Effect of artemisinin on improving islet function in rats fed with maternal high-fat diet.

BACKGROUND: Maternal high-fat diet (HFD) is a detrimental factor in developing glucose intolerance, obesity, and islet dysfunction. However, the effect of artemisinin on maternal HFD and whether it is related to the alterations of islet function is seldom studied since artemisinin treatments not only attenuate insulin resistance (IR) and restore islet ß cell function in Diabetes mellitus type 2. METHODS: Female rats were randomly fed a HFD (45% kcal from fat), HFD + artemisinin, or a regular chow diet (RCD) before pregnancy and during gestation. Glucose metabolism and the ß cell phenotypes were assessed. RESULTS: Maternal HFD increased islet load in female rats, proliferation of pancreatic ß cells, increased insulinogen, and decreased insulin secretion response to high glucose stimulation with delayed insulin release, increased fasting glucose, and glucose area under the curve compared with the general diet group. HFD inhibited expression of Foxo1 and PAX6 in female rats. Under the effect of both HFD and pregnancy, islet load was further increased, insulinogen was further increased, and fasting insulin level and fasting glucose were higher than RCD fed general-pregnancy group. ALDH1a3 transdifferentiation and PAX6, Foxo1, and PDX1 expression were increased in islets of high-fat pregnant rats. When adding artemisinin in HFD treated pregnant rats, islet function was significantly improved. CONCLUSIONS: Intervention with artemisinin in maternal HFD resulted in reduced islet size, decreased number of ß-cells and improved islet microcirculation, insulin processing shear process, decreased insulinogen/insulin ratio, and restored islet function through increased expression of PC1/3.

Bisphenol mixtures, metal mixtures and type 2 diabetes mellitus: Insights from metabolite profiling.

BACKGROUND: Little is known about the combined effect of bisphenol mixtures and metal mixtures on type 2 diabetes mellitus (T2DM) risk, and the mediating roles of metabolites. METHODS: The study included 606 pairs of T2DM cases and controls matched by age and sex, and information of participants was collected through questionnaires and laboratory tests. Serum bisphenol and plasma metal concentrations were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Widely targeted metabolomics was employed to obtain the serum metabolomic profiles. Conditional logistic regression models were used to assess the single associations of bisphenols and metals with T2DM risk after multivariable adjustment. Additionally, the joint effects of bisphenol mixtures and metal mixtures were examined using quantile-based g-computation (QG-C) models. Furthermore, differential metabolites associated with T2DM were identified, and mediation analyses were performed to explore the role of metabolites in the associations of bisphenols and metals with T2DM risk. RESULTS: The results showed bisphenol mixtures were associated with an increased T2DM risk, with bisphenol A (BPA) identified as the primary contributor. While the association between metal mixtures and T2DM remained inconclusive, cobalt (Co), iron (Fe), and zinc (Zn) showed the highest weight indices for T2DM risk. A total of 154 differential metabolites were screened between the T2DM cases and controls. Mediation analyses indicated that 9 metabolites mediated the association between BPA and T2DM, while L-valine mediated the association between Zn and T2DM risk. CONCLUSIONS: The study indicated that BPA, Co, Fe, and Zn were the primary contributors to increased T2DM risk, and metabolites played a mediating role in the associations of BPA and Zn with the risk of T2DM. Our findings contribute to a better understanding of the mechanisms underlying the associations of bisphenols and metals with T2DM.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Association between exposure to perfluoroalkyl substances and uric acid in Chinese adults.

BACKGROUND: A growing body of evidence suggests the deleterious effects of perfluoroalkyl substances (PFASs) on kidney, but little is known on the association between PFASs joint exposure and uric acid. METHODS: Serum PFASs concentrations were measured in 661 participants recruited from Tianjin, China using liquid chromatography/mass spectrometry. The associations of single PFASs exposure with uric acid levels and hyperuricemia were assessed using multivariable linear and logistic regression models, respectively. Restricted cubic spline models were established to investigate the dose-response relationships between PFASs concentrations and uric acid levels. Bayesian Kernel Machine Regression (BKMR) model with a hierarchical variable selection was performed to assess the joint effect of PFASs on uric acid. RESULTS: Potassium perfluoro-1-octanesulfonate (PFOS) and perfluoro-n-octanoic acid (PFOA) were the dominated contributors with median concentrations of 16.80 ng/ml and 9.42 ng/ml, respectively. Increased PFOA concentration (per log2-unit) was associated with elevated uric acid level (ß = 0.088, 95% CI: 0.033-0.143) and higher risk of hyperuricemia (OR = 1.134, 95% CI: 1.006-1.289). Conversely, the estimated change of uric acid associated with log2-unit increment in perfluoro-n-decanoic acid (PFDA) was -0.081 mg/dL (95% CI: -0.154, -0.009). A significant linear dose-response pattern was found between log2-transformed PFOA concentration and uric acid level. BKMR analyses indicated a non-significant overall effect of PFASs mixture on uric acid. CONCLUSIONS: Significant associations between PFOA and PFDA and uric acid, and between PFOA and hyperuricemia were found in the single-pollutant models, but the joint effect of PFASs mixture on uric acid was not observed in the BKMR model, which provided new insights in regulation policies and risk assessment of PFASs.

[The relationship between the level of N-terminal pro-B-type natriuretic peptide and prognosis in patients with sepsis].

OBJECTIVE: To detect the relationship between the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and prognosis in patients with sepsis. METHODS: A prospective controlled study was conducted. Sixty cases, including 39 sepsis and 21 severe sepsis, were enrolled from May 2010 to October 2011 in intensive care unit (ICU) of Second Hospital of Tianjin Medical University. The serum level of NT-proBNP was determined and acute physiology and chronic health evaluation II (APACHEII) score was calculated on the 1st and 3rd day. The receiver operator characteristic curve (ROC curve) was draw. According to the 28-day prognosis, all patients were divided into the survival group (n=42) or the death group (n=18). At the same time 30 healthy people were enrolled as control group. RESULTS: The level of NT-proBNP in the sepsis patients on the 1st and 3rd day were significantly higher than those of healthy controls (65.77±34.78 ng/L, 74.23±42.12 ng/L vs. 48.36±35.53 ng/L, P<0.05 and P<0.01). The level on 1st day of the severe sepsis group was higher than sepsis group (71.69±32.86 ng/L vs. 50.11±36. 98 ng/L, P<0.05), but there was no statistically significance on the 3rd day. The level of NT-proBNP in death group was increased gradually and significantly higher than that of survival group on the 3rd days (99.20±44.34 ng/L vs. 66.79±39.28 ng/L, P<0.05), but no difference was found on the 1st day. The APACHEII score of severe sepsis group were much higher than those of sepsis group on the 1st and 3rd day (1st day:23.92±7.57 vs. 14.87±6.50, 3rd day:19.28±8.80 vs. 10.43±7.27, both P<0.01). The APACHEII score of death group were also much higher than those of survival group on the 1st and 3rd day (1st day:26.71±6.72 vs. 18.83±7.84, 3rd day:31.11±5.06 vs. 13.80±7.27, both P<0.01). The cut point for the evaluation of sepsis prognosis were NT-proBNP≥63.5 ng/L and APACHEII score≥20, which sensitivity were 65.4% and 88.5%, and specificity were 62.5% and 69.4% respectively. CONCLUSION: Serum NT-proBNP levels elevation imply the poor prognosis in patients with sepsis.

Short-term outcomes in patients with lung cancer-associated acute ischemic stroke.

BACKGROUND: To investigate the independent risk factors of poor short-term outcomes in patients with lung cancer-associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short-term outcomes. METHODS: We retrospectively enrolled patients with lung cancer-associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0-2) and poor outcomes (score 3-6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS. RESULTS: A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short-term outcomes were significantly higher in D-dimer (OR = 1.001, 95% CI: 1.000-1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008-1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802-19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity. CONCLUSION: In this study, we have identified three independent risk factors associated with poor short-term outcomes in pLCAIS: higher NC, CRP, and D-dimer levels. These findings may be helpful for clinicians in identifying poor short-term outcomes patients.

The evaluation of cellular immune function in elderly patients with systemic lupus erythematosus.

BACKGROUND/AIMS: To evaluate cellular immune function in systemic lupus erythematosus (SLE) patients over 60 years old, the association between antinuclear antibody (ANA) titers and the ratio of CD4+ /CD8+ was analyzed in this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in a healthy elderly population was also investigated. METHODS: Serum ANA titers were assayed by indirect immunofluorescence (IIF) and the CD4+ /CD8+ T-cell ratio was determined by flow cytometry in 76 SLE patients and 30 healthy control individuals. IIF of cytoplasm and nuclear and nucleolar staining were performed on samples taken from 286 healthy elderly individuals. ENA levels were determined using a strip enzyme immunoassay among patients that tested positive for ANAs. RESULTS: ANA titers were negative in the 30 control individuals, but were positive in the 76 SLE patients. Based on ANA titers, the SLE patients were stratified to low (≤ 1:320), medium (1:640 to 1:1,280), and high (≥ 1:2,560) titer groups. The average CD4+ /CD8+ ratio of the SLE group was significantly lower than that of the control group. Among the 286 healthy elderly volunteers, 59 (20.63%) tested positive for ANAs. A homogeneous pattern was present in 47.46% of those 59 patients and a granule pattern in the karyoplasm was present in 33.90%. Furthermore, of the 59 patients, ENAs immunoassay was positive in 18 (30.51%); Sjogren syndrome-related antigen A (SSA)/52 kd and Sjogren syndrome antigen B (SSB)/La were the two major antibodies. CONCLUSION: The significantly lower CD4+ /CD8+ ratio among SLE patients over 60 years old is associated with deregulated immune responses and the development of SLE. A low ANA titer (1:160) is common in healthy elders, emphasizing the importance of considering age when determining if the evaluation of ANA titers is to be included in autoimmune disease diagnosis.