Extraction, Purification, and Structural Characterization of Polysaccharides from Sanghuangporus vaninii with Anti-Inflammatory Activity.

In order to obtain homogeneous Sanghuangporus vaninii polysaccharides with antioxidant and anti-inflammatory activities, a response surface method (RSM) was used to compare the polysaccharide extraction rate of hot water extraction and ultrasonic-assisted extraction from Sanghuangporus vaninii. The optimal conditions for ultrasonic-assisted extraction were determined as follows: an extraction temperature of 60 °C, an extraction time of 60 min, a solid-liquid ratio of 40 g/mL, and an ultrasonic power of 70 W. An SVP (Sanghuangporus vaninii polysaccharides) extraction rate of 1.41% was achieved. Five homogeneous monosaccharides were obtained by gradient ethanol precipitation with diethylaminoethyl-cellulose (DEAE) and SephadexG-100 separation and purification. The five polysaccharides were characterized by high performance liquid chromatography, the ultraviolet spectrum, the Fourier transform infrared spectrum, TG (thermogravimetric analysis), the Zeta potential, and SEM (scanning electron microscopy). The five polysaccharides had certain levels of antioxidant activity in vitro. In addition, we the investigated the anti-inflammatory effects of polysaccharides derived from Sanghuangporus vaninii on lipopolysaccharide (LPS)-induced RAW 264.7 cells and Kupffer cells. Further, we found that SVP-60 significantly inhibited the levels of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-induced RAW 264.7 cells and promoted the level of the anti-inflammatory cytokine IL-10 in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our study provides theoretical support for the potential application of Sanghuangporus vaninii in the field of antioxidant and anti-inflammatory activities in vitro.

Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia-Ischemia.

BACKGROUND: Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. PURPOSE: To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. STUDY TYPE: Prospective. POPULATION: A total of 42 neonates (24 males and 18 females). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). STATISTICAL TESTS: One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. RESULTS: For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. DATA CONCLUSION: For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

MRI Evaluation of Indomethacin Suppositories in the Prevention of Complications of Pancreatitis and Hyperamylasemia after Choledocholithiasis ERCP Based on Image Denoising Algorithm.

Objective: To explore the value of MRI evaluation of indomethacin suppositories in the prevention of pancreatitis and hyperamylasemia in patients with common bile duct calculi after endoscopic retrograde cholangiopancreatography (ERCP) based on image denoising algorithm. Methods: A retrospective analysis in August 2020 to December 2021. Because of the common bile duct calculi hospitalized parallel ERCP operation, 89 cases of patients, according to the different postoperative treatments, were divided into group A (n = 44) and group B (n = 45), in which A set of separate application inhibits the pancreatic enzyme secretion after surgery drug treatment, and B group on the basis of group A linked with indole beauty Xinshuan treatment. The incidence of postoperative pancreatitis and hyperamylasemia was compared between the two groups. The levels of serum amylase were compared between the two groups. Patients in group B were diagnosed with pancreatitis by conventional MRI and MRI with denoising algorithm, respectively, and the imaging characteristics and diagnosis rate differences of the two methods were observed. ROC curve was drawn to evaluate the diagnostic efficacy of MRI denoising algorithm for postoperative pancreatitis and serum amylase level detection for hyperamylasemia. Results: The incidence of postoperative pancreatitis and hyperamylasemia in group B was significantly lower than that in group A (P < 0.05). There were 6 cases of postoperative pancreatitis in group B, 2 cases (33.33%) were diagnosed by conventional MRI, and 5 cases (83.33%) were diagnosed by MRI based on denoising algorithm. Although there was no significant difference in diagnosis rate between the two methods, the number of cases of pancreatitis diagnosed by MRI based on denoising algorithm was slightly higher than that by conventional MRI. Compared with conventional MRI images, MRI images with denoising algorithm showed that the number of cases with pancreatic swelling, the number of cases with pancreatic duct/bile duct dilation, and the number of cases with abdominal effusion were all high (all P < 0.05). ROC results showed that the area under the curve of MRI with denoising algorithm for the diagnosis of postoperative pancreatitis was 0.855, and the sensitivity was 89.40%. The specificity was 83.20%, and the area under the curve of serum amylase for postoperative hyperamylasemia was 0.893, the sensitivity was 89.80%, and the specificity was 85.20%, all of which had high diagnostic efficacy. Conclusion: MRI results of denoising algorithm suggest that indomethacin suppositories can effectively reduce the incidence of postoperative pancreatitis and hyperamylasemia after ERCP, which is worthy of clinical application.

Developmental pattern of association fibers and their interaction with associated cortical microstructures in 0-5-month-old infants.

Association fibers connect the cortical regions and experience rapid development involving myelination and axonal growth during infancy. Yet, the spatiotemporal patterns of microstructural changes along these tracts, as well as the developmental interaction between the white matter (WM) tracts and the cortical gray matter (cGM) connected to them, are mostly unknown during infancy. In this study, we performed a diffusion MRI-based tractography and microstructure study in a cohort of 89 healthy preterm-born infants with gestational age at birth between 28.1∼36.4 weeks and postmenstrual age at scan between 39.9∼59.9 weeks. Results revealed that several C-shaped fibers, such as the arcuate fasciculus, cingulum, and uncinate fasciculus, demonstrated symmetrical along-tract profiles; and the horizontally oriented running fibers, including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus, demonstrated an anterior-posterior developmental gradient. This study characterized the along-tract profiles using fixel-based analysis and revealed that the fiber cross-section (FC) of all five association fibers demonstrated a fluctuating increase with age, while the fiber density (FD) monotonically increase with age. NODDI was utilized to analyze the microstructural development of cGM and indicated cGM connected to the anterior end of the association fibers developed faster than that of the posterior end during 0-5 months. Notably, a mediation analysis was used to explore the relation between the development of WM and associated cGM, and demonstrated a partial mediation effect of FD in WM on the development of intracellular volume (ICV) in cGM and a full mediation effect of ICV on the growth of FD in most fibers, suggesting a predominant mediation of cGM on the WM development. Furthermore, for assessing whether those results were biased by prematurity, we compared preterm- and term-born neonates with matched scan age, gender, and multiple births from the developing human connectome project (dHCP) dataset to assess the effect of preterm-birth, and the results indicated a similar developmental pattern of the association fibers and their attached cGM. These findings presented a comprehensive picture of the major association fibers during early infancy and deciphered the developmental interaction between WM and cGM in this period.

Early Development and the Functional Correlation of Brain Structural Connectivity in Preterm-Born Infants.

Exuberant axon growth and competitive pruning lead to dramatic and comprehensive changes in white matter pathways of the infant brain during the first few postnatal months, yet the development of structural configuration in early infancy has not been fully characterized. This study aimed to investigate the developmental trajectory of structural connectivity reflecting relative fiber density in 43 preterm-born infants aged 0-3 months of corrected age without any complications utilizing probabilistic tractography based on fiber orientation distribution and to explore the potential function correlation associated with the network properties based on the Chinese Communication Development of Infant at 10 months of corrected age. The findings revealed significant increases in global efficiency, local efficiency, normalized clustering coefficient, and small-worldness (p adj < 0.001 for each), while the normalized characteristic path length showed a non-significant decrease with age (p adj = 0.118). Furthermore, those findings were validated by another parcelation strategy. In addition, the early local efficiency was found to be significantly correlated with words understood at 10 months of corrected age. A unique developmental pattern of structural networks with enhancing efficiency and the small-world property was found in early infancy, which was different from those of neonates or toddlers. In addition, this study revealed a significant correlation between local efficiency and late language comprehension, which indicated that enhanced structural connectivity may lay the structural foundation for language specialization.

Effects of Daily Iron Supplementation on Motor Development and Brain Connectivity in Preterm Infants: A Diffusion Magnetic Resonance Study.

