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Biomedical subjects

D Ji

Publications and source records attributed to D Ji.

14 recordsLinked to original sources

Downregulation of cAMP-dependent protein kinase inhibitor gamma is required for BMP-2-induced osteoblastic differentiation.

Osteoblasts, normally derived from undifferentiated mesenchymal precursor cells, acquire their characteristic phenotypes when induced by various regulatory factors, one of which is bone morphogenetic protein-2 (BMP-2). Our recent studies suggest that expression of cAMP-dependent protein kinase (PKA) inhibitor G (PKIG) is down-regulated as human mesenchymal stromal cells (MSCs) undergo BMP-2-induced osteoblastic differentiation. This raises our hypothesis that the PKA pathway is involved in osteogenesis. In this report, we demonstrated that PKIG in human MSCs and its murine homologue PKA inhibitor gamma (PKIgamma) in murine pre-myoblast C2C12 cells were down-regulated when these cells were treated with BMP-2. On the contrary, the PKA activity of C2C12 cells was increased upon BMP-2 treatment. Overexpression of PKIgamma in C2C12 cells was shown to repress mRNA expression of early osteoblastic markers osterix and type I collagen while inhibiting the PKA activity. This correlated with decreased alkaline phosphatase (ALP) activities. Furthermore, inhibition of the PKA activity using its specific inhibitor KT5720 was found to have the similar effect, whereas 8-Br-cAMP, a specific PKA activator, accelerated BMP-2-induced ALP activities. Finally, this study showed that BMP-2 treatment promoted activities of transcription regulatory elements including cAMP response element (CRE) and activating protein-1 (AP1). This effect of BMP-2 was diminished in PKIgamma-overexpressed C2C12 cells. Taken together, our results indicate that the activation of the PKA pathway may be one of key BMP-2-activated signaling events that lead to osteogenesis and that downregulation of PKIgamma may be prerequisite for the PKA activation during the osteoblastic differentiation of precursor cells.

Alkaline Phosphatase↗

[Cloning of genes transactivated by nonstructural protein 4A of hepatitis C virus.].

BACKGROUND: To construct a subtractive cDNA library of genes transactivated by NS4A protein of hepatitis C virus with suppression subtractive hybridization technique (SSH). METHODS: The mRNA was isolated from Hep G2 cells transfected pcDNA3.1(-)-NS4A and pcDNA3.1(-) empty vector, respectively, then the cDNA was synthesized. SSH method was employed to analyze the differentially expressed RNA sequence between the two groups. The twice enriched PCR products were subcloned into T/A vectors to set up the subtractive library. Amplification of the library was carried out with E.coli strain JM109. The cDNA was sequenced and analyzed in comparison with those in GenBank with Blast search after PCR. RESULTS: The amplified library contained 36 positive clones. Colony PCR showed that 36 clones contained 200-1000 bp inserts. Sequence analysis was performed in 25 clones, and the full length sequences were obtained with bioinformatics method. Altogether 20 kinds of coding sequences were achieved, which consisted of 18 kinds of known and 2 kinds of unknown ones. The obtained sequences may be target genes transactivated by NS4A protein of HCV, among which some genes coding for proteins involved in cell cycle regulation, cell apoptosis, signal transduction pathway and tumour development. CONCLUSION: A subtractive library of genes transactivated by NS4A protein of HCV was constructed successfully, which brought some new clues for studying the biological functions and pathogenesis of the viral proteins.

Cloning, Molecular↗

Decomposition of 2-naphthalenesulfonate in aqueous solution by ozonation with UV radiation.

This study investigates the ozonation of 2-naphthalenesulfonate (2-NS) combined with ultraviolet (UV) radiation. Naphthalenesulfonic acids are of importance as dye intermediates for the dye and textile auxiliary industries. Its derivatives, such as 2-NS, have been found in rivers and tannery effluents causing pollution problems. Thus, the 2-NS is of concern for the aquatic pollution control especially in the surface and waste waters. Ozonation combined with UV radiation is employed for the removal of 2-NS in the aqueous solution. Semibatch ozonation experiments were proceeded under different reaction conditions to study the effects of ozone dosage and UV radiation on the oxidation of 2-NS. The concentrations of 2-NS and sulfate are analyzed at specified time intervals to elucidate the decomposition of 2-NS. In addition, values of pH and oxidation reduction potential are continuously measured in the course of experiments. Total organic carbon is chosen as a mineralization index of the ozonation of 2-NS. The mineralization of 2-NS via the ozonation is remarkably enhanced by the UV radiation. These results can provide useful information for the proper removal of 2-NS in the aqueous solution by the ozonation with UV radiation.

