Biomedical subjects

Guohui Li

Publications and source records attributed to Guohui Li.

18 recordsLinked to original sources

PubMed2025

Decoding Arginine Dimethylation Isomers via pH-Tuned Reactivity with Methylglyoxal: A Chemical Approach for Functional Proteomics.

Arginine dimethylation, encompassing asymmetric and symmetric configurations, represents a fundamental post-translational modification. Despite sharing identical chemical formulas, the two arginine dimethylation isomers exhibit different or even opposite biological effects. Therefore, it is necessary to determine their specific structure before conducting a further biological investigation. However, current methods for arginine dimethylation analysis face great challenges in efficient isomer differentiation, preventing the functional investigation of arginine dimethylation. To overcome this obstacle, herein, we introduce a novel chemical strategy leveraging pH-tuned reactivity with methylglyoxal (MGO) to decode these dimethylation isomers. By utilizing molecular dynamics simulation analysis, we revealed the different chemical reactivities of asymmetrically and symmetrically dimethylated arginine when reacted with MGO at different pH conditions. This property enabled the development of a pH-tuned chemical strategy by combining the MGO reaction with boronate affinity enrichment to simultaneously enrich and differentiate the dimethylation isomers. This strategy can effectively distinguish dimethylated arginine isomers in complex cell samples, and the good feasibility of this strategy was verified by orthogonal validation with the neutral loss. Of the obtained data set, this strategy identified sDMA at R112 of SNRPN, which is confirmed to be modified by PRMT5. Further functional analysis reveals its crucial role in maintaining protein stability and in regulating spliceosome assembly. Overall, by transforming the inherent pH sensitivity of MGO reactions into a powerful analytical tool, our work establishes the first chemical platform for functional proteomic dissection of arginine dimethylation isomers, which paves the way for further regulating mechanism investigations of protein methylation.

Pyruvaldehyde↗

PubMed2006

Finite reservoir replica exchange to enhance canonical sampling in rugged energy surfaces.

A "finite reservoir" replica exchange method is presented to further enhance sampling upon the regular replica exchange method (REM) in a rugged energy surface. The present method can facilitate important sampling more efficiently by exchanging structures with configurations randomly selected from a finite-sized reservoir; this finite reservoir is pregenerated and updated by a mechanism of replica exchange with neighboring "temperature" simulations. In practice, this proposal revises exchange schedule in REM simulations in order to make productive exchange for conformational "tunneling" more frequent.

Journal Article↗

PubMed2006

Biogenic emissions of isoprenoids and NO in China and comparison to anthropogenic emissions.

In this study, a regional dynamical model (WRF) is used to drive biogenic emission models to calculate high resolution (10x10 km) biogenic emissions of isoprene (C(5)H(8)), monoterpenes (C(10)H(16)), and nitric oxide (NO) in China. This high resolution biogenic inventory will be available for the community to study the effect of biogenic emissions on photochemical oxidants in China. The biogenic emissions are compared to anthropogenic emissions to gain insight on the potential impact of the biogenic emissions on tropospheric chemistry, especially ozone production in this region. The results show that the biogenic emissions in China exhibit strongly diurnal, seasonal, and spatial variations. The isoprenoid (including both isoprene and monoterpenes) emissions are closely correlated to tree density and strongly vary with season and local time. During winter (January), the biogenic isoprenoid emissions are the lowest, resulting from lower temperature and solar radiation, and highest in summer (July) due to higher temperature and solar radiation. The biogenic NO emissions are also higher during summer and lower during winter, but the magnitude of the seasonal variation is smaller than the emissions of isoprene and monoterpenes. The biogenic emissions of NO are widely spread out in the northern, eastern, and southern China regions, where high-density agricultural soil lands are located. Both biogenic NO and isoprenoid emissions are very small in western China. The calculated total biogenic emission budget is smaller than the total anthropogenic VOC emission budget in China. The biogenic isoprenoid and anthropogenic VOC emissions are 10.9 and 15.1 Tg year(-1), respectively. The total biogenic and anthropogenic emissions of NO are 5.9 and 11.5 Tg(NO) year(-1), respectively. The study shows that in central eastern China, the estimated biogenic emissions of isoprenoids are very small, and the anthropogenic emissions of VOCs are dominant in this region. However, in northeastern and southern China, there are relatively large biogenic emissions of isoprenoids, leading to an important impact on the ozone production in these regions. Furthermore, the emissions of isoprenoids are highest during summer and noontime, which correlates to the peak of ozone production period. For example, the ratio between summer and winter for the emissions of isoprenoids is about 15 in China. As a result, the biogenic emissions of isoprenoids are significantly larger than the anthropogenic emissions of VOCs in China during daytime in summer. Biogenic NO emissions are mostly produced by agricultural soils which co-exist with large populations and human activity. As a result, the biogenic emissions of NO are mostly overlapped with the anthropogenic emissions of NO, leading to the enhancement in NO concentrations in the high anthropogenic NO emission regions. Finally, the future emissions of isoprene and monoterpenes over China are estimated. The results show that the future biogenic emissions may increase significantly due to land cover changes in central eastern China, which could have a very important impact on ozone formation in this region. However, these estimates are highly uncertain and are presented as a potential scenario to show the importance of possible changes of biogenic emissions in China.

