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Biomedical subjects

Feng Cheng

Publications and source records attributed to Feng Cheng.

At least 19 recordsLinked to original sources

Late onset of severe graft-versus-host disease following liver transplantation.

Graft versus host disease (GVHD) is an uncommon but lethal complication following liver transplantation that results from the engraftment of T lymphocytes associated with the liver graft. It usually occurs 2 to 6 weeks after the procedure. We herein report a case of late onset of severe GVHD 4 months after cadaveric liver transplantation for hepatocellular carcinoma in a 54-year-old woman, which was characterized by refractory diarrhea and abdominal pain. Moreover we discuss risk factors of GVHD including the recipient age and cytomegalovirus (CMV) infection.

Abdominal Pain↗

Early experiences on living donor liver transplantation in China: multicenter report.

BACKGROUND: Because of the lack of brain death laws in China, the proportion of cadaveric organ donation is low. Many patients with end-stage liver disease die waiting for a suitable donor. Living donor liver transplantation (LDLT) would reduce the current discrepancy between the number of patients on the transplant waiting list and the number of available organ donors. We describe the early experience of LDLT in the mainland of China based on data from five liver transplant centers. METHODS: Between January 2001 and October 2003, 45 patients with end-stage liver disease received LDLT at five centers in China. The indication and timing, surgical techniques and complications, nonsurgical issues including rejection, infection, and advantages of LDLT in the series were reviewed. Actuarial patient and graft survival rates were calculated by using the Kaplan-Meier product-limit estimate. Statistical analysis was completed by using SPSS 10.0. RESULTS: All LDLT recipients were cirrhotic patients, except for one man with fulminant hepatic failure. Among the 45 cases of LDLT, 35 (77.8%) were performed in one center (the First Affiliated Hospital of Nanjing Medical University). The overall 1 and 3 year survival rate of the recipients was 93.1% and 92.0%, respectively. Of the 45 LDLT donors, there were 3 cases of biliary leakage, 2 subphrenic collections, 1 fat liquefaction around the incision and 1 biliary peritonitis after T tube removal. All donors recovered completely. CONCLUSIONS: LDLT provides an excellent approach to addressing the problem of donor shortage in China even though the operation is complicated, uncompromising and difficult with respect to the safety of the donors and receptors. Despite early technical hurdles having been overcome, perfection of technique is still necessarily. At present, LDLT is a good choice for the patients with irreversible liver disease.

Adolescent↗

[Adult-to-adult living donor liver transplantation for decompensated end-stage liver diseases].

OBJECTIVE: To summarize our clinical experience in adult-to-adult living donor liver transplantation (ALDLT). METHODS: Clinical data of 12 patients with ALDLT performed in our center from September 2000 to June 2005 were analyzed, retrospectively. RESULTS: Left lobe (segments II, III, IV, including the middle hepatic veins) transplantation was performed in 3 patients and right lobe (segments V, VI, VII, VIII, with or without the middle hepatic veins) transplantation was performed in 9 patients. Donors: There were no operative deaths. The median operative time was 6.20+/-1.40 hours and their blood loss ranged from 300 ml to 1200 ml. Postoperative complications included biliary fistula (1 donor) and wound fat liquefaction (1 donor). During a 6-12 months follow-up, no long-term complications were found. Recipients: The operating time ranged from 5 to 11 hours and their blood loss ranged from 800 to 7000 ml. Modified outflow reconstruction, microvascular reconstruction of the hepatic artery and duct-to-duct biliary reconstruction were done during the recipient operations. The median cold ischemia time was 1.90+/-0.50 hours. The median anhepatic phase of recipients was 1.63+/-0.43 hours. Graft/recipient weight ratio (GRWR) was (1.20+/-0.26)%. One recipient presented a postoperative complication of biliary fistula and another recipient died 1 month after the operation from serious infection. The other 11 recipients had long-term survivals. CONCLUSION: ALDLT is an effective treatment for decompensated end-stage liver disease patients and is relatively safe for the donors.

Adult↗

[Adult to adult living donor liver transplantation for decompensated end stage liver disease].

