Influenza vaccine uptake among children and older adults in China: a secondary analysis of a quasi-experimental study.

BACKGROUND: Influenza vaccination is the key to prevent influenza-related disease, especially among high-risk populations. However, influenza vaccine uptake in China is low. This secondary analysis of a quasi-experimental trial aimed to understand factors associated with influenza vaccine uptake among children and older people stratified by funding context. METHODS: A total of 225 children (aged 0.5-8 years) and 225 older people (aged 60 years or above) were recruited from three clinics (rural, suburban and urban) in Guangdong Province. Participants were allocated into two groups based on funding contexts: a self-paid group (N = 150, 75 children and 75 older adults) in which participants paid full price for their vaccination; and a subsidized group (N = 300, 150 children and 150 older adults) in which varying levels of financial support was provided. Univariate and multivariable logistic regressions were conducted stratified by funding contexts. RESULTS: Overall, 75.0% (225/300) of participants in the subsidized group and 36.7% (55/150) in the self-paid group got vaccinated. Older adults had lower vaccination rates than children in both funding groups, while both age groups showed much higher uptake in the subsidized group than in the self-paid group (aOR = 5.96, 95% CI: 3.77-9.42, p = 0.001). In the self-paid group, having prior influenza vaccination history of children (aOR:2.61, 95%CI: 1.06-6.42) or older people (aOR:4.76, 95%CI: 1.08-20.90) was associated with increased influenza vaccine uptake compared to those who had no prior vaccination experiences in the family. While in the subsidized group, participants who got married or lived with partners (aOR = 0.32, 0.10-0.98) had lower vaccination uptake than single ones. Trust in providers' advice (aOR = 4.95, 95%CI:1.99, 12.43), perceived effectiveness of the vaccine (aOR: 12.18, 95%CI: 5.21-28.50), and experienced influenza-like illnesses in the family in the past year (aOR = 46.52, 4.10, 533.78) were associated with higher vaccine uptake. CONCLUSIONS: Older people had suboptimal vaccine uptake compared to children in both contexts and need more attention to enhance influenza vaccination. Tailoring interventions to different vaccine funding contexts may help improve influenza vaccination: In self-paid context, motivating people to accept their first ever influenza vaccination may be a promising strategy. In subsidized context, improving public confidence in vaccine effectiveness and providers' advice would be useful.

Abnormal miRNA-30e Expression is Associated with Breast Cancer Progression.

BACKGROUND: microRNAs (miRNAs) are involved in the regulation of various cellular processes, such as differentiation, proliferation, metabolism, and apoptosis, and they have been implicated in several diseases, including cancers. METHODS: To assess the role of miRNA in the progression of breast cancer, we performed TaqMan-based miRNA profiling for plasma from patients with breast cancer (n = 53), unrelated diseases (n = 40), or matched healthy controls (n = 40), and for breast tumors or adjacent non-tumors (n = 41). RESULTS: We selected 18 miRNAs with predicted roles in breast cancer and demonstrated that let-7i (p = 0.019), let-7a (p = 0.02), and miR-650 (p = 0.008) were significantly up-regulated in plasma; miR-21 (p < 0.001) is up-regulated in breast cancer tissue, and miR-30e was down-regulated in both plasma (p < 0.001) and breast cancer tissues (p = 0.004). Plasma miR-30e expression was shown to be statistically associated with age (p = 0.0402) and clinical stage (p = 0.007). However, receiver-operating characteristic curve analyses suggested that miR-30e expression cannot significantly differentiate breast cancer from healthy tissue or plasma. Consistent with a potential role for miR-30e in breast cancer, three predicted targets of miR-30e (RAB11A, BNIP3L, and RAB32) are up-regulated in breast cancer tissue. CONCLUSIONS: These findings suggest that reduced miR-30e correlates with the clinical stage of breast cancer. It is worthwhile to further explore that the potential role of miR-30e as a tumor suppressor in breast cancer, as well as its potential therapeutic utility.

Adenovirus-Mediated E2F-1 Gene Transfer Augments Gemcitabine-Induced Apoptosis in Human Colon Cancer Cells.

