Dual-modality imaging of endothelial progenitor cells transplanted after ischaemic photothrombotic stroke.

AIMS: Stroke is a refractory cerebral blood circulation disorder. Endothelial progenitor cells (EPCs) participate in the repair and regeneration of vascular injury through the combination of cell replacement and bystander effects. Here, we evaluated the biological function of EPCs in treating a mouse model of cerebral ischaemic stroke, using dual-mode bioluminescence and magnetic resonance imaging to trace EPCs in vivo. MAIN METHODS: We constructed a viral vector with a luciferase-enhanced green fluorescent protein (Luc-eGFP) reporter gene for bioluminescence imaging (BLI) detection, and simultaneously synthesized the magnetic resonance imaging (MRI) contrast agent, nano-sized superparamagnetic iron oxide (USPIO), to co-label human umbilical cord blood-derived EPCs (hEPCs). The labelled hEPCs were transplanted into mice with stroke, and the biological behaviours of the cells in-vivo were studied using BLI and MRI, and methods of molecular biology and histology. KEY FINDINGS: Comparing the two cell transplantation routes by BLI confirmed that many cells transplanted via the left ventricular route homed to ischaemic brain tissue. The dual-modality-imaging showed the prognosis of in-vivo tracking cells after transplantation in ischaemic tissues at different time points. Histological staining and neurological function scores confirmed that EPC transplantation can improve the symptoms of nerve deficit in the mouse stroke model. Histological staining revealed that cell transplantation can lead to recovery of neurological function after stroke, via various processes. These include reduced blood brain barrier permeability, recovery of white matter and of myelin, and the enhancement of neuroneogenesis. SIGNIFICANCE: Dual-modality imaging revealed EPCs as potential candidates for the treatment of ischaemic stroke.

Targeting Early Apoptosis in Acute Ischemic Stroke with a Small-Molecule Probe.

Inhibiting apoptotic cells helps ameliorate ischemic injury. Actually, only the apoptotic cells in early stage could be rescued. Molecular imaging of the early apoptosis would make sense in ischemic stroke; however, few of apoptosis molecular probes could specifically target early apoptosis. This study developed a small-molecule early apoptosis targeting probe CYS-F, which was synthesized by cystine with fluorescein isothiocyanate dyes. And the final molecular weight of CYS-F was only 1013 Da, which was much smaller than the traditional apoptosis marker annexin V. CYS-F showed excellent early apoptosis targeting ability both in vitro and in vivo. And CYS-F was cleared rapidly from the circulation with a blood half-life of 1.325 h. A favorable match was obtained between the images in fluorescence imaging and magnetic resonance imaging in stroke models. The target-to-background ratio of the lesions on 0 h was negative, which reflected the decreased blood flow. Multimodal molecular imaging showed the therapeutic effect of cystamine was dose dependence and CYS-F could also predict the outcome of ischemic stroke at an early stage. The versatility of CYS-F provides a comprehensive and convenient route for clinical decision-making in acute ischemic stroke.

Bioluminescence imaging of transplanted human endothelial colony-forming cells in an ischemic mouse model.

Ischemic strokes are devastating events responsible for high mortality and morbidity worldwide each year. Endothelial colony-forming cell (ECFC) therapy holds promise for stroke treatment; however, grafted ECFCs need to be monitored better understand their biological behavior in vivo, so as to evaluate their safety and successful delivery. The objectives of this study are to visualize the fate of infused human cord blood derived ECFCs via bioluminescence imaging (BLI) in an ischemic stroke mouse model and to determine the therapeutic effects of ECFC transplantation. ECFCs derived from human umbilical cord blood were infected with lentivirus carrying enhanced green fluorescent protein (eGFP) and firefly luciferase (Luc2) double fusion reporter gene. Labeled ECFCs were grafted into a photothrombotic ischemic stroke mouse model via intra-arterial injection though the left cardiac ventricle. The homing of infused cells and functional recovery of stroke mice were evaluated using BLI, neurological scoring, and immunohistochemistry. Significantly, BLI signals were highest in the brain on day 1 and decreased steadily until day 14. GFP-positive cells were also found surrounding infarct border zones in brain sections using immunohistochemical staining, suggesting that ECFCs properly homed to the ischemic brain tissue. Using a modified neurological severity score assay and histological analysis of brain slices with CD31 immunostaining in brain tissue, double cortin analysis, and the TdT-mediated dUTP nick end labeling (TUNEL) assay, we demonstrated functional restoration, improved angiogenesis, neurogenesis, and decreased apoptosis in ischemic mice after ECFC infusion. Collectively, our data support that ECFCs may be a promising therapeutic agent for stroke.

Dual-reporter Imaging and its Potential Application in Tracking Studies.

By tracking reporter molecules such as green fluorescent protein and luciferase, researchers can determine physiological status and follow processes both in vitro and in vivo.Here, we describe a dual-reporter imaging method, in which a fusion of eGFP and Luc2 is introduced into hosts using lentiviral particles based on HIV-1. The fusion molecule is both fluorescent and bioluminescent, and is therefore ideal as an optical marker in clinical and research applications.We characterized multiple technical indices of the molecule,including sensibility, biocompatibility, lifetime, and others.Lentiviral particles carrying the reporter were strongly infective in endothelial progenitor (EPC) and GL261 glioma cells,as well as in live mice. By transforming Luc2-eGFP into hosts, morphological and quantitative data can be collected not only from tissue specimens but also from live animal models.

Altered interhemispheric functional coordination in chronic tinnitus patients.

Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC), to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus.

