Aged ; Atrophic Vaginitis ; drug therapy ; Capsules ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Middle Aged ; Suppositories ; administration & dosage ; Treatment Outcome

Adult ; Arsenic Poisoning ; etiology ; Female ; Humans ; Male ; Middle Aged ; Organotin Compounds ; poisoning ; Water Pollution ; Young Adult

OBJECTIVETo investigate the effect of peroxisiome proliferator activated receptor-α (PPAR-α) on the regulation of cardiomyocyte hypertrophy and the relationship between the effect of PPAR-α with PI3K/Akt//mTOR signal pathway.

METHODSCardiomyocyte hypertrophy was induced by isoproterenol (ISO). The cell surface area was measured by image analysis system (Leica). The expressions of atrial natriuretic peptide (ANP), β-myosin heavy chain (β-MHC) and PPAR-α mRNA were detected by qRT-PCR. The protein expressions of Akt, mTOR and P70S6K were detected by Western blot. The expression of PPAR-α was suppressed by RNAi.

RESULTS(1) The expression of PPAR-α was significantly reduced in cardiomyocyte hypertrophy. PPAR-α activator Fenofibrate (Feno) increased the expression of PPAR-α and suppressed cardiomyocyte hypertrophy. The inhibitory effect of Feno on cardiomyocyte hypertrophy was reversed by PPAR-α RNAi. (2) Feno significantly inhibited the increase of the protein expressions of p-Akt, p-mTOR and p-p70S6K in ISO induced cardiomyocyte hypertrophy, which could be blocked by PPAR-α RNAi. (3) PI3K antagonist LY294002 (LY) or mTOR antagonist rapamycin (RAPA) markedly-inhibited cardiomyocyte hypertrophy. The inhibitory effects of LY or RAPA on cardiomyocyte hypertrophy were reversed by PPAR-α RNAi.

CONCLUSIONPPAR-α can negatively regulate cardiomyocyte hypertrophy. The effect might be associated with PPAR-α inhiting PI3K/ Akt/mTOR signal pathway.

Atrial Natriuretic Factor ; metabolism ; Cardiomegaly ; metabolism ; Cells, Cultured ; Fenofibrate ; pharmacology ; Humans ; Isoproterenol ; adverse effects ; Myocytes, Cardiac ; drug effects ; metabolism ; Myosin Heavy Chains ; metabolism ; PPAR alpha ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Messenger ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVETo study the effect of Modified Dachengqi Decoction (MDD) as whole course therapy on mediators of inflammation in severe acute pancreatitis (SAP) model rats, and to compare interventional advantages over intestinal mucosal barrier (IMB) of SAP rats between whole course therapy of MDD and early stage therapy of MDD.

METHODSTotally 190 SD rats were divided into five groups according to random digit table, i.e., the sham-operation group, the model group, the octreotide (OT) group, the early stage MDD treatment group, the whole course MDD treatment group, 38 in each group. SAP models were established with retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct. Three hours after modeling normal saline (NS) was administered to rats in the sham-operation group and the model group by gastrogavage, once per 12 h.1.35 µg/100 g OT was subcutaneously injected to rats in the OT group, once every 8 h. 0.4 mL/100 g MDD was administered to rats in the early stage MDD treatment group, and 6 h later changed to NS (once per 12 h).0.4 mL/100 g MDD was administered to rats in the whole course MDD treatment group, once every 12 h. The accumulative survival rate and morphological manifestations of pancreas and small intestine were observed under microscope 48 h after modeling. Pathologic scores of the pancreas and small intestine were conducted at 4, 6, 24, and 48 h after modeling. Contents of serum amylase (AMY), alanine transaminase (ALT), and TNF-α were also detected. The expression of high mobility group box protein 1 (HMGB1) in the small intestine tissue was also detected by Western blot. The positive rate of bacterial translocation in mesenteric lymph nodes (MLNs) was observed within 48 h. Correlations between serum TNF-α or HMGB1 in small intestinal tissue and pathological scores of the pancreas or the small intestine were analyzed.

RESULTSThe accumulative survival rate was 100. 0% in the sham-operation group, 79. 2% in the whole course MDD treatment group, 70. 8% in the OT group, 45. 8% in the early stage MDD treatment group, and 37.5% in the model group. At 6 h after modeling, pathological scores decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 24 and 48 h after modeling, pathological scores of the pancreas and the small intestine decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P <0. 05). At 6, 24, and 48 h after modeling, serum contents of AMY and ALT both decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 48 h after modeling serum contents of AMY and ALT both decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). At 6 h after modeling serum TNF-α levels decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 6, 24, and 48 h after modeling the level of HMGB1 in the small intestinal tissue decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). Of them, HMGB1 levels at 24 and 48 h were lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). The number of MLNs bacterial translocation at 48 h after modeling was lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group and the model group (P < 0.05). Serum TNF-α contents within 6 h were positively correlated with pathological scores of pancreas (r = 0.579, P < 0.01). ROC curve showed that serum TNF-α contents could predict the severity of SAP (ROC = 0.990, 95% Cl: 0.971 to 1.000). HMGB1 in the small intestine was positively correlated with pathological scores of the small intestine (r = 0.620, P < 0.01).

CONCLUSIONSEarly stage use of MDD could effectively reduce the release of TNF-α, while whole course use of MDD could effectively inhibit the expression of HMGB1. The latter could preferably attenuate injuries of the pancreas and the small intestine, lower MLNs bacterial translocation, and elevate the survival rate.

