Melatonin Improves Glucose Homeostasis and Insulin Sensitivity by Mitigating Inflammation and Activating AMPK Signaling in a Mouse Model of Sleep Fragmentation.

Sleep fragmentation (SF) can increase inflammation and production of reactive oxygen species (ROS), leading to metabolic dysfunction. SF is associated with inflammation of adipose tissue and insulin resistance. Several studies have suggested that melatonin may have beneficial metabolic effects due to activating AMP-activated protein kinase (AMPK).

Sleep Fragmentation Accelerates Carcinogenesis in a Chemical-Induced Colon Cancer Model.

Aims of this study were to test whether sleep fragmentation (SF) increased carcinogenesis and to investigate the possible mechanisms of carcinogenesis in a chemical-induced colon cancer model. In this study, eight-week-old C57BL/6 mice were divided into Home cage (HC) and SF groups. After the azoxymethane (AOM) injection, the mice in the SF group were subjected to SF for 77 days.

Coexistence of Moderate-to-Severe Obstructive Sleep Apnea and Inflammation Accelerates the Risk of Progression of Arterial Stiffness: A Prospective 6-Year Study.

Both obstructive sleep apnea (OSA) and inflammation have now been recognized as imposing substantial cardiometabolic risk. However, no prospective study has reported whether the coexistence of OSA and inflammation exacerbates the progressive arterial stiffening. Thus, the purpose of this study is to examine whether these conditions increase the risk of the progression of arterial stiffening.

A cancer cell-specific benzoxadiazole-based fluorescent probe for hydrogen sulfide detection in mitochondria.

The present work describes the design and biological applications of a novel colorimetric and fluorescence turn-on probe for hydrosulfide detection. The probe was designed to introduce hemicyanine as the fluorescent skeleton and 7-nitro-1,2,3-benzoxadiazole as the recognition site. The optical properties and responses of the probe towards HS, anions and some biothiols indicate an impressively high selectivity of the probe towards HS such that it can be effectively used as an indicator for monitoring the level of HS in living cells.

Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b.

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo.

Protection and immune modulation of activated human vaginal epithelial cells by Aurea helianthus extract.

Aurea helianthus extract is associated with various properties including anti-melanogenesis, anti-oxidation, tumorigenic suppression, and immunoregulation; however, the mechanism by which it executes the immunomodulation of human vaginal epithelial cells (HVECs) remains elusive. We established three immunological functions of the extract. First, it mediated tumorigenic suppression in HVECs.

Biological effects of melatonin on human adipose‑derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are capable of differentiating into other cell types and exhibit immunomodulatory effects. MSCs are affected by several intrinsic and extrinsic signaling modulators, including growth factors, cytokines, extracellular matrix and hormones. Melatonin, produced by the pineal gland, is a hormone that regulates sleep cycles.

Environmental Benzopyrene Attenuates Stemness of Placenta-Derived Mesenchymal Stem Cells via Aryl Hydrocarbon Receptor.

The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated.

A pH-Responsive Glycyrrhetinic-Acid-Modified Small-Molecule Conjugate for NIR Imaging of Hepatocellular Carcinoma (HCC).

We report a glycyrrhetinic-acid (GA)-decorated small-molecule conjugate for pH-triggered near-infrared (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our in vitro studies demonstrated that the conjugate, referred to as NIR-GA, was efficiently taken up by liver cancer cell lines such as HepG2 and Huh7 through an endocytic pathway mediated by GA receptors. As suggested by co-localization studies, NIR-GA mainly localized in the lysosome, where the acidic pH results in the activation of the fluorescent dye through H -triggered spirolactam ring opening to give strong fluorescence in the NIR region.

The co-existence of elevated high sensitivity C-reactive protein and homocysteine levels is associated with increased risk of metabolic syndrome: A 6-year follow-up study.

Accumulating evidence has revealed that both high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) are associated with increased risk of metabolic syndrome (MetS) and cardiovascular disease. However, it is unclear whether the coexistence of these conditions accelerates the risk of metabolic syndrome (MetS). We hypothesized that the combination of high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) levels could exacerbate the development of MetS in a large prospective cohort study.

Obstructive sleep apnoea is associated with progression of arterial stiffness independent of obesity in participants without hypertension: A KoGES Prospective Cohort Study.

Accumulating evidence shows that obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. However, there are no published prospective studies on the relationship between OSA and the progression of arterial stiffness. We hypothesised that OSA would increase the risk of arterial stiffness progression, independent of obesity.

Peptide ligand-mediated endocytosis of nanoparticles to cancer cells: Cell receptor-binding- versus cell membrane-penetrating peptides.

The endocytosis-mediating performances of two types of peptide ligands, cell receptor binding peptide (CRBP) and cell membrane penetrating peptide (CMPP), were analyzed and compared using a common carrier of peptide ligands-human ferritin heavy chain (hFTH) nanoparticle. Twenty-four copies of a CMPP(human immunodeficiency virus-derived TAT peptide) and/or a CRBP (peptide ligand with strong and specific affinity for either human integrin(α β ) or epidermal growth factor receptor I (EGFR) that is overexpressed on various cancer cells) were genetically presented on the surface of each hFTH nanopariticle. The quantitative level of endocytosis and intracellular localization of fluorescence dye-labeled CRBP- and CMPP-presenting nanoparticles were estimated in the in vitro cultures of integrin- and EGFR-overexpressing cancer and human dermal fibroblast cells(control).

Concurrent Presence of Obstructive Sleep Apnea and Elevated Homocysteine Levels Exacerbate the Development of Hypertension: A KoGES Six-year Follow-up Study.

