Biomedical subjects

Yan Yu

Publications and source records attributed to Yan Yu.

At least 73 records · Page 4Linked to original sources

PubMed2004

Identification of two new genes involved in twitching motility in Pseudomonas aeruginosa.

Mu transposition complexes were used for transposon mutagenesis of Pseudomonas aeruginosa strain PA68. Mu DNA transposition complexes were assembled with MuA transposase and an artificial mini-Mu transposon in vitro, and introduced into Pseudomonas aeruginosa by electroporation. Eight mutants deficient in twitching motility were isolated. Southern blotting confirmed that the insertions had occurred as single events. DNA sequencing of the region flanking the insertion in the twitching-motility mutants revealed that the mini-Mu transposon had inserted into six different genes, PAO171, PA1822, PAO413, PA4959, PA4551 and PA5040. Four of these have previously been proven to be needed for twitching motility, whereas the PA1822 and PA0171 genes have not previously been shown to be required for twitching motility. The twitching-motility defect in the PA1822 mutant was partially complemented by providing the PA1822 gene in trans, and the defect in the PA0171 mutant was fully complemented when PA0171 was provided. A PA0171 mutant and a PA1822 mutant were constructed by gene replacement in the P. aeruginosa PAO1 strain. These mutants were deficient in twitching motility, showing that both the PA1822 and the PA0171 gene are involved in twitching motility.

Base Sequence↗

PubMed2004

Contribution of gene loss to the pathogenic evolution of Burkholderia pseudomallei and Burkholderia mallei.

Burkholderia pseudomallei is the causative agent of melioidosis. Burkholderia thailandensis is a closely related species that can readily utilize l-arabinose as a sole carbon source, whereas B. pseudomallei cannot. We used Tn5-OT182 mutagenesis to isolate an arabinose-negative mutant of B. thailandensis. Sequence analysis of regions flanking the transposon insertion revealed the presence of an arabinose assimilation operon consisting of nine genes. Analysis of the B. pseudomallei chromosome showed a deletion of the operon from this organism. This deletion was detected in all B. pseudomallei and Burkholderia mallei strains investigated. We cloned the B. thailandensis E264 arabinose assimilation operon and introduced the entire operon into the chromosome of B. pseudomallei 406e via homologous recombination. The resultant strain, B. pseudomallei SZ5028, was able to utilize l-arabinose as a sole carbon source. Strain SZ5028 had a significantly higher 50% lethal dose for Syrian hamsters compared to the parent strain 406e. Microarray analysis revealed that a number of genes in a type III secretion system were down-regulated in strain SZ5028 when cells were grown in l-arabinose, suggesting a regulatory role for l-arabinose or a metabolite of l-arabinose. These results suggest that the ability to metabolize l-arabinose reduces the virulence of B. pseudomallei and that the genes encoding arabinose assimilation may be considered antivirulence genes. The increase in virulence associated with the loss of these genes may have provided a selective advantage for B. pseudomallei as these organisms adapted to survival in animal hosts.

Animals↗

PubMed2004

[The study of optimal conditions of electroporation in Pseudomonas aeruginosa].

A P. aeruginosa strain PA68 isolated from the sputum of a patient suffering from bronchiectasis was used as the recipient strain. Optimum conditions including growth stage of the strain, electroshock voltage, concentration and preservation of competent cell were defined for the electroporation of PA68 with plasmid pSMC28. It was showed that the highest transformation efficiency was up to 1.68 x 10(3) CFU/microgram DNA under the optimum conditions in which the competent cells were collected at logarithmic growth phase (OD(540) = 0.7-0.8) and concentrated to about 10(11) cells/ml, the mixture of the competent cells and plasmid pSMC28 was eletroporated at 2.6 kV. With this optimal condition, Mu transponson complexes have been successfully transformed into P. aeruginosa strain PA68 and the obtained efficiency was 2.47 x 10(4) CFU/microgram DNA. This is the first time to electroporate Mu transposon complexes into Pseudomonas spp. The artificial Mu transposons could integrate into bacterial genomes at a single site randomly. Then the phenotype change was the result of the gene inactivation caused by Mu transposon insertion. That will be very helpful for the study of genomic function of Pseudomonas spp.

DNA Transposable Elements↗

PubMed2004

[High mobility group box-1 protein activates Janus kinase-signal transducer and activator of transcription pathway in rat peritoneal macrophages].

