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Interferons (IFNs) produced by airway epithelial cells are crucial in defending against pathogens. Fluctuations in IFN-λ levels may influence coronavirus disease 19 (COVID-19) severity. However, conflicting data have been reported regarding serum IFN-λ concentrations in COVID-19 patients. To address this, we evaluated serum IFN-λ levels over time in moderate and severe COVID-19 patients and their association with cytokine production and clinical parameters using the enzyme-linked immunosorbent assay (ELISA) and the Bio-Plex Pro Human Cytokine 17-plex Assay. Results from testing 51 COVID-19 patients showed that 68% lacked detectable serum IFN-λ. Among non-IFN-λ secretors, severe COVID-19 predominated. In contrast, IFN-λ secretors displayed stable IFN-λ levels in moderate cases, while severe cases showed a decline over time, which persisted even after recovery. A negative correlation was observed between IFN-λ levels and inflammatory markers. This, combined with an increase in tumor necrosis factor alpha (TNF-α) and clinical improvement, suggests a regulatory role for IFN-λ in promoting faster recovery. Despite this, survival rates were similar between the groups, indicating that while IFN-λ influences the course of the disease, it does not directly affect overall survival. In conclusion, IFN-λ is vital, but not unique, for the antiviral response and COVID-19 recovery. Simultaneously, serum IFN-λ deficiency signifies severe COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurotrophins (NT) might be associated with the pathophysiology of obstructive sleep apnea (OSA) due to concurrent intermittent hypoxia and sleep fragmentation. Such a relationship could have implications for the health and overall well-being of patients; however, the literature on this subject is sparse. This study investigated the alterations in the serum protein concentration and the mRNA expression of the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NTF3), and neurotrophin-4 (NTF4) proteins following a single night of continuous positive airway pressure (CPAP) therapy. This study group consisted of 30 patients with OSA. Venous blood was collected twice after a diagnostic polysomnography (PSG) and PSG with CPAP treatment. Gene expression was assessed with a quantitative real-time polymerase chain reaction. An enzyme-linked immunosorbent assay was used to determine the protein concentrations. After CPAP treatment, BDNF, proBDNF, GDNF, and NTF4 protein levels decreased (p = 0.002, p = 0.003, p = 0.047, and p = 0.009, respectively), while NTF3 increased (p = 0.001). Sleep latency was correlated with ΔPSG + CPAP/PSG gene expression for BDNF (R = 0.387, p = 0.038), NTF3 (R = 0.440, p = 0.019), and NTF4 (R = 0.424, p = 0.025). OSA severity parameters were not associated with protein levels or gene expressions. CPAP therapy could have an impact on the posttranscriptional stages of NT synthesis. The expression of different NTs appears to be connected with sleep architecture but not with OSA severity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 orMMP-9 specific siRNA to minimizeMMP-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 ofMMP-9 may also benefit patients affected by this disease. [ABSTRACT FROM AUTHOR]

Classic atherosclerosis risk factors do not explain all cases of chronic heart disease. There is significant evidence that gut microbiota may influence the development of atherosclerosis. The widespread prevalence of chronic Helicobacter pylori (H. pylori, HP) infections suggests that HP can be the source of components that stimulate local and systemic inflammatory responses. Elevated production of reactive oxygen species during HP infection leads to cholesterol oxidation, which drives atherogenesis. The aim of this study is to explore the link between persistent HP infection and a high-fat diet in the development of proinflammatory conditions that are potentially proatherogenic. An in vivo model of Caviae porcellus infected with HP and exposed to an experimental diet was investigated for the occurrence of a proinflammatory and proatherogenic endothelial environment. Vascular endothelial primary cells exposed to HP components were tested in vitro for oxidative stress, cell activation and apoptosis. The infiltration of inflammatory cells into the vascular endothelium of animals infected with HP and exposed to a high-fat diet was observed in conjunction with an increased level of inflammatory markers systemically. The arteries of such animals were the least elastic, suggesting the role of HP in arterial stiffness. Soluble HP components induced transformation of macrophages to foam cells in vitro and influenced the endothelial life span, which was correlated with Collagen I upregulation. These preliminary results support the hypothesis that HP antigens act synergistically with a high-fat diet in the development of proatherogenic conditions. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that they have no competing interests. Ethics approval and consent to participate: All studies involving animals were approved by the IACUC at the University of Texas Health Science Center, and conform to National Institutes of Health guidelines.