Arylsulfonates↗

Synaptic plasticity and nicotine addiction.

Nicotine, the main addictive component of tobacco, activates and desensitizes nicotinic acetylcholine receptors (nAChRs). In that way, nicotine alters normal nicotinic cholinergic functions. Among the myriad of psychopharmacological effects that underlie the addiction process, nicotine influences nAChR participation in synaptic plasticity. This influence has particular importance in the mesocorticolimbic dopamine system, which serves during the reinforcement of rewarding behaviors.

Animals↗

Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity.

This study reveals mechanisms in the mouse hippocampus that may underlie nicotinic influences on attention, memory, and cognition. Induction of synaptic plasticity, arising via generally accepted mechanisms, is modulated by nicotinic acetylcholine receptors. Properly timed nicotinic activity at pyramidal neurons boosted the induction of long-term potentiation via presynaptic and postsynaptic pathways. On the other hand, nicotinic activity on interneurons inhibited nearby pyramidal neurons and thereby prevented or diminished the induction of synaptic potentiation. The synaptic modulation was dependent on the location and timing of the nicotinic activity. Loss of these synaptic mechanisms may contribute to the cognitive deficits experienced during Alzheimer's diseases, which is associated with a loss of cholinergic projections and with a decrease in the number of nicotinic receptors.

2-Amino-5-phosphonovalerate↗

A retrospective study of continuous renal replacement therapy versus intermittent hemodialysis in severe acute renal failure.

OBJECTIVE: To investigate the efficacy of continuous renal replacement therapy (CRRT) versus intermittent hemodialysis (IHD) in patients with severe acute renal failure (ARF). METHODS: One hundred and ninety-three severe ARF patients who received renal support between December 1978 and December 1998 were involved in this study. Of them, 101 (52.3%) were treated with CRRT (CRRT group), and 92 (47.7%) with IHD (IHD group). RESULTS: Sixty (59.4%) patients in the CRRT group got through the acute phase of disease and 41 (40.6%) patients did not survive while in the IHD group 59 (64.1%) patients survived and 33 (35.9%) patients did not. No significant difference in survival rate was found between the two groups. 24 of 64 patients (37.5%) in the CRRT group with multiple organ dysfunction syndrome (MODS) survived, while in the IHD group, 8 out of 44 (27.3%) survived, their survival rate was much lower than that in the CRRT group. Patients in CRRT group were more severely ill, as manifested by lower mean arterial pressure, higher APACHE II score, more dysfunctioned organs and requiring mechanical ventilation and vasopressor support as compared with patients in the IHD group, CRRT was found to improve hemodynamic stability with a better fluid balance and control of biochemical status, increased nutritional intake and a shorter duration of acute renal failure (P < 0.05). CONCLUSION: CRRT perhaps may be the best choice in the treatment of severe ARF patients, for it can offer several distinct advantages compared to IHD. These may contribute to improving the survival rate of ARF patients, particularly those that are critically ill patients.

Acute Kidney Injury↗

[The effects of dialysate and ultrafiltration flow rate on solute clearance during continuous renal replacement therapy].

OBJECTIVE: To study the solute clearance during various forms of continuous renal replacement therapy(CRRT) and test the formulas that allow the prediction of the influence of dialysate and ultrafiltration flow rate on small solute removal during CRRT. METHOD: Five patients with acute renal failure were included in the study and were treated by venovenous CRRT using the PRISMA predilution system. Solute clearance of urea nitrogen(UN), creatinine(Cr), uric acid(Ua), phosphate(P) and beta(2)-microglobulin(beta(2)-M) were evaluated during CRRT with different dialysates and ultrafiltration flow rates. RESULTS: The determined clearance of small molecular solutes during continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis(CVVHD) was similar with the following formulas: K(UF) = (Q(UF)/60) x Q(B)/(Q(B) + Q(UF)/60) (in CVVH), Kd = Q(D)/60 (in CVVHD), where K is the clearance, Q(B), Q(D) and Q(UF) are blood, dialysate and ultrafiltration flow rates, respectively. There was very significant correlation between calculated values of K(UF) and observed clearances of small solutes such as UN, Cr, Ua and P during CVVH, between calculated values of Kd and observed clearances of UN, Cr, Ua but not P during CVVHD (P < 0.001). Clearances of UN, Cr, Ua and P during CVVHD were greater than those during CVVH, but clearance of beta(2)-M during CVVHD was less than that during CVVH. Interaction between convection and diffusion was found during continuous venovenous hemodiafiltration (CVVHDF). CONCLUSIONS: The previous formulas can provide with the prediction of the clearance of small molecular solutes during CVVH and CVVHD. The present results demonstrate that diffusion is more efficient in removing small solutes than convection but less efficient in removing large solutes than convection. There is interaction between convection and diffusion during CVVHDF.

