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.     

The ultrasound appearances of neonatal renal vein thrombosis

Renal vein thrombosis (RVT) is the most frequently occurring vascular condition in the new-born kidney. The predisposing factors include dehydration, sepsis, birth asphyxia, maternal diabetes, polycythaemia and the presence of an indwelling umbilical venous catheter. (RVT) may present clinically with a flank mass, haematuria, hypertension or renal failure. Many imaging modalities have been employed, but ultrasound is the technique most commonly used in the evaluation of neonates with suspected RVT. Thrombosis commences in the small renal veins and subsequently propagates via larger interlobar veins to the main renal vein and inferior vena cava (IVC). The ultrasound appearances depend upon the stage at which the examination is performed and extent of the thrombus. Initially, the interlobular and interlobar thrombus appears as highly echogenic streaks. These streaks commence in a peripheral, focal segment of the involved kidney and only persist for a few days. In the first week the affected kidney swells and becomes echogenic with prominent echopoor medullary pyramids. Later, the swelling increases and the kidney becomes heterogenous with loss of corticomedullary differentiation. Grey scale ultrasound readily demonstrates thrombus within the renal vein and IVC. Adrenal haemorrhage is a recognized association and may be identified ultrasonically. Colour Doppler scanning provides additional information. In the early stages of RVT, colour Doppler may demonstrate absent intrarenal and renal venous flow. Ultimately, the kidney may recover, show focal scarring or become atrophic. Thus, ultrasound provides an accessible and reliable tool in the assessment of suspected neonatal RVT.     

Long-term follow-up (8 to 17 years) after thromboexclusion operation for thoracic aortic aneurysms

Forty-eight Russell's viper bite patients (40 males, 8 females), age ranging from 16-76 years were studied. Out of 48 patients, 14 were found to have a prolonged whole blood clotting time test (WBCT) (i.e. incoagulable blood) (Group 1); 23 had a normal WBCT (i.e. clotted blood) (Group II); and 11 patients had a normal WBCT on admission which changed to non-clotting during the clinical course (Group III). Four patients from group I developed hypotension and 2 expired. The serum cortisol concentration (mean +/- SEM) on admission among groups I and II were 639 +/- 45.6 and 424 +/- 33.2 nmol/l respectively. The blood cortisol level in 35 subjects (controls) were 370.7 +/- 17.7 nmol/l (mean +/- SEM). There was a significant rise of blood cortisol in patients with incoagulable blood when compared to controls at the time of admission to the hospital (p < 0.05); but there was no significant difference among those patients with clotted blood. A much higher mean serum cortisol level was observed in 4 patients with hypotension as compared to 10 patients without shock. These patients with hypotension according to our study shown to have a favorable response to steroid therapy and eventually recovered. Whether higher doses of steroid in addition to antiserum confer extra benefit in suppressing nonspecific venom effects on the pituitary and/or adrenal is not known.     

Study of impurity induced modifications in amorphous N-type (GeSe3·5)100−x Bi x using high pressure technique

The technique of high pressure is utilized to study the carrier transport behaviour in doped and undoped bulk amorphous (GeSe_3·5)_100−x Bi _x (x=0, 2, 4, 10) down to liquid nitrogen temperature to observe impurity induced modifications in amorphous semiconductors. It is observed that pressure induced effects in lightly doped (2 at % Bi) and heavily doped (x=4, 10) semiconductors are markedly different. Results are discussed in view of the incorporation behaviour of the bismuth impurity.     

Acidity and basicity of hydrotalcite derived mixed Mg-Al oxides studied by test reaction of MBOH conversion and temperature programmed desorption of NH3 and CO2

Mg-Al hydrotalcites intercalated with five different interlayer anions—CO₃²⁻, SO₄²⁻, Cl⁻, HPO₄²⁻ or terephthalate—were synthesized by either the coprecipitation or ion-exchange method. The structure of the as-synthesized samples and the presence of intended anions in the interlayer gallery of hydrotalcites were determined by X-ray diffraction and FTIR spectroscopy. On calcination at 600 °C the materials were transformed into mixed metal oxides. The kind of the counterbalancing anions present in the parent hydrotalcite influences strongly textural parameters of the obtained Mg-Al oxides. Both temperature-programmed desorption of NH₃ and CO₂, and test reaction of 2-methyl-3-butyn-2-ol (MBOH) conversion were used to determine the acidity and basicity of the samples. The hydrotalcite derived mixed Mg-Al oxides showed the presence of Brønsted and Lewis acid and base sites. However, the strong basic character of the solids caused that acetone and acetylene were observed as the major products of MBOH conversion.     

A role for Edman degradation in proteome studies

Advances in protein database design and the software used to access the sequence data has led to progress in using protein attributes such as amino acid composition and peptide masses to identify proteins separated by two-dimensional electrophoresis. However, Edman degradation remains the principal technique for protein identification and it presents a significant bottleneck in the progress towards rapid protein identification. Simple modifications to the sequencing hardware, which automate the delivery of protein spots into the sequencer, and parallel sequencing of the protein spots represent a significant advance in the use of Edman degradation to rapidly generate the powerful protein attribute, an N-terminal sequence tag.     

Functional and defective components of avian endogenous virus long terminal repeat enhancer sequences

Oncogenic avian retroviruses, such as Rous sarcoma virus (RSV) and the avian leukosis viruses, contain a strong enhancer in the U3 portion of the proviral long terminal repeat (LTR). The LTRs of a second class of avian retroviruses, the endogenous viruses (ev) lack detectable enhancer activity. By creating ev-RSV hybrid LTRs, we previously demonstrated that, despite the lack of independent enhancer activity in the ev U3 region, ev LTRs contain sequences that are able to functionally replace essential enhancer domains from the RSV enhancer. A hypothesis proposed to explain these data was that ev LTRs contain a partial enhancer that includes sequences necessary but not sufficient for enhancer activity and that these sequences were complemented by RSV enhancer domains present in the original hybrid constructs to generate a functional enhancer. Studies described in this report were designed to define sequences from both the ev and RSV LTRs required to generate this composite enhancer. This was approached by generating additional ev-RSV hybrid LTRs that exchanged defined regions between ev and RSV and by directly testing the requirement for specific motifs by site-directed mutagenesis. Results obtained demonstrate that ev enhancer sequences are present in the same relative location as upstream enhancer sequences from RSV, with which they share limited sequence similarity. In addition, a 67-bp region from the internal portion of the RSV LTR that is required to complement ev enhancer sequences was identified. Finally, data showing that CArG motifs are essential for high-level activity, a finding that has not been previously demonstrated for retroviral LTRs, are presented.