The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

Vitellaria paradoxa nutshells from seven sub-Saharan countries as potential herbal medicines for treating diabetes based on chemical compositions, HPLC fingerprints and bioactivity evaluation.

The aim of the study was to determine the feasibility of the Vitellaria paradoxa nutshell as a new medicinal resource for treating diabetes. A total of forty-one compounds were identified by HPLC-DAD-Q-TOF-MS and phytochemical methods in V. paradoxa nutshell methanol extract. Based on HPLC fingerprints, four characteristic constituents were quantified and the origin of twenty-eight V. paradoxa nutshells from seven sub-Saharan countries was compared, which were classified into three groups with chemometric method. Twenty-eight samples contained high total phenolic content, and exhibited moderate-higher antioxidant activity and strong α-glucosidase inhibitory activity. Furthermore, all fractions and isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities, and α-glucosidase inhibitory action mechanism of four characteristic constituents including protocatechuic acid, 3, 5, 7-trihydroxycoumarin, (2R, 3R)-(+)-taxifolin and quercetin was investigated via molecular docking method, which were all stabilized by hydrogen bonds with α-glucosidase. The study provided an effective approach to waste utilization of V. paradoxa nutshell, which would help to resolve waste environmental pollution and provide a basis for developing potential herbal resource for treating diabetes.

Hyperbaric oxygen therapy in experimental and clinical stroke.

Stroke, which is defined as a neurologic deficit caused by sudden impaired blood supply, has been considered as a common cause of death and disability for decades. The World Health Organization has declared that almost every 5 seconds a new stroke occurs, placing immense socioeconomic burdens. However, the effective and available treatment strategies are still limited. Additionally, the most effective therapy, such as thrombolysis and stenting for ischemic stroke, generally requires a narrow therapeutic time window after the event. A large majority of patients cannot be admitted to hospital and receive these effective treatments for reperfusion timely. Hyperbaric oxygen therapy (HBOT) has been frequently applied and investigated in stroke since 1960s. Numerous basic and clinical studies have shown the beneficial efficacy for neurological outcome after stroke, and meanwhile many underlying mechanisms associated with neuroprotection have been illustrated, such as cerebral oxygenation promotion and metabolic improvement, blood-brain barrier protection, anti-inflammation and cerebral edema, intracranial pressure modulation, decreased oxidative-stress and apoptosis, increased vascular and neural regeneration. However, HBOT in human stroke is still not sufficiently evidence-based, due to the insufficient randomized double-blind controlled clinical studies. To date, there are no uniform criteria for the dose and session duration of HBOT in different strokes. Furthermore, the additional effect of HBOT combined with drugs and other treatment strategies are being investigated recently. Therefore, more experimental and clinical research is imperative to identify the mechanisms more clearly and to explore the best protocol of HBOT in stroke treatment.

[Investigation of the temperature-dependent spectral characteristics of colloidal PbSe nanocrystals].

In the present paper colloidal PbSe nanocrystals were prepared with the particle size of 3.8 and 5.8 nm, and the temperature- dependent optical properties of colloidal PbSe nanocrystals were investigated. The experimental data show that the band gap, photoluminescence peak wavelength, photoluminescence intensity and full width at half-maximum of colloidal PbSe nanocrystals will change with variations in temperature and size at room temperature. The band gap of colloidal PbSe nanocrystals with the particle size of 3.8 nm shifts towards red when the temperature increases. However, the blue shift occurs when the particle size is 5.8 nm. The photoluminescence intensity of colloidal PbSe nanocrystals drops and the full width at half-maximum will increases with the increase in temperature.

[Incidence of oral hairy leukoplakia in human immunodeficiency virus-seropositive adult patients in Yunnan, China].

OBJECTIVE: To study the incidence rates, clinical characteristics of oral hairy leukoplakia (OHL) and its relation to the immune status in a sample of human immunodeficiency virus (HIV)-infected adults in Yunan, China. METHODS: 1 060 adult patients with HIV from January 2008 to June 2010 were evaluated. The age, gender, education grade, diagnosis time of HIV-infected, route of transmission, xerostomia, oral candidiasis, high active antiretroviral therapy and CD4 lymphocytes counts. The occurrence of OHL was recorded by oral examination. The relationship of CD4 lymphocytes counts and the incidence of OHL were analyzed by statistical methods. RESULTS: There were 94 OHL patients in 1 060 HIV patients (8.9%). The average age of the OHL patients was (39.33 +/- 10.45) years old. 90% OHL was found on the two lateral aspect of the tongue. The CD4 lymphocytes of 70.2% OHL patients were less than 200 mm-3. CONCLUSION: OHL is a frequent finding in patients with indicates severe immunosuppression and associated with the reduction of CD4 lymphocytes.