miR-3934 regulates the apoptosis and secretion of inflammatory cytokines of basophils via targeting RAGE in asthma.

BACKGROUND: Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. METHODS: miR-3934 was detected as a down-regulated miRNA in basophils by sequencing analysis. Next, the expression levels of miR-3934 in peripheral blood mononuclear cells of 50 asthma patients and 50 healthy volunteers were examined by RT-qPCR methods. The basophils were then treated with AGEs and transfected with miR-3934 mimics. The apoptosis levels were examined by flow cytometry assay; and the expression levels of cytokines were detected using the ELISA kits. Finally, the Western blot was performed to examined the expression of key molecules in the TGF-ß/Smad signaling pathway. RESULTS: miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. CONCLUSION: Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-ß/Smad signaling.

Development of Risk Prediction Model for Muscular Calf Vein Thrombosis with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: This study aims to establish a risk prediction model for muscular calf vein thrombosis (MCVT) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The research sample consisted of 248 patients with AECOPD and all of them underwent vascular ultrasounds of both lower limbs in this retrospective study. Univariate analysis and multivariate logistic regression analysis were conducted on factors with significant group differences to screen for the independent risk factors of MCVT. A nomogram to predict the risk of MCVT was constructed and validated with bootstrap resampling. Results: According to the exclusion criteria, 240 patients were included for analysis, divided into the MCVT group (n = 81) and the non-MCVT group (n = 159). Multivariate logistic regression analyses showed that hypertension, elevated MPV, reduced albumin (ALB), elevated D-dimer and bed rest ≥3 days were independent risk factors for MCVT in AECOPD. A nomogram model for predicting AECOPD with MCVT was established based on them. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for the prediction model and the simplified Wells score was 0.784 (95% CI: 0.722-0.847) and 0.659 (95% CI: 0.583-0.735), respectively. The cut-off value and Youden index of prediction model were 0.248 and 0.454, respectively. At the same time, the sensitivity, specificity, positive predictive value, and negative predictive value of the prediction model were 85.9%, 59.5%, 84.6%, and 77.4%, respectively. The sensitivity and specificity of the simplified Wells score were 67.9% and 56.3%, respectively. Validation by the use of bootstrap resampling revealed optimal discrimination and calibration, and the decision analysis curve (DAC) suggested that this prediction model involved high clinical practicability. Conclusion: We developed a nomogram that can predict the risk of MCVT for AECOPD patients. This model has the potential to assist clinicians in making treatment recommendations and formulating corresponding prevention measures.

Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion.

Purpose: Metagenomic next-generation sequencing (mNGS) is a novel technique of pathogens detection that plays an increasingly important role in clinical practice. In this study, we explored the application value of mNGS in pulmonary infection combined with pleural effusion applied to samples of pleural effusion fluid. Patients and Methods: We reviewed 80 cases of pulmonary infection with pleural effusion between August 2020 and October 2021. Among them, 40 patients were placed in the mNGS group and underwent both culture and mNGS testing; the patients in the control group were only subjected to culture test. The effectiveness of mNGS was evaluated for microbial composition and diagnostic accuracy in every pleural effusion specimen type. Results: We found that the positive rate of mNGS was 70% (28/40). The comparison between mNGS and culture method resulted that the sensitivity was 100% (95% CI: 29.2-100%) and the specificity was 64.9% (95% CI: 47.5-79.8%). The positive predictive value of mNGS was 18.8% (95% CI, 13.0-26.3%), and the negative predictive value was 100%. The most commonly identified potential pathogens were bacteria, such as Streptococcus, Prevotella, Parvimonas, Porphyromonas and Gemella. The most detected fungal infection was Candida and Pneumocystis. A total of 11 patients were identified as mixed infection by mNGS. Treatment regimen adjustments were made according to mNGS results and the overall length of hospital stay in the mNGS group was shorter compared to that of the control group. Conclusion: In this study, mNGS produced higher positive rates than the culture method in detecting pathogens in the pleural effusion specimens. The technology performed satisfactorily, providing more diagnostic evidence and reducing the length of hospital stay.

