Experimental study of sediment wash-off process over urban road and its dependence on particle size distribution.

Sediment originating from the urban road runoff is a main contributor to water pollution in urban areas. The size of the road sediment varies significantly, but its influence on sediment wash-off process has not been well investigated. In this study, sediments with different particle size distributions have been used in rainfall-runoff experiments over idealized urban road surface. The results show that, under the same experimental conditions, the capacity factor CF increases with the decrease of the median particle diameter D50, which is the dominant influencing factor on CF. The wash-off coefficient k is affected by both D50 and the grading of sediment. During the wash-off process, D50 of the sediment collected at the outlet increases with time. Such a grain coarsening phenomenon is particularly apparent when the road is originally covered with very fine sediments. Furthermore, the presence of coarse grains slows down the transport of fine sediment whose size is smaller than 14 µm. This shielding effect significantly affects the sediment wash-off process in the early stage of a rainfall event, while later on the interaction between particles of different sizes becomes unimportant. This study advances the understanding of sediment wash-off mechanism on urban road surface.

Dynamic Evaluation of the Rectus Abdominis Muscle before and after Delivery by Ultrasonography.

Objective: To evaluate the changes of rectus abdominis thickness and inter-rectus distance before and after delivery with high-frequency ultrasound. Methods: A total of 148 pregnant women at 12 weeks of gestation who underwent prenatal examination in our hospital from January 2019 to March 2020 were selected, and 140 of them cooperated with rectus abdominis examination. According to the results of rectus abdominis examination 42 days after delivery, 97 patients were divided into the DRA group with rectus abdominis isolated and 43 patients were divided into the normal group with rectus abdominis not isolated. At 12 weeks, 24 weeks, and 37 weeks of pregnancy, 3 days and 42 days after delivery, the thickness and spacing of the left and right rectus abdominis muscle were measured by high-frequency ultrasound along the white linea at three positions: 5 cm above the navel, 3 cm below the umbilical edge, and 3 cm below the navel. Results: The thickness of rectus abdominis at 5 cm above the navel, 3 cm below the navel, and at the navel margin of the abdominal white line in the pregnant women of the two groups was gradually decreased with the increase of the pregnancy cycle and gradually recovered after delivery. At 42 days after delivery, the thickness of rectus abdominis in the DRA group was significantly lower than that in the normal group, which was 5 cm above the umbilicus, 3 cm below the umbilicus, and the umbilical margin of the abdominal white line (P < 0.05). The space between rectus abdominis 5 cm above the navel, 3 cm below the navel, and the navel margin of the abdominal white line in the pregnant women of the two groups was gradually increased with the increase of the pregnancy cycle and gradually recovered after delivery. At 37 weeks of pregnancy, 3 days after delivery, and 42 days after delivery, the space of rectus abdominis along the umbilicus 5 cm above, 3 cm below the umbilicus, and the umbilicus border of the abdominal white line in the DRA group was significantly larger than that of the normal group (P < 0.05). Conclusion: Ultrasound can accurately measure the inter-rectus distance and rectus thickness, accurately evaluate the degree of DRA, and realize the one-stop evaluation from prenatal diagnosis and prediction to postpartum rehabilitation monitoring, so as to intervene during pregnancy and reduce the risk of postpartum DRA.

microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82.

OBJECTIVE: Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82). METHODS: miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model. RESULTS: miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis. CONCLUSION: The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.

Myeloid-derived suppressor cells (MDSCs) and mechanistic target of rapamycin (mTOR) signaling pathway interact through inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in asthma.

