Alterations of oral microbiota in patients with obstructive sleep apnea-hypopnea syndrome treated with continuous positive airway pressure: a pilot study.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for cardiovascular diseases, including hypertension. In our previous study, it was demonstrated that oral microbiota alteration in patients with OSAHS, particularly in the genera Aggregatibacter and Porphyromonas, may influence the development of hypertension. Continuous positive airway pressure (CPAP) is the main therapy for OSAHS and OSAHS-associated hypertension. However, the role of oral microbiota post CPAP treatment remains unknown. METHODS: We conducted 16S rDNA pyrosequencing and bioinformatic analyses to compare the bacterial composition of oral specimens from patients with OSAHS before and after overnight CPAP treatment. RESULTS: This approach enabled a relatively comprehensive description of oral microbiota, with decreases in Gemella and increases in Staphylococcus, f_Lachnospiraceae, Parabacteroides, and f_Ruminococcaceae after CPAP treatment. CONCLUSION: Alteration of oral microbiota may shed new insight on the underlying pathogenesis of OSAHS-associated hypertension.

Dexamethasone Versus Prednisone or Prednisolone for Acute Pediatric Asthma Exacerbations in the Emergency Department: A Meta-Analysis.

OBJECTIVE: This study evaluates the efficacy and tolerability of dexamethasone (DEX) as an alternative to prednisone/prednisolone (PRED) for the treatment of pediatric asthma exacerbations in emergency department (ED). METHODS: Fixed-effects meta-analyses of selected endpoints were performed by using data taken from relevant studies identified by following a priori eligibility criteria after a comprehensive literature search in several electronic databases. RESULTS: Data from 10 studies (3208 pediatric asthma patients [1616 DEX treated and 1592 PRED treated], 4.77 years [95% confidence interval, 3.80-5.56 years], 63% [57.76%-62.68%] males) were used. Risk of vomiting drug was significantly lower in DEX group than in PRED group (risk ratio, 0.29 [0.18-0.48]; P ˂ 0.00001). Emergency department stay between DEX and PRED treated patients was statistically different (0.16 [0.03-0.40] hours; P = 0.02) but may not be clinically meaningful. The number of ß-agonist therapies received by DEX- and PRED-treated patients was similar. Treatments with both DEX and PRED were associated with improvement in asthma status assessment scores, and there was no significant difference between the groups. There were also no differences between the groups in hospitalization rate, ED revisit rate, and hospital admission rate after relapse. CONCLUSIONS: Dexamethasone is a suitable alternative to PRED for the treatment of pediatric asthma exacerbation in ED.

Dynamic spatiotemporal expression pattern of limbal stem cell putative biomarkers during mouse development.

Limbal stem cells (LSCs), a subpopulation of limbal epithelial basal cells, are crucial to the homeostasis and wound healing of corneal epithelium. The identification and isolation of LSCs remains a challenge due to lack of specific LSCs biomarkers. In this study, Haematoxylin-eosin (HE), 4', 6-diamidino-2-phenylindole (DAPI), and immunohistochemistry (IHC) stains were performed on the pre- and post-natal limbus tissues of mice which has the advantage of more controllable in term of sampling age relative to human origin. By morphological analysis, we supported that there is an absence of the Palisades of Vogt (POV) in the mouse. The development of prenatal and neonatal cornea was dominated by its stroma, whereas after eyelids opened at P14, the corneal epithelial cells (CECs) quickly go stratification in response to the liquid-air interface. Based on IHC staining, we found that the expression of LSCs putative biomarkers in limbal epithelial basal cells appeared in chronological order as follows: Vim = p63 > CK14 > CK15 (where = represents same time; > represents earlier), and in corneal epithelial basal cells were weakened in chronological order as follows: Vim > p63 > CK15 > CK14, which might also represent the stemness degree. Furthermore, the dynamic spatial expression of the examined LSCs putative biomarkers during mouse development also implied a temporal restriction. The expression of Vim in epithelial cells of mouse ocular surface occurred during E12-E19 only. The expression of CK15 was completely undetectable in CECs after P14, whereas the others putative molecular markers of LSCs, such as p63 and CK14, still remained weak expression, suggesting that CK15 was suitable to serve as the mouse LSCs biomarkers after P14. In this study, our data demonstrated the dynamic spatiotemporal expression pattern of LSCs putative biomarkers in mouse was age-related and revealed the time spectrum of the expression of LSCs in mouse, which adds in our knowledge by understanding the dynamic expression pattern of biomarkers of stem cells relate to maintenance of their stemness.

MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways.

BACKGROUND Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. RESULTS The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. CONCLUSIONS Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.

A review of the association between oral bacterial flora and obstructive sleep apnea-hypopnea syndrome comorbid with cardiovascular disease.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS), a common sleep disorder, has been shown to be an independent risk factor for cardiovascular disease (CVD). Recent studies have focused on the important roles of microorganisms in human health; for example, microorganisms are reportedly associated with obesity, metabolic disorders, and CVD. The number of oral bacteria in patients with OSAHS is considerably higher than that in healthy individuals, and infection with oral bacterial pathogens is associated with the development of CVD. However, whether changes in the oral microbiota mediate the development of OSAHS and CVD remains unknown. METHODS: Therefore, we attempted to review the association between changes in oral microbiota in patients with OSAHS and the development of CVD. RESULTS: Oral microbiota possibly acts via multiple pathways including direct invasion, platelet aggregation, immune response, inflammatory response, and oxidative stress response, leading to the development of CVD in patients with OSAHS. In particular, the strains Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia have demonstrated profound effects. OSAHS leads to changes in the oral bacterial flora and thus may facilitate the occurrence and development of CVD. CONCLUSION: We propose that the underlying mechanism of CVDs resulting from oral microbiota in patients with OSAHS should be elucidated in further studies.

Correction to: Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model.

In the article that appeared on Page: 341-348, Vol 23 (15 September 2018) of the Sleep and breathing [1], one error was discovered in Figure 3. The picture of Normoxia and CIH in 100X is the same one. The corrected version of Figure 3 is presented here.

ß-Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF-ß/Smad signaling pathway.

BACKGROUND: Benign airway stenosis is easily to recur as a result of hyperplastic airway granulation tissues. Our previous study proved that a Chinese drug, ß-elemene, could inhibit the proliferation of fibroblasts cultured from these tissues, which could decrease the recurrence rate of this disease. METHODS: To find out the mechanism for this effect, we first cultured normal human airway fibroblasts and human airway granulation fibroblasts with different concentrations of ß-elemene for the same time or the same dose of ß-elemene for different times to explore the dose/time-effect relationship between the drug and these cells. Then we used gene microarray to screen out the most important pathway by which the drug influenced human airway granulation fibroblasts. At last, we assessed the condition of this pathway in human airway granulation fibroblasts and verified the effect of this drug on this pathway. RESULTS: ß-Elemene inhibited the proliferation of human airway granulation fibroblasts in a dose but no time-dependent manner and did not affect normal human airway fibroblasts. Affecting the expression of transforming growth factor ß (TGF-ß)/Smad pathway may be the key mechanism for this effect. This pathway was activated in human airway granulation fibroblasts and ß-elemene inhibited it in a dose-dependent manner. This effect was similar to the pathway inhibitor, SB431542, and exogenous TGF-ß could attenuate this effect. CONCLUSION: These results indicated that suppressing TGF-ß/Smad pathway was possibly the key mechanism by which ß-elemene inhibits the proliferation of human airway granulation fibroblasts. This pathway may be a promising target to treat benign airway stenosis.

Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities.

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3-4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.

Management of Persistent Air Leaks Using Endobronchial Autologous Blood Patch and Spigot Occlusion: A Multicentre Randomized Controlled Trial in China.

BACKGROUND: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. OBJECTIVE: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. METHODS: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. RESULTS: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. CONCLUSION: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.

Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model.

