ACE2 deficiency exacerbates obesity-related glomerulopathy through its role in regulating lipid metabolism.

Obesity-related glomerulopathy is a secondary glomerular disease and its incidence has been increased globally in parallel with the obesity epidemic. ORG emerged as a growing cause of end-stage renal disease in recent years. Unbalanced production of adipokines at the adipose tissue as well as low-grade inflammatory processes play central roles in ORG progression. ORG mouse model with ACE2-knockout was generated and kidney injury was evaluated by biochemistry and histological staining assays. Protein and mRNA expressions were quantified by ELISA, western blot or qRT-PCR methods. ACE2 deficiency aggravated ORG-related renal injuries and stimulated both lipid accumulation and inflammatory responses. Further, Nrf2 pathway was deactivated upon ACE2-knockout. By contrast, ACE2 overexpression reactivated Nrf2 pathway and ameliorated ORG symptoms by decreasing fat deposition and reducing inflammatory responses. Our data demonstrated that ACE2 exerted the beneficial effects by acting through Nrf2 signaling pathway, suggesting the protective role of ACE2 against lipid accumulation and inflammatory responses in ORG pathogenesis.

Encapsulation of Zanthoxylum bungeanum essential oil to enhance flavor stability and inhibit lipid oxidation of Chinese-style sausage.

BACKGROUND: Zanthoxylum bungeanum essential oil (ZBEO) is a popular seasoning, commonly used in the food industry. It contains many easily degraded and highly volatile bioactive substances. Control of the stability of the bioactive substances in ZBEO is therefore very important in the food industry. RESULTS: In this study, microencapsulation was applied to improve ZBEO stability. The key parameters for microcapsule preparation were optimized by the Box-Behnken design method, and the optimum conditions were as follows: ratio of core to wall, 1:8; ratio of hydroxypropyl-α-cyclodextrin (HPCD) to soy protein isolate (SPI), 4; total solids content, 12%; and homogenization speed, 12 000 rpm. Antioxidant experiments have indicated that tea polyphenols (TPPs) effectively inhibited hydroxy-α-sanshool degradation in ZBEO microcapsules. Application of ZBEO microcapsules in Chinese-style sausage effectively inhibited lipid oxidation in sausages and protected hydroxy-α-sanshool and typical volatiles from volatilization and degradation during sausage storage. CONCLUSION: The results suggested that ZBEO microencapsulation is an effective strategy for improving the stability of its bioactive components and flavor ingredients during food processing. © 2022 Society of Chemical Industry.

Lack of Association Between Helicobacter pylori Infection and the Risk of Thyroid Nodule Types: A Multicenter Case-Control Study in China.

The prevalence of Helicobacter pylori infection is high worldwide, while numerous research has focused on unraveling the relationship between H. pylori infection and extragastric diseases. Although H. pylori infection has been associated with thyroid diseases, including thyroid nodule (TN), the relationship has mainly focused on potential physiological mechanisms and has not been validated by large population epidemiological investigations. Therefore, we thus designed a case-control study comprising participants who received regular health examination between 2017 and 2019. The cases and controls were diagnosed via ultrasound, while TN types were classified according to the guidelines of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Moreover, H. pylori infection was determined by C14 urea breath test, while its relationship with TN type risk and severity was analyzed using binary and ordinal logistic regression analyses. A total of 43,411 participants, including 13,036 TN patients and 30,375 controls, were finally recruited in the study. The crude odds ratio (OR) was 1.07 in Model 1 (95% CI = 1.03-1.14) without adjustment compared to the H. pylori non-infection group. However, it was negative in Model 2 (OR = 1.02, 95% CI = 0.97-1.06) after being adjusted for gender, age, body mass index (BMI), and blood pressure and in Model 3 (OR = 1.01, 95% CI = 0.97-1.06) after being adjusted for total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein on the basis of Model 2. Control variables, including gender, age, BMI, and diastolic pressure, were significantly correlated with the risk of TN types. Additionally, ordinal logistic regression results revealed that H. pylori infection was positively correlated with malignant differentiation of TN (Model 1: OR = 1.06, 95% CI = 1.02-1.11), while Model 2 and Model 3 showed negative results (Model 2: OR = 1.01, 95% CI = 0.96-1.06; Model 3: OR = 1.01, 95% CI = 0.96-1.05). In conclusion, H. pylori infection was not significantly associated with both TN type risk and severity of its malignant differentiation. These findings provide relevant insights for correcting possible misconceptions regarding TN type pathogenesis and will help guide optimization of therapeutic strategies for thyroid diseases.

IκB kinase promotes Nrf2 ubiquitination and degradation by phosphorylating cylindromatosis, aggravating oxidative stress injury in obesity-related nephropathy.

BACKGROUND: Obesity-related nephropathy (ORN) has become one of the leading causes of end-stage renal disease and has tripled over the past decade. Previous studies have demonstrated that decreased reactive oxygen species production may contribute to improving ORN by ameliorating oxidative stress injury. Here, IκB kinase (IKK) was hypothesized to inactivate the deubiquitination activity of cylindromatosis (CYLD) by activating the phosphorylation of CYLD, thus promoting the ubiquitination of NF-E2-related factor 2 (Nrf2) and further aggravating oxidative stress injury of the kidney in ORN. This study was aimed to confirm this hypothesis. METHODS: Haematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Oil Red O staining were performed to assess histopathology. Dihydroethidium (DHE) staining and MDA, SOD, CAT, and GSH-PX assessments were performed to measure reactive oxygen species (ROS) production. Immunohistochemical (IHC) staining, qRT-PCR and/or western blotting were performed to assess the expression of related genes. JC-1 assays were used to measure the mitochondrial membrane potential (ΔΨm) of treated HK-2 cells. Co-immunoprecipitation experiments (Co-IP) were used to analyse the interaction between CYLD and Nrf2 in ORN. RESULTS: ORN in vivo and in vitro models were successfully constructed, and oxidative stress injury was detected in the model tissues and cells. Compared with the control groups, the phosphorylation level of CYLD increased while Nrf2 levels decreased in ORN model cells. An IKK inhibitor reduced lipid deposition, ROS production, CYLD phosphorylation levels and ΔΨm in vitro, which were reversed by knockdown of CYLD. Nrf2 directly bound to CYLD and was ubiquitinated in ORN cells. The proteasome inhibitor MG132 activated the Nrf2/ARE signalling pathway, thereby reversing the promoting effect of CYLD knockdown on oxidative stress. CONCLUSION: IKK inactivates the deubiquitination activity of CYLD by activating the phosphorylation of CYLD, thus promoting the ubiquitination of Nrf2 and further aggravating oxidative stress injury of the kidney in ORN. This observation provided a feasible basis for the treatment of kidney damage caused by ORN.