Metagenomic Approaches Reveal Strain Profiling and Genotyping of Klebsiella pneumoniae from Hospitalized Patients in China.

Klebsiella pneumoniae is a leading cause of highly drug-resistant infections in hospitals worldwide. Strain-level bacterial identification on the genetic determinants of multidrug resistance and high pathogenicity is critical for the surveillance and treatment of this clinically relevant pathogen. In this study, metagenomic next-generation sequencing was performed for specimens collected from August 2020 to May 2021 in Ruijin Hospital, Ningbo Women and Children's Hospital, and the Second Affiliated Hospital of Harbin Medical University. Genome biology of K. pneumoniae prevalent in China was characterized based on metagenomic data. Thirty K. pneumoniae strains derived from 14 sequence types were identified by multilocus sequence typing. The hypervirulent ST11 K. pneumoniae strains carrying the KL64 capsular locus were the most prevalent in the hospital population. The phylogenomic analyses revealed that the metagenome-reconstructed strains and public isolate genomes belonging to the same STs were closely related in the phylogenetic tree. Furthermore, the pangenome structure of the detected K. pneumoniae strains was analyzed, particularly focusing on the distribution of antimicrobial resistance genes and virulence genes across the strains. The genes encoding carbapenemases and extended-spectrum beta-lactamases were frequently detected in the strains of ST11 and ST15. The highest numbers of virulence genes were identified in the well-known hypervirulent strains affiliated to ST23 bearing the K1 capsule. In comparison to traditional cultivation and identification, strain-level metagenomics is advantageous to understand the mechanisms underlying resistance and virulence of K. pneumoniae directly from clinical specimens. Our findings should provide novel clues for future research into culture-independent metagenomic surveillance for bacterial pathogens. IMPORTANCE Routine culture and PCR-based molecular testing in the clinical microbiology laboratory are unable to recognize pathogens at the strain level and to detect strain-specific genetic determinants involved in virulence and resistance. To address this issue, we explored the strain-level profiling of K. pneumoniae prevalent in China based on metagenome-sequenced patient materials. Genome biology of the targeted bacterium can be well characterized through decoding sequence signatures and functional gene profiles at the single-strain resolution. The in-depth metagenomic analysis on strain profiling presented here shall provide a promising perspective for culture-free pathogen surveillance and molecular epidemiology of nosocomial infections.

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.

Downregulation of miR-3934 in Peripheral Blood Mononuclear Cells of Asthmatic Patients and Its Potential Diagnostic Value.

BACKGROUND: The present study focused on the potential clinical significance of miR-3934 in the occurrence and development of asthma. METHODS: 80 asthma and 80 healthy controls were recruited in this study. The peripheral blood mononuclear cells (PBMCs) and serum samples of the asthma patients as well as the healthy controls were isolated, and the expression levels of miR-3934 in PBMCs were examined by RT-qPCR methods. Furthermore, the relationship between the level of miR-3934 in PBMCs and the disease severity has been analyzed, and the potential diagnostic value of miR-3934 was evaluated by the receiver operating characteristics (ROC) curve. Finally, the expression level of IL-6, IL-8, and IL-33 have been detected using the ELISA kits, and Pearson's correlation analysis was performed to investigate the relationship between the level of miR-3934 in PBMCs and the serum expression of those inflammatory cytokines in asthma patients. RESULTS: miR-3934 was dramatically decreased in PBMCs of the asthma patients, and miR-3934 was markedly reduced in PBMCs of patients with severe asthma vs. mild asthma. Furthermore, ROC analysis showed that levels of miR-3934 in PBMCs can distinguish asthma patient, especially the severe asthma patients from the controls. Finally, the levels of miR-3934 in PBMCs were negatively correlated with the serum levels of IL-6, IL-8, and IL-33 in asthma patients, respectively. CONCLUSIONS: miR-3934 was downregulated in PBMCs of asthmatic patients and may function as a potential diagnosis biomarker.

