and ASA. Cell cultures, exposed to 7-kCh or ASA alone or pulsed with the H. pylori antigenic complex—Glycine acid extract (GE), urease (UreA), cytotoxin associated gene A (CagA) protein or lipopolysaccharide (LPS), alone or with 7-kCh and ASA—were examined for ROS, apoptosis, cell integrity, interleukin (IL)-8, the activation of signal transducer, the activator of transcription 3 (STAT3), and wound healing. ASA and 7-kCh alone, and particularly in conjunction with H. pylori components, increased the ROS level and the rate of apoptosis, which was followed by cell disintegration, the activation of STAT3, and IL-8 elevation. AGS cells were unable to undergo wound healing. The cell ROS response to H. pylori components may be elevated by 7-kCh and ASA.

Helicobacter pylori colonizes the human gastric mucosa, causing chronic inflammation, peptic ulcers and gastric cancer. A cascade of harmful processes results from the interaction of these bacteria with the gastric epithelium. To investigate these processes in terms of upregulation of oxidative stress and cell apoptosis and downregulation of the pro-regenerative activity of cells. We employed an in vivo guinea pig model at 7 or 28 days postinoculation with H. pylori, corresponding to an acute or chronic stage of infection, respectively, and an in vitro model of guinea pig primary gastric epithelial cells and fibroblasts treated with bacterial components: glycine acid extract (GE), urease subunit A (UreA), cytotoxin-associated gene A protein (CagA) and lipopolysaccharide (LPS). Cells were evaluated for metabolic activity (MTT reduction), myeloperoxidase (MPO) and metalloproteinase (MMP-9) secretion, lipid peroxidation (4-hydroxynonenal (4HNE)), migration (wound healing), proliferation (Ki-67 antigen) and cell apoptosis (TUNEL assay; Bcl-xL, Bax, Bcl-2 expression; caspase 3 cleavage). Significant infiltration of the gastric mucosa by inflammatory cells in vivo in response to H. pylori was accompanied by oxidative stress and cell apoptosis, which were more intense 7 than 28 days after inoculation. The increase in cell proliferation was more intense in chronic than acute infection. H. pylori components GE, CagA, UreA, and LPS upregulated oxidative stress and apoptosis. Only H. pylori LPS inhibited cell migration and proliferation, which was accompanied by the upregulation of MMP-9. H. pylori infection induces cell apoptosis in conjunction with increased oxidative stress. Elevated apoptosis protects against deleterious inflammation and neoplasia; however, it reduces cell integrity. Upregulation of cell migration and proliferation in response to injury in the milieu of GE, CagA or UreA facilitates tissue regeneration but increases the risk of neoplasia. By comparison, downregulation of cell regeneration by H. pylori LPS may promote chronic inflammation.

Obstructive sleep apnea (OSA) is associated with circadian rhythm dysregulation plausibly through affecting clock genes. The study’s purpose was to investigate the effect of one-night continuous positive airway pressure treatment (CPAP treatment) on circadian clock genes: BMAL1 , CLOCK , CRY1 , and PER1 at mRNA and protein levels. The study included 30 OSA patients, who underwent diagnostic polysomnography (PSG) and next a one-night effective CPAP treatment with PSG monitoring (CPAP). The blood was collected in the evening before and the morning after PSG and CPAP. Protein levels and mRNA expression were measured using ELISA and qRT-PCR, respectively. The increase in PER1 expression was observed in the morning after compared to the evening before CPAP ( p  = 0.005); additionally, PER1 protein level decreased in the morning after CPAP compared to the morning after PSG ( p  = 0.035). In CLOCK protein levels significant changes were observed: an increase in the morning after CPAP compared to the morning after PSG ( p  = 0.049), an increase in the morning after CPAP compared to the evening before ( p  = 0.006), and an increase in difference between the morning after and evening before CPAP vs. difference between morning after and evening before PSG ( p  = 0.012). Obtained results suggest that even short-term effective CPAP treatment might reverse circadian clock signaling pathway disruption in OSA.

