Adult ; Deferoxamine ; adverse effects ; therapeutic use ; Humans ; Lung Diseases, Interstitial ; chemically induced ; Male ; Myelodysplastic Syndromes ; drug therapy

Objective:To study the effects of IL 6、IL 1? and TNF? on the expression of c fos and c jun,which may provide the foundation for a further study in clinic.Methods:Used the a model of primary culture of human fetal cerebral neurons in serum free medium,by DNA RNA dot blot hybrdization.Results:The expression of c fos and c jun was increased between 15 min to 30 min after stimulation,reached a maximum at 1 h and declined over the subsequent 1 h.Conclusion:IL 6、IL 1? and TNF ? have induce the expression of c fos and c jun during development of human fetal cerebral neurons in vitro at the level of transcription.

Objective:To study the effects of Il 6?IL 1??TNF? on the growth and development of cultured human fetal cerebral neurons.Methods:Established the model of primary culture of human fetal cerbral neurons in SFFD,by morphological observation and MTT assay.Results:IL 6 and IL 1? both promote the survival of neurons and IL 6 also promote the outgrowth of neuritis and differentiation of neurons in culture.TNF ? continuously inhibit the survival of neurons.Conclusion:IL 6?IL 1??TNF? can effect the development of cultured neurons.IL 6 and IL 1? both may effect as neurotrophic factor in the survival?growth and development by indirect mechanism.TNF? directly show neurotoxin effect in culture.

Objective To investigate the immunoregulatory effects of bone marrow-derived mesenehy-real stem ceils (BMSCs) combined with leflunomide (LEF) on mice T-lymphocytes in vitro. Methods BMSCs from BALB/c mice were isolated and expanded. The purity of BMSCs was identified by flow cytometry (FCM). The BALB/c mice's spleen lymphocytes were isolated by using EZ-Sep<'TM> Mouse 1X. Under ConA stimulation, spleen lymphocytes were pretreated with LEF, then washed and co-cuhured with BMSCs. We set up four groups to investigate in this study: group A, spleen lymphocytes alone; group B, spleen lymphocytes with BM- SCs; group C, LEF-pretreated spleen lymphocytes alone and the group D, LEF-pretreated spleen lymphocytes with BMSCs. T-lymphocytes proliferation was assessed by MTT. FCM was used to analysis T-lymphocytes apoptosis and surface markers of CD69 and CD28. The mRNA expression of interleukin (IL)-2, IL-10 were detected by real-time RT-PCR. Results In vitro, the T-lymphocytes'values of A570 nm were significantly lower in group B and group C, compared with group A (group B vs group C vs group A, 0.578±0.042 vs 0.502± 0.040 vs 0.778±0.035, P<0.01), while the value of A<,570 nm>in group D was 0.218±0.033, which was also obviously lower than that in group B and group C (P<0.01). There were no suppressing effects on T-lympho-cytes'activation and expression of IL-2 had been observed. The proportion of apoptotic T-lymphocytes in group B and group D were (2.29±0.32)％ and (4.22±0.98)％, which was significandy lower than that in group A (8.08±1.20) (P<0.01). The expression of IL-10 in group B and C were also lower than that in group A (group B vs group C vs group A, 0.098±0.039 vs 0.054±0.022 vs 1.000, P<0.01 ). Either, the expression of IL-10 in group D was 0.023±0.015, which was obviously lower than that in group B and group C (P<0.01). Conclusion BMSCs combined with LEF show synergistic immunoregulatary effects on mice's T-lymphoeytes.

OBJECTIVETo demonstrate the effects and mechanisms of Qifu decoction( QFD) on renal interstitial fibrosis (RIF) in model rats with yang-deficiency syndrome.

METHODThe rats were randomly divided into 3 groups, the Sham group (Group A), the Model group (Group B), the Qifu decoction group (Group C) and the Enalapril group (Group D). The RIF model was established by adenine administrated and unilateral ureteral obstruction (UUO) of the left ureter. After the model was successfully established, the rats in Group C and D were administrated with QFD or the Enalapril suspension,while the rats in Group A and B were administrated with distilled water. All rats were administrated for 3 weeks. Before administration and at the end of week 1, 2 and 3, the rats were weighted, and 24 h urinary protein excretion (Upro), urinary β2-microglobulin (Uβ2-MG) and urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats were killed after administration for 3 weeks. Blood and renal tissues were collected, renal morphology and tubulointerstitial morphology were evaluated, respectively. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), blood urea nitrogen (BUN), serum creatinine (Scr) and uric acid (UA) were detected, respectively. The protein expressions of E-cadherin, α-smooth muscle actin(α-SMA), transforming growth factor-β1 (TGF-β1), onnective tissue growth factor (CTGF) extracellular signal-regulated protein kinase 1/2(ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in kidney were evaluated, respectively.

RESULTQFD ameliorated serum cAMP level and the rate of cAMP/cGMP, attenuated urinary β2-MG level, NAG level and renal tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions in the kidney. However, QFD had no influence on renal function in vivo. In addition, these effects were better than those of the model rats treated by Enalapril.

CONCLUSIONQFD could alleviate yang-deficiency parameters, as well as urinary β2-MG level and NAG level in model rats induced by adenine administration and UUO. Moreover, QFD could improve EMT and RIF by up-regulating E-cadherin protein expression, and down-regulating α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions, the key molecular in ERK1/2 signaling pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; Fibrosis ; Kidney ; drug effects ; pathology ; Kidney Diseases ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications ; Yang Deficiency ; complications

Objective To investigate the effect of external fixator on repairing the vascular injuries in the knee and calf.Methods From May 2004 to October 2010,208 patients (234 sides) with vascular injuries in knee and calf,treated with external fixation,were retrospectively analyzed,including 192 males (217 sides) and 16 females (17 sides) with an average age of 39.6 years (range,14-67).Blood vessel damage:the popliteal artery injury in 84 patients (86 sides),the anterior tibial artery injury in 36 (46),the posterior tibial artery injury in 41(49),the anterior tibial artery and the posterior tibial artery injury in 47 (53).Complete ischemic of the injured distal limb existed in 129 patients(141 sides),incomplete ischemia in 79 patiets (93 sides).All patients underwent emergency surgery.The AO external fixators were used in 164 patients,the chuangsheng inlaid external fixators in 37,and the hybrid external fixators in 7.The injured vessels were anastomosed directly,or indirectly with great saphenous vein.The wounds were treated with phase Ⅰ bandage,skin grafts,flap transplantation or VSD suction.Results One hundred and ninty four patients obtained successful limb salvage; but 14 patients underwent amputation owing to serious damage of limb and poor general condition.One hundred and twenty seven patients underwent the second stage debridement combined with skin graft or flap transplantation; 24 patients underwent the first stage free skin graft or flap transplantation;wound cicatrized by oneself in 43 patients.One hundred and forty eight patients were followed up for 8 months to 3 years.External fixators were removed after an average of 7.2 months (range,1-18).The average healing time of fracture in 102 patients was 5.6 months (range,3-13).Forty patients suffered bone nonunion or bone defect; after treated by fracture fixation,bone graft or bone transport,all of them got bone union.Conclusion The external fixation can shorten operation time as well as the time of limb ischemia,which is an effective option on repairing vascular injuries in knee and calf.

This study investigated the abnormal expression of ATP synthase β-subunit (ATPsyn-β) in pancreas islets of rat model of polycystic ovary syndrome (PCOS) with type 2 diabetes mellitus (T2DM),and the secretion function changes after up-regulation of ATP5b.Sixty female SD rats were divided into three groups randomly and equally.The rat model of PCOS with T2DM was established by free access to the high-carbohydrate/high-fat diet,subcutaneous injections of DHEA,and a single injection of streptozotocin.The pancreas was removed for the detection of the ATPsyn-β expression by immunohistochemical staining,Western blotting and reverse transcription-PCR (RT-PCR).The pancreas islets of the rats were cultured,isolated with collagenase Ⅴ and purified by gradient centrifugation,and the insulin secretion after treatment with different glucose concentrations was tested.Lentivirus ATP5b was successfully constructed with the vector of GV208 and transfected into the pancreas islets for the over-expression of ATPsyn-β.The insulin secretion and intracellular ATP content were determined after transfection of the PCOS-T2DM pancreas islets with Lenti-ATP5b.The results showed that the expression of ATPsyn-β protein and mRNA was significantly decreased in the pancreas of PCOS-T2DM rats.The ATP content in the pancreas islets was greatly increased and the insulin secretion was improved after the up-regulation of ATPsyn-β in the pancreas islets transfected with lenti-ATP5b.These results indicated that for PCOS,the ATPsyn-β might be one of the key factors for the attack of T2DM.