BACKGROUND: E2F-1 is a transcription factor that stimulates cellular proliferation and cell cycle progression. E2F-1 alone is sufficient to stimulate cells to initiate DNA synthesis, and this unscheduled entry into S phase is a potent trigger of apoptosis. Gemcitabine, a novel pyrimidine analogue with structural and metabolic similarities to cytarabine, also can efficiently induce apoptosis, especially for cancer cells that are already in S phase. Gemcitabine has established antitumor activity against solid tumors, including head and neck, ovarian, and non-small cell lung cancers. Therefore, we hypothesized that exogenous E2F-1 expression could accumulate cells in the S phase and thus sensitize them to gemcitabine. METHODS: We constructed an adenoviral vector (AdCMVE2F-1) to transduce the exogenous E2F-1 gene into human cancer cells. Infection of human colon cancer cells with AdCMVE2F-1 resulted in the overexpression of E2F-1 mRNA and protein in a dose-dependent manner and consequently induced accumulation in S phase as measured by FACS analysis. To assess the synergistic antitumor effect of AdCMVE2F-1 and gemcitabine, the human colon cancer cel lines SW620, DLD-1, and LoVo were infected with AdCMVE2F-1 at various multiplicities of infection and then exposed to various concentrations of gemcitabine 24 hours after infection. RESULT: Isobologram analysis showed that E2F-1-transduced cancer cells exhibited higher sensitivity to gemcitabine treatment compared to control virus-infected cells. Treatment with AdCMVE2F-1 plus gemcitabine enhanced endogenous p53 expression in LoVo cells, which contain wild-type p53; however, the finding that the synergistic effect can also be observed in mutant p53-expressing SW620 and DLD-1 cells suggests that wild-type p53 function may not be necessary for the therapeutic effects of this drug combination. Conclusions: Our data demonstrate that overexpression of ectopic E2F-1 protein may render cels more sensitive to gemcitabine-mediated apoptosis, an outcome that has important general implications for the treatment of human cancer.

Circulating microRNA Signatures Associated with Childhood Asthma.

BACKGROUND: MicroRNAs (miRNAs) exist stably and reproducibly in plasma and may be used as biomarkers for various diseases. Little is known about circulating miRNAs in the peripheral blood of juvenile patients with asthma. METHODS: In this study, we used hybridization arrays to compare the miRNA expression profiles among 6 juvenile patients with or without asthma. Using quantitative PCR (qPCR), we verified the expression levels of these miRNAs in plasma from patients with asthma (n = 40) and healthy subjects (n = 14). RESULTS: Our results showed that the levels of plasma miR-Let7C, miR-486, and miR-1260a in childhood asthma patients were significantly higher than in healthy controls (p < 0.01). Additionally, miR-1260a is correlated with the treatment schedule of these patients and patients with long treatment times had higher expression of miR-1260a than short treatment times; miR494 was significantly associated with challenge, and miR-3162-3p was significantly associated with MEF25 in asthma patients suggesting a potential correlation of miRNA levels with clinical disease parameters. Receiver operator characteristic analysis confirmed that the levels of miR-3162-3p could be used to discriminate childhood asthma patients from healthy subjects (area under the curve of 0.821), suggesting it may be a potential diagnostic biomarker. CONCLUSIONS: These results indicate that circulating miR-3162-3p and miR-1260a should be further evaluated as potential non-invasive biomarkers in diagnosis and treatment for childhood asthma.

Specific immunoglobulin G4 correlates with Th2 cytokine reduction in patients with allergic asthma treated by Dermatophagoides pteronyssinus subcutaneous immunotherapy.

