OBJECTIVETo observe the effects of Dioscornin Tablet (DT) containing serum on nuclear factor of kappa B (NF-kappaB) p65, signal transducer and activator of transcription 3 (STAT3), and vascular endothelial growth factor (VEGF) mRNA expressions in rats' synovial cell strain 364 (RSC-364) induced by interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha), and to investigate the underlying mechanisms for DT to inhibit angiogenesis of rheumatoid arthritis (RA).

METHODSIn this experiment, the vehicle control group, the cell model group, the DT containing serum group, and the positive control group (Tripterygium containing serum) were set up. The DT containing serum and the Tripterygium containing serum were prepared. The RA cell model was established by IL-17 combined TNF-alpha induced injury in RSC-364. The RA cells were intervened by DT containing serum and Tripterygium containing serum respectively. The DNA binding activity of NF-kappaB p65 was detected using TransAM NF-kappaB p65. The expression of STAT3 was observed using Western blot. The VEGF mRNA expressions were detected by real-time quantitative PCR.

RESULTSCompared with the vehicle control group, the NF-kappaB p65 activity, the expressions of STAT3 and VEGF mRNA increased significantly in RSC-364 induced by IL-17 +TNF-alpha (P < 0.01, P < 0.05). Compared with the model group, the NF-kappaB p65 activity, the expressions of STAT3 and VEGF mRNA decreased significantly in the DT containing serum group and the positive control group (P < 0.01, P < 0.05). There was no statistical difference between the two groups (P > 0.05).

CONCLUSIONDT inhibited the VEGF mRNA expression through inhibiting the NF-kappaB p65 activity and the STAT3 protein expression in the Janus kinase (JAK)-signal transducer and activating transcription factor pathway, thus inhibiting the angiogenesis of RA.

Animals ; Arthritis, Rheumatoid ; pathology ; Cells, Cultured ; Diosgenin ; analogs & derivatives ; pharmacology ; Interleukin-17 ; adverse effects ; Male ; Neovascularization, Pathologic ; pathology ; RNA, Messenger ; pharmacology ; Rats ; Rats, Wistar ; STAT3 Transcription Factor ; metabolism ; Serum ; Signal Transduction ; Synovial Membrane ; cytology ; drug effects ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; adverse effects ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).

METHODSTotally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.

RESULTSCompared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.

CONCLUSIONSGood curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Angiotensin II ; Animals ; C-Reactive Protein ; Chronic Disease ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Edema ; Heart ; Heart Failure ; drug therapy ; Heart Ventricles ; Medicine, Chinese Traditional ; Natriuretic Peptide, Brain ; Qi ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Thyrotropin ; Ventricular Function, Left

OBJECTIVETo establish and evaluate chronic heart failure (CHF) rat model of Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BSES).

METHODSTotally 40 SD rats were randomly divided into the normal control group (Control), the propylthiouracil (PTU) group, the adriamycin (ADR), and the ADR + PTU group. Normal saline was used as equivalent solvent of each group. Rats in the Control group were intragastrically and intraperitoneally injected with normal saline. Rats in the PTU group were intragastrically injected with PTU suspension and intraperitoneally injected with normal saline. Rats in the ADR group were intragastrically injected with ADR solution and intraperitoneally injected with normal saline. And rats in the ADR + PTU group were intragastrically injected with PTU suspension and intraperitoneally injected with ADR solution. The dose of PTU was 0.2% of daily forage weight, once daily. The dose of ADR was 3.5 mg/kg, once per week. The modeling lasted for 6 weeks. Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), Tri-iodothyronine (T3), tetra-iodothyronine(T4), thyroid stimulating hormone (TSH) as well as heart, lung, liver weight indices and their pathological sections were integrated and compared.

RESULTSCompared with the Control group, LVEF, LVFS, BNP, HR, RR, heart, lung, liver weight indices, urine output, ear temperature, EST, and T3, T4, and TSH changed significantly in the ADR group, the PTU group, and the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure occurred in pathological sections of heart, lung, and liver. Compared with the ADR group, LVEF, LVFS, BNP, and lung, liver weight indices, urine output, ear temperature, T3, T4, and TSH changed significantly in the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure were more serious in pathological sections of heart, lung, and liver. Compared with the PTU group, LVEF, LVFS, BNP, HR, RR, urine output, EST, T4, heart and lung weight indices changed significantly in the ADR + PTU group with statistical significance (P < 0.05), and pathological changes of heart failure were quite serious in pathological sections of heart, lung, and liver.

