Fucoidan Improves Early Stage Diabetic Nephropathy via the Gut Microbiota-Mitochondria Axis in High-Fat Diet-Induced Diabetic Mice.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Fucoidan, a polysaccharide containing fucose and sulfate group, ameliorates DN. However, the underlying mechanism has not been fully understood. This study aimed to explore the effects and mechanism of fucoidan on DN in high-fat diet-induced diabetic mice. A total of 90 C57BL/6J mice were randomly assigned to six groups (n = 15) as follows: normal control (NC), diabetes mellitus (DM), metformin (MTF), low-dose fucoidan (LFC), medium-dose fucoidan (MFC), and high-dose fucoidan (HFC). A technique based on fluorescein isothiocyanate (FITC-sinistin) elimination kinetics measured percutaneously was applied to determine the glomerular filtration rate (GFR). After 24 weeks, the mice were sacrificed and an early stage DN model was confirmed by GFR hyperfiltration, elevated urinary creatinine, normal urinary albumin, tubulointerstitial fibrosis, and glomerular hypertrophy. Fucoidan significantly improved the GFR hyperfiltration and renal fibrosis. An enriched SCFAs-producing bacteria and increased acetic concentration in cecum contents were found in fucoidan groups, as well as increased renal ATP levels and improved mitochondrial dysfunction. The renal inflammation and fibrosis were ameliorated through inhibiting the MAPKs pathway. In conclusion, fucoidan improved early stage DN targeting the microbiota-mitochondria axis by ameliorating mitochondrial oxidative stress and inhibiting the MAPKs pathway.

Clinical performance of AMA-M2, anti-gp210 and anti-sp100 antibody levels in primary biliary cholangitis: When detected by multiplex bead-based flow fluorescent immunoassay.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy, characterized by the presence of some autoantibodies in the serum. This study aimed to evaluate the clinical significance of AMA-M2, anti-gp210 and anti-sp100 antibody levels detected by multiplex bead-based flow fluorescent immunoassay (MBFFI) in PBC. METHODS: This study cohort included 238 PBC patients, 81 autoimmune hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE) patients, and 118 healthy controls. Serum AMA-M2, anti-gp210 and anti-sp100 antibody were detected by MBFFI and immunoblotting assay (IBT). The relationship between three antibody levels and cirrhosis, liver function, cholestasis markers and therapeutic effect to ursodesoxycholic acid (UDCA) was evaluated in PBC. RESULTS: MBFFI were presented good coincidence rate (87.39%-95.38%) with IBT. The level of AMA-M2, anti-gp210 and anti-sp100 antibodies in PBC patients were higher than other disease group and healthy controls (p ＜ .01). When compared with the healthy controls group, the AUC of AMA-M2, anti-gp210 and anti-sp100 antibodies were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210 antibody levels have diagnostic value in patients with liver cirrhosis (AUC: 0.7567). We found that when combine detect these three antibodies, the sensitivity was higher than individually detection. High level of serum anti-gp210 antibody could be related to worse liver function and more severe cholestasis in PBC patients. Moreover, serum antibody levels may decrease or remained flat in patients who responded well to UDCA. CONCLUSION: The detection of AMA-M2, anti-gp210 and anti-sp100 antibody levels by MBFFI showed good performance in the diagnosis of PBC. Serum anti-gp210 antibody level is related to cirrhosis, poor liver function and severe cholestasis in PBC.

Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014.