Background: The modulations of lymphocyte subsets and cytokine production due to subcutaneous allergen immunotherapy (SCIT) are not fully clarified. Objective: We investigated the changes in T-lymphocyte subsets and serum Dermatophagoides pteronyssinus-specific immunoglobulin G4 (Der-p sIgG4), as well as cytokine production during Der-p SCIT, in patients with allergic asthma. Methods: This study involved 20 patients with allergic asthma who were receiving 156-week Der-p SCIT and 20 patients without SCIT (non-SCIT). We measured symptom and medication scores (SMS), serum Der-p sIgG4 levels, CD4+CD25+Foxp3+ T regulatory (Treg), CD4+IL-4-IFN-γ+ T-helper (Th) 1, and CD4+IL-4+IFN-γ- Th2 lymphocyte percentages in peripheral blood mononuclear cells (PBMCs) with/without Der-p extract stimulation at weeks 0, 4, 12, 16, 52, 104, and 156. Cytokine release inhibition assays were performed by incubation with serum from SCIT and non-SCIT patients, Der-p allergen, and PBMCs. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1 were evaluated in supernatant. Results: We found that SCIT patients had significantly lower SMS after week 52. Der-p sIgG4 levels in SCIT patients significantly increased at week 16 compared with non-SCIT subjects. CD4+IL-4+IFN-γ- Th2% in SCIT patients showed a significant decrease from weeks 104-156 compared with week 0, while no change was observed in CD4+CD25+Foxp3+ Treg and CD4+IL-4-IFN-γ+ Th1 percentages. IL-5, IL-13, IL-4, IL-17, and TNF-α levels in supernatant of PBMCs cultured with serum of SCIT patients after 16 weeks showed significant lower levels compared with non-SCIT patients, and showed significant reverse associations with Der-p sIgG4 levels. Conclusion: SCIT induced Dep-p sIgG4 may be involved in downregulating Th2 cytokine production in Der-p allergic asthma patients.

Effectiveness of a pay-it-forward intervention compared with user-paid vaccination to improve influenza vaccine uptake and community engagement among children and older adults in China: a quasi-experimental pragmatic trial.

BACKGROUND: China has low seasonal influenza vaccination rates among priority populations. In this study, we aimed to evaluate a pay-it-forward strategy to increase influenza vaccine uptake in rural, suburban, and urban settings in China. METHODS: We performed a quasi-experimental pragmatic trial to examine the effectiveness of a pay-it-forward intervention (a free influenza vaccine and an opportunity to donate financially to support vaccination of other individuals) to increase influenza vaccine uptake compared with standard-of-care user-paid vaccination among children (aged between 6 months and 8 years) and older people (≥60 years) in China. Recruitment took place in the standard-of-care group until the expected sample size was reached and then in the pay-it-forward group in primary care clinics from a rural site (Yangshan), a suburban site (Zengcheng), and an urban site (Tianhe). Participants were introduced to the influenza vaccine by project staff using a pamphlet about influenza vaccination and were either asked to pay out-of-pocket at the standard market price (US$8·5-23·2; standard-of-care group) or to donate any amount anonymously (pay-it-forward group). Participants had to be eligible to receive an influenza vaccine and to have not received an influenza vaccine in the past year. The primary outcome was vaccine uptake. Secondary outcomes were vaccine confidence and costs (from the health-care provider perspective). Regression methods compared influenza vaccine uptake and vaccine confidence between the two groups. This trial is registered with ChiCTR, ChiCTR2000040048. FINDINGS: From Sept 21, 2020, to March 3, 2021, 300 enrolees were recruited from patients visiting three primary care clinics. 55 (37%) of 150 people in the standard-of-care group (40 [53%] of 75 children and 15 [20%] of 75 older adults) and 111 (74%) of 150 in the pay-it-forward group (66 [88%] of 75 children and 45 [60%] of 75 older adults) received an influenza vaccine. People in the pay-it-forward group were more likely to receive an influenza vaccine compared with those in the standard-of-care group (adjusted odds ratio [aOR] 6·7 [95% CI 2·7-16·6] among children and 5·0 [2·3-10·8] among older adults). People in the pay-it-forward group had greater confidence in vaccine safety (aOR 2·2 [95% CI 1·2-3·9]), importance (3·1 [1·6-5·9]), and effectiveness (3·1 [1·7-5·7]). In the pay-it-forward group, 107 (96%) of 111 participants donated money for subsequent vaccinations. The pay-it-forward group had a lower economic cost (calculated as the cost without subtraction of donations) per person vaccinated (US$45·60) than did the standard-of-care group ($64·67). INTERPRETATION: The pay-it-forward intervention seemed to be effective in improving influenza vaccine uptake and community engagement. Our data have implications for prosocial interventions to enhance influenza vaccine uptake in countries where influenza vaccines are available for a fee. FUNDING: Bill & Melinda Gates Foundation and the UK National Institute for Health Research.

The adaptor protein CIKS/ACT1 is necessary for collagen-induced arthritis, and it contributes to the production of collagen-specific antibody.