BACKGROUND: Down-regulation of mechanistic target of rapamycin (mTOR) activity in myeloid-derived suppressor cells (MDSCs) has been shown to promote inducible nitric oxide (NO) synthase (iNOS) expression and NO production. Importantly, pharmacological inhibition of iNOS blocks MDSCs recruitment in immunological hepatic injury. As bronchial asthma is also an immune disease, whether mTOR could interact with MDSCs via iNOS and NO or not is unclear. OBJECTIVE: The aim of this study was to determine whether mTOR could interact with MDSCs via iNOS and NO in asthma. METHODS: Ovalbumin-induced asthma mouse model was established to perform our investigation, and asthmatic markers were evaluated by hematoxylin and eosin (H&E), immunohistochemistry (IHC), and periodic acid-Schiff (PAS) staining. The levels of iNOS and NO in serum were determined by enzyme linked immunosorbent assay (ELISA). Mice lung tissues were stained with antibodies against phosphorylated (p)-mTOR, and p-p70S6K, and yellow/brown staining was considered as giving a positive signal, meanwhile, the protein levels of p-mTOR, and p-p70S6K were also detected using western blot assay. Mice iNOS activity was determined by radioimmunoassay. RESULTS: Tumor-derived MDSCs in asthmatic mice were regulated by mTOR and iNOS. mTOR pathway activation in asthmatic mice was regulated by iNOS and tumor-derived MDSCs. NO production in asthmatic mice was regulated by mTOR and tumor-extracted MDSCs. Positive correlation of iNOS with mTOR pathway and serum MDSCs was observed. CONCLUSION: The data indicated that rapamycin, an inhibitor of mTOR, blocked iNOS and NO production during asthma onset. Thus, our results revealed potential novel targets for asthma therapy.

Tumor-derived MDSCs inhibit airway remodeling in asthmatic mice through regulating IL-10 and IL-12.

Myeloid-derived suppressor cells (MDSCs), a group of newly discovered and heterogeneous myeloid-derived immunosuppressive cells, play an important role in the progress of asthma, however, the specific mechanism is still largely unclear. Our previous study has indicated that during the onset of asthma, the accumulation of MDSCs and the level of serum interleukin (IL)-10 increased, while the level of IL-12 decreased. The present study aimed to investigate whether tumor-derived MDSCs could inhibit airway remodeling in asthmatic mice through regulating IL-10 and IL-12 secretion. To perform our investigation, we established a mouse model of breast cancer, and the extracted MDSCs from breast caner mouse model were injected into a mouse model of asthma induced by ovalbumin (OVA). Then, asthmatic airway remodeling of mice was analyzed and the levels of IL-10 and IL-12 in the serum and bronchoalveolar lavage fluid (BALF) of mice were detected. In addition, the correlation of MDSCs with the levels of IL-10 and IL-12 in the transplantation group was analyzed. The transplantation of tumor-derived MDSCs into asthmatic mice significantly improved airway remodeling, decreased MDSCs and the expression of IL-10, and significantly increased the expression of IL-12. Besides, we confirmed that IL-10 was positively correlated with MDSCs, while IL-12 was negatively correlated with MDSCs. The results indicated that tumor-derived MDSCs could reduce IL-10 level, increase the level of IL-12, and thus correct the Th1/Th2 imbalance in asthmatic mice. In summary, our results revealed that tumor-derived MDSCs could serve as a potential novel target for asthma therapy.

[Nutritional assessment and clinical application of nutritional risk screening tools in critically ill children].

OBJECTIVE: To investigate the nutritional status of critically ill hospitalized children and to explore the value of nutritional risk screening tools in the nutritional risk assessment. METHODS: The clinical data of 211 critically ill children who were admitted to the pediatric intensive care unit from November 2017 to April 2018 were collected to evaluate their nutritional status on admission and at discharge. Two nutritional risk screening tools, STRONGkids and PYMS, were used for nutritional risk screening in the 211 children. RESULTS: Among the 211 patients, 68 (32.2%) were found to have malnutrition on admission, with 34 cases each of moderate and severe malnutrition. Moderate or high nutritional risk was found in 154 cases (73.0%) with STRONGkids and 165 cases (78.2%) with PYMS. Using weight-for-age Z-score as the gold standard to evaluate the efficacy of the two nutritional risk screening tools, the areas under the receiver operating characteristic curves of STRONGkids and PYMS were 0.822 and 0.759 respectively. Both tools had a significant clinical value in screening for malnutrition (P<0.05), but there was no significant difference in clinical efficacy between them (P>0.05). With the optimal cut-off value of 3 points, the sensitivities of STRONGkids and PYMS for screening of malnutrition were 92.1% and 76.2% respectively. The children with moderate or high nutritional risk on admission had a significantly poorer prognosis than those with low nutritional risk (P=0.014 and 0.001 respectively). The children with severe malnutrition had a significantly poorer prognosis than those with normal nutrition (P=0.0009). CONCLUSIONS: The detection rates of malnutrition and nutritional risk are high in critically ill children. Malnutrition/high nutritional risk is related to a poor prognosis. Both STRONGkids and PYMS have a clinical value for nutritional risk screening in critically ill children, and they have similar clinical efficacy; however, STRONGkids is more sensitive.

