Diagnostic Value of Imaging and Serological Biomarkers in Pulmonary Sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of an unknown aetiology. It can exist in many organs. Pulmonary and intrathoracic lymph nodes are most commonly involved. Lung sarcoidosis is uncommon in Asia. However, due to the large population of our country and the development of bronchoscopy, percutaneous lung puncture, and other medical technologies, the number of pulmonary sarcoidosis patients is on the rise. Pulmonary sarcoidosis patients have no obvious symptoms in the early stage, and the clinical manifestations in the later stage may vary from person to person. Eventually, the disease progresses to life-threatening pulmonary fibrosis. Therefore, patients with pulmonary sarcoidosis should receive a timely diagnosis. In recent years, the imaging features and serologic biomarkers of pulmonary sarcoidosis have been continuously studied. The diagnostic value of imaging and serologic biomarkers for pulmonary sarcoidosis is summarized below.

Organic-Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme.

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods. The energy harvesting and hot-electron migration are remarkably expedited by a spontaneous organic-inorganic heterointerface holding a Fermi level-induced interfacial electric field. The accumulated hot electrons are then fully utilized by conductive Fe-CDs to boost enzymatic catalysis toward overproduced reactive oxygen species. By synergizing with localized heating from hot-electron decay, FeCG achieves rapid and potent disinfection with an antibacterial efficiency of 99.6% on Escherichia coli within 5 min and is also effective (94.2%) against Staphylococcus aureus. Our work presents crucial insights into the organic-inorganic heterointerface in advanced plasmonic biocidal nanozymes.

Electron Lock Manipulates the Catalytic Selectivity of Nanozyme.

Nanomaterials with enzyme-mimicking functions, termed nanozymes, offer attractive opportunities for biocatalysis and biomedicine. However, manipulating nanozyme selectivity poses an insurmountable hurdle. Here, we propose the concept of an energy-governed electron lock that controls electron transfer between nanozyme and substrates to achieve selectivity manipulation of enzyme-like catalysis. An electron lock can be constructed and opened, via modulating the nanozyme's electron energy to match the energy barrier of enzymatic reactions. An iron-doped carbon dot (FeCD) nanozyme with easy-to-regulate electron energy is selected as a proof of concept. Through regulating the conduction band which dominates electron energy, activatable oxidase and selective peroxidase (POD) with substrate affinity 123-fold higher than that of natural horseradish peroxidase (HRP) is achieved. Furthermore, while maintaining selectivity, FeCDs exhibit catalytic kinetics comparable to that of HRP upon transforming photons into electrons. Superior selectivity, efficient catalysis, and undetectable biotoxicity energize FeCDs as potent targeted drugs on antibiotic-resistant bacterial abscesses. An electron lock provides a robust strategy to manipulate selectivity toward advanced nanozymes.

Efficacy of omalizumab in adult patients with allergic bronchopulmonary aspergillosis: a multicentre study in China.

Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.

Bioinspired hot-spot engineering strategy towards ultrasensitive SERS sandwich biosensor for bacterial detection.

Surface-enhanced Raman spectroscopy (SERS) sandwich biosensors have received tremendous attention in early diagnosis of bacterial infections. However, efficiently engineering nanoscale plasmonic hots pots (HS) towards ultrasensitive SERS detection still remains challenging. Herein, we propose a bioinspired synergistic HS engineering strategy to construct ultrasensitive SERS sandwich bacterial sensor (named USSB), by coupling bioinspired signal module and plasmonic enrichment module to synergistically boost the number and intensity of HS. The bioinspired signal module is based on dendritic mesoporous silica nanocarrier (DMSN) loaded with plasmonic nanoparticles and SERS tag, while magnetic Fe3O4 nanoparticles coated with Au shell are employed in plasmonic enrichment module. We demonstrate that DMSN effectively shrank nanogaps between plasmonic nanoparticles to improve HS intensity. Meanwhile, plasmonic enrichment module contributed to plenty of additional HS inside and outside individual "sandwich". Ascribing to the boosted number and intensity of HS, the constructed USSB sensor exhibits ultrahigh detection sensitivity (7 CFU/mL) and selectivity towards model pathogenic bacteria of Staphylococcus aureus. Remarkably, the USSB sensor enables fast and accurate bacterial detection in real blood samples of septic mice, achieving early diagnosis of bacterial sepsis. The proposed bioinspired synergistic HS engineering strategy opens up a new direction for constructing ultrasensitive SERS sandwich biosensors, and may promote their advancing applications in the early diagnosis and prognosis of devastating diseases.

