Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis.

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. METHODS: In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. RESULTS: Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-ß treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-ß-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-ß/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-ß/Smad signaling pathway in NSCLC cells. CONCLUSION: In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-ß/Smad signaling pathway and represents a novel therapeutic target for NSCLC.

CO2 Adsorption on N-Doped Porous Biocarbon Synthesized from Biomass Corncobs in Simulated Flue Gas.

This study was to develop a low-cost N-doped porous biocarbon adsorbent that can directly adsorb CO2 in high-temperature flue gas from fossil fuel combustion. The porous biocarbon was prepared by nitrogen doping and nitrogen-oxygen codoping through K2CO3 activation. Results showed that these samples exhibited a high specific surface area of 1209-2307 m2/g with a pore volume of 0.492-0.868 cm3/g and a nitrogen content of 0.41-3.3 wt %. The optimized sample CNNK-1 exhibited a high adsorption capacity of 1.30 and 0.27 mmol/g in the simulated flue gas (14.4 vol % CO2 + 85.6 vol % N2) and a high CO2/N2 selectivity of 80 and 20 at 25 and 100 °C and 1 bar, respectively. Studies revealed that too many microporous pores could hinder CO2 diffusion and adsorption due to the decrease of CO2 partial pressure and thermodynamic driving force in the simulated flue gas. The CO2 adsorption of the samples was mainly chemical adsorption at 100 °C, which depended on the surface nitrogen functional groups. Nitrogen functional groups (pyridinic-N and primary and secondary amines) reacted chemically with CO2 to produce graphitic-N, pyrrolic-like structures, and carboxyl functional groups (-N-COOH). Nitrogen and oxygen codoping increased the amount of nitrogen doping content in the sample, but acidic oxygen functional groups (carboxyl groups, lactones, and phenols) were introduced, which weakened the acid-base interactions between the sample and CO2 molecules. It was demonstrated that SO2 and water vapor had inhibition effects on CO2 adsorption, while NO nearly has no effect on the complex flue gas. Cyclic regenerative adsorption showed that CNNK-1 possessed excellent regeneration and stabilization ability in complex flue gases, indicating that corncob-derived biocarbon had excellent CO2 adsorption in high-temperature flue gas.

Analysis of Correlation Between Serum Hypoxia-Inducible Factor-1α, Uric Acid, and Inflammatory Factor Levels and Lung Function in Patients with AECOPD.

Objective: To investigate the correlation between the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels, and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The clinical data of patients with chronic obstructive pulmonary disease (40 cases) from March 2020 to March 2021 were retrospectively analyzed. According to the disease condition in patients with chronic obstructive pulmonary disease, they were divided into acute exacerbation stage (observation group, 20 cases) and stable stage (control group, 20 cases). All patients' basic data such as age, sex, and course of disease were collected and sorted out, and the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels (procalcitonin, interleukin-6, and high-sensitivity C-reactive protein), and the index of their pulmonary function were measured. The profiles of serum hypoxia-inducible factor-1 alpha and uric acid, levels of inflammatory factors, and pulmonary function indices were measured and compared between the observation and control groups. The correlation between patients' serum hypoxia-inducible factor-1α, uric acid, and inflammatory factors and lung function was analyzed. Results: There was no difference in basic data between the observation group and the control group, P > .05. Serum hypoxia-inducible factor-1α, uric acid, and levels of inflammatory factors were all higher in the observation group than the control group, and the differences are significant (P < .05). There was significant difference in lung function indexes between the observation group and the control group (P < .05). Serum hypoxia-inducible factor-1α, uric acid, and inflammatory factor levels were negatively associated with pulmonary function indices. Conclusion: The more serious the condition of AECOPD patients is, the levels of serum hypoxia inducible factor -1α, uric acid and inflammatory factors gradually increase, and the lung function tends to decline.

Long non-coding RNA MSC-AS1 facilitates the proliferation and glycolysis of gastric cancer cells by regulating PFKFB3 expression.

Long non-coding RNA musculin antisense RNA 1 (lncRNA MSC-AS1) has been recognized as an oncogene in pancreatic cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and renal cell carcinoma. However, the functional significance of MSC-AS1 and its underlying mechanism in gastric cancer (GC) progression remain unclear. In this study, we demonstrated that the expression of MSC-AS1 in GC tissues was significantly higher than that in non-tumor tissues. Moreover, the elevated level of MSC-AS1 was detected in GC cells (MKN-45, AGS, SGC-7901, and MGC-803) compared to normal GES-1 gastric mucosal cells. The cancer genome atlas (TCGA) data further indicated that the high level of MSC-AS1 was closely correlated with advanced tumor stage and poor prognosis of GC. Next, we revealed that MSC-AS1 knockdown inhibited the proliferation, glucose consumption, lactate production, and pyruvate production of MGC-803 cells. Conversely, MSC-AS1 overexpression enhanced the proliferation and glycolysis of AGC cells. Mechanistically, modulating MSC-AS1 level affected the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), but did not impact the levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) in GC cells. Based on this, we reversed the MSC-AS1 knockdown-induced the inhibition of cell proliferation and glycolysis by restoring PFKFB3 expression in MGC-803 cells. In conclusion, MSC-AS1 facilitated the proliferation and glycolysis of GC cells by maintaining PFKFB3 expression.

Photodynamic Therapy with Tumor Cell Discrimination through RNA-Targeting Ability of Photosensitizer.

Photodynamic therapy (PDT) represents an effective treatment to cure cancer. The targeting ability of the photosensitizer is of utmost importance. Photosensitizers that discriminate cancer cells can avoid the killing of normal cells and improve PDT efficacy. However, the design and synthesis of photosensitizers conjugated with a recognition unit of cancer cell markers is complex and may not effectively target cancer. Considering that the total RNA content in cancer cells is commonly higher than in normal cells, this study has developed the photosensitizer QICY with RNA-targeting abilities for the discrimination of cancer cells. QICY was specifically located in cancer cells rather than normal cells due to their stronger electrostatic interactions with RNA, thereby further improving the PDT effects on the cancer cells. After intravenous injection into mice bearing a xenograft tumor, QICY accumulated into the tumor location through the enhanced permeability and retention effect, automatically targeted cancer cells under the control of RNA, and inhibited tumor growth under 630 nm laser irradiation without obvious side effects. This intelligent photosensitizer with RNA-targeting ability not only simplifies the design and synthesis of cancer-cell-targeting photosensitizers but also paves the way for the further development of highly efficient PDTs.

A novel group decision making method based on CoCoSo and interval-valued Q-rung orthopair fuzzy sets.

Interval-valued q-rung orthopair fuzzy set (IVq-ROFS) is a powerful tool for dealing with uncertainty. In this paper, we first propose a new method for aggregating multiple IVq-ROFSs, which is easier to understand and implement in the multi-attribute group decision making process compared to current aggregation operators. Secondly, this paper introduces a new fuzzy entropy with parameters based on IVq-ROFS, which is highly flexible due to its adjustable parameters. Based on this, the IVq-ROFS-based attribute weight calculation method is proposed to obtain the objective weights of the attributes, which is more reasonable and objective than the existing methods. Then, for the dimensional differences between the three compromise scores in the original Combined Compromise Solution (CoCoSo) method, the enhanced compromise scores are proposed. These scores are obtained by normalizing the three dependent compromise scores, ensuring that they fall within the same range. Finally, a novel CoCoSo mothed on IVq-ROFS using the proposed fuzzy entropy and enhanced compromise scores is presented. The proposed method is highly adaptable and scalable, not limited to IVq-ROFS. The excellent performance and robustness of the proposed method are verified in sepsis diagnosis applications.

A new multi-attribute group decision-making method based on Einstein Bonferroni operators under interval-valued Fermatean hesitant fuzzy environment.