Prediction of adverse clinical outcomes in patients with coronavirus disease 2019.

OBJECTIVE: This study aims to investigate blood and biochemical laboratory findings in patients with coronavirus disease (COVID-19) and analyze the potential predictors of poor outcome in patients with COVID-19. METHODS: The clinical, laboratory, and outcome data of 87 patients with COVID-19 were collected and retrospectively analyzed. Only data collected at the time of admission were used in the analysis for predictors of poor outcome. These patients were divided into two groups: the adverse prognosis group (36 patients) and the non-adverse prognosis group (51 patients). The adverse prognosis of COVID-19 patients was defined as admission to the intensive care unit or death. RESULTS: On the univariate analysis, age, white blood cell (WBC) count, neutrophil counts, lymphocytes count, neutrophils-to-lymphocytes ratio (NLR), interleukin-6, albumin-to-globulin ratio (AGR), albumin, lactate dehydrogenase, glutamyl transpeptidase, and blood glucose were found to be the significant predictors. On the multivariate analysis, the predictors of poor outcome of patients with COVID-19 were NLR (OR = 2.741, [95% CI = 1.02 ~ 7.35], P = .045) and IL-6 (OR = 1.405, [95% CI = 1.04 ~ 1.89, P = .025]). The receiver operating characteristic (ROC) curve revealed that the AUC of NLR, interleukin-6, pneumonia severity index (PSI) score, and Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65) score were 0.883, 0.852, 0.824, and 0.782, respectively. CONCLUSION: High interleukin-6 (6 pg/mL, cuff value) and NLR (4.48, cuff value) can be used to predict poor outcomes in patients with COVID-19 on admission, thus can serve as a beneficial tool for timely identifying COVID-19 patients prone to poor outcome and reduce patient mortality through early intervention.

IFN-γ regulates the transformation of microglia into dendritic-like cells via the ERK/c-myc signaling pathway during cerebral ischemia/reperfusion in mice.

Cerebral ischemia-reperfusion injury induces a secondary immune inflammatory reaction that exacerbates brain injury and clinical prognosis. Dendritic cells (DCs) and microglia are both important regulators of neuroinflammation. Studies have confirmed that a large number of cells express the DC surface marker CD11c in the ischemic area, and some of these cells also express microglial markers. However, the specific mechanism of transformation between microglia and DCs and their roles in the process of cerebral ischemia-reperfusion injury are still not clear. In this study, we established a mouse model and flow cytometry was used to detect the expression of mature DC surface molecules in activated microglia. IFN-γ knockout mice were used to determine the regulatory effect of IFN-γ on microglial transformation. We found that CD11c+ cells were derived from microglia after ischemia-reperfusion injury, and this group of cells highly expressed MHC-II molecules and other costimulatory molecules, such as CD80 and CD86, which were regulated by IFN-γ and its downstream signaling molecules ERK/c-myc. In summary, our results showed in cerebral ischemia-reperfusion injury, IFN-γ regulates the transformation of microglia to DC-like cells. Microglial-derived DC-like cells possess the ability to present antigens and activate naïve T cells which is regulated by the ERK/c-myc signaling pathway.

Prediction of the Severity of the Coronavirus Disease and Its Adverse Clinical Outcomes.