PURPOSE: Obstructive sleep apnea (OSA) is associated with renal impairs. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis and autophagy. The present study aims to evaluate the effect of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of OSA. MATERIALS AND METHODS: Mice were randomly allocated to normoxia, CIH, and CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12 weeks. Mice in the CIH+telmisartan group received telmisartan administration. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax and cleaved caspase-3 were conducted for evaluating apoptosis in kidney tissue. While the autophagy-related proteins, beclin-1 and LC3, were also observed via western blotting. RESULTS: The percentage of apoptotic cell in the CIH group was significantly higher than that of normoxia group; meanwhile, Bax and cleaved caspase-3 protein levels were increased in the CIH group than those of normoxia group (all p < 0.05). Compared with the normoxia group, mice in the CIH group had greater autophagy-related proteins (beclin-1 and LC3) expression. When compared to the CIH group, both the renal apoptosis and autophagy in the CIH+telmisartan group were decreased. CONCLUSION: The CIH accelerates renal apoptosis and autophagy levels. Telmisartan ameliorating those levels suggests that it might prevent renal impairs from the CIH in OSA patients.

Time Series Multiple Channel Convolutional Neural Network with Attention-Based Long Short-Term Memory for Predicting Bearing Remaining Useful Life.

This paper proposes two deep learning methods for remaining useful life (RUL) prediction of bearings. The methods have the advantageous end-to-end property that they take raw data as input and generate the predicted RUL directly. They are TSMC-CNN, which stands for the time series multiple channel convolutional neural network, and TSMC-CNN-ALSTM, which stands for the TSMC-CNN integrated with the attention-based long short-term memory (ALSTM) network. The proposed methods divide a time series into multiple channels and take advantage of the convolutional neural network (CNN), the long short-term memory (LSTM) network, and the attention-based mechanism for boosting performance. The CNN performs well for extracting features from data with multiple channels; dividing a time series into multiple channels helps the CNN extract relationship among far-apart data points. The LSTM network is excellent for processing temporal data; the attention-based mechanism allows the LSTM network to focus on different features at different time steps for better prediction accuracy. PRONOSTIA bearing operation datasets are applied to the proposed methods for the purpose of performance evaluation and comparison. The comparison results show that the proposed methods outperform the others in terms of the mean absolute error (MAE) and the root mean squared error (RMSE) of RUL prediction.

Effects of Maillard reaction products in a glucose-glycine alcoholic solution on antioxidative and antimutagenic activities.

BACKGROUND: Marinating meat with alcohol, such as wine and beer, is a common culinary practice in cultures worldwide. In this study we use a model marination solution comprising 0.2  mol L-1 glucose-0.2  mol L-1 glycine buffered to pH 4.3 containing either 0 or 50% ethanol and mimicked the cooking process by heating for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous ion chelating ability), and free radical neutralization ability generated from 1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) were determined. Ames testing was performed. RESULTS: Results indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative assays in a dose-dependent manner from 0.16 to 10.00 mg mL-1 . However, MRPs from the alcoholic model were superior. In Ames testing, MRPs from both models are neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate. However, MRPs from the alcoholic model exhibited a higher inhibitory effect on the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous model. This result is consistent with the observation that MRPs with higher antioxidative capacity exhibit superior antimutagenic activity, suggesting that there are more different products in the alcoholic model. CONCLUSION: Our results add to the current knowledge about the antioxidative and antimutagenic properties of MRPs arising when food is cooked in the presence of ethanol. © 2018 Society of Chemical Industry.

Erythropoietin levels in patients with sleep apnea: a meta-analysis.

Currently available data regarding the blood levels of erythropoietin (EPO) in sleep apnea (SA) patients are contradictory. The aim of the present meta-analysis was to evaluate the EPO levels in SA patients via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. EPO levels in SA group and control group were extracted from each eligible study. Weight mean difference (WMD) or Standard mean difference (SMD) with 95% confidence interval (CI) was calculated by using fixed-effects or random effect model analysis according to the degree of heterogeneity between studies. A total of 9 studies involving 407 participants were enrolled. The results indicated that EPO levels in SA group were significantly higher than that in control group (SMD 0.61, 95% CI 0.11-1.11, p = 0.016). Significantly higher EPO levels were found in patients with body mass index <30 kg/m2, and cardiovascular complications in the subsequent subgroup analysis (both p < 0.05). High blood EPO levels were found in SA patients in the present meta-analysis.

Assessing causality between obstructive sleep apnea with the dyslipidemia and osteoporosis: a Mendelian randomization study.

Purpose: This study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques. Methods: Utilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348). Results: The MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis. Conclusion: The study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.

Effect of Telmisartan on local cardiovascular oxidative stress in mouse under chronic intermittent hypoxia condition.

