Serum adropin level is associated with endothelial dysfunction in patients with obstructive sleep apnea and hypopnea syndrome.

OBJECTIVE: Adropin is a recently discovered peptide hormone that plays a vital role in metabolism and cardiovascular-cerebrovascular function. The purpose of this study is to investigate the role of circulating adropin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and further determine the relationship between serum adropin concentration and endothelial dysfunction in patients with OSAHS. METHODS: Forty polysomnography-diagnosed patients with OSAHS and 21 age and sex-matched healthy controls were enrolled in the current study. Serum adropin level, endothelial function parameters including flow-mediated dilatation (FMD) of brachial artery, endothelin-1 (ET-1), and nitric oxide (NO) were measured in all participants. RESULTS: Serum adropin levels were significantly lower in patients with OSAHS compared to the control subjects. FMD was lower and serum ET-1 levels were higher in patients with OSAHS compared to control subjects. No significant difference was seen in serum NO levels between the two groups. Multivariate linear regression analysis revealed that serum adropin level was positively associated with FMD and negatively correlated with AHI. Additionally, serum adropin levels were lower in patients with OSAHS who had endothelial dysfunction compared with those patients without endothelial dysfunction. The receiver operating characteristic (ROC) analysis showed that area under the curve (AUC) for serum adropin in predicting endothelial dysfunction status in patients with OSAHS was 0.815 (95% CI 0.680-0.951, p = 0.001). The cutoff value of serum adropin level was less than 235.0 pg/mL, which provided the sensitivity and specificity of 81% and 75%, respectively, for the detection of endothelial dysfunction in patients with OSAHS. CONCLUSION: Lower circulating adropin levels are closely associated with endothelial dysfunction in patients with OSAHS. Circulating adropin level may serve as an early biomarker to predict the development of endothelial dysfunction before the emergence of clinical symptoms in patients with OSAHS.

Toll-like receptor-4 deficiency alleviates chronic intermittent hypoxia-induced renal injury, inflammation, and fibrosis.

BACKGROUND: Obstructive sleep apnea (OSA)-associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered renal damage. This study aims to investigate the role of toll-like receptor-4 (TLR4) in underlying mechanism involved chronic intermittent hypoxia (CIH)-induced renal damage. METHODS: C57BL/6J mice with normal TLR4 (TLR4 WT) or deficient TLR4 (TLR4 KO) were divided into four groups and exposed to normal air (NA) and CIH: TLR4 WT + NA, TLR4 KO + NA, TLR4 WT + CIH, and TLR4 KO + CIH. CIH lasted for 8 h/day and 7 days/week for 6 weeks. Renal injury and inflammation were evaluated by histology and ELISA. Renal tubular apoptosis, macrophages, and fibroblasts recruitment were determined by TUNEL assay, immunofluorescence, and western blot. RESULTS: In response to CIH, TLR4 deficiency alleviated renal histological injury, renal dysfunction, and fibrosis. TLR4 deficiency ameliorated renal dysfunction (serum BUN and creatinine) and tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL, and western blot of apoptotic protein (caspase-3, c-caspase-3, and Bax/Bcl-2 ratio). Furthermore, we also found TLR4 deficiency abrogated CIH-induced macrophages (CD68) and fibroblasts (α-SMA) recruitment, further reducing expression of extra-cellular matrix protein (collagen I and collagen IV) and inflammatory cytokines release (IL-6, TNF-α, and MCP-1). Finally, we used immunohistochemistry to demonstrate that TLR4 deficiency attenuated increased expression of MyD88 and NF-kB p65 after CIH treatment. CONCLUSIONS: Our data suggest that TLR4 plays a vital role in CIH-induced renal injury, inflammation and fibrosis, and inhibition of TLR4 probably provides a therapeutic potential for CIH-induced kidney damage.

Acute Q fever pneumonia diagnosed by metagenomic next-generation sequencing.

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.