RESUMEN
We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.
Asunto(s)
Antidepresivos/uso terapéutico , Benzaldehídos/uso terapéutico , Depresión/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Animales , Antidepresivos/farmacología , Benzaldehídos/farmacología , Depresión/metabolismo , Modelos Animales de Enfermedad , Quinasa I-kappa B/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/metabolismoRESUMEN
PURPOSE: To evaluate the efficacy of eight different surgical treatments based on maxillomandibular advancement (MMA), which has emerged in recent years, for adult obstructive sleep apnoea (OSA) patients. METHODS: The literature was searched from January 2010 to May 2020 for studies of adult OSA patients with different types of MMA procedures to perform a network meta-analysis. The outcomes were changes in the apnoea-hypopnoea index (AHI), the lowest pulse oxygen saturation (SpO2 min) and the Epworth Sleepiness Scale (ESS). Treatment hierarchy was summarized according to the rank charts. RESULTS: Eight studies were included and encompassed a total of 227 adult patients diagnosed with OSA. Among them, 225 patients underwent combined surgery or simple MMA surgery, including modified maxillomandibular advancement (MMMA),counterclockwise maxillomandibular advancement (CMMA), drug-induced sleep endoscopy and maxillomandibular advancement (MMA + DISE), transoral robotic surgery and maxillomandibular advancement (MMA + TORS), uvulopalatopharyngoplasty (UPPP), maxillomandibular advancement and uvulopalatopharyngoplasty (MMA + UPPP), uvulopalatopharyngoplasty with uvula preservation and maxillomandibular advancement (MMA + HUPPP); MMA consisting of Le Fort I osteotomy and bilateral inverted-L osteotomy (ILOs), genioplasty and iliac bone grafting; and MMA consisting of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty. The results showed that the most effective surgical treatment is MMA + HUPPP [- 56.79 (WMD); 95% confidence interval (CI): - 113.02 to - 3.33] (P < 0.00001), which was far superior to other approaches. CONCLUSION: MMA combined with HUPPP had the highest efficacy. The MMA consisted of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty; CMMA and MMA + TORS are likely also great choices.