This study aims to investigate blood and biochemical laboratory findings in patients with severe coronavirus disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes and to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Further, the patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin ratio, lactate dehydrogenase level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic curve revealed that the combination of IL-6 level, absolute lymphocyte count, and age is superior to a single factor as predictors for severe COVID-19, regardless of whether it is in terms of the area under the curve or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.

miR-223-5p Suppresses Tumor Growth and Metastasis in Non-Small Cell Lung Cancer by Targeting E2F8.

miR-223-5p has been demonstrated to regulate the development and progression of various cancers, such as hepatocellular carcinoma, breast cancer, and gastric carcinoma. However, the role of miR-223-5p in non-small cell lung cancer (NSCLC) requires further investigation. In this study, we found that the expression of miR-223-5p was significantly downregulated in NSCLC tissues and cell lines. Moreover, the expression level of miR-223-5p is negatively correlated with the malignance of NSCLC. We found that overexpression of miR-223-5p remarkably suppressed the proliferation of NSCLC cells in vitro and in vivo. miR-223-5p overexpression also led to reduced migration and invasion in NSCLC cells. Mechanistically, we found that E2F8, a key transcription factor involved in many kinds of biological processes, was a direct target gene of miR-223-5p. Overexpression of miR-223-5p significantly decreased the mRNA and protein levels of E2F8 in NSCLC cells. We also showed that restoration of E2F8 rescued the proliferation, migration, and invasion of miR-223-5p-overexpressing NSCLC cells. Taken together, our findings demonstrated that miR-223-5p suppressed NSCLC progression through targeting E2F8.

Construction of a transcription factor­long non­coding RNA­microRNA network for the identification of key regulators in lung adenocarcinoma and lung squamous cell carcinoma.

The interactions of microRNAs (miRNAs), transcription factors (TFs) and their common target long non­coding RNAs (lncRNAs) can lead to the production of TF­miRNA­lncRNA (TML) network motifs. These motifs are functional regulators that perform a wide range of biological processes, such as carcinogenesis. However, TML network motifs have not been systematically identified, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, a computational integration approach was performed using multiple sources in order to construct a global TML network for LUAD and LUSC. The analysis revealed several dysregulated TML network motifs, which were common between the two lung cancer subtypes or specific to a single cancer subtype. In addition, functional analysis further indicated that the TML network motifs may potentially serve as putative biomarkers in LUAD and LUSC. The associations between drug treatments and dysregulated TML network motifs were also examined. Collectively, the present study elucidated the roles of TML network motifs in LUAD and LUSC, which may be beneficial for understanding the pathogenesis of lung cancer and its potential treatment.

FOXP3 polymorphisms in interstitial lung disease among Chinese Han population: A genetic association study.

INTRODUCTION: Both genetic and environmental factors are implicated in the pathogenesis of interstitial lung disease (ILD). Single-nucleotide polymorphisms (SNPs) in FOXP3 genes were implicated in the causation of some autoimmune diseases; however, association of these genes and ILD has not been reported. OBJECTIVES: To investigate whether FOXP3 polymorphisms are associated with ILD in a representative Chinese population. METHODS: One hundred and fifty-seven ILD patients and 170 healthy controls were recruited; SNPs were genotyped by the Sequenom MassARRAY platform and SHEsis was used to estimate the haplotype frequencies of SNPs. RESULTS: The CC and TC genotypes of FOXP3 rs2280883 were associated with a significantly higher risk of connective tissue disease-associated ILD (CTP-ILD) than the TT genotype (P = .006). Patients with idiopathic interstitial pneumonia (IIP) showed a significantly higher frequency of rs3761547 (GG genotype) and rs3761549 (CC genotype) polymorphisms of FOXP3 as compared to that in controls (P = .038 and P = .026, respectively). The rs2294021 (TC genotype) was less frequently observed among IIP patients as compared to that in controls (P = 0.029). In addition, the FOXP3 CAATC haplotype was associated with a greater risk for CTD-ILD (P =.048) as compared to controls, and the FOXP3 TCCCC haplotype showed an increased IIP risk (P = .001); however, patients with the FOXP3 TACTT haplotype showed a significant protective effect against IIP (P = .036). CONCLUSION: FOXP3 polymorphisms may be important markers to determine susceptibility to IIP or CTP-ILD in Chinese population.

