Hydrous mantle plume promoted the generation of continental flood basalts in the Tarim large igneous province.

Recent research on the water content of large igneous provinces (LIPs) has revealed that water has a significant impact on the formation of LIPs. However, most studies focus on the water content of mafic-ultramafic rocks, while relatively little attention has been paid to the water content of continental flood basalts (CFB), which form the major part of LIPs and are characterized by huge volumes (> 1 × 105 km3) and short eruption times. Here, we determined water contents of clinopyroxene crystals from the Akesu diabase, which is co-genetic with flood basalts of the Tarim LIP in China. Based on these measurements, we obtained a water content of higher than 1.23 ± 0.49 wt.% for the parental magma to the Tarim CFB and a minimum water content of 1230 ± 490 ppm for the mantle source, thus indicating the presence of a hydrous mantle plume. Combined with previous studies, our results suggest that water plays a key role in the formation of the Tarim LIP. Additionally, the whole-rock compositions of the Akesu diabase indicate a contribution of pyroxenite in the mantle source. This is consistent with a model, in which water was brought into the Tarim mantle plume by a subducted oceanic plate that entered the deep mantle.

[Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis].

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Resolution of an insidious and migratory Mycobacterium tuberculosis-associated secondary organizing pneumonia: a case report and literature review.

BACKGROUND: Organizing pneumonia (OP) is a rare interstitial lung disease. Secondary organizing pneumonia (SOP) caused by Mycobacterium tuberculosis (MTB) is extremely rare. Migratory MTB-associated SOP is more deceptive and dangerous. When insidious tuberculosis (TB) is not recognized, SOP would be misdiagnosed as cryptogenic organizing pneumonia (COP). Use of steroid hormone alone leads to the progression of TB foci or even death. Clues of distinguishing atypical TB at the background of OP is urgently needed. CASE PRESENTATION: A 56-year-old female patient was hospitalized into the local hospital because of cough and expectoration for more than half a month. Her medical history and family history showed no relation to TB or other lung diseases. Community-acquired pneumonia was diagnosed and anti-infection therapy was initialized but invalid. The patient suffered from continuous weigh loss. More puzzling, the lesions were migratory based on the chest computed tomography (CT) images. The patient was then transferred to our hospital. The immunological indexes of infection in blood and pathogenic tests in sputum and the bronchoalveolar lavage fluid were negative. The percutaneous lung puncture biopsy and pathological observation confirmed OP, but without granulomatous lesions. Additionally, pathogen detection of the punctured lung tissues by metagenomics next generation sequencing test (mNGS) were all negative. COP was highly suspected. Fortunately, the targeted next-generation sequencing (tNGS) detected MTB in the punctured lung tissues and MTB-associated SOP was definitely diagnosed. The combined therapy of anti-TB and prednisone was administrated. After treatment for 10 days, the partial lesions were significantly resorbed and the patient was discharged. In the follow-up of half a year, the patient was healthy. CONCLUSIONS: It is difficult to distinguish SOP from COP in clinical practice. Diagnosis of COP must be very cautious. Transient small nodules and cavities in the early lung image are a clue to consider TB, even though all pathogen tests are negative. tNGS is also a powerful tool to detect pathogen, ensuring prompt diagnosis of TB-related SOP. For clinicians in TB high burden countries, we encourage them to keep TB in mind before making a final diagnosis of COP.

Diagnosis of fetal total anomalous pulmonary venous connection based on the post-left atrium space ratio using artificial intelligence.

OBJECTIVE: To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence. METHODS: We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set. RESULTS: Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively. CONCLUSION: Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio.

[Effects of shell composition in shell-core structured nanoparticles on oral physiological barrier and bioavailability].

The present study prepared shell-core nanoparticles comprising poly(lactic-co-glycolic acid)(PLGA) cores encapsulated by shells composed of mixed lipids(Lipoid S100 and DSPE-PEG 2000) or polymer F127 to investigate the effects of shell composition on overcoming physiological barriers of gastrointestinal mucus and intestinal epithelial cells and improving bioavailability.The results are expected to provide references for the research on the improvement of the oral bioavailability of Chinese medicine by nanocar-riers. Silibinin(SLB) was used as a model drug to prepare PLGA nanoparticles coated with the shell of mixed lipids(SLB-LPNs) or F127(SLB-FPNs) via a modified nanoprecipitation method.Transmission electron microscopy showed that both LPNs and FPNs were spherical with a core-shell structure.The average particle sizes of SLB-LPNs and SLB-FPNs were(94.13±2.23) and(95.42±4.91) nm, respectively.The Zeta potential values were(-39.3±2.8) and(-17.0±0.2) mV, respectively.X-ray diffraction analysis revealed the presence of SLB in the two types of nanoparticles in a molecular or amorphous state.The ability of nanoparticles to cross both the mucus and epithelial barriers were evaluated using the cellular internalization kinetics assay.LPNs showed a higher rate of cell internalization than FPNs, indicating that LPNs could penetrate the mucus layer and become internalized by cells more rapidly.As revealed by the in vivo pharmacokinetic assay in rats with SLB suspension as the reference, the relative oral bioavailability of SLB-LPNs and SLB-FPNs was 400.37% and 923.31%, respectively.The effect of SLB-FPNs in improving oral bioavailability was more significant than that of SLB-LPNs.In summary, shell composition can influence the ability of nanoparticles to overcome oral physiological bar-riers, such as the mucus layer and intestinal epithelial cells, and improve oral bioavailability.Shell-core structured nanoparticles are promising nanocarriers for oral drug delivery systems.

Fetal atrial appendage aneurysm: Prenatal diagnosis by echocardiography and prognosis.

BACKGROUND: Congenital atrial appendage aneurysm (AAA) is a rare malformation which can coexist with potentially lethal complications. We aimed to summary echocardiographic characteristics and prognosis of fetal AAA. METHODS: We retrospectively analyzed the echocardiographic data of 17 fetuses with AAA，and their outcomes or pathological reports were also collected. RESULTS: Eight fetuses with left AAA (LAAA) and 9 fetuses with right AAA (RAAA) were identified. Five fetuses were diagnosed with other cardiac defects. Two fetuses with RAAA presented with arrhythmias, including atrial premature beats (n = 1) and bradyarrhythmia (n = 1). LAAA could be detected by four-chamber view (50.0%) and short-axis view (100.0%). RAAA could be detected by four-chamber view (100.0%), and view of right ventricular inflow tract (33.3%). There were three cases with mild pericardial effusion. Three cases with complex cardiac defects were selectively terminated, with confirmation of LAAA by autopsy in one case. Fourteen fetuses were born. After following 2 (range, 1-5) years, the AAA disappeared in one case with LAAA and two cases with RAAA. While, 11 cases were still diagnosed with AAA. Atrial premature beats with RAAA, which appeared in prenatal period, still persisted after birth. CONCLUSION: Congenital AAA is a rare abnormality in utero. The short-axis view and the four-chamber view were the most useful views to detect fetal AAA. Fetal AAA may disappear in childhood. Atrial tachyarrhythmias in utero may exist persistently after birth. Patients with AAA should be followed up closely and appropriate intervention should be taken when complications appeared.

[Event-related potentials of working memory impairment in children with primary nocturnal enuresis].

OBJECTIVE: To study the cognitive neural mechanism of working memory impairment in children with primary nocturnal enuresis using event-related potential (ERP). METHODS: A total of 14 children with primary nocturnal enuresis were enrolled as enuresis group, and 14 normal children were enrolled as control group. The learning-recognition task test was applied, and the ERP components (P2, N2, and P3) at Fz lead while identifying old pictures (learned) and new ones (unlearned) were measured and compared between the two groups. RESULTS: While identifying the old pictures, the enuresis group had a lower amplitude of P2 and N2 than the control group (P<0.05). There were no significant differences between the two groups in the latency of P2, N2, and P3 and the amplitude of P3. While identifying the new pictures, the enuresis group had a longer latency of P2 and a significantly lower amplitude of N2 than the control group (P<0.05). There were no significant differences between the two groups in the amplitude of P2 and P3 and the latency of N2 and P3. CONCLUSIONS: Compared with normal children, the children with primary nocturnal enuresis have reduced abilities of classified information extraction, a prolonged reaction time, and reductions in memory capacity, memory consolidation, and conflict monitoring, which causes working memory impairment.

Prenatal diagnosis of Berry syndrome by fetal echocardiography: A report of four cases.

