Characterization of human and mouse peroxiredoxin IV: Evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species

The aim of this study was to identify and characterize human and mouse Prx-IV. We identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal presequence coding for signal peptide. The amino acid sequences of mature mouse and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously, we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of multiloci genetic crosses. Here we performed further comparative analysis of mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx-IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete human Prx-IV locus was identified. The size of 7 exons and the sequences of the splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is abundantly expressed in many tissues. However, we could not detect Prx-IV in the conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically found in the nucleus-excluded region of cultured mouse cells. Intracellularly, overexpression of mouse Prx-IV prevented the production of reactive oxygen species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular redox signaling.published_or_final_versio

Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma

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Auto-Conforming Ergonomic Chair

The Auto-Conforming Ergonomic (ACE) Chair is an office chair that will adjust itself to comfortably support anyone that sits in it. By sensing the position of the seated user, the ACE Chair can intelligently adjust the backrest, seat, and armrests to provide the user with unparalleled ergonomic support and seating comfort

Reduction of liver stiffness following resolution of acute flares of chronic hepatitis B

Background: Measuring liver stiffness is becoming more popular as a non-invasive tool for assessing liver fibrosis. Aim: To assess the effect of severe hepatitis B flare on liver stiffness and determine factors that correlate with liver stiffness measurements. Methods: Twenty-nine patients with severe hepatitis B flare (ALT > 10 × upper limit of normal) were followed up for 1 year. Serial transient elastography was performed at the time of flare, 3-6, and 12 months after flare. Results: At the time of flare, the median liver stiffness was 16.8 kPa, with no patients having normal liver stiffness (<6 kPa). There was a significant decrease in liver stiffness from baseline to 3-6 months (16.8 vs. 7.9 kPa, respectively, P < 0.001), and a further smaller decline from 3-6 to 12 months (7.9 vs. 6.9 kPa, respectively, P = 0.039). By 12 months, 10 (34%) had normalized their liver stiffness. Baseline parameters which correlated with liver stiffness include bilirubin, ALT, albumin, prothrombin time and platelet levels (all P < 0.05). Conclusion: Liver stiffness was increased in patients with severe hepatitis B flares, with return to near normal levels by 6 months. Transient elastography for proper assessment of liver fibrosis should be performed at least 6 months after flare. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 31 May 201

The use of transient elastography in the management of chronic hepatitis B

There has been increasing interest in noninvasive methods of assessing liver fibrosis over the last decade. The use of transient elastography in measuring liver stiffness has become the forefront of a wide range of noninvasive tools. Most of the other methods are based on measurements of biomarkers associated with fibrosis. There are several reasons for its wide acceptance, including the ease of performing a scan, the short procedure time, the results being immediately available on completion of the examination, and its reproducibility. For chronic hepatitis B (CHB), the cut-off values for F3 and F4 fibrosis range between 7.5–12.0 and 11.0–13.4 kPa, respectively, although the cut-offs may be slightly lower in those with normal ALT. In addition to measuring liver fibrosis, recent studies have demonstrated several other roles for transient elastography, including selecting patients who will benefit from antiviral therapy, monitoring response to antiviral therapy, and predicting long-term outcomes. However, there are limitations associated with transient elastography, including the confounding effects of inflammatory activity, and to a lesser extent, steatosis, on liver stiffness. There is also reduced accuracy observed in lower fibrosis stages (F0–F2). Furthermore, the incidences of failed and unreliable scan have been reported to be ~ 3 and 16%, respectively. Although liver biopsy can be avoided in an estimated 50–60% using transient elastography, in situations where liver stiffness measurement is nondiagnostic or inconsistent with the clinical picture, a biopsy is still recommended. Further studies are needed to consolidate the role of transient elastography in the management of CHB, and for incorporation of this method into current treatment guidelines

Simultaneous or Sequential Orthogonal Gradient Formation in a 3D Cell Culture Microfluidic Platform

Biochemical gradients are ubiquitous in biology. At the tissue level, they dictate differentiation patterning or cell migration. Recapitulating in vitro the complexity of such concentration profiles with great spatial and dynamic control is crucial in order to understand the underlying mechanisms of biological phenomena. Here, a microfluidic design capable of generating diffusion-driven, simultaneous or sequential, orthogonal linear concentration gradients in a 3D cell-embedded scaffold is described. Formation and stability of the orthogonal gradients are demonstrated by computational and fluorescent dextran-based characterizations. Then, system utility is explored in two biological systems. First, stem cells are subjected to orthogonal gradients of morphogens in order to mimic the localized differentiation of motor neurons in the neural tube. Similarly to in vivo, motor neurons preferentially differentiate in regions of high concentration of retinoic acid and smoothened agonist (acting as sonic hedgehog), in a concentration-dependent fashion. Then, a rotating gradient is applied to HT1080 cancer cells and the change in migration direction is investigated as the cells adapt to a new chemical environment. The response time of ≈4 h is reported. These two examples demonstrate the versatility of this new design that can also prove useful in many applications including tissue engineering and drug screening.National Science Foundation. Science and Technology Center for Emergent Behaviors of Integrated Cellular Systems (Grant No. CBET-0939511)National Institutes of Health (U.S.) (NIH NRSA/UNCF Merck

Chronic hepatitis B: whom to treat and for how long? Propositions, challenges, and future directions

Recent guidelines of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver 2008 update of the “Asian-Pacific consensus statement on the management of chronic hepatitis B” offer comprehensive recommendations for the general management of chronic hepatitis B (CHB). These recommendations highlight preferred approaches to the prevention, diagnosis, and treatment of CHB. Nonetheless, the results of recent studies have led to an improved understanding of the disease and a belief that current recommendations on specific therapeutic considerations, including CHB treatment initiation and cessation criteria, particularly in patient populations with special circumstances, can be improved. Twelve experts from the Asia-Pacific region formed the Asia-Pacific Panel Recommendations for the Optimal Management of Chronic Hepatitis B (APPROACH) Working Group to review, challenge, and assess relevant new data and inform future updates of CHB treatment guidelines. The significance of and controversy about reported findings were discussed and debated in an expert meeting of the Working Group in Beijing, China, in November 2008. This review paper attempts to identify areas requiring improved CHB management and provide suggestions for future guideline updates, with special emphasis on treatment initiation and duration