A long story: from suspicion to identification of non-diabetic renal diseases in patients with diabetic mellitus.
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Biomedical subjects
Publications and source records attributed to Gang Liu.
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DNA polymerase eta (PolH) is the product of the xeroderma pigmentosum variant (XPV) gene and a well-characterized Y-family DNA polymerase for translesion synthesis. Cells derived from XPV patients are unable to faithfully bypass UV photoproducts and DNA adducts and thus acquire genetic mutations. Here, we found that PolH can be up-regulated by DNA breaks induced by ionizing radiation or chemotherapeutic agents, and knockdown of PolH gives cells resistance to apoptosis induced by DNA breaks in multiple cell lines and cell types in a p53-dependent manner. To explore the underlying mechanism, we examined p53 activation upon DNA breaks and found that p53 activation is impaired in PolH knockdown cells and PolH-null primary fibroblasts. Importantly, reconstitution of PolH into PolH knockdown cells restores p53 activation. Moreover, we provide evidence that, upon DNA breaks, PolH is partially colocalized with phosphorylated ATM at gamma-H2AX foci and knockdown of PolH impairs ATM to phosphorylate Chk2 and p53. However, upon DNA damage by UV, PolH knockdown cells exhibit two opposing temporal responses: at the early stage, knockdown of PolH suppresses p53 activation and gives cells resistance to UV-induced apoptosis in a p53-dependent manner; at the late stage, knockdown of PolH suppresses DNA repair, leading to sustained activation of p53 and increased susceptibility to apoptosis in both a p53-dependent and a p53-independent manner. Taken together, we found that PolH has a novel role in the DNA damage checkpoint and that a p53 target can modulate the DNA damage response and subsequently regulate p53 activation.
Myosin VI is an unconventional motor protein, and its mutation is responsible for the familiar conditions sensorineural deafness and hypertrophic cardiomyopathy. Myosin VI is found to play a key role in the protein trafficking and homeostasis of the Golgi complex. However, very little is known about how myosin VI is regulated and whether myosin VI has a function in the DNA damage response. Here, we found that myosin VI is regulated by DNA damage in a p53-dependent manner and possesses a novel function in the p53-dependent prosurvival pathway. Specifically, we show that myosin VI is induced by p53 and DNA damage in a p53-dependent manner. We found that p53 directly binds to, and activates, the promoter of the myosin VI gene. We also show that the intracellular localization of myosin VI is substantially altered by p53 and DNA damage in a p53-dependent manner such that the pool of myosin VI in endocytic vesicles, membrane ruffles, and cytosol migrates to the Golgi complex, perinuclear membrane, and nucleus. Furthermore, we show that knockdown of myosin VI attenuates activation of p53 and impairs Golgi complex integrity, which makes myosin VI-deficient cells susceptible to apoptosis upon DNA damage. Taken together, we found a novel function for p53 in the maintenance of Golgi complex integrity and for myosin VI in the p53-dependent prosurvival pathway.
One polysaccharide deacetylase gene was cloned from Bacillus thuringiensis and designated pdaA. Disruption of pdaA did not affect vegetative growth and sporulation but obviously affected spore germination. When L-alanine was added into the spore suspension, the spores of the pdaA disruption mutant showed a slow and partial reduction in absorbance at OD600 and became phase pale gray compared with phase dark of the wild-type strain. In contrast with the outgrowing of wild-type spores after germination, the pdaA mutant spores were blocked at the stage of spore germination. Transmission electron micrographs revealed a significant difference between the pdaA mutant and the wild-type strain in the spore cortex. Introduction of the pdaA gene into the pdaA disruption mutant complemented the germination-negative phenotype. Reverse transcription--polymerase chain reaction showed that pdaA was transcribed after incubation for 10 h in CCY medium.
High purity one-dimensional ZnO nanobelts were synthesized by thermally evaporating commercial ZnS powders in a hydrogen-oxygen mixture gas at 1050 degrees C. It was found that these ZnO nanobelts had a single crystal hexagonal wurtzite structure growing along the [0001] direction. They had a rectangle-shaped cross-section with typical widths of 20 to 100 nanometers and lengths of up to hundreds of micrometers with lattice constants of a = 0.325 nm and c = 0.520 nm. The self-catalytic hydrogen-oxygen assisted growth of ZnO nanobelt is discussed. The photoluminescence (PL) characterization of the ZnO nanobelts shows strong near-band UV emission (about 383 nm) and one broad peak at 501 nm, which indicates that the ZnO nanobelts have good potential application in optoelectronic devices.
OBJECTIVE: To explore the vascular reactivity of abdominal aorta to agonists of alpha-adrenergic receptors in rat with high level transection of the spinal cord, and to quantify the expression of alpha-AR mRNA subtypes, in order to investigate relationship between alpha-AR and hyperreactivity of abdominal aorta. METHODS: Four weeks after transection of the spinal cord at the level of 4th thoracic vertebra, the rats were sacrificed, and abdominal aorta rings were adopted to assay sensitivity to phenylephrine and clonidine with isolated organ perfusion system. Alpha(1A)-AR, alpha(1B)-AR, alpha(1D)-AR, alpha(2A)-AR, alpha(2B)-AR, alpha(2C)-AR mRNA expressions were quantified by real time polymerase chain reaction (PCR). RESULTS: Compared with abdominal aorta, of rat with sham operation, reactivity of aorta of rat after transection of spinal cord to clonidine was significantly higher (P<0.05 or P<0.01), but difference of vascular reactivity to phenylephrine between them was not significant (P>0.05). Expressions of alpha(1A)-AR mRNA, alpha(1D)-AR mRNA, alpha(2A)-AR mRNA, alpha(2B)-AR mRNA, alpha(2C)-AR mRNA were significantly higher (P<0.05 or P<0.01), while the expression of alpha(1B)-AR mRNA did not vary significantly. CONCLUSION: Vascular hyperreactivity to agonist of alpha(2)-AR may be the mechanism of hyperreactivity of abdominal aorta in rat after transection of spinal cord. Although alpha(1)-AR mRNA expression is higher in aorta of rat with spinal cord injury, vascular hyperreactivity is not the result of upregulation of alpha(1)-AR sensitivity.
OBJECTIVE: To establish a mouse model of systemic lupus erythematosus(SLE) and to discuss the role of environmental factors in the pathogenesis of SLE. METHODS: Thirty 10-week-old female BALB/c mice were divided into the model group and control group. The model mice received a single intraperitoneal injection of 0. 5 mL of pristane, while control mice received a single i.p. injection of 0. 5 mL of 0.9% NS. Autoantibodies and proteinuria were detected before injection and monthly thereafter. 8 months after injection, all mice were bled to death. Kidneys were excised to observe the histopathologic evidence of glomerulonephritis. RESULTS: After pristane injection, antinuclear antibody(ANA) and anti-dsDNA antibody appeared in sera as early as 3 months and 4 months respectively. At 8 months, the incidence rates of ANA and anti-dsDNA antibody were 87.5% and 47.8% respectively. The protein concentration of urine in most mice was > or =1+ (300 mg/L). Light microscopy and immunofluorescence of kidney sections indicated glomerulonephritis. In control group, only one serum was ANA low-titer positive and another was anti-dsDNA antibody low-titer positive. The protein concentration of urine was < or = 1+. The histopathology and immunofluorescence showed no evidence of glomerulonephritis. Spearman correlation analysis indicated that anti-dsDNA antibody was correlated with proteinuria (r = 0.538, P = 0.003). CONCLUSION: The murine lupus model can be successfully established in female BALB/c mouse with a single i. p. injection of 0. 5 mL of pristane and the specific autoantibody anti-dsDNA for SLE has appeared in sera of BALB/c mice.
OBJECTIVE: To evaluate the value of X-ray and spiral computed tomography (SCT) in the diagnosis of Swyer-James syndrome (SJS). METHODS: A total of 28 patients, 12 males and 16 females, were studied retrospectively. Ages ranged from 11 to 57 years, the mean age was 32 years. All patients underwent inspiratory chest X-ray films, 5 with expiratory chest films and 1 with bronchogram. Furthermore, inspiratory and expiratory SCT scans were performed. The SCT findings were analyzed and compared with X-ray films. RESULTS: SCT demonstrated 56 lobes with hyperlucency and diminished vascularity. The size of 51 lobes were smaller and 5 were normal. X-ray films showed that hyperlucency was only in 29 lobes, in which 19 lobes were small-sized and the other 10 lobes normal. There were 56 lobes with air-trapping on expiratory SCT scans, but only 5 lobes with air-trapping on expiratory X-ray films. Bronchogram in 1 case demonstrated bronchiectasis and bronchiolitis obliterans. SCT showed 24 patients with bronchiectasis, 9 patients with tuberculosis, 10 patients with bronchiolitis, and 2 with segmental collapse. CONCLUSION: SCT scan is superior to chest radiography in the diagnosis and differential diagnosis of SJS.
OBJECTIVE: To observe the effects of cyclooxygenase (COX)-2 inhibitor on apoptosis of hypoxic myocardial cells in vitro. METHODS: The myocardial cells were obtained from new-born Wistar rats, and were dispersed to single cell with trypsin. The cells in 4th-6th passages were randomly divided into 24 samples (every sample contained 1 x 10(5) cells): normal control group, hypoxic myocardial cells control group; hypoxic myocardial cells+NS-398 (20 micromol/L) and hypoxic myocardial cells+aspirin (100 microg/L). During culture, oxygen was replaced by N(2), and the cells were cultivated in 5% CO(2)+95% N(2) at 37 centigrade for 6 hours. Either interventional medicine or same amount of dimethyl sulphoxide was added to the cells 30 minutes before hypoxia. The expression of COX-1 and COX-2 in cultured myocardial cells in vitro was examined with Western blot. The apoptosis percentage of cells in each group was examined with flow cytometry. After centrifuging the culture medium under low temperature, 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) and thromboxane B(2) (TXB(2)) were determined with radioimmunoassay (RIA). RESULTS: There was no significant difference in the expression of COX-1 among the groups. The expression of COX-2 was higher in all acute hypoxic myocardial cells groups compared with the control group. Neither aspirin nor NS-392 inhibited the expression of COX-2. The positive percentage of apoptosis of cultured myocardial cells ranked as follow: hypoxic+NS-398 group, hypoxic +aspirin group, hypoxic control group and normal control group. The differences of apoptosis rate between hypoxic+NS-398 group and other groups were significant (all P<0.05). The levels of TXB(2) in each group of cell medium ranked in the following order: normal control group, hypoxic +NS-398 group, hypoxic+aspirin group and hypoxic control group. The difference of TXB(2) level between hypoxic+NS-398 group and hypoxic control group was significant(P<0.05). The levels of 6-keto-PGF(1alpha) in each culture medium ranked in the following order: normal control group, hypoxic+aspirin group, hypoxic+NS-398 group and hypoxic control group. The difference between hypoxic+NS-398 group and hypoxic control group was significant (P<0.05). The ratio of TXB(2)/6-keto-PGF(1alpha) showed no significant difference (P>0.05) among groups. CONCLUSION: The results suggest that acute hypoxia could directly induce cultured myocardial cells to express COX-2, but do not effect expression of COX-1. Hypoxia could elevate the level of 6-keto-PGF(1alpha) and TXB(2) in culture medium. COX-2 inhibitor (NS-398) could lessen the elevation, but it could not change the ratio between TXB(2) and 6-keto PGF(1alpha). NS-398 could increase apoptosis percentage of hypoxic myocardial cells in vitro, and the effect is independent of other inflammatory cells.
BACKGROUND: Cardiac arrest (CA) during orthotopic liver transplantation (OLT) is rare but it threatens the lives of patients. The cause of perioperitive CA is not fully understood. We reported the occurrence of CA in 5 patients after unclamping of the vena cava and investigated the relationship between CA and associated variables. METHODS: Five patients with CA after graft reperfusion during OLT in our unit from November 1996 to September 2003 were retrospectively reviewed. Analyzed data included donor and recipient demographic data, and recipient operative and postoperative events. RESULTS: Five (2.1%) of 240 patients undergoing OLT experienced CA 5 minutes after graft reperfusion. Two patients died of resuscitation failure. Hyperkalemia and metabolic acidosis after revascularization were observed in some patients. The five patients had hypothermia and hypocalcemia, and one had pulmonary embolism. CONCLUSIONS: CA is one of the syndromes after reperfusion. Many factors such as hyperkalemia, acidosis or pulmonary embolism combined with hypothermia and hypocalcemia during the operation seem to contribute to the occurrence of CA.
OBJECTIVE: To reveal functional activity mapping during anticipation of dental pain with non-invasive fMRI technique, and to offer therapeutic possibilities for treating chronic oral facial pain psychologically. METHODS: 8 right handed patients with dentinalgia of the right maxillary bicuspid were included in this study. Block design was adopted, BOLD level during anticipation epoch (on) was contrasted with that of rest (off). Functional MRI scan covering the whole brain was carried out. The fMRI data were analyzed by SPM2 software with t-test to generate the activation map. RESULTS: Increased BOLD signals during dental pain anticipation were found dominantly on the left side in inferior, middle frontal gyrus/BA10,46, postcentral gyrus/BA2,3, middle frontal gyrus/BA8, precentral gyrus/BA44 and cerebellum. CONCLUSION: Anticipation of dental pain by itself can activate brain regions, especially prefrontal areas, SI, SMA and cerebellum. The results of pain anticipation are consisted with previous studies except that there is no activation in insula and cingulate cortex. Sensory, motor, cognitive and emotional activation in dental pain anticipation may indicate that brain nociceptive network can be affected by hint.
OBJECTIVE: To investigate the effects of E-cadherin on the biologic behavior of SUM149, an inflammatory breast cancer cell line. METHODS: SUM149 cells were transfected with dominant-negative mutant E-cadherin expressing plasmid. The positive clones with higher expression of dominant-negative E-cadherin mutant were identified by RT-PCR and fluorescent flow cytometry method. The differences in cell growth, proliferation and invasion between positive clones and controls were compared. RESULTS: Whereas the proliferation of positive clones was of no change, compared with controls, the ability of invasion was decreased and the mRNA levels of MMP-1 and MMP-9 were downregulated. Gelatin zymography analysis also confirmed the decreasing expression of MMP-9 in the positive clones. CONCLUSION: In this cell line model, down-regulation of E-cadherin can inhibit the ability of invasion of this inflammatory breast cancer cell line.