The -137G>C polymorphism in interleukin-18 promoter region and cancer risk: evidence from a meta-analysis of 21 studies.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. The association of -137G>C polymorphism in the promoter region of IL-18 with cancer risk is still elusive based on current genetic association studies. We performed this meta-analysis to determine whether the -137G>C polymorphism is associated with cancer risk. A comprehensive search was conducted for databases of PubMed, EMBASE, and China National Knowledge Infrastructure. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was detected by Egger's and Begg's test. Twenty-one eligible studies including 3,498 cancer patients and 5,222 controls were identified and analyzed. In the overall analysis, no significant association between -137G>C polymorphism and cancer risk was observed. In the sub-group analyses of ethnicities, the -137G>C polymorphism significantly increased cancer risk in Asian population (GC/CC vs. GG: OR = 1.313, 95% CI = 1.053-1.638, heterogeneity P < 0.001) but not in Caucasian population. Further stratified analyses showed that the variant -137C allele was significantly associated with increased risk of nasopharyngeal carcinoma (C vs. G: OR = 1.484, 95% CI = 1.193-1.847, heterogeneity P = 0.213). No publication bias was detected. We provide evidence that the -137G>C polymorphism in IL-18 promoter region significantly increases cancer risk in Asian population but not in Caucasian population, and the variant -137C allele is associated with increased risk of nasopharyngeal carcinoma.

Findings from 2010 Global Adult Tobacco Survey: implementation of MPOWER policy in China.

OBJECTIVE: To assess the implementation of five key tobacco control policies in China: protection from second-hand smoke (SHS); offering help to quit; health warnings regarding tobacco use; the enforcement of bans on tobacco advertising, promotion, and sponsorship; and increasing tobacco taxes and prices. METHODS: Using 2010 Global Adults Tobacco Survey in China (GATS-China), 10 indicators are used to assess the implementation of five key tobacco control policies of MPOWER in China. RESULTS: Overall, 63.3% and 72.7% of adults noticed people smoking indoor workplaces and public places, respectively. Approximately 60% of smokers were not asked about their smoking habits and approximately 67% were not advised to quit on their visit to a health worker. Sixty percent of adults noticed health warning messages on cigarette packaging and in the media in the last 30 days, 63.6% stated that they would not consider quitting. Twenty percent of respondents noticed tobacco advertising, promotion, and/or sponsorship activities in the 30 days prior to the survey. Among them, 76.3% noticed the direct advertising and 50% noticed from TV programs. Although purchasing price of one pack of cigarettes ranged from 1 to 200 RMB, 50% of current smokers (about 150 million) spent 5 RMB or less on one pack of cigarette. The expenditure on 100 packets of cigarettes represents 2% of 2009 GDP per capita. CONCLUSION: The average score for the implementation of the 5 policies of MPOWER in China is 37.3 points, indicating tobacco control policies in China is poor and there is a large gaps from the FCTC requirements.

Population-based survey of secondhand smoke exposure in China.

OBJECTIVE: To determine the extent of secondhand smoke exposure in China, and to explore the potential associated factors. METHODS: This study was a nationally representative household survey examining secondhand smoke exposure of non-institutionalized men and women aged 15 and older using a global standardized geographically clustered sample design. A total of 13,354 people completed the individual questionnaire with questions on gender, age, educational level, residence, profession, potential factors associated with secondhand smoke exposure, and workplace smoking policy. The data were used to determine whole population estimates of secondhand smoke exposure. RESULTS: Among non-smokers aged 15 years and older, it was estimated that 72.4% (556 million) were exposed to secondhand smoke, with 52.5% (292 million) exposed to secondhand smoke daily. The prevalence of secondhand smoke exposure was 74.1% for men, 71.6% for women, 70.5% for urban populations, and 74.2% for rural populations. The rates were 67.3%, 63.3%, and 72.7% respectively, within the household, indoor workplaces and public places. Secondhand smoke exposure was significantly reduced in workplaces with a smoking ban but not in workplaces with a partial smoking ban. CONCLUSION: Although China has made some progress toward a smoke-free environment there remains a high degree of exposure to secondhand smoke.

Awareness of tobacco-related health hazards among adults in China.

OBJECTIVE: To determine the level of awareness of the hazards of tobacco smoking and secondhand smoke inhalation among adults in China. METHODS: Household surveys were conducted with a total of 13,354 respondents aged 15 years or over from 100 counties of 28 Chinese provinces using a stratified multi-stage geographically clustered sample design. RESULTS: The findings revealed that 81.8% of the population was aware that smoking causes serious diseases, and 27.2% and 38.7% were aware that smoking causes stroke and heart attack, respectively. Only 64.3% of respondents were aware that secondhand smoke can cause serious diseases, and 27.5%, 51.0%, and 52.6% were aware that secondhand smoke causes heart disease in adults, lung disease in children and lung cancer in adults, respectively. Awareness regarding smoking-related hazards across all participants was significantly associated with several factors, including gender, smoking status, urban/rural residency, education level and exposure to tobacco control publicity in the last 30 days. Awareness regarding tobacco-related hazards in smokers was significantly associated with urban/rural residency, education level, exposure to tobacco control publicity in the last 30 days, and physician's advice. Awareness relating to the hazards of inhaling secondhand smoke was associated with smoking status, urban/rural residency, age, education level, and exposure to tobacco control publicity in the last 30 days. Medical professionals were found to know more about the health hazards of tobacco compared with people in other types of employment. CONCLUSIONS: Overall awareness of the health hazards of tobacco has improved in the last 15 years in China, but is still relatively poor. Improved means of communicating information and more effective warning labels on cigarette packaging are necessary for increasing public awareness of tobacco hazards, particularly among rural residents and people with less education.