Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

A study on pulmonary function in children with obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: To investigate the pulmonary function of children with obstructive sleep apnea syndrome. METHODS: A total of 328 children aged 3 to 12 years old who were evaluated for a sleep disorder from January 2022 to June 2023 were selected as the observation group, classified into mild, moderate, and severe categories based on the apnea hypopnea index. The number of children with mild, moderate, and severe obstructive sleep apnea is 228, 62, and 28 respectively. Additionally, 126 healthy individuals aged 3 to 13 years old undergoing health examinations during the same period were selected as the control group. All subjects underwent sleep respiratory monitoring, pulmonary function tests, and impulse oscillometry. Comparative analysis was performed on pulmonary function indices (forced vital capacity, maximum ventilation, inspiratory capacity, total lung capacity, and inspiratory reserve volume), and respiratory impedance indices (resonant frequency, total respiratory impedance, viscous resistance at 5 Hz, 20 Hz, and 35 Hz). Pulmonary function indices were also compared among patients in the observation group with mild, moderate, and severe conditions. RESULTS: In the observation group, the FVC pre% of patients decreased by 10.5 ± 5.99 compared to the control group. The MVV of the control group decreased by 28.10 ± 2.22 compared to patients in the observation group. The IC of the control group decreased by 0.68 ± 0.44 compared to patients in the observation group. The TLC of the control group decreased by 1.354 ± 0.51 compared to patients in the observation group. The ERV of the control group decreased by 0.53 ± 0.30 compared to patients in the observation group. Additionally, the Fres, Zrs, R5, R20, and R35 of the observation group were higher than those of the control group by 10.73 ± 0.18, 1.78 ± 0.24, 0.11 ± 0.17, 0.86 ± 0.13, and 0.02 ± 0.21, respectively. In sum, the pulmonary function indices of the observation group were significantly lower than those of the control group, while the respiratory impedance indices were higher (P < 0.05). Within the observation group, the pulmonary function indices of severe patients were lower than those of moderate and mild patients, and moderate patients had lower pulmonary function indices than mild patients (P < 0.05). CONCLUSION: The pulmonary function of children with obstructive sleep apnea syndrome is impaired and varies in severity. There are significant differences in pulmonary function, underscoring the importance of monitoring pulmonary function in these children for clinical assessment and treatment prognosis.

Treatment of Work Type II Congenital First Branchial Cleft Anomalies: A Summary of 35 Cases.

Objective: This study aims to summarize the data and treatment of 35 children with Work type II congenital first branchial cleft anomalies (CFBCAs) to provide significant insights into the correlation between these anomalies and the facial nerve. Methods: A total of 35 children diagnosed with Work type II CFBCAs who received treatment at the Department of Otolaryngology-Head and Neck Surgery at Shenzhen Children's Hospital from August 2017 to March 2023 were analyzed retrospectively. Pearson chi-square tests and Fisher's exact tests were used to examine the relationship between clinical characteristics and the location of the lesion, which included the superficial and deep surfaces as well as the area between the branches of the facial nerve. Results: All 35 children underwent open incision and complete resection of fistulae. During the surgery, the lesions were found to be in the superficial facial nerve in 12 (34.3%) cases, between branches in 5 (14.3%) cases, and in the deep facial nerve in 18 (51.4%) cases. In those patients, lesions in females, with a lower edge of the lesion located below the angle of the mandible and the presence of a tympanic membranous attachment, are more likely to be located deep to the facial nerve or between its branches. The difference is statistically significant (P = .007, .032, .015). Conclusion: The treatment principle of Work type II CFBCAs consists of achieving a quiescent stage of inflammation, followed by a complete resection of the lesion on the premise of preserving facial nerve function. Certain clinical features of this disease can predict the relationship between the lesion and the facial nerve. The lesions in females, with a lower edge of the lesion located below the angle of the mandible, non-cystic type of Olsen, and the presence of tympanic membranous attachment, tend to be located deep to the facial nerve or between its branches.

5-Bromo-3,4-dihydroxybenzaldehyde stabilizes diabetic retinal neurovascular units by inhibiting the inflammatory microenvironment.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness characterized by damage to the retinal neurovascular unit, which is caused by hyperglycemia-induced metabolic and inflammatory responses. 5-Bromo-3,4-dihydroxybenzaldehyde (BDB) is a compound derived from marine red algae and known for its anti-inflammatory effects. METHODS: This study aimed to investigate the potential protective effects of BDB on DR using primary human retinal vascular endothelial cells and retinal tissue explants. The analysis involved assessing vascular integrity, expression of tight junction protein, hyperglycemia-induced permeability, and retinal ganglion cell (RGC) apoptosis. The protective effect of BDB in maintaining the diabetic retinal neurovascular units was verified using type 1 diabetic mouse models. Additionally, the inhibitory effect of BDB on the levels of inflammatory cytokines TNF-α, IL-1ß, and IL-6 were examined. RESULTS: In vitro experiments revealed that BDB promoted vascular integrity, inhibited the transcription of pro-inflammatory factors, and alleviated hyperglycemia-induced permeability. BDB also protected RGC from hyperglycemia-induced apoptosis. In diabetic mice models, BDB treatment maintained the integrity of diabetic retinal neurovascular units and inhibited the secretion of TNF-α, IL-1ß, and IL-6. CONCLUSION: BDB demonstrated a protective effect on DR by inhibiting the secretion of inflammatory factors, suggesting its potential as a therapeutic agent for the treatment of DR. Further research is warranted to validate its safety and efficacy for clinical application.

5-Bromo-3,4-dihydroxybenzaldehyde attenuates endothelial cells injury from high glucose-induced damage.

Hyperglycemia triggers metabolic and inflammatory responses, which lead to vascular inflammation and consequently induce microvascular and/or macrovascular diabetic complications. 5-bromo-3,4-dihydroxybenzaldehyde (BDB), a marine red algae-derived bromophenol compound, is found to have diverse bioactivities, including the effect of anti-inflammation and anti-diabetes, though the mechanism of which is still unclear. To evaluate the anti-vasculopathy of BDB and explore the possible mechanism involved. Firstly, MTT assay was used to optimize the treatment concentration of glucose and BDB with HUVECs. Subsequently, we adopted two concentrations of BDB (50 µM and 100 µM) to verify the protective effect of BDB on vascular model, which was established by HUVECs from high glucose (30 mM)-induced damage. The cell migration and tube formation were used to evaluate the function of HUVECS. Moreover, the related mechanisms were analyzed by assays for flow cytometry, ELISA, qPCR, intracellular ROS and western blot. The present study demonstrated that BDB could protect endothelial cells from apoptosis caused by high glucose treatment. BDB also significantly reduced the secretion of inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, induced by high glucose, which was also in agreement to the decrease of p65 protein expression and activities of NF-ĸB regulated by BDB. The reactive oxygen species (ROS) production and phosphorylation of 38 protein expression were also down-regulated by BDB compared to high glucose alone treatment. Furthermore, BDB reserved the endothelial cells functions of migration and tube formation under high glucose condition, which suggested that BDB could be a potential candidate in treating vascular inflammation induced by hyperglycemia.