Berry syndrome is a rare congenital cardiac malformation. We describe 4 cases of Berry syndrome diagnosed by fetal echocardiography. Based on our experience, the three-vessel view is important for diagnosing the aortopulmonary window and aortic origin of the right pulmonary artery. Furthermore, the true cross-sectional and sagittal views obtained by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch are required to image the interruption or coarctation of the aortic arch. An early and accurate prenatal diagnosis of Berry syndrome is feasible and helps to improve patient outcomes.

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer.

Although numerous long non-coding RNAs (lncRNAs) have been identified to be important in human cancer, their potential regulatory roles in epithelial tumorigenesis and tumor progression in ovarian cancer remain unclear. The purpose of the present study was to investigate lncRNAs that were differentially expressed (DE) in epithelial ovarian cancer and to explore their potential functions. The lncRNA profiles in five pairs of human epithelial ovarian cancer tissues and their adjacent normal tissues were described using microarrays. The results of the microarray analysis revealed that 672 upregulated and 549 downregulated (fold-change ≥2.0) lncRNAs were DE between the cancerous and normal tissues. Reverse transcription-quantitative polymerase chain reaction was used to validate the microarray results using four upregulated (RP11-1C1.7, XLOC_003286, growth arrest-specific 5 and ZNF295-AS1) and four downregulated (protein tyrosine kinase 7, maternally expressed gene 3, AC079776.2 and ribosomal protein lateral stalk subunit P0 pseudogene 2) lncRNAs. Furthermore, gene ontology and pathway analyses were used to carry out functional analyses of the candidate genes of DE lncRNAs. The results identified lncRNAs with significantly altered expression profiles in human epithelial ovarian cancer cells compared with those in adjacent normal cells. These data offer new insights into the occurrence and development of epithelial ovarian cancer, and these lncRNAs may provide novel molecular biomarkers for further research on epithelial ovarian cancer.

Intramyocardial Dissecting Hematoma after Acute Myocardial Infarction-Echocardiographic Features and Clinical Outcome.

OBJECTIVES: Intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI) is a rare form of subacute cardiac rupture and hence management uncertainties. The objective of this study was to describe the clinical course of a small series of IDH patients and to review the available evidence for managing similar cases. METHODS: Eight IDH patients from our center had echocardiographic, coronary angiographic and clinical outcome data reviewed. PubMed was also searched for IDH following MI. Cases were divided into three groups and compared according to the dissection location. RESULTS: In our 8 patients, 3 had septal, 1 right ventricular (RV), and 4 left ventricular (LV) dissection. Five were medically treated and 3 surgically repaired. Reviewing the literature revealed 68 IDH patients, of mean age 66 ± 10 years, 43 males. The percentage of IDH involving the LV free wall, septal, and RV free wall were 47%, 26.5%, and 26.5%, respectively. In the cohort as a whole, mortality was not different between surgically and medically treated patients (33.3% vs. 54.3%, P = 0.08), neither based on the IDH location (P = 0.49). While surgical and medical treatment of the LV free wall (20.0% vs. 40.9%, P = 0.25) and septal (46.2% vs. 60.0%, P = 0.60) were not different, surgical repair of RV free wall had significantly better survival (30.0% vs. 87.5%, P = 0.015). The LVEF (P = 0.82), mitral regurgitation (P = 0.49) failed to predict mortality. CONCLUSION: While survival following medical and surgical treatment of LV IDH is not different, patients with RV free wall dissection benefit significantly from surgical repair.

Down-regulation of miR-150 induces cell proliferation inhibition and apoptosis in non-small-cell lung cancer by targeting BAK1 in vitro.

Non-small-cell lung cancer (NSCLC) is one of the most common causes of cancer-related death. Our investigations show that miR-150 is a typical microRNA that is overexpressed in human NSCLC. We characterized the effects of miR-150 overexpression in NSCLC cells and found that down-regulation of miR-150 expression inhibited cell proliferation and induced cell apoptosis in vitro; additionally, up-regulation of miR-150 levels had the opposite effect on tumor growth and progression. Furthermore, we found that the mechanism of the miR-150 effects on NSCLC cells was associated with alterations in the expression of human BRI1-associated receptor kinase 1 (BAK1). miR-150 may function as an oncogene in NSCLC cells by directly targeting BAK1. Thus, these data highlight a novel molecular interaction between miR-150 and BAK1 and provide a novel strategy for NSCLC therapy via the down-regulation of miR-150 expression.