OBJECTIVE: To investigate the potential signal transduction mechanism in high mobility group box-1 protein (HMGB1)-induced inflammatory response in rat peritoneal macrophages. METHODS: Peritoneal macrophages obtained from male Wistar rats were incubated for 3 days before they were stimulated by HMGB1 (10 microg/ml). At various time points after HMGB1 stimulation, macrophages were denatured directly in cell culture flasks to detect activation of Janus kinase-2 (JAK2), signal transducer and activator of transcription-1 (STAT1) and STAT3 by immunoprecipitation, Western blotting and electrophoretic mobility shift assay, respectively. RESULTS: HMGB1 stimulation could activate STAT1 and STAT3 in peritoneal macrophages in 2 hours, among them the activation of STAT3 appeared to be the quickest, peaking as early as 10 minutes after stimulation. But no marked change in JAK2 activity was observed within 2 hours following HMGB1 stimulation. CONCLUSION: These data suggest that Janus kinase-signal transducer and activator of transcription pathway might be involved in regulation of HMGB1-induced inflammatory response in peritoneal macrophages.

Animals↗

PubMed2004

[Established prolonged selenium deficiency of the SD rat animal model breed third generation in series].

OBJECTIVE: To establish selenium deficiency of the breed third generation SD rats animal model in series. METHODS: A Se-deficient diet mainly based on Se-deficient yeast. Groups of six female and six male SD rats original generation (F0) were fed on one of the five diets: (1) selenium- and iodine-adequate control group (Se+I+ group. Selenium: 0.1-0.3 microg/g, iodine > or = 0.2 microg/g), (2) selenium-deficient iodine-adequate group 1 (Se-I+ group. Selenium: 0.02 microg/g, iodine > or = 0.2 microg/g), (3) selenium-deficient iodine-adequate group 2 (Se-I+ group2. Selenium: 0.005 microg/g, iodine > or = 0.2 microg/g), (4) selenium-adequate iodine-deficient group (Se+I- group. Selenium: 0.1-0.3 microg/g, iodine: 0.04 microg/g), (5) selenium- and iodine-deficient group (Se-I- group. Selenium: 0.01 microg/g, iodine: 0.04 microg/g). Selenium-deficient iodine-adequate group2 had been deled since generation 1 (F1). Serum Se and thyroid hormone concentrations, whole blood glutathione peroxidase (GSH-Px) activities, the weight, childbearing and livability were examined. RESULTS: There were durative lower Se concentrations in serum and lower GSH-Px activities in blood, and the weight, childbearing and livability reduced in Se- group and Se-I- group from F0 to F3. CONCLUSION: We have established prolonged selenium deficiency of the SD rat animal model breed third generation in series successfully.

Animals↗

PubMed2004

[Influence of escharectomy during shock stage on the systemic and intestinal immune function in scalded rats].

OBJECTIVE: To investigate the influence of escharectomy during shock stage on systemic and intestinal immune function and its mechanism in scalded rats. METHODS: Ninety-six Wistar rats were employed in the study of which 8 were used as normal control group. The donor skin from the trunk in twenty-four rats were preserved in liquid nitrogen. The other 64 rats were subjected to 30% full-thickness scalding, and they were randomly divided into A (n = 24, no treatment after scalding), B (n = 24) and C (n = 16) groups. Physiological saline was intraperitoneally injected (50 ml/kg) on the 24 post-scalding hours to the rats in the B and C groups. The rats in B group underwent escharectomy during shock stage, and the excision wounds were covered with the cryo-preserved alloskin. The rats in C group received the same treatment as in B group but at 72 post-scalding hours. The change in the proliferative ability of splenic lymphocytes, the plasma and intestinal tissue content of interleukin 2 (IL-2), the contents of sIgA in intestinal mucus, and the content of DAO in the intestinal tissue were observed on 2, 4 and 8 post burn days (PBD) in A and B groups and also on 4 and 8 PBD in C group, respectively. RESULTS: The splenocytic proliferative ability, IL-2 level in the plasma and intestinal tissue, and the sIgA content in intestinal mucus in the rats in A, B and C groups were lower than that in control group at all time points (P < 0.05). The proliferative ability of splenic lymphocytes in B group on 4 and 8 PBD and in C group on 8 PBD respectively was similar to that in control group. Whereas the IL-2 content in plasma and in intestinal tissue was higher in B and C groups than that in A group (P < 0.01). The sIgA content in intestinal mucus in B group was twice of that in C group respectively [(3.51 +/- 2.14) mg/g vs (1.40 +/- 0.64) mg/g, (3.03 +/- 0.95) mg/g vs (1.52 +/- 1.26) mg/g (P < 0.05 or P < 0.01)] on 4 and 8 PBD. The DAO activity in the intestinal tissue in A group was lower than that in control and B group (P < 0.05) on 4 and 8 PBD. CONCLUSION: Escharectomy during shock stage might be beneficial to the recovery of the systemic and intestinal immune functions in rats with scalding injury.

