Updates on the Immune Cell Basis of Hepatic Ischemia-Reperfusion Injury

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes

Large-scale preparation of active caspase-3 in E. coli by designing its thrombin-activatable precursors

<p>Abstract</p> <p>Background</p> <p>Caspase-3, a principal apoptotic effector that cleaves the majority of cellular substrates, is an important medicinal target for the treatment of cancers and neurodegenerative diseases. Large amounts of the protein are required for drug discovery research. However, previous efforts to express the full-length caspase-3 gene in <it>E. coli </it>have been unsuccessful.</p> <p>Results</p> <p>Overproducers of thrombin-activatable full-length caspase-3 precursors were prepared by engineering the auto-activation sites of caspase-3 precursor into a sequence susceptible to thrombin hydrolysis. The engineered precursors were highly expressed as soluble proteins in <it>E. coli </it>and easily purified by affinity chromatography, to levels of 10–15 mg from 1 L of <it>E. coli </it>culture, and readily activated by thrombin digestion. Kinetic evaluation disclosed that thrombin digestion enhanced catalytic activity (<it>k</it>_cat/<it>K</it>_<it>M</it>) of the precursor proteins by two orders of magnitude.</p> <p>Conclusion</p> <p>A novel method for a large-scale preparation of active caspase-3 was developed by a strategic engineering to lack auto-activation during expression with amino acid sequences susceptible to thrombin, facilitating high-level expression in <it>E. coli</it>. The precursor protein was easily purified and activated through specific cleavage at the engineered sites by thrombin, generating active caspase-3 in high yields.</p

Potassium chloride elicits enhancement of bilobalide and Ginkgolides production by Ginkgo biloba cell cultures

This study investigated the ability of potassium chloride (KCl) to elicit the production of bilobalide (BB), ginkgolide A (GA) and ginkgolide B (GB) by Ginkgo biloba cell suspension cultures. The salt stress by KCl treatments increased production of BB, GA and GB in both suspended cells and cultured medium. Especially, treatment of KCl 800 mM of highest concentration was stimulated emission into cultured medium BB, GA and GB compounds accumulated in cells. Although KCl 800 mM severely inhibited cells growth, the maximum content of GA and GB in cells was obtained in the treatment of KCl 800 mM, which was 1.9 and 4.0 times higher than the control. These results thus suggest that salt stress can afford enhanced production of secondary metabolites by plant cell cultures

Prenatal Diagnosis of Bilateral Pulmonary Agenesis: a Case Report

We report a case of bilateral pulmonary agenesis (BPA), which was suspected during a prenatal US examination and diagnosed by fetal magnetic resonance imaging (MRI). BPA is an extremely rare congenital anomaly and, although many fetal structural defects can be detected with a high degree of confidence after introducing high-resolution US, the prenatal diagnosis of BPA remains problematic. Other thoracic abnormalities, such as a congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, and pulmonary sequestration, should be excluded from the list of possible diagnoses before coming to the conclusion of BPA, because BPA is absolutely incompatible with extrauterine life, and an accurate internal diagnosis can prevent a futile intervention from being performed.Lee EY, 2008, RADIOLOGY, V247, P632, DOI 10.1148/radiol.2473062124Moreno-Alvarez O, 2008, ULTRASOUND OBST GYN, V31, P164, DOI 10.1002/uog.5201Obenauer S, 2008, CLIN IMAG, V32, P48, DOI 10.1016/j.clinimag.2007.08.019Joshi S, 2007, EARLY HUM DEV, V83, P789, DOI 10.1016/j.earlhumdev.2007.09.007Jeanty C, 2007, ULTRASOUND OBST GYN, V29, P378, DOI 10.1002/uog.3958Nazir Z, 2006, J PEDIATR SURG, V41, P1165, DOI 10.1016/j.jpedsurg.2006.02.012Gabarre JA, 2005, J ULTRAS MED, V24, P865Levine D, 2003, RADIOLOGY, V228, P379, DOI 10.1148/radiol.2282020604Vettraino IM, 2003, J ULTRAS MED, V22, P723Yang JI, 2003, J CLIN ULTRASOUND, V31, P214, DOI 10.1002/jcu.10157Laudy JAM, 2000, ULTRASOUND OBST GYN, V16, P284Kalache KD, 1997, FETAL DIAGN THER, V12, P360ENGELLENNER W, 1989, PEDIATR PATHOL, V9, P725

Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+ T cells and CD4+ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression