Search tips
Search criteria

Results 1-25 (116)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  Increased intracranial pressure in mini-pigs exposed to simulated solar particle event radiation 
Acta astronautica  2014;94(2):807-812.
Changes in intracranial pressure (ICP) during space flight have stimulated an area of research in space medicine. It is widely speculated that elevations in ICP contribute to structural and functional ocular changes, including deterioration in vision, which is also observed during space flight. The aim of this study was to investigate changes in OP occurring as a result of ionizing radiation exposure (at doses and dose-rates relevant to solar particle event radiation). We used a large animal model, the Yucatan mini-pig, and were able to obtain measurements over a 90 day period. This is the first investigation to show long term recordings of ICP in a large animal model without an invasive craniotomy procedure. Further, this is the first investigation reporting increased ICP after radiation exposure.
PMCID: PMC4166565  PMID: 25242832
Intracranial pressure; ionizing radiation; minipig
2.  A Pilot Study Examining Depressive Symptoms, Internet Use, and Sexual Risk Behavior among Asian Men Who Have Sex With Men 
Public health  2013;127(11):10.1016/j.puhe.2013.04.017.
In the present paper, we present a preliminary examination of the association of depression level, internet use, meeting sexual partners online, and unprotected sexual activity among Asian men who have sex with men (MSM). Because depression level has been previously linked to increased levels of sexual risk behavior, and heightened levels of Internet use has been linked to greater depressive symptoms, the present pilot research jointly examines these factors. We found that those with higher levels of depression, measured using the CES-D, spent more time online, met significantly more sexual partners online, and reported a significantly higher number of unprotected sexual acts. Based on this initial evidence, we conclude that incorporating CES-D to screen for depression can serve as an important tool for addressing underlying dynamics of sexual risk behaviors.
PMCID: PMC3851606  PMID: 24074630
3.  Interleukin-17 enhances immunosuppression by mesenchymal stem cells 
Han, X | Yang, Q | Lin, L | Xu, C | Zheng, C | Chen, X | Han, Y | Li, M | Cao, W | Cao, K | Chen, Q | Xu, G | Zhang, Y | Zhang, J | Schneider, R J | Qian, Y | Wang, Y | Brewer, G | Shi, Y
Cell Death and Differentiation  2014;21(11):1758-1768.
IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNγ and TNFα, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1−/− MSCs, IFNγ and TNFα could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.
PMCID: PMC4211372  PMID: 25034782
4.  Coupled ferroelectric polarization and magnetization in spinel FeCr2S4 
Scientific Reports  2014;4:6530.
One of the core issues for multiferroicity is the strongly coupled ferroelectric polarization and magnetization, while so far most multiferroics have antiferromagnetic order with nearly zero magnetization. Magnetic spinel compounds with ferrimagnetic order may be alternative candidates offering large magnetization when ferroelectricity can be activated simultaneously. In this work, we investigate the ferroelectricity and magnetism of spinel FeCr2S4 in which the Fe2+ sublattice and Cr3+ sublattice are coupled in antiparallel alignment. Well defined ferroelectric transitions below the Fe2+ orbital ordering termperature Too = 8.5 K are demonstrated. The ferroelectric polarization has two components. One component arises mainly from the noncollinear conical spin order associated with the spin-orbit coupling, which is thus magnetic field sensitive. The other is probably attributed to the Jahn-Teller distortion induced lattice symmetry breaking, occuring below the orbital ordering of Fe2+. Furthermore, the coupled ferroelectric polarization and magnetization in response to magnetic field are observed. The present work suggests that spinel FeCr2S4 is a multiferroic offering both ferroelectricity and ferrimagnetism with large net magnetization.
PMCID: PMC4185382  PMID: 25284432
5.  A Syndemic including Cigarette Smoking and Sexual Risk Behaviors among a Sample of MSM in Shanghai, China 
Drug and alcohol dependence  2013;132(0):265-270.
We explored possible correlates of cigarette smoking and their associations with levels of smoking among a sample of Chinese men who have sex with men (MSM). We also explored the syndemic associations of substance use and psychosocial problems on sexual risk behaviors.
Cross-sectional data collection from 404 MSM in Shanghai, China.
