Environmental Exposure ; adverse effects ; Hearing Loss ; etiology ; Humans ; Noise, Occupational ; adverse effects ; Occupational Diseases ; etiology ; Occupational Exposure ; adverse effects ; Risk Factors ; Smoking ; adverse effects ; Vibration ; adverse effects

Humans ; Noise, Occupational ; adverse effects ; Occupational Exposure ; standards

Objective To explore the effect of TLR2 on collagen Ⅰ(colⅠ) in adipose tissue of high-fat-diet induced obese mice.Methods Male C57bl/6J mice and TLR2 knockout mice were divided into groups according to high fat diet or normal chow.Total collagen, TLR2, colⅠ, MMP1, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were measured at the end of the experiments.Results Total collagen, TLR2, colⅠ, MMP2, TIMP1, colⅠα1 mRNA, and colⅠα2 mRNA in adipose tissue increased while MMP1 in adipose tissue decreased in mice with high fat diet.Decreased levels of total collagen, colⅠ, MMP2, TIMP1, colⅠα1 mRNA and colⅠα2 mRNA in adipose tissue were detected in TLR2 gene knockout mice with high fat diet.However, there was an increased level of MMP1 in TLR2 gene knockout mice with high fat diet.Conclusion In high-fat-diet induced obese mice, deposition of colⅠ in adipose tissue seems to be alleviated by TLR2 gene knockout via MMP1 and TIMP1.

Occupational Medicine ; education

Objective To study the effects of oxymatrine as inhibitor of hemorrhagic fever with renal syndrome virus (HFRSV) infection in vitro and in vivo.Methods In vitro studies,a dose of oxymatrine without cytotoxicity and 76-118 strain of HFRSV was taken to treat Vero cells in three ways:①After treated with oxymatrine for 48 h,Vero cells were attacked by HFRSV at dilution of 10-1 ～ 10-6,respectively for 24 h before changing to maintenance medium; ②Vero cells were first attacked by HFRSV of 10-1 ～ 10-6 dilution respectively,then oxymatrine was used for 48 h before changing to maintenance medium; ③Vero cells were attacked by HFRSV at dilution of 10-1 ～ 10-6 respectively,and meanwhile treated with oxymatrine for 48 h before changing to maintenance mcdium.Each dilution handled four porocytes,and four positive controls were set up at the same time.Indirect immunofluorescence assay (IFA) was performed to determine the inhibitory effect of oxymatrine in experimental group and positive control.In vivo studies,thirty 2-week-old hamsters,weighing about 30-40 g,were divided into experimental and control groups according to body weight,n =15.These aninals were inoculated intraperitoneally with HFRSV in 100TCID50(0.1 ml each); on days 4-13,0.1 ml of oxymatrine 1:100 were given to each hamster in experimental group daily by intraperitoneal injection,while the same amount of saline was given to the control ones.Lung tissue of hamsters was then dissected out to slice to be identified by immunofluorcscence stain.Results It was demonstrated that oxymatrine with the diluted fractions of 1:8 was safe in vitro.When the virus dilution of HFRSV was l0-4,compared with control groups,the differences were statistically significant in method 2 and 3 (z =-2.53,-2.53,all P ＜ 0.05),while no statistical significance in method 1 (z＝5.36,P＞ 0.05).When the virus dilution of HFRSV was 10-1 ～ 10-3,10-5,10-6,the differences were not statistically significant (z--0.00,-0.32,-0.19,4.21,4.21,all P ＞ 0.05).In vivo studies,compared with control group,the differences were statistically significant in experimental group (z =-3.85,P ＜ 0.05).Conclusion Oxymatrine significantly inhibites HFRSV.

Shikonin, the main active ingredient of Lithospermum, and its derivatives have been proved to have antitumor effects, and the anti-tumor mechanisms involve multiple targets. Based on recent literatures, this review focuses on the antitumor effects and its mechanisms. More emphases are given on the aspects of induction of apoptosis, induction of necrosis, acting on matrix metalloproteinase, acting on the protein tyrosine kinase and antiangiogenesis. The current status and problems of shikonin derivatives in antitumor effects are simply summarized and lookout for the development of antitumor drugs with shikonin as leading compounds.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Humans ; Lithospermum ; chemistry ; Matrix Metalloproteinase 9 ; metabolism ; Naphthoquinones ; isolation & purification ; pharmacology ; therapeutic use ; Necrosis ; Neoplasms ; drug therapy ; metabolism ; pathology ; Neovascularization, Pathologic ; prevention & control ; Plants, Medicinal ; chemistry ; Protein-Tyrosine Kinases ; metabolism ; Reactive Oxygen Species ; metabolism