Objectives: The aim of the study is to demonstrate the characteristic of motor development and MRI changes of related brain regions in preterm infants with different iron statuses and to determine whether the daily iron supplementation can promote motor development for preterm in early infancy. Methods: The 63 preterm infants were grouped into non-anemia with higher serum ferritin (NA-HF) group and anemia with lower serum ferritin (A-LF) group according to their lowest serum Hb level in the neonatal period as well as the sFer at 3 months old. Forty-nine participants underwent MRI scans and Infant Neurological International Battery (INFANIB) at their 3 months. At 6 months of corrected age, these infants received the assessment of Peabody Developmental Motor Scales (PDMS) after 2 mg/kg/day iron supplementation. Results: In total, 19 preterm infants were assigned to the NA-HF group while 44 preterm infants to the A-LF groups. The serum ferritin (sFer) level of the infants in A-LF group was lower than that in NA-HF group (44.0 ± 2.8 mg/L vs. 65.1 ± 2.8 mg/L, p < 0.05) and was with poorer scores of INFANIB (66.8 ± 0.9 vs. 64.4 ± 0.6, p < 0.05) at 3 months old. The structural connectivity between cerebellum and ipsilateral thalamus in the NA-HF group was significantly stronger than that in the A-LF group (n = 17, 109.76 ± 23.8 vs. n = 32, 70.4 ± 6.6, p < 0.05). The decreased brain structural connectivity was positively associated with the scores of PDMS (r = 0.347, p < 0.05). After 6 months of routine iron supplementation, no difference in Hb, MCV, MCHC, RDW, and sFer was detected between A-LF and NA-HF groups as well as the motor scores of PDMS-2 assessments. Conclusion: Iron status at early postnatal period of preterm infant is related to motor development and the enrichment of brain structural connectivity. The decrease in brain structural connectivity is related to the motor delay. After supplying 2 mg/kg of iron per day for 6 months, the differences in the iron status and motor ability between the A-LF and NA-HF groups were eliminated.

Diffusion MRI of the infant brain reveals unique asymmetry patterns during the first-half-year of development.

The human brain demonstrates anatomical and functional lateralization/asymmetry between the left and right hemispheres, and such asymmetry is known to start from the early age of life. However, how the asymmetry changes with brain development during infancy remained unknown. In this study, we aimed to systematically investigate the spatiotemporal pattern of brain asymmetry in healthy preterm-born infants during the first-half-year of development, using high angular resolution diffusion MRI. Sixty-five healthy preterm-born infants (gestational age between 25.3-36.6 weeks) were scanned with postmenstrual age (PMA) ranging from term-equivalent age (TEA) to 6-months. At the regional level, we performed a region-of-interest-based analysis by segmenting the brain into 63 symmetrical pairs of regions, based on which the laterality index was assessed and correlated with PMA. At the voxel level, we performed a fixel-based analysis of each fiber component between the native and left-right flipped data, separately in TEA-1 month, 1-3 months, and 3-6 months groups. The infant brains demonstrated extensive regions with structural asymmetry during their first half-of-year of life. A distinct central-peripheral asymmetry pattern was observed in mean diffusivity, namely, leftward lateralization in the neocortex and rightward asymmetry in the deep brain regions. Besides, the posterior brain demonstrated a higher lateralization index compared with the anterior brain in all metrics, which is congruent with the brain developmental pattern from caudal to rostral. Regionally, language processing regions showed a rightward asymmetry, while visuospatial processing regions exhibited leftward lateralization in fractional anisotropy, fibre density, and fibre cross-section measurements, and most white matter regions were lateralized to the left in these measurements. The laterality index of several regions (12 out 63) demonstrated significant developmental changes in mean diffusivity. At the fixel level, the fiber cross-section of inferior fronto-occipital fasciculus showed significant leftward asymmetry and the extent of asymmetry increased with PMA. In summary, the results revealed unique spatiotemporal patterns of macro- and micro-structural asymmetry in early life, which dynamically changed with age. These findings may contribute to the understanding of brain development during infancy.

Imaging features of pharyngeal hairy polyps in infants.

