Li Xp

Elevated expression of miR-146, miR-139 and miR-340 involved in regulating Th1/Th2 balance with acute exposure of fine particulate matter in mice

ABSTRACT Airborne fine particulate matter (PM2.5) is detrimental to human health, and frequently leads to a variety of lung diseases. Recently, IARC conclude that particulate matter is carcinogenic to humans (level one). However, the pulmonary toxicological mechanism induced by PM2.5 remains obscure. Our previous studies confirmed that PM2.5 hurt the human immune system by means of causing the imbalance of Th1/Th2 lymphocytes. MicroRNAs (miRNAs) are post‐transcriptional gene suppressors and potential mediators of environmental effects, which play an important role in the regulation of CD4+T lymphocyte differentiation. In order to further understand the roles of microRNAs in regulating the imbalance of Th1/Th2 differentiation triggered by PM2.5, mice were subjected to intratracheal instillation of 2.5, 10, or 20 mg/kg PM2.5 in this study. Mice were euthanized on the 1st, 7th and 14th day to screen out differential miRNAs in lung tissue by employing the miRNA microarray. The expression levels of IL‐4 and IFN‐&ggr; in bronchoalveolar lavage fluid (BALF) were quantified by ELISA and their mRNA expressions in lung tissue were detected by qRT‐PCR. The experiment demonstrated that 10 differential miRNAs (miR‐146a, ‐146b, ‐139, ‐129, ‐340, ‐691, ‐181a, ‐155, ‐21‐3p, and ‐21‐5p) were up‐regulated. IL‐4 levels were found decreased, nevertheless, IFN‐&ggr; levels were increased, and the IL‐4/IFN‐&ggr; ratio was inclined to Th1 shifting. Besides that, we also found that miRNA‐691, ‐181a, ‐146a, ‐146b, ‐21a‐3p, ‐21a‐5p, and ‐340 had a positive linear correlation with BALF IFN‐&ggr;, while a negative linear correlation between microRNAs (miR‐146, ‐139, ‐340, ‐21, and ‐181a) and the IL‐4/IFN‐&ggr; level of BALF was observed. In conclusion, elevated microRNAs profiles correlated with T lymphocyte immune imbalance, driving a Th1‐biased immune response after acute PM2.5 exposure. These findings improve our understanding of the toxicological pathways of PM2.5 exposure. HighlightsIt is first time to further understand that elevated microRNAs profiles correlated with T lymphocyte imbalance after PM exposure.Ten differential miRNAs were up‐regulated after PM exposure in mice lung tissue by employing the miRNA Microarray.MicroRNAs provide novel insights into aid in design of new therapeutic strategies to prevent PM2.5‐induced toxicity.

Should all endometrioid uterine cancer patients undergo systemic lymphadenectomy

OBJECTIVE To evaluate the potential benefits of systemic pelvic and para-aortic lymphadenectomy in endometrioid uterine cancer patients. METHODS We conducted a retrospective study on 244 cases of endometrioid uterine cancer that involved surgery in the Center of Gynecologic Oncology, Peking University Peoples Hospital, Beijing, from January 2000 to May 2008. We conducted staging for each case to ensure accordance with FIGO 2009 surgical staging criteria. Clinical data, including histology, age at diagnosis, surgical procedure, adjuvant therapy, date of death or last follow-up, and date and sites of recurrence were collected for each patient. RESULTS Among 244 endometrioid uterine cancer patients, 207 cases (84.8%) underwent systemic pelvic lymphadenectomy. Among these cases, pelvic lymph nodes in 17 cases (8.2%) exhibited tumor metastasis. Systemic aortic lymphadenectomy was performed in 127 cases (52.0%) among 244 total patients. Five cases (3.9%) exhibited positive aortic lymph nodes, of which four exhibited positive pelvic lymph nodes. We investigated the impact of positive retroperitoneal lymph nodes on staging: 4 (4/161, 2.5%), 6 (6/29, 20.7%), 6 (6/35, 17.1%), 1 (1/8) and 1 (1/6) case changed to stage IIIc from stage Ia, Ib, II, IIIa, and IIIb, respectively. Tumor-free and overall survival did not differ between patients who underwent pelvic lymphadenectomy or not (P > 0.05). Tumor-free survival improved in stage Ib pelvic lymphadenectomy patients (P = 0.040); para-aortic lymphadenectomy did not improve patient survival in all stages (P > 0.05). CONCLUSION Systemic lymphadenectomy is not warranted in stage Ia endometrioid uterine cancer.

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

Background:Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. Methods:In a prospective, open-label study, budesonide 200 &mgr;g twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. Results:Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients −0.468, −0.478, and −0.426, respectively). Conclusions:The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.