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurring upper airway obstructions, leading to disrupted sleep and systemic complications. The complexity of OSA suggests intricate interactions between neuromodulators and circadian clock genes. This study aimed to explore the expression levels of circadian rhythm genes and neurotrophins (NTs) in OSA patients compared to controls. Participants (166 OSA patients, 64 controls) were enrolled. Blood samples collected post-polysomnography (PSG), underwent RNA extraction from peripheral blood lymphocytes and RT-PCR was performed for gene expression analysis. In the OSA group, the expression of BMAL1 , CLOCK , CRY1 , PER1 , NPAS2 , NR1D1 , and HIF-1β was positively correlated with BDNF expression ( p  < 0.05 for all). Conversely, in the control group, only PER1 mRNA showed a correlation with BDNF expression ( R  = 0.280, p  = 0.017). NF-κβ expression demonstrated a positive correlation with BMAL1 , CLOCK , CRY1 , PER1 , NPAS2 , NR1D1 , HIF-1α , and HIF-1β expressions in both groups ( p  < 0.05 for all). HIF-1α and HIF1-β mRNA expressions were positively correlated with BMAL1 , CLOCK , CRY1 , PER1 , NPAS2 , and NR1D1 expressions regardless of the presence of OSA ( p  < 0.05 for all). The study underscores the intricate interactions among circadian rhythm genes, NTs, and transcription factors in OSA, providing a basis for potential targeted therapeutic interventions.

Obstructive sleep apnea (OSA) is characterized by co-occurrence with affective disorders. Our study aims to investigate the association of circadian clock gene expressions, and the presence and severity of depressive symptoms in OSA patients. The study included 184 individuals, who underwent polysomnography (PSG) and had their peripheral blood collected in the evening before and the morning after the PSG. Patients were divided into two groups: the OSA (apnea-hypopnea index (AHI) > 5) and the control group (AHI < 5). RNA was extracted from peripheral blood leukocytes. Expression levels of the selected genes ( BMAL1 , CLOCK , PER1 , CRY1 , NPAS2 , and NR1D1 ) were assessed by qRT-PCR. Questionnaire data was collected in the morning (including the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Chronotype Questionnaire (CQ), and Montgomery–Åsberg Depression Rating Scale (MADRS)). The expression of all examined circadian clock genes in OSA patients was upregulated in the morning compared to the evening (except NPAS2 ). No differences were observed between OSA and control groups at either time point. Additionally, there was a positive correlation between the severity of depressive symptoms (assessed with MADRS) and morning expression of circadian genes in the group of OSA patients. Finally, in multivariable linear regression, ISI score ( B  = 0.750, p  < 0.001), AM score of CQ ( B  = 0.416, p  = 0.007), and morning PER1 gene expression ( B  = 4.310, p  = 0.042) were found to be predictive factors for greater severity of depression symptoms in OSA patients. Dysregulated circadian clock gene expression in OSA patients is linked to depressive symptom severity, suggesting circadian disruption may underlie affective symptoms in OSA.

Chronic obstructive pulmonary disease (COPD) is associated with severe chronic inflammation that promotes irreversible tissue destruction. Moreover, the most broadly accepted cause of COPD is exposure to cigarette smoke. There is no effective cure and significantly, the mechanism behind the development and progression of this disease remains unknown. Our laboratory has demonstrated that Bruton’s tyrosine kinase (Btk) is a critical regulator of pro-inflammatory processes in the lungs and that Btk controls expression of matrix metalloproteinase-9 (MMP-9) in the alveolar compartment. For this study apolipoprotein E null (ApoE−/−) mice were exposed to SHS to facilitate study in a COPD/atherosclerosis comorbidity model. We applied two types of treatments, animals received either a pharmacological inhibitor of Btk or MMP-9 specific siRNA to minimize MMP-9 expression in endothelial cells or neutrophils. We have shown that these treatments had a protective effect in the lung. We have noted a decrease in alveolar changes related to SHS induced inflammation in treated animals. In summary, we are presenting a novel concept in the field of COPD, i.e., that Btk may be a new drug target for this disease. Moreover, cell specific targeting of MMP-9 may also benefit patients affected by this disease.

NSAID-exacerbated respiratory disease (N-ERD) is a bronchial asthma phenotype characterized by the coexistence of NSAID hypersensitivity, lower airway symptoms, and severe chronic sinusitis with nasal polyps. This study examined the cytokine profiles in the upper airways of patients with N-ERD compared to those of patients with NSAID-tolerant asthma, allergic rhinitis (AR), and healthy controls. 89 patients were included in the N-ERD, AR, asthma, and control groups. The minimally invasive nasosorption technique was used to collect nasal mucosal lining fluid. Inflammatory mediators were quantified using a Bio-Plex Multiplex System. IL-6 levels in nasal samples (NSs) were higher in all patient groups than in the controls. No significant differences were observed in the nasal levels of all analyzed cytokines between patients with N-ERD and those with asthma or AR alone. Cluster analysis identified two distinct inflammatory phenotypes within the N-ERD group based on nasal cytokine profiles, although these did not correlate with clinical features. A logistic regression model showed that only serum TNF-α levels and the severity of nasal obstruction significantly differentiated patients with N-ERD from the other groups. The results demonstrate that while patients with N-ERD exhibit heterogeneity in upper airway inflammatory profiles, this does not necessarily translate into differences in clinical presentation.

