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 value of adenosine tissue Doppler stress eehoeardiography on ischemic myocardium.Methods Routine dosage (140 μg· kg-1 · min-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 ochocardiography before and 3 min,6 rain 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).Results CAG identified 18 CAD and 22 non-CAD patients with 159 ischemie 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 iachemic and non-ischemic segments (all P＜0.05).The baseline Sm and Em in isehemic segments were significant lower than non-ischemic segments [(3.16±1.20) cm/svs (4.03+1.27) cm/s,P＜0.01;(3.75±1.67) cm/s vs (4.66±1.70) orals,P＜0.05].At peak stress the differences in Sm and Em were mere 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 isehemic segments compared those in non-isehemic 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 (AUG) in peak stress was seen in Se by ROC curve analysis (AUG=0.740,with sensitivity 67%and specificity 83%).Conclusion Parameters derived from TDI offer reliable and accurate information on ischemic myocardium during adenosine stress echocardiography.

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 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

The ubiquitin-proteasome pathway is the principal mechanism for the degradation of short-lived proteins in eukaryotic cells. Recently, proteasome inhibitors have been shown to induce apoptosis in many kinds of human malignant cells. In this study, the mechanism of apoptosis induced by proteasome inhibitor in leukemic cells was examined. Evaluated by MTT assay, treatment of leukemic cells with Z-LLL-CHO, a reversible proteasome inhibitor, induced cell death in a dose-dependent manner. Appearance of the sub G(0)/G(1) fraction of cell cycle observed in flow cytometry assay suggested the induction of apoptosis, which was further proved by typical DNA ladder and morphological study. Western blot displayed the cleavage of bcl-2 into a shortened 22 kD fragment and the decrease in the levels of caspase-3 precursor. A highly sensitive colorimetric assay was employed and the elevation of caspase-3 activity was detected in both cell lines after treatment with Z-LLL-CHO. By comparison, these results showed that the leukemic cell line M-07e and KG-1a, which both express bcl-2 at a relative high level, had different susceptibility to undergo apoptosis induced by Z-LLL-CHO, which possibly due to their different levels of expression and activation of caspase-3 precursor, as well as their different degree of bcl-2 cleavage after treated by Z-LLL-CHO.

Abnormalities, Multiple ; diagnosis ; surgery ; Anus, Imperforate ; surgery ; Colon ; abnormalities ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Ischium ; abnormalities ; Treatment Outcome ; Twins, Conjoined ; surgery

Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid, hypusine, which is formed post-translationally. Although eIF-5A and its hypusine modification are essential for eukaryotic cell viability, the precise physiological function of it has remained elusive. The aim of the study is to investigate how hypusine formation modulate the proliferation, cell cycle and apoptosis in leukaemia cells. The effects of 1,7-diaminoheptane (DAH), a potent inhibitor of deoxyhypusine synthase, on proliferation and cell viability of leukemia cell lines (Mo7e, TF-1 and THP-1) and MCF-7 cells, were investigated. eIF-5A expression level was detected after cell synchronization. The results showed that inhibition of cell proliferation by DAH was in a concentration-dependent manner while apoptosis was also induced at the same time. Upon treatment of the cell lines with DAH, cell growth was inhibited. Cell cycle analysis showed that DAH induced cell growth arrest at the G(1)-S boundary of the cell cycle. In synchronized MCF-7 cells, the expression level of eIF-5A peaked at G(1) phase but very low at S and G(2)/M phases. It is concluded that hypusine formation of eIF-5A exits in the regulation of cell cycle and the results suggest that eIF-5A is involved in the expression of proteins regulating transition of G(1)-S phase of cell cycle.
Cell Line, Tumor ; Diamines ; pharmacology ; G1 Phase ; physiology ; Humans ; Lysine ; analogs & derivatives ; metabolism ; Peptide Initiation Factors ; physiology ; RNA-Binding Proteins ; S Phase ; physiology