MSM exhibit a high prevalence of smoking (66.3%). Both light and heavy smoking were associated with alcohol and drug use, depression, intimate partner violence, sexual attitudes, and gay identity (though the associations for light smokers were moderate compared to those for heavy smokers).
Our findings indicate the presence of a health syndemic among MSM, and suggest that smoking prevention and cessation and other substance abuse interventions should be integrated into efforts preventing sexual risk behaviors among MSM.
PMCID: PMC3726538  PMID: 23517682
Chinese MSM; Smoking; Health Syndemics; prevention; cessation
6.  Kinetics of Neutrophils in Mice Exposed to Radiation and/or Granulocyte Colony-Stimulating Factor Treatment 
Radiation research  2013;180(2):177-188.
Astronauts have the potential to develop the hematopoietic syndrome as a result of exposure to radiation from a solar particle event (SPE) during exploration class missions. This syndrome is characterized by a reduction in the number of circulating blood cells (cytopenias). In the present study the effects of SPE-like proton and γ radiation on the kinetics of circulating neutrophils were evaluated during a one-month time period using mice as a model system. The results revealed that exposure to a 2 Gy dose of either SPE-like proton or γ radiation significantly decreased the number of circulating neutrophils, with two nadirs observed on day 4 and day 16 postirradiation. Low circulating neutrophil count (neutropenia) is particularly important because it can increase the risk of astronauts developing infections, which can compromise the success of the mission. Thus, two granulocyte colony-stimulating factors (G-CSFs), filgrastim and pegfilgrastim were evaluated as countermeasures for this endpoint. Both forms of G-CSF significantly increased neutrophil counts in irradiated mice, however, the effect of pegfilgrastim was more potent and lasted longer than filgrastim. Using the expression of CD11b, CD18 and the production of reactive oxygen species (ROS) as markers of neutrophil activation, it was determined that the neutrophils in the irradiated mice treated with pegfilgrastim were physiologically active. Thus, these results suggest that pegfilgrastim could be a potential countermeasure for the reduced number of circulating neutrophils in irradiated animals.
PMCID: PMC4126650  PMID: 23829559
7.  Multispecies coexistence of trees in tropical forests: spatial signals of topographic niche differentiation increase with environmental heterogeneity 
Neutral and niche theories give contrasting explanations for the maintenance of tropical tree species diversity. Both have some empirical support, but methods to disentangle their effects have not yet been developed. We applied a statistical measure of spatial structure to data from 14 large tropical forest plots to test a prediction of niche theory that is incompatible with neutral theory: that species in heterogeneous environments should separate out in space according to their niche preferences. We chose plots across a range of topographic heterogeneity, and tested whether pairwise spatial associations among species were more variable in more heterogeneous sites. We found strong support for this prediction, based on a strong positive relationship between variance in the spatial structure of species pairs and topographic heterogeneity across sites. We interpret this pattern as evidence of pervasive niche differentiation, which increases in importance with increasing environmental heterogeneity.
PMCID: PMC3712412  PMID: 23782876
species coexistence; tropical forest; niche differentiation; neutral theory; spatial pattern; cross-pair overlap distribution
8.  Feasibility and Willingness of Using E-technologies for HIV Prevention and Research Targeting Chinese MSM 
Nehl, EJ | He, N | Wang, X | Lin, L | Wong, FY | Yu, F
AIDS care  2012;25(7):926-930.
This pilot study examines the feasibility and willingness for three types of e-technologies for HIV prevention and research among a sample of men who have sex with men (MSM) in Chengdu, China. A total of 605 self-identified MSM (200 HIV seropositive, 405 HIV negative) were recruited through a community-based HIV/AIDS service organization and completed a cross-sectional survey. The majority used cell phones for voice and text (99% and 95%), used e-mail (53%), and Tencent QQ (an Instant messaging technology) (83%); (54%) indicated they would participate in future research studies; and (77%) provided contact information for at least one e-technology. In multivariate analyses, those who were not official city residents, those better educated, and those who were HIV seropositive were more likely to provide contact information. This research indicates that MSM in China would be likely to engage in e-technology research and studies should explore these innovative communication methods.
PMCID: PMC3722859  PMID: 23061806
Chinese MSM; HIV Prevention; e-technologies; Internet; Mobile Phone
9.  Sociodemographic and sexual behavior characteristics of an online MSM sample in Guangdong, China 
AIDS care  2013;26(5):648-652.
