Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertrophy ; drug therapy ; enzymology ; genetics ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

OBJECTIVE: To evaluate the pharmacological effects of Liangyuan Pipagao on cough reflex and ciliary action. Liangyuan Pipagao is a compound preparation of traditional Chinese medicine. METHODS: Cough was induced by aerosol citric acid in guinea pigs and aerosol capsacin in mice. Excretion function of the airway in mice was determined by phenol red method. Ciliary movement function of frog esophagus was examined by a migration method of charcoal granules. RESULTS: Liangyuan Pipagao inhibited both the citric acid-induced cough in guinea pigs and capsacin-induced cough in mice. ID(50)value 2.64 g/kg (95%Cl1.12 approximately 6.19) and 11.40 g/kg (95%Cl5.76 approximately 22.58) respectively. Further, Liangyuan Pipagao increased phenol red excretion in mice airways and stimulated ciliary action of frog esophagusin a dose-dependent fashion. ED(50) value 7.70 g/kg (95%Cl 4.62 approximately 12.83) and EC(25) value 1.07 X 10(-4) (95% Cl 0.394 approximately 2.92x10(-4)) respectively. CONCLUSION: Liangyuan Pipagao a traditional Chinese medicine may have anti-tussive as well as expectorant actions.

OBJECTIVETo evaluate the value of adenosine tissue Doppler stress echocardiography on ischemic myocardium.

METHODSRoutine dosage (140 microgxkg(-1)xmin(-1) IV for 6 min) adenosine stress echocardiography was performed on 40 patients with chest pain for diagnosis of coronary artery disease (CAD). The images of left ventricular myocardial motion were acquired by tissue Doppler imaging (TDI) based on traditional 2D stress echocardiography before and 3 min, 6 min after adenosine stress (GE Vivid 7, USA). The myocardial velocity, strain and strain rate in 16 segments were offline measured and analyzed on ECHOPAC software. The results were compared with that of coronary angiography (CAG).

RESULTSCAG identified 18 CAD and 22 non-CAD patients with 159 ischemic segments and 465 non-ischemic segments. Adenosine significantly increased the systolic velocity (Sm), early diastolic velocity (Em), late diastolic velocity (Am), peak systolic strain (Smax), systolic strain rate (SRs), early diastolic strain rate (SRe) and late diastolic strain rate (SRa) both ischemic and non-ischemic segments (all P < 0.05). The baseline Sm and Em in ischemic segments were significant lower than non-ischemic segments [(3.16 +/- 1.20) cm/s vs (4.03 +/- 1.27) cm/s, P < 0.01; (3.75 +/- 1.67) cm/s vs (4.66 +/- 1.70) cm/s, P < 0.05]. At peak stress the differences in Sm and Em were more significant [(3.98 +/- 1.63) cm/s vs (5.07 +/- 1.52) cm/s; (4.51 +/- 2.32) cm/s vs (6.52 +/- 2.56) cm/s; P < 0.01]. The reductions on Smax and Se were more significant in ischemic segments compared those in non-ischemic segments (16.91% +/- 3.35% vs 19.56% +/- 5.47%, P < 0.01 and 9.53% +/- 2.89% vs 13.06% +/- 4.63%, P < 0.001). The biggest area under curve (AUC) in peak stress was seen in Se by ROC curve analysis (AUC = 0.740, with sensitivity 67% and specificity 83%).

CONCLUSIONParameters derived from TDI offer reliable and accurate information on ischemic myocardium during adenosine stress echocardiography.

Adenosine ; Diastole ; Echocardiography, Doppler ; Echocardiography, Stress ; Humans ; Myocardium

OBJECTIVETo identify two differentiation-associated proteins induced by rhIL-6 in M1 mouse myeloid leukemia cells.

