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.     

Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.     

Sonochemical synthesis of PANI-BiVO4-GO semiconductor nanocomposite highly efficient visible-light photocatalytic performance

Abstract

Polyaniline/Bismuth Vanadate/Graphene Oxide (PANI-BiVO₄-GO) or BGPA composite was prepared by sonochemical deposition of bismuth vanadate-graphene oxide (BiVO₄) nanoparticles on the surface of polyaniline (PANI). The best photocatalytic degradation performance was obtained by 5wt% BGPA composites for MB, RhB, and SO dyes, which is approximately 4 times higher than that of 1% BGPA. Meanwhile, the photocatalytic stability of BiVO₄ was significantly improved by introducing PANI into the PANI-BiVO₄-GO composite. The dramatic promotion of the photocatalytic degradation performance and the photocatalytic stability can be attributed to the formation of a heterojunction free electron between PANI and BiVO₄-GO. The existence of those extra free electrons can dramatically enhance the efficiency of the photogenerated electrons, which accelerate the transfer of photogenerated holes from BiVO₄-GO to PANI, and therefore inhibit the self-oxidation of BiVO₄.     

Hepatoprotective Potency of Chrysophanol 8-O-Glucoside from Rheum palmatum L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway

Rhubarb is a well-known herb worldwide and includes approximately 60 species of the Rheum genus. One of the representative plants is Rheum palmatum, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of R. palmatum inhibited hepatic stellate cell (HSC) activation by transforming growth factor β1 (TGF-β1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-O-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-O-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-O-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-O-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-β1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-O-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-O-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-O-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.     

Understanding trust in ms-commerce: The roles of reported experience,linguistic style,profile photo,emotional, and cognitive trust

This paper examines what influences trust in mobile social commerce environment. Drawing on trust-based acceptance model (i.e. cognitive and emotional trust) and online review features (i.e. profile photo, linguistic style, and reported experience), we examine how these factors affect trust in mobile social commerce. Hypotheses were tested using survey data. The results of our model showed that there are significant influences of profile photo, reported experience, cognitive, and emotional trust towards trust in ms-commerce. This work contributes to existing literature by examining the roles of previous trust in mobile payments and online reviews on trust in mobile social commerce.     

Flexible Piezoelectric Acoustic Sensors and Machine Learning for Speech Processing

Flexible piezoelectric acoustic sensors have been developed to generate multiple sound signals with high sensitivity, shifting the paradigm of future voice technologies. Speech recognition based on advanced acoustic sensors and optimized machine learning software will play an innovative interface for artificial intelligence (AI) services. Collaboration and novel approaches between both smart sensors and speech algorithms should be attempted to realize a hyperconnected society, which can offer personalized services such as biometric authentication, AI secretaries, and home appliances. Here, representative developments in speech recognition are reviewed in terms of flexible piezoelectric materials, self-powered sensors, machine learning algorithms, and speaker recognition.     

Optimization of C/TiCx duplex diffusion barrier coatings for SiCf/Ti composites based on interfacial structure evolution exploration

Introducing a carbon single coating is a popular method used to protect SiC_f/Ti composites from severe interface reactions. However, carbon coatings lose their protective effect on SiC fibres at high temperature, even after a short period time. As such, given the strong demand for high temperature applications in aeronautics and astronautics a more coating which is more effective at high temperatures is desirable. In order to improve the high temperature interfacial stability of SiC_f/Ti composites, a C/TiC_x duplex coating system with different C contents in TiC_x was introduced to explore the protection of fibres at 1200?°C for 1?h. The results show that the C/quasi-stoichiometric TiC coating system protects the SiC fibres most effectively. Based on insights from the evolution of the interface structure, TiC_x has been identified as an interfacial reaction product from the C single coating, exhibiting a gradient in C content and grain size, which is different from a deposited TiC layer with a well-distributed composition and structure. The different coating structure gives rise to different ability to resist C diffusion at high temperatures, in which poor resistance ability appears in TiC_x interfacial reaction layer coming from C single coating due to short-circuit diffusion in C-rich fine-grained TiC layer and fast intracrystalline diffusion trigged by amounts of vacancies in sub-stoichiometric coarse-grained TiC layer. Therefore, C/quasi-stoichiometric TiC duplex coatings with a thick, coarse-grained quasi-stoichiometric TiC layer could effectively inhibit C diffusion by comparison to C single coatings, and is more effective than C/rich-carbon TiC duplex coatings due to the existence of short-circuit diffusion in the latter. As such, C/quasi-stoichiometric TiC duplex coatings appear to be an optimal diffusion barrier for SiC_f/Ti composites at high temperature.