Faced with the increasing complexity and uncertainty of decision-making information, interval-valued Fermatean hesitant fuzzy sets (IVFHFSs) were presented as a novel mathematical model that handled uncertain data more effectively. However, existing multi-attribute group decision-making (MAGDM) methods based on IVFHFSs do not thoroughly investigate the operational laws. Also, these existing MAGDM methods do not take into account the connections between attributes and are less flexible. To address these issues, this paper proposes a new MAGDM method based on Einstein Bonferroni operators under IVFHFSs. First, we thoroughly examine the operational laws of Einstein t-norms under the IVFHFSs to further extend the study of the operational laws. Then, we introduce the interval-valued Fermatean hesitant fuzzy Einstein Bonferroni mean operator and the interval-valued Fermatean hesitant fuzzy Einstein weighted Bonferroni mean operator under Einstein t-norms. Our suggested aggregation operators consider the relationship between attributes and are far more flexible in comparison to the current approaches. Later, a novel MAGDM method based on Einstein Bonferroni operators under the IVFHFSs is given. Finally, the practicality and validity of the proposed method are demonstrated by a cardiovascular disease diagnosis application.

A storage mechanism of data access record on consortium chain based on master-slave blocks.

Although data on the blockchain cannot be tampered with, malicious access by insiders can also lead to data leakage. Access records of block are an important basis for tracing the source of data breaches; however, access records themselves may be tampered with. Therefore, it is important to study how to protect the block access records. So far, the protection of block access records has not received much attention. To make block access records a protected data resource as well, this paper proposes a storage mechanism of data access record on consortium chain based on master-slave blocks. In this mechanism, the master block is used to store data resources, and the slave block of the master block is used to store access records of the master block. This method ensures that the slave block has the security characteristics of the single chain block, making the access record traceable and immutable. The storage mechanism's viability is confirmed by real-world experimentation. The proposed mechanism outperforms the single chain in terms of data query performance, according to the testing results on public data sets.

A risk prediction nomogram for resistant hypertension in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are liable to have resistant hypertension (RH) associated with unfavorable cardiovascular events. It is of necessity to predict OSA patients who are susceptible to resistant hypertension. Hence, we conducted a retrospective study based on the clinical records of OSA patients admitted to Yixing Hospital Affiliated to Jiangsu University from January 2018 to December 2022. According to different time periods, patients diagnosed between January 2018 and December 2021 were included in the training set (n = 539) for modeling, and those diagnosed between January 2022 and December 2022 were enrolled into the validation set (n = 259) for further assessment. The incidence of RH in the training set and external validation set was comparable (P = 0.396). The related clinical data of patients enrolled were collected and analyzed through univariate analysis and least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a nomogram. Finally, five variables were confirmed as independent risk factors for OSA patients with RH, including smoking, heart disease, neck circumference, AHI and T90. The nomogram established on the basis of variables above was shown to have good discrimination and calibration in both the training set and validation set. Decision curve analysis indicated that the nomogram was useful for a majority of OSA patients. Therefore, our nomogram might be useful to identify OSA patients at high risk of developing RH and facilitate the individualized management of OSA patients in clinical practice.

Dose-response relationship between sleep duration and cardiovascular metabolic multimorbidity among older adults in China: A nationwide survey.