Public health research and interventions often assume that men who have sex with men (MSM) who use the Internet in China have similar characteristics to those in Western countries, though with little empirical evidence. This study aimed to describe and examine the sociodemographic and basic sexual behavioral characteristics of an online sample of MSM in Guangdong, China. In 2010, a total of 1100 MSM were recruited from an lesbian, gay, bisexual, and transgender (LGBT)-oriented website and were asked about their sociodemographic and sexual behavior characteristics. The majority of the participants (77.9%) self-identified as homosexual, and the mean age was 30.0 years (SD = 6.7). About 80% of the participants had attained a college degree and only 4.8% were unemployed. About 60% had a monthly salary of more than CNY 3000 (476 USD), and more than 10% were married. The majority (71.7%) had used condoms in the last anal sex. Nearly half of the participants have never been tested for HIV or other sexually transmitted infections (STIs) (47.3% and 47.7%, respectively). More than 80% were willing to be contacted by researchers after the survey. Findings indicate that the sociodemographic characteristics of Chinese MSM who use the Internet are relatively similar to those in the Western countries. However, Chinese MSM are less likely to self-identify as homosexual and be tested for HIV and other STIs than Western MSM. On a positive note, Chinese MSM would be likely to engage in e-technology research showing potential feasibility of an online HIV/STI intervention.
PMCID: PMC4075317  PMID: 24124988
Chinese MSM; Internet; intervention; demographics; HIV testing
10.  The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance in Mice by Restoring Hyperoxia-Compromised Macrophage Function 
Molecular Medicine  2014;20(1):238-247.
Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patients with respiratory distress. However, prolonged exposure to hyperoxia compromises the ability of the macrophage to phagocytose and clear bacteria. Previously, we showed that the exposure of mice to hyperoxia elicits the release of the nuclear protein high mobility group box-1 (HMGB1) into the airways. Extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS-21 [3-(2,4 dimethoxybenzylidene)-anabaseine dihydrochloride], an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could inhibit hyperoxia-induced HMGB1 release into the airways, enhance macrophage function and improve bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. GTS-21 (0.04, 0.4 and 4 mg/kg) or saline was systemically administered via intraperitoneal injection to mice that were exposed to hyperoxia (≥99% O2) and subsequently challenged with PA. We found that systemic administration of 4 mg/kg GTS-21 significantly increased bacterial clearance, decreased acute lung injury and decreased accumulation of airway HMGB1. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophagelike cell line, were incubated with different concentrations of GTS-21 in the presence of 95% O2. The phagocytic activity of macrophages was significantly increased by GTS-21 in a dose-dependent manner. In addition, hyperoxia-induced hyperacetylation of HMGB1 was significantly reduced in macrophages incubated with GTS-21. Furthermore, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from these macrophages. Our results indicate that GTS-21 is effective in improving bacterial clearance and reducing acute lung injury by enhancing macrophage function via inhibiting the release of nuclear HMGB1. Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections.
PMCID: PMC4069272  PMID: 24664237
11.  Effect of SPE-like Proton or Photon Radiation on the Kinetics of Mouse Peripheral Blood Cells and Radiation Biological Effectiveness Determinations 
Astrobiology  2013;13(6):570-577.
Exploration missions outside low-Earth orbit are being planned; therefore, it is critical to understand the risk astronauts would be exposed to in the space environment, especially during extravehicular activities (EVAs). Reductions in white blood cell (WBC) numbers can occur as a result of exposure to solar particle event (SPE) radiation. The aim of the present study was to determine the duration of the effects on blood cell numbers from exposure to a single whole-body dose of SPE-like proton radiation or photon radiation as well as to determine the radiation biological effectiveness (RBE) values at those times when radiation exposure causes blood cell numbers to experience the most critical effects when using mice as a model. Our results indicate that both types of radiation cause significant reductions in the numbers of all blood cell types at different times post-irradiation. The RBE values were not significantly different from 1.0. These results indicate that the risk estimations for astronauts from exposure of mice to SPE-like proton radiation are comparable to those previously made for doses of standard reference radiations, suggesting that countermeasures should be developed for the decreases in blood cell counts observed following the exposure of mice to SPE radiation. Key Words: Proton radiation—Gamma radiation—Blood cell counts—Solar particle event. Astrobiology 13, 570–577.