OBJECTIVE: The objective of this study is to explore the protective effect of an angiotensin receptor blocker (ARB) on local cardiovascular angiotensin II (AngII) and oxidative stress markers such as malondialdehyde (MDA), NADPH oxydase p47(phox), and 8-hydroxy-2'-deoxyguanosine/8-hydroxyguanosine (8-OHdG/8-OHG) of mice that had chronic intermittent hypoxia (CIH). METHODS: Thirty-two healthy male C57B6J mice were randomly divided into four groups: CIH (12 weeks of CIH), ARB (CIH+Telmisartan), air control (room air delivery), and blank control (no treatment). AngII, p47(phox), and 8-OHdG/8-OHG were detected in mouse cardiocytes by immunohistochemistry. MDA was measured with the thiobarbituric acid method. MEASUREMENTS AND RESULTS: The highest AngII levels occur in the ARB treatment group (P < 0.05), followed by the CIH group (which was higher than the two control groups; P = 0.000). The levels of p47(phox) were statistically higher in the CIH group than in the other groups (P = 0.000) and lower in the ARB group (but still higher than in the two control groups, P = 0.000). The levels of 8-OHdG/8-OHG were the highest in the CIH group (P < 0.05), followed by the ARB group (which was higher than the two control groups, P = 0.000). The levels of MDA in the myocardial homogenate of mice were the highest in the CIH group (P = 0.000). CONCLUSIONS: Based on the above results, it can be concluded that Telmisartan may protect mouse cardiocytes from oxidative stress damage due to CIH.

Correlation between morphological features of the anterior cruciate ligament: A quantitative study using a porcine model.

Introduction: Knowledge of the morphological features of the anterior cruciate ligament (ACL) is critical for accurate reconstruction of it. This study aimed to explore the quantitative correlations among different morphological features of the ACL, thus to provide useful information for improving anatomical reconstruction techniques and designing artificial ligaments. Methods: 19 porcine knees were fixed at full extension using 10% formalin and were dissected to expose the ACL. ACL lengths were measured using a caliper. Mid-substances of the ACL were cut and scanned using X-ray microscopy, and the cross-sectional area (CSA) was measured at the isthmus. Margins of direct and indirect bone insertion sites were distinguished and marked. Measurements were performed on digital photographs to obtain the areas of bone insertions. Statistical analysis using nonlinear regression was used to identify potential correlations among the measurements. Results: The results showed that the CSA at the isthmus was significantly correlated with the total area of the bone insertion sites and the area of tibial insertion. The area of the tibial insertion was significantly correlated with the area of its direct insertion site. In contrast, the area of the femoral insertion was significantly correlated with the area of its indirect insertion site. The area of the indirect tibial insertion showed a weak correlation with the length of ACL, whereas the length of the ACL was not able to predict or be predicted by any other parameters. Conclusions: The CSA at the ACL isthmus is more representative for assessing the size of the ACL. However, ACL length has little correlation with the CSA of the isthmus or bone insertion sites, and thus should be evaluated independently for ACL reconstruction.

Advances and perspectives of nanozymes in respiratory diseases.

Respiratory diseases, some of the most common human diseases, have become a prominent public health and medical problem. Feasible treatment and prevention strategies are still required to prepare for respiratory emergencies. Nanotechnology has provided new technological conceptions in respiratory disease-related applications and inspired the exploration of various multifunctional nanomaterials. Among them, "nanozymes" with enzyme-like activities and nanomaterials' physicochemical properties may propel the development in this field. Over the past few decades, nanozymes have distinguished themselves in the fields of biosensing, biomedicine, imaging, and environmental protection due to their outstanding enzymatic properties, reactive oxygen species-regulating mechanism, high stability, modifiability, mass production, and others. Herein, this article reviews the research progress of nanozymes in diagnosing, treating, and preventing respiratory diseases, hoping to bring new ideas for promoting nanozymes and their beneficial applications in respiratory diseases.

Immunoregulatory Effect of Short-Chain Fatty Acids from Gut Microbiota on Obstructive Sleep Apnea-Associated Hypertension.

