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.     

Consistent modeling of capacitances and transit times of GaAs-based HBTs

This paper investigates how time delays and capacitances observed under small-signal conditions can be consistently accounted for in heterojunction bipolar transistor (HBT) large-signal models. The approach starts at the circuit level by mapping the large-signal equivalent circuit (which consists of charge and current sources) to the well-known small-signal circuit (which consists of capacitances, transit-time, and resistances). It is shown that and how bias dependent charge sources at either pn-junction impact transit-time, base-collector capacitance, and their mutual dependence. It is demonstrated for the example of a GaAs-based HBT that the interrelation of the elements is observed in measurements as predicted. The results of the investigation enhance understanding of HBT model characteristics and provide a criterion to check model consistency.     

Analysis of the Survivability of GaN Low-Noise Amplifiers

This paper presents a detailed analysis of the stressing mechanisms for highly rugged low-noise GaN monolithic-microwave integrated-circuit amplifiers operated at extremely high input powers. As an example, a low-noise amplifier (LNA) operating in the 3-7-GHz frequency band is used. A noise figure (NF) below 2.3 dB is measured from 3.5 to 7 GHz with NF<1.8 dB between 5-7 GHz. This device survived 33 dBm of available RF input power for 16 h without any change in low-noise performance. The stress mechanisms at high input powers are identified by systematic measurements of an LNA and a single high electron-mobility transistor in the frequency and time domains. It is shown that the gate dc current, which occurs due to self-biasing, is the most critical factor regarding survivability. A series resistance in the gate dc feed can reduce this gate current by feedback, and may be used to improve LNA ruggedness     

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.