Combined systemic immune-inflammatory index and prognostic nutritional index predict outcomes in advanced non-small cell lung cancer patients receiving platinum-doublet chemotherapy.

Background: Systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) could evaluate the therapeutic efficacy and prognosis in different tumors. However, no studies investigated the SII-PNI score to predict outcomes in non-small cell lung cancer (NSCLC) patients treated with platinum-doublet chemotherapy. The aim of this study was to investigate the SII-PNI score in predicting outcomes in non-small cell lung cancer (NSCLC) patients treated with platinum-doublet chemotherapy. Materials and methods: Our study retrospectively analyzed clinical data from 124 patients with advanced NSCLC receiving platinum-doublet chemotherapy. The SII and PNI were calculated based on peripheral blood cell counts and serum albumin, and the optimal cut-off values were determined using receiver operating characteristic (ROC). All patients were divided into three groups according to the SII-PNI score. The association between the SII-PNI score and the clinicopathological characteristics of the patients was examined. The Kaplan-Meier and Cox regression models were used to assess progression-free survival (PFS)and overall survival (OS). Results: There was no significant correlation between SII, PNI at baseline and chemotherapy response in patients with advanced NSCLC (p>0.05). However, after receiving 4 cycles of platinum-doublet chemotherapy, the SII of the SD group (p=0.0369) and PD group (p=0.0286) was significantly higher than that of the PR group. At the same time, the PNI of the SD group (p=0.0112) and the PD group (p=0.0007) was significantly lower than that of the PR group. The PFS of patients with SII-PNI scores of 0, 1, and 2 were 12.0, 7.0, and 5.0 months, and the OS of patients with SII-PNI scores of 0, 1, and 2 were 34.0, 17.0, and 10.5 months, respectively. There was statistical significance among the three groups (all p <0.001). Multivariate analyses showed that the chemotherapy response of progressive disease (PD) (HR, 3.508; 95% CI, 1.546-7.960; p=0.003) and SII-PNI score of 2 (HR, 4.732; 95% CI, 2.561-8.743; p < 0.001) were independently associated with a shorter OS. The uses of targeted drugs (HR, 0.543; 95% CI, 0.329-0.898; p=0.017) and immune checkpoint inhibitors (HR, 0.218; 95% CI, 0.081-0.584; p=0.002) were protective factors for OS in patients with NSCLC. Conclusion: Compared with baseline parameters, the correlation between SII, PNI after 4 cycles of chemotherapy and the chemotherapy effect was more significant. The SII-PNI score after 4 cycles of chemotherapy is an effective prognostic biomarker for advanced NSCLC patients treated with platinum-doublet chemotherapy. Patients with a higher SII-PNI score had a worse prognosis.

Exosomal MFI2-AS1 sponge miR-107 promotes non-small cell lung cancer progression through NFAT5.

BACKGROUND: Non-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies. METHODS: The relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models. RESULT: Exosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis. CONCLUSION: We demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.

Prognostic factors of survival in patients with non-small cell lung cancer: a competing risk model using the SEER database.

Background: To explore the prognostic factors of survival in non-small cell lung cancer (NSCLC) patients using the competing risk analysis. Methods: This was a retrospective cohort study. NSCLC patients with complete data were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Outcomes were censored, cancer-specific mortality in NSCLC, and other-cause mortality. Gray's test was used in univariable analysis, and a multivariable Fine-Gray competing risk model with backward elimination was used to explore the prognostic factors of survival. The screened variables were incorporated into a random survival forest (RSF) model for the prediction of 1-, 3-, and 5-year survival in patients with NSCLC. Receiver operator characteristic (ROC) curves, calibration curves, the value of area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance. Results: Totally 1,251 eligible patients were included, 678 (54.20%) patients were cancer-specific mortality, and 128 (10.23%) patients were other-cause mortality. The median follow-up time was 26 months. Age, primary site, N stage, M stage, surgery type, tumor size, and lymph nodes (LNs) count were included in the multivariable Fine-Gray model for further analysis (P<0.05). The six most important features (surgery type, tumor size, M stage, LNs count, N stage, and primary site) were included in the competing risk analysis using the RSF model. The value of AUC for predicting 1-, 3-, and 5-year survival in the testing set were 0.796, 0.804, and 0.792, respectively. Calibration curves were well-fitted. DCA curves showed that the RSF model had similar or greater clinical net benefits in survival compared with the 8th edition the American Joint Committee on Cancer (AJCC) staging. The good performance of the RSF model under different surgery types, T, N, and M stages. Conclusions: We conducted a competing risk analysis using the RSF model for predicting the 1-, 3-, and 5-year survival of NSCLC. We generated a web calculator (https://github.com/YingChen19/Prognostic-factors-of-long-term-survival-of-non-small-cell-lung-cancer), which could provide a convenient assessment and could help improve the prognosis and survival of NSCLC.