PMCID: PMC3689168  PMID: 23980767
12.  Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model 
Cell Death & Disease  2014;5(4):e1178-.
Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial–mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.
PMCID: PMC4001313  PMID: 24743733
immunoadjuvant; high-intensity focused ultrasound; lung metastasis; breast cancer; epithelial–mesenchymal transition
13.  High Mobility Group Box–1 Mediates Hyperoxia-Induced Impairment of Pseudomonas aeruginosa Clearance and Inflammatory Lung Injury in Mice 
Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patients with respiratory distress. However, a significant number of patients on ventilators exhibit enhanced susceptibility to infections and develop ventilator-associated pneumonia (VAP). Pseudomonas aeruginosa (PA) is one of the most common species of bacteria found in these patients. Previously, we demonstrated that prolonged exposure to hyperoxia can compromise the ability of alveolar macrophages (AMs), an essential part of the innate immunity, to phagocytose PA. This study sought to investigate the potential molecular mechanisms underlying hyperoxia-compromised innate immunity against bacterial infection in a murine model of PA pneumonia. Here, we show that exposure to hyperoxia (≥ 99% O2) led to a significant elevation in concentrations of airway high mobility group box–1 (HMGB1) and increased mortality in C57BL/6 mice infected with PA. Treatment of these mice with a neutralizing anti-HMGB1 monoclonal antibody (mAb) resulted in a reduction in bacterial counts, injury, and numbers of neutrophils in the lungs, and an increase in leukocyte phagocytic activity compared with mice receiving control mAb. This improved phagocytic function was associated with reduced concentrations of airway HMGB1. The correlation between phagocytic activity and concentrations of extracellular HMGB1 was also observed in cultured macrophages. These results indicate a pathogenic role for HMGB1 in hyperoxia-induced impairment with regard to a host’s ability to clear bacteria and inflammatory lung injury. Thus, HMGB1 may provide a novel molecular target for improving hyperoxia-compromised innate immunity in patients with VAP.
PMCID: PMC3604087  PMID: 23087050
hyperoxia; bacterial infection; macrophage function; HMGB1
14.  Acute effects of solar particle event radiation 
Journal of Radiation Research  2014;55(Suppl 1):i66-i67.
A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animals exposed to space flight stressors combined with the types of radiation expected during an SPE. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations: gamma rays or electrons). All animal studies described have been approved by the University of PA IACUC. Some conclusions from recent CARR investigations are as follows: (i) the relative biological effectiveness (RBE) values for SPE-like protons compared with standard reference radiations (gammas or electrons) for white blood cells (WBCs) vary greatly between mice, ferrets and pigs, with the RBE values being greater in ferrets than those in mice, and considerably greater in pigs compared with those in ferrets or mice [1, 2]. This trend for the data suggests that the RBE values for WBCs in humans could be considerably greater than those observed in small mammals, and SPE proton radiation may be far more hazardous to humans than previously estimated from small animal studies. (ii) Very low doses of SPE proton radiation (25 cGy) increase blood clotting times in ferrets, and the low SPE-like dose rate has more severe effects than high dose rate radiation [3]. (iii) Results from pig and ferret studies suggest that disseminated intravascular coagulation is a major cause of death at doses near the LD50 level for SPE-like proton and gamma radiation. (iv) Exposure to SPE-like proton or gamma radiation, in combination with simulated microgravity (hindlimb suspension), leads to a very high level of morbidity/mortality in mice given a bacterial challenge with non-toxic levels of Pseudomonas aeruginosa or Klebsiella pneumoniae; the threshold for this effect was 1.5 Gy. (v) T-cell activation was reduced in mice exposed to SPE-like radiation with or without simulated hypogravity (either partial weight suspension or hindlimb suspension) (e.g. [4]). (vi) Radiation and simulated hypogravity had synergistic effects on immune system biological endpoints (e.g. [5]). (vii) Pigs exposed to simulated SPE radiation exhibited increases in intracranial pressure that remained elevated over the 90-day experimental period. (viii) A major sparing effect of SPE-like low dose rate radiation (compared with the results for high dose rate radiation) was observed for ferret emesis parameters, such that the differences between the results for ferret exposure to low dose rate radiation (50 cGy/h) and controls were not statistically significant (for doses up to 2 Gy). For high dose rate SPE proton radiation, the threshold value for retching was 75 cGy, and for ferret vomiting, it was 1 Gy.