AIMS AND OBJECTIVES: The purpose of this study was to explore the relationship between the duration of sleep per day and cardiovascular metabolic multimorbidity (CMM) in older adults and to identify how many hours of sleep per day can lead to a lower risk of CMM in older adults. BACKGROUND: CMM are a common syndrome in the older adults. There may be an association between sleep duration and CMM in older adults, with both insomnia and sleep deprivation having an impact on the health of older adults. Therefore, it is important to explore the possibility that older adults who sleep for a few hours per day may have a lower prevalence of CMM. METHODS: The study included 9710 older adults. The sleep duration in this study was assessed by the question "How many hours of sleep do you currently get in a day? ". Older adults were defined as having CMM when they had two or more of the five categories of hypertension, diabetes, heart disease, stroke or cardiovascular disease, dyslipidemia. We used multivariate logistic regression analysis to explore the association among sleep duration and CMM. Restrictive cubic splines were used to examine the shape of the association among sleep duration and the CMM. The STROBE checklist was used for this cross-sectional study. RESULTS: The mean age was 84.78 ± 11.73 years, with 55.5 % being female. Of the total sample, 21.3 % were CMM. When all covariates were adjusted, there was dose-response relationship between sleep duration and CMM. The dose-response relationship between CMM and sleep duration showed that older adults had a lower risk of cardiovascular and metabolic multimorbidity when they slept 9 h and 10 h per day. CONCLUSION: With the increasing population of older adults, the number of older adults suffering from CMM continues to rise, and adequate sleep time can effectively prevent the occurrence of CMM. We should pay attention to the sleep problem of the older adults. RELEVANCE TO CLINICAL PRACTICE: This study provided information for healthcare providers to identify circumstances that increase cardiovascular metabolic multimorbidity and suggest the appropriate sleep duration per day to reduce the risk of disease in older adults. PATIENT OR PUBLIC CONTRIBUTION: Because of the public database data used in this study, all data were collected by survey agency personnel, so this section is not applicable to this study.

A new multi-attribute decision making approach based on new score function and hybrid weighted score measure in interval-valued Fermatean fuzzy environment.

Interval-valued Fermatean fuzzy sets (IVFFSs) were introduced as a more effective mathematical tool for handling uncertain information in 2021. In this paper, firstly, a novel score function (SCF) is proposed based on IVFFNs that can distinguish between any two IVFFNs. And then, the novel SCF and hybrid weighted score measure were used to construct a new multi-attribute decision-making (MADM) method. Besides, three cases are used to demonstrate that our proposed method can overcome the disadvantages that the existing approaches cannot obtain the preference orderings of alternatives in some circumstances and involves the existence of division by zero error in the decision procedure. Compared with the two existing MADM methods, our proposed approach has the highest recognition index and the lowest error rate of division by zero. Our proposed method provides a better approach to dealing with the MADM problem in the interval-valued Fermatean fuzzy environment.

Risk Factors of Readmission Within 90 Days for Chronic Obstructive Pulmonary Disease Patients with Frailty and Construction of an Early Warning Model.

Objective: This study aimed to explore the risk factors for readmission within 90 d in Chronic Obstructive Pulmonary Disease (COPD) patients with frailty and construct a clinical warning model. Methods: COPD patients with frailty hospitalized in the Department of Respiratory and Critical Care Medicine of Yixing Hospital, Affiliated to Jiangsu University, were retrospectively collected from January 1, 2020, to June 30, 2022. Patients were divided into readmission and control groups according to readmission within 90 d. The clinical data of the two groups were evaluated by univariate and multivariate logistic regression analyses to identify readmission risk factors within 90 d in COPD patients with frailty. Then, a risk quantitative early warning model was constructed. Finally, the model's prediction efficiency was evaluated, and external verification was carried out. Results: The multivariate logistic regression analysis showed that BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model for these patients was established as follows: Logit (p) = -1.896 + (-0.166 × BMI) + (0.969 × number of hospitalizations in the past year ≥ 2) + (0.265 × CCI) + (0.405 × REFS) + (-3.209 × 4MGS), and presented an area under the ROC curve (AUC) of 0.744 [95% CI: 0.687-0.801]. The AUC of the external validation cohort was 0.737 (95% CI: 0.648-0.826), and the AUC of the LACE warning model was 0.657 (95% CI:0.552-0.762). Conclusion: The BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model presented a moderate predictive value for assessing the risk of readmission within 90 d in these patients.

Associations of Clinical Characteristics and Intestinal Flora Imbalance in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients and the Construction of an Early Warning Model.

OBJECTIVE: Establish a simple predictive model and scoring rule that is suitable for clinical medical staff in respiratory departments to assess intestinal flora imbalance occurrence in stable chronic obstructive pulmonary disease (COPD) patients. METHODS: From January 1, 2019, to December 31, 2020, COPD patients (195 cases) - who attended the Outpatient Department, Respiratory and Critical Care, Yixing Hospital, Jiangsu University - were enrolled in a cross-sectional study. Based on stool examination results, patients were divided into experimental (41 cases) and control (154 cases) groups. Single-factor and logistic regression analyses were performed with the baseline data of the two groups to obtain a new predictive model, which was further simplified. RESULTS: Five predictive factors composed the model: body mass index (BMI), serum albumin (ALB), Charlson's Comorbidity Index (CCI), gastrointestinal symptom score (GSRs), and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The model to predict intestinal flora imbalance in stable COPD patients had an area under the ROC curve (AUC) of 0.953 [95% CI (0.924, 0.982)]. After simplifying the scoring rules, the AUC was 0.767 [95% CI (0.676, 0.858)]. CONCLUSION: In the current study, we obtained a model that could effectively predict intestinal flora imbalance risk in stable COPD patients, being suitable for implementation in early treatments to improve the prognosis. Moreover, all indicators can be easily and simply obtained.

Lycium barbarum Polysaccharide Inhibited Hypoxia-Inducible Factor 1 in COPD Patients.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by irreversible airflow obstruction. Pathogenic mechanisms underlying COPD remain largely unknown. Objective: The current study was designed to explore serum concentration of hypoxia-inducible factor 1α (HIF-1α) in stable COPD patients and the potential effect of Lycium barbarum polysaccharides (LBP) on HIF-1α protein expression. Methods: Serum HIF-1α was quantified by ELISA in 102 stable COPD patients before and after 2-week orally taken LBP (100 mL/time, twice daily, 5-15 mg/mL). Correlation of serum LBP and lung function (FEV1%) or blood gas (PO2 and PCO2) was also analyzed. As a control, 105 healthy subjects were also enrolled into this study. Results: Serum concentration of HIF-1α was significantly higher in the stable COPD patients (37.34 ± 7.20 pg/mL) than that in the healthy subjects (29.55 ± 9.66 pg/mL, P<0.001). Oral administration of LBP (5 mg/mL, 100 mL, twice daily for 2 weeks) not only relieved COPD symptoms but also significantly reduced serum HIF-1α concentration (36.94 ± 9.23 vs 30.49 ± 6.42 pg/mL, P<0.05). In addition, level of serum HIF-1α concentration was significantly correlated with PCO2 (r = 0.283, P<0.001), but negatively and significantly correlated with PO2 (r = -0.490, P=0.005) or FEV1%(r = -0.420, P=0.018). Conclusion: These findings suggested that activation of HIF-1 signaling pathway may be involved in the pathophysiology of COPD and that stabilization of serum HIF-1α concentration by LBP might benefit the stable COPD patients.

Two-Step Pretreatment of Corn Stover Silage Using Non-ionic Surfactant and Ferric Nitrate for Enhancing Sugar Recovery and Enzymatic Digestibility of Cellulose.

Corn stover silage (CSS) is regarded as a promising feedstock for bioethanol production. The two-step pretreatment using a sequential non-ionic surfactant and ferric nitrate pretreatment was investigated for improving the enzymatic hydrolysis of CSS. The first-step pretreatment using non-ionic surfactant (Tween-80, 2.0 wt.%) at 60 °C for 60 min achieved 30.48% the removal of lignin. Compared with the raw material, the cellulose content of first-step treated CSS increased by 15.86%. The second step using ferric nitrate resulted in 94.56% hemicellulose removal and achieved 72.53% cellulose purity at 130 °C for 30 min, while the yields of furfural and HMF were only 0.36 and 0.32 g/100 g dry material, respectively. The maximum enzymatic digestibility of the two-step treated CSS was 90.98% with a low cellulose dosage (15 FPU/g-glucan), which was approximately 32.07% higher than that of the first-step pretreatment only with Tween-80.