Air Pollutants↗

PubMed2006

Inhibitory effects of lanthanum chloride on extracellular matrix in injury tissues of rats.

The propose of the present study is to investigate the effects of lanthanum chloride (LaCl(3)), a rare earth compound, on extracellular matrix molecules in rat wound tissues, hoping to provide a clue for further study in reducing excessive extracellular matrix formation in trauma and burn, as well as in fibrous disorders. In order to elucidate its action mechanism, we investigated its effects on fibroblast apoptosis, intracellular calcium, collagen synthesis and expression, and fibronectin mRNA expression. We found that treatment with 0.25 ml of 50 mM (1.5mg/injection) LaCl(3) for three consecutive days induced fibroblast apoptosis and inhibited collagen synthesis and expression. Comparing to control, at day 14 after wounding, apoptosis and the level of intracellular calcium in wound tissues were significantly increased, but at day 28 after wounding, apoptosis was not continually increased and gradually became normal. In contrast, the amount of (3)H-proline incorporation and the expression of type I and III collagen decreased at days 14 and 28 after wounding by LaCl(3)-treatment. The expression of fibronectin mRNA was not significant changed at days 14 and 28 after-wounding by LaCl(3)-treatment as compared to the control. The results suggest that LaCl(3) may reduce the extracellular matrix formation at certain concentrations during wound healing and be worth further study as an anti-fibrous agent. Because lanthanides have been used to clinical treatment with antibacterial agents in burn, it may be more suitable for the treatment of severe burn.

Animals↗

PubMed2006

Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes.

Motivated by the long-term goal of understanding vectorial biological processes such as proton transport (PT) in biomolecular ion pumps, a number of developments were made to establish combined quantum mechanical/molecular mechanical (QM/MM) methods suitable for studying chemical reactions involving significant charge separation in the condensed phase. These developments were summarized and discussed with representative problems. Specifically, free energy perturbation and boundary potential methods for treating long-range electrostatics were implemented to test the robustness of QM/MM results for protein systems. It was shown that consistent models with sufficient sampling were able to produce quantitatively satisfactory results, such as pKa for titritable groups in the interior of T4-lysozyme, while an inconsistent treatment of electrostatics or lack of sufficient sampling may produce incorrect results. Modifications were made to an approximate density functional theory (SCC-DFTB) to improve the description of proton affinity and hydrogen-bonding, which are crucial for the treatment of PT in polar systems. Test calculations on water autoionization showed clearly that both improvements are necessary for quantitatively reliable results. Finally, the newly established SCC-DFTB/MM-GSBP protocol was used to explore mechanistic issues in carbonic anhydrase (CA). Preliminary results suggest that PT in CA occurs mainly through short water wires containing two water molecules in a thermally activated fashion. Although longer water wires occur with similar frequencies, PT along those pathways, on average, has substantially higher barriers, a result not expected based on previous studies. The fluctuations of water molecules peripheral to the water wire were found to make a larger impact on the PT energetics compared to polar protein residues in the active site, which are largely pre-organized and therefore have less tendency to reorganize during the reaction.

