PKM2 promotes proinflammatory macrophage activation in ankylosing spondylitis.

Macrophages play a critical role in ankylosing spondylitis by promoting autoimmune tissue inflammation through various effector functions. The inflammatory potential of macrophages is highly influenced by their metabolic environment. Here, we demonstrate that glycolysis is linked to the proinflammatory activation of human blood monocyte-derived macrophages in ankylosing spondylitis. Specifically, ankylosing spondylitis macrophages produced excessive inflammation, including TNFα, IL1ß, and IL23, and displayed an overactive status by exhibiting stronger costimulatory signals, such as CD80, CD86, and HLA-DR. Moreover, we found that patient-derived monocyte-derived M1-type macrophages (M1 macrophages) exhibited intensified glycolysis, as evidenced by a higher extracellular acidification rate. Upregulation of PKM2 and GLUT1 was observed in ankylosing spondylitis-derived monocytes and monocyte-derived macrophages, especially in M1 macrophages, indicating glucose metabolic alteration in ankylosing spondylitis macrophages. To investigate the impact of glycolysis on macrophage inflammatory ability, we treated ankylosing spondylitis M1 macrophages with 2 inhibitors: 2-deoxy-D-glucose, a glycolysis inhibitor, and shikonin, a PKM2 inhibitor. Both inhibitors reduced proinflammatory function and reversed the overactive status of ankylosing spondylitis macrophages, suggesting their potential utility in treating the disease. These data place PKM2 at the crosstalk between glucose metabolic changes and the activation of inflammatory macrophages in patients with ankylosing spondylitis.

Metabolomics in gestational diabetes mellitus: A review.

Gestational diabetes mellitus (GDM), a common complication of pregnancy, is a type of diabetes that is first detected and diagnosed during pregnancy. The incidence of GDM is increasing annually and is associated with many adverse pregnancy outcomes. Early prediction of the risk of GDM and intervention are thus important to reduce adverse pregnancy outcomes. Studies have revealed a correlation between the levels of amino acids, fatty acids, triglycerides, and other metabolites in early pregnancy and the occurrence of GDM. The development of high-throughput technologies used in metabolomics has enabled the detection of changes in the levels of small-molecule metabolites during early pregnancy, which can help reflect the overall physiological and pathological status of the body and explore the underlying mechanisms of the development of GDM. This review sought to summarize current research in this field and provide data for the development of strategies to manage GDM.

Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study.

PURPOSES: Adipokine alterations contribute to the development and remission of nonalcoholic fatty-liver disease (NAFLD). Adipsin is one of the most abundant adipokines and is almost exclusively produced by adipocytes. However, data on adipsin in human NAFLD are limited and controversial. We performed this study to investigate the association between adipsin and the remission of NAFLD in middle-aged and elderly Chinese adults. METHODS: Whether adipsin is associated with the remission of NAFLD in a 3-year community-based prospective cohort study was investigated. Baseline levels of adipsin were measured in serum samples collected from 908 NAFLD participants. NAFLD was diagnosed using abdominal ultrasonography. Logistic regression analysis and a multiple stepwise logistic regression model including different variables were conducted to evaluate the association between serum adipsin levels and the remission of NAFLD. RESULTS: During a mean follow-up of 3.14 ± 0.36 years, 247 (27.20%) participants with NAFLD at baseline were in remission. At baseline, serum adipsin concentration was positively correlated with body mass index (r: 0.39, p < 0.001), insulin (r: 0.31, p < 0.001), and homeostasis model assessment of insulin resistance (r: 0.31, p < 0.001) and was inversely associated with NAFLD remission with a fully adjusted odds ratio (OR) of 0.28 (0.16-0.48) (p trend < 0.001). In a multiple stepwise logistic regression model, circulating adipsin independently predicted NAFLD remission (OR: 0.284, 95% confidence interval [CI]: 0.172-0.471, p for trend <0.001). The area under the receiver operating characteristic curve was 0.751 (95% CI: 0.717-0.785) (p < 0.001) for the prediction model of NAFLD remission. CONCLUSIONS: We provide evidence for an association between serum adipsin levels and the remission of NAFLD in a community-based prospective cohort study. Serum adipsin can be a potential biomarker for predicting NAFLD remission.

