Serum untargeted metabolomics analysis of the mechanisms of evodiamine on type 2 diabetes mellitus model rats.

Evodiamine (EVO) is an alkaloid extracted from Evodia rutaecarpa and has various pharmacological activities, including hypolipidemic, anti-inflammatory, anti-infective, and antitumor effects. However, the therapeutic effects of EVO on type 2 diabetes mellitus (T2DM) and the possible mechanisms remain unknown. In this study, we used a T2DM rat model using a high-fat diet (HFD) combined with streptozotocin (STZ) injections followed by treatment with EVO. First, we evaluated the therapeutic effects of EVO on T2DM rats, following which we evaluated the anti-inflammatory and anti-oxidative effects of EVO on T2DM rats. Finally, we analyzed the metabolic regulatory mechanism of EVO in T2DM rats using an untargeted metabolomics approach. The results showed that EVO treatment alleviated the hyperglycemia, hyperlipidemia, insulin resistance (IR), and pathological changes of the liver, pancreas and kidneys in T2DM rats. Moreover, EVO treatment ameliorated the oxidative stress and decreased the serum levels of pro-inflammatory cytokines in T2DM model rats. Serum untargeted metabolomics analysis indicated that the EVO treatment affected the levels of 26 metabolites, such as methionine, citric acid, cholesterol, taurocholic acid, pilocarpine, adrenic acid, and other metabolites. These metabolites were mainly related to the amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways. In conclusion, EVO can reduce blood glucose and improve oxidative stress and inflammatory response in T2DM rats. These functions are related to the regulation of amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways.

A cohort study of T helper 17 cell-related cytokine levels in tear samples of systemic lupus erythematosus and Sjögren's syndrome patients with dry eye disease.

OBJECTIVES: Sjögren's syndrome (SS) is the most common autoimmune disease with dry eye (DE) syndrome and some systemic lupus erythematosus (SLE) patients are also with DE syndrome. The occurrence of immune-related DE disease is closely related to T helper (Th) 17 cells in SS patients, and SLE patients have abnormal levels of multiple Th17 cell-related cytokines in their blood. However, the degree of expression of these cytokines in blood differs from that in tears. We hypothesised that the occurrence of DE symptoms in SLE and SS patients may be related to Th17 cells. METHODS: In this study, Th17 cell-related cytokines, including interleukin (IL)-1ß, IL-2, IL-4, interferon-γ, IL 6, IL-8, IL-17F, tumour necrosis factor (TNF)-α, IL-21, IL-22, and IL-23 were analysed in tear samples of DE, SLE, and SS patients. Ocular surface examinations for patients with DE symptoms, including tear secretion test (Schirmer I Test, SIT) and tests for ocular surface disease index (OSDI), tear break-up time (BUT), and corneal fluorescein stain (CFS), were performed and compared between the following patient groups: normal healthy people (control group, n=30), patients with simple DE disease (DE group, n=13), SLE patients with DE disease (SLE group, n=17), and SS patients with DE disease (SS group, n=18). RESULTS: The expression of Th17 cell-related cytokines in each tear sample was analysed using Luminex assay. The SIT and BUT scores of the SLE group were lower than those of the control (p<0.001) and DE (p<0.05) groups. However, SIT, BUT, CFS, and OSDI scores were not significantly different between SLE and SS patients. TNF-α, IL-6, IL-8, and IL-21 levels in tear samples were higher in DE, SLE, and SS patients (p<0.05) than in control individuals. IL-2 and IL-4 levels in tear samples of SLE patients were higher than DE (p<0.001) but lower than the control (p<0.001) group patients. IL-23 levels in tear samples of DE, SLE, and SS patients were all lower than those in the control group (p<0.001). SIT, BUT, CFS, and OSDI results showed that the DE symptoms of SLE and SS patients were more severe than those of the DE group. CONCLUSIONS: It is known that cytokine expression levels in tears are different from those in blood. Abnormal regulation of the Th17 cell pathway may be related to the occurrence of DE disease in SLE and SS patients, and Th17 cell-related cytokines, such as IL-8 and IL-21, may be potential therapeutic targets for treating SLE or SS DE disease.