OBJECTIVE: To analyze the maternal mortality ratio (MMR) of residential and migrant women in Beijing. METHODS: A retrospective study from 1995 to 2004 was performed to analyze data from the maternal death cases. RESULTS: The MMR of resident and migrant of Beijing from 1995 to 2004 were 17.9 and 51.3 per ten thousand respectively. The main reasons of maternal deaths among residents were embolism (21.2%), hypertensive disorder complicating pregnancy (18.3%), postpartum hemorrhage (14.4%) and ectopic pregnancy/heart disease (9.6%). The main reasons of migrant maternal deaths were postpartum hemorrhage (25.2%), embolism (19.7%), hypertensive disorder complicating pregnancy (17.3%) and liver disease (9.5%). The avoidable deaths were accounted for 18.9%. CONCLUSION: The MMR in Beijing local residents was close to that in developed countries. To further reduce MMR in Beijing would depend on the better administration of related issues among floating population. Poor quatily delivery must be banned together with strengthening the training programs on health workers. It is also important to improve the knowledge and skills of medical staff for rescuing the complications of pregnancy and ectopic pregnancy.
Ghrelin woas recently de-orphaned as an endogenous ligand of growth hormone secretagogue receptor (GHS-R), and is implicated as a short-term meal initiator and a long-term energy balance regulator. Administration of ghrelin causes increases in food intake and body weight in both rodents and humans. Inhibiting its actions with GHS-R anti-sense oligonucleotides, anti-ghrelin antibodies, and peptide antagonists leads to decreased food intake and weight loss in rodents. Despite the much-publicized promise of providing a novel approach for anti-obesity treatment, limited progress has been made in developing small-molecule GHS-R antagonists and no such compound has been advanced to clinical trials. This review will summarize the recent progress in small-molecule GHS-R antagonists and offer some insight into this area of research based on the experience at Abbott Laboratories.
OBJECTIVE: To clone and express Cox7a2, one mitochondrial respiratory chain related gene, and to identify its recombinant protein. METHODS: The coding region of Cox7a2 was amplified from primary cultured mouse Leydig cells by RT-PCR. The PCR product was cloned into pGEX4T-1 vector by BamH I and EcoR I sites, and confirmed by DNA sequencing. The recombinant fusion protein vector was transformed and expressed into BL21. The recombinant fusion protein was identified by Western blotting. RESULTS: The entire coding region of Cox7a2 was cloned and expressed. The fusion protein was identified by anti-GST monoclonal antibody using Western blotting. CONCLUSION: The cloning of Cox7a2 and the expression of the recombinant protein would help to study the detailed function of Cox7a2, one respiratory chain related and highly differently expressed gene in the tissues of aging testes.
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Truffles, which belong to ascomycetes, are rare wild growing edible mushrooms; their fruit body contains high nutritive value composition, and their polysaccharide constituents have potential medical applications. In the present paper, Fourier transform infrared (FTIR) spectroscopy was used for obtaining vibrational spectra of mushrooms of truffles growing in mountains of Yunnan province, southwest China. The results show that the mushrooms exhibit characteristic spectra. The two strongest absorption bands appear at about 1 077 and 1 042 cm(-1), respectively. The spectra exhibit complicated patterns between 1200 and 750 cm(-1), which may be used as fingerprints to discriminate different species of truffles. Great changes were also found between mold and healthy truffles, showing major differences observed in the bands of protein. In addition, some vibrational-spectrum differences were observed among the same species of truffles from different growing areas. It is showed that FTIR can provide valuable information about the chemical constituents of intact truffles prior to any extraction method is used.
OBJECTIVE: To study the expression and localization of ATP50 by construction of ATP50-pEYFP-N1 in primary cultured mouse Leydig cells. METHODS: Primary cultured mouse Leydig cells were confirmed by 3B-HSD staining. ATP50 was cloned into pEYFP-N1 between Bam HI and Eco RI sites. Cell-transfection and living-cell fluorescence imaging microscopy were employed to investigate the sub-cellular localization of YFP-ATP50 in TM3 mouse Leydig cells. RESULTS: ATP50 green fluorescent protein was well co-localized with red fluorescence mitochondrion marker-Mitotracker in TM3 mouse Leydig cells. CONCLUSION: ATP50 was expressed in primary cultured mouse Leydig cells. The fluorescent expression vector of ATP50 was constructed successfully and YFP-ATP50 was located in mitochondria in TM3 mouse Leydig cells, which provided a useful clue for further research on the steroidogenesis dysfunction in aging males.