Epidemic characteristics of Mycoplasma pneumoniae infection: a retrospective analysis of a single center in Suzhou from 2014 to 2020.

Background: Mycoplasma pneumoniae (M. Pneumoniae) is a common pathogen of respiratory tract infections, but there is still a lack of detailed investigation on the large sample of M. Pneumoniae infection in the all age population. And patients with severe M. Pneumoniae pneumonia (SMPP) still have a certain risk of death. How to identify the clinical characteristics and population of patients with SMPP as soon as possible is still an urgent problem in clinical practice. Methods: Demographic characteristics, patient clinical information, and laboratory data of 81,131 patients with respiratory tract infections (RTIs) in the Affiliated Suzhou Hospital of Nanjing Medical University from 2014 to 2020 were retrospectively collected from all patient records. The serum particle agglutination (PA) test was used to determine M. Pneumoniae infection by detecting specific antibodies. The white blood cell count, the proportion of neutrophils and lymphocytes, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels between children and adults with SMPP were compared by Student's t-test; other clinical features were analyzed by χ2 test or Fisher's exact test. Results: A total of 81,131 patients with RTIs were included, and 21,582 (26.60%) M. Pneumoniae immunoglobulin M (IgM)-positive patients were detected. From 2014 to 2020, the annual proportions of M. Pneumoniae RTIs were 23.60%, 28.18%, 38.08%, 27.05%, 23.44%, 25.26%, and 18.33%, respectively. In terms of seasonal distribution, April-June and September-November were the peak seasons of M. Pneumoniae infection each year. Children and women have a high proportion of M. Pneumoniae infection. The peak age of M. Pneumoniae infection was between 4 and 14 years old. There were 301 cases of SMPP, including 281 children and 20 adults (8 cases of pregnant women). Children and pregnant women accounted for a high proportion of SMPP. Children with SMPP had more extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels compared with adults. Conclusions: M. Pneumoniae infection has seasonal, sex, and age distribution trends. Children and pregnant women accounted for a high proportion of SMPP. Extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels may be helpful to identify SMPP in children than in adults.

Plasmonic Nanozymes: Leveraging Localized Surface Plasmon Resonance to Boost the Enzyme-Mimicking Activity of Nanomaterials.

Nanozymes, a type of nanomaterials that function similarly to natural enzymes, receive extensive attention in biomedical fields. However, the widespread applications of nanozymes are greatly plagued by their unsatisfactory enzyme-mimicking activity. Localized surface plasmon resonance (LSPR), a nanoscale physical phenomenon described as the collective oscillation of surface free electrons in plasmonic nanoparticles under light irradiation, offers a robust universal paradigm to boost the catalytic performance of nanozymes. Plasmonic nanozymes (PNzymes) with elevated enzyme-mimicking activity by leveraging LSPR, emerge and provide unprecedented opportunities for biocatalysis. In this review, the physical mechanisms behind PNzymes are thoroughly revealed including near-field enhancement, hot carriers, and the photothermal effect. The rational design and applications of PNzymes in biosensing, cancer therapy, and bacterial infections elimination are systematically introduced. Current challenges and further perspectives of PNzymes are also summarized and discussed to stimulate their clinical translation. It is hoped that this review can attract more researchers to further advance the promising field of PNzymes and open up a new avenue for optimizing the enzyme-mimicking activity of nanozymes to create superior nanocatalysts for biomedical applications.