Netrin-1 elicits metastatic potential of non-small cell lung carcinoma cell by enhancing cell invasion, migration and vasculogenic mimicry via EMT induction.

Ectopic expression of netrin-1 has been validated in several cancers including non-small cell lung cancer (NSCLC). Recent research confirms the critical role of netrin-1 in NSCLC growth and its prognostic value. Unfortunately, its contribution in NSCLC metastasis remains elusive. Here, netrin-1 had relatively high expression in NSCLC tissues and cells, especially in high metastatic groups. Notably, netrin-1 overexpression aggravated the malignant metastatic behavior of NSCLC cells, including cell invasion, migration, and vasculogenic mimicry (VM), whereas netrin-1 depression reversely dampened the metastatic potential. Mechanism analysis confirmed that elevation of netrin-1 induced the typical morphological changes of epithelial-to-mesenchymal transition (EMT) and increased the expression of EMT markers, including E-cadherin down-regulation and N-cadherin up-regulation. Consistently, netrin-1 inhibition inversely antagonized the occurrence of EMT. Moreover, netrin-1 also activated the oncogenic pathways of PI3K/AKT and ERK signaling. More importantly, blocking these pathways with their antagonists LY294002 or U0126 reversed the effects of netrin-1 overexpression on cell invasion, migration, EMT, and VM formation. Collectively, the current data suggest that netrin-1 can act as a pro-metastatic factor in NSCLC by enhancing cell invasion, migration, and VM via PI3K/AKT and ERK-mediated EMT process, thereby implicating netrin-1 as a novel promising therapeutic target against aggressive NSCLC.

Association of IL-6 polymorphisms with chronic obstructive pulmonary disease risk: meta-analysis of genetic association, gene expression and expression quantitative trait locus analysis.

AIM: IL-6 might play an important role in the mechanism of chronic obstructive pulmonary disease (COPD). This study assessed the relationship of rs1800796 and rs1800797 of IL-6 with COPD. MATERIALS & METHODS: We conducted meta-analysis and gene expression analysis using published datasets to examine the associations between IL-6 SNPs and COPD. RESULTS: rs1800796 was significantly associated with COPD, yielding a pooled odds ratio of 0.52 (95% CI: 0.33-0.84; p = 0.007), and showed cis-expression quantitative trait locus associations (p = 0.02148). Differential gene expression analysis found that IL-6 was upregulated in COPD cases compared with controls. The associations of rs1800797 with COPD were not significant. CONCLUSION: The findings showed that rs1800796 was associated with COPD in Europeans and might affect COPD risk through disturbing IL-6 gene expression.

Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment.

The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.

Overexpression of MAC30 is associated with poor clinical outcome in human non-small-cell lung cancer.

The aim of this study was to detect MAC30 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Quantitative real-time RT-PCR was performed to examine the expression of MAC30 mRNA in 20 cases of NSCLC and corresponding non-tumor tissue samples. Immunohistochemistry was performed to detect the expression of MAC30 in 95 NSCLC tissues. We found that the expression levels of MAC30 mRNA in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level MAC30 expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Patients with high expression levels of MAC30 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high MAC30 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of MAC30 may play an important role in the progression of NSCLC and MAC30 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

The in vitro effects of advanced glycation end products on basophil functions.

BACKGROUND: Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. METHODS: We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. RESULTS: Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. CONCLUSIONS: AGEs seem to act on human basophils; they suppress the cells' longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs.

Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils.

