In order to evaluate the effects of a topical application of homologous fibronectin on the healing of skin wounds, we made 2 excisional wounds on the back skin of each rat, applied ointment with or without fibronectin purified from citrated homologous plasma, and evaluated the effect according to wound size and microscopic findings. Excised lesions treated with carrier alone, but the difference was significant only in the early phase of wound healing, 2 and 3 days, according to wound size and microscopic changes. A significant decrease in wound size could be found in both groups, treated with ointment containing and not containing fibronectin, between day 4 and 9 when wound contraction was a major contributor to wound closure. Therefore it can be concluded that topical application of fibronectin has a beneficial effect on wound healing during its early phase, but no significant influence on wound contraction.
Administration, Topical ; Animals ; Fibronectins/blood/*therapeutic use ; Ointment Bases ; Rats ; Rats, Inbred Strains ; Skin/pathology ; Wound Healing/*drug effects

Topical fibronectin, autologous and homologous, was used to treat nine patients (eleven eyes) with persistent corneal epithelial defects and corneal ulcers that failed to improve with standard therapy. The fibronectin was purified from autologous and homologous plasma by gelatin-Sepharose 4B affinity chromatography and administered topically, 500 micrograms/ml five times a day, for three weeks. Complete or nearly complete reepithelialization was achieved in all patients regardless of the source of fibronectin, autologous or homologous. But healing times varied. The average healing time was 41.7 +/- 14.7 days (35.7 +/- 12.4 days for autologous, 50.8 +/-14.4 days for homologous). Ocular symptoms were relieved significantly, and no side effects were observed. Over an average follow-up period of 5.2 months, no recurrences were noted. The results showed that homologous, as well as autologous, fibronectin was effective in patients with persistent corneal epithelial defects and corneal ulcers.
Administration, Topical ; Adult ; Aged ; Blood Proteins/isolation & purification ; Chromatography, Affinity ; Corneal Diseases/*drug therapy ; Corneal Ulcer/*drug therapy ; Epithelium/drug effects ; Female ; Fibronectins/administration & dosage/isolation & purification/*therapeutic use ; Humans ; Male ; Middle Aged ; Visual Acuity ; Wound Healing/drug effects

To study preliminarily the effect of Jiawei Bazhen decoction combined with oxytocin in promoting cervical ripening of full-term pregnancy women who were in the deficiency of qi and blood type through the syndrome differentiation of traditional Chinese medicine (TCM). 180 patients that met the inclusion criteria of the study were randomly divided into three groups: the control group(oxytocin group), the treatment group (Jiawei Bazhen decoction combined with oxytocin group), the blank control group (expected and observation group). Cervical maturity score (Bishop score), vaginal and cervical secretions fetal fibronectin (FFN), the result of induced labor, the result of mother and baby were observed in each group before and after treatment. The result comes out that the cervical Bishop score of pregnant women for treatment group were significantly higher than the control group and blank control group after treatment (P < 0.05). The FFN of pregnant women for the treatment group were significantly different from the control group and blank control group after treatment (P < 0.05). The pregnancy outcome of the three groups: the labor rate and rate of vaginal delivery of the treatment group were higher than the other two groups, and the difference was statistically significant (P < 0.05). The cesarean section rate of the treatment group was significantly lower than the other two groups, the difference was also statistically significant (P < 0.05). The three groups did not appear the phenomenon of neonatal asphyxia. Jiawei Bazhen decoction combined with oxytocin is effective in producing cervical ripening and induce labor. It is convenient, safe and reliable, for it is no obvious adverse effects on mother and fetus, but effective in reducing the rate of cesarean section, and playing a positive role in promoting natural delivery.
Adult ; Cervical Ripening ; drug effects ; metabolism ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fibronectins ; secretion ; Humans ; Labor, Induced ; Oxytocin ; administration & dosage ; Pregnancy ; Pregnancy Complications ; drug therapy ; metabolism ; physiopathology ; Pregnancy Outcome ; Qi ; Vagina ; drug effects ; secretion ; Young Adult

OBJECTIVEInhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated.

METHODSThirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system.

RESULTSThe count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P < 0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P < 0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P < 0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P < 0.05), the difference between group A and B was significant.

CONCLUSIONInhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.

Administration, Inhalation ; Airway Remodeling ; drug effects ; immunology ; Allergens ; administration & dosage ; immunology ; Animals ; Asthma ; chemically induced ; drug therapy ; immunology ; Bronchitis, Chronic ; chemically induced ; drug therapy ; immunology ; Bronchoalveolar Lavage Fluid ; immunology ; Budesonide ; administration & dosage ; pharmacology ; Collagen Type III ; metabolism ; Disease Models, Animal ; Eosinophils ; immunology ; Extracellular Matrix ; immunology ; Fibronectins ; metabolism ; Glucocorticoids ; administration & dosage ; pharmacology ; Guinea Pigs ; Immunohistochemistry ; Lung ; drug effects ; immunology ; Male ; Ovalbumin ; administration & dosage ; immunology

The clinical efficacy was investigated of topical homologous fibronectin on persistent corneal epithelial defects of various etiologies. Fibronectin was purified from blood bank homologous plasma by gelatin-Sepharose 4B affinity chromatography. Twenty eight eyes of twenty five patients with persistent corneal epithelial defects and sterile corneal ulcers that failed to improve with standard therapy were treated by the instillation of homologous fibronectin eyedrops 5 times a day (500 microgram/ml). Complete reepithelialization was achieved in all patients except two eyes due to uncontrolled glaucoma and the taking of steroids. The healing time tended to be different depending on the duration of persistent corneal epithelial defects and the severity of underlying diseases. The mean +/- standard deviation duration of epithelial defect was 68.18 +/- 77.80 days. Average healing time was 42.07 +/- 17.47 days. Ocular symptoms were relieved significantly and no side effects were observed. Over an average follow-up period of about 8 months, two cases of recurrences were noted. These results show that homologous fibronectin was also effective in patients with persistent corneal epithelial defects and corneal ulcers.
Administration, Topical ; Adult ; Aged ; Child ; Corneal Diseases/blood/*drug therapy ; Epithelium/drug effects ; Female ; Fibronectins/blood/*therapeutic use ; Humans ; Infant ; Male ; Middle Aged ; Ophthalmic Solutions/therapeutic use ; Wound Healing/drug effects

OBJECTIVETo investigate the effect of epithelial-mesenchymal transition (EMT) on the expression of microRNAs (miRNAs) in lung cancer A549 cells.

METHODSTransforming growth factor beta-1 (TGF-beta 1) in different concentrations was used to induce EMT in lung cancer A549 cells. The morphological changes were observed under phase-contrast microscope. The changes of EMT-related proteins were analyzed by Western blot. The changes of miRNAs expression after EMT were detected by microRNA (miRNA) array. Real time quantitative RT-PCR was applied to verify the reliability of miRNA array results.

RESULTSThe lung cancer A549 cells became elongated and the cell-cell junction became loose after EMT. The epithelial protein marker E-cadherin was down-regulated and the mesenchymal protein markers vimentin and fibronectin up-regulated. There were 51 miRNAs showing statistically significant changes of expression more than double (P<0.05) after EMT. Among them 18 were up-regulated and 33 down-regulated. Of them, mir-33a was down-regulated by 92.8% and mir-193a-3p by 86.5%. Real time quantitative RT-PCR showed that mir-33a was down-regulated by 73.1% and mir-193a-3p by 56.6%.

