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Biomedical subjects

S Guan

Publications and source records attributed to S Guan.

At least 19 recordsLinked to original sources

Protocatechuic acid suppresses MPP+ -induced mitochondrial dysfunction and apoptotic cell death in PC12 cells.

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia (A.) oxyphylla, showed antioxidant neuroprotective effect in our previous study. Here, we investigated the effect of PCA on the MPP(+)-induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. The apoptosis in MPP(+)-induced PC12 cells was associated with loss of mitochondrial membrane potential, the formation of reactive oxygen species (ROS), GSH depletion, activation of caspase-3 and down-regulation of Bcl-2. In contrast, treatment of PC12 cells with PCA significantly prevented the above-mentioned mitochondrial dysfunction. Our data pointed to the potential clinical application/use of PCA to overcome neurodegenerative diseases such as Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

Protocatechuic acid from Alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells.

An ethyl acetate extract of Alpinia oxyphylla was found to possess neuroprotective activity against 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apotosis and oxidative stress in cultured PC12 cells. From the extract, a phenolic compound was isolated through bioassay-guided fractionation and identified as protocatechuic acid (PCA) by IR, MS, and (1)H and (13)C NMR spectroscopy. It was the first time which was isolated from the kernels of A. oxyphylla. Exposure of PC12 cells to 1mM MPP(+) may cause significant viability loss and apoptotic cell death. PCA stimulated PC12 cellular proliferation and markedly attenuated MPP(+)-induced apoptotic cell death in a dose-dependent manner. By observing the nuclear morphological changes and flow cytometric analysis, PCA showed its significant effect on protecting PC12 cells against MPP(+)-induced apoptosis. Meanwhile, PCA enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in PC12 cells. In addition, PCA also dose-dependently reduced the hydrogen peroxide (H(2)O(2))- or sodium nitroprusside (SNP)-induced cell death in PC12 cells. The results suggest that PCA may be one of the primary active components in the kernels of A. oxyphylla and provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

Characterization of Tetrahymena histone H2B variants and posttranslational populations by electron capture dissociation (ECD) Fourier transform ion cyclotron mass spectrometry (FT-ICR MS).

This work describes the nature and sequence information content of the electron capture dissociation mass spectra for the intact Tetrahymena histone H2B. Two major variants of this protein were present bearing nominal modifications of both +42 and +84 Da. This work describes identification of the nature of these two modifications. For example, using gas-phase selection and isolation of the +42-Da modified species, from a background of two H2B variants each present in six or more posttranslationally modified isoforms, we were able to determine that this +42-Da modification isoform bears trimethylation rather than acetylation. LC-CIDMS analysis was also employed on digested preparations to obtain complementary detail of the nature of site-specific posttranslational modifications. This study establishes that integration of the information from these two datasets provides a comprehensive map of posttranslational occupancy for each particular covalent assemblage selected for structural investigation.

Amino Acid Sequence↗

Characterization of binding and utilization of hemoglobin by Prevotella nigrescens.

The ability of Prevotella nigrescens to utilize and bind to hemoglobin was investigated. Growth studies showed that P. nigrescens was able to utilize hemoglobin efficiently as an iron source. Binding of P. nigrescens to hemoglobin was demonstrated by dot blot assay. Heat and trypsin treatments of the bacteria led to a decrease in activity. Globin gave nearly complete inhibition of activity. Additionally, lactoferrin partially inhibited activity. In contrast, transferrin, cytochrome C and catalase exerted little or no inhibitory effect. Although the sugars tested did not affect activity, several of the amino acids tested, including arginine, cysteine, histidine and lysine, inhibited activity. In a solid phase assay, 41-, 56- and 59-kDa proteins of P. nigrescens reacted with hemoglobin. These results suggest that P. nigrescens utilizes hemoglobin for growth and 41-, 56- and 59-kDa proteins may be involved in hemoglobin binding.