OBJECTIVE: CIKS/ACT1 is an adaptor molecule that is necessary for signaling by members of the interleukin-17 cytokine family. The aim of this study was to determine whether this adaptor is required for the initiation of collagen-induced arthritis (CIA). If it is required, then CIKS-mediated signaling could be a potential target for therapeutic intervention in patients with rheumatoid arthritis (RA). METHODS: CIA model studies were performed with CIKS-deficient and CIKS-sufficient mice on an otherwise wild-type (WT) C57BL/6 background or on a C57BL/6 background lacking Fcγ receptor IIb (FcγRIIb). In addition, collagen antibody-induced arthritis (CAIA) studies were performed in WT and CIKS-deficient mice. Pathologic changes of arthritis were evaluated by visual inspection of the paws, by histochemical analysis of tissue sections, and by measurements of collagen-specific antibodies. RESULTS: Pathologic changes of CIA were readily induced in WT mice, with exacerbation of the changes in FcγRIIb-deficient mice. In contrast, CIKS-deficient mice were protected from all aspects of CIA pathology, even on an FcγRIIb-deficient background. The absence of CIKS completely prevented neutrophil infiltration into joints, bone erosion, and cartilage damage; furthermore, the production of type II collagen (CII)-specific antibodies was reduced. In contrast to the CIA model, CIKS-deficient mice in the CAIA model remained susceptible to arthritis. CONCLUSION: CIKS-mediated signaling is necessary for the pathogenesis of CIA, but not CAIA. These findings suggest critical functions of CIKS during the development of arthritis in the CIA model, including in the formation of CII antibodies, and they mark the CIKS adaptor as a potential therapeutic target in RA.

The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation.

IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production, and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses that these two cytokines elicit. We identify CD11c(+) macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.

Kaempferide improves oxidative stress and inflammation by inhibiting the TLR4/IκBα/NF-κB pathway in obese mice.

OBJECTIVES: Kaempferide (Ka), a major natural active component of Tagetes erecta L, has numerous pharmacological effects such as anti-obesity, anticancer, and anti-hypertension. However, there is no clear evidence that Ka is directly related to inflammation and oxidative stress in obese mice. We aimed to explore the effects of Ka on inflammation and oxidative stress and its mechanism. MATERIALS AND METHODS: The obese mice were induced by a high-fat diet (HFD). The anti-obesity effect was tested by liver and body weight, liver and adiposity index, and white adipose tissue. Blood sample analysis was used to detect the hypolipidemic and hypoglycemic effects. The anti-oxidation effect was assessed using GSH, SOD, MDA, CAT, T-AOC, and other indicators. The anti-inflammatory effect was assessed using TNF-α, MCP-1, and Adiponectin. Western blot and Real-Time PCR were used to evaluate the related signaling pathways. RESULTS: Obesity, glycolipid metabolism disorder, inflammation, and oxidative stress developed in HFD mice. These changes can be effectively alleviated by Ka treatment for 16 weeks. Further studies have suggested that these beneficial effects of Ka may be associated with inhibition of the TLR4/IκBα/NF-κB signaling pathways. CONCLUSION: Ka possesses important anti-obesity, hypoglycemic, and hypolipidemic effects. The mechanism may be causally associated with the TLR4/IκBα/NF-κB signaling pathway, which improves inflammation and oxidative stress.

Prediction and Verification of the Major Ingredients and Molecular Targets of Tripterygii Radix Against Rheumatoid Arthritis.