OBJECTIVE: To summarize the clinical experience and some principal surgical techniques of adult to adult living donor liver transplantation (ALDLT). METHODS: The clinical data of 9 patients receiving ALDLT from September 2000 to September 2004 in liver transplantation center in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively. The left lobe (segments II, III, IV, including the middle hepatic veins) was transplanted in 3 patients, and the right lobe (segments V, VI, VII, VIII, not including the middle hepatic veins) was transplanted in 6 patients. RESULTS: There was no operative death in donors. The median operative time was (6.2+/-1.4) hours. The blood loss ranged from 300 to 1,200 ml. Postoperative complications included biliary fistula (1 donor) and wound fat liquefaction (1 donor). They were followed up for 6-12 months, and no long term complications were found. In recipients, the operating time ranged from 5 to 11 hours. The blood loss ranged from 800 to 7,000 ml. Modified outflow reconstruction method, microvascular reconstruction of the hepatic artery and duct to duct biliary reconstruction were performed in recipients. The median cold ischemic time of the grafts was (1.9+/-0.5) hours. The mean non hepatic stage of recipients was (98+/-26) minutes. Graft/recipient weight ratio (GRWR) was (1.20+/-0.26)%. One recipient presented postoperative complication of biliary fistula. One recipient died of serious infection 1 month postoperatively. The other 8 recipients enjoyed longterm survival. CONCLUSION: The procedure of ALDLT is an effective method in the treatment of decompensated end stage liver disease, and it is relatively safe for the donor. Reconstruction of vessels is the key surgical technique in the operative procedure.

Adult↗

A solid state 13C NMR, crystallographic, and quantum chemical investigation of chemical shifts and hydrogen bonding in histidine dipeptides.

We report the first solid-state NMR, crystallographic, and quantum chemical investigation of the origins of the 13C NMR chemical shifts of the imidazole group in histidine-containing dipeptides. The chemical shift ranges for Cgamma and Cdelta2 seen in eight crystalline dipeptides were very large (12.7-13.8 ppm); the shifts were highly correlated (R2= 0.90) and were dominated by ring tautomer effects and intermolecular interactions. A similar correlation was found in proteins, but only for buried residues. The imidazole 13C NMR chemical shifts were predicted with an overall rms error of 1.6-1.9 ppm over a 26 ppm range, by using quantum chemical methods. Incorporation of hydrogen bond partner molecules was found to be essential in order to reproduce the chemical shifts seen experimentally. Using AIM (atoms in molecules) theory we found that essentially all interactions were of a closed shell nature and the hydrogen bond critical point properties were highly correlated with the N...H...O (average R2= 0.93) and Nepsilon2...H...N (average R2= 0.98) hydrogen bond lengths. For Cepsilon1, the 13C chemical shifts were also highly correlated with each of these properties (at the Nepsilon2 site), indicating the dominance of intermolecular interactions for Cepsilon1. These results open up the way to analyzing 13C NMR chemical shifts, tautomer states (from Cdelta2, Cepsilon1 shifts), and hydrogen bond properties (from Cepsilon1 shifts) of histidine residue in proteins and should be applicable to imidazole-containing drug molecules bound to proteins, as well.

Carbon Isotopes↗

Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human.

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002-2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.

Amino Acid Substitution↗

Living-related liver transplantation for Wilson's disease.

Orthotopic liver transplantation has been applied to the treatment of Wilson's disease (WD), living-related liver transplantation (LRLT) has also been indicated for WD with increasing frequency. Between January 2001 and November 2003, 22 LRLTs were performed on patients (19 pediatric, three adults) with WD in liver transplantation center. Two patients were transplanted because of a presentation coexistent with fulminant hepatic failure. Twenty presented with chronic advanced liver disease with (n = 9) or without (n = 11) associated neurologic manifestations. All the recipients had low serum ceruloplasmin levels with a mean value of 12.8 +/- 3.2 mg/dl before transplantation and increased to an average of 26.0 +/- 3.6 mg/dl after LRLT at the latest evaluation. The survival patients with neurologic manifestations such as tremor, dysarthia, dysphagia, dystonia and sialorrhea had improved after LRLT. This suggests that LRLT not only resolves the hepatic but also ameliorates the neurologic consequences of WD.

Adolescent↗

Investigation of elemental content distribution in femoral head slice with osteoporosis by SRXRF microprobe.

A synchrotron radiation X-ray fluorescence microprobe analysis technique was used to scan a slice of the femoral head from its periphery to its center, via cartilage, compact, and spongy zones in order to determine the distribution and the way inorganic substances are lost in bone tissue. The sample preparation and experimental apparatus are described in detail. The quantitative computerized tomography of elemental distribution, such as Ca, P, K, Fe, Zn, Sr, and Pb in bone slice tissue, including cartilage, substantial compact, and substantial spongy, is investigated. Combined with the correlation among P, K, Zn, Sr, and Ca, the route of loss of minerals and the physiological functions of some metal elements in bone are also discussed.