Kimura disease with Allergic Bronchopulmonary Aspergillosis: a case report.

BACKGROUND: Kimura disease (KD) is a rare chronic idiopathic condition of unknown etiology that is prevalent in Asian males. It often causes subcutaneous lumps and enlarged lymph nodes, especially in head and neck region. But KD is also a systemic disease that can involve multiple organs, such as the kidneys and skin. CASE PRESENTATION: We report a 62-year-old Chinese man who presented with paroxysmal cough, enlarged inguinal lymph nodes, recurrent skin itching, and elevated IgE antibodies specific to A. fumigatus. After a comprehensive review, the final diagnosis for this patient was KD with Allergic Bronchopulmonary Aspergillosis (ABPA). CONCLUSIONS: The age of onset and the location of the lump involved were not characteristic for the illness. This case report described the patient's diagnosis and treatment process. This case report serves to arouse the attention of multidisciplinary team to explore the potential relationship between KD and ABPA. It will contribute to preventing the misdiagnosis and missed diagnosis of KD.

Epidemiology and risk factors of chronic obstructive pulmonary disease in Suzhou: a population-based cross-sectional study.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) in Suzhou remains still unknown. The aim of this study was to quantify the disease burden and assess the risk factors of COPD. METHODS: This was a population-based, cross-sectional study of adults aged 40 years and older in Suzhou. A total of 4,864 adults were identified from June 2018 to December 2018 and 4,725 adults were finally recruited. Subjects underwent post-bronchodilator spirometry and were diagnosed according to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD). RESULTS: The data from 4,725 adults were ultimately included in the final analysis. The overall prevalence of COPD in subjects aged 40 and older was 12.4%, while it was 12.3% in men and 12.5% in women. Risk factors identified by multivariable logistic analysis were age (P<0.05, OR =2.29, 95% CI, 1.83-2.88) and underweight (BMI <18.5 kg/m2) (P<0.05, OR =1.57, 95% CI, 1.01-2.44). COPD patients also displayed weaker grip strength (P<0.001). Approximately half (50.7%) the COPD patients were asymptomatic, and compared with asymptomatic COPD patients, symptomatic COPD patients were older (69.5 vs. 67.2, P<0.05), smoked more frequently (12.1 vs. 7.1 pack year, P<0.05), had a more severe GOLD stage (stage I 27.0% vs. 39.4%, stage II 50.2% vs. 46.8%, stage III 17.0% vs. 11.1%, stage IV 5.8% vs. 2.7%, P<0.05), and a worse lung function index (FEV1, FVC, PEF, FEF25, FEF50, FEF75, FEF2575) (P<0.05). CONCLUSIONS: COPD was found to be highly prevalent in adults aged 40 years and older in Suzhou. Age and underweight were major risk factors of COPD. Half of the COPD patients were asymptomatic, and displayed decreased lung function upon the onset of respiratory symptoms. Therefore, spirometry screening is essential for the early detection and management of COPD.

No intrauterine vertical transmission in pregnancy with COVID-19: A case report.

The coronavirus disease 2019 (COVID-19) has been a worldwide pandemic diseases, nearly 400,000 people died at now. The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. The SARS-COV-2 nucleic acid test results of these specimens were negative. There is no evidence of intrauterine vertical transmission during delivery in the third trimester, but the data are limited and need to be further explored.

Diagnostic Value of Non-Real-Time Radial Probe Endobronchial Ultrasound (RP-EBUS) Guided Positioning Method for Peripheral Pulmonary Lesions.

