Cytoplasmic signaling involved in sonoporation-induced apoptosis andmitosis repression of myeloid leukemia cells

Sonoporation is known to be a transient phenomenon that may disrupt thehomeostasis of living cells. In this work, we showed that sonoporation may beartime-lapse impact on cellular viability through up-regulation of cytoplasmicsignaling proteins related to apoptosis and cell-cycle arrest. Our experimentswere done on HL-60 leukemia cells (10 6 cells/ml), and sonoporationwas induced via the use of 1% v/v microbubbles and 1-min. pulsed ultrasoundexposure (0.5MPa peak negative pressure, 1MHz center frequency, 10% duty cycle,1 kHz pulse repetition frequency). The transient nature of sonoporation in thesecells was confirmed by performing scanning electron microscopy on selected cellsamples that were fixed respectively after a few seconds into the ultrasoundexposure and one minute after the end of exposure. Cytoplasmic signaling changesof these cells were studied at four post-sonoporation time points (4h, 8h, 12h,24h) using western blot analysis. Five signaling proteins related to apoptosisand mitosis were analyzed in this work: 1) PARP (for DNA repair); 2)cleaved-PARP (fragments due to cleavage by pro-apoptotic caspase proteins); 3)Bcl-2 (inhibitor for mitochrondrial release of pro-apoptotic molecules); 4) Bax(complement of Bcl-2); 5) Cdc-2 (regulator for cell mitosis). Three key resultswere found from the cytoplasmic signaling analysis. First, PARP levels werereduced over the monitoring period whilst cleaved-PARP had increased inexpression, and in turn they indicate that the cells' anti-apoptotic responseswere dampened following sonoporation and pro-apoptotic caspase proteins werelikely activated. Second, drop in Bcl-2 and rise in Bax were observed, and thesesuggest that the mitochondrion was involved in apoptotic signal transductioninside sonoporated cells. Third, Cdc-2 was seen to decrease, implying thatmitosis was repressed in sonoporated cells. © 2010 IEEE.published_or_final_versionThe 2010 IEEE International Ultrasonics Symposium, San Diego, CA., 11-14 October 2010. In Proceedings of IEEE IUS, 2010, p. 1771-177

Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: a proteomic study

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Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury

Lipopolysaccharide (LPS) has been implicated as one of the major cause of Gram-negative bacteria-induced sepsis that are life-threatening syndromes occurring in intensive care unit patients. Many natural products derived from medicinal plants may contain therapeutic values on protecting endotoxemia-induced sepsis by virtue their ability to modulate multiple pro-inflammatory cytokines. In the present study, we show that Salvia miltiorrhiza (SM) BUNGE or Danshen, used in treatment of various systemic and surgical infections in the hospitals of China, was able to block the lethal toxicity of LPS in mice via suppression of TNF-α release and protection on liver injury. The ability of SM to suppress LPS-induced TNF-α release is further confirmed by in vitro experiments conducted on human peripheral blood leukocytes (PBL) and the RAW 264.7 macrophage cell line. Immunophenotyping by flow cytometry shows improved T-helper cell (CD4) and T-suppressor cells (CD8) ratio in SM-treated PBL and splenocytes of LPS-challenged mice. The drop in plasma glutamate-pyruvate transaminase (GPT) induced by LPS provides evidence that SM can protect hepatic damage. The present study explains some known biological activities of SM, and supports the clinical application of SM in the prevention of inflammatory diseases induced by Gram-negative bacteria. © 2005 Elsevier B.V. All rights reserved.postprin

Jacobi-Predictor-Corrector Approach for the Fractional Ordinary Differential Equations

We present a novel numerical method, called {\tt Jacobi-predictor-corrector approach}, for the numerical solution of fractional ordinary differential equations based on the polynomial interpolation and the Gauss-Lobatto quadrature w.r.t. the Jacobi-weight function $\omega(s)=(1-s)^{\alpha-1}(1+s)^0$. This method has the computational cost O(N) and the convergent order $IN$, where $N$ and $IN$ are, respectively, the total computational steps and the number of used interpolating points. The detailed error analysis is performed, and the extensive numerical experiments confirm the theoretical results and show the robustness of this method.Comment: 24 pages, 5 figure

First two cases of living related liver transplantation with complicated anatomy of blood vessels in Beijing