Activation of the mTOR signaling pathway is required for asthma onset.

The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments.

Personalized Analysis by Validation of Monte Carlo for Application of Pathways in Cardioembolic Stroke.

BACKGROUND Cardioembolic stroke (CES), which causes 20% cause of all ischemic strokes, is associated with high mortality. Previous studies suggest that pathways play a critical role in the identification and pathogenesis of diseases. We aimed to develop an integrated approach that is able to construct individual networks of pathway cross-talk to quantify differences between patients with CES and controls. MATERIAL AND METHODS One biological data set E-GEOD-58294 was used, including 23 normal controls and 59 CES samples. We used individualized pathway aberrance score (iPAS) to assess pathway statistics of 589 Ingenuity Pathways Analysis (IPA) pathways. Random Forest (RF) classification was implemented to calculate the AUC of every network. These procedures were tested by Monte Carlo Cross-Validation for 50 bootstraps. RESULTS A total of 28 networks with AUC >0.9 were found between CES and controls. Among them, 3 networks with AUC=1.0 had the best performance for classification in 50 bootstraps. The 3 pathway networks were able to significantly identify CES versus controls, which showed as biomarkers in the regulation and development of CES. CONCLUSIONS This novel approach could identify 3 networks able to accurately classify CES and normal samples in individuals. This integrated application needs to be validated in other diseases.

[HMGB1/TLR4/NF-κB signaling pathway and role of vitamin D in asthmatic mice].

OBJECTIVE: To investigate the changes in the mRNA and protein expression of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in lung tissues of asthmatic mice and the interventional effect of vitamin D. METHODS: A total of 48 BALB/c mice were randomly divided into control group, asthma group, and 1,25-(OH)2D3 intervention group, with 16 mice in each group. An animal model of asthma was established, and lung tissue samples were taken in each group at weeks 1 and 2 of ovalbumin challenging. Conventional hematoxylin-eosin staining was used to measure airway wall thickness. Immunohistochemical staining was used to observe the expression of HMGB1, TLR4, and NF-κB in lung tissues. Quantitative real-time PCR and Western blot were used to investigate the changes in the mRNA and protein expression of HMGB1, TLR4, and NF-κB. RESULTS: At weeks 1 and 2 of ovalbumin challenging, compared with the control group, the asthma group had a significant increase in airway wall thickness and the intervention group had a significant reduction compared with the asthma group (P<0.05). The asthma group had significantly higher mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower mRNA expression of TLR4 and NF-κB than the asthma group (P<0.05). At week 1 of ovalbumin challenging, there was no significant difference in the mRNA expression of HMGB1 between the intervention group and the asthma group (P>0.05). At week 2, the intervention group had a significant reduction in the mRNA expression of HMGB1 compared with the asthma group (P<0.05). At weeks 1 and 2 of ovalbumin challenging, the asthma group had significantly higher protein expression of HMGB1, TLR4, and NF-κB in lung tissues than the control group, and the intervention group had significantly lower expression than the asthma group (P<0.05). Airway wall thickness was positively correlated with the mRNA expression of HMGB1, TLR4, and NF-κB in lung tissues (r=0.804, 0.895, and 0.834; P<0.05). CONCLUSIONS: The HMGB1/TLR4/NF-κB signaling pathway plays an important role in the pathogenesis of asthma, and an appropriate amount of 1,25-(OH)2D3 has a regulatory effect on this pathway and may prevent the progression of asthma. Therefore, 1,25-(OH)2D3 is expected to become a new choice for the treatment of asthma.

Characterizing Dysregulated Networks in Individual Patients with Ischemic Stroke Based on Monte Carlo Cross-Validation.

The purpose of this study was to introduce a new method to elucidating the molecular mechanisms in ischemic stroke. Genes from microarray data were performed enrichment to biological pathways. Dysregulated pathways and dysregulated pathway pairs were identified and constructed into networks. After Random Forest classification was performed, area under the curve (AUC) value of main network was calculated. After 50 bootstraps of Monte Carlo Cross-Validation, six pairs of pathways were found for >40 times. The best main network with AUC value = 0.735 was identified, including 14 pairs of pathways. Compared with the traditional method (gene set enrichment analysis), although a small part of pathways were shared, most of the pathways were closely related with ischemic stroke. The best network may give new insights into the underlying molecular mechanisms in ischemic stroke. It may play pivotal roles in the progression of ischemic stroke and particular attention should be focused on them for further research.