PMCID: PMC3941513
15.  Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China 
Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.
PMCID: PMC4051179  PMID: 24519131
China; Diabetes; Insulin resistance; Lipidosis; Nonalcoholic fatty liver disease; Obesity
16.  Experimental observation of ferrielectricity in multiferroic DyMn2O5 
Scientific Reports  2014;4:3984.
One of the major breakthroughs associated with multiferroicity in recent years is the discovery of ferroelectricity generated by specific magnetic structures in some magnetic insulating oxides such as rare-earth manganites RMnO3 and RMn2O5. An unresolved issue is the small electric polarization. Relatively large electric polarization and strong magnetoelectric coupling have been found in those manganites of double magnetic ions: magnetic rare-earth R ion and Mn ion, due to the strong R-Mn (4f-3d) interactions. DyMn2O5 is a representative example. We unveil in this work the ferrielectric nature of DyMn2O5, in which the two ferroelectric sublattices with opposite electric polarizations constitute the ferrielectric state. One sublattice has its polarization generated by the symmetric exchange striction from the Mn-Mn interactions, while the polarization of the other sublattice is attributed to the symmetric exchange striction from the Dy-Mn interactions. We present detailed measurements on the electric polarization as a function of temperature, magnetic field, and measuring paths. The present experiments may be helpful for clarifying the puzzling issues on the multiferroicity in DyMn2O5 and other RMn2O5 multiferroics.
PMCID: PMC3913922  PMID: 24496324
17.  Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury☆☆☆ 
Redox Biology  2014;2:314-322.
Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation.
Graphical abstract
•Exposure to hyperoxia results in accumulation of high levels of airway HMGB1 that precede inflammatory acute lung injury (ALI).•Airway HMGB1 is critical in mediating hyperoxia-induced inflammatory ALI via recruiting leukocytes including neutrophils.•Extracellular HMGB1-accumulated upon prolonged exposure to hyperoxia is hyperacetylated, existing in different redox states.•Small molecule EP, administrated even after the onset of hyperoxic exposure, can mitigate hyperoxia-induced inflammatory ALI by inhibiting HMGB1 release into the extracellular milieu.
PMCID: PMC3926109  PMID: 24563849
ALI, acute lung injury; BALF, bronchoalveolar lavage fluids; EP, ethyl pyruvate; GST, gluthatione-s-transferase; HMGB1, high mobility group box protein 1; MV, mechanical ventilation; NLS, nuclear localization signal; PMNs, polymorphonuclear neutrophils; RA, room air; rHMGB1, recombinant HMGB1; ROS, reactive oxygen species; Hyperoxia; Macrophage; HMGB1; Hyperacetylation; Redox state
18.  A modified bicanalicular intubation procedure to repair canalicular lacerations using silicone tubes 
Liang, X | Lin, Y | Wang, Z | Lin, L | Zeng, S | Liu, Z | Li, N | Wang, Z | Liu, Y
Eye  2012;26(12):1542-1547.
To explore a modified technique for silicone intubation for the repair of canalicular lacerations.
The surgery was performed on 35 eyes in 35 adult patients from October 2007 to September 2009. Using a modified soft probe, silicone tubes were inserted through the lacrimal punctum and left in the bicanaliculi for 3–10 months.
The surgery was performed successfully in all cases. The tubes were removed after 3–10 months (mean 5.3±1.8 months). The mean follow-up time after tube removal was 13.8 months (range, 6–22 months). Lower punctum splitting occurred in one case (2.86%) after the surgery. No other complications associated with the silicone tubes occurred. All the tubes were removed successfully without any difficulty. No iatrogenic injuries occurred during tube removal.
The modified bicanalicular intubation procedure described here is an effective and atraumatic procedure for the management of canalicular lacerations in adults, and it is associated with fewer complications than the traditional sutures of canalicular lacerations.
PMCID: PMC3522846  PMID: 23060024
modified; canalicular laceration; tube intubation
19.  Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance 
Nutrition & Diabetes  2013;3(12):e99-.
Background and Objectives:
High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial.
We investigated the metabolic consequences of mice fed a (a) regular diet, (b) ‘Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80+CD11c+ macrophages and anti-inflammatory F4/80+CD11c− macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat.
We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing ‘Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to ‘Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis.
Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS-R antagonists may represent a novel therapy for insulin resistance.
PMCID: PMC3877431  PMID: 24366371
ghrelin receptor; HFCS; macrophages; inflammation; insulin resistance; liver steatosis
20.  Xerochrysium gen. nov. and Bettsia, genera encompassing xerophilic species of Chrysosporium 
IMA Fungus  2013;4(2):229-241.
On the basis of a study of ITS sequences, Vidal et al. (Rev. Iber. Micol. 17: 22, 2000) recommended that the genus Chrysosporium be restricted to species belonging to Onygenales. Using nrLSU genes, we studied the majority of clades examined by Vidal et al. and showed that currently accepted species in Chrysosporium phylogenetically belong in six clades in three orders. Surprisingly, the xerophilic species of Chrysosporium, long thought to be a single grouping away from the majority of Chrysosporium species, occupy two clades, one in Leotiales, the other in Eurotiales. Species accepted in Leotiales are related to the sexual genus Bettsia. One is the type species B. alvei, and related asexual strains classified as C. farinicola, the second is C. fastidium transferred to Bettsia as B. fastidia. Species in the Eurotiales are transferred to Xerochrysium gen. nov., where the accepted species are X. xerophilum and X. dermatitidis, the correct name for C. inops on transfer to Xerochrysium. All accepted species are extreme xerophiles, found in dried and concentrated foods.
PMCID: PMC3905941  PMID: 24563835
Eurotiales; food spoilage; Leotiales; molecular systematics; Onygenales; taxonomy
21.  Controllable Disorder in a Hybrid Nanoelectronic System: Realization of a Superconducting Diode 
Scientific Reports  2013;3:2274.
We have studied a hybrid nanoelectronic system which consists of an AlGaAs/GaAs two-dimensional electron gas (2DEG) in close proximity (~70 nm) to an Al superconducting nanofilm. By tuning the current through the Al film, we can change the conductance of the 2DEG and furthermore vary the effective disorder in the Al superconducting film in a controllable way. When a high current is injected into the film, screening which couples the Al film and the 2DEG results in a collapse of anti-symmetric behavior in the current-voltage characteristics, V(I) ~ -V(-I), which holds true in a conventional superconductor. Our results may open a new avenue of experimentally realizing a superconducting diode.
PMCID: PMC3721077  PMID: 23881449
22.  Comparison of regenerated and non-regenerated oxidized cellulose hemostatic agents 
European Surgery  2013;45(4):213-220.
Oxidized cellulose is a well known and widely used surgical hemostat. It is available in many forms, but manufactured using either a nonregenerated or regenerated process.
This study compares the fiber structure, pH in solution, bactericidal effectiveness, and hemostatic effectiveness of an oxidized nonregenerated cellulose (ONRC; Traumastem®) and an oxidized regenerated cellulose (ORC; Surgicel® Original).
In vitro, fiber structures were compared using scanning electron microscopy, pH of phosphate buffer solution (PBS) and human plasma were measured after each cellulose was submerged, and bactericidal effect was measured by plating each cellulose with four bacteria. In vivo, time to hemostasis and hemostatic success were compared using a general surgery nonheparinized porcine liver abrasion model and a peripheral vascular surgery heparinized leporine femoral vessel bleeding model.
Ultrastructure of ONRC fiber is frayed, while ORC is smooth. ORC pH is statistically more acidic than ONRC in PBS, but equal in plasma. No difference in bactericidal effectiveness was observed. In vivo, ONRC provided superior time to hemostasis relative to ORC (211.2 vs 384.6 s, N = 60/group) in the general surgery model; and superior hemostatic success relative to ORC at 30 (60 vs. 15 %; OR: 13.5; 95 % CI: 3.72–49.1, N = 40/group), 60 (85 vs. 37.5 %; OR: 12.3; 95 % CI: 3.66–41.6), and 90 s (97.5 vs 70.0 %; OR: 21.1, 95 % CI: 2.28–195.9) in the peripheral vascular model.
