USP14 inhibitor IU1 prevents ventilator-induced lung injury in rats.

The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation. USP14 removes the ubiquitin chain of I-κB, therefore inducing I-κB degradation and increasing cytokine release. The purpose of this study was to examine the protecting roles and mechanisms of USP14 inhibitor on I-κB expression and lung injury induced by high tidal volume ventilation in normal rat lung. Male Sprague-Dawley rats were divided into follows: Two ventilation modalities were used: rats in Groups LD (low volume + DMSO) and LI (low volume + IU1) received ventilation with a tidal volume of 8 ml/kg, while the rats in Groups HD (high volume + DMSO) and HI (high volume + IU1) were ventilated with a tidal volume of 40 ml/kg. The levels of lung wet-to-dry weight ratio were used as indicators of water metabolism in lung tissue; the detection of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid was used to indicate inflammatory response, while lung injury was assessed by injury score and morphological changes under light microscope. The USP14 and I-κB protein level was measured in lung tissue by Western blot. Our results indicated that administration of IU1 alleviated ventilator-induced lung injury which was accompanied by reduced MPO activity, wet-to-dry weight ratio, lower TNF-α, IL-1ß, IL-6 and IL-8 levels and increased I-κB expression in lung tissue. IU1 could significantly alleviate ventilator-induced rat lung injury by attenuate intrapulmonary inflammatory response.

Cell permeability, migration, and reactive oxygen species induced by multiwalled carbon nanotubes in human microvascular endothelial cells.

Multiwalled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level.

Cell permeability, migration, and reactive oxygen species induced by multiwalled carbon nanotubes in human microvascular endothelial cells.

Multiwalled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level.

Multi-walled carbon nanotube-induced gene expression in the mouse lung: association with lung pathology.

Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n=80) exposed to 0, 10, 20, 40, or 80µg of MWCNT by pharyngeal aspiration at 7 and 56days post-exposure using quantitative PCR assays. At 7 and 56days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7days post-exposure were attenuated at 56days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs.

[Hepatitis virus infection and bone marrow transplantation].

Hepatitis virus infection is a special problem in China and the role of Hepatitis virus infection in allogeneic bone marrow transplantation (BMT) is not well-defined. In this study, 106 BMT patients were included for analysis of the role of virus infection in allo-BMT. Seven and 65 of 106 patients were found to have HBV infection and HCV infection, respectively. Neither HBV infection and HCV infection interfered with the engraftment of bone marrow cells nor increased the rate of AGVHD, CGVHD, VOID. Neither HBV infection nor HCV infection prohibited allo-BMT. But Hepatitis virus infection can cause mild to moderate liver dysfunction, even death because of acute liver function failure, active prevention and treatment of hepatitis virus infection remains necessary. In this respect, rh-interferon is useful.

[Intravenous placental immunoglobulin for treatment of chronic graft versus host disease].

Intravenous placental immunoglobulin (IV Pt IG) was used for the treatment of chronic graft versus host disease (CGVHD) in 30 patients who are refractory to steroid and cyclosporinic A. 15 (50%) patients showed excellent response and 11 (36.66%) good response. The total response rate is 86.66%. The dosage of IV Pt IG was 4 gm/day in adults by intravenous infusion. Effectiveness of IV PtIG was discerned within 2 weeks. The plasma levels of IgG, IgA and IgM were tested before and after IV PtIG treatment. There was no significant statistical difference between the plasma IgG, IgA, IgM levels in pre- and post-treatment period. The efficacy of IV PtIG against CGVHD is therefore ascribed to its pharmacological effect.

Demonstration of the anti-viral activity of garlic extract against human cytomegalovirus in vitro.

The in vitro anti-viral activity of garlic extract (GE) on human cytomegalovirus (HCMV) was evaluated by tissue culture, plaque reduction and early antigen assay. A dose dependent inhibitory effect of GE was evident when GE was applied simultaneously with HCMV. But the effect was stronger when the monolayers were pretreated with GE. In addition, the anti-viral effect of GE persisted long in infected cells after its being removed from the culture medium. The strongest anti-viral effect of GE was demonstrated when it was applied continuously. It is therefore recommended that clinical use of GE against HCMV infection should be persistent and the prophylactic use of GE is preferable in immunocompromised patients.

Allogeneic bone marrow transplantation for the treatment of leukemia.

Eighteen patients with leukemia have received HLA-identical allogeneic bone marrow transplantation (BMT) at our hospital since 1981. Fifteen of these patients have been living without relapse. for prophylaxis of GVHD, MTX was used in 8 patients, and cyclosporine (CSP) together with MTX in 6 patients, 3 received multiple agents at much smaller dosage, including monoclonal antibody. All patients received intravenous placental gamma-globulin, and 16 received garlic extract. Three patients died. One, who neither received MTX, nor CSP died of hyperacute GVHD, one who did not receive garlic extract died of GMV pneumonia, and the third one died of tuberculosis 18 months after BMT.