Effect of different 1, 25-(OH)2D3 doses on high mobility group box1 and toll-like receptors 4 expression in lung tissue of asthmatic mice.

We established a mouse model of asthmatic airway remodeling. To investigate the effects of different doses of 1,2 5-(OH)2D3 on airway remodeling, expression of high mobility group box 1 (HMGB1) and Toll-like receptors 4 (TLR4) in asthmatic mice. The female mice (BALB/c) groups consisted of a control group, asthma group and 1,2 5-(OH)2D3 low, middle, high dose group. Each group contained 10 mice. An asthmatic mice model was induced by ovalbumin. The control group and asthma group used physiological saline instead. 1,2 5-(OH)2D3 low, middle and high dose group was given different doses of 1,2 5-(OH)2D3 respectively. Changes in mice airway structure were observed by hematoxylin-eosin (H&E). The expression of HMGB1 and TLR4 in molecular lever were monitored by RT-PCR. We used immunohistochemistry to test HMGB1 and TLR4 protein levels. Obvious changes were noted in the airway of OVA-induced asthma mice compared with the control group by HE. These changes were less pronounced in mice receiving the low and middle doses of 1,2 5-(OH)2D3, but were more pronounced in mice receiving the highest dose of 1,2 5-(OH)2D3. Immunohistochemistry showed that expression of HMGB1 and TLR4 in the asthma group was higher than the control group. And low and middle dose group was decreased compared with asthma group, while higher than the control group; high dose group had an increased expression compared with the asthma group. From RT-PCR we got the same results as immunohistochemistry. In the asthmatic airway remodeling animal model, the appropriate amount of 1,2 5-(OH)2D3 reduced airway remodeling in asthmatic mice, and decreased the expression of HMGB1 and TLR4 in the asthmatic mice. However, over dose might play detrimental effect.

[Effects of different doses of 1,25-(OH)2D3 on expression of HMGB1 and IL-17 in the lungs of asthmatic mice].

OBJECTIVE: To study the effects of 1,25-(OH)(2)D(3) on airway remodeling and expression of high mobility group box 1 (HMGB1) and IL-17 in asthmatic mice. METHODS: Fifty female mice were randomly divided into 5 groups: control, asthma, low-dose, middle-dose, and high-dose intervention groups (n=10 each). Asthma was induced by intraperitoneal injections of ovalbumin (OVA) and aerosol inhalation of OVA solution. The low-dose, middle-dose, and high-dose intervention groups were administered with 1,25-(OH)(2)D(3) solution at the dosage of 1, 4 and 10 µg/kg respectively by intraperitoneal injections before asthma challenge. The airway structural changes were assessed by hematoxylin and eosin staining. mRNA expression levels of HMGB1 and IL-17 in the lung tissues were evaluated by RT-PCR. The protein levels of HMGB1 and IL-17 in the lung tissues were observed by immunohistochemistry. RESULTS: The airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were higher in the untreated asthma group than in the control group (P<0.05). The airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 were lower in the middle-dose and low-dose intervention groups than in the untreated asthma group, and the middle-dose intervention group demonstrated lower airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 than in the low-dose intervention group (P<0.05). However, the airway wall thickness, protein and mRNA expression levels of HMGB1 and IL-17 in the high-dose intervention group were higher than in the untreated asthma group (P<0.05). CONCLUSIONS: HMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of HMGB1 and IL-17 may be involved in the airway remodeling process in asthmatic mice. A moderate amount of 1,25-(OH)(2)D(3) can improve the airway remodeling, but a higher dose of 1,25-(OH)(2)D(3) may affect adversely the airway remodeling process.

Single molecule investigation of Ag+ interactions with single cytosine-, methylcytosine- and hydroxymethylcytosine-cytosine mismatches in a nanopore.