Adult↗

[Effects of YM injection on oxidative stress injury in renal warm ischemia/reperfusion].

OBJECTIVE: This study was undertaken to determine whether YM injection would attenuate warm I/R injury in mice. METHODS: Renal warm I/R was induced in C57BL/6 males, and the mice were sacrificed 24 hours post-reperfusion. YM was given intraperitoneally 12 hours and 30 min before I/R. The effects of YM on oxidative stress and proinflammatory mediators caused by renal I/R injury were assayed. RESULTS: Renal I/R caused severe injuries in the kidneys of mice. In the presence of YM at doses of 5, 15 and 25 mg/kg, the kidney malondialdehyde (MDA) content reduced by 16.6%, 25.0% and 35.5% respectively, and the kidney superoxide dismutase (SOD) activities were elevated by about 38.7%, 48.3% and 76.1% respectively. ICAM-1 expression was dramatically suppressed in the presence of YM (25 mg/kg). CONCLUSION: YM attenuates the renal warm I/R injury at least partially via decreasing the neutrophils infiltration and suppressing the over-expression of adhesion molecules.

Animals↗

Inhibition of isoprene biosynthesis pathway enzymes by phosphonates, bisphosphonates, and diphosphates.

We have investigated the docking of a variety of inhibitors and substrates to the isoprene biosynthesis pathway enzymes farnesyl diphosphate synthase (FPPS), isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IPPI) and deoxyxylulose-5-phosphate reductoisomerase (DXR) using the Lamarckian genetic alogorithm program, AutoDock. The docked ligand structures are predicted with a approximately 0.8 A rms deviation from the structures determined crystallographically. The errors found are a function of the number of atoms in the ligand (R = 0.91, p < 0.0001) and, to a lesser extent, on the resolution of the crystallographic structure (R = 0.70, p < 0.008). The structures of three isoprenoid diphosphates docked to the FPPS enzyme reveal strong electrostatic interactions with Mg(2+), lysine and arginine active site residues. Similar results are obtained with the docking of four IPPI inhibitors to the IPPI enzyme. The DXR substrate, deoxyxylulose-5-phosphate, is found to dock to Mn(2+)-NADPH-DXR in an almost identical manner as does the inhibitor fosimdomycin to Mn(2+)-DXR (ligand heavy atom rms deviation = 0.90 A) and is poised to interact with NADPH. Bisphosphonate inhibitors are found to bind to the allylic binding sites in both eukaryotic and prokaryotic FPPSs, in good accord with recent crystallographic results (a 0.4 A rms deviation from the X-ray structure with the E. coli enzyme). Overall, these results show for the first time that the geometries of a broad variety of phosphorus-containing inhibitors and substrates of isoprene biosynthesis pathway enzymes can be well predicted by using computational methods, which can be expected to facilitate the design of novel inhibitors of these enzymes.

Aldose-Ketose Isomerases↗

The protective mechanism of Yisheng Injection against hepatic ischemia reperfusion injury in mice.

AIM: Hepatic ischemia/reperfusion injury may cause acute inflammatory, significant organ damage or dysfunction, and remains an important problem for liver transplantation. Our previous in vivo and in vitro studies demonstrated that Yisheng injection (YS), a traditional Chinese medicine, had protective effect on ischemia/reperfusion injury. In this study, we examined whether YS had protective effect for hepatic ischemia/reperfusion injury and explored its protective mechanism. METHODS: Hepatic warm ischemia/reperfusion was induced in mice. YS at different doses (5, 10, 20 mg/kg) was injected intraperitoneally 24 h and 1 h before ischemia and a third dose was injected intravenously just before reperfusion. The hepatocellular injury, oxidative stress, neutrophil recruitment, proinflammatory mediators and adhesion molecules associated with hepatic ischemia/reperfusion injury were assayed by enzyme-linked immunosorbent assay (ELISA), immunohistochemical assay and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Undergoing 90 min of ischemia and 6 h of reperfusion caused dramatical injuries in mouse livers. Administration of YS at doses of 5, 10 and 20 mg/kg effectively reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), from 3 670+/-463 U/L, 2 362+/-323 U/L and 12 752+/-1 455 U/L in I/R group to 1 172+/-257 U/L, 845+/-193 U/L and 2 866+/-427 U/L in YS (20 mg/kg) treated group, respectively (P<0.01). The liver myeloperoxidase (MPO) and malondialdehyde (MDA) contents were decreased from 1.1+/-0.2 (U/mg protein) and 9.1+/-0.7 (nmol/mg protein) in I/R group to 0.4+/-0.1 (U/mg protein) and 5.5+/-0.9 (nmol/mg protein) in YS (20 mg/kg) treated group, respectively (P<0.01). Moreover, the serum levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 55+/-9.9 (pg/mL) in I/R group to 16+/-4.2 (pg/mL) (P<0.01). Furthermore, the over-expressions of TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) were suppressed by YS treatment in a dose-dependent manner. CONCLUSION: YS attenuates hepatic warm ischemia/reperfusion injury by reducing oxidative stress and suppressing the over-expression of proinflammatory mediators and adhesion molecules.