BACKGROUND: Vitamin D deficiency (VDD) may increase the risk of hypertension in women of childbearing age, who may be exposed to secondhand smoke (SHS) simultaneously. Till now, few studies have investigated the joint effects of VDD and SHS on hypertension in this population. We evaluated whether exposure to SHS modified the association between VDD and hypertension. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) 2007-2014 were analyzed. Our research subjects were 2826 nonsmoking and nonpregnant women of childbearing age (20-44 years old). Hypertension was defined based either on systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg or on now taking prescribed medicine for hypertension. The directed acyclic graphs (DAG) and the back-door criterion were used to select a minimal sufficient adjustment set of variables (MSAs) that would identify the unconfounded effect of 25(OH)D and hypertension. The interactive effect of VDD and SHS on hypertension was evaluated by using logistic regression models, followed by strata-specific analyses. RESULTS: The prevalence of VDD in the hypertension group was significantly higher than that in the non-hypertension group (48.2% vs 41.0%, P = 0.008), as well as the exposure rate of SHS (39.1% vs 33.8%, P = 0.017). VDD was independently associated with nearly 50% increased risk of hypertension [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.01, 2.04], while no significant association was observed between SHS and hypertension. However, SHS showed a significant synergistic effect on VDD with a higher aOR of 1.79 (95% CI: 1.14, 2.80) (Pinteraction = 0.011). This synergistic effect was more obvious when stratified by BMI (in overweight women, aOR, 95% CI =4.74, 1.65-13.60 for interaction vs 2.33, 1.01-5.38 for VDD only) and race (in Non-Hispanic Black women, aOR, 95% CI =5.11, 1.58-16.54 for interaction vs 2.69, 1.10-6.62 for VDD only). CONCLUSION: There exist synergistic effects of SHS and VDD on the prevalence of hypertension in American women of childbearing age, with more significant effects in women who were overweight or Non-Hispanic Black. Further studies are warranted to verify this finding in other populations, and the molecular mechanisms underlying the joint effect of SHS and VDD need to be elucidated.

Dietary n-3 and n-6 fatty acid intakes and NAFLD: A cross-sectional study in the United States.

BACKGROUND AND OBJECTIVES: PUFAs play critical roles in the development of nonalcoholic fatty liver disease (NAFLD). This study examined the associations between dietary n-3 and n-6 PUFA intake and NAFLD risk in a US population. METHODS AND STUDY DESIGN: Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 was used in this cross-sectional study. Data on dietary n-3 and n-6 PUFAs were extracted through two 24-h dietary recall interviews, and the dietary n-3 and n-6 PUFA intakes were adjusted by weight. NAFLD was defined based on the US fatty liver index (FLI) value ≥30. Multivariable logistic regression models and restricted cubic spline models were applied to investigate the associations between dietary n-3 and n-6 PUFA intakes and NAFLD risk. RESULTS: Dietary n-3 and n-6 PUFA intakes were inversely associated with NAFLD risk. The multivariable-adjusted OR (95% CI) of NAFLD for the highest versus lowest quartile of dietary n-3 and n-6 PUFA intakes was 0.24 (0.17-0.35) and 0.18 (0.13-0.26), respectively. In stratified analyses by sex and age, the negative associations between dietary n-3 and n-6 PUFA intakes and NAFLD risk were significant in men, women, and individuals younger and older than 45 years. Dose-response analyses indicated that NAFLD risk was associated with dietary n-3 and n-6 PUFA intakes in a nonlinear manner. CONCLUSIONS: Dietary n-3 and n-6 PUFA intakes were inversely associated with NAFLD risk in US adults.

Anti-dsDNA, anti-nucleosome, anti-C1q, and anti-histone antibodies as markers of active lupus nephritis and systemic lupus erythematosus disease activity.

INTRODUCTION: Previous studies of anti-dsDNA, nucleosome (Nucl), histone (His), and C1q antibodies have revealed their clinical value in systemic lupus erythematosus (SLE). However, the correlation between four autoantibodies and SLE activity, lupus nephritis (LN) remains controversial, and data are insufficient on longitudinal monitoring. This study aimed at evaluating the value of these autoantibodies in active LN, and their performance on cross-sectional evaluating and longitudinal monitoring of SLE disease activity. METHODS: Serum levels of four autoantibodies in 114 SLE patients, 219 other autoimmune disease patients (OAD), and 59 healthy controls were assayed by a quantitative immunoassay. Sera of 38 inpatients were obtained again after treatment. RESULTS: We found that serum levels of four autoantibodies were significantly higher in SLE than OAD patients (p < 001), active LN than non-renal SLE patients (p < .05), and higher in SLE patients with moderate and severe disease activity than mild disease activity (p < .01). Horizontally, serum level of each autoantibody was correlated with SLE disease activity index (SLEDAI) (p < .05), and correlation coefficient of anti-dsDNA was the highest (r = .585). For longitudinal monitoring, the decreased levels of four autoantibodies were found following treatment (p < .001). Serum level variations of these antibodies were positively correlated with variations of SLEDAI (p < .05). The correlation coefficient of anti-Nucl was the highest (r = .629). Although the levels of C3 and C4 increased after treatment, the change was not related to the change of SLEDAI (p > .05). CONCLUSIONS: Anti-C1q, anti-dsDNA, anti-Nucl, and anti-His perform well in diagnosing active LN and monitoring SLE disease activity. They could be indicators of active LN and SLE disease activity.

