Shucheng Hua

microRNA‐1274a, a modulator of sorafenib induced a disintegrin and metalloproteinase 9 (ADAM9) down‐regulation in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with poor prognosis. Sorafenib, a multikinase inhibitor, has been widely used to treat patients with advanced HCC in clinic. We postulated that microRNAs (miRNA) might be involved in HCC target‐chemotherapy with sorafenib. MiRNA profile of HepG2 was evaluated after cells were treated with vehicle or sorafenib and alterations in miRNA expression occurred with 14 miRNAs. MiR‐1274a, which is up‐regulated by sorafenib, could significantly repress expression of ADAM9, a protease that is involved in sorafenib target‐therapy of HCC, in HCC cells. Taken together, our data emphasizes a new miRNA‐based mechanism of sorafenib antitumor therapy.

Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

Purpose A new type of polymeric micelle (PM) was assembled using a polyethylene glycol (PEG)-linked (PEGylated) amphiphilic copolymer and d-tocopheryl PEG1000 succinate (TPGS1000). The micelles were used to deliver doxorubicin (DOX) and curcumin (CUR) for alleviating multidrug resistance (MDR) in lung cancer cells while enhancing the therapeutic efficacy of DOX. Methods Micelles loaded with DOX and CUR were assembled using a film-forming technique. Micelles were used to treat A549/Adr cells to find out whether micelles had the ability to reverse the MDR of A549/Adr cells. Some investigations were conducted using tumor-bearing mice to assess whether these micelles had enhanced antitumor efficacy as compared to DOX alone or the combination of DOX and CUR. Results Some micelles (DOX + CUR)–PMs had a small average size of about 17 nm and showed definite ability to deliver both DOX and CUR into DOX-resistant A549/Adr cells. The PMs had high cytotoxicity toward A549/Adr cells when the applied equivalent DOX dose was 1 µg/mL or higher. The cellular uptake of (DOX + CUR)–PMs into A549/Adr cells was found to be associated with an energy-dependent, caveolae-mediated, and clathrin-independent mechanism. (DOX + CUR)–PMs helped to prolong the circulation of DOX or CUR as compared to the individual administration of DOX or CUR, and they exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects of DOX. Conclusion TPGS1000 and CUR could synergistically reverse DOX-resistance of A549/Adr cells. In vivo examinations confirmed that the micelles had the capability to increase the plasma concentration of DOX or CUR, as well as to prolong their respective blood circulation. These micelles were able to significantly inhibit tumor growth in Lewis lung carcinoma tumor-bearing mice while reducing the side effects of DOX. The micelles showed potential in the treatment of lung cancer.

Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up

Objective To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. Methods Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. Results One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. Conclusion Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.

miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.

Associations of Overweight, Obesity and Related Factors with Sleep-Related Breathing Disorders and Snoring in Adolescents: A Cross-Sectional Survey

Background: Sleep-related breathing disorders (SRBD) have been identified as a major public health problem closely related to adolescent obesity. We aimed to estimate the prevalences of SRBD and snoring in adolescents in Changchun City, Northeastern China, and to evaluate the associated factors in this population. Methods: In total, 1955 adolescents aged 11–18 years were recruited in Changchun City using stratified cluster sampling. Parents and caretakers of children completed the questionnaires, which included demographic characteristics, anthropometric parameters and a pediatric sleep questionnaire (SRBD scale). Logistic regression was used to analyze the relationship between SRBD, snoring and other factors. Results: The prevalences of SRBD and snoring in our population were 3.7% and 3.3%, respectively, and the prevalences of overweight and obesity were 12.6% and 4.9%. Multivariate logistic regression showed that urban residence (OR = 2.356, 95%CI: 1.251–4.435) and post-term birth (OR = 3.275, 95%CI: 1.396–7.683) were significantly associated with SRBD. Preterm birth (OR = 2.255, 95%CI: 1.021–4.980) and parental education level of university and above (OR = 0.265, 95%CI: 0.083–0.850) were significantly associated with snoring. Overweight (OR = 2.063, 95%CI: 1.062–4.006) was also related to snoring. Conclusions: The prevalences of SRBD and snoring were similar to those reported in previous studies. Urban residence and post-term birth were important influencing factors for SRBD; overweight, highest parental education level (university and above) and preterm birth were key factors affecting snoring in adolescents.