Transforming growth factor-?_1 (TGF-?_) mRNA or protein expression in renal cortex of diabetic rats was assessed by real-time quantitative RT-PCR with SYBR Green,immunohistochemistry or Western blot.After melatonin treatment,the expressions of TGF-?_1 mRNA and protein were decreased,suggesting that beneficial effect of melatonin may result from its antioxidative property and inhibiting TGF-?_1 expressions.

Objective To study the effects of thrombolysis on short- and long-term outcome in acute cerebral infarction patients. Methods The patients accepted thrombolysis and remained severe neurologic deficits were as observation group (n=29), and the patients without thrombolysis matching the onset time and severity of disease were as control group (n=94). They were assessed with National Institute of Health Stroke Scale (NIHSS), Manual Muscle Test (MMT), Brunnstrom Grade, modified Barthel Index (MBI) when they admitted and discharged, and with modified Rankin Scale (mRS) 6 months later. Results The scores of MMT, MBI and Brunnstrom grade improved in both groups when discharged (P<0.05), except the NIHSS in the control group, and the scores of NIHSS and MBI improved more in the observation group than in the control group (P<0.05). The score of mRS was better in the observation group than in the control group 6 months later (P<0.05). Conclusion Thrombolysis can improve the neurologic function and activities of daily living in the acute stage of cerebral infarction, as well as the long-term outcome of activities.

To observe the effects of total flavones of Metasequoia glyptostroboides Hu et Cheng (TFM) on volume-overload cardiac hypertrophy and the expression of c-Fos protein in rat. Methods　Volume-overload cardiac hypertrophy of rat was induced by aortocaval shunts. The rats were given ig TFM (400, 40 and 4 mg/kg/d). c-Fos protein in the ventricles were measured by immunocytochemical study. Results　TFM at the above dosage decreased heart weight and contents of RNA and protein in the myocardium, inhibited the expression of c-Fos protein in the ventricles. Conclusion　TFM can prevent volume-overload cardiac hypertrophy in rats. The inhibitory effects on the expression of c-Fos protein may be its mechanism in the molecular level.

Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 10(-6) mg/ml gemcitabine treated group, 10(-4) mg/ml TNP-470 treated group and gemcitabine+TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor (KDR), in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine (10(-6) mg/ml) alone and TNP-470 (10(-4) mg/ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549 cells compared to the control (P>0.05), 10(-6) mg/ml gemcitabine in combination with 10(-4) mg/ml TNP-470 had significant effect (P<0.01). Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone (P<0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.
Adenocarcinoma ; drug therapy ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexanes ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; drug therapy ; Neoplasm Metastasis ; Protein Structure, Tertiary ; Sesquiterpenes ; administration & dosage ; Vascular Endothelial Growth Factor A ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-1 ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis

Australia ; Environmental Monitoring ; Humans ; Occupational Health ; Safety Management ; methods ; organization & administration

OBJECTIVETo assess the effect and adverse reaction of total glucosides of paeony capsule (TGPC) in combining with citirizine for the treatment of chronic urticaria.

METHODSA total of 120 patients were assigned to two groups by lottery, 65 in the treated group and 55 in the control group. They all were orally treated with citirizine tablet 10 mg per day, but to the treated group, additional 0.2 g TGPC was given three times per day, the therapeutic course for both groups was 4 weeks. The effectiveness of treatment was observed, and the changes of total symptom score, serum levels of interleukin-4 (IL-4), and immunoglobulin E (IgE) were measured before and after treatment. Moreover, a follow-up was carried out one month after ending the treatment.

RESULTSThe dropped cases were two in the treated group and seven in the control group; so, the study was accomplished on 63 patients in the treated group and 48 patients in the control group. The total effective rate was assessed at 73.02% (46/63) in the treated group, which was significantly higher than 47.92% (23/48) in the control group (P<0.01). After treatment, the total symptom score decreased in both groups, but the decrement in the treated group was more significant (P<0.05). Serum levels of IL-4 and IgE in the treated group lowered significantly, while the changes in the control group were insignificant, so statistical significant differences were shown between groups (P<0.01). A follow-up study showed that the relapse rate in the treated group was 30.00% (6/20), while that in the control group was 90.00% (9/10), and the former was lower than the latter (P<0.01). Adverse reactions, revealed as drowsiness, dizziness, and weakness, were seen in eight cases and seven cases in the two groups, respectively. Besides, mild diarrhea occurred in two cases of the treated group.

CONCLUSIONSThe treatment of TGPC combining citirizine shows definite curative effect in treating chronic urticaria, with low relapse rate and without evident adverse reaction. Its therapeutic effect might be realized by means of regulating patients' immune function. Besides, the medication should be continued for a rather long period to achieve the full effect.

Adolescent ; Adult ; Anti-Allergic Agents ; adverse effects ; therapeutic use ; Capsules ; Cetirizine ; adverse effects ; therapeutic use ; Chronic Disease ; Drug Therapy, Combination ; Female ; Glucosides ; adverse effects ; therapeutic use ; Humans ; Immunoglobulin E ; blood ; Interleukin-4 ; blood ; Male ; Middle Aged ; Paeonia ; chemistry ; Phytotherapy ; Recurrence ; Treatment Outcome ; Urticaria ; blood ; drug therapy ; Young Adult

It is reported that aristolochic acid(AA)not only has the definite nephrotoxicity but also causes the 3 different types of aristolochic acid nephropathy(AAN),which is different from the mutational signature of AA in inducing hepatocellular carcinomas.The clinical features of AA-induced nephrotoxicity include the lack of specific symptoms,a small amount of tubular proteinuria,the progressive renal failure,anemia and the extensive renal interstitial fibrosis with few infiltrated cells,along with tubular atrophy.The molecular mechanisms of AA-indueed nephrotoxicity mainly refer to the induction of renal cellular apoptosis by affecting microRNAs(miRNAs),endoplasmic reticulum stress and oxidative stress directlyor indirectly.In addition,renal inflammation is probably related to the molecular mechanism of AA-induced nephrotoxicity.The therapeutic strategies of AA-induced nephrotoxicity contain the low-dosage of glucocorticoids,prostaglandin E1,bone marrow mesenchymal stem cells and Chinese herbal compound prescriptions and their extracts.Recently Chinese government has maintained strict controls on Chinese medicinal materials and Chinese traditional patent medicines containing AA,so that the incidences of AA-induced nephrotoxicity and AAN have been decreasing year by year.Nevertheless,Chinese herbal medicines (CHM) related drug-induced kidney injury(DKI)cannot be ignored,in which,establishing the evaluation methods of nephrotoxicity of CHM is the key point to understand the molecular mechanisms and explore the therapeutic strategies.

OBJECTIVETo investigate the frequencies of human leuckocyte antigens (HLA) -A, B and DRB1 alleles in Chinese patients with primary biliary cirrhosis (PBC) using polymerase chain reaction-based techniques, and to assess the correlation of HLA molecules with other clinical and laboratory profiles.

METHODSGenotyping of HLA-A, B, and DRB1 were performed in 65 well-characterized patients with primary biliary cirrhosis and 431 healthy controls with PCR amplification with sequence-specific primers (PCR-SSP).

RESULTSThe frequency of DRB1*0701 was increased to 29.2% compared with 13.9% in the controls (PC < 0.05, OR = 2.55, 95% CI: 1.4 approximately 4.6). No association was found with HLA-DRB1*08 which had been constantly reported. The A*2 allele (53.8%) was more frequent in the PBC patient group but without a significant statistical difference. The frequencies for the other A, B and DRB1 alleles were similar between patients and healthy controls. There was no difference between patients with or without DRB1*0701 in some clinical and laboratory profiles.

CONCLUSIONSusceptibility to primary biliary cirrhosis in Chinese is associated with DRB1*0701 allele and differs from people in North America, South America, North Europe and even in Japan, but the association is not restricted to any particular subgroup of patients. Valine at position 78 of HLA DRbeta1 may play an important role in the pathogenesis of primary biliary cirrhosis.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Female ; HLA Antigens ; genetics ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-DR Antigens ; genetics ; Humans ; Liver Cirrhosis, Biliary ; genetics ; immunology ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo compare differences of angiogenesis among collagen- chitosan, collagen-sulfonated carboxymethyl chitosan porous scaffolds and acellular dermal matrix after these three different scaffolds with silicone membrane were transplanted on the wounds of full thickness burn, and the wound repair of different scaffolds with epidermis grafting on.