Accumulating evidence has revealed that obstructive sleep apnea (OSA) and high homocysteine (Hcy) levels play important roles in the increased risk of hypertension and cardiovascular disease. We investigated whether the presence of elevated Hcy levels among individuals with OSA increase the risk of hypertension in a cohort study. A total of 1825 participants were selected from the cohort study.

Overlap syndrome of COPD and OSA in Koreans.

Overlap syndrome of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) leads to increased morbidity and mortality. There have been no reports available on the overlap syndrome for Koreans. Our primary aim was to identify prevalence and predictors of the overlap syndrome in Koreans.

Concurrent presence of inflammation and obstructive sleep apnea exacerbates the risk of metabolic syndrome: A KoGES 6-year follow-up study.

Obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Both OSA and inflammation play key roles in increased risk of cardiovascular disease (CVD). Thus, we hypothesized that the combination of inflammation and OSA could accelerate the development of metabolic syndrome (MetS) in a large cohort study.

The association between irritable bowel syndrome and the coexistence of depression and insomnia.

Objective: The individual occurrence of depression or insomnia is a risk factor for irritable bowel syndrome (IBS), but few researchers have evaluated the association between comorbid depression and insomnia and IBS. The aim of the present study is to explore the relationship between IBS and the coexistence of depression and insomnia in a Korean population-based cohort study.

Methods: A total of 3429 individuals who were enrolled in the Korean Genome and Epidemiology Study were analysed.

Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study.

Obstructive sleep apnea syndrome (OSA) has been recognized as a common health problem, and increasing obesity rates have led to further remarkable increases in the prevalence of OSA, along with more prominent cardiovascular morbidities. Though previous studies have reported an independent relationship between elevated high sensitivity C-reactive protein (hsCRP) levels and OSA, the issue remains controversial owing to inadequate consideration of obesity and various confounding factors. So far, few population based studies of association between OSA and hsCRP levels have been published.

Variants in C-reactive protein and IL-6 genes and susceptibility to obstructive sleep apnea in children: a candidate-gene association study in European American and Southeast European populations.

Background: Preliminary evidence indicates that variants of the C-reactive protein (CRP) and IL-6 genes might be associated with the presence of obstructive sleep apnea (OSA) in childhood. Thus a candidate-gene association study was conducted to investigate the association of four variants of the CRP gene (1444C/T, -717T/C, 1861C/T, and 1919A/T) and two variants of the IL-6 gene (-174G/C and 597G/A) with OSA in a cohort of European American and Greek children.

Methods: The genetic risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (ORG), which is a model-free approach.

Substance P and neurokinin 1 receptors as potential therapeutic targets in children with OSA.

Background: Increased substance P (SP) levels and abundant expression of neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful in treating OSA.

Methods: The effects of SP and the NK1 antagonist GR-82334 were examined on mixed cell cultures prepared from dissociated tonsils harvested intraoperatively from children with OSA and RI. Proliferation was assessed by [3H]-thymidine or 5-ethynyl-2'-deoxyuridine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-1β) was assessed in supernatants by enzyme-linked immunosorbent assay.

TREM-1 and pentraxin-3 plasma levels and their association with obstructive sleep apnea, obesity, and endothelial function in children.

Background: Obstructive sleep apnea (OSA) is a common health problem in children and increases the risk of cardiovascular disease (CVD). Triggering receptor expressed on myeloid cells-1 (TREM-1) plays an important role in innate immunity and amplifies inflammatory responses. Pentraxin-3 is predominantly released from macrophages and vascular endothelial cells, plays an important role in atherogenesis, and has emerged as a biomarker of CVD risk.

Novel pharmacological approaches for treatment of obstructive sleep apnea in children.

Introduction: The lymphadenoid tissues in the upper airway are sparse and organized lympho-epithelial structures playing an important role against foreign pathogens, with the palatine tonsils being the major components of the lymphoid tissues contained in the Waldeyer's ring. Obstructive sleep apnea (OSA) has emerged as a very frequent condition in the pediatric age range that is associated with substantial neurobehavioral, cardiovascular and metabolic morbidities. Adenotonsillar hypertrophy is the major pathophysiological contributor to OSA occurrence in children.

C-reactive protein and obstructive sleep apnea syndrome in children.

Obesity has emerged as one of the most important epidemics in the western hemisphere, and as its prevalence continues to increase in children, the associated risk for cardiovascular and metabolic complications follows parallel increases in prevalence, and reflects activation of underlying inflammatory pathways. The obstructive sleep apnea syndrome (OSAS) is a frequent condition in children associated with intermittent upper airway obstruction during sleep, its prevalence is markedly increased in the presence of obesity, and is associated with activation of similar inflammatory mechanisms as those activated by obesity, suggesting that the 2 disorders may reciprocally contribute to their adverse consequences. C-reactive protein (CRP) is a prototypic marker of inflammation that has repeatedly shown promise as a potentially reliable biomarker of cardiovascular morbidity.

DNA methylation in inflammatory genes among children with obstructive sleep apnea.

Background: Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions.

Methods: DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes.

Endothelial dysfunction in children without hypertension: potential contributions of obesity and obstructive sleep apnea.

Background: Endothelial dysfunction can develop in the context of both obesity and obstructive sleep apnea (OSA) in children. However, the potential interactions between OSA and obesity have not been defined.

Methods: Children who were prepubertal and nonhypertensive were recruited.

Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms?

Pediatric obstructive sleep apnea (OSA) may lead to neurocognitive dysfunction, but not in everyone affected. The frequencies of NADPH oxidase (NOX) polymorphisms in the p22phox subunit were similar between children with OSA and controls, except for rs6520785 and rs4673, the latter being significantly more frequent among the OSA children without deficits than with deficits (p<0.02).