Acute Kidney Injury↗

Interaction of oxo-bridged vanadium(III) phenanthroline and bipyridine dimers with DNA.

Cationic mu-oxo V(III) dimers of the type [V2OL4Cl2]2+ (L = 1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline; or 2,2'-bipyridine) are shown to interact very strongly with DNA and to lead ultimately to its degradation. Spectroscopic binding studies, electrophoreses, DNA melting temperature experiments, and other tests on the parent 1,10-phenthroline complex all yield results consistent with tight binding. However, the exact nature of the binding--i.e., intercalative, groove binding, electrostatic, or covalent--remains unclear. Resonance Raman spectroscopy is found to be a powerful method for studying the interaction of these mu-oxo V(III) dimers with DNA and shows that in frozen aqueous solution, the parent complex [V2O(phen)4Cl2]2+ undergoes initial aquation, followed by the reaction of the aquated species with the DNA. Once the V(III) dimer is bound to the DNA, redox takes place, leading to the formation of alkaline-sensitive lesions. Hydrogen peroxide is implicated as a partner in this redox event, based on the effects of the enzymes SOD and catalase.

Animals↗

Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons.

Nicotinic acetylcholine receptors (nAChRs) are expressed in the hippocampus, and their functional roles are beginning to be delineated. The effect of nAChR activation on the activity of both interneurons and pyramidal neurons in the CA1 region was studied in rat hippocampal slices. In CA1 stratum radiatum with muscarinic receptors inhibited, local pressure application of acetylcholine (ACh) elicited a nicotinic current in 82% of the neurons. The majority of the ACh-induced currents were sensitive to methyllycaconitine, which is a specific inhibitor of alpha7-containing nAChRs. Methyllycaconitine-insensitive nicotinic currents also were present as detected by a nonspecific nAChR inhibitor. The ACh-sensitive neurons in the s. radiatum were identified as GABAergic interneurons by their electrophysiological properties. Pressure application of ACh induced firing of action potentials in approximately 70% of the interneurons. The ACh-induced excitation of interneurons could induce either inhibition or disinhibition of pyramidal neurons. The inhibition was recorded from the pyramidal neuron as a burst of GABAergic synaptic activity. That synaptic activity was sensitive to bicuculline, indicating that GABA(A) receptors mediated the ACh-induced synaptic currents. The disinhibition was recorded from the pyramidal neuron as a reduction of spontaneous GABAergic synaptic activity when ACh was delivered onto an interneuron. Both the inhibition and disinhibition were sensitive to either methyllycaconitine or mecamylamine, indicating that activation of nicotinic receptors on interneurons was necessary for the effects. These results show that nAChRs are capable of regulating hippocampal circuits by exciting interneurons and, subsequently, inhibiting or disinhibiting pyramidal neurons.

Acetylcholine↗

Suppression of morphine withdrawal by electroacupuncture in rats: dynorphin and kappa-opioid receptor implicated.