Anthocyanin supplementation at different doses improves cholesterol efflux capacity in subjects with dyslipidemia-a randomized controlled trial.

BACKGROUND/OBJECTIVES: Numerous clinical trials have confirmed that supplementation with purified anthocyanins has favorable effects on metabolic diseases, but the dose-response of dyslipidemia to anthocyanin supplementation remains unclear. This study aimed to investigate the effect of anthocyanin supplementation in different doses on lipid profile. SUBJECTS/METHODS: We randomly assigned 176 dyslipidemic subjects aged 35-70 to three purified anthocyanin groups (40 mg/day, n = 45; 80 mg/day, n = 42; 320 mg/day, n = 43) and a placebo group (n = 46). Anthropometric parameters, serum lipid profiles, and cholesterol efflux capacity (CEC) were measured at baseline, and at the end of 6 and 12 weeks. RESULTS: After 12 weeks of supplementation, significant differences in CEC (P = 0.033), high-density lipoprotein cholesterol (HDL-C) (P = 0.043), and apolipoprotein A-I (ApoA-I) (P = 0.022) were observed between four groups. Compared with placebo, 320 mg/day anthocyanin significantly increased CEC (35.8%, 95% CI: 11.5-60.2%; P = 0.004), HDL-C (0.07 mmol/L, 95% CI: 0.01-0.14; P = 0.003), and ApoA-I (0.07 g/L, 95% CI: 0.01-0.12; P = 0.008). Linear trend analysis showed that anthocyanin supplementation has a strong dose-response relationship with CEC (P = 0.002), HDL-C (P = 0.038), and ApoA-I (P = 0.023). Moreover, the enhancement of CEC showed positive correlations with the increase in HDL-C (r = 0.215, P < 0.01) and APOA-I (r = 0.327, P < 0.01). CONCLUSIONS: Anthocyanin supplementation at 0-320 mg/day for 12 weeks enhances CEC in a dose-response manner in dyslipidemic subjects. Anthocyanin supplementation doses of 80-320 mg/day can improve serum HDL-C levels and HDL-induced CEC.

Analysis of antinuclear antibody titers and patterns by using HEp-2 and primate liver tissue substrate indirect immunofluorescence assay in patients with systemic autoimmune rheumatic diseases.

BACKGROUND: Indirect immunofluorescence assay (IIFA) is viewed as a preliminary standard to assess antinuclear antibodies (ANAs). Our aim was to explore ANA positivity rate, titers, and patterns in patients with systemic autoimmune rheumatic diseases (SARD), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), and mixed connective tissue disease (MCTD), compared with healthy controls (HC). METHODS: Assess antinuclear antibody titers and patterns were retrospectively identified and compared by IIFA using human epithelial cells (HEp-2) and primate liver tissue substrate according to international consensus in SARD. Serum complement 3 (C3), C4, and immunoglobulin G were compared among subgroups with different ANA titers. The positive predictive values (PPV) for different ANA titers were calculated. RESULTS: There were a total of 3510 samples, including 2034 SLE, 973 RA, 155 SSc, 309 pSS, and 39 MCTD cases. There was no difference in age between HC and SARD, excluding RA. ANA positivity rate in SARD and HC was 78.7% and 12.2%, respectively. A titer of ≥1:320 revealed a PPV of 84.0% in SARD. SLE patients with ANA titers ≥1:320 had significantly lower levels of C3 and C4. AC-4 (31.2%) was the major pattern in patients with SARD, followed by AC-5 (23.9%) and AC-1 (18.8%). SLE mostly presented with AC-4 (30.3%). Several mixed patterns provided a significant hint for SSc and SLE. The major pattern in HC was AC-2 (12.2%). CONCLUSIONS: Assess antinuclear antibody positivity, titers, and patterns display differences in various SARD, contributing to the classification of SARD.