Both cytosine-Ag-cytosine interactions and cytosine modifications in a DNA duplex have attracted great interest for research. Cytosine (C) modifications such as methylcytosine (mC) and hydroxymethylcytosine (hmC) are associated with tumorigenesis. However, a method for directly discriminating C, mC and hmC bases without labeling, modification and amplification is still missing. Additionally, the nature of coordination of Ag(+) with cytosine-cytosine (C-C) mismatches is not clearly understood. Utilizing the alpha-hemolysin nanopore, we show that in the presence of Ag(+), duplex stability is most increased for the cytosine-cytosine (C-C) pair, followed by the cytosine-methylcytosine (C-mC) pair, and the cytosine-hydroxymethylcytosine (C-hmC) pair, which has no observable Ag(+) induced stabilization. Molecular dynamics simulations reveal that the hydrogen-bond-mediated paring of a C-C mismatch results in a binding site for Ag(+). Cytosine modifications (such as mC and hmC) disrupted the hydrogen bond, resulting in disruption of the Ag(+) binding site. Our experimental method provides a novel platform to study the metal ion-DNA interactions and could also serve as a direct detection method for nucleobase modifications.

[Effect of 1,25-(OH)2D3 on expression of HMGB1 and TLR4 in the lungs of asthmatic mice].

OBJECTIVE: To investigate the effects of 1,25-(OH)(2)D(3) on the airway remodeling and expression of high-mobility group box 1 (HMGB1) and Toll-like receptor 4 (TLR4) in the lungs among asthmatic mice. METHODS: Thirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)(2)D(3) intervention groups. An asthmatic mouse model was established by intraperitoneal injection and aerosol inhalation of ovalbumin. The intervention group was given 1,25-(OH)(2)D(3) by intraperitoneal injection 0.5 hour before each aerosol inhalation, while the control group used normal saline instead. The hematoxylin-eosin staining was used to observe the mouse airway structural changes. The mRNA and protein expression of HMGB1 and TLR4 was measured by RT-PCR and immunohistochemistry, respectively. Pearson correlation analysis was performed. RESULTS: The asthma group had a significantly increased airway wall thickness compared with the control group (P<0.05); the intervention group had a significantly lower increase in airway wall thickness than the asthma group (P<0.05). The mRNA and protein expression of HMGB1 and TLR4 was significantly higher in the asthma group than in the control group (P<0.05); the mRNA and protein expression of HMGB1 and TLR4 in the intervention group was significantly lower than that in the asthma group, but still higher than that in the control group (P<0.05). A positive correlation was found between the protein expression of HMGB1 and TLR4 (P<0.01), and so was their mRNA expression (P<0.01). CONCLUSIONS: HMGB1 and TLR4 may be involved in asthmatic airway remodeling. 1,25-(OH)(2)D(3) can reduce the airway remodeling in asthmatic mice, which may be related to the downregulation of HMGB1 and TLR4 expression in the lungs of asthmatic mice.

Peripheral blood MDSCs, IL-10 and IL-12 in children with asthma and their importance in asthma development.

OBJECTIVE: To investigate myeloid-derived suppressor cell (MDSC) accumulation and interleukin 10 (IL-10) and interleukin 12 (IL-12) levels during the onset of asthma in both pediatric patients and mouse models, as well as their possible roles in the development of asthma. METHODS: Peripheral blood samples were gathered from children with asthma attacks (attack group) and alleviated asthma (alleviated group), as well as two control groups, children with pneumonia and healthy children. The pathological characteristics of asthma in asthmatic mice, budesonide-treated asthmatic mice, and normal control mice were also evaluated by immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining. RESULTS: MDSC accumulation and serum IL-10 levels were significantly elevated in the children with asthma compared with the budesonide-treated alleviated group, normal healthy controls, and pneumonia controls (p<0.05), whereas those in the latter three groups showed no statistical differences (p>0.05). The level of serum IL-12 in the asthmatic children was drastically reduced compared to the budesonide-treated alleviated group, healthy controls, and pneumonia controls (p<0.05), whereas the latter three groups showed no significant differences in their serum IL-12 levels. The percentage of MDSCs in children with asthma was positively correlated with the level of serum IL-10 and negatively correlated with the level of serum IL-12. The levels of MDSCs and IL-10 in asthmatic mice were significantly higher than those in the normal control mice (both p<0.05) and were reduced after budesonide treatment (both p<0.05). IL-12 expression in the asthmatic mice was significantly lower than the control and was increased upon budesonide treatment (both p<0.05). CONCLUSION: During the onset of asthma, the accumulation of MDSCs and the level of serum IL-10 increase, while the level of IL-12 decreases. These fluctuations may play an important role in the development of asthma.

