Lu Yanrong

Circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes in smoking-related interstitial fibrosis

Cigarette smoking is the major risk factor for smoking-related interstitial fibrosis (SRIF). Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We found 6 months of chronic mainstream smoking exposure induced SRIF in C57 mice, which was associated with pronounced enhanced oxidative stress, bronchoalveolar inflammation and fibrosis but not apoptosis of alveolar septal cell. We used Affymetrix microRNA (miRNA) arrays to determine the temporal alteration in global gene expression of peripheral blood during the progression of diffuse pulmonary interstitial fibrosis in C57 mice. Microarray analysis revealed the upregulation of 3 miRNAs (miR-92b, miR-700 and miR-668) and the downregulation of 5 miRNAs (let-7e, miR-142-5p, miR-350, miR-19a and miR191*) in the peripheral blood of mice exposed to mainstream smoking for 1, 2, 3 and 6 months. We proposed that circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes of SRIF related interstitial fibrosis.

Circulating biomarkers of hazard effects from cigarette smoking.

Smoking, leading to over 438,000 annual deaths in the US and 92 billion US dollars in lost productivity, is an important risk factor for several diseases. Global smoking statistics for 2002 have shown that 80,000 to 100,000 children worldwide start smoking every day. Human biomonitoring nowadays has provided an efficient and cost-effective means of measuring human exposures and biological effects of smoking. To review the utility of biomarkers in reflecting the hazard from cigarette smoking, we comprehensively searched the Cochrane Library, Medline and EMbase from 1966 to May 2010 with the language limit of English. We found that the currently used biomarkers, such as tobacco-specific metabolites, smoking-induced genotoxic products, may not scientifically reflect the hazard from cigarette smoking. More research is needed to find out more effective biomarkers for estimating hazards from cigarette smoking. This paper is expected to help researchers understand the current utilization of biomarkers related to cigarette smoking and to provide suggestive guides to tobacco companies in producing less-toxic cigarettes, thus to provide a safe way to smoke.Smoking, leading to over 438,000 annual deaths in the US and 92 billion US dollars in lost productivity, is an important risk factor for several diseases. Global smoking statistics for 2002 have shown that 80,000 to 100,000 children worldwide start smoking every day. Human biomonitoring nowadays has provided an efficient and cost-effective means of measuring human exposures and biological effects of smoking. To review the utility of biomarkers in reflecting the hazard from cigarette smoking, we comprehensively searched the Cochrane Library, Medline and EMbase from 1966 to May 2010 with the language limit of English. We found that the currently used biomarkers, such as tobacco-specific metabolites, smoking-induced genotoxic products, may not scientifically reflect the hazard from cigarette smoking. More research is needed to find out more effective biomarkers for estimating hazards from cigarette smoking. This paper is expected to help researchers understand the current utilization of biomarkers related to cigarette smoking and to provide suggestive guides to tobacco companies in producing less-toxic cigarettes, thus to provide a safe way to smoke.

In vitro anti-tumor immune response induced by dendritic cells transfected with recombinant adenovirus carrying mutant k-ras genes

SummaryThe specific anti-tumor immune response induced by mouse bone marrow dendritic cells (DCs) transfected with recombinant adenovirus carrying mutant k-ras genes was investigated. DCs were generated from mouse bone marrow in the presence of rmGM-CSF (3.3 ng/mL) and rmIL-4 (1.3 ng/mL) and detected by FACS, and then transfected with the recombinant adenovirus encoding mutant k-ras gene. The efficacy of transfection and T cell stimulating activity of DCs were detected. CTL activity of the mice vaccinated with DCs was observed. The results showed that DCs had dendritic veiled morphology. BmDCs highly expressed B7-1 (80%), B7-2 (77%), MHC II (70%), CD11c (65%), CD40 (70%) and CD54 (96%) with FACS, and no significant difference in the expression was observed before and after the transfection (P>0.05). The DCs transfected by mutant k-ras gene could significantly stimulate lymphocytes proliferation as compared with those transfected by Ad-c or non-modified DCs (P<0.05). DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16. The specific cytotoxicity against Lewis lung cancer in Ad-k-ras/12-transduced DC group was significantly higher than those in the control, vector and non-transfected DCs groups (P<0.05). It was concluded that special antitumor response could be induced by DCs transfected with recombinant adenovirus carrying mutant k-ras genes.