Tripterygii Radix exhibits good clinical efficacy and safety in rheumatoid arthritis (RA) patients, but its effective components and mechanism of action are still unclear. The purpose of this study was to explore and verify the major ingredients and molecular targets of Tripterygii Radix in RA using drug-compounds-biotargets-diseases network and protein-protein interaction (PPI) network analyses. The processes and pathways were derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The most important compounds and biotargets were determined based on the degree values. RA fibroblast-like synoviocytes (RA-FLS) were separated from RA patients and identified by hematoxylin and eosin (HE) staining and immunohistochemistry. The purity of RA-FLS was acquired by flow cytometry marked with CD90 or VCAM-1. RA-FLS were subjected to control, dimethyl sulfoxide (control), kaempferol, or lenalidomide treatment. Cell migration was evaluated by the transwell assay. The relative expression of biotarget proteins and cytokines was analyzed by western blotting and flow cytometry. In total, 144 chemical components were identified from Tripterygii Radix; kaempferol was the most active ingredient among 33 other components. Fourteen proteins were found to be affected in RA from 285 common biotargets. The tumor necrosis factor (TNF) signaling pathway was predicted to be one of the most latent treatment pathways. Migration of RA-FLS was inhibited and the expression of protein kinase B (AKT1), JUN, caspase 3 (CASP3), TNF receptor 1 and 2 (TNFR1 and TNFR2), interleukin-6 (IL-6), and TNF-α was significantly affected by kaempferol. Thus, this study confirmed kaempferol as the effective component of Tripterygii Radix against RA-FLS and TNF signaling pathway and its involvement in the regulation of AKT1, JUN, CASP3, TNFR1, TNFR2, IL-6, and TNF-α expression.

Jinwujiangu Capsule Treats Fibroblast-Like Synoviocytes of Rheumatoid Arthritis by Inhibiting Pyroptosis via the NLRP3/CAPSES/GSDMD Pathway.

Jinwujiangu capsule (JWJGC) is a traditional Chinese medicine formula used to treat rheumatoid arthritis (RA). However, whether its mechanism is associated with pyroptosis remains unclear. In this study, the ability of JWJGC to inhibit the growth of fibroblast-like synoviocytes of RA (RA-FLS) through pyroptosis was evaluated. The cells isolated from patients with RA were identified by hematoxylin and eosin (H&E) staining, immunohistochemistry, and flow cytometry. After RA-FLS were treated with different concentrations of JWJGC-containing serum, the cell proliferation inhibition rate, expression of caspase-1/3/4/5, NOD-like receptor protein 3 (NLRP3), gasdermin-D (GSDMD), and apoptosis-associated speck-like protein containing a CARD (ASC), concentrations of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), the activity of lactic dehydrogenase (LDH), and pyroptosis were evaluated. The results showed that JWJGC increased the proliferative inhibition rate, decreased the expression of caspase-1/3/4/5, GSDMD, NLRP3, and ASC, suppressed the expression of IL-1ß and IL-18, induced the activity of LDH, and downregulated the number of double-positive FITC anti-caspase-1 and PI. Generally, our findings suggest that JWJGC can regulate NLRP3/CAPSES/GSDMD in treating RA-FLS through pyroptosis.

Novel anti-obesity effect of scutellarein and potential underlying mechanism of actions.

AIMS: Scutellarein (Sc), a natural compound and an active ingredient of Erigeron breviscapus (vant.), shows anti-inflammatory and antioxidant properties and has the potential for obesity treatment. However, no previous in vivo study has been conducted to assess the role of Sc in obesity. This study investigated the effects of Sc on obesity and associated hyperlipidemia and fatty liver and explores the underlying mechanisms of action in a mouse model. METHODS: The study was conducted using a well-established mouse model of obesity induced by high-fat diet (HFD) feeding. Anti-obesity effects were assessed using body weight, abdominal circumference, white adipose tissue, adiposity index, and fatty liver index. Lipid lowering and liver protective effects were examined by blood sample analysis. Lipid dystopia deposition was confirmed by liver pathological sections. The signaling pathways of lipid metabolism and cytokine/inflammatory mediator were evaluated using Real-Time PCR and Western blot. RESULTS: Central obesity, dyslipidemia, inflammation, and hepatic steatosis were developed in mice fed with HFD. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated all obesity indicators tested. Further studies revealed the antagonistic effect of Sc on hyperlipidemia was a result of the repression of the lipid synthesis pathway, de novo pathway, HMGCR, promoting fatty acid oxidation (PPARα, CPT-1a) and increased cholesterol output (PPARγ-LXRα-ABCA1). The anti-inflammatory effect was attributed to blocking the expression of inflammatory genes, including TNF-α, IL-6, NF-κB. CONCLUSIONS: These results suggest that Sc possesses important novel anti-obesity effects accompanying lipid lowering and anti-inflammation-based liver protective effects. These favorable effects are causally associated with the suppression of gene expression of inflammatory cytokines and fine regulation of genes responsible for energy metabolism. Our results advance the understanding of the pharmacological actions of Sc, and provides a role for Sc in effective management of obesity.