[Effect of 1,25-(OH)2D3 on expression of TIM-4 in the lungs of asthmatic mice].

OBJECTIVE: To establish a mouse model of asthmatic airway remodeling and investigate the effects of 1,25-(OH)2D3 on airway structure and T cell immunoglobulin mucin protein-4 (TIM-4) expression in asthmatic mice. METHODS: Thirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)2D3 intervention groups. An asthmatic mouse model was induced using ovalbumin. Lung tissue of the mice was collected, mRNA expression of TIM-4 was evaluated by RT-PCR and airway remodeling and protein expression of TIM-4 were observed by hematoxylineosin staining and immunohistochemistry. RESULTS: Typical airway remodeling was found in the asthma group, and TIM-4 expression in this group was significantly higher than in the control group (105±9 vs 42±5; P<0.05). Compared with the asthma group, the 1,25-(OH)2D3 intervention group showed improvement in airway remodeling and a decrease in TIM-4 expression (78±6) (P<0.05). CONCLUSIONS: TIM-4 may be involved in the airway remodeling of mice. As a new type of immunoregulator, 1,25-(OH)2D3 can downregulate expression of TIM-4 in the lungs and improve airway remodeling in asthmatic mice.

[Effects of bacterial lipopolysaccharide on serum IL-4, serum IL-8 and pulmonary VEGF expression in mice with asthma].

OBJECTIVE: To study the regulatory role of bacterial lipopolysaccharide (LPS ) in the development of bronchial asthma by examining the effects of LPS on serum IL-4, serum IL-8 and pulmonary vascular endothelial growth factor (VEGF) expression in mice with asthma. METHODS: Twenty-seven BALB/c mice were randomly assigned into control, asthma and LPS-treated asthma groups (n=9 each). Serum IL-4 and IL-8 concentrations were measured using ELISA. VEGF expression in lung tissues was examined using the immunohistochemical method. RESULTS: Serum IL-4 and IL-8 concentrations in the asthma group were significantly higher than in the control group (P<0.05). LPS treatment significantly decreased serum IL-4 and IL-8 concentrations compared with the asthma group (P<0.05), although levels were significantly higher than in the control group (P<0.05). Airway VEGF expression in the asthma group was significantly higher than in the control group (P<0.05). LPS treatment significantly decreased airway VEGF expression compared with the asthma group (P<0.05), although concentrations remained higher than in the control group (P<0.05). CONCLUSIONS: LPS can decrease serum IL-4, serum IL-8 and pulmonary VEGF expression in mice with asthma, and thus can possibly reduce both airway inflammation and airway vascular remodeling.

Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation.

[Expression of Galectin-9 and Tim-3 in lungs of mice with asthma].

OBJECTIVE: To study the expression of Galectin-9 and Tim-3 in lungs of mice with asthma and the effect of rosiglitazone (PPAR-γ agonist) on their expression. METHODS: Fortyfive BALB/c SPF female mice were randomized into control group and asthma groups with and without rosiglitazone intervention. After ovalbumin stimulation and rosiglitazone intervention the pathological changes of the lung tissues were observed. Galectin-9 and Tim-3 mRNA levels in lung tissues were determined using RT-PCR. The levels of IL-4 and IFN-γ in peripheral blood were measured using ELISA. RESULTS: The expression of Galectin-9 and Tim-3 mRNA of lung tissues in the untreated asthma group increased significantly compared with the control and the rosiglitazone treated groups (P<0.05). A significantly increased blood expression of IL-4 and a significantly decreased blood expression of IFN-γ were found in the untreated asthma group compared with the control and the rosiglitazone-treated groups (P<0.05). The expression of Galectin-9 and Tim-3 mRNA was positively correlated with blood IL-4 level (r=0.792, r=0.794 respectively; P<0.05), but negatively correlated with blood IFN-γ level (r=-0.692, r=-0.757 respectively; P<0.05). CONCLUSIONS: Galectin-9 and Tim-3 mRNA levels in lungs increase in mice with asthma and significantly correlate with the levels of blood Th1/Th2 cytokines. This suggests that Galectin-9 and Tim-3 are closely related to inflammatory process in asthma. Rosiglitazone treatment may decrease the expression of Galectin-9 and Tim-3.