The intestine is the largest bacterial ecosystem and immune response organ of the human body. The microbiota regulates the metabolic and immune functions of the host through their metabolites. Short-chain fatty acids (SCFAs) are part of the metabolites of the gut microbiota (GM), providing energy to intestinal epithelial cells and regulating the immune system. A decrease in SCFA-producing bacteria, imbalanced effector T-helper cells (Th cells), and increasing corresponding inflammatory cytokine were found in both animal models and clinical patients with obstructive sleep apnea (OSA) and hypertension (HTN). Intervention with probiotics, prebiotics, or postbiotics in animal models simulating OSA-associated HTN restored blood pressure to normal, which allows the hypothesis that GM are involved in the pathophysiology of OSA-induced HTN patients through their metabolites' SCFAs; however, the exact regulatory mechanism is not completely clear. This review describes the potential mechanisms of SCFAs, a major metabolite of the GM, in the pathology of OSA-induced HTN, from the perspective of immune system regulation in the available studies.

Disturbances of the Gut Microbiota, Sleep Architecture, and mTOR Signaling Pathway in Patients with Severe Obstructive Sleep Apnea-Associated Hypertension.

Intermittent hypoxia and sleep fragmentation are pathophysiological processes involved in obstructive sleep apnea (OSA) which affect gut microbiota, sleep architecture, and mTOR signaling pathway. However, the involvement of these elements in the pathogenesis mechanism of OSA-associated hypertension remains unclear. Therefore, this study investigated whether the OSA-associated hypertension mechanism is regulated by the gut microbiota and mTOR signaling pathway. Patients were diagnosed by polysomnography; their fecal samples were obtained and analyzed for their microbiome composition by 16S ribosomal RNA pyrosequencing and bioinformatics analysis. Transcript genes on fasting peripheral blood mononuclear cells (PBMCs) were examined using Illumina RNA-sequencing analysis. Totally, we enrolled 60 patients with severe OSA [without hypertension (n = 27) and with hypertension (n = 33)] and 12 controls (neither OSA nor hypertension). Results revealed that severe-OSA patients with hypertension had an altered gut microbiome, decreased short-chain fatty acid-producing bacteria (P < 0.05), and reduced arginine and proline metabolism pathways (P=0.001), compared with controls; also, they had increased stage N1 sleep and reduced stages N2 and N3 sleep accompanied by repeated arousals (P < 0.05). Analysis of PBMCs using the Kyoto Encyclopedia of Genes and Genomes database showed that the mTOR signaling pathway (P=0.006) was the most important differential gene-enriched pathway in severe-OSA patients with hypertension. Our findings extend prior work and suggest a possibility that the regulation of the mTOR signaling pathway is involved in developing OSA-associated hypertension through its interaction with the disturbance of the gut microbiome and sleep architecture.

Transcriptome analysis identifies the differentially expressed genes related to the stemness of limbal stem cells in mice.

Limbal stem cells (LSCs) reside in the basal layer of limbal epithelial cells (LECs). They are crucial for maintenance of corneal epithelium homeostasis and corneal wound healing. Their stemness is determined by their gene expression pattern. Despite of several positive identifiers have been reported, the unique biomarker for LSCs still remain elusive. Differentially expressed genes (DEGs) between stem cells and differentiated cells affect the fate of stem cells via specific signaling pathway. In order to understand the DEGs in the LSCs, RNA-seq was firstly conducted using a mouse model. A total of 1907 up-regulated DEGs and 395 down-regulated DEGs were identified in the limbus (L) compared to central cornea (CC) and conjunctiva (Cj). Reliability of the expression of genes from RNA-seq analysis was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. The expression pattern of putative biomarkers was considered to be age-related. In up-regulated DEGs GO analysis, 570 gene ontology (GO) terms were significantly enriched. Five groups of genes related with biological processes from these significantly enriched GO terms comprised ionic transport, regulation of tissue development, muscle contraction, visual perception, and cell adhesion, which were clustered as a weighted similar network. Whereas, in down-regulated DEGs GO analysis, 61 GO terms were significantly enriched and only one group of ATP biosynthesis and metabolic process were clustered. Furthermore, we identified 55 signaling pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG) database based on up-regulated genes and 14 KEGG pathways based on down-regulated genes. In this study, we provide a landscape of the expression of putative LSCs biomarkers and stemness-related signaling pathways in a mouse model. Our findings could aid in the identification of LSC niche factors that may be related to the stemness of the LSCs.