A new method to predict hospital mortality in severe community acquired pneumonia.

BACKGROUND & AIMS: The aim of this study is to develop a new method that is able to accurately predict the 28day hospital mortality in patients with severe community acquired pneumonia (SCAP) at an early stage. METHODS: We selected 37,348 SCAP patients in ICU from 173 hospitals during 2011.1-2013.12. The predictive factors for 28day hospital mortality were evaluated retrospectively. All cases underwent intensive care, blood routine, blood biochemical tests and arterial blood gas analysis. Under the Classification and Regression Tree (CART) analysis, a new clinical scoring system was developed for early prediction in SCAP patients. The receiver-operating characteristic (ROC) curve was plotted to calculate the area under the receiver operating characteristic curve (AUC). RESULTS: A novel clinical model named CLCGH scoring system, including Serum creatinine (Cr) >259.5µmol/L, leukocyte (WBC)>17.35×109/L, C-reactive protein (CRP)>189.4µg/mL, GCS≤9 and serum HCO3-≤17.65mmol/L, was carried out and each index was an independent factor for hospital mortality in SCAP. In validation cohort, the AUC of the new scoring system was 0.889 for prediction of hospital mortality, which was similar to SOFA score 0.877, APACHEII score 0.864, and was better than the PSI score 0.761 and CURB-65 score 0.767. CONCLUSIONS: The new scoring system CLCGH is an efficient, accurate and objective method to predicate the early hospital mortality among SCAP patients.

Synthesis, characterization and anticancer activities of transition metal complexes with a nicotinohydrazone ligand.

The reaction of divalent transition metal salts and (E)-N'-(1-(pyridin-2-yl)ethylidene)nicotinohydrazide (penh) led to the formation of [Mn(penh)2] (complex 1), [Co(penh)2] (complex 2), [Cu(penh)2] (complex 3) and [Cd (penh)2] (complex 4) complexes. The four complexes were characterized using elemental analyses, infrared spectra and single-crystal X-ray diffraction analyses. Subsequently, the complexes were used for in vitro cell level experiments to determine potential antitumor effects. The results demonstrated that the complexes exhibited a similar structure; however, they were crystallized with distinct space groups. In comparison with the uncomplexed penh ligand, all four complexes were able to markedly decrease the proliferation rate of various types of tumor cell, including the human lung cancer cell line A549, human gastric cancer cell line BGC823 and human esophageal cancer cell line Eca109, in a concentration-dependent manner. Furthermore, the complexes promoted tumor cell apoptosis, as demonstrated in the apoptosis assay, and this was confirmed using electrophoresis.

Using fluorescently-labeled magnetic nanocomposites as a dual contrast agent for optical and magnetic resonance imaging.

Dual-modality imaging probes synergistically combine magnetic resonance (MR) and fluorescence into a single nanocomposite. This promising technique affords a new level of flexibility for molecular imaging uses in biomedical research. In this study, we report a new strategy for the synthesis of a novel attapulgite nanorod-based atta@Fe3O4@[Ru(bpy)2(fmp)]Cl2 nanocomposite (atta@Fe3O4@Ru NC). Our synthesized NC has both photoluminescent and magnetic properties, bright fluorescence, as well as significant magnetic resonance. Transmission electron microscopy, energy dispersive spectroscopy, fluorescence spectrometry, and magnetization measurements were all used to validate its properties. In vitro studies showed that our functionalized NC had high cellular biocompatibility and was successfully used to label living cells through endocytosis of cells. Moreover, a CCK8 assay showed that even high concentrations of the atta@Fe3O4@Ru NC had low toxicity. Finally, the intravenous administration of the atta@Fe3O4@Ru NC to a rabbit model of hepatic carcinoma resulted in a marked and negatively enhanced T2-weighted MRI in both normal liver and tumor, which can further enhance the visibility of the liver cancer tissue and normal liver tissue. Collectively, these results suggest that the atta@Fe3O4@Ru NC can be used for tumor discovery and diagnosis.

Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3.

BACKGROUND: Imiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. This study investigated whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3. METHODS: Thirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of T-bet and GATA-3 were measured by Western blot. RESULTS: It was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines and increased Th1 type cytokines mRNA and protein levels; 4) modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production. CONCLUSION: Imiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Th1 phenotype.

[Imbalanced T cell-specific transcription factors T-bet and GATA-3 and relationship to airway inflammation in asthmatic rats].

OBJECTIVE: To identify the change of the mRNA and protein expression of T-bet and GATA-3 in lung tissues, and to investigate the association between the imbalanced T cell-specific transcription factors T-bet/GATA-3 and the airway inflammation in asthmatic rats. METHODS: Twenty-four male SD rats were randomly divided into a control group and an asthmatic group. Airway responsiveness was measured and the change of airway histology was observed. The concentrations of interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in the lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: The expiration resistance after injection of acetylcholine chloride (20, 40, 80, 160 microg/ml) in the asthmatic group was (6.26 +/- 0.85), (11.55 +/- 3.09), (28.74 +/- 5.94), (3,710.83 +/- 197.49) cm H2O.ml(-1).s(-1) respectively; and that in the control group was (1.51 +/- 0.18), (2.15 +/- 0.36), (6.08 +/- 1.06), (37.17 +/- 6.12) cm H2O.ml(-1).s(-1) respectively; the difference being significant between the two groups (all P < 0.01). In the asthmatic group, the numbers of eosinophils and lymphocytes, the thicknesses of WA/Pi and ASM/Pi were (26.0 +/- 1.6)/mm(2), (45.2 +/- 3.2)/mm(2), 12.0 +/- 1.4, 6.7 +/- 0.6, respectively; and those of the control group were (2.9 +/- 1.2)/mm(2), (8.8 +/- 1.8)/mm(2), 6.4 +/- 0.8, 2.7 +/- 0.5, respectively; all were significantly different between the two groups (all P < 0.01). In the asthmatic group, the concentrations of IL-4, IL-5, and IFN-gamma in BALF were (23.4 +/- 0.7) pg/ml, (24.8 +/- 0.5) pg/ml, (21.7 +/- 1.1) pg/ml, respectively, and those of the control group were (9.3 +/- 0.3) pg/ml, (12.5 +/- 0.3) pg/ml, (65.8 +/- 2.1) pg/ml, respectively; all were significantly different between the two groups (all P < 0.01). In the control group, the mRNA ratio of T-bet to GATA-3 (0.73 +/- 0.32) was significantly increased compared with the asthmatic group (0.06 +/- 0.09, P < 0.01). There was also a significant difference in the ratio of protein expression of T-bet to GATA-3 between the control group (0.75 +/- 0.25) and the asthmatic group (0.09 +/- 0.04, P < 0.01). The ratio of protein expression of T-bet and GATA-3 was correlated negatively with expiration resistance (r = -0.959, -0.919, -0.949, all P < 0.01), the numbers of eosinophils and lymphocytes in lung tissues (r = -0.832, -0.831, all P < 0.01), the thicknesses of WA/Pi and ASM/Pi (r = -0.837, -0.863, all P < 0.01) and the concentrations of IL-4, IL-5 in BALF (r = 0.921, 0.920, all P < 0.01), the mRNA of IL-4, IL-5 in lung tissues (r = -0.964, -0.931, all P < 0.01), but positively with the concentrations of IFN-gamma in BALF and the mRNA of IFN-gamma in lung tissues (r = -0.934, 0.983, all P < 0.01). CONCLUSION: Imbalance of transcription factors T-bet and GATA-3, a reflection of the immune imbalance in asthma, may play a key role in the formation of airway inflammation in the disease.