Circular RNA_0025843 Alleviated Cigarette Smoke Extract Induced Bronchoalveolar Epithelial Cells Ferroptosis.

Purpose: Circular RNA (circRNA) plays an important role in various biological processes. However, their functions in cigarette smoke extract (CSE) induced human normal lung epithelial cells (BEAS-2B) injury remain vague. The study aimed to explore circRNA expression profiles and reveal their potential roles in CSE-treated BEAS-2B cells. Methods: 5% CSE exposure for 24 hours were used to build the BEAS-2B cells ferroptosis model. Differentially expressed circRNAs (DECs) were identified by next-generation RNA sequencing. Six randomly selected DECs were validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis were conducted to clarify the potential functions of the DECs. Furthermore, the role of hsa_circ_0025843 in CSE-related BEAS-2B cells ferroptosis was confirmed. Results: 5% CSE exposure induced BEAS-2B cells ferroptosis. Fifty-one up-regulated cirRNAs and 80 down-regulated circRNAs were revealed in CSE-treated BEAS-2B cells. Hsa_circ_0003461, hsa_circ_0007548, hsa_circ_0025843, hsa_circ_0068896, hsa_circ_0005832, and hsa_circ_0053378 were selected randomly to validate the reliability of next-generation RNA sequencing by qRT-PCR. After KEGG pathway analysis, DECs were found to participate in the process of EGFR tyrosine kinase inhibitor resistance and glycerophospholipid metabolism. The knockdown of hsa_circ_0025843 significantly alleviated CSE-induced BEAS-2B cells ferroptosis. Conclusion: The study indicated the circRNA expression profiles in CSE-treated BEAS-2B cells. Hsa_circ_0025843 alleviated CSE induced BEAS-2B cells ferroptosis, which might be a potential therapeutic target of CSE related lung injury.

The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury.

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Expression alteration of serum exosomal circular RNAs in obstructive sleep apnea patients with acute myocardial infarction.

PURPOSE: Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction (AMI). However, circRNAs expression pattern in obstructive sleep apnea (OSA) with AMI remains unknown. The aim was to investigate circRNAs expression alteration in serum exosomes derived from OSA patients with AMI. METHODS: The serum exosomal circRNAs profile of three healthy subjects, three OSA without AMI and three OSA with AMI were analyzed using high-throughput sequencing. Bioinformatic analyses were carried out to assess potential core circRNAs and functional analyses were conducted to study biological functions. RESULTS: Compared to healthy subjects, there were 5225 upregulated and 5798 downregulated circRNAs in exosomes from OSA with AMI patients. And our study also identified 5210 upregulated and 5813 downregulated circRNAs in OSA with AMI patients compared to OSA without AMI. The differential expression of 2 circRNAs (hsa_circRNA_101147, hsa_circRNA_101561) between healthy subjects and OSA without AMI, and 4 circRNAs (hsa_circRNA_101328, hsa_circRNA_104172, hsa_circRNA_104640, hsa_circRNA_104642) between healthy subjects and OSA with AMI were confirmed by qRT-PCR. In addition, we demonstrated that miR-29a-3p targeted hsa_circRNA_104642 directly. CONCLUSIONS: This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets.

The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury.

PURPOSE: Obstructive sleep apnea (OSA) is related to increased risk of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS). METHODS: AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis. RESULTS: The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of ferroptosis and ERS. Inhibition of ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS. CONCLUSIONS: Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.

Assessment of bone mineral density and bone metabolism in young men with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Hypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age). METHODS: Consecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, ß-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA). RESULTS: The population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO2 (ß = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1-L4 BMD, LaSO2 (ß = 0.304, p = 0.037), BMI (ß = 0.393, p = 0.008) for femur neck BMD and BMI (ß = 0.720, p = 0.002) for hip total BMD. CONCLUSIONS: Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Generation of cylindrical vector vortex beams using a biconical glass rod.

This Letter proposes a biconical glass rod for generating a cylindrical vector vortex (CVV) beam. Based on the principle of total internal reflection and the cylindrical symmetry structure of the glass rod, a circularly polarized incident beam with a constant phase distribution can be converted into a CVV beam, which possesses both a spatially inhomogeneous polarization and a helical phase distribution. The polarization azimuth of the CVV beam can be tuned with the aid of a polarization rotator composed of two cascade half-wave plates. The design theory is presented, and the feasibility of the design is demonstrated experimentally.