Animals↗

Binding analyses between Human PPARgamma-LBD and ligands.

The binding characteristics of a series of PPARgamma ligands (GW9662, GI 262570, cis-parinaric acid, 15-deoxy-Delta(12,14)-prostaglandin J(2), LY171883, indomethacin, linoleic acid, palmitic acid and troglitazone) to human PPARgamma ligand binding domain have been investigated for the first time by using surface plasmon resonance biosensor technology, CD spectroscopy and molecular docking simulation. The surface plasmon resonance biosensor determined equilibrium dissociation constants (KD values) are in agreement with the results reported in the literature measured by other methods, indicating that the surface plasmon resonance biosensor can assume a direct assay method in screening new PPARgamma agonists or antagonists. Conformational changes of PPARgamma caused by the ligand binding were detected by CD determination. It is interesting that the thermal stability of the receptor, reflected by the increase of the transition temperature (T(m)), was enhanced by the binding of the ligands. The increment of the transition temperature (DeltaT(m)) of PPARgamma owing to ligand binding correlated well with the binding affinity. This finding implies that CD could possibly be a complementary technology with which to determine the binding affinities of ligands to PPARgamma. Molecular docking simulation provided reasonable and reliable binding models of the ligands to PPARgamma at the atomic level, which gave a good explanation of the structure-binding affinity relationship for the ligands interacting with PPARgamma. Moreover, the predicted binding free energies for the ligands correlated well with the binding constants measured by the surface plasmon resonance biosensor, indicating that the docking paradigm used in this study could possibly be employed in virtual screening to discover new PPARgamma ligands, although the docking program cannot accurately predict the absolute ligand-PPARgamma binding affinity.

Apoproteins↗

[Living donor liver transplantation treatment of Wilson's disease complicated with neuropathy].

OBJECTIVE: To investigate living donor liver transplantation for Wilson disease with neurologic features. METHODS: From Jan 2001 to Mar 2003, fifteen cases of living donor liver transplantation were performed for Wilson Disease (WD), five of those were complicated with neurologic features. A retrospective analysis was given for cooper metabolism and neurologic features. RESULTS: All operation were living related liver transplantation and donors were mothers. Four left lobes with hepatic middle vein and one right lobe without hepatic middle vein were harvested from donors, and graft volume to recipient body weight ratio was 0.79 approximately 1.08. One patient occurred hepatic artery thrombosis and performed retransplantation later, the other recipients recovered satisfactorily. All patients showed Extrapyramidal sign and three patients companying with language handicap and dyskinesia alleviated postoperation follow-up between 2 and 16 months. All recipients are alive and remain well, and none have developed signs of recurrent WD. CONCLUSION: Living donor liver transplantation is effective treatment for WD complicated with nervous system symptom, ceruloplasmin is normal and Kayser-Fleischer ring and nervous system symptom are to various extents.

Adolescent↗

Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing.

Potassium ion (K(+)) channels are attractive targets for rational drug design. Based upon a three-dimensional model of the eukaryotic K(+) channels, the docking virtual screening approach was employed to search the China Natural Products Database. Compounds were ranked according to the relative binding energy, favorable shape complementarity, and potential of forming hydrogen bonds with the K(+) channel. Four candidate compounds found by virtual screening were investigated by using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. When applied extracellularly, compound 1 markedly depressed the delayed rectifier K(+) current (I(K)) and fast transient K(+) current (I(A)), whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory effect on I(K). Intracellular application of the four compounds had no effect on both the K(+) currents.