Arginine↗

[Clinical observation of the microanatomical relation between pituitary stalk and pituitary adenoma].

OBJECTIVE: To observe the microanatomical relation between the pituitary stalk and pituitary adenoma so as to find practical approach to protect the pituitary stalk during operation. METHODS: At the level of diaphragm sellae, the laterality of pituitary stalk was assessed in 71 cases by its location to the line connecting the mid-points of tuberculum sellae and dorsum sellae. In 46 cases the level of diaphragma sellae was regarded as the clock dial so as to determine the location by hour of the pituitary stalk. RESULTS: The laterality of pituitary stalk was observed in 61 cases, among which the pituitary stalk was on the left side in 17 cases, on the right side in 41 cases, and at the posterior middle site in 13 cases. Location by hour was observed in 46 cases, among which 13 cases were at 5 o'clock, 11 at 6 o'clock, 7 at 7 o'clock, 5 at 4 o'clock, 4 at 3 o'clock, 2 at 2 o'clock, 2 at o'clock, and 2 at 11 o'clock respectively. CONCLUSION: The location of pituitary stalk is related to the direction of growth of tumor in the sella and not related to its extension above the sella. The pituitary stalk can be used as the marker to find normal pituitary tissue.

Adenoma↗

[Anatomicopathological relation between facial nerve and large vestibular Schwannoma].

OBJECTIVE: To study the anatomicopathological relation between facial nerve and large vestibular schwannoma. METHODS: Operation by suboccipital retrosigmoid sinus approach was performed on 40 cases with large vestibular schwannoma, During the operation, the anatomicopathological relation between the facial nerve and the vestibular schwannoma was observed directly. RESULTS: The facial nerve was found to be located ventrally (deep under the tumor), dorsally (over the tumor), at the upper pole of the tumor (near the tentorium cerebelli), at the lower pole of the tumor (near the rear group cranial nerves), or aberrant (unable to be identified because of infiltration of tumor). In 31 cases, mainly with parenchymatous tumor, the facial nerve was flat in shape. In 9 cases, mainly with cystic tumor, the facial nerve was bandlike. CONCLUSION: The facial nerve varies greatly in neuroanatomy among patients with large vestibular schwannoma. Strengthening of operative monitoring can increase the safety of operation.

Adult↗

Functional analysis of the galactosyltransferases required for biosynthesis of D-galactan I, a component of the lipopolysaccharide O1 antigen of Klebsiella pneumoniae.

D-Galactan I is an O-antigenic polymer with the repeat unit structure [-->3)-beta-D-Galf-(1-->3)-alpha-D-Galp-(1-->], that is found in the lipopolysaccharide of Klebsiella pneumoniae O1 and other gram-negative bacteria. A genetic locus containing six genes is responsible for the synthesis and assembly of D-galactan I via an ATP-binding cassette (ABC) transporter-dependent pathway. The galactosyltransferase activities that are required for the processive polymerization of D-galactan I were identified by using in vitro reactions. The activities were determined with endogenous lipid acceptors in membrane preparations from Escherichia coli K-12 expressing individual enzymes (or combinations of enzymes) or in membranes reconstituted with specific lipid acceptors. The D-galactan I polymer is built on a lipid acceptor, undecaprenyl pyrophosphoryl-GlcpNAc, a product of the WecA enzyme that participates in the biosynthesis of enterobacterial common antigen and O-antigenic polysaccharide (O-PS) biosynthesis pathways. This intermediate is directed into D-galactan I biosynthesis by the bifunctional wbbO gene product, which sequentially adds one Galp and one Galf residue from the corresponding UDP-sugars to form a lipid-linked trisaccharide. The two galactosyltransferase activities of WbbO are separable by limiting the UDP-Galf precursor. Galactosyltransferase activity in membranes reconstituted with exogenous lipid-linked trisaccharide acceptor and the known structure of D-galactan I indicate that WbbM catalyzes the subsequent transfer of a single Galp residue to form a lipid-linked tetrasaccharide. Chain extension of the D-galactan I polymer requires WbbM for Galp transferase, together with Galf transferase activity provided by WbbO. Comparison of the biosynthetic pathways for D-galactan I and the polymannose E. coli O9a antigen reveals some interesting features that may reflect a common theme in ABC transporter-dependent O-PS assembly systems.

Bacterial Proteins↗

Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs.

OBJECTIVE: To study the effects of tetrandrine, a Chinese herbal medicine, on the action potential (AP), contraction as well as sarcoplasmic reticulum (SR) calcium uptake of myocardium in guinea-pigs and dogs. METHODS: Changes in AP, dV/dt, peak tension (PT) and dT/dt of myocardial cells were studied using the technique of glass electrode. Changes of the calcium uptake rate by sarcoplasmic reticulum and release of inorganic phosphate from sarcoplasmic reticulum were assessed with biochemical techniques. RESULTS: Tetrandrine exerts a concentration-dependent and frequency-dependent negative inotropic effect and shortens action potential duration. Tetrandrine depresses both dT(E)/dt and dT(L)/dt as well as the tension of myocardium, and reduces dV/dt and amplitude only in the slow action potential, thus implying that tetrandrine blocks the slow calcium channel. In addition, compared with thapsigargin, a specific inhibitor of Ca(2+)-ATPase on SR, tetrandrine more apparently suppresses the contraction of the myocardium. CONCLUSIONS: Tetrandrine is a wide-range calcium antagonist of plant origin. Not only it blocks the voltage-operated calcium channels as other authors reported, but also may play an important role in affecting the function of Ca(2+)-ATPase and calcium release channels on SR. From this study, we also suggest that the calcium channel appears to be more critical than SR for the contraction of myocardium.

Action Potentials↗

20-O-acylcamptothecin derivatives: evidence for lactone stabilization.

Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pH > or =8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.

Acylation↗

[Detection of fetal cells in maternal blood by fluorescence in situ hybridization].

OBJECTIVE: To isolate fetal nucleated cells from maternal blood and determine its fetal origin. METHODS: Enrichment and isolation of nucleated cells in maternal blood from 20 samples in the first trimester of pregnancy, 20 samples in the mid-trimester of pregnancy, and 15 samples after delivery. Fluorescence in situ hybridization was performed using Y specific probe PY3.4 to identify fetal cells. RESULTS: Fifteen women in the first trimester and 15 women in the mid-trimester of pregnancy carried male fetuses. The rates of positive cells were 1:6528.0 and 1:2783.8 respectively, and there was a highly significant difference when these rates were compared with the positive cells rate of the 10 female fetuses in the same trimesters. No significant difference in positive cells rate was found between 1 week after delivery and the mid-trimester of pregnancy, nor was it found between 3 months after delivery and the 10 samples of female fetuses in the same time. CONCLUSION: These data suggest that fetal cells can be detected as early as from 50 days of gestation in maternal blood, in the meantime, the rate of fetal cells will increase with gestational age. One week after delivery, fetal cells still exist, and 3 months after delivery, the fetal cells will no longer be detected.

Female↗

[Experimental study on anti-fatigue effect of shenfu injection on diaphragmatic muscle].

OBJECTIVE: To study the effect of Shenfu injection (SFI) on function of diaphragmatic muscle in rabbits. METHODS: Taking the transdiaphragmatic pressure (Pdi), diaphragmatic electromyogram (EMGdi) and diaphragmatic evoked potential (DEP) as criteria for observation, the diaphragmatic fatigue (DiF) was induced by stimulating bilateral phrenic nerve for 30 minutes. Pdi, EMGdi and DEP induced by stimulation with different frequency (Fc) were recorded before and after treatment. Then the high/low (H/L) frequency ratio and central Fc were calculated and analysed by variance analysis and q test. RESULTS: After administration of 2 ml/kg of SFI, the Pdi, H/L, Fc and amplitude of DEP were markedly increased and latent phase of DEP was shortened by the drug, in comparing with those before treatment, P < 0.05. CONCLUSION: SFI has the effect in antagonizing diaphragmatic fatigue.

Animals↗

[Multiple organ dysfunction syndrome after open chest wound and seawater immersion: experimental study].

OBJECTIVE: To evaluate the effect of seawater immersion on multiple organ dysfunction syndrome (MODS) after chest trauma. METHODS: Twenty health dogs were divided into two groups. Right open pneumothorax was induced in both control group (n = 10) and experimental group (n = 10). After induction of chest trauma, animals in the experimental group were immersed in artificial seawater. Blood samples were taken at seven different intervals for assessing blood gas, plasma level of TNFalpha, and IL-1 beta. Changes of serum alanine aminotransferase (ALT), aspartate amino-transferase (AST), creatine kinase (CK) lactate dehydrogenase (LDH) and creatinine (Cr) were measured. At the end of study, lung was harvested for assessing lung water content and ratio of wet weight and dry weight. RESULTS: A significant elevation of ALT, AST, CK and LDH was observed in both groups. Organ functional parameters in the experimental group were consistent with the failure standard at 30 minutes after seawater immersion, and those in the control group at 4 hours. Post-trauma mortality and incidence of MODS were much higher in the experimental group than those in the control group (P < 0.01). The plasma levels of TNFalpha and IL-1 beta significantly increased at 30 minutes and reached the highest level at 60 minutes after seawater immersion. The time of peak level appeared earlier in the experimental group than that in the control group. CONCLUSION: Seawater immersion after open chest trauma results in high incidence of MODS and high mortality rate due to progressive dysfunction of multiple organs.

Animals↗

Combinatorial discovery of oxidative dehydrogenation catalysts within the Mo-V-Nb-O system.

Combinatorial methodologies were used for the synthesis and screening of mixed metal oxide heterogeneous catalysts. Primary screening at low reactant conversions at a throughput of greater than 10,000 catalyst compositions per month was performed by using simultaneous MS and photothermal deflection spectroscopy on spatially separated thick film catalysts with approximately 200 microg per catalyst prepared by using automated liquid dispensing. Secondary screening under realistic operating conditions was performed at a throughput of greater than 3,000 catalyst compositions per month on approximately 50 mg of catalyst in an array of fixed bed microreactors with gas chromatograph detection. The approach was validated by the discovery of catalysts with superior performance to those previously described for the oxidative dehydrogenation of ethane to ethylene. We show the full implementation and integration of combinatorial methodologies for synthesis, screening, discovery, and optimization of multicomponent heterogeneous catalysts.

Journal Article↗

Drug delivery of anticancer agents: water soluble 4-poly (ethylene glycol) derivatives of the lignan, podophyllotoxin.

This paper reports on the synthesis and in vivo oncolytic activity of a series of water-soluble acyl derivatives of polyethylene glycol (PEG) conjugated podophyllotoxin. Some analogs of the polymer conjugate showed significantly better activity in a murine leukemia model than native podophyllotoxin suspended in an intralipid emulsion. Additionally, when tested intravenously against a solid lung tumor (A549) model, some conjugated analogs were equivalent to the podophyllotoxin/intralipid emulsion, while those compounds demonstrating slower rates of plasma hydrolysis (in vitro) appeared to cause greater toxicity. There appeared to be an overall correlation between the in vivo antitumor activity of the conjugate and its rate of hydrolysis in vitro, with those showing faster release possessing greater antitumor activity. In conclusion, the solubilization and predictable release of podophyllotoxin from a PEG carrier was achieved and resulted in some derivatives demonstrating, at a minimum, equivalency with podophyllotoxin when administered on an equal molar basis. Further studies may be warranted to assess the PEG-conjugates pharmacokinetics and therapeutic indices in leukemic models.

Animals↗

Drug delivery systems employing 1,4- or 1,6-elimination: poly(ethylene glycol) prodrugs of amine-containing compounds.

A general methodology for synthesizing poly(ethylene glycol) (PEG) prodrugs of amino-containing compounds has been developed and constitutes the basis for solubilization of insoluble drugs, extending plasma circulating half-lives and, in the case of anticancer agents, apparent tumor accumulation. Thus, we have successfully designed PEG conjugated specifiers or "triggers" as part of a double-prodrug strategy that relies, first, on enzymatic separation of PEG followed by the classical and rapid 1,4- or 1, 6-benzyl elimination reaction releasing the amine (drug) bound in the form of a carbamate. The prodrug trigger was comprised of ester, carbonate, carbamate, or amide bonds in order to secure predictable rates of hydrolysis. Further refinement of the hydrolysis was accomplished by the introduction of steric hindrance through the use of ortho substituents on the benzyl component of the prodrug. This modification led to longer circulating plasma half-lives of the final tripartate form. The "ortho" effect also had the beneficial effect of directing nucleophilic attack almost exclusively to the activated benzyl 6-position of the heterobifunctional intermediates. In vivo testing of the PEG daunorubicin prodrugs (transport forms) prepared in the course of this study ultimately identified the type 1 carbamate (34b), with a circulating t(1/2) of 4 h, as the most effective derivative for solid tumor growth inhibition.

Amines↗

Inhibition of Na-K-ATPase activity and gene expression by a myeloma light chain in proximal tubule cells.

BACKGROUND: Light chain nephrotoxicity is frequently associated with Fanconi syndrome characterized by amino-aciduria, glycosuria, phosphaturia, and bicarbonaturia. The mechanisms of these transport abnormalities are unknown. To determine the role of Na-K-ATPase, we examined the effects of a lambda-light chain on both the activity and gene expression of Na-K-ATPase in primary cultures of rat proximal tubule cells. METHODS: The lambda-light chain used here was isolated from urine of a patient with multiple myeloma and previously shown to inhibit sodium-dependent phosphate and glucose transport in proximal tubule cells. Na-K-ATPase was determined spectrophotometrically and the gene expression by Northern analysis in cells exposed to light chain. RESULTS: In cells exposed to 200 mumol/L light chain Na-K-ATPase activity was reduced significantly, up to 73%, at 2, 24, and 48 hours compared with control cells (N = 12, P < 0.001). Northern analysis showed that in cells exposed to light chain for 24 and 48 hours the message for the alpha-1 isoform of Na-K-ATPase was suppressed significantly compared with control cells. The messages for GAPDH, beta-actin, and 28 S RNA in light chain exposed cells were also depressed in comparison with control cells. This light chain also significantly inhibited thymidine incorporation by proximal tubule cells in a dose-dependent manner. CONCLUSIONS: These data suggest a general toxicity to cells by this light chain and indicate that inhibitory effects on both the activity and gene expression of Na-K-ATPase may be an important mechanism of light chain cytotoxicity on proximal tubule cells.

Animals↗

[Lateral approaches for treatment of petroclival region tumor].

OBJECTIVE: To summarize the operation experience of resecting petroclival region tumors by lateral approaches. METHODS: (1) Ameliorate pterion approach; (2) temporal-occipital transtentorial-transpetrous approach; (3) transpetrous combined with supratentorial and infratentorial presigmoid approach; (4) far lateral transcondylar approach were applied for 61 patients with petroclival region tumor. RESULTS: Of the 61 tumors studied, 54 were completely resected, 6 were nearly complete and 1 was subtotally resected. No patient died in this group, 37 patients were followed up, and all showed satisfying results. 45% of the patients had CNs deficit, with III, VI, V, VIII, IX, X, XII nerve deficits most commonly seen. CONCLUSION: Lateral approaches are recommended for total resection of petroclival region tumors. HoVDever the operative techniques are complex and potential risks of morbidity exist.

Adolescent↗