Background: Hypoxia-inducible factor 1 (HIF-1) affects the circadian clock in obstructive sleep apnea (OSA) and may have a bidirectional relationship with circadian mechanisms. This study examined the link between circadian clock and HIF-1 in OSA patients versus controls. Methods: 70 participants underwent polysomnography (PSG), and were assigned into OSA (apnea–hypopnea index (AHI) ≥ 5, n = 54) or control (AHI < 5, n = 16) groups. BMAL1 (brain and muscle ARNT like 1), CLOCK (circadian locomotor output cycles kaput), PER1 (period 1), CRY1 (cryptochrome 1), HIF-1α, and HIF-1β gene expressions and protein levels were measured in evening and morning samples, collected before and after PSG. Results: The OSA group was characterized by increased CLOCK, CRY1, PER1 and HIF-1a protein levels, both in the morning and evening (all p < 0.05), and decreased morning expression of BMAL1 (p = 0.02). Associations between almost all circadian clock gene expressions and both HIF-1 subunits were observed in the OSA group at both time points (all p < 0.05), apart from association between PER1 and HIF-1α in the morning (R = 0.050, p = 0.73). In controls, only a correlation between HIF-1α levels and CRY1 expression in the morning (R = 0.588, p = 0.02) was found. Conclusions: OSA affects the circadian clock and HIF-1 pathway, with increased CLOCK, CRY1, PER1, and HIF-1α protein levels observed in OSA patients. The interplay between these systems may involve complex posttranscriptional and posttranslational mechanisms.

Introduction. This study aimed to investigate the relationship between obstructive sleep apnea (OSA), circadian rhythms, and individual sleep–wake preferences, as measured by chronotype, and to assess the association between circadian clock gene expression and subjective sleep-related variables. Methods: A total of 184 individuals were recruited, underwent polysomnography (PSG), and completed questionnaires including a chronotype questionnaire (CQ), insomnia severity index (ISI), and Epworth sleepiness scale (ESS). Blood samples were collected in the evening before and morning after PSG. Gene expression analysis included BMAL1, CLOCK, PER1, CRY1, NPAS2, and NR1D1. Results: In the OSA group, the subjective amplitude (AM score of CQ) positively correlated with all circadian clock genes in the morning (R ≥ 0.230 and p < 0.05 for each one), while the morningness–eveningness (ME score of CQ) was only associated with the evening BMAL1 level (R = 0.192; p = 0.044). In healthy controls, insomnia severity correlated with evening expression of BMAL1, PER1, and CRY1. Conclusions: The findings highlight the complex interplay between OSA, circadian rhythms, and sleep-related variables, suggesting potential determinants of morning chronotype in OSA and implicating disrupted circadian clock function in subjective feelings of energy throughout the day. Further research is warranted to elucidate underlying mechanisms and guide personalized management strategies.

Obstructive sleep apnea (OSA) has been linked to disruptions in circadian rhythm and neurotrophin (NFT) signaling. This study explored the link between neuromodulators, chronotype, and insomnia in OSA. The participants (n = 166) underwent polysomnography (PSG) before being categorized into either the control or the OSA group. The following questionnaires were completed: Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Chronotype Questionnaire (morningness-eveningness (ME), and subjective amplitude (AM). Blood samples were collected post-PSG for protein level assessment using ELISA kits for brain-derived neurotrophic factor (BDNF), proBDNF, glial-cell-line-derived neurotrophic factor, NFT3, and NFT4. Gene expression was analyzed utilizing qRT-PCR. No significant differences were found in neuromodulator levels between OSA patients and controls. The controls with insomnia exhibited elevated neuromodulator gene expression (p < 0.05). In the non-insomnia individuals, BDNF and NTF3 expression was increased in the OSA group compared to controls (p = 0.007 for both); there were no significant differences between the insomnia groups. The ISI scores positively correlated with all gene expressions in both groups, except for NTF4 in OSA (R = 0.127, p = 0.172). AM and ME were predicting factors for the ISI score and clinically significant insomnia (p < 0.05 for both groups). Compromised compensatory mechanisms in OSA may exacerbate insomnia. The correlation between chronotype and NFT expression highlights the role of circadian misalignments in sleep disruptions.