The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Objective: The aim of this study is to create a nomogram for accurately predicting the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and provide a reference for clinical treatment. Methods: Three hundred and twenty-three patients with ISSNHL were admitted from September 2014 to November 2020. The clinical data were retrospectively reviewed. Prognostic factors for ISSNHL were assessed based on univariate and multivariate logistic regression analysis and used to create a nomogram. Nomogram performance in terms of predictive and discriminatory ability was evaluated by calculating the concordance index (C-index) and generating calibration plots. Results: The overall hearing improvement rate was 41.4%, comprising complete recovery (13.3%), marked recovery (17.0%), and slight recovery (11.1%). Multivariate logistic regression analysis showed that age, symptoms of vertigo, interval between onset and treatment, low-density lipoprotein, and type of hearing loss were independent predictors of ISSNHL. A nomogram based on these 5 factors had a C index of 0.798 (95% confidence interval 0.750-0.845). Conclusions: Age, vertigo, interval between onset and treatment, low-density lipoprotein level, and type of hearing loss are closely associated with hearing recovery. The nomogram may enable prediction of the prognosis of ISSNHL and facilitate clinical decision-making.

Prognosis of Idiopathic Sudden Sensorineural Hearing Loss: The Nomogram Perspective

Efficacy and safety of standardized Ginkgo biloba L. leaves extract as an adjuvant therapy for sudden sensorineural hearing loss: A systematic review and meta-analysis.

Obstructive sleep apnea is the most common sleep‐related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life and work performance as well as an increased risk of death. Standard treatment seems to have limited effects on cardiovascular and metabolic aspects of the disease, emphasising the need for early diagnosis and additional therapeutic approaches. Recent evidence suggests that the dysregulation of circadian rhythms, processes with endogenous rhythmicity that are adjusted to the environment through various cues, is involved in the pathogenesis of comorbidities. In patients with obstructive sleep apnea, altered circadian gene expression patterns have been demonstrated. Obstructive respiratory events may promote circadian dysregulation through the effects of sleep disturbance and intermittent hypoxia, with subsequent inflammation and disruption of neural and hormonal homeostasis. In this review, current knowledge on obstructive sleep apnea, circadian rhythm regulation, and circadian rhythm sleep disorders is summarised. Studies that connect obstructive sleep apnea to circadian rhythm abnormalities are critically evaluated. Furthermore, pathogenetic mechanisms that may underlie this association, most notably hypoxia signalling, are presented. A bidirectional relationship between obstructive sleep apnea and circadian rhythm dysregulation is proposed. Approaching obstructive sleep apnea as a circadian rhythm disorder may prove beneficial for the development of new, personalised diagnostic, therapeutic and prognostic tools. However, further studies are needed before the clinical approach to obstructive sleep apnea includes targeting the circadian system.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jsr.13875

Is obstructive sleep apnea a circadian rhythm disorder?

Clinical features and prognosis of severe-to-profound sudden sensorineural hearing loss.

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for metabolic syndrome (MetS). Recent studies have indicated that circadian clock genes were dysregulated in OSA. In addition, it is clear that the impairment of circadian clocks drives the progression of MetS. Therefore, we hypothesized that circadian rhythm disruption links OSA with MetS. Methods: A total of 118 participants, who underwent polysomnography (PSG) and were diagnosed as healthy snorers (control, n = 29) or OSA (n = 89) patients based on the apnea–hypopnea index (AHI), were enrolled in the present study. General information, anthropometric data, blood biochemical indicators, clock gene expressions, and levels of oxidative and inflammatory indicators were collected, determined, and compared in all the participants. Results: We found that Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Differentiated embryo chondrocyte 1 (Dec1) were upregulated, while Period 1 (Per1) was reduced in OSA patients. In addition, these changing trends were closely associated with the hypoxia indicator of AHI and have a significant impact on the presence of MetS components, such as hyperglycemia (Dec1 and Per1, p < 0.05 and 0.001, respectively), hypertension (Bmal1 and Dec1, p < 0.001 and 0.01, respectively), hyperlipidemia (Dec1, p < 0.01), and obesity (Dec1, p < 0.05). Notably, expressions of Dec1 correlated with IR and predicted the presence of MetS in OSA patients. Finally, we also observed that Dec1 expression was interrelated with levels of both oxidative indicators and inflammatory biomarkers (IL-6) in OSA. Conclusion: This study concluded that circadian clock disruptions, especially Dec1, link OSA with MetS in an oxidative and inflammatory-related manner. Circadian clock Dec1 can be used as a specific biomarker (p < 0.001) and therapeutic target in OSA combined with Mets patients.

Circadian clock disruptions link oxidative stress and systemic inflammation to metabolic syndrome in obstructive sleep apnea patients

OBJECTIVE To define the impact of hyperlipidemia as a coexisting factor on the prognosis of Idiopathic Sudden Sensorineural Hearing Loss (ISSHL), we prospectively analysed the Lipid-lowering therapy Group (LLTG) data compared with Control Group (CG) data to determine the effects of Lipid intervention on the prognosis of sudden hearing loss. DESIGN A prospective, non-randomized study. SETTING Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China. PARTICIPANTS A total of 653 in-patient SSHL patients were enrolled between January 2014 to August 2018. MAIN OUTCOME MEASURES From January 2014 to August 2018, 653 patients with ISSHL who also had hyperlipidemia as coexisting factor were identified. Patients enrolled in LLTG (n = 200) or CG (n = 453) were compared by a propensity score matching analysis (PSM, caliper = 0.01, n = 2) to balance pre-existing clinical characteristics. After matching, the effective rate of different hyperlipidemia types and different types of audiogram in both groups were performed by Cochran-Mantel-Haenszel test (CMH). RESULTS After PSM, 440 patients were studied (146 in LLTG, 294 in CG), and the influence of interference factors was balanced, meanwhile, the final hearing level was better in LLTG than CG (P = .043), and hearing gain was higher in LLTG than CG (P = .006). Cure rate (32.9%), significant improvement rate (22.6%) and the total effective rate (76.0%) in LLTG were better than that in CG group (26.5%, 15.6% and 63.6%) after the Pearson chi-square test (P < .05). Analysis with the Cochran-Mantel-Haenszel test showed that the total effective rate was better in LLTG than CG respectively (P = .009) in each different hyperlipidemia types, and there were statistically significant differences in TG higher group (TG Group; P = .018). Moreover, the total effective rate was better in LLTG than CG (P = .006) for all patterns of audiogram, and there were statistically significant differences in flat audiogram (P = .043). CONCLUSIONS Lipid-lowering therapy can improve the curative effect of sudden hearing loss patients combined with hyperlipidemia. There was a significant difference in the total effective rate of TG Group after lipid intervention, suggesting that there might be causal relationship between TG and sudden hearing loss. There was a significant difference in the total effective rate between flat audiogram, which may suggest flat hearing loss was more likely caused by vascular dysfunction.

Impact of hyperlipidemia as a coexisting factor on the prognosis of idiopathic sudden sensorineural hearing loss: A propensity score matching analysis.

Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.

The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway

Background: Few studies focused on the prognosis of sudden sensorineural hearing loss (ISSHL) of aged people.Objectives: The aim of this study is to analyze the characteristics, treatment, and prog...

Characteristics and prognosis of idiopathic sudden sensorineural hearing loss in aged people: a retrospective study.

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Circadian clock disruptions link oxidative stress and systemic inflammation to metabolic syndrome in obstructive sleep apnea patients

Impact of hyperlipidemia as a coexisting factor on the prognosis of idiopathic sudden sensorineural hearing loss: A propensity score matching analysis.

The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway

Characteristics and prognosis of idiopathic sudden sensorineural hearing loss in aged people: a retrospective study.