Impact of upper airway configuration on CPAP titration assessed by CT during Müller's maneuver in OSA patients.

PURPOSE: Continuous positive airway pressure (CPAP) is the current gold-standard treatment for moderate to severe obstructive sleep apnea (OSA), and upper airway anatomy plays an increasingly important role in evaluating the efficacy of CPAP therapy. The aim of this observational study was to investigate the influence of upper airway anatomy on CPAP titration in OSA patients assessed by computed tomography (CT) during Müller's maneuver. METHODS: Consecutive patients under investigation for OSA by undergoing polysomnography and CT scan of the upper airway while awake were enrolled. Successful full-night manual titration was performed to determine the optimal CPAP pressure level for OSA patients in supine position using a nasal mask. RESULTS: A total of 157 subjects (134 males and 23 females) were included. Both apnea-hypopnea index (AHI) and LaSO2 significantly correlated with CPAP titration level, upper airway length (UAL), distance from mandibular plane to hyoid bone (MPH), and neck circumference (all p < 0.05). There were significant positive correlations between CPAP titration level and UAL (r = 0.348, p = 0.000) and MPH (r = 0.313, p = 0.002). Stepwise multiple linear regression analyses were performed to evaluate the independent predictors of AHI, LaSO2, and CPAP titration level. CPAP titration level was identified as an independent explanatory variable for AHI and LaSO2 after adjustment for confounders. Multiple linear regression analyses also indicated that body mass index (BMI) and UAL were independently associated with CPAP titration level (all p < 0.05). CONCLUSIONS: Upper airway abnormalities combined with anthropometric parameters play important roles in CPAP titration for OSA patients, providing additional insight into the factors influencing OSA treatment strategies. UAL and BMI should be taken into consideration when choosing CPAP titration level to improve CPAP compliance.

Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) has raised world concern for global epidemic since December, 2019. Limited data are available for liver function in COVID-19 patients. We aimed to investigate the risk factors related to liver injury in the COVID-19 patients. METHODS: A retrospective study was performed in non-ICU Ward at Jinyintan Hospital from February 2, 2020 to February 23, 2020. Consecutively confirmed COVID-19 discharged cases were enrolled. The clinical characteristics of patients with liver injury and without liver injury were compared. RESULTS: A total of 79 COVID-19 patients were included. 31.6%, 35.4% and 5.1% COVID-19 patients had elevated levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin respectively. Median value of ALT, AST and bilirubin for entire cohort was 36.5 (17.5 ~ 71.5) U/L, 34.5 (25.3 ~ 55.3) U/L and 12.7 (8.1 ~ 15.4) mmol/L respectively. There were no significant differences in age, previous medical history and symptoms between the two groups. Males were more likely to have liver injury when infected with COVID-19 (P < .05); compared with patients without liver injury, patients with liver injury had increased levels of white blood cell counts, neutrophils, CRP and CT score (P < .05) and had a longer length of stay (P < .05). Logistic regression analyses suggested that the extent of pulmonary lesions on CT was a predictor of liver function damage (P < .05). CONCLUSIONS: Liver injury is common in non-ICU hospitalized COVID-19 patients. It may be related to systemic inflammation. Intense monitoring and evaluation of liver function in patients with severe pulmonary imaging lesions should be considered.

The association between glycometabolism and nonalcoholic fatty liver disease in patients with obstructive sleep apnea.

PURPOSE: Growing evidence has revealed that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes. This study aimed to assess the association between glycometabolism and NAFLD in patients with obstructive sleep apnea (OSA). METHODS: Patients with suspected OSA were enrolled consecutively and then underwent polysomnography, liver ultrasound, and biochemical measurements. Logistic regressions were used to identify factors associated with NAFLD. RESULTS: In total, 415 patients were included. The prevalence of NAFLD in the non-OSA, mild OSA, moderate OSA, and severe OSA groups was 37.21%, 69.09%, 68.34%, and 78.08%, respectively. Stepwise logistic regression suggested that percentage of total sleep time spent with oxygen saturation of < 90% (TS90), lowest oxygen saturation (LaSO2), and homeostatic model assessment of insulin resistance (HOMA-IR) were independently associated with NAFLD in all subjects, after adjusting for confounders (odds ratio [OR] = 1.037, p = 0.014; OR = 1.056, p = 0.004; OR = 0.732, p = 0.009; respectively). TS90, LaSO2, and HOMA-IR were also independent predictors for NAFLD in patients with mild and moderate OSA, whereas TS90, LaSO2, and ODI were independent predictors for NAFLD in patients with severe OSA. CONCLUSIONS: There is a relationship between OSA and NAFLD, and the combination of disordered glycometabolism and intermittent hypoxia may act as a "two hit" mechanism to promote the development of NAFLD. Furthermore, intermittent hypoxia alone was an independent predictor for NAFLD in severe OSA patients.