Effect of activated autologous monocytes/macrophages on wound healing in a rodent model of experimental diabetes.

AIM: We aimed to evaluate the effectiveness of the application of activated autologous monocytes/macrophages (Mo/Mp) on wound healing in diabetic rats. METHODS: Sixty male SD rats were equally divided into the following: control group (normal, nondiabetic), PBS-treated diabetic group, and tumor necrotic factor alpha (TNF-α) plus interferon-γ (IFN-γ)-stimulated or unstimulated Mo/Mp-treated diabetic group. Full-thickness round wounds (1cm×1cm) were created in the right hind foot of rats and the wounds were treated with PBS or Mo/Mp on day 1 after injury. In the following 14 days, the percentage of wound contraction was measured, histologic examination was performed with hematoxylin and eosin staining, and vascular endothelial growth factor (VEGF) in the wound was evaluated by Western blot analysis. RESULTS: Diabetic rats exhibited impaired wound healing with delayed angiogenesis and VEGF expression. The early application of TNF-α plus IFN-γ-stimulated autologous Mo/Mp to diabetic wounds significantly improved the delayed wound healing through the stimulation of angiogenesis and re-epithelization, as well as restoring the defect in VEGF expression. CONCLUSIONS: Mo/Mp activated by TNF-α and IFN-γ promotes diabetic wound healing and normalizes the defect in VEGF regulation associated with diabetes-induced skin-repair disorders.

Childhood bronchial tuberculosis: report of one case and literature review.

OBJECTIVE: To explore the early diagnosis of childhood bronchial tuberculosis (BTB). METHODS: The clinical data of a 9-year-old boy with long-term chronic cough were retrospectively analyzed, and the relevant literature was reviewed. RESULTS: The pediatric patient was suspected to be with bronchial asthma due to long-term chronic cough, and was confirmed to be with "nasopharyngeal tuberculosis" during surgery. Purified protein derivative (PPD) (5 IU) showed moderately positive results. Chest X-ray showed the atelectasis of left lower lobe, which was suspected to be caused by bronchial tuberculosis. Chest CT and three-dimensional airway reconstruction showed atelectasis of left lower lobe, increased air volume of the left upper lung, left deviation of the mediastinum, bronchiolitis obliterans in the left lower lobe, and narrowing of the left upper lobe bronchus, suggesting the presence of bronchial tuberculosis. The bronchoscopy showed necrosis of the left main bronchus and mucosal congestion and edema, and then bronchial tuberculosis was confirmed. In addition to the systemic anti-TB treatment, transluminal interventions including local drug injection and balloon angioplasty under bronchoscope were applied routinely and achieved good effectiveness. CONCLUSIONS: Patients with long-term chronic cough should be cautiously managed in clinical settings. Examinations including PPD test, chest CT, three-dimensional airway reconstruction, and bronchoscopy should be performed as early as possible to confirm the potential existence of bronchial tuberculosis. Meanwhile, appropriate interventional treatment under bronchoscopy should be promptly applied to provide optimal protection of bronchi and lung, restore the damaged lung function, and minimize the complications.

Invasion potential of H22 hepatocarcinoma cells is increased by HMGB1-induced tumor NF-κB signaling via initiation of HSP70.

The functional relationship and cross-regulation between damage-associated molecular patterns and NF­κB in the tumor microenvironment remains unclear. In the present study, high-mobility group protein B1 (HMGB1) was secreted in response to feed second phase of NF­κB activation from heat shock protein (HSP) 70 that may result in a higher invasion potential of hepatocarcinoma cells. HSP70 promoted the proliferation of H22 hepatocarcinoma cells through Toll-like receptor (TLR) 2 and TLR4 signaling and induced the early phosphorylation of NF-κB, which reached maximum levels within 30 min. However, HSP70 promoted the upregulation of Beclin-1 expression via Jun N-terminal kinase (JNK) activation in tumor cells and the release of HMGB1 from tumor cells. Inhibition of Beclin-1/c-JNK production prevented the second, but not the first, phase of NF-κB phosphorylation, implicating Beclin-1/c-JNK in the second phase of phosphorylation. HSP70 induced Beclin-1-derived HMGB1 production at 4 h, which occurred before the rise in the second phosphorylation that occurred at 6 h. Exogenous HMGB1 also induced the rapid phosphorylation of NF-κB and upregulated the expression of MMP-9, inhibited the rapid phosphorylation of NF-κB and reduced MMP-9 by receptor for advanced glycation end products (RAGE) inhibitor that prevented HMGB1-induced cell invasion in vitro, which demonstrated that the biological significance of HMGB1/RAGE is key to the second, but not the first, phase of NF-κB phosphorylation in tumor cells. HSP70 triggered a positive feedback loop of NF-κB activation in H22 cells. The second phase of NF-κB phosphorylation mediated by HSP70 is implicated in the increase of tumor cell malignant invasion.

