The association of diabetes with progression of sleep-disordered breathing based on a prospective cohort.

AIM: Prospective studies suggest that sleep-disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep-disordered breathing. METHODS: The participants from Sleep Heart Health Study underwent two polysomnograms at a 5-year interval. The relationship of baseline diabetes to change in the apnoea-hypopnoea index (AHI) was examined based on general linear models, adjusting for demographics, lifestyles, history of hypertension, pulmonary function, length of follow-up and baseline AHI. RESULTS: In total, 161 of the 2603 participants were diagnosed with diabetes at the first polysomnograms. Compared with participants without diabetes, those with diabetes had a higher baseline and larger increases in follow-up AHI and obstructive apnoea index (oAI). Diabetes increased 2.52 events per hour (95% confidence interval 0.45-4.59; p = .017) for AHI change and 1.13 events per hour (95% confidence interval 0.04-2.23; p = .042) for oAI change, respectively. In addition, subgroup analysis suggested that the association was consistent across baseline obstructive sleep apnoea severity and body mass index groups. CONCLUSIONS: Baseline diabetes was associated with worsening sleep-disordered breathing over 5 years, which mainly increased the change in AHI and oAI.

LINC08148 promotes the caveola-mediated endocytosis of Zika virus through upregulating transcription of Src.

Long non-coding RNAs (lncRNAs) represent a new group of host factors involved in viral infection. Current study identified an intergenic lncRNA, LINC08148, as a proviral factor of Zika virus (ZIKV) and Dengue virus 2 (DENV2). Knockout (KO) or silencing of LINC08148 decreases the replication of ZIKV and DENV2. LINC08148 mainly acts at the endocytosis step of ZIKV but at a later stage of DENV2. RNA-seq analysis reveals that LINC08148 knockout downregulates the transcription levels of five endocytosis-related genes including AP2B1, CHMP4C, DNM1, FCHO1, and Src. Among them, loss of Src significantly decreases the uptake of ZIKV. Trans-complementation of Src in the LINC08148KO cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the Src transcription through associating with its transcription factor SP1. This work establishes an essential role of LINC08148 in the ZIKV entry, underscoring a significance of lncRNAs in the viral infection. IMPORTANCE: Long non-coding RNAs (lncRNAs), like proteins, participate in viral infection. However, functions of most lncRNAs remain unknown. In this study, we performed a functional screen based on microarray data and identified a new proviral lncRNA, LINC08148. Then, we uncovered that LINC08148 is involved in the caveola-mediated endocytosis of ZIKV, rather than the classical clathrin-mediated endocytosis. Mechanistically, LINC08148 upregulates the transcription of Src, an initiator of caveola-mediated endocytosis, through binding to its transcription factor SP1. This study identifies a new lncRNA involved in the ZIKV infection, suggesting lncRNAs and cellular proteins are closely linked and cooperate to regulate viral infection.

Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1.

Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain protein 2 (SUN2) linking cytoskeleton and nucleoskeleton in the flavivirus replication. CRISPR/Cas9-mediated knockout of SUN2, but not SUN1, significantly reduces the replication of Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV). In contrast, SUN2 does not affect the infection of non-flaviviridae RNA viruses. All three regions of SUN2 are required for its proviral effect. Mechanistically, SUN2 facilitates rearrangement of cytoskeleton and formation of replication organelles induced by viral infection, and hence promotes viral RNA synthesis. SUN2 is required for the interaction between cytoskeleton actin and ZIKV nonstructural protein 1 (NS1). Expression of dominant negative Nesprin-1 and Nesprin-2, which connect SUN2 to cytoskeleton proteins, alleviates the interaction between actin and NS1 and reduces viral replication levels. In a neonatal mouse infection model, SUN2 knockout dramatically alleviates the in vivo ZIKV replication and development of neuropathology. This work elucidates that recruitment of cytoskeleton proteins by flavivirus is coordinated by nuclear membrane proteins SUN2 and Nesprins, providing evidence for a link between nuclear membrane proteins and flavivirus infection.

Association of obstructive sleep apnea with cardiometabolic diseases and cardiovascular mortality.

