Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

A Hybrid Analytic Model for the Effective Prediction of Different Stages in Chronic Kidney Ailments

Wireless Personal Communications - Chronic kidney disease (CKD) is a gradual loss of kidney function over the period of time and it is irrevocable once functionality reaches the critical state....     

The Central Lyapunov Limit Theorem and the Property of the Asymptotic Normality of the Sequence of Stable Polynomial Coefficients

Journal of Computer and Systems Sciences International - It is shown that the Lyapunov theorem on the distribution properties of the sum of random variables with different distribution densities...     

Mammogram pectoral muscle removal and classification using histo-sigmoid based ROI clustering and SDNN

Multimedia Tools and Applications - Mammograms are the images used by radiologists to diagnose breast cancer. Breast cancer is one of the most common cancers in women. The early detection of breast...     

A comparison of emulsifiers for the formation of oil-in-water emulsions: stability of the emulsions within 9 h after production and MR signal properties

Objective

To provide a basis for the selection of suitable emulsifiers in oil-in-water emulsions used as tissue analogs for MRI experiments. Three different emulsifiers were investigated with regard to their ability to stabilize tissue-like oil-in-water emulsions. Furthermore, MR signal properties of the emulsifiers themselves and influences on relaxation times and ADC values of the aqueous phase were investigated.

Materials and methods

Polysorbate 60, sodium dodecyl sulfate (SDS) and soy lecithin were used as emulsifiers. MR characteristics of emulsifiers were assessed in aqueous solutions and their function as a stabilizer was examined in oil-in-water emulsions of varying fat content (10, 20, 30, 40, 50%). Stability and homogeneity of the oil-in-water emulsions were evaluated with a delay of 3 h and 9 h after preparation using T₁ mapping and visual control. Signal properties of the emulsifiers were investigated by ¹H-MRS in aqueous emulsifier solutions. Relaxometry and diffusion weighted MRI (DWI) were performed to investigate the effect of various emulsifier concentrations on relaxation times (T₁ and T₂) and ADC values of aqueous solutions.

Results

Emulsions stabilized by polysorbate 60 or soy lecithin were stable and homogeneous across all tested fat fractions. In contrast, emulsions with SDS showed a significantly lower stability and homogeneity. Recorded T₁ maps revealed marked creaming of oil droplets in almost all of the emulsions with SDS. The spectral analysis showed several additional signals for polysorbate and SDS. However, lecithin remained invisible in ¹H-MRS. Relaxometry and DWI revealed different influences of the emulsifiers on water: Polysorbate and SDS showed only minor effects on relaxation times and ADC values of aqueous solutions, whereas lecithin showed a strong decrease in both relaxation times (r_1,lecithin = 0.11 wt.%⁻¹ s⁻¹, r_2,lecithin = 0.57 wt.%⁻¹ s⁻¹) and ADC value (Δ(ADC)_lecithin =  − 0.18 × 10^–3 mm²/s⋅wt.%) with increasing concentration.

Conclusion

Lecithin is suggested as the preferred emulsifier of oil-in-water emulsions in MRI as it shows a high stabilizing ability and remains invisible in MRI experiments. In addition, lecithin is suitable as an alternative means of adjusting relaxation times and ADC values of water.