Assessment of FGFR1 Over-Expression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening.

Lung cancer, caused mainly by smoking, is one of the most prevalent diseases in China, resulting in high mortality rates. The increasing incidence of chronic disease due to lung cancer places a huge burden on the welfare and cost to the Chinese society. Amplification of the fibroblast growth factor receptor 1 (FGFR1) is associated with high incidence and mortality in lung cancer patients. FGFR1 signaling is implicated in oncogenic traits such as proliferation, cell survival, angiogenesis, and migration. Targeting FGFR1 and its ligand basic FGF (bFGF) is a key step forward in developing new therapies for this crippling disease. Lung adenocarcinoma is the most common subtype of non-small-cell lung cancer. In this study, A549, a lung adenocarcinoma cell line widely used in vitro as a model for drug metabolism and as a transfection host, was used to study FGFR1. A stable lentiviral FGFR1 over-expression system in lung cancer cells is described for the study of anti-lung cancer drug candidates targeting FGFR1. Ligand binding to FGFR1 activates the PI3K/Akt/mTOR signaling pathway and increases adhesion, invasion, and migration in this model. Using a unique FGF monoclonal antibody developed in the laboratory, the overactive PI3K pathway was effectively blocked, abrogating the negative metastatic signaling pathways in lung cancer cells. Importantly, this model provides an effective and simple screening kit for anti-FGF1 drug compounds for lung cancer treatment and a tool for understanding the molecular mechanisms of the FGFR1 signaling pathway in lung cancer. Furthermore, this toolkit based on a FGFR1 lentiviral construct model is transferrable to study FGFR1 signaling in any type of cancer cell.

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD.

Role of deregulated microRNAs in non-small cell lung cancer progression using fresh-frozen and formalin-fixed, paraffin-embedded samples.

Non-small cell lung cancer (NSCLC) is responsible for the highest number of cancer-associated mortalities worldwide, and the five-year survival rate is <15% following the initial diagnosis. MicroRNAs (miRNAs) serve important functions in a number of human diseases, including cancer. The present study investigated the expression status, clinical relevance and functional role of miRNA in NSCLC. miRNA expression profiling was performed in lung adenocarcinoma and adjacent unaffected lung tissues using 47 groups of fresh-frozen (FF) and 45 of formalin-fixed, paraffin-embedded (FFPE) samples from 11 pulmonary bulla. miR-21, -30e, -363 and -623 were further examined for differential expression in two independent cohorts. Other miRNAs, including miR-5100 and miR-650, were upregulated, while miR-10a and -26b were downregulated in FF NSCLC tissues. The associations between these miRNAs and their clinicopathological features were also investigated. miR-363, -10a and -145 were associated with lymph node status (P=0.002, 0.005 and 0.007, respectively) and miR-650 and -145 were associated with differentiation (P=0.01 and 0.05, respectively). No associations were identified for the other miRNAs examined. In the FFPE NSCLC samples, miR-30e-5p correlated with the differentiation of the tissue (P=0.011). The present study indicates that these miRNAs may be appropriate candidates for molecular diagnostic and prognostic markers in NSCLC.

AMPK is required for PM2.5-induced autophagy in human lung epithelial A549 cells.

The aim is to investigate the molecular mechanisms underlying the PM2.5-induced autophagy in human lung cancer epithelial cells (A549). The effects of the PM2.5 on morphological and biochemical markers of autophagy in A549 were analyzed by electron microscopy, GFP-LC3 puncta was observed by confocal fluorescence microscope. The effects of phosphorylation of AMPK, mTOR, AKT, ERK, JNK, and p53 on LC3II in A549 were observed following PM2.5 exposure; the role of autophagy in PM2.5-induced apoptosis was examined using 3-methyladenine and rapamycin. PM2.5 induced morphological and biochemical markers of autophagy in A549. Phosphorylation of AMPK and dephosphorylation of mTOR were observed following PM2.5 treatment, and AMPK inhibitor blocked LC3B-II expression. In addition, we demonstrated that PM2.5-induced autophagy confers a pro-survival role in host defense.