[Plasma temperature calculation and coupling mechanism analysis of laser-double wire hybrid welding].

The plasma radiation of laser-double wire hybrid welding was collected by using fiber spectrometer, the coupling mechanism of arc with laser was studied through high-speed photography during welding process, and the temperature of hybrid plasma was calculated by using the method of Boltzmann plot. The results indicated that with laser hybrid, luminance was enhanced; radiation intensity became stronger; arc was attracted to the laser point; cross section contracted and arc was more stable. The laser power, welding current and arc-arc distance are important factors that have great influence on electron temperature. Increase in the laser power, amplification of welding current and reduction of arc-arc distance can all result in the rise of temperature.

Diagnostic value of an ROC curve of the size of the antepartum foramen ovale in the prediction of puerperal atrial septal defect.

The aim of this study was to determine the diagnostic value of an ROC curve of the antepartum foramen ovale (AFO) size and the ratio of FO size to aorta (AO) size (FO/AO) for the prediction of puerperal atrial septal defect in different gestational weeks (DGWs). A total of 958 cases were divided into five groups according to number of gestational weeks. Comparisons of FO size, AO size and FO/AO were determined by variance analysis. The correlations between FO size, AO size and gestational age were determined using regression analysis and comparisons between atrial septal defect (ASD) diagnosed in DGWs and normal cardiac FO size and FO/AO were analyzed by t-test. ROC curve analysis was used for FO size and FO/AO to predict the demarcation point of puerperal ASD (pASD). The differences between FO size and AO size in the five groups at DGWs were statistically significant (P=0.000). The sizes of FO and AO increased with gestational age. The differences among pASD, normal cardiac FO size and FO/AO were statistically significant (P=0.000). FO size in the five DGW groups (18-22, 23-26, 27-30, 31-34 and 35-40 weeks) was able to predict the demarcation points of pASD, which were 5.02, 5.15, 6.55, 8.55 and 7.90 mm, respectively. The prediction of pASD with AFO size and FO/AO was accurate and may provide reliable reference values in the clinic.

MicroRNA expression profiling of mature ovarian teratomas.

MicroRNAs (miRNAs) are a class of endogenous, small, non-coding RNAs that regulate gene expression by targeting mRNAs and inhibiting expression via translation repression or RNA degradation. Emerging evidence indicates that miRNAs play a crucial role in the pathogenesis of human diseases, including tumor development. We profiled the miRNA expression between mature ovarian teratoma samples and matched normal tissues using miRNA microarrays, followed by validation with quantitative RT-PCR (qRT-PCR). The most highly expressed miRNAs in mature ovarian teratoma tissues were miRNA-520a-5p, miRNA-26b*, miRNA-421, miRNA-492 and miRNA-555, with a 1.3- to 2.6-fold change, whereas the least expressed miRNAs were miRNA-142-3p, let-7a, miRNA-19a, miRNA-34a, miRNA-620, miRNA-934, miRNA-657, miRNA-720, miRNA-22, miRNA-629 and miRNA-214, with a decreased level of 55-87% compared with normal tissues. The findings of the present study are the first to provide an altered miRNA profile for mature ovarian teratomas and differentially expressed miRNAs, which, if validated in future studies, may be essential in the pathogenesis of mature ovarian teratomas.

Efficient in vitro siRNA delivery and intramuscular gene silencing using PEG-modified PAMAM dendrimers.