Computer Simulation↗

PubMed2005

Direct determination of reaction paths and stationary points on potential of mean force surfaces.

A simulation approach is introduced for directly determining reaction paths and stationary points on potential of mean force (PMF) surfaces associated with molecular events that occur in complex environments. The nudged elastic band approach was employed to search for steepest descent paths on the PMF surface using the relevant PMF derivatives from a series of local simulations. The steepest descent path on the PMF surface corresponds to the minimum PMF path (i.e. the path with the lowest local PMF barrier), which contains important information about stationary points (e.g. saddle points) on the PMF surface, which in turn can provide useful insights into the thermodynamics and kinetics for the process of interest. By working with the PMF defined in a low-dimensional sub-space rather than a potential energy function of full molecular dimensionality, the main features of the process under study are concisely represented and the orthogonal degrees of freedom are adequately sampled with the appropriate canonical distribution at the desired temperature (e.g. 300 K). Therefore, minimum PMF paths carry statistically meaningful mechanistic information and are complementary to reaction paths of full molecular dimensionality proposed in previous studies. The NEB based path optimization method is direct in the sense that no information regarding the global PMF surface is necessary for the determination of the local reaction path and stationary points along this path. Since only low-dimensional quantities (paths) are searched for, the PMF-path method is expected to scale better in terms of dimension of the PMF sub-space than those aims to fully explore multi-dimensional PMF surfaces. Test applications on simple molecular systems, the alanine di-peptide in vacuum and in solution and a micro-solvated proton-wire, indicate that reliable PMF paths can be determined for both conformational isomerization and chemical reaction processes. However, highly accurate PMF derivatives are required for determining more quantitative observables, such as the free energy profile along the minimum PMF path. Therefore, effective numerical algorithms for calculating local PMF derivatives and systematic protocols for defining the relevant sub-space are the main focus in the near future. Finally, we emphasize that the minimum PMF path defined here includes thermal (e.g. entropic) effects associated with the orthogonal degrees of freedom, but finite kinetic energies associated with the PMF degrees of freedom are not included; this can be improved by adopting a different definition of the reaction path, such as the maximum flux path, on the PMF surface, or thermally sampling all degrees of freedom orthogonal to the one-dimensional path.

Alanine↗

PubMed2004

Normal-mode analysis suggests protein flexibility modulation throughout RNA polymerase's functional cycle.

To explore the domain-scale flexibility of bacterial RNA polymerase (RNAP) throughout its functional cycle, block normal-mode analyses (BNM) were performed on several important functional states, including the holoenzyme, the core complex, a model of RNAP bound to primarily duplex DNA, and a model of the ternary elongation complex. The calculations utilized a molecular mechanics (MM) force field with physical interactions; this is made possible by the use of BNM and the implementation of a sparse-matrix diagonalization routine. The use of homology models necessitated the MM force field rather than the simpler elastic network model (ENM). From the MM/BNM, we have systematically and semiquantitatively calculated the atomic fluctuations in the four functional states without bias due to crystal packing or other artifactual forces. We have observed that both alpha subunits and the omega subunit are rigid, in line with their roles as structural motifs that are not mechanistically involved in RNAP's functional cycle. It has been observed that the beta subunit has two highly mobile domains; these are commonly known as the beta1 and beta2 domains. Our calculations suggest that the flexibility of these domains is modulated throughout the functional cycle and that they move entirely independently of each other unless DNA is bound. From an energetic perspective, we have shown the beta2 domain can flex into and out of the cleft, forming interactions with DNA in the TEC as has been previously proposed. Our calculations also confirm that the beta' subunit's likely flexibility into and out of the DNA binding cleft is energetically allowed. These two observations validate that both of the RNAP crab claw's pincers are mobile, as both beta and beta' have substantial flexibility.