Investigation and analysis of HEp 2 indirect immunofluorescence titers and patterns in various liver diseases.

INTRODUCTION: Antinuclear antibody (ANA) testing using indirect immunofluorescence assay (IIFA) is a common and economical method which contributes to detect systemic autoimmune diseases (SARD) and autoimmune liver diseases (AILD). The primary aim of our study was to investigate ANA positivity and their patterns in multiple liver diseases, including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), and hepatic carcinoma (HCC). Besides, we also compared the ANA titers and patterns in patients with liver disease, SARD, and healthy controls (HC). METHODS: A total of 2537 patients with SARD, 137 PBC cases, 57 AIH cases, 3420 HBV cases, 769 HCV cases, 268 HCC cases, and 1073 HC were retrospectively assessed. The titers and patterns of ANA were detected with the IIFA method. RESULTS: ANA positivity rate was considerably discernible between these diseases, which is 90.1% in SARD, 93.4% in PBC, 49.1% in AIH, 19.1% in HBV, 13.9% in HCV, and 23.5% in HCC. Moreover, only 4.9% of HCC cases, 2.5% of HBV patients, and 1.6% of HCV patients had an ANA titer ≥ 1:320. The mixed pattern which composed of at least two patterns majorly lied in PBC. AC-15 and AC-21 was frequently related to liver diseases; the former pattern was more frequently found in AIH (84.2%) and PBC (8.8%), and the latter pattern was easily seen in PBC (62.2%) and HCC (22.6%). The positive rate of ANA in HC was 12.2%, and its major pattern was AC-2. CONCLUSIONS: There are differences in ANA positivity among patients with SARD and various liver diseases. Some mixed patterns may provide important evidence for the diagnosis of PBC. Clinicians should pay attention to ANA patterns and titer during the interpretation of this test. Key Points • Defining the clinical relevance of antinuclear antibody (ANA) using indirect immunofluorescence assay in the context of diseases can be an important tool for the clinician in the diagnostic work-up of patients with liver diseases. • The mixed pattern of ANA is majorly found in primary biliary cirrhosis (PBC). ANA patterns including AC-15 and AC-21 are frequently related to liver diseases. AC-15 is more often found in autoimmune hepatitis (AIH) (84.2%) and PBC (8.8%), and AC-21 is easily found in PBC (62.2%, and hepatic carcinoma (HCC) (22.6%). • ANA positivity can be seen in 19.1% of hepatitis B virus infection (HBV) cases, 13.9% of hepatitis C virus infection (HCV) cases, and 23.5% of HCC cases. Only 2.5% of HBV patients, 1.6% of HCV patients, and 4.9% of HCC cases have an ANA titer ≥ 1:320.

Comparison of chemiluminescence microparticle immunoassay, indirect immunofluorescence assay, linear immunoassay and multiple microbead immunoassay detecting autoantibodies in systemic lupus erythematosus.

The aim of study was to detect antinuclear antibodies (ANA) using indirect immunofluorescence assay (IIFA), linear immunoassay (LIA), chemiluminescence microparticle immunoassay (CMIA), multiple microbead immunoassay (MBI) and to compare these four methods in the performance of diagnosing systemic lupus erythematosus (SLE). Serum ANA were detected in 147 SLE cases and 42 healthy controls (HCs). The sensitivity, specificity, accuracy, positive predictive value and agreement, the area under the curve of four methods in diagnosing were calculated. Finally, a diagnostic model through logistic regression was constructed. The sensitivity of CMIA and IIFA in diagnosing SLE was 89.08% and 89.12%, higher than other two methods (P < .01), while highest specificity lied in CMIA (95.24%) and LIA (95.24%). The accuracy was highest in CMIA (91.01%), and lowest in LIA (83.07%). CMIA and the other three methods had good agreement, especially with LIA (κ = .798, 95% CI, 0.708-0.88). ANA-IIFA (OR = 1.016, P < .001) and anti-SSA antibodies (OR = 1.017, P = .043) were finally included in the SLE diagnostic model, with AUC value of 0.964 (95% CI, 0.936-0.991). SLE patients exhibited 14 various ANA patterns, especially AC-1, AC-4, and AC-5. Antibodies against SSA and dsDNA were mostly seen with AC-1 and AC-4 patterns, while antibodies against RNP, Sm, SSA, dsDNA, nucleosome and PO were most frequently observed with AC-5 pattern in SLE. CMIA method is a reliable screening test for detections of antibodies related to SLE. Using ANA-IIFA and anti-SSA antibodies by CMIA can discriminate SLE patients from HCs effectively.

Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study.

CONTEXT: SHBG, a homodimeric glycoprotein produced by hepatocytes has been shown to be associated with metabolic disorders. Whether circulating SHBG levels are predictive of later risk of nonalcoholic fatty liver disease (NAFLD) remains unknown. In this study, we prospectively investigated the association between SHBG and NAFLD progression through a community-based cohort comprising 3389 Chinese adults. METHODS: NAFLD was diagnosed using abdominal ultrasonography. Serum SHBG levels were measured by chemiluminescent enzyme immunometric assay, and their relationship with NAFLD development and regression was investigated after a mean follow-up of 3.09 years using multivariable logistic regression. RESULTS: Basal SHBG was negatively associated with NAFLD development, with a fully adjusted odds ratio (OR) and its 95% confidence interval (CI) of 0.22 (0.12-0.40) (P < .001). In contrast, basal SHBG was positively associated with NAFLD regression, with a fully adjusted OR of 4.83 (2.38-9.81) (P < .001). Multiple-stepwise logistic regression analysis showed that SHBG concentration was an independent predictor of NAFLD development (OR, 0.28 [0.18-0.45]; P < .001) and regression (OR, 3.89 [2.43-6.22]; P < .001). In addition, the area under the receiver operating characteristic curves were 0.764 (95% CI, 0.740-0.787) and 0.762 (95% CI, 0.738-0.785) for the prediction models of NAFLD development and regression, respectively. CONCLUSIONS: Serum SHBG concentration is associated with the development and regression of NAFLD; moreover, it can be a potential biomarker for predicting NAFLD progression, and also a novel preventive and therapeutic target for NAFLD.

Hypouricemic and nephroprotective roles of anthocyanins in hyperuricemic mice.

Hyperuricemia (HUA) is a universal metabolic disorder characterized by a high level of uric acid in the serum. Anthocyanins (ACNs) are a group of natural flavonoids that have shown favourable bioactivities in the metabolic syndrome but the effect on uric acid metabolism remains underexplored. The present study investigated the hypouricemic effects of ACNs in a mice model and further studied the potential mechanisms. ICR mice based on a high-yeast diet were administered potassium oxonate (PO, 280 mg per kg body weight) and inosine (400 mg per kg body weight) to induce a hyperuricemia model, meanwhile, ACNs were supplemented by gavage. The mice were sacrificed after 3 weeks of treatment. ACN administration significantly reduced serum uric acid (SUA), blood urea nitrogen (BUN) and serum creatinine (Scr) levels and suppressed xanthine oxidase (XOD) activity in mice serum and liver. In addition, ACNs down-regulated the expression of hepatic XOD, caspase-1, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and regulated the expression of renal urate transporters URAT1, GLUT9, ABCG2, OAT1, OAT3, OCT1, OCT2, OCTN1 and OCTN2. According to histological analysis, ACN treatment exhibited hepatoprotective and nephroprotective effects in hyperuricemic mice. In conclusion, ACNs reduced urate production and promoted uric acid excretion from the renal system, which suggests the potential of ACNs for the future treatment of HUA.