BACKGROUND The aim of this study was to analyze the diagnostic value of thin bronchoscopy lung biopsy for peripheral pulmonary lesions under non-real-time guidance of radial ultrasound (RP-EBUS). MATERIAL AND METHODS We used a retrospective analysis of ultrasound images of 165 patients with peripheral pulmonary disease admitted to Suzhou Municipal Hospital Affiliated to Nanjing Medical University from February 2016 to December 2018 who were given RP-EBUS examination. Ultrasound images were obtained for all patients. There were 76 patients treated using traditional positioning method as the control group; 89 patients were treated by probe combined with bronchoscopy positioning method as the research group where the biopsy of the lesion along the path of the ultrasound probe was taken. The positive rate of the 2 methods was observed, and the factors affecting the quality of ultra-thin bronchoscopy under RP-EBUS non-real-time guidance were analyzed. RESULTS The detection rate of the study group was 77.64%, which was significantly higher than that in control group, which was 63.16% (χ²=5.238, P<0.05). The number of biopsies in the study group was 6±1.25, which was significantly lower than that of the control group which was 9±1.87 (t=4.116, P<0.05). The diagnostic positive rate of the RP-EBUS probe was significantly higher than that of the RP-EBUS probe (χ²=5.081, P<0.05). CONCLUSIONS The diagnostic positive rate of RP-EBUS non-real-time guided subtotal bronchoscopy lung biopsy for peripheral lung disease using probe combined with bronchoscopy positioning method was higher than the traditional positioning method, and the number of biopsies in the study group was significantly lower than that in the control group, which was related to the size, location, whether the probe was wrapped, or the characteristics of the ultrasound image.

miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2.

microRNAs have been reported to play vital role in lung cancer proliferation and metastasis; the role of miR-4326 in tumor progression has not been studied. Here, we studied the effect of miR-4326 on lung cancer cell proliferation; we found that miR-4326 was significantly upregulated in lung cancer tissues determined using TCGA dataset and clinical specimens, meanwhile it was also upregulated in lung cancer cells. Overexpression of miR-4326 promoted lung cancer cell proliferation analyzed by MTT, soft agar growth, and BrdU incorporation assay, while miR-4326 knockdown suppressed lung cancer cell proliferation. We found miR-4326 targets tumor suppressor adenomatous polyposis coli 2 (APC2), which is a negative regulator of Wnt pathway, by binding to the 3'UTR of APC2. Wnt pathway could increase Cyclin D1 and c-MYC expression, we also found that miR-4326 could increase their expression, suggesting that APC2 was the target of miR-4326. Moreover, double knockdown of APC2 and miR-4326 promoted lung cancer cell proliferation, confirming that miR-4326 promoted lung cancer cell proliferation by inhibiting APC2.

Zoledronic acid inhibits infiltration of tumor-associated macrophages and angiogenesis following transcatheter arterial chemoembolization in rat hepatocellular carcinoma models.

Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC. The present study focused on the changes in TAMs following TACE, and explored the effects of TACE in combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models. Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed by histological analysis and flow cytometry. Tumor angiogenesis was measured as the mean vessel density, and initial slope was calculated from dynamic contrast enhancement MRI. Local and systemic levels of vascular endothelial growth factor (VEGF) were determined by western blotting or an ELISA, respectively. The results revealed that TACE inhibited tumor growth at 7 days following the procedure, but this inhibition was attenuated at 14 days following the procedure compared with the sham TACE control. If combined with ZA treatment, TACE exhibited a stable inhibition effect on tumor growth until the end of observation. Investigation of the underlying mechanisms demonstrated that TACE combined with ZA treatment inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared with the TACE alone group at 14 days following the procedure. Additionally, the combination treatment significantly inhibited secretion of VEGF in the present models. In conclusion, ZA treatment enhanced the effects of TACE through inhibiting TAM infiltration and tumor angiogenesis in rat HCC models.

miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B.

Lung cancer is the leading cause of cancer death worldwide, microRNAs play critical role in the initiation and development of lung cancer. Here, we used MTT assay, colony formation assay, soft agar growth assay and BrdU incorporation assay to investigate miR-937's role in lung cancer. We found that miR-937 was upregulated in lung cancer tissues and cells. Overexpression of miR-937 in A549 promoted anchorage -dependent and -independent growth, whereas knockdown of miR-937 reduced this effect. Meanwhile, we also found miR-937 overexpression increased CCND1 and c-Myc levels in both mRNA and protein levels, knockdown of miR-937 reduced this effect, confirming miR-937 promoted cell proliferation. Mechanism analyses found polyphosphate 4-phosphatase type II (INPP4B) was the target of miR-937, miR-937 directly bound to the 3'UTR of INPP4B, knockdown of INPP4B in A549 with miR-937 inhibitor promoted anchorage -dependent and -independent growth, suggesting miR-937 contributed to cell proliferation of lung cancer by inhibiting INPP4B, it might be a valuable target for lung cancer therapy.

Suppression of cyclin D1 by plasmid-based short hairpin RNA ameliorated experimental pulmonary vascular remodeling.