Bacterial Proteins↗

PubMed2004

A normal mode analysis of structural plasticity in the biomolecular motor F(1)-ATPase.

Normal modes have been used to explore the inherent flexibility of the alpha, beta and gamma subunits of F(1)-ATPase in isolation and as part of the alpha(3)beta(3)gamma complex. It was found that the structural plasticity of the gamma and beta subunits, in particular, correlates with their functions. The N and C-terminal helices forming the coiled-coil domain of the gamma subunit are highly flexible in the isolated subunit, but more rigid in the alpha(3)beta(3)gamma complex due to interactions with other subunits. The globular domain of the gamma subunit is structurally relatively rigid when isolated and in the alpha(3)beta(3)gamma complex; this is important for its functional role in coupling the F(0) and F(1) complex of ATP synthase and in inducing the conformational changes of the beta subunits in synthesis. Most important, the character of the lowest-frequency modes of the beta(E) subunit is highly correlated with the large beta(E) --> beta(TP) transition. This holds for the C-terminal domain and the nucleotide-binding domain, which undergo significant conformational transitions in the functional cycle of F(1)-ATPase. This is most evident in the ligand-free beta(E) subunit; the flexibility in the nucleotide-binding domain is reduced somewhat in the beta(TP) subunit in the presence of Mg(2+).ATP. The low-frequency modes of the alpha(3)beta(3)gamma complex show that the motions of the globular domain of the gamma subunit and of the C-terminal and nucleotide binding domains of the beta(E) subunits are coupled, in accord with their function. Overall, the normal mode analysis reveals that F(1)-ATPase, like other macromolecular assemblies, has the intrinsic structural flexibility required for its function encoded in its sequence and three-dimensional structure. This inherent plasticity is an essential aspect of assuring a small free energy cost for the large-scale conformational transition that occurs in molecular motors.

Models, Molecular↗

PubMed2004

Analysis of functional motions in Brownian molecular machines with an efficient block normal mode approach: myosin-II and Ca2+ -ATPase.

The structural flexibilities of two molecular machines, myosin and Ca(2+)-ATPase, have been analyzed with normal mode analysis and discussed in the context of their energy conversion functions. The normal mode analysis with physical intermolecular interactions was made possible by an improved implementation of the block normal mode (BNM) approach. The BNM results clearly illustrated that the large-scale conformational transitions implicated in the functional cycles of the two motor systems can be largely captured with a small number of low-frequency normal modes. Therefore, the results support the idea that structural flexibility is an essential part of the construction principle of molecular motors through evolution. Such a feature is expected to be more prevalent in motor proteins than in simpler systems (e.g., signal transduction proteins) because in the former, large-scale conformational transitions often have to occur before the chemical events (e.g., ATP hydrolysis in myosin and ATP binding/phosphorylation in Ca(2+)-ATPase). This highlights the importance of Brownian motions associated with the protein domains that are involved in the functional transitions; in this sense, Brownian molecular machines is an appropriate description of molecular motors, although the normal mode results do not address the origin of the ratchet effect. The results also suggest that it might be more appropriate to describe functional transitions in some molecular motors as intrinsic elastic motions modulating local structural changes in the active site, which in turn gets stabilized by the subsequent chemical events, in contrast with the conventional idea of local changes somehow getting amplified into larger-scale motions. In the case of myosin, for example, we favor the idea that Brownian motions associated with the flexible converter propagates to the Switch I/II region, where the salt-bridge formation gets stabilized by ATP hydrolysis, in contrast with the textbook notion that ATP hydrolysis drives the converter motion. Another useful aspect of the BNM results is that selected low-frequency normal modes have been identified to form a set of collective coordinates that can be used to characterize the progress of a significant fraction of large-scale conformational transitions. Therefore, the present normal mode analysis has provided a stepping-stone toward more elaborate microscopic simulations for addressing critical issues in free energy conversions in molecular machines, such as the coupling and the causal relationship between collective motions and essential local changes at the catalytic active site where ATP hydrolysis occurs.

Algorithms↗

PubMed2004

Lanthanum inhibited the binding of LPS with monocyte and CD 14 expression upregulation.

To investigate the effects of lanthanum chloride on binding of LPS to monocyte and CD 14 expression upregulation induced by LPS, human monocytes were analyzed by flow cytometry (FCM). The results indicated that lanthanum chloride could decrease the binding rate of LPS with monocyte significantly. LPS upregulated the expression of CD 14 on monocyte in a dose dependant manner, however, lanthanum chloride could inhibit the increase of CD 14 expression on monocytes by halves.

Flow Cytometry↗

PubMed2003

What is so special about Arg 55 in the catalysis of cyclophilin A? insights from hybrid QM/MM simulations.

Potential of mean force (PMF) simulations with a hybrid QM/MM potential function were used to analyze the catalytic mechanism of human cyclophilin A (CypA). PMF calculations were performed for proline isomerization of peptides in solution, the wild-type CypA, and several CypA mutants. With an approximate density functional theory, the self-consistent-charge density functional tight binding (SCC-DFTB) as the QM level, and CHARMM 22 force field as MM, satisfactory energetics compared to available experiments were obtained. Calculations for the Arg55Ala and zero-charge-Arg55 mutants clearly indicated that Arg 55 significantly stabilizes the isomerization transition state through electrostatic interactions. However, the decrease in the average distance (thus the increase in interaction) between Arg 55 and the substrate amide N in going from the stable states to the transition state is mainly due to the pyramidalization of the amide N rather than motions associated with Arg 55. Although the nanosecond simulations cannot exclude the existence of sub-millisecond collective motions proposed on the basis of recent elegant NMR relaxation and line-shape analyses, the energetics obtained for the various enzyme systems here indicate that the contribution from motions of active site residues to catalysis is expected to be small. Instead, the present simulations support that the structural stability rather than mobility of the preorganized active site is more important. Through hydrogen-bonding interactions among the substrate, Arg 55, Gln 63, and Asn 102, the active site of the wild-type enzyme is structurally very stable and puts Arg 55 in a favorable position to perform its catalytic role in the transition state. This is further illustrated with the somewhat unexpected prediction that Arg55Lys is largely catalytically inactive, because Lys does not have the unique bifurcating construct of the guanidino group in Arg and thus the active site of Arg55Lys cannot accommodate Lys in a position capable of providing electrostatic stabilization of the isomerization transition state. Among all the enzyme systems studied, the wild-type CypA is the only one that selects the syn/exo transition state, while the syn/endo conformation is also present in the mutants, which is another reason for their higher barriers. Finally, the present analysis indicated that the population of near-attack-conformations (NAC) is not relevant to catalysis in CypA.

Arginine↗

PubMed2003

Human epithelial cancers secrete immunoglobulin g with unidentified specificity to promote growth and survival of tumor cells.

Immunoglobulins (Igs) are found thus far only to be produced by differentiated B lymphocytes. By immunohistochemistry analysis, in situ hybridization, and laser capture microdissection-assisted single-cell PCR, we demonstrate that human cancers of epithelial origin, including carcinomas of breast, colon, liver, lung, established epithelial cancer lines, as well as some normal lung tissues, also produce IgG in both cytoplasmic and secreted forms. Furthermore, blockade of tumor-derived IgG by either antisense DNA or antihuman IgG antibody increased programmed cell death and inhibited growth of cancer cells in vitro. More importantly, administration of antihuman IgG antibody also suppressed the growth of an IgG-secreting carcinoma line in immunodeficient nude mice. Our results support a role of tumor-derived IgG as growth factor for epithelial cancers. Prevalent expression of IgG in human carcinomas and its growth-promoting functions may have important implications in growth regulation and targeted therapy of human cancers.

Amino Acid Sequence↗

PubMed2002

A coarse-grained normal mode approach for macromolecules: an efficient implementation and application to Ca(2+)-ATPase.