ONRC provides superior hemostasis and equivalent bactericidal effectiveness relative to ORC, which is likely due to its fiber structure than acidity.
PMCID: PMC3739866  PMID: 23950762
Traumastem; Surgicel; Cellulose; Oxidized cellulose; Hemostasis; Liver abrasion; Liver square; Celstat; Fibrin pad
23.  Combined Central and Peripheral Stimulation to Facilitate Motor Recovery After Stroke: The Effect of Number of Sessions on Outcome 
Proof-of-principle studies have demonstrated transient beneficial effects of transcranial direct current stimulation (tDCS) on motor function in stroke patients, mostly after single treatment sessions.
To assess the efficacy of multiple treatment sessions on motor outcome.
The authors examined the effects of two 5-day intervention periods of bihemispheric tDCS and simultaneous occupational/physical therapy on motor function in a group of 10 chronic stroke patients.
The first 5-day period yielded an increase in Upper-Extremity Fugl-Meyer (UE-FM) scores by 5.9 ± 2.4 points (16.6% ± 10.6%). The second 5-day period resulted in further meaningful, although significantly lower, gains with an additional improvement of 2.3 ± 1.4 points in UE-FM compared with the end of the first 5-day period (5.5% ± 4.2%). The overall mean change after the 2 periods was 8.2 ± 2.2 points (22.9% ± 11.4%).
The results confirm the efficacy of bihemispheric tDCS in combination with peripheral sensorimotor stimulation. Furthermore, they demonstrate that the effects of multiple treatment sessions in chronic stroke patients may not necessarily lead to a linear response function, which is of relevance for the design of experimental neurorehabilitation trials.
PMCID: PMC3666327  PMID: 22258156
motor impairment; noninvasive brain stimulation; occupational therapy; stroke recovery; transcranial direct current stimulation; tDCS
24.  Phase II trial of temsirolimus in patients with metastatic breast cancer 
Preclinical models suggested that activating mutations of the PIK3CA gene are associated with sensitivity to inhibitors of the mammalian target of rapamycin (mTOR). In breast cancers, PIK3CA mutations are associated with estrogen receptor (ER) positivity. We therefore performed an open-label single arm phase II study of the rapamycin analog, temsirolimus, at a dose of 25 mg weekly, in women with pretreated breast cancers that were positive for ER, PR, or HER2. Archived formalin-fixed paraffin embedded tumor was collected for immunohistochemical evaluation of components of the PI3K/Akt/mTOR pathway and PIK3CA mutation analysis. Thirty-one patients were enrolled. There were no major objective responses; however, three patients had stable disease for over 24 weeks. Twenty-three tumor samples were available for mutational analysis. There were five tumors with PIK3CA mutations; no association was found between prolonged stable disease and PIK3CA mutation or any immunohistochemical marker. There was a trend toward improved progression free survival (PFS) for patients with positive nuclear staining for phospho-Akt308. One patient remains on study four and a half years after starting therapy; her tumor did not have a PIK3CA mutation. We conclude that single agent temsirolimus has minimal activity in a population of women with heavily pretreated breast cancer. We found no evidence that either absence of immunohistochemical staining for PTEN or mutations in the hotspot domains of PIK3CA in the primary tumor were associated with clinical benefit.
PMCID: PMC3658119  PMID: 22245973
Rapamycin; Temsirolimus; Breast cancer; PIK3CA; Treatment; PTEN
25.  Predicting functional motor potential in chronic stroke patients using diffusion tensor imaging 
Human Brain Mapping  2011;33(5):1040-1051.
Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter-hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)-derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF) and transcallosal fibers connecting primary motor cortices (M1-M1). Ipsilesional corticospinal tracts (PT, aMF) and M1-M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age-matched healthy controls. Partial correlations revealed that greater gains in motor functions were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1-M1 diffusivity had the greatest predictive value. An additional slice-by-slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI-derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient’s individual recovery potential and in determining optimal neurorehabilitative interventions.
PMCID: PMC3175010  PMID: 21538700
alternate motor fibers; corticospinal tract; directional diffusivity; fractional anisotropy; inter-hemispheric interaction; motor impairment; pyramidal tract; transcallosal fibers

Results 1-25 (116)