CONCLUSIONADR + PTU was an appropriate method to establish CHF rat model of XQD-BSES.

Animals ; Edema ; Heart Failure ; diagnosis ; Heart Ventricles ; Humans ; Judgment ; Models, Animal ; Qi ; Rats ; Ventricular Function, Left

Adult ; Female ; Humans ; Middle Aged ; Myxoma ; pathology ; surgery ; Vulvar Neoplasms ; pathology ; surgery

OBJECTIVETo study the chemical constituents from the active fractions against HIV in vitro, a crude ethanolic extract of Illicium simonsii.

METHODThe compounds were isolated with column chromatography methods. MS and NMR spectroscopic methods were used to determine the structures of the compounds.

RESULTSeven compounds were isolated from the active fractions against HIV in vitro of the 90% ethanol extract and their structures were elucidated as (+)-catechin (1), (-)-epicatechin (2), (+)-catechin 3-O-alpha-L-rhamnopyranoside (3), kaempferol 3-O-alpha-L-rhamnopyranoside (4), quercetin 3-O-alpha-L-rhamnopyranoside (5), erigeside C (6) and daucosterol (7).

CONCLUSIONSeven compounds were isolated from this plant for the first time, but none of them exhibited active against HIV in vitro. Compounds 3 and 6 were isolated from this genus for the first time.

Catechin ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Ethanol ; chemistry ; Glycosides ; chemistry ; Illicium ; chemistry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Rhamnose ; analogs & derivatives ; chemistry ; Sitosterols ; chemistry

BACKGROUND: Investigation on epidemiologic features of knee osteoarthritis in many areas of China has been much reported. However, multicenter studies with large samples have been rarely reported. The published papers cannot give a good description about the epidemiologic features of knee osteoarthritis. OBJECTIVE: To evaluate the epidemiologic features of knee osteoarthritis in the patients aged over 40 years in China. METHODS: Meta-analysis was used to evaluate the data extracted from papers published 2001-2016 on the epidemiology of knee osteoarthritis in the middle-aged and elderly in China. The prevalence rate of knee osteoarthritis in the patients over 40 years of age was summarized, with every 10 years as group, and then analyzed on Stata 12.0 software. RESULTS AND CONCLUSION: Twenty-six articles were included, involving 42 199 people aged more than 40 years old. The total prevalence rate of knee osteoarthritis at the age above 40 years old in China was 17.0% (95% CI:16.7%-17.4%),the prevalence rate was 12.3% in male and 22.2% in female(P<0.05).Noticeably,the prevalence rate increased with age.The total prevalence rate in northern China was 16.1%(95% CI:15.6%-16.6%),12.2% in male and 21.4% in female;the total prevalence in southern China was 18.0%(95%CI:17.5%-18.5%), 12.3% in male and 23.1% in female. There was no significant difference in the prevalence rate between northern and southern China(P>0.05).The total prevalence rate in rural China was 23.6%(95%CI:16.7%-30.4%),with 15.4% in male and 28.1% in female;and the total prevalence in urban China was 20.0%(95% CI:16.2%-23.9%),with 13.7% in male and 24.3% in female. There was no significant difference in the prevalence rate between rural and urban China (P > 0.05). These results suggest that knee osteoarthritis in China is a common disease, characterized by increased prevalence with age, relatively significant difference between male and female, but no difference between northern and southern China as well as between rural and urban China. It is of great significance to timely propagate and perform interventional strategies for prevention and treatment of knee osteoarthritis in China.

The hybrid xylanase TB was constructed by the substitution of the N-terminus segment of the Streptomyces olivaceoviridis xylanase XYNB with corresponding region of Thermomonosporafusca xylanase TfxA. The hybrid gene tb, encoding the TB, was correctly expressed in Escherichia coli BL21 and Pichia pastoris GS115. TB was purified and its enzymatic properties were determined. The results revealed that the optimal temperature and optimal pH of TB were at 70 degrees C and 6.0, which have been obviously improved compared with those of XYNB. The thermostability of TB were all about six-fold of XYNB's after incubating the properly diluted enzyme solutions at 80 degrees C and 90 degrees C for 3min, respectively. The pH stability of TB was 5 to approximately 9, which was narrower than that of XYNB. Still, TB remains a high specific activity as XYNB does. Analysis of a homology modeling and sequence similarity were used to reveal the factors influencing the enzymatic properties of TB and the discussion for the relationship between structure and function of xylanase was given.
Amino Acid Sequence ; Base Sequence ; Desulfurococcaceae ; enzymology ; genetics ; Endo-1,4-beta Xylanases ; genetics ; metabolism ; Enzyme Stability ; Escherichia coli ; enzymology ; genetics ; Hot Temperature ; Molecular Sequence Data ; Pichia ; enzymology ; genetics ; Protein Engineering ; methods ; Recombinant Fusion Proteins ; genetics ; metabolism ; Streptomyces ; enzymology ; genetics ; Structure-Activity Relationship