A block normal mode (BNM) algorithm, originally proposed by Tama et al., (Proteins Struct. Func. Genet. 41:1-7, 2000) was implemented into the simulation program CHARMM. The BNM approach projects the hessian matrix into local translation/rotation basis vectors and, therefore, dramatically reduces the size of the matrix involved in diagonalization. In the current work, by constructing the atomic hessian elements required in the projection operation on the fly, the memory requirement for the BNM approach has been significantly reduced from that of standard normal mode analysis and previous implementation of BNM. As a result, low frequency modes, which are of interest in large-scale conformational changes of large proteins or protein-nucleic acid complexes, can be readily obtained. Comparison of the BNM results with standard normal mode analysis for a number of small proteins and nucleic acids indicates that many properties dominated by low frequency motions are well reproduced by BNM; these include atomic fluctuations, the displacement covariance matrix, vibrational entropies, and involvement coefficients for conformational transitions. Preliminary application to a fairly large system, Ca(2+)-ATPase (994 residues), is described as an example. The structural flexibility of the cytoplasmic domains (especially domain N), correlated motions among residues on domain interfaces and displacement patterns for the transmembrane helices observed in the BNM results are discussed in relation to the function of Ca(2+)-ATPase. The current implementation of the BNM approach has paved the way for developing efficient sampling algorithms with molecular dynamics or Monte Carlo for studying long-time scale dynamics of macromolecules.

Algorithms↗

PubMed2002

[The relationship between arterial blood oxygen pressure and the changes in blood biochemical indices after partial liquid ventilation in canine inhalation injury].

OBJECTIVE: To explore the therapeutic effects of partial liquid ventilation on canine inhalation injury. METHODS: Mongrel dogs were inflicted with steam inhalation injury and were employed as the model. Partial liquid ventilation was accomplished by slow instillation of into the lungs. The changes in blood superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and arterial oxygen pressure (PaO(2)) were determined. RESULTS: The blood levels of MDA and NO at 2 postburn hours (PBHs) increased obviously but those of SOD and PaO(2) decreased significantly when compared with those before injury (P < 0.05). The blood levels of SOD, MDA, NO and PaO(2) recovered to near preinjury levels after partial liquid ventilation. CONCLUSION: Partial liquid ventilation might be helpful in the management of inhalation injury by raising blood oxygen pressure, antagonizing lipid peroxidation and reducing the in vivo NO production.

Animals↗

PubMed2002

[Respiratory support with high frequency jet ventilation in severely burned patients with inhalation injury during early postburn stage].

OBJECTIVE: To observe the effects of respiratory support with high frequency jet ventilation (HFJV) in severely burned patients with inhalation injury during early postburn stage. METHODS: Twenty severely burned patients with TBSA of 79.6 +/- 29.3% and inhalation injury were enrolled in the study. Nineteen cases received tracheostomy after admission and only one received nasal intubation. All the patients underwent HFJV to correct hypoxia. The changes in blood gas analysis, respiratory rate and pulse were recorded before and 11 days after the ventilation. RESULTS: Tracheostomy was performed on 2.7 +/- 2.4 postburn days (PBDs), and HFJV was given during 4.4 +/- 2.9 PBDs. PaO(2) was evidently higher during 1 - 3 days after HFJV than that before the ventilation (P < 0.01) and remained at high level for 1 week after HFJV. There was no change in PaCO(2), respiratory rate and pulse during the ventilation. CONCLUSION: HFJV was beneficial in improving oxygenation and without any obvious side effects during the early management of severely burned patients with inhalation injury. This might be an optimal respiratory support pattern.

Adult↗

PubMed2002

[An exploration of the preventive effects on lanthanum chloride on enteral bacterial translocation in scalded rats].