Assessment of Upper-Airway Configuration in Obstructive Sleep Apnea Syndrome With Computed Tomography Imaging During Müller Maneuver.

BACKGROUND: The purpose of this observational study was to investigate the relationship between upper-airway configuration assessed by CT imaging during the Müller maneuver state and the severity of obstructive sleep apnea syndrome (OSAS). METHODS: A total of 358 snoring subjects who underwent standard polysomnography and upper-airway configuration by using CT imaging were enrolled. According to the apnea-hypopnea index (AHI), subjects were classified into 4 groups: snoring group (simple snoring), AHI < 5; mild OSAS, 5 ≤ AHI < 15; moderate OSAS, 15 ≤ AHI < 30; and severe OSAS, AHI ≥ 30. We also divided the upper airway into 3 parts, named the nasopharynx, oropharynx, and hypopharynx, from the CT scan and evaluated the minimal cross-sectional area (mCSA) and the shape of each airway level and calculated upper-airway length and distance from mandibular plane to hyoid bone (MPH). RESULTS: Multivariate logistic stepwise regression analysis identified body mass index (BMI), mCSA of nasopharynx, upper-airway length, and MPH as risk factors for the severity of OSAS. When subdivided for BMI and sex, upper-airway length was a risk factor for OSAS in non-obese (BMI < 27 kg/m2) and male subjects, and MPH was a risk factor only in obese (BMI ≥ 27 kg/m2) subjects. Meanwhile, mCSA of nasopharynx was significantly associated with the severity of OSAS independent of BMI. CONCLUSIONS: Subjects with severe OSAS have more significant abnormalities of the upper airway. Obesity, mCSA of nasopharynx, upper-airway length, and MPH may contribute to the severity of OSAS. Obesity and sex should be taken into account when evaluating the abnormalities of upper-airway anatomy in snorers and patients with OSAS.

[Relationship between obstructive sleep apnea-hypopnea syndrome and high sensitivity C-reactive protein in non-obese subjects].

OBJECTIVE: To evaluate the relationship between high sensitivity C-reactive protein (hs-CRP) level and the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) in non-obese patients. METHODS: A total of 65 patients with suspected OSAHS were recruited. Those with a history of cardiovascular or cerebrovascular events, arterial hypertension, chronic obstructive pulmonary disease, diabetes mellitus and smoking were excluded. All subjects were examined by polysomnography. Subjects with an apnea-hypopnea index (AHI) ≥ 5 were considered to have OSAHS. They were divided into mild, moderate and severe OSAHS groups and those with an AHI < 5 were accepted into the control group. The serum level of hs-CRP, a biomarker for cardiovascular disease, was measured with peripheral venous blood samples. RESULTS: There were 53 males and 12 females with a mean age 44.3 ± 12.2 years and a body mass index (BMI) <25 kg/m(2). The serum levels of hs-CRP were significantly higher in OSAHS patients than those of the controls (geometric mean [95% confidence interval] 0.416 [0.288-0.600] vs 0.749 [0.559-1.003] mg/L, P < 0.05). Mean levels of hs-CRP did not differ between the group with mild-to-moderate OSAHS and the control group. However, the severe OSAHS group had a higher level of hs-CRP than the control group (P = 0.004). A significant positive relationship existed between hs-CRP and AHI (r = 0.407, P = 0.001) . According to stepwise multivariate analysis, only AHI was a reliable predictor for elevated serum level of hs-CRP among all these related factors (R(2) = 0.166, P = 0.001). CONCLUSION: The severity of OSAHS is associated with an elevated serum level of hs-CRP in non-obese patients.