METHODSProtein spots were excised from 2-D gels and digested in-gel with trypsin. The trypsin lysis products were first analyzed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) through peptide mass fingerprinting and then performed peptide sequencing by nano-electrospray ionization mass spectrometry/mass spectrometry (nano-ESI-MS/MS). The database search was finished with the Mascot search engine (http://www.matrixscience.co.uk) using the data processed through MaxEnt3 and MasSeq.

RESULTSThe two proteins were not revealed by peptide mass fingerprint using MALDI-TOF-MS, while they were respectively identified as Destrin and Putative protein after the sequence of their trypic peptides were obtained by the nano-ESI-MS/MS techniques.

CONCLUSIONNano-ESI-MS/MS technique can successfully identify the two differentiation-associated proteins induced by rhIL-6 and has great advantage in protein analysis.

Actin Depolymerizing Factors ; Amino Acid Sequence ; Animals ; Apoptosis ; Cell Transformation, Neoplastic ; drug effects ; Destrin ; Interleukin-6 ; analysis ; pharmacology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Mice ; Microfilament Proteins ; analysis ; Molecular Sequence Data ; Nanotechnology ; Recombinant Proteins ; pharmacology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Tumor Suppressor Proteins ; analysis

OBJECTIVETo explore the association of hepatocellular carcinoma (HCC) with environmental factors through analyzing birth order data from pedigree sibships.

METHODSA birth order study was conducted based on the methods of Greenwood and Haldane for 100 probands and 22 affected siblings from 100 pedigrees in a cohort which was followed up for 8 years in Haimen, Jiangsu, China.

RESULTSThe findings from the Greenwood method suggested that there was a tendency for cases of HCC to concentrate at lower birth orders of 1 to 3. With the effects of hepatitis B virus on the birth orders being controlled, the same tendency was also observed. The results from Haldane method showed that difference between actual value and expected value of 6A was more than the double standard deviation. Sigma 6A(actual value) = 1,806, Sigma 6A(expected value) = 1,988, the absolute value of (Sigma 6A(actual value) - Sigma 6A(expected value))/the square root of Sigma V6A = 2.1657 (0.02 < P < 0.05). The actual value of 6A was lower than the expected value of 6A suggesting that individuals at lower birth orders were at a higher risk of suffering from HCC. In addition, through data from ecologic research, there was a decreasing tendency of mortality of HCC within 10 years after the prevalence of tap water in Haimen city. The correlation coefficient by Spearman test was -0.818 (P < 0.01). The contribution of the quality of drinking water in the locality to the onset of HCC was found among people born in earlier period.

CONCLUSIONSThere was a tendency that the onset of HCC cases concentrating was at lower birth orders in this research, which was inconsistent with several reports of foreign authors' which showed a reverse tendency. According to the ecological results, it was suggested that long-term drinking of ditch-water was responsible for the tendency of cases of HCC concentrating at lower birth orders. There were also certain effects of environmental factors exerted on the onset of HCC being discovered.

Adult ; Birth Order ; Carcinoma, Hepatocellular ; epidemiology ; etiology ; China ; epidemiology ; Cohort Studies ; Family Health ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; epidemiology ; etiology ; Male ; Middle Aged ; Water Pollutants, Chemical ; adverse effects ; Water Supply

OBJECTIVETo determine the distribution of HCV genotypes among volunteer blood donors in Guangzhou.

METHODSSix-nine HCV RNA-positive samples were collected from volunteer blood donors in Guangzhou. NS5B fragments of HCV were amplified followed by DNA sequencing and phylogenetic analysis.

RESULTSHCV genotypes were determined for 67 samples. Among them, the subtypes 1b, 2a, 3a, 3b, 6a and 6n were detected at the frequencies of 37.31%, 4.48%, 7.46%, 4.48%, 44.78% and 1.49%, respectively.

CONCLUSIONHCV 1b and 6a are the most predominant two subtypes among volunteer blood donors in Guangzhou.

Blood Donors ; China ; Genotype ; Hepacivirus ; classification ; genetics ; isolation & purification ; Humans ; Phylogeny ; RNA, Viral ; genetics ; Sequence Analysis, DNA