OBJECTIVE: To explore the preventive effect of lanthanum chloride on enteral bacterial translocation in scalded rats. METHODS: Ninety Sprague-Dawley (SD) rats were employed in the study and randomly divided into three groups, i.e. normal control (A), burn control (B) and treatment (C) groups. Plasmid PUC19 labelled by JM109 was transfected to Escherichia coli (E. coli), so that restriction endonuclease finger - print image spectrum analysis could be applied to the tracing and quantification of the translocation of E. coli from intestine to mesenteric lymph nodes (MLNs) and blood. The intestinal tissue contents of endotoxin (ET), nitric oxide (NO), nitric oxide synthase (NOS), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. RESULTS: It was identified that the bacteria in MLNs and blood exhibited the same gene map with those from gastric gavage in B and C groups. But the bacterial quantity in MLNs in C group on 3 postburn day (PBD) was much lower than that in B group (P < 0.05). The intestinal MDA content in C group on 1 and 3 PBDs was obviously higher than that in B group (P < 0.05). CONCLUSION: Bacteria (E. coli) could be translocated from gut to MLNs and blood, which could be evidently alleviated by lanthanum chloride by means of its bactericidal property, inhibition of NOS activity, so that NO production decreased, and its ability to increase SOD activity leading to less production of MDA.

Animals↗

PubMed2002

[The influence of lanthanum chloride on the TNFalpha expression of murine peritoneal macrophages stimulated by lipopolysaccharide].

OBJECTIVE: To explore the influence of lanthanum chloride on the TNFalpha expression of murine peritoneal macrophages stimulated by lipopolysaccharide (LPS). METHODS: Murine peritoneal macrophages (Mphi) were isolated, cultured and then stimulated by LPS. The influence of lanthanum chloride on the TNFalpha secretion and TNFalphamRNA expression of murine Mphi stimulated by LPS was determined by ELISA method and SYBR green fluorescence quantitative RT-PCR. Forty BALB/C mice were randomly divided into two groups and were treated by lethal dose of LPS and lanthanum chloride processed LPS, respectively. The mortality within 7 days was observed. RESULTS: The TNFalpha secretion and TNFalphamRNA expression level of the Mphi from mice treated by lanthanum chloride processed LPS were obviously lower than those by LPS only (P < 0.01). The mortality of the mice treated by lethal dose of LPS which has been processed by lanthanum chloride was significantly lower than that by lethal dose of LPS only. CONCLUSION: Lanthanum chloride possessed the capacity of lowering down the toxicity of LPS and inhibiting the TNFalpha secretion and TNFalphamRNA expression in murine Mphi stimulated by LPS.

Animals↗

PubMed2002

[The influence of high frequency partial liquid ventilation on the cardiopulmonary function in dogs with inhalation injury].

OBJECTIVE: To investigate the influence of high frequency partial liquid ventilation (HFJV) on the cardiopulmonary function in dogs with inhalation injury. METHODS: Sixteen mongrel dogs inflicted by hot steam inhalation were subjected to severe inhalation injury and were randomly divided into control (C) and treatment (T) groups. The dogs in both groups were all given HFJV. In addition, the dogs in T group were simultaneously supplied with perfluorocarbon liquid (3 ml/kg) into the lungs slowly via tracheal intubation for liquid ventilation. The blood gas analysis, pulmonary compliance, airway resistance and hemodynamic parameters were determined at 30, 60 and 90 minutes after ventilation. RESULTS: The PaO(2) in T group increased progressively, which was significantly higher than the post-injury value at all time points (P < 0.05). While the PaO(2) in C group exhibited no difference to the post-injury value at all time points. The PaCO(2) in T group increased obviously and was higher than the post-injury value at 60 and 90 post-ventilation minutes (P < 0.05). Furthermore, the PaO(2) in all the time points in T group was a little higher than that in C group (P > 0.05) and PaCO(2) in T group was much higher than that in C group at 90 min after ventilation (P < 0.05). But there was no difference between the two groups in terms of dynamic/static pulmonary compliance and airway resistance as well as the hemodynamics. CONCLUSION: Compared with simple HFJV, high frequency partial liquid ventilation seemed to be beneficial to the oxygenation after inhalation injury and to be no influence on the hemodynamics.

Airway Resistance↗