Comparison of MRI Features of Epithelioid Hepatic Angiomyolipoma and Hepatocellular Carcinoma: Imaging Data From Two Centers.

Introduction: Epithelioid hepatic angiomyolipoma (Epi-HAML) can easily be misdiagnosed as a malignant tumor such as hepatocellular carcinoma (HCC) because of the low-fat content on imaging. We analyzed and compared the magnetic resonance imaging (MRI) features of Epi-HAML and HCC, which would aid in disease diagnosis. Methods: We included 30 pathologically confirmed patients with Epi-HAML and 80 with HCC, who underwent both MRI unenhanced scan and three-phase contrast-enhanced MRI scan. The clinical and MRI features of the two groups were summarized and analyzed. Results: Epi-HAML showed significant differences compared to HCC group in terms of clinical features such as sex preference, age, concomitant diseases (hepatitis B and cirrhosis), and elevated plasma alpha-fetoprotein (AFP) (P < 0.001). In addition, there were statistically significant differences between both tumor types with regard to conventional MRI findings such as a solitary tumor (100 vs. 83.8%, P = 0.018), well-defined (93.3 vs. 71.3%, P = 0.027), mild hyperintensity (40.0 vs. 3.7%, P < 0.001) on DWI with high b-value, fat within the tumor (43.3 vs. 8.8%, P < 0.001), and rare necrosis (3.3 vs. 26.3%, P = 0.016). Besides, Epi-HAML displayed significant differences compared to HCC in terms of contrast-enhanced MRI characteristics such as draining hepatic vein (30.0 vs. 3.8%, P < 0.001), portal vein tumor thrombus (0 vs. 13.8%, P = 0.033), hypointensity at delayed phase (70.0 vs. 95%, P = 0.001), intra-tumor vessel at delayed phase (36.7 vs. 10.0%, P = 0.003), pseudocapsule (20.0 vs. 78.8%, P < 0.001), and prolonged enhancement (56.7 vs. 1.2%, P < 0.001). Conclusion: Epi-HAML frequently occurs in middle-aged women and usually lacks characteristic clinical symptoms. Typically, Epi-HAML presents as an isolated and well-defined tumor with rich vasculature. Specific MRI features such as intra-tumor fat, intra-tumor vessel, draining hepatic vein, prolonged enhancement, and lack of capsule may contribute to a more confident diagnosis of Epi-HAML.

Dynamic enhancement patterns of small-diameter mass-forming intrahepatic cholangiocarcinomas on contrast-enhanced magnetic resonance imaging: Challenges faced by the radiologist.

Contrast-enhanced magnetic resonance imaging (MRI) characteristics of small-diameter mass-forming intrahepatic cholangiocarcinomas (ICCs) (diameter ≤3 cm) are still unclear.This study focused on imaging findings of small mass-forming ICCs. The MRI findings for small-diameter mass-forming ICCs were summarized, and the enhancement features of small ICC nodules with different diameters [2 groups were defined: a smaller nodule group (ICC diameter <2 cm) and a larger nodule group (ICC diameter >2 cm)] were compared on contrast-enhanced MRI.In our study, there were 41 small ICC nodules in 41 patients, including 30 men and 11 women (average age, 56 years). The nodules were characterized by peripheral hyperintense in the arterial phase on contrast-enhanced MRI. In the different diameter groups, peripheral hyperintense was the most common in the larger nodule group (56% vs 12%, P < .05) and hypointense was more common in the smaller nodule group (25% vs 0%, P < .05) in the arterial phase on contrast-enhanced MRI. Smaller nodules mainly showed progressive enhancement, whereas larger nodules mainly showed peripheral continuous enhancement (56% vs 6%, P < .05).The small-diameter mass-forming ICC nodules mainly show peripheral continuous enhancement on contrast-enhanced MRI; however, those with diameters <2 cm commonly show progressive enhancement.