Background Following the accelerated speed of population aging in China,the incidence of cataract is rising gradually.Researches indicated that senescenee marker protein-30 ( SMP-30 ) is closely associated with the occurring and developing of cataract. Objective This study was to investigate the expression of SMP-30 in human lens epithelial cells(LECs) of age-related cataract and study the relationship between SMP-30 and apoptosis.Methods Capsulotomy was performed on 80 eyes of 59 patients with simple cortex age-related cataract and 70 eyes of 53 age-matched patients with nucleus age-related cataract.The anterior capsular specimens were obtained by circularly capsulorhexis during the operation.Expressions of the SMP-30 protein and mRNA in the LECs of two types of cataract were detected using immunochemistry and real-time PCR respectively.Apoptosis of the LECs was assayed by TUNEL.The differences of expression of SMP-30 and apoptosis were compared between the two types of cataract.Results Immunochemistry showed that SMP-30 was expressed in cytoplasm of LECs.The expression intensity of SMP-30 was higher in the center zone compared with periphery zone.The apoptosis rate of LECs was significantly higher in the center of the anterior capsule than the periphery in both two types of cataract ( nucleus cataract:19.34％±0.11％ vs 8.32 ％ ± 0.57 ％,P =0.025 ; cortex cataract:42.07 ％ ± 0.86 ％ vs 13.55 ％ ± 0.64 ％,P =0.010 ).The expression amount of SMP-30 mRNA was lower at the periphery than the center of lens in both two types of cataract (nucleus cataract:45.21±2.79 vs 76.42±11.21,P=0.042 ;cortex cataract:108.32±4.32 vs 206.34±15.67,P=0.037 ),and that of nucleus cataract was significantly lower than cortex cataract (60.02±9.08 vs 157.33 ± 13.01,P =0.034),and the apoptosis rate of LECs was declined in the nucleus cataract group compared with the cortex cataract group ( 14.05％ ±0.22％ vs 27.70％ ±0.81％,P =0.007 ). Conclusions LECs apoptosis exists in age-related cataract.SMP-30 probably plays an important role in the formation of cataract.

Epithelial to mesenchymal transition (EMT) has been proposed as a key role leading to the progressive tubulo-interstitial fibrosis (TIF). The tubular EMT is an highly regulated process involving four key steps including: loss of epithelial cell adhesion, de novo smooth muscle actin expression and actin reorganization, disruption of tubular basement membrane,and enhanced cell migration and invasion. These crucial processes are closely connected to the relative actions on many signaling pathways in EMT. Additionally, increasing evidences suggest that some Chinese herbal medicines and their extracts, such as Astragali Radix, Cordyceps, Salvia miltiorrhiza, as well as Chinese. herbal prescriptions including Astragalus Angelica mixture and Supplementing Qi and activating blood circulation decoction, could intervene the related events controlling EMT both in vitro and in vivo. Chinese herbal medicines could ameliorate TIF by intervening the course of EMT.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Gene Expression Regulation ; drug effects ; Humans ; Kidney Tubules ; cytology ; drug effects ; metabolism ; Signal Transduction ; drug effects

OBJECTIVEN-acetyltransferase 2 (NAT2) and cytochrome P450 2EI (CYP2E1) play a crucial role in the drug metabolic process. The aim of this study was to understand the genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han Chinese pediatric population in order to provide a theoretical basis for individualized drug treatment.

METHODSA total of 341 (211 males and 130 females) randomly sampled Han Chinese children, aged from 2 months to 14 years, were enrolled in this study. Genotyping was carried out by PCR method, and metabolic phenotypes were identified.

RESULTSIn this study population, wild genotype was found as a major genotype in seven SNPs of NAT2, rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931. The frequency of NAT2 fast metabolism was highest (61.3%), followed by middle to slow metabolism (34.1%). Wild genotype also predominated in the four SNPs of CYP2E1 (rs2031920, rs3813867, rs6413432 and rs72559720) named as CYP2E1*5, *6 and *2, with a frequency of 61.3%, 60.1% and 99.4% respectively. As the relationship between CYP2E1 genotype and phenotype was unknown, phenotyping of CYP2E1 was not done.

CONCLUSIONSThe important SNPs of NAT2 and CYP2E1 are predominantly wild genotype in the Han Chinese pediatric population. Fast metabolic phenotype predominates in important SNPs of NAT2.

Adolescent ; Arylamine N-Acetyltransferase ; genetics ; Child ; Child, Preschool ; China ; ethnology ; Cytochrome P-450 CYP2E1 ; genetics ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Phenotype ; Polymorphism, Single Nucleotide