Pseudogene DUXAP8 Promotes Cell Proliferation and Migration of Hepatocellular Carcinoma by Sponging MiR-490-5p to Induce BUB1 Expression.

Hepatocellular Carcinoma (HCC) currently remains one of the most lethal malignancies worldwide. Recently, long non-coding RNAs (lncRNAs) had been demonstrated to play a crucial role in the progression of multiple human cancers, including HCC. In this study, we found that lncRNA DUXAP8 was upregulated in tumor samples and served as an oncogene in HCC. Bioinformatics analysis showed that DUXAP8 was significantly associated with the regulation of centrosome organization, homologous recombination, meiotic cell cycle process, sister chromatid segregation, nuclear chromosome segregation, and RNA export from the nucleus. The knockdown of DUXAP8 significantly suppresses cell proliferation and the cell cycle but induces cell apoptosis in HCC. Mechanically, the present study showed that DUXAP8 serves as a sponge of MiR-490-5p to promote the expression of BUB1 in HCC. Although the underlying regulatory mechanisms of DUXAP8 in HCC require further investigation, this study, for the first time, showed that DUXAP8 can serve as a new therapeutic target for HCC.

Poor Vitamin D Status in Active Pulmonary Tuberculosis Patients and Its Correlation with Leptin and TNF-α.

Vitamin D deficiency (VDD) is common in tuberculosis (TB) and may be implicated in the etiology of the disease and in its clinical course. The aim of this study was to investigate the association between leptin, inflammatory markers and VD status in TB patients, stratified for presence or absence of diabetes mellitus (DM). Two hundred ninety-nine TB patients were recruited from October 2015 to August 2016. Also, 91 normal controls were included. The information including socio-demographics, dietary intake and living habits was obtained by face-to-face interview. Serum concentrations of leptin and TNF-α, CRP and IL-6 were compared between TB patients with and without severe VDD (SVDD). Pearson's correlation was used to analyze the association between TNF-α, leptin and 25-hydroxyvitamin D (25(OH)D). A significantly higher prevalence of VDD and SVDD was observed in TB patients compared with normal controls (93.0% vs 70.3%, 65.9% vs 3.3% respectively). Concentration of leptin was significantly lower, while TNF-α higher in TB patients with SVDD compared to those without (p<0.05). After adjustment for confounders, leptin was positively associated with 25(OH)D (r=0.210, p=0.002) with similar correlation in TB patients with DM (r=0.240, p=0.020). A negative association between TNF-α and 25(OH)D was observed (r=-0.197, p=0.003), which was significant only in the subgroup without DM (r=-0.304, p=0.001). Our findings indicate that a higher VD status in TB patients may be related to higher immune activity and less serious tissue damage, and that this relation is different according to presence or absence of DM co-morbidity.

Evaluation of blood zinc, calcium and blood lead levels among children aged 1-36 months.

BACKGROUND: Early childhood lead exposure is associated with numerous adverse health effects. Biomonitoring among susceptible populations, such as children, has not been previously conducted. The aim of the study is to evaluate the blood lead (Pb) and total blood calcium (Ca) levels; blood zinc (Zn) levels. METHODS: A cross-sectional study was designed to collect healthy children age 1- 36 months (Mean ± SD: 1.5 ± 0.6 age, 60% boys) in the study from January 2010 to September 2011. RESULTS: The overall mean blood Pb levels were 42.18 ± 12.13 µg/L, the overall mean blood Zn and total blood Ca concentrations were 62.18 ± 12.33 µmol/L and 1.78 ± 0.13 mmol/L, respectively. The prevalence of elevated blood Pb levels in all children was 1.3%. A significant difference was found between female and male subjects for the blood Pb and Zn. After controlling for gender and age, there was a weak positive correlation between total blood Ca and Zn level. CONCLUSIONS: The blood Pb levels had a significant negative correlation with total blood Ca level after adjusting for age and gender, and these findings suggest that Pb had effect on positive blood Zn and total blood Ca levels; parents should pay more attention to the nutrition of girls.