CONCLUSIONEpithelial-mesenchymal transition has effects on the expression of miRNAs, and miRNAs may regulate the invasion and metastasis of lung cancer cells via EMT.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Cadherins ; metabolism ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; drug effects ; Fibronectins ; metabolism ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Transforming Growth Factor beta1 ; administration & dosage ; pharmacology ; Vimentin ; metabolism

OBJECTIVESTo explore the effects and significance of Huanshuai Recipe Oral Liquid (, HSR), a formula with supplementing qi, nourishing blood and activating blood on restructuring glomerular microvasculature and expression of vascular endothelial growth factor (VEGF) in subtotal nephrectomized (SNX) rats.

METHODSA total of 76 male Wistar rats were randomly divided into four groups: 16 in the sham-operated group and fed with tap water 10 mL/kg per day; 20 in the model group were operated with 5/6 SNX and fed with tap water 10 mL/ kg per day; 20 SNX rats in the HSR group were treated with HSR 10 mL/kg per day; 20 SNX rats in the losartan group were treated with losartan 40 mg/kg per day. Serum creatinine (SCr) and urinary protein excretion (Upro) were examined at the 2nd, 4th, 8th, and 12th weeks of the treatment, and the remnant kidneys were harvested. Changes in histological microstructure were evaluated using light microscopy, and the expression of VEGF was detected by using ELISA.

RESULTSUpro, microvasculature injury and glomerulosclerosis were found to be alleviated in HSR and Losartan groups, respectively. The change of VEGF expression showed positive correlation with glomerular capillary area and peritubular capillary number (r=0.448, r=0.422, P<0.01), but negative correlation with that of SCr and Upro (r=-0.592, r=-0.481, P<0.01).

CONCLUSIONSHSR could regulate the VEGF expression, reduce the loss of microvasculature, which demonstrated similar renal protective effects to losartan in SNX rats. Examination of Chinese herbal medicine influence on VEGF signaling and restructuring renal microvasculature may elucidate the molecular mechanism of renal protection to a certain degree.

Administration, Oral ; Animals ; Capillaries ; drug effects ; metabolism ; pathology ; Collagen Type IV ; metabolism ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Extracellular Matrix ; drug effects ; metabolism ; Fibronectins ; metabolism ; Immunohistochemistry ; Kidney Cortex ; drug effects ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; blood supply ; drug effects ; pathology ; physiopathology ; Microvessels ; drug effects ; Nephrectomy ; Proteinuria ; blood ; drug therapy ; physiopathology ; Rats ; Rats, Wistar ; Time Factors ; Vascular Endothelial Growth Factor A ; metabolism

This study is to investigate the effects of fluvastatin on the activation of p38 mitogen-activated protein kinase (p38 MAPK) and cAMP response element-binding protein (CREB1) in glomerular mesangial cells under high concentration of glucose. High concentration glucose and fluvastatin were used to stimulate the cultured rat glomerular mesangial cells (GMCs) in vitro. The protein expressions of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting. TGF-beta1 and fibronectin (FN) mRNA were measured with reverse transcription and polymerase chain reaction (RT-PCR). The protein synthesis of laminine (LN) and type IV collagen in the supernatants of the GMCs were detected with radioimmunoassay. Compared with low glucose control group, the expressions of p-p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-beta1 mRNA and FN mRNA, LN and type IV collagen in the supernatants were increased significantly in GMCs under high concentration glucose medium. The expression levels of p-p38 MAPK, p-CREB1, TGF-beta1 mRNA, and FN mRNA, LN and type IV collagen in the supernatants were significantly lower in the fluvastatin group than those in the high concentration glucose group. It is concluded that fluvastatin can inhibit over production of TGF-beta1 and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB1.
Amino Acids, Diamino ; metabolism ; Animals ; Cell Proliferation ; Cells, Cultured ; Collagen Type IV ; metabolism ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Fatty Acids, Monounsaturated ; pharmacology ; Fibronectins ; genetics ; metabolism ; Glucose ; administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Indoles ; pharmacology ; Male ; Mesangial Cells ; cytology ; metabolism ; Phosphorylation ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism