Research progress of chronic diseases in hyperandrogenized animal models / 中国药理学通报

Chronic disease is defined as a persistent, recurrent illness with long course. Common symptoms include insulin resistance, dyslipidemia, chronic inflammation, and so on. It is well known that chronic dehydroepiandrosterone (DHEA) or dihydrotestosterone (D H T) exposure induces symptoms in rats or mice. These animals possess characteristics of obesity, ovarian dysfunction, vascular endothelial dysfunction, inflammation, and so on. In addition, DHT-treated animals have been used to explore insulin resistance, dyslipidemia, and biorhythm disorder. DHEA-treated animals were fit to detect ovarian stress. Although DHEA-treated animals does not apply to studies of metabolic diseases such as hyperlipidemia, DHEA-treated animals under high fat diet represent the related phenotypes. Based on the previous research, it can be predicted that new achievements will be made in endometrial development, ovarian cell function, inflammation modulation, atherosclerotic, and biorhythm disorder by using these hyperandrogenic animal models.

Expression and significance of VEGF and p53 in rat degenerated intervertebral disc tissues

OBJECTIVE@#To discuss the expression and significance of vascular endothelial growth factor (VEGF) and p53 expression in rat degenerated intervertebral disc (IVD) tissues.@*METHODS@#A total of 78 even-aged Sprague-Dawley (SD) rats (observation group) were chosen to establish a rat IVD degeneration model with anterior limbs and tail-removing method. Three months after modeling, rats were executed and degenerated IVD tissues were obtained for pathological biopsy so as to observe VEGF and p53 expression thereof. Meanwhile, IVD tissues from 8 healthy rats were gained for comparison.@*RESULTS@#Capillary infiltration was found in 62.8% of cases in observation group. Positive expression of VEGF and p53 was seen in 74.4% and 59.0% of cases respectively with a co-expression rate of 53.8%. VEGF and p53 expression in degenerated IVD tissues with capillary infiltration was higher than that in non-infiltration group (P<0.05).@*CONCLUSIONS@#A coordinate expression of VEGF and p53 in rat degenerated IVD tissues is demonstrated, indicating that they are both involved in neovascularization and infiltration, which accelerates IVD degeneration.

Keutel syndrome with tracheal stenosis as the major symptom: case report and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, diagnosis and therapy of Keutel syndrome, and thereby to minimize the misdiagnosis.</p><p><b>METHOD</b>Data of a case of Keutel syndrome diagnosed at the Provincial Hospital Affiliated to Shandong University were analyzed and related literature were reviewed.</p><p><b>RESULT</b>An 8-month-26-day-old boy was presented with inspiratory and expiratory stridor and wheezing after movement on lung auscultation. His craniofacial appearance was characterized by midfacial hypoplasia with a broad depressed nasal bridge. The nose was small and flat. A grade 2-3/6 systolic murmur was heard between the second and third ribs at left edge of the sternum. The end phalanges of his fingers were thickened. Chest radiograph showed tracheobronchial cartilage calcification and tracheobronchial stenosis. Echocardiographic examination revealed the right pulmonary stenosis. With endoscopic surgery, antiobstructive and antibiotic therapy clinical symptoms were improved. Three weeks later he died of lung reinfection after he was discharged from our hospital. English literature search with "Keutel syndrome" as the key word at "PubMed" showed 22 articles covering 26 patients, and the clinical symptoms were hearing loss (91%), persistent respiratory symptoms (68%), recurrent otitis media/sinusitis (67%), growth development delay (52%) in turn, and signs were brachytelephalangism (100%), low nasal bridge (95%), midfacial hypoplasia (93%), cardiac murmur (69%), and auxiliary examinations showed abnormal cartilage calcification (100%), pulmonary arterial stenosis (72%), tracheobronchial stenosis (50%).</p><p><b>CONCLUSION</b>The diagnosis of Keutel syndrome should be considered in patients with brachytelephalangism, abnormal cartilage calcification, peripheral pulmonary stenosis, and midfacial hypoplasia. Tracheal stenosis was main clinical manifestation in part of patients.</p>