OBJECTIVETo study the effect of eucalyptus globulus oil on the activity of nuclear factor-kappaB(NF-kappaB) in THP-1 cell line.

METHODSTHP-1 cells were cultured with or without eucalyptus globulus oil at different concentrations (1, 10, 100 mg x L(-1), 30 min) before being stimulated with lipopolysaccharide (LPS, 1 mg x L(-1), 30 min). The location of NF-kappaB p65 subunit (NF-kappaB/p65) in THP-1 cells was detected by indirect immunofluorescence and laser scanning confocal microscope. The expression of NF-kappaB/p65 in nuclei was measured by Western-blot analysis.

RESULTThe FITC-label NF-kappaB/p65 was mainly located in the nuclei after THP-1 cells were stimulated with LPS. Whereas, no fluorescence were seen in the nuclei of cells pretreated with eucalyptus globulus oil. This effect on NF-kappaB/p65 nuclear translocation was in a concentration dependent manner.

CONCLUSIONEucalyptus globulus oil inhibits the nuclear translocation of NF-kappaB induced by LPS in THP-1 cells.

Active Transport, Cell Nucleus ; drug effects ; Blotting, Western ; Cell Line ; Dose-Response Relationship, Drug ; Eucalyptus ; chemistry ; Humans ; Lipopolysaccharides ; pharmacology ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Plant Oils ; pharmacology ; Tosyllysine Chloromethyl Ketone ; pharmacology

This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.
Cation Transport Proteins ; antagonists & inhibitors ; Down-Regulation ; Guanidines ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Interleukin-8 ; metabolism ; K562 Cells ; Phosphorylation ; drug effects ; Pyridines ; pharmacology ; Sodium-Hydrogen Exchanger 1 ; Sodium-Hydrogen Exchangers ; antagonists & inhibitors ; Sulfones ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

This study was aimed to investigate whether the inhibition of NHE1 activity and intracellular acidification can reverse resistance of leukemia cells to the imatinib and to explore downstream signal molecule networks of BCR/ABL in the cells of chronic myelocytic leukemia (CML) patients. The mRNA and protein expression of P-glycoprotein (Pgp) and the drug accumulation were assayed after acidifying the primary leukemia cells of patients or K562/DOX and K562/G01 cells. The effects of intracellular acidification of primary leukemia cells on the phosphorylation level changes of ERK1/2 and p38 MAPK were analyzed by Western blot. The results showed that the intracellular concentration of drugs in the advanced patients increased and the sensitivity of K562/DOX and K562/G01 cells to imatinib was enhanced after intracellular acidification or treatment with NHE1 inhibitor cariporide. With downregulation of intracellular pH, the phosphorylation of p38 MAPK decreased in advanced patients and the phosphorylation of ERK1/2 increased within 3 min and then decreased after 30 min. SB203580, the specific inhibitor of p38 MAPK, displayed a synergistic effect with the inhibitor of NHE1 to downregulate the mRNA and protein expression of Pgp. It is concluded that the inhibiton of NHE1 can significantly decrease the protein expression of Pgp in K562/DOX and K562/G01 cells, increase the accumulation of Rhodamine123 and doxorubicin in the cells of advanced patients and enhance the sensitivity of cells to imatinib in which the p38 MAPK signal transduction pathways involves.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Benzamides ; pharmacology ; Cation Transport Proteins ; antagonists & inhibitors ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Enzyme Inhibitors ; pharmacology ; Gene Expression Regulation, Leukemic ; Humans ; Imatinib Mesylate ; Imidazoles ; pharmacology ; K562 Cells ; MAP Kinase Signaling System ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Pyrimidines ; pharmacology ; Sodium-Hydrogen Exchanger 1 ; Sodium-Hydrogen Exchangers ; antagonists & inhibitors ; metabolism ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism