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Azole fungicides are one class of the most extensively applied current-use pesticides. Tebuconazole is a common azole fungicide that has been frequently detected in aquatic ecosystems, thus raising concerns about its ecological safety. However, adverse effects of tebuconazole remain largely unknown, especially with regard to endocrine function in aquatic organisms. In the present study, sexually immature zebrafish were exposed to different concentrations of tebuconazole (0.05, 0.20 and 0.50 mg/L) for 60 days in order to test for transgenerational toxicity on the thyroid endocrine system. Thyroid hormone homeostasis, neuronal, and cardiovascular development were investigated in the F1 generation, which were reared in tebuconazole-free water. In the F0 generation, exposure to 0.20 and 0.50 mg/L tebuconazole reduced both thyroxine (T4) and 3,5,3’-triiodothyronine (T3) levels in females, while the T3 levels were unchanged in males. Decreased heart rate was found in F1 larvae, as well as diminished T4 levels in F1 eggs/larvae. We also observed significantly increased expression of ugt1ab mRNA in two generations of zebrafish. Moreover, expression of mRNA associated with neuronal development (e.g. α1-tubulin, mbp, gap43) and cardiovascular development (e.g. cacna1ab, tnncal) were significantly downregulated in F1 larvae at 5 and 10 dpf. In addition, tebuconazole was detected in F1 eggs following parental exposure, indicating maternal transfer. This study demonstrated that tebuconazole can be transferred to offspring from exposed parents, causing thyroid endocrine disruption and developmental toxicity.



Necroptosis is suggested to have an important role in the pathogenesis of rhabdomyolysis induced acute kidney injury (AKI). In this study, the renoprotective effect of diacerein on glycerol-induced AKI was investigated. Twenty four male albino rats were included in this study and divided into four groups: (group I) saline control group, (group II) glycerol-treated group, (groups III&IV) diacerein + glycerol -treated groups (25 and 50 mg/kg/day) respectively. Renal malondialdehyde (MDA) level in addition to catalase and heme oxygenase (HO) activities were estimated. Comet assay and histopathological changes were evaluated. The levels of pro-apoptotic Bcl-2-associated X (Bax) protein, tumor necrosis factor alpha (TNF-α) and receptor-interacting serine/threonine-protein kinases 3 (RIPK3) were measured by ELISA. RIPK3 and mixed lineage kinase domain-like pseudokinase (MLKL) mRNA expression were assessed by real time PCR. Glycerol treatment caused significant renal histological abnormalities and functional impairment (increased urea and creatinine). Increased levels of renal MDA with concomitant decrease in renal catalase activity and significant DNA damage in comet assay were observed. High expression of RIPK3 and MLKL in the glycerol-treated group with marked elevation of Bax, TNF-α and RIPK3 levels and HO-1 activity were also documented. Diacerein treatment dependently attenuated glycerol induced structural and functional changes in kidney and significantly elicit reduction of renal tissue oxidative damage whereas it decreased renal expression of RIPK3 and MLKL, and decreased Bax, TNF-α and RIPK3 levels and HO-1 activity.



These results demonstrated that diacerein might have potential application in the amelioration of AKI via its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic effects.

Relationship Between Angiopoietin-Like Protein 8 and Fasting Serum Triglyceride Level

Posted by H Yamada, I Kusaka, R Saikawa, et al. on 2019-04-15 14:19:00




The aim of the study was to evaluate the correlation between angiopoietin-like protein 8 (ANGPTL8) and metabolic parameters in non-diabetic healthy humans.



We enrolled 30 healthy Japanese adults (25 men and five women). After 9 h of fasting, we collected blood samples and analyzed the ANGPTL8, lipoprotein lipase (LPL), plasma lipid and glucose metabolic parameters. In addition, we performed 75-g oral glucose tolerance test (OGTT) and measured adipokines (tumor necrosis factor-α, leptin and adiponectin).



Median serum ANGPTL8 level was 224 (167 - 437) pg/mL, and serum ANGPTL8 level positively correlated with serum triglyceride level (r = 0.42, P = 0.021) and negatively correlated with LPL level (r = -0.44, P = 0.015). ANGPTL8 level showed no correlation with body mass index (BMI), waist-hip ratio, and homeostasis model assessment of insulin resistance (HOMA-IR) or with adipose tissue-derived adiponectin and leptin levels. Further, ANGPTL8 showed no association with glucose and insulin levels after 75-g OGTT.



Serum ANGPTL8 level negatively correlated with LPL levels in healthy Japanese adults. Regulation of ANGPTL8 could be a promising therapeutic target for hypertriglyceridemia.



The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Bystander Me45 Melanoma Cells Increase Damaging Effect in UVC-irradiated Cells

Posted by A Krzywon, M Widel. on 2019-03-29 10:38:00



The aim of our study was to investigate the possible mechanism(s) of the bystander effect induced by UVC light in malignant melanoma Me45 cells that were co‐incubated with irradiated cells of the same line. We have found that the UVC band effectively generated apoptosis, premature senescence, single and double DNA strand breaks and reduced clonogenic survival of bystander cells. However, in the feedback response, the bystander cells intensified damage in directly irradiated cells, especially seen at the level of apoptosis and survival of clonogenic cells. Pretreatment of bystander cells with inhibitor of inducible nitric oxide synthase blocks this signaling. It seems that the mediators of this phenomenon produced and secreted by neighboring cells are superoxide, nitric oxide and TGF‐β. The reverse deleterious effect caused by cells not exposed to UVC in directly exposed cells is opposed to the protective/rescue effect exerted by the bystander cells in the case of ionizing radiation known in the literature. Whether this opposite adverse effect is a feature of only Me45 melanoma cells or whether it is a general phenomenon occurring between cells of other types exposed to ultraviolet radiation requires further research.

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