Insulin resistance is a critical factor in the development of metabolic disorders, including type 2 diabetes (T2DM). However, its molecular mechanisms remain incompletely understood. In this study, we found that F-box only protein 2 (FBXO2), a substrate recognition component of the Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex, was upregulated in livers of obese mice. Furthermore, using a protein purification approach combined with high-performance liquid chromatography/tandem mass spectrometry, we carried out a system-wide screening of FBXO2 substrates, in which the insulin receptor (IR) was identified as a substrate for FBXO2. SCF acts as an E3 ligase targeting the IR for ubiquitin-dependent degradation to regulate insulin signaling integrity. As a result, adenovirus-mediated overexpression of FBXO2 in healthy mice led to hyperglycemia, glucose intolerance, and insulin resistance, whereas ablation of FBXO2 alleviated diabetic phenotypes in obese mice. Therefore, our results identify SCF as an E3 ligase for the IR in the liver, which might provide a novel therapeutic target for treating T2DM and related metabolic disorders.
Background: Intracranial vertebral artery dissection aneurysms (VADAs) may cause acute ischemia or hemorrhage, in which case urgent endovascular treatment will be needed. Although the majority of patients obtain a good functional outcome after surgery, a surprising finding has been a poor quality of life (QOL) in follow-up. The purpose of this study was to evaluate clinical efficacy in reconstructive endovascular therapy for acute intracranial VADAs and to analyze the factors contributing to subsequent QOL. Methods: In this prospective study, 33 consecutive VADA patients with subarachnoid hemorrhage were recruited for comparison with 37 VADA patients with posterior circulation cerebral ischemia. All VADA patients were treated using a reconstructive strategy. Clinical, radiological, neurological, and cognitive data, as well as QOL, were assessed at admission and 6 months after surgery. Stoke Specific Quality of Life (SS-QOL) was evaluated for patients with good functional outcome [modified Ranking Scale (mRS) scoring 0-2] for subgroup analysis. Predictors for QOL at follow-up were analyzed by regression model. Results: Immediate angiography after surgery showed complete VADA obliteration in 57 (81.4%) patients and partial obliteration in 13 (18.6%) patients. Three (4.3%) cases suffered from perioperative complications, comprising two cases of stent thrombosis in the hemorrhagic group and one case of posterior inferior cerebellar artery occlusion in the ischemic group. Twenty-five (75.8%) patients in the hemorrhagic group and 30 (81.1%) patients in the ischemic group had a favorable outcome (mRS scoring 0-2) at 6-month follow-up. Follow-up angiography displayed that one case of recurrence occurred separately in both groups. Fifteen of the 33 hemorrhagic patients (45.5%) and 19 of the 37 ischemic patients (51.4%) rated QOL at follow-up as bad (SS-QOL score ≤ 3.9) despite a good functional outcome. Severity of neurological disorder and impaired neurocognition at baseline in VADA patients are proved to be independent predictors for the decline of QOL according to regression analysis. Conclusion: Reconstructive endovascular therapy for acute intracranial VADAs is a safe and effective method with a low complication rate. VADAs lead to impaired QOL Gao et al. Quality of Life in VADAs Reconstructive Therapy at 6-month follow-up, which is attributable to multiple factors. This study demonstrated that neurological and cognitive status at baseline is of significant importance for QOL after VADAs.
Yogurt, a traditional fermented dairy product, is made with a starter that contains Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. The aim of this study was to investigate the effects of different concentrations of epigallocatechin gallate (EGCG; 0, 0.5, 1.0, 3.0, and 5.0 mg/mL) on the growth, metabolism, and acid production of lactic acid bacteria, as well as the texture, stability, and antioxidant activity of fermented milk (yogurt). The results showed that a low concentration of EGCG had no significant effect on the acid production capacity of the starter or on the water-holding capacity of the yogurt but did increase its viscosity. A high concentration (5.0 mg/ mL) of EGCG delayed the acid production rate of the starter and decreased the water-holding capacity, but significantly increased the antioxidant activity of yogurt. The addition of EGCG significantly increased the hardness of yogurt. Therefore, EGCG can improve the texture of fermented milk and enhance its antioxidant activity and stability, thus improving the overall quality of yogurt.
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