Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

Association between lipoproteins and telomere length in US adults: data from the NHANES 1999-2002.

BACKGROUND: Evidence regarding the correlation between lipoproteins and telomere length in US adults is limited. We aimed to investigate whether lipoproteins was associated with telomere length using US National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 6468 selected participants were identified in the NHANES Data Base (1999-2002). The independent and dependent variables were lipoproteins and telomere length, respectively. The covariates included demographic data, dietary data, physical examination data, and comorbidities. RESULTS: In fully-adjusted model, we found that 0.1 differences of telomere length were positively associated with HDL-C [0.19 (95% CI 0.07, 0.31)], while the associations between LDL-C [0.19 (95% CI -0.27, 0.65)], TG [- 1.00 (95% CI -2.09, 0.07) and telomere length were not detected. By nonlinearity test, only the relationship between HDL-C and telomere length was nonlinear. The inflection point we got was 1.25. On the left side of the inflection point (telomere length ≤ 1.25), a difference in 0.1 of telomere length was associated with 0.50 difference in HDL-C. CONCLUSION: After adjusting for demographic data, dietary data, physical examination data, and comorbidities, telomere length is not associated with LDL-C and TG, but is positively associated with HDL-C when telomere length is less than 1.25.

Estimated glomerular filtration rate and arterial stiffness in Japanese population: a secondary analysis based on a cross-sectional study.

BACKGROUND: Evidence regarding the relationship between estimated glomerular filtration rate (eGFR) and arterial stiffness is limited, and the data analysis is not sufficient to clarify the true relationship between the two. We aimed to investigate the relationship between eGFR and brachial-ankle pulse wave velocity (baPWV) in Japanese. METHODS: The present study was a cross-sectional study. Nine hundred twelve Japanese men and women, aging 24-84 years old, received a health medical check-up program including the results from baPWV inspection and various standardized questionnaires in a health examination center in Japan. The main outcome measures included eGFR, baPWV, fatty liver and postmenopausal status. Abdominal ultrasonography was used to diagnose fatty liver. Postmenopausal state was defined as beginning 1 year after the cessation of menses. RESULTS: The average age of the 912 selected participants was 51.5 ± 9.6 years old, and about 57.6% of them were male. The participants' eGFR distribution was median 69.29 (min 39, max 122.28). The results of multivariate linear regression showed eGFR was not independently associated with baPWV after adjusting potential confounders (ß = - 1.11, 95%CI -2.25 to 0.03), this is inconsistent with the result of eGFR (quartile) as a categorical variable (p for trend was 0.038). A non-linear relationship was detected between eGFR and baPWV, whose point was 77.05. The effect sizes and the confidence intervals of the left and right sides of inflection point were - 2.80 (- 4.41 to - 1.19) and 1.84 (- 0.50, 4.17), respectively. Subgroup analysis showed, the change in the elderly population is more pronounced (P for interaction = 0.018; - 2.83 with ≤60 year vs - 6.12 with > 60 year). The same trend was also seen in hypertensive people (P for interaction = 0.018; - 4.55 with hypertension vs - 0.82 with non-hypertension). CONCLUSION: The relationship between eGFR and baPWV is non-linear. eGFR was negatively related to baPWV when eGFR is less than 77.05.

Dietary and physical activity of adult patients with type 2 diabetes in Zhejiang province of eastern China: Data from a cross-sectional study.

AIMS/INTRODUCTION: Lifestyle management helps improve the clinical outcome of patients with type 2 diabetes. The present study aimed to obtain lifestyle data on the dietary and physical activity of adult type 2 diabetes patients in Zhejiang province of eastern China for better patient education and improvement of clinical management. MATERIALS AND METHODS: A cross-sectional survey of 607 adult type 2 diabetes patients was carried out in 12 hospitals within eight cities of Zhejiang province. Data were collected for sex, age, basic physical measurement (blood pressure, height, weight, waist circumference and hip circumference), dietary favor and habit (vegetarian diets vs meat diets, preference of salty or light flavors), detailed dietary intake (24-h recall method), as well as the weekly physical activity. RESULTS: The mean age of the patients in the analysis was 56.39 ± 12.29 years, and 38.71% of the patients had higher levels of body mass index than recommended. The average daily total energy intake was 1887.71 ± 575.10 kcal. The percentage of calories from carbohydrate, protein and fat were 61.36 ± 11.59%, 13.29 ± 3.37% and 25.35 ± 11.16%, respectively. For physical activity, the patients generally spent most of their daily time sitting and sleeping, and the time for moderate vigorous activity was limited. CONCLUSIONS: Adult patients with type 2 diabetes in Zhejiang province have a relatively high carbohydrate and low protein diet, with very limited physical activity. Patient education to achieve a better lifestyle intervention needs to improve in this region.