To investigate the effects of Losartan,an angiotensinⅡ(AngⅡ)receptor(AT_1) antagonist,on pancreatic stellate cells(PSCs)and its possible mechanisms.Methods (1)PSCs were isolated from pancreatic cancerous samples to test the expressions of AT_1 and collagenⅠafter incubated with AngⅡor/and Losartan.(2)Ninety S-D rats were divided into normal group,control group and treatment group,with 30 rats in each.The rats in control and treatment groups were induced pancreatic fibrosis by injection of 2% trinitrobenenze sulfonic acid(TNBS)into biliopancreatic duct.Rats in treat- ment group were then treated with Losartan by garage daily and rats in control group were only given distilled water.The rats were sacrificed on day 3,7,14,21 and 28,respectively,and pancreas were removed.The histological abnormalities were observed by electron microscope.The mRNAs of trans- forming growth factor?_1(TGF?_1)and procollagenⅠwere detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of TGF?_1 and?-smooth muscle actin(?-SMA)proteins was assessed by immunohistochemistry and the level of?-SMA protein was quantified by Western blot. Results In vitro,there existed AT_1 expression in PSCs,and Losartan reduced expression of collagenⅠ.Losartan treatment reversed the histological abnormalities observed by electron microscope,com- pared to treatment with distill water.The expression of?-SMA,TGF?_1 and procollagenⅠwere signifi- cantly higher in the control group than those in normal group and were reduced by Losartan to different extent in treatment group.Conclusion AT_1 antagonist can inhibit the activation and the profibrogenic action of PSCs by blocking AT_1 receptor-mediated pathways.

AIM: The study was undertaken to investigate the effort of Dexamethasone (DEX) on cultured rabbit corneal epithelial (RCE) cells and rabbit corneal epithelial wound healing.METHODS: For the in vitro experiments, primary cultures of RCE cells were used. DEX in different concentrations was added to cultured RCE cells. The effects were measured with tetrazolium salt (MTT)method and flow cytometry. For the in vivo wound-healing experiments, a central corneal deepithelialization was created and were treated with 0.1g/L DEX eyedrop randomly explain how randomly. Epithelial wound healing was evaluated clinically and analyzed histopathologically using light microscopy along with immunohistochemical staning and electronic microscopy.RESULTS: Less than 0.1g/L DEX didn't influence survival rate in cell culture conditions by MTT assay. Flow cytometric studies revealed that 0.1g/L DFX had no effect on cellular growth phase in cultured rabbit corneal epithelial cells. The mean time of the epithelial healing was significantly shorter in the DEX-treated group than in the control group at 24h. There were strong proliferative-cell-nuclear-antigen(PCNA) expressions in newly generated epithelial cells of both groups. The Dex-treated group had a more regular architecture of stromal lamella and significantly less inflammatory response than the control group under electronic microscopy.CONCLUSION: Less than 0.1g/L DEX had no inhibiting effect on cultured rabbit corneal epithelial cell growth.0.1g/L DEX eye drops can effectively promote epithelial growth and reduce inflammatory response, which may have useful clinical application at the early stage of corneal wound healing process.

AIMTo study the pharmacokinetics of genistein at different doses in Beagle dogs.

METHODSSuspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSThe plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.

CONCLUSIONDue to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.

Animals ; Anticarcinogenic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Dogs ; Dose-Response Relationship, Drug ; Female ; Genistein ; administration & dosage ; blood ; pharmacokinetics ; Glucuronides ; blood ; pharmacokinetics ; Male

This study was aimed to investigate the role of B-cell lymphoma 2 (BCL-2) in pathogenesis of hyperleukocytic acute myeloid leukemia (AML). The levels of intracellular BCL-2 in 48 AML patients were detected by flow cytometry (FCM). Serum levels of BCL-2 in 40 AML patients were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that the serum levels of BCL-2 in hyperleukocytic AML and non-hyperleukocytic AML patients were significantly higher than that in normal controls (P < 0.05), but intracellular BCL-2 levels were not significantly different, as compared with normal controls (P > 0.05). There were no difference of intracellular and serum BCL-2 levels between hyperleukocytic and non-hyperleukocytic AML patients (P > 0.05). The serum and intracellular levels of BCL-2 between hyperleukocytic AML, non-hyperleukocytic AML patients and normal controls were not statistically correlated. It is concluded that leukemic cells in AML patients produce and secrete too much BCL-2, which may be involved in the pathogenesis of leukemia disease. However, the anti-apoptosis effect of BCL-2 has no significant impact on the pathogenesis of hyperleukocytic AML.
Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; blood ; pathology ; Male ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; blood