Animals ; Bacterial Translocation ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; HMGB1 Protein ; Intestinal Mucosa ; drug effects ; Octreotide ; Pancreas ; Pancreatitis ; drug therapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Taurocholic Acid ; Tumor Necrosis Factor-alpha

A fragment sized 400bp of White spot syndrome virus（WS SV，formerly de signated NOSV），recovered from recombinant plasmid pAFD, was labeled with Digox igenin as a probe to detect dynamic distribution of WSSV within 120h and 72h in crawfishes（Cambarus proclarkii） inoculated WSSV by oral taking and injecti on r espectively. Stomach epithelium, intestine epithelium, heart, gill, haemolymph, muscle, hepatopancreas, hypoderm, connective tissue and ovary of infected crawfi shes were examined for WSSV. In both groups, WSSV was first detected in heamoly mph at 12h p.i. and then disappeared. Again it was detected at 96h p.i. only in oral infection group and maintained till 120h p.i., but it didn't appear at 72h p.i. in injection group. WSSV in heart, muscle was detected at 36h p.i. in oral infection group and 24h p.i. in injection group respectively, and then increased generally. In addition, WSSV in intestine epithelium, connective tissue, ovary of oral infection group and intestine epithelium, hypoderm, ovary of injection g roup could also be detected. In dead crawfishes after 120h and 72h p.i. in two groups, WSSV could be detected in all the examined tissues and it demonstrated t hat systemic infection occurred in the animales. The tissue containing more amo unts of WSSV was hypoderm in oral infection group, while intestine epithelium, g ill, hypoderm, ovary in injection infection group. It deduced that WSSV first a ppears in haemolymph and then goes into heart, muscle and other tissues and prol iferates in them. Once again, WSSV is released into heamolymph resulting in syst emic infection till crawfishes' death.

Objective To construct microvessel angiogenesis model in nonobese diabetic/severe combined immunodeficient disease(NOD/SCID) leukemia mice.Methods Divided NOD/SCID mice into group A:blank group;group B:endothelial cell(EC) injection group;group C:leukemia model mice with EC injection group.Microvessel density(MVD) in bone marrow was calculated with cnemis slice after immunohistochemistry dyeing.Evaluated leukemia burden in leukemia model mice.Results Bone marrow MVD in group C was significantly more than group B.Microvessels in leukemia mice had disordered branches and irregular cavity.The morphism of vessels was immature.Conclusions Microvessel angiogenesis model in NOD/SCID leukemia mice has been constructed successfully.It can be used in the study of anti-angiogenesis in leukemia and relative researches.

OBJECTIVETo identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.

METHODSGenomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced.

RESULTSBy DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls.

CONCLUSIONMutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.

Base Sequence ; DNA Mutational Analysis ; Epidermolysis Bullosa Simplex ; genetics ; pathology ; Exons ; Female ; Humans ; Hyperpigmentation ; genetics ; pathology ; Keratin-14 ; genetics ; Keratin-5 ; genetics ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA

Objective To explore whether the expression level of heparanase (HPA) and its coagulation proteins on leukemic blast membrane could determine the hemostatic balance on the surface of leukemia cells.Methods Forty patients of leukemia were studied,and 20 patients with iron dificient anemia as the control group.Expression of tissue factor (TF),heparanase (HPA),tissue factor pathway inhibitor (TFPI),and urokinase plasminogen activator receptor (UPAR) on leukemic blast surfaces were analyzed by flowcytometry.Results The expression of TF,UPAR,and HPA in AML,ALL,CML,CLL and CRAL groups were significantly higher compared with the control group (t =.3.289,3.507,2.701,P ＜0.05; t =2.498,0.802,3.090,P ＜0.05; t =2.642,3.308,2.696,P ＜0.05; t =3.417,3.434,2.382,P ＜0.05; t =2.193,2.272,2.263,P ＜0.05).There were no significantly differences between the leukemic cell expression of TFPI and the control group (P ＞0.05).Expression of TF,UPAR,HPA in AML patients were significantly higher than ALL,CML and CLL groups (t =2.463,2.179,2.276,P ＜0.05; t =2.637,2.402,2.095,P ＜0.05; t =2.548,2.425,2.412,P ＜0.05).The levels of TF,UPAR and HPA in M3,M4 and M5 patients were higher than that of M1,M2 groups (P ＜0.05).There were no significantly differences among M3,M4 and M5 (P ＞0.05).Conclusions These results suggest that TF,UPAR and HPA are predominately expressed on leukemic blast surface,particularly in M3and M4,5 subtypes.The expression of coagulation proteins on blast membrane might determine the hemostatic balance on the surface of leukemia cells.

The tail suspension test (TST), forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were used to evaluate the anti-depressant effect of supercritical CO2 extract from Compound Chaigui Fang (FFCGF). A nuclear magnetic resonance (NMR)-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight, sucrose preference, crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats' urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats' body weight, sucrose preference, crossings and rearings in CUMS, which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed, which were consistent with the results of behavioral tests. Decreased levels of acetic acid, succinic acid, 2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism, lipid metabolism and amino acid metabolism.
Animals ; Antidepressive Agents ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Behavior, Animal ; drug effects ; Body Weight ; Carbon Dioxide ; chemistry ; Depression ; drug therapy ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Male ; Mice

Adenocarcinoma ; metabolism ; pathology ; Adult ; Antigens, CD34 ; metabolism ; Biopsy ; Diagnosis, Differential ; Follow-Up Studies ; Hemangioendothelioma, Epithelioid ; diagnostic imaging ; metabolism ; pathology ; surgery ; Humans ; Lung ; metabolism ; pathology ; Lung Neoplasms ; diagnostic imaging ; metabolism ; pathology ; surgery ; Male ; Mesothelioma ; metabolism ; pathology ; Middle Aged ; Multimodal Imaging ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Positron-Emission Tomography ; Thoracoscopy ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary ; metabolism ; pathology