Our previous work has demonstrated that 100-Hz electroacupuncture (EA) or 100-Hz transcutaneous electrical nerve stimulation (TENS) was very effective in ameliorating the morphine withdrawal syndrome in rats and humans. The mechanism was obscure. (1) Rats were made dependent on morphine by repeated morphine injections (5-140 mg/kg, s.c., twice a day) for eight days. They were then given 100-Hz EA for 30 min 24 h after the last injection of morphine. A marked increase in tail flick latency (TFL) was observed. This effect of 100-Hz EA could be blocked by naloxone (NX) at 20 mg/kg, but not at 1 mg/kg, suggesting that 100-Hz EA-induced analgesia observed in morphine-dependent rats is mediated by kappa-opioid receptors. (2) A significant decrease of the concentration of dynorphin A (1-17) immunoreactivity (-ir) was observed in the spinal perfusate in morphine-dependent rats, that could be brought back to normal level by 100-Hz EA. (3) 100-Hz EA was very effective in suppressing NX-precipitated morphine withdrawal syndrome. This effect of EA could be prevented by intrathecal administration of nor-BNI (2.5 micrograms/20 microliters), a kappa-opioid receptor antagonist, or dynorphin A (1-13) antibodies (25 micrograms/20 microliters) administered 10 min prior to EA. In conclusion, while the steady-state spinal dynorphin release is low in morphine-dependent rats, it can be activated by 100-Hz EA stimulation, which may be responsible for eliciting an analgesic effect and ameliorating morphine withdrawal syndrome, most probably via interacting with kappa-opioid receptor at spinal level.

Animals↗

[Treatment of severe acute renal failure with continuous renal replacement therapy].

OBJECTIVE: To present the experience in 101 severe acute renal failure (ARF) patients treated with continuous renal replacement therapy (CRRT) in our hospital from May 1986 to January 1999. METHODS: Patients'age, sex, previous health status and characteristics of renal failure were recorded. The acute physiology and chronic health evaluation II (APACHE II) score were calculated before CRRT treatment. RESULTS: 60 (59.4%) patients survived the acute phase of their illness, and 41 (40.6%) patients died. In the survival group, there were significantly less patients with pre-renal causes of renal failure and refractory course of uremia, low APACHE II score before treatment and less need of mechanical ventilation or vasoactive supporting. No difference was found in the percentage of oliguria between the survival and total group. CONCLUSION: CRRT is the treatment of first choice in ARF, especially in those complicated cases with severe parachymal renal diseases. The patients' age, previous health status, APACHE II score before CRRT, delayed occurrence of acute renal failure, need of mechanical ventilation and vasoactive drugs were predictors of a worse prognosis in severe ARF patient. The prognosis of renal type ARF patients improved with CRRT.

Acute Kidney Injury↗

Effect of chitosan on renal function in patients with chronic renal failure.

The effects of chitosan have been investigated on eighty patients with renal failure undergoing long-term stable haemodialysis treatment. The patients were tested after a control treatment period of 1 week. Half were fed 30 chitosan tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan effectively reduced total serum cholesterol levels (from 10.14 +/- 4.40 to 5.82 +/- 2.19 mM) and increased serum haemoglobin levels (from 58.2 +/- 12.1 to 68 +/- 9.0 g L-1). Significant reductions in urea and creatinine levels in serum were observed after 4 weeks of chitosan ingestion. The feeling of physical strength, the appetite and the sleep of patients in the treatment group had improved significantly after 12 weeks of ingestion, compared with those of patients in the control group. During the treatment period, no clinically problematic symptoms were observed. These data suggest that chitosan might be effective treatment for renal failure patients, although the mechanism of the effect should be investigated further.

Administration, Oral↗

Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat with subtotal nephrectomy.

OBJECTIVE: To investigate 1) the glomerular mRNA expression and protein activity of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs and MDA levels, in the chronic phase of subtotal nephrectomized rats. METHODS: The adult male Spregue-Dawley rats were randomly divided into three groups at the first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8), group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1% in the rat chow. At the 12th week after P was administrated, all of the rats were sacrificed to remove left kidney for the determination of glomerular level of MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern blot analysis as well as a histological examination. RESULTS: In 5/6 Nx, serum cholesterol, proteinuria increased and creatinine clearance decreased progressively with age as compared with that in sham. Those abnormalities as well as glomerulosclerosis index (GI) ameliorated with the administration of probucol at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs 5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx]. The probucol therapy also significantly improved the decrease of glomerular Mn-SOD and GSH-Px both at mRNA level and protein activity and the increase of glomerular MDA content. CONCLUSIONS: We demonstrated a deficiency of glomerular AOEs in the chronic phase of remnant kidney, which may contribute to the progression of renal injury. The protective effects of probucol on both renal functional impairment and the development of glomerulosclerosis may be partially associated with improving surviving glomerular AOEs.

Animals↗