Effects of budesonide on HIF-1α and VEGF expression and airway remodeling in an asthmatic mouse model / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model.</p><p><b>METHODS</b>Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 μg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated.</p><p><b>RESULTS</b>Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF.</p><p><b>CONCLUSIONS</b>Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.</p>

Mechanism of conditioned immune response in curing bronchial asthma in mice / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the mechanism of effect of conditioned immune response in curing bronchial asthma.</p><p><b>METHODS</b>An experimental asthma modal was produced on healthy BALB/C mice (female, 4 - 6 weeks old) by sensitization and stimulation with ovalbumin (OV A). Totally 105 mice were divided into 7 groups randomly with 15 in each and treated differently: in group CIR(1), noise was used as conditioned stimulus (CS) and budesonide and salbutamol as unconditioned stimulus (UCS) respectively, a conditioned immune response model of mice with asthma was established by the combination of CS and UCS 7 times (7 days), then the mice were given CS only, and the combination were given once a week for 20 weeks. In group CIR(2) saccharin (SAC) was taken as CS, and the other treatments were the same as the group CIR(1). In the group of conventional therapy, the mice were given inhalation of nebulized budesonide and salbutamol only for 20 weeks. In the group of lower dose conventional therapy, the mice were given nebulized inhalation of budesonide and salbutamol for the first 7 days, then once a week for 20 weeks. In the noise group the mice were given noise only everyday for 20 weeks. In SAC group the mice were treated with SAC only everyday for 20 weeks. In the blank control group the mice were treated with placebo for 20 weeks. The mice in all the groups were stimulated with OVA once a day. The mice in the healthy control group were given PBS inhalation for 20 weeks. After 20 weeks therapy, the bronchoalveolar lavage fluid (BALF) was taken for eosinophils (EOS) counting. The spleens were taken to obtain CD4(+)T lymphocytes and the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7), IL-4, IFN-gamma and IL-17 were detected by flow cytometry.</p><p><b>RESULTS</b>(1) The percent of EOS of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that of blank control (P < 0.01), and there was no significant difference among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). (2) The expression of nAChRalpha7, IL-4 and IL-17 of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that in blank control group, IFN-gamma was much higher (P < 0.01), and no significant difference was found among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). There was a positive correlation between nAChRalpha7 and IL-4 (r = 0.76, P < 0.01), nAChRalpha7 and IL-17 (r = 0.46, P < 0.01). There was a negative correlation between nAChRalpha7 and IFN-gamma (r = 0.69, P < 0.01). (3) In the groups treated with lower dose of conventional therapy, noise, SAC and blank control, the epithelial tissue of airway were much thicker, the lumens were much narrower, and inflammatory cells and collagen fibers were much more than in the healthy control group, and after therapy, the inflammation in groups CIR(1), CIR(2) and conventional therapy was significantly improved.</p><p><b>CONCLUSION</b>The conditioned immune response models established by both noise and SAC as CS and budesonide and salbutamol as UCS can downregulate nAChRalpha7 on CD4(+)T lymphocytes, regulate the function of CD4(+)T lymphocytes, and achieve the same therapeutic efficacy in treatment of asthma.</p>

Study on post-translational processing and active forms of the novel metastasis-associated protein SNC19 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship between SNC19 protein and cancer metastasis.</p><p><b>METHODS</b>Expression of SNC19 protein in cancer cell lines and tissues was examined by Western blot analysis using anti-SNC19 monoclonal antibody. In addition, Psectag2A-SNC19(ORF) eukaryotic expression vector was constructed and transfected into BCAP37 cells. After the target protein was expressed and purified, processing forms of SNC19 protein were further identified using anti-His mAb and each form was assayed for its gelatinase activity.</p><p><b>RESULTS</b>Different expression and post-translational processing of the SNC19 proteins in the cancer cell lines and intestinal tissues were detected.BCAP37 cells transfected full-length SNC19 (ORF) generated two different sized proteins in cell lysates, 120 and 75 kD; 75 kD was detected to have proteolytic activity by gelatin zymography.</p><p><b>CONCLUSION</b>SNC19 protein presents different expression and post-translational processing in the cancer cells and tissues, of which 75 kD was identified to have gelatinase activity.</p>