Basophils are the rarest leukocytes in human blood, but they are now recognized as one of the most important immunomodulatory as well as effector cells in allergic inflammation. Leptin, a member of the IL-6 cytokine family, has metabolic effects as an adipokine, and it is also known to participate in the pathogenesis of inflammatory reactions. Because there is an epidemiologic relationship between obesity and allergy, we examined whether basophil functions are modified by leptin. We found that human basophils express leptin receptor (LepR) at both the mRNA and surface protein levels, which were upregulated by IL-33. Leptin exerted strong effects on multiple basophil functions. It induced a strong migratory response in human basophils, similar in potency to that of basophil-active chemokines. Also, leptin enhanced survival of human basophils, although its potency was less than that of IL-3. Additionally, CD63, a basophil activation marker expressed on the cell surface, was upregulated by leptin, an effect that was neutralized by blocking of LepR. Assessments of basophil degranulation and cytokine synthesis found that leptin showed a strong priming effect on human basophil degranulation in response to FcεRI aggregation and induced Th2, but not Th1, cytokine production by the cells. In summary, the present findings indicate that leptin may be a key molecule mediating the effects of adipocytes on inflammatory cells such as basophils by binding to LepR and activating the cellular functions, presumably exacerbating allergic inflammation.

Pulmonary responses to polyhydroxylated fullerenols, C(60)(OH)(x).

Although many scientists have been attracted by polyhydroxylated fullerenols for their radical-scavenging and antioxidant ability in vivo and in vitro and their potential use as a drug or for drug delivery, there is little information on their pulmonary toxicological properties. The aim of this study was to investigate the effect of polyhydroxylated derivatives of fullerene on Sprague-Dawley rats after intratracheal instillation. Polyhydroxylated fullerenols [C(60)(OH)(x), x = 22, 24] were administered intratracheally (1, 5 or 10 mg per rat). Following 3-day exposures, the lungs of the rats were assessed using bronchoalveolar lavage fluid biomarkers and a pathological evaluation of lung tissue. Exposures to 1 mg per rat did not induce adverse pulmonary toxicity, while the two other doses induced cell injury effect, oxidative/nitrosative stress and inflammation, showing that C(60)(OH)(x) produced responses in a dose-dependent manner. The dosage of C(60)(OH)(x) retained in lung and the ensuing aggregation might be the main factor in the process. Our results might shed light on the possible use of C(60)(OH)(x) as an inhaled drug.

[Effects of tetrandrine on pulmonary capillary permeability in rats with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To observe the effects of tetrandrine (Tet) on the pulmonary capillary permeability in rats with acute lung injury induced by intravenous injection of lipopolysaccharide (LPS). METHODS: Thirty-two healthy male Wistar rats were randomly divided into 4 groups: the model group, the normal group, the Tet prevention group and the Tet treatment group, 8 in each group. All rats except those in the normal group, were established into acute lung injury model by intravenous injection of LPS. Intravenous injection of Tet (20 mg/ kg) were given to the Tet prevention group 30 min before and to the Tet treatment group 30 min after modeling respectively, and equal volume of normal saline was given to the other two groups instead. Arterial blood samples were collected to determine PaO2 and PaCO2 at the time points of immediately after modeling (0 h), 0.5 h, 2 h, 4 h, 6 h. The animals were sacrificed by the end of the experiment, the wet/dry weight ratio of lung (W/ D), neutrophil percentage in bronchoalveolar lavage fluid (BALF), concentration of TNF-a in peripheral blood and BALF by ELISA, and content of malonaldehyde (MDA) in lobus inferior pulmonis homogenate by thio barbituric acid colorimetric method were determined. Pathological change of the upper lobe of lung was examined and lung injury was scored as well. RESULTS: As compared with that in the model group, the level of PaO2 was higher in Tet prevention group at 0.5 h, 2 h, 4 h, 6 h and in the Tet treatment group at 2 h, 4 h, 6 h (P< 0.05); and the content of TNF-alpha, MDA and neutrophil percentage in BALF, as well as W/D and lung injury score were lower in the Tet prevention group and the Tet treatment group (P <0.05). Pathological changes of lung in the two Tet groups were all better than those in the model group. CONCLUSION: Early intervention with tetrandrine shows a protectiv effect on rats against acute lung injury induced by intravenous injection of LPS.