Animals↗

Steered molecular dynamics simulation on the binding of NNRTI to HIV-1 RT.

HIV-1 reverse transcriptase (RT) is the primary target for anti-AIDS chemotherapy. Nonnucleoside RT inhibitors (NNRTIs) are very potent and most promising anti-AIDS drugs that specifically inhibit HIV-1 RT. The binding and unbinding processes of alpha-APA, an NNRTI, have been studied using nanosecond conventional molecular dynamics and steered molecular dynamics simulations. The simulation results show that the unbinding process of alpha-APA consists of three phases based on the position of alpha-APA in relation to the entrance of the binding pocket. When alpha-APA is bound in the binding pocket, the hydrophobic interactions between HIV-1 RT and alpha-APA dominate the binding; however, the hydrophilic interactions (both direct and water-bridged hydrogen bonds) also contribute to the stabilizing forces. Whereas Tyr-181 makes significant hydrophobic interactions with alpha-APA, Tyr-188 forms a strong hydrogen bond with the acylamino group (N14) of alpha-APA. These two residues have very flexible side chains and appear to act as two "flexible clamps" discouraging alpha-APA to dissociate from the binding pocket. At the pocket entrance, two relatively inflexible residues, Val-179 and Leu-100, gauge the openness of the entrance and form the bottleneck of the inhibitor-unbinding pathway. Two special water molecules at the pocket entrance appear to play important roles in inhibitor recognition of binding and unbinding. These water molecules form water bridges between the polar groups of the inhibitor and the residues around the entrance, and between the polar groups of the inhibitor themselves. The water-bridged interactions not only induce the inhibitor to adopt an energetically favorable conformation so the inhibitor can pass through the pocket entrance, but also stabilize the binding of the inhibitor in the pocket to prevent the inhibitor's dissociation. The complementary steered molecular dynamics and conventional molecular dynamics simulation results strongly support the hypothesis that NNRTIs inhibit HIV-1 RT polymerization activity by enlarging the DNA-binding cleft and restricting the flexibility and mobility of the p66 thumb subdomain that are believed to be essential during DNA translocation and polymerization.

Acetamides↗

Virtual screening on natural products for discovering active compounds and target information.

Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.

Biological Products↗

Copper metabolism after living related liver transplantation for Wilson's disease.

AIM: Liver transplantation is indicated for Wilson's disease (WD) patients with the fulminant form and end-stage liver failure. The aim of this study was to review our experience with living-related liver transplantation (LRLT) for WD. METHODS: A retrospective review was made for WD undergoing LRLT at our hospital from January 2001 to February 2003. RESULTS: LRLT was carried out in 15 patients with WD, one of them had fulminant hepatic failure and the others had end-stage hepatic insufficiency. The mean age of the patients was 14.5 +/- 2.5 years (range 6 to 20 years). All the recipients had low serum ceruloplasmin levels with a mean value of 126.8 +/- 34.8 mg/L before transplantation. The serum ceruloplasmin levels increased to an average of 238.6 +/- 34.4 mg/L after LRLT at the latest evaluation, between 2 and 27 months after transplantation. A marked reduction in urinary copper excretion was observed in all the recipients after transplantation. Among the eight recipients with preoperative Kayser-Fleischer (K-F) rings, this abnormality resolved completely after LRLT in five patients and partially in three. All the recipients are alive and remain well, and none has developed signs of recurrent WD after a mean follow-up period of 15.4 +/- 9.3 months (range 2-27 months) except one who died of severe rejection. The donors were 14 mothers and 1 father. The serum ceruloplasmin levels were within normal limits in all the donors (mean: 220 +/- 22.4 mg/L). The mean donor age was 35.0 +/- 4.0 years (range, 30 to 45 years). Two donors had biliary leakage and required reoperation. Grafts were harvested as follows: four right lobe grafts without hepatic middle vein and eleven left lobe grafts with hepatic middle vein. The grafts were blood group-compatible in all recipients. Two patients had hepatic artery thrombosis and underwent retransplantation. CONCLUSION: LRLT is a curative procedure in Wilson's disease manifested as fulminant hepatic failure and/or end-stage hepatic insufficiency. After liver transplantation, the serum ceruloplasmin level can increase to its normal range while urinary copper excretion decreases. Grafts chosen from heterozygote carriers do not appear to confer any risk of recurrence in recipients.

Adolescent↗