Our previous study has demonstrated that a plasmid-based short hairpin RNA (shRNA) against cyclin D1 could attenuate the pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in smoking rats. In this report, we examined the efficiency of this shRNA plasmid in monocrotaline-induced pulmonary vascular remodeling. A single injection of monocrotaline induced pulmonary vascular remodeling and cyclin D1 over-expression in pulmonary vascular smooth muscle. The shRNA successfully suppressed the up-regulation of cyclin D1 in pulmonary vessels of monocrotaline-treated rats. Moreover, this shRNA decreased the percentage of muscularized vessels and the wall thickness of pulmonary vessels. So, we concluded that plasmid-based shRNA against cyclin D1 ameliorated pulmonary vascular remodeling in monocrotaline-treated rats. Cyclin D1 might be a potential target for the therapy of pulmonary vascular remodeling and pulmonary hypertension.

Administration of nonviral gene vector encoding rat beta-defensin-2 ameliorates chronic Pseudomonas aeruginosa lung infection in rats.

BACKGROUND: Beta-defensin-2 (BD-2) plays an important role in host defense against pathogenic microbe challenge by its direct antimicrobial activity and immunomodulatory functions. The present study aimed to determine whether genetic up-regulation of rat BD-2 (rBD-2) could ameliorate chronic Pseudomonas aeruginosa lung infection in rats. METHODS: Plasmid-encoding rBD-2 was delivered to lungs in vivo using linear polyethylenimine at 48 h before challenging with seaweed alginate beads containing P. aeruginosa. Macroscopic and histopathological changes of the lungs, bacterial loads, inflammatory infiltration, and the levels of cytokines/chemokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, kertinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2)] were measured at 3 and 7 days post-infection (p.i.). RESULTS: The overexpression of rBD-2 resulted in a significant increase in animal survival rate (at 3 days p.i.), a significant decrease in bacterial loads in the lungs (at 3 and 7 days p.i.), and significantly milder lung pathology. In addition, the overexpression of rBD-2 led to increased infiltration of polymorphonuclear neutrophils (PMN), and elevated protein expression of cytokines/chemokines (IL-1beta, TNF-alpha, KC and MIP-2) at the early stage of infection (at 3 days p.i.), at the same time as being dramatically decreased at the later stage of infection (at 7 days p.i.). CONCLUSIONS: Genetic up-regulation of rBD-2 increased animal survival rate, and reduced bacterial loads in lungs after bacterial infection. The overexpression of rBD-2 also modulated the production of several cytokines/chemokines and increased PMN recruitment at the early stage of infection. Our findings indicate that the enhancement of BD-2 may be an efficacious intervention for chronic P. aeruginosa lung infection.

Expression of the Th1-specific cell-surface protein Tim-3 increases in a murine model of atopic asthma.

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is preferentially expressed on Th1-helper type T-cells and functions to repress the Th1-mediated immune response. However, the role of Tim-3 during the inflammatory pathogenesis of asthma remains unclear. This study determines the expression level of Tim-3 in CD4+ T-cells within the peripheral blood and bronchoalveolar lavage fluid (BALF) isolated from a murine model of atopic asthma and explores the potential role of Tim-3 during the inflammatory response. Mice were randomly divided into normal control, asthma day 1, and asthma day 7 groups, and peripheral blood T lymphocytes and BALF cells were collected. The ratio of Tim-3+/CD4+ cells among the total CD4+cell populations from peripheral blood and BALF was determined by flow cytometry, and the expression of the Tim-3 mRNA was determined by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). In contrast with the normal control group, the ratio of Tim-3+/CD4+:CD4+ cells and the level of Tim-3 mRNA in both the peripheral blood T lymphocytes and BALF cells among the asthma day 1 and asthma day 7 groups were significantly increased (p < 0.01), and those in the asthma day 7 group were higher than the asthma day 1 group (p < 0.05). There was also a positive correlation between the ratio of Tim-3+/CD4+:CD4+ detected in BALF and that the ratio detected in peripheral blood T lymphocytes (r = 0.84, p < 0.01). Therefore, the expression of Tim-3 is increased in CD4+ T-cells following airway challenge and likely affects asthma-induced inflammation by repressing the Th1-mediated immune response.