BACKGROUND: Obstructive sleep apnea (OSA) is one of the leading respiratory disorders, increasing the risk of cardiometabolic diseases. In the study, we investigated the association between OSA and the risk of cardiometabolic diseases and all-cause and cardiovascular mortality in adults. METHODS: Participants were enrolled in the National Health and Nutrition Examination Survey. The baseline covariates were compared between participants with and without OSA status. Multivariable logistic regression was performed to explore the association between OSA and cardiometabolic diseases, while Cox proportional regression was performed for all-cause and cardiovascular mortality. RESULTS: OSA status was positively associated with higher risks of cardiometabolic diseases, including hypertension (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.14-1.45; p < 0.001), diabetes (OR 1.46, 95% CI 1.22-1.76; p < 0.001), and cardiovascular diseases (OR 1.29, 95% CI 1.08-1.54; p = 0.006) after adjusting for numerous covariates. However, no associations of OSA with all-cause or cardiovascular mortality were observed. CONCLUSION: OSA was associated with a higher risk of hypertension, diabetes, and cardiovascular diseases, but had no significant association with all-cause or cardiovascular mortality in adults.

Triglyceride Glucose Index Was a Predictor of 6-Month Readmission Caused by Pulmonary Infection of Heart Failure Patients.

Objectives: Insulin resistance is associated with the prognosis of heart failure (HF) patients. The triglyceride glucose (TyG) index is a simple marker of insulin resistance. However, it remains unclear whether the TyG index is associated with the incidence of readmission in patients with HF. Methods: We enrolled 901 patients with completed records on serum triglyceride and glucose in our study. The TyG index was calculated as log (fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2). There were 310 cases of readmission and the average TyG index was 7.8 ± 0.7. Restricted cubic spline was fitted to explore the linearity of TyG index associating with 6-month readmission of HF patients. Logistic regression analysis was performed to explore the association between TyG index quartile and the incidence of 6-month readmission. Results: Only the 6-month readmission was significantly different among TyG quartiles, and it was the highest (41.9%) in the lowest quartile (ranging 6.17∼7.36). the TyG index was nonlinearly associated with 6-month readmission (p for nonlinearity = 0.009), with the lower level of TyG index increasing the risk of 6-month readmission. Besides, multivariable logistic analysis showed that the lowest TyG quartile was associated with a higher incidence of 6-month readmission in the unadjusted model (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.18-2.57; p=0.005), partially adjusted model (OR 1.82, 95%CI 1.22-2.72; p=0.004), and fully-adjusted model (OR 1.65, 95%CI 1.09-2.45; p=0.024). The association was consistent across gender and diabetes group. Conclusion: A lower TyG index independently increased the risk of 6-month readmission in HF patients, which could be a prognostic factor in heart failure.

Verbascoside protects from LPS-induced septic cardiomyopathy via alleviating cardiac inflammation, oxidative stress and regulating mitochondrial dynamics.

BACKGROUND: Verbascoside (VB), as an active component of multiple medicinal plants, has been proved to exert anti-oxidative, anti-aging and neuroprotective effects. This study was designed to investigate whether VB could play a cardioprotective role in septic heart injury. METHODS: Mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to induce sepsis. The treatment group received an intraperitoneally injection of VB (20 mg/kg) before LPS challenge. Transthoracic echocardiography, ELISA, immunofluorescence, and qPCR were performed to assess the effect of VB on heart function, oxidative stress, inflammation and apoptosis. Transmission electronic microscopy and immunoblotting were used to evaluate the mitochondrial morphology and biogenesis of the septic heart. In vitro experiments were also performed to repeat above-mentioned assays. RESULTS: Compared with LPS group, the VB treatment group showed improved cardiac function in sepsis. VB alleviated oxidative stress and inflammatory cell infiltration, as well as cardiomyocyte apoptosis. Specifically, VB could restore sepsis-induced mitochondrial alterations via regulating mitochondrial biogenesis. These results were also confirmed in in vitro experiments. CONCLUSION: Verbascoside could protected from sepsis-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and apoptosis, as well as promoting mitochondrial biogenesis.

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis.

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.

Neural Respiratory Drive Measured Using Surface Electromyography of Diaphragm as a Physiological Biomarker to Predict Hospitalization of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients. METHODS: COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated. RESULTS: We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO2, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO2/FiO2in the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO2/FiO2, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004-1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort. CONCLUSIONS: The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.

Association between the -1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis.

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being -1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between -1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for -1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the -1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169-4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879-4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787-1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737-1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the -1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.