METHODSAngiogenesis in different dermal scaffolds, the wound surface and epidermis survival were observed in 1, 2, and 3 weeks after the three different scaffolds were respectively transplanted on wounds of full thickness burn with debridement in 6 Bama miniature pigs (total 18 pigs in 3 groups). At the same time, CD34 positive signals (neo-forming microvessels) were detected by immunohistochemical staining. The wounds without any scaffold transplantation were studied as the control.

RESULTSAngiogenesis had been fundamentally finished in 2 weeks after implantation of collagen- sulfonated carboxymethyl chitosan porous scaffold. And fundamental angiogenesis in collagen- chitosan porous scaffolds and acellular dermal matrix needed at least 3 weeks. Neo-forming micro-vessels perpendicular to wound beds with these three different scaffolds were more than those in the control wounds without scaffold. CD34 positive signals (neo-forming micro-vessels) were significantly higher in wounds at the second week than those in wounds at the first week. And those in wounds at the third week were significantly higher than those in wounds at the second week in all wounds with different scaffold transplantations and the control wounds. CD34 positive signals in the group of sulfonated carboxymethyl chitosan porous scaffold on the 1st, 2nd and 3rd week after the scaffold transplantation were significantly higher than those corresponding signals in the other three groups. Epidermis on the sulfonated carboxymethyl chitosan porous scaffold which had been transplanted on burn wound for 1 week could survive perfectly, however, epidermis on the collagen- chitosan porous scaffold or acellular dermal matrix could not survive until these two scaffolds had been transplanted on the burn wounds for at least 2 weeks.

CONCLUSIONSThese three different scaffolds could repair the full thickness skin defects caused by burn, and angiogenesis of sulfonated carboxymethyl chitosan porous scaffold is the best.

Animals ; Burns ; surgery ; Chitosan ; analogs & derivatives ; Collagen ; Disease Models, Animal ; Female ; Silicones ; Skin Transplantation ; Skin, Artificial ; Swine ; Swine, Miniature ; Tissue Scaffolds

OBJECTIVETo investigate the roles and differences of angiogenesis of different dermal scaffolds on wound contraction and apoptosis during full-thickness burn wound repair.

METHODSWounds were observed at different time after the collagen-sulfonated carboxymethyl chitosan porous scaffold or collagen-chitosan porous scaffold or acellular dermal matrix were respectively transplanted on wounds of full thickness burn with debridement in Bama miniature pigs. At the same time, vessels and myo-fibroblasts expressing α-smooth muscle action(α-SMA) and apoptosis in wounds of different time were detected in situ by immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling. The burn wounds without any scaffold transplantation were studied as the control.

RESULTSWounds with different scaffolds transplantation were different from granulation wounds. Vessels expressing α-SMA had been increasing continuously in the wounds from 1 to 3 weeks after different scaffolds transplantation and decreased in wounds after epidermis had been grafted for 2 weeks on surface of the scaffolds transplanted on wounds for 2 weeks. Vessels expressing α-SMA were the most in the wounds with collagen-sulfonated carboxymethyl chitosan porous scaffold transplantation and the least in the control wounds without dermal scaffold at different time. Myo-fibroblasts expressing α-SMA was the least in the wounds with collagen-sulfonated carboxymethyl chitosan porous scaffold transplantation and the peak of expressions was on the 2nd week, however, the peak in the wounds with the other two scaffolds transplantation and in the control wound without dermal scaffold was on the 3rd week. Myo-fibroblasts expressing α-SMA was the most in the control wounds. Apoptosis had been increasing continuously in the transplantation wounds from 2 to 4 weeks after different scaffolds transplantation, however, apoptosis had begun to increase continuously from 3 to 4 weeks in the control wounds. Apoptosis was the most in the wounds with collagen-sulfonated carboxymethyl chitosan porous scaffold transplantation and the least in the control wounds without dermal scaffold from 3 to 4 weeks.

CONCLUSIONSulfonated carboxymethyl chitosan can promote migration of reparative cells and angiogenesis, and it can repair full-thickness burn wound fast and well.

Animals ; Apoptosis ; Burns ; pathology ; surgery ; Chitosan ; analogs & derivatives ; pharmacology ; Collagen ; Disease Models, Animal ; Female ; Skin Transplantation ; Skin, Artificial ; Swine ; Tissue Scaffolds