Antecedentes: La primera infancia la exposición al plomo se asocia con numerosos efectos adversos a la salud. Biomonitoring entre poblaciones sensibles, como niños, no ha sido previamente realizado. El objetivo del estudio es evaluar la sangre de plomo (PB) y el total de los niveles de calcio en la sangre (CA), zinc (Zn) los niveles de sangre. Métodos: Un estudio transversal fue diseñado para recoger los niños sanos de edad 1 - 36 meses (media ± SD: 1,5 ± 0,6 edad, 60% de los niños) en el estudio a partir de enero de 2010 a septiembre de 2011. Resultados: La media global sangre PB niveles fueron 42.18 ± 12.13 µg / l, la media general y total de sangre sangre Zn ca las concentraciones eran 62,18 ± 12.33 µ mol / l y 1,78 ± 0,13 mmol / l, respectivamente.La prevalencia de sangre elevados niveles de PB en todos los niños fue de 1,3%.Una diferencia significativa se encontró entre hembra y macho sujetos para la sangre, Pb y Zn.Despues de controlar por edad y género, existe una débil correlación positiva entre el total de sangre CA y Zn. Conclusiones: La sangre PB niveles había una correlación negativa significativa con total sangre CA nivel tras ajustar por edad y género, y estos hallazgos sugieren que la PB tuvo efecto en la sangre total positivo de Zn y sangre CA Los niveles; los padres deben prestar más atención a la nutrición de las niñas.

Evaluation of blood zinc, calcium and blood lead levels among children aged 1-36 months / Evaluación de sangre, zinc, calcio y el nivel de plomo en la sangre entre los niños de 1 a 36 meses

Background: Early childhood lead exposure is associated with numerous adverse health effects. Biomonitoring among susceptible populations, such as children, has not been previously conducted. The aim of the study is to evaluate the blood lead (Pb) and total blood calcium (Ca) levels; blood zinc (Zn) levels. Methods: A cross-sectional study was designed to collect healthy children age 1- 36 months (Mean ± SD: 1.5 ± 0.6 age, 60% boys) in the study from January 2010 to September 2011. Results: The overall mean blood Pb levels were 42.18 ± 12.13 μg/L, the overall mean blood Zn and total blood Ca concentrations were 62.18 ± 12.33 μmol/L and 1.78 ± 0.13 mmol/L, respectively. The prevalence of elevated blood Pb levels in all children was 1.3%. A significant difference was found between female and male subjects for the blood Pb and Zn. After controlling for gender and age, there was a weak positive correlation between total blood Ca and Zn level. Conclusions: The blood Pb levels had a significant negative correlation with total blood Ca level after adjusting for age and gender, and these findings suggest that Pb had effect on positive blood Zn and total blood Ca levels; parents should pay more attention to the nutrition of girls (AU)

Antecedentes: La primera infancia la exposición al plomo se asocia con numerosos efectos adversos a la salud. Biomonitoring entre poblaciones sensibles, como niños, no ha sido previamente realizado. El objetivo del estudio es evaluar la sangre de plomo (PB) y el total de los niveles de calcio en la sangre (CA), zinc (Zn) los niveles de sangre. Métodos: Un estudio transversal fue diseñado para recoger los niños sanos de edad 1 - 36 meses (media ± SD: 1,5 ± 0,6 edad, 60% de los niños) en el estudio a partir de enero de 2010 a septiembre de 2011. Resultados: La media global sangre PB niveles fueron 42.18 ± 12.13 μg / l, la media general y total de sangre sangre Zn ca las concentraciones eran 62,18 ± 12.33 μ mol / l y 1,78 ± 0,13 mmol / l, respectivamente.La prevalencia de sangre elevados niveles de PB en todos los niños fue de 1,3%.Una diferencia significativa se encontró entre hembra y macho sujetos para la sangre, Pb y Zn. Despues de controlar por edad y género, existe una débil correlación positiva entre el total de sangre CA y Zn. Conclusiones: La sangre PB niveles había una correlación negativa significativa con total sangre CA nivel tras ajustar por edad y género, y estos hallazgos sugieren que la PB tuvo efecto en la sangre total positivo de Zn y sangre CA Los niveles; los padres deben prestar más atención a la nutrición de las niñas (AU)