BACKGROUND: Hairy polyps are the most common congenital deformity of the oral-nasopharynx/oral cavity in infants, which may lead to severe complications in the newborns. However, few studies have been published with respect to their radiological features, and most are case reports. OBJECTIVE: This study aimed to analyze radiological features of the oral­nasopharyngeal hairy polyps and to identify the radiological features with the highest diagnostic value. MATERIALS AND METHODS: From 2014 to 2019, pediatric cases pathologically diagnosed as hairy polyps and having received radiological examination at the Children's Hospital Affiliated to Zhejiang University were retrospectively analyzed. Radiological evaluations were conducted on tumor size, location, morphology, density or signal features as well as the enhancement pattern. RESULTS: A total of six infants were recruited. Clinical features observed in these cases included choking on milk with cyanosis, intermittent dyspnea, oropharyngeal mass, and snoring. Lesions were derived from the left tubal torus in three out of six cases, from the left lateral aspect of soft palate in one, from the left lateral pharyngeal wall in one, and from the right tubal torus in one. They were shown as pedicled polyp-like well-circumscribed mass with fat density or signal as well as a stalk on CT or MRI. In the contrast-enhanced scan, the fat components were not enhanced, while the stalk was mildly enhanced. CONCLUSION: Hairy polyps had typical radiological features. Hairy polyps should be considered for pedicled polyp-like well-circumscribed mass in the oral-nasopharynx of infants with fat density or signal as well as a stalk.

Feasibility of oscillating and pulsed gradient diffusion MRI to assess neonatal hypoxia-ischemia on clinical systems.

Diffusion-time- (td) dependent diffusion MRI (dMRI) extends our ability to characterize brain microstructure by measuring dMRI signals at varying td. The use of oscillating gradient (OG) is essential for accessing short td but is technically challenging on clinical MRI systems. This study aims to investigate the clinical feasibility and value of td-dependent dMRI in neonatal hypoxic-ischemic encephalopathy (HIE). Eighteen HIE neonates and six normal term-born neonates were scanned on a 3 T scanner, with OG-dMRI at an oscillating frequency of 33 Hz (equivalent td ≈ 7.5 ms) and pulsed gradient (PG)-dMRI at a td of 82.8 ms and b-value of 700 s/mm2. The td-dependence, as quantified by the difference in apparent diffusivity coefficients between OG- and PG-dMRI (ΔADC), was observed in the normal neonatal brains, and the ΔADC was higher in the subcortical white matter than the deep grey matter. In HIE neonates with severe and moderate injury, ΔADC significantly increased in the basal ganglia (BG) compared to the controls (23.7% and 10.6%, respectively). In contrast, the conventional PG-ADC showed a 12.6% reduction only in the severe HIE group. White matter edema regions also demonstrated increased ΔADC, where PG-ADC did not show apparent changes. Our result demonstrated that td-dependent dMRI provided high sensitivity in detecting moderate-to-severe HIE.

[Application of vacuum stretcher combined with feeding in cranial magnetic resonance imaging examination for neonates: a prospective randomized controlled study].

OBJECTIVE: To study the effect and safety of vacuum stretcher combined with feeding in cranial magnetic resonance imaging (MRI) examination for neonates. METHODS: A prospective study was performed for the neonates with hyperbilirubinemia, with a gestational age of >34 weeks and stable vital signs, who needed cranial MRI examination and did not need oxygen inhalation hospitalized in the Department of Neonatology, Children's Hospital of Zhejiang University School of Medicine, from September to November, 2019. The neonates were randomly divided into a vacuum stretcher combined with feeding group and a conventional sedation group. Vital signs were monitored before, during, and after MRI examination. The success rate of MRI procedure was recorded. RESULTS: A total of 80 neonates were enrolled in the study, with 40 neonates in the vacuum stretcher combined with feeding group and 40 in the conventional sedation group. The vacuum stretcher combined with feeding group had a significantly higher success rate of MRI procedure than the conventional sedation group (P<0.05). As for the neonates who underwent successful MRI examination, the fastest heart rate after examination in the vacuum stretcher combined with feeding group was significantly lower than that in the conventional sedation group (P<0.05), while there were no significant differences between the two groups in transcutaneous oxygen saturation, respiratory rate, and body temperature before and after MRI examination (P>0.05). No complications, such as apnea, acute allergic reactions, and malignant fever, were observed. CONCLUSIONS: Vacuum stretcher combined with feeding can improve the success rate of MRI procedure and reduce the use of sedatives, and meanwhile, it does not increase related risks.

Enhancement of anti-tumor effect of plasmid DNA-carrying MUC1 by the adjuvanticity of FLT3L in mouse model.

AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy; however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L) has been exploited for its ability to increase the proliferation of dendritic cells (DCs). The aim of the present study was to investigate whether co-administration of an adjuvant plasmid expressing mouse Flt3L and a DNA vaccine of the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice intramuscularly (i.m.), followed by electroporation. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model of MUC1-expressing tumors was established. RESULTS: The results showed that co-administration of an adjuvant plasmid and a DNA vaccine stimulated the production of higher titers of specific antibodies and a T cell response and suppressed the growth of subcutaneous tumors expressing MUC1. Collectively, our results indicate that a plasmid expressing murine Flt3L could stimulate stronger immune responses. CONCLUSION: These observations emphasize the potential of Flt3L as an adjuvant for colon cancer DNA vaccines.

Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells.

Lung cancer is the primary malignancy of the lung and is the leading cause of cancer­associated mortality in China. Multidrug resistance (MDR) is an essential aspect of lung cancer treatment failure and a popular topic of investigation in tumor studies. Previous studies have demonstrated that soluble resistance­related calcium­binding protein (Sorcin) is involved in the MDR of various types of human tumor, and that silencing Sorcin was able to reverse the MDR of several types of cultured human cancer cells. However, the effect and potential mechanism underlying the ability of Sorcin to reverse MDR in human lung cancer remains to be fully elucidated. The present study examined the role of Sorcin in the reversal of MDR in human lung cancer A549/DDP cells. The effects included increased drug sensitivity to cisplatin, apoptotic rate, cell cycle arrest in the G2/M phase and intracellular accumulation of rhodamine­123, and decreased expression of multidrug resistance gene 1, lung resistance protein, multidrug resistance­associated protein, glutathione S­transferase π, ATP­binding cassette transporter A2 (ABCA2), ABCA5, B­cell lymphoma 2 and P­glycoprotein, and the depletion of glutathione in Sorcin­silenced A549/DDP cells. The present study also revealed that there was a downregulation of p­Akt and phosphorylated extracellular signal­regulated kinase (p­ERK), and a decreased transcriptional activation of nuclear factor κB, signal transducer and activator of transcription (STAT)3, STAT5 and nuclear factor of activated T­cells following silencing of Sorcin. The results indicated that Sorcin may be used as a potential therapeutic target for MDR through inhibiting the Akt and ERK pathways in human lung cancer.

Effects of chronic exposure to Aspergillus fumigatus on epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats.

Epidemiologic studies suggest that increased concentrations of airborne spores of Aspergillus fumigatus closely relate to asthma aggravation. Chronic exposure to A. fumigatus aggravates airway inflammation, remodeling, and airway hyperresponsiveness in asthmatic rats. The effects of chronic exposure to A. fumigatus on epidermal growth factor receptor (EGFR) expression in the airway epithelial cells of asthmatic rats remain unclear. This study aimed to investigate the effects of chronic exposure to A. fumigatus on injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression in the airway epithelial cells of asthmatic rats. A rat model of chronic asthma was established using ovalbumin (OVA) sensitization and challenge. Rats with chronic asthma were then exposed to long-term inhalation of spores of A. fumigatus, and the dynamic changes in injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression were observed and analyzed. Chronic exposure to A. fumigatus could aggravate airway epithelial cell damage, upregulate the expression of EGFR and its ligands EGF and TGF-α, promote goblet cell metaplasia, and increase airway responsiveness in rats with asthma. Chronic exposure to A. fumigatus upregulates the expression of EGFR and its ligands in asthmatic rats. The EGFR pathway may play a role in asthma aggravation induced by exposure to A. fumigatus.

[Effects of chronic Aspergillus fumigatus exposure on the expression of mucin 5AC in the airways of asthmatic rats].

OBJECTIVE: To explore the effects of chronic Aspergillus fumigatus (Af) exposure on the expression of mucin 5AC (MUC5AC) in the airways of asthmatic rats. METHODS: Fifty-six male Wistar rats were randomly divided into 8 groups: chronic asthma (group A), chronic asthma plus Af spores inhalation for 1 week (group B), 3 weeks (group C) and 5 weeks (group D), chronic asthma plus saline inhalation for 5 weeks (group E), OVA-sensitized and-saline-challenged group (group F) and OVA-sensitized and-saline-challenged plus Af spores inhalation for 5 weeks (group G) (each n = 8). The airway resistance (Raw) and the change rate of Raw after acetylcholine provocation were detected using a computerized system. The level of MUC5AC mRNA in the lung tissue was measured by RT-PCR, and the expression of MUC5AC in airway epithelial cells were demonstrated by immunohistochemistry. The concentration of IL-13 in BALF was measured by ELISA. The extent of goblet cell hyperplasia was evaluated on periodic acid-Schiff stain (PAS) lung sections. RESULTS: In group B, C, and D, the level of MUC5AC mRNA (MUC5AC mRNA/ß-actin mRNA) (1.9 ± 0.4, 2.3 ± 0.6, 2.9 ± 0.8, respectively), the integrated optical density (value A) of MUC5AC positive stain in airway epithelial cells (278 ± 58, 566 ± 64, 891 ± 80, respectively), the concentration of IL-13 in BALF (µg/L) (96 ± 16, 136 ± 22, 197 ± 34, respectively), and the ratio of goblet cell area to epithelial cell area(%) (16 ± 5, 23 ± 7, 36 ± 9, respectively), were higher than those in group A, E, F and G (all P < 0.05). The change rate of Raw(%) in group C and D (61.91 ± 5.26 and 84.69 ± 6.38) were higher than that in group A, E, F and G (all P < 0.05). The level of MUC5AC mRNA and the value A of MUC5AC were positively correlated with the ratio of goblet cell area to epithelial cell area (r = 0.578, P < 0.05;r = 0.614, P < 0.05, respectively) and the change rate of Raw (r = 0.638, P < 0.05;r = 0.564, P < 0.05, respectively) in group B, C and D. CONCLUSION: Chronic Aspergillus fumigatus exposure upregulated the expression of MUC5AC in the airway epithelial cells and induced goblet cell hyperplasia, resulting in increased airway hypersensitivity in rats with chronic asthma.

Chronic Aspergillus fumigatus exposure upregulates the expression of mucin 5AC in the airways of asthmatic rats.

BACKGROUND: Airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. Chronic Aspergillus fumigatus (A. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (GCH) and mucus hypersecretion in a rat model of asthma. The effects of chronic A. fumigatus exposure on the expression of airway mucin 5AC (MUC5AC) are unknown. METHODS: The rat model of chronic asthma was set up by systemic sensitization and repeated challenge to ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. The changes of MUC5AC expression, the extent of GCH, and airway hyperreactivity (AHR) were measured after exposure to the fungus. RESULTS AND CONCLUSIONS: Chronic exposure to A. fumigatus upregulates the expression of MUC5AC, and induces GCH in the airways of asthma rats, and the remodeling changes of the airway epithelium was positively correlated with AHR. Upregulation of MUC5AC and induction of GCH may be mechanisms by which chronic A. fumigatus exposure promotes the progression of asthma.

Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.

BACKGROUND AND OBJECTIVE: Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated. METHODS: The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus. RESULTS: Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma. CONCLUSIONS: Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.

[The changes of advanced glycation end products in a rat liver fibrosis model and the interventional effect of aminoguanidin].

OBJECTIVE: To study the changes of advanced glycation end products (AGEs) in different phases of a rat liver fibrosis model induced by CCl4, and the interventional effect of aminoguanidin (AG). METHODS: Fifty-four SD rats were divided into three groups: a control group, a CCl4 model group and an intervention group. Their blood serum AGEs and hyaluronic acid (HA) and AGEs in their liver homogenates were measured. These measurements were correlatively assessed to the degrees of liver fibrosis at different phases of the rat model before and after the intervention with aminoguanidin. RESULTS: The content of AGEs in their blood sera and liver homogenates, and the level of blood serum HA, and the score of liver fibrosis degree at week 12 in our rat liver fibrosis mode groups were significantly higher than those in the control group (P < 0.01). In the intervention group with aminoguanidin, these figures were lower than those in the liver fibrosis model group (P < 0.05). The content of AGEs in their blood sera and liver homogenates had a linear correlation with the level of HA in their blood sera. CONCLUSION: The contents of AGEs in their blood sera and liver homogenates were increased in the late phase of our rat liver fibrosis model. To some extent, the level of AGEs may reflect the fibrosis degree of the rat livers. Aminoguanidin has an interventional effect in our CCl4 induced rat liver fibrosis model.