Although siRNA techniques have been broadly applied as a tool for gene knockdown, substantial challenges remain in achieving efficient delivery and in vivo efficacy. In particular, the low efficiency of target gene silencing in vivo is a critical limiting step to the clinical application of siRNA therapies. Poly(amidoamine) (PAMAM) dendrimers are widely used as carriers for drug and gene delivery; however, in vivo siRNA delivery by PAMAM dendrimers remains to be carefully investigated. In this study, the effectiveness of G5 and G6 PAMAM dendrimers with 8% of their surface amines conjugated to MPEG-5000 was studied for siRNA delivery in vitro and for intramuscular in vivo delivery in mice. The results from the PEG-modified dendrimers were compared to the results from the parent dendrimers as well as Lipofectamine 2000 and INTERFERin. Both PEG-modifed dendrimers protect the siRNA from being digested by RNase and gave high transfection efficiency for FITC-labeled siRNA in the primary vascular smooth muscle cells (VSMC) and mouse peritoneal macrophages. The PEG-modified dendrimers achieved knockdown of both plasmid (293A cells) and adenovirus-mediated green fluorescence protein (GFP) expression (Cos7 cells) in vitro with efficiency similar to that shown for Lipofectamine 2000. We further demonstrated in vivo that intramuscular delivery of GFP-siRNA using PEG-modified dendrimer significantly suppressed GFP expression in both transiently adenovirus infected C57BL/6 mice and GFP transgenic mice.

[Effects of astragaloside IV on the expressions of transforming growth factor-ß1 and thymic stromal lymphopoietin in a murine model of asthma].

OBJECTIVE: To observe the effects of astragaloside IV on the airway remodeling and the expressions of transforming growth factor (TGF)-ß1 and thymic stromal lymphopoietin (TSLP) in a murine model of asthma. METHODS: Forty-eight BALB/c mice were randomly divided into 4 groups, i.e. control group, asthma group, astragaloside IV group and budesonide group (n = 12 each). The BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks while the mice in the astragaloside IV group were intragastrically administered with astragaloside IV (50 mg/kg) daily for 8 consecutive weeks. Pulmonary functions were measured to evaluate the resistance of expiration. And pulmonary histopathological analysis was performed to observe the infiltration of inflammatory cells, the hyperplasia of airway global cells and the deposition of collagen. The levels of interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid (BALF) were measured by ELISA (enzyme linked immunosorbent assay). The pulmonary expression of α-SMA (alpha-smooth muscle actin) was evaluated by immunohistochemistry. The mRNA and protein expressions of TGF-ß1 and TSLP were measured by real-time PCR (polymerase chain reaction) and Western blot respectively. RESULTS: The treatment of astragaloside IV or budesonide led to a sharp decrease in airway resistance compared with the asthma group at a concentration of acetylcholine in 30 µg/kg (P < 0.05). The PAS(+) epithelial/bronchial epithelial cells, the area of collagen staining and α-SMA staining area were significantly elevated in the asthma group compared with the control group (all P < 0.01) while those in the astragaloside and budesonide groups were obviously inhibited compared with the asthma group (all P < 0.05). The BALF levels of IL-4 and IL-13 were markedly elevated in the asthma group versus the control group (P < 0.01) while those markedly decreased in the astragaloside and budesonide groups versus the asthma group (all P < 0.05). The relative expressions of TGF-ß1 and TSLP mRNA (5.23 ± 1.44, 5.70 ± 1.65) were significantly up-regulated in the asthma group versus the control group (1.02 ± 0.21, 1.02 ± 0.25) (P < 0.01) while those in the astragaloside (2.27 ± 0.65, 2.97 ± 1.03) and budesonide groups (2.10 ± 0.57, 3.32 ± 1.11) were obviously down-regulated versus the asthma group (all P < 0.05). The protein levels of TGF-ß1 and TSLP in the asthma group (0.89 ± 0.11, 0.74 ± 0.10) were markedly elevated versus the control (0.39 ± 0.04, 0.44 ± 0.05), the astragaloside (0.51 ± 0.08, 0.59 ± 0.12) and the budesonide groups (0.55 ± 0.08, 0.60 ± 0.08) (all P < 0.05). CONCLUSION: Astragaloside IV can suppress the progression of airway inflammation, airway hyperresponsiveness and remodeling in a murine model of asthma. The above effects may be partially due to the inhibited expressions of TGF-ß1 and TSLP.

Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.