Aim: Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. Though it has been succeeded in many centers worldwide, the safety of the donor is still a major concern, especially in donors with anatomy variation. We succeeded in performing the first two cases of living related liver transplantation with complicated anatomy of blood vessels as a way to overcome cadaveric organ shortage in Beijing. Methods: Two patients, with congenital liver fibrosis and congenital biliary atresia were performed with living donor liver transplantation in our hospital and then followed up from November 12 to December 13, 2001. The two living donors, mother and father, were healthy aged 34 and 35 years. One right lobe (segment V, VI, VII, VIII) and one left lateral lobe (segment II and III) were used. The grafts weighed 394 g and 300 g. The ratio of graff weight to the standard liver volume (SLV) of donors was 68% and 27%. The graft weight to recipient body weight ratio was 3.2% and 4.4%. The graft weight to recipient estimated standard liver mass (ESLM) ratio was 63% and 85%. The two donors had complicated blood vessel variation. Results: Two patients undergone living donor liver transplantation had good results. Abnormal liver function with high bilirubin level appeared in a few days after operation, bur liver function returned to normal one month after operation with bilirubin level almost decreased to near normal. No bleeding, thrombosis, infection and bile leakage occurred. One had an acure rejection and recovered. The two donors recovered in two weeks. One had slight fever because of a little collection in abdomen and recovered after paracentesis and drainage. Conclusion: Living donor liver transplantation has been proved to be a good way that offers a unique opportunity of getting a timely liver graft as a response to shortage of pediatric donors, though it could be a technically difficult operation if there is anatomical variation. Copyright © 2004 by The WJG Press.published_or_final_versio

Antibiotics Increase Gut Metabolism and Antioxidant Proteins and Decrease Acute Phase Response and Necrotizing Enterocolitis in Preterm Neonates

Background: The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. Methodology/Principal Findings: Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased. Conclusions/Significance: Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates. © 2012 Jiang et al.published_or_final_versio

Highly phosphorescent platinum(II) emitters: photophysics, materials and biological applications

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Short-Term Prognosis of Transient Ischemic Attack and Predictive Value of the ABCD2 Score in Hong Kong Chinese

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Insufficient activity of MAPK pathway is a key monitor of Kidney-Yang Deficiency Syndrome.

OBJECTIVE: To explore the genetic characteristics and molecular regulator of Kidney-Yang Deficiency Syndrome (KDS). DESIGN: A typical KDS family was collected using a questionnaire of cold feeling and a 40-item scoring table of KDS based on Traditional Chinese Medicine (TCM), by single-blind method repeated annually over three years. Their transcriptomes were assayed by microarray and validated by RT-PCR and ELISA. Simultaneously, 10 healthy volunteers were recruited as controls and the same protocols were performed. RESULTS: This typical KDS family has 35 members, of whom 11 were evaluated as having severe KDS and 6 as having common KDS. Results of the cDNA microarray revealed that there were 420 genes/expressed sequence tags differentially expressed in KDS transcriptomes, indicating a global functional impairment in the mass-energy-information carrying network of KDS patients, involving energy metabolism, signal transduction, development, cell cycle, and immunity. Pathway analysis by gene set enrichment assay (GSEA) and other tools demonstrated that mitogenic activated protein kinase (MAPK) is among the most insufficiently activated pathways, while the oxidative phosphorylation and glycolysis/gluconeogenesis pathways, the two main pathways relevant to ATP synthesis, were among the most excessively activated pathways in KDS patients. Results of RT-PCR and ELISA confirmed the status of insufficient activity of the MAPK pathway. CONCLUSION: KDS patients undergo overall attenuated functions in the mass-energy-information carrying network. The marked low level of energy output in KDS may be primarily attributed to the insufficient activity of the MAPK pathway, which may be a key monitor for the abnormal energy metabolism and other impaired activities in KDS.published_or_final_versio

DNA content of a functioning chicken kinetochore

© The Author(s) 2014. In order to understand the three-dimensional structure of the functional kinetochore in vertebrates, we require a complete list and stoichiometry for the protein components of the kinetochore, which can be provided by genetic and proteomic experiments. We also need to know how the chromatin-containing CENP-A, which makes up the structural foundation for the kinetochore, is folded, and how much of that DNA is involved in assembling the kinetochore. In this MS, we demonstrate that functioning metaphase kinetochores in chicken DT40 cells contain roughly 50 kb of DNA, an amount that corresponds extremely closely to the length of chromosomal DNA associated with CENP-A in ChIP-seq experiments. Thus, during kinetochore assembly, CENP-A chromatin is compacted into the inner kinetochore plate without including significant amounts of flanking pericentromeric heterochromatin. © 2014 The Author(s).Wellcome Trust [grant number 073915]; Wellcome Trust Centre for Cell Biology (core grant numbers 077707 and 092076); Darwin Trust of Edinburg