Animals↗

PubMed2003

Automatic localization of implanted seeds from post-implant CT images.

An automatic localization method of implanted seeds from a series of post-implant computed tomography (CT) images is described in this paper. Post-implant CT studies were obtained for patients who underwent prostate brachytherapy. Bright areas were segmented using binary thresholding in each CT slice, and geometrical information on these areas was collected. Large areas (possibly containing two connected seeds) were split into smaller ones by geometry-based filtering in each slice. The area connectivity along the longitudinal direction was analysed using a geometry-based connection search algorithm executed on every area slice by slice, so that the connected areas were combined into one object. The weighted centroid of each object was taken as the seed position. This method was tested on a seed-containing prostate phantom as well as using CT studies from patients. Statistical analysis demonstrates that it can achieve above 99% detection rate with reliable localization accuracy and high speed. It is reliable and convenient for localizing implanted seeds on CT and can be used to assist post-implant dosimetry for prostate brachytherapy.

Algorithms↗

PubMed2003

The immunolocalisation of VEGF in the articular cartilage of sheep mandibular condyles.

INTRODUCTION: Vascular endothelial growth factor (VEGF) has recently been found to be essential for hypertrophic chondrocyte apoptosis and angiogenesis at the growth plate of long bones, indicating a central role in endochondral ossification. VEGF has more recently, also been shown to be expressed in articular cartilage chondrocytes in human osteoarthritic and rheumatoarthritic joints but not healthy adult joints. To investigate the role of VEGF in the fibrocartilage of the temporomandibular joint, this study aimed to document the presence and distribution of VEGF in the condylar articular cartilage of sheep temporomandibular joints. METHODS: Mandibular condyles of the temporomandibular joints of five 18-month old Wether sheep were fixed, decalcified, paraffin embedded and sectioned. The sections were analyzed using immunohistochemistry for VEGF. RESULTS: VEGF was found to be localised predominantly to the proliferative and maturing layers of chondrocytes in the condylar fibrocartilage of the temporomandibular joints. Articular cartilage is an avascular and alymphatic tissue. As such, the localisation of VEGF to the articular cartilage of normal temporomandibular joint condyles suggests a role for VEGF other than angiogenesis. CONCLUSION: VEGF is shown here for the first time to be present in mandibular condylar cartilage, leading us to propose a possible role in non-angiogenic extracellular matrix remodeling.

Animals↗

PubMed2003

Use of a polymeric device to deliver growth factors to a healing fracture.

BACKGROUND: Fracture healing is a cascade of events regulated by systemic and local factors. Local growth factors are believed to play an integral role. The present study evaluates the effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) using a controlled delivery system in a closed rodent femoral fracture model. METHODS: Female Wistar rats (n = 144) were used in the present study. Animals were randomly allocated to six groups, with each group divided into three time-points of 2, 4 and 8 weeks. Two groups had growth factor administered. The others had no operation or sham operations. Growth factors were delivered to the fracture site using a specialised delivery system. This consisted of a Kirschner-wire coated with ethylene vinyl acetate co-polymer embedded with growth factors, inserted as an intramedullary nail. Fractures were effected with a three-point bending device. Femurs were tested in four-point bending and structural properties of peak load and stiffness were obtained from the load-displacement graphs. Specimens were prepared for qualitative analysis under a light microscope and using immunohistochemistry, specimens were analysed for expression of bFGF, IGF-1 and transforming growth factor beta (TGF-beta). RESULTS: The growth factor-treated groups exhibited larger calluses at 2 and 4 weeks. Four-point bending showed weaker structural properties (stiffness and peak load) at 4 weeks in both growth factor-treated groups. Administration of bFGF or IGF-1 increased the ratio of cartilaginous to mesenchymal tissues in the fracture callus compared with non-treated animals at 2 and 4 weeks. Immunostaining intensity and distribution of both growth factors in the treated groups was greater than the non-treated groups. CONCLUSION: Exogenous delivery of bFGF or IGF-1 alters the course of fracture healing.

Animals↗

PubMed2003

The role of nerve growth factor and brain-derived neurotrophic factor in inferior alveolar nerve regeneration in distraction osteogenesis.

Distraction osteogenesis (DO) has become the mainstay of treatment of mandibular hypoplasias. Despite the clinical acceptance of the technique in the last decade, little is known of the biological mechanism of bone and soft tissue regeneration. The biological response of peripheral nerves to distraction has not been well documented. This study examined the role of two neurotrophic molecules, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in DO on nerve regeneration of the inferior alveolar nerve (IAN) in an ovine mandible model. Twelve animals were randomly divided into three groups and distracted at 5, 10, and 15 days using a mandibular osteotomy and uniaxial external distractor. The mental nerves and the IAN from the distracted site were harvested at the end of the distraction period and examined for the presence of NGF and BDNF using immunohistochemistry. Nerve growth factor expression was increased at both sites, whereas BDNF was only expressed at the mental nerve on the distracted side. Nerve growth factor and BDNF are involved in the response of the peripheral nerves to injury. Mechanical force applied to the IAN by distraction may lead to detachment of Schwann cells from their axons, leading to segmental degeneration. The resulting myelin sheath debris may serve as a trigger for higher expression of NGF and BDNF, facilitating Schwann cell proliferation and remyelination of the affected segment. Distraction of the mandible may serve as a source of subacute injury to the IAN and influence NGF and BDNF.

Animals↗

PubMed2003

The potential role of Staphylococcal enterotoxin B in rats with postburn Staphylococcus aureus sepsis.

Staphylococcal enterotoxin B (SEB) is an important member of the superantigen family, which exerts a number of pathological effects in the human, as well as susceptible animals. The present study was conducted to observe the time course and tissue distribution of SEB in postburn Staphylococcus aureus infection; meanwhile, the relationship between SEB and multiple organ dysfunction was also studied. Eighty-six male Wistar rats were randomly divided into four groups as follows: normal control group (n = 10); scald control group (n = 10); postburn sepsis group (n = 50) in which rats inflicted with 20% total body surface area (TBSA) III degrees scald followed by SEB-producing S. aureus challenge were further divided into 0.5-, 2-, 6-, 12-, and 24-h subgroups, with 10 rats in each subgroup; and SEB monoclonal antibody (MAb) treatment group (n = 16) in which a dose of 4 mg/kg SEB MAb was given intravenously just before S. aureus challenge, and the rats were further divided into 2- and 6-h subgroups. It was found that after thermal injury combined with S. aureus infection, SEB was widely distributed to the liver, kidneys, lungs, and heart, exacerbating the pathophysiology of multiple organ dysfunction induced by postburn sepsis. At the same time, the gene and protein expressions of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were also markedly upregulated in various tissues. Early treatment with SEB-specific MAb-MAb2D(1)-could markedly decrease SEB levels in plasma as well as in various tissues, and could significantly reduce the 6-h mortality rate (17.64% [3/17] vs. 55.6% [20/36], P = 0.02). These data suggested that neutralization of SEB is effective in ameliorating S. aureus sepsis and subsequent multiple organ damage, which might be attributed to its inhibitory effect on inflammatory mediator formation.

Animals↗

PubMed2003

Significance of biopterin induction in rats with postburn Staphylococcus aureus sepsis.

It has been demonstrated that biopterin, an essential cofactor of nitric oxide synthase (NOS), plays an important role in the pathogenesis of endotoxin-induced shock, yet its biological significance in gram-positive sepsis remains unclear. In this study, we adopted a rat model of postburn Staphylococcus aureus sepsis to investigate the potential role of biopterin in the pathogenesis of gram-positive sepsis. Wistar rats were inflicted with a 20% total body surface area (TBSA) full-thickness scald injury followed by S. aureus challenge, and then guanosine triphosphate-cyclohydrolase I (GTP-CHI) mRNA expression and biopterin levels in liver, kidneys, lungs, and heart were determined. We found that after S. aureus challenge, GTP-CHI gene expressions and biopterin levels were markedly upregulated in various tissues. Meanwhile, multiple organ dysfunction was induced by S. aureus challenge. It was shown that cardiac GTP-CHI mRNA expression and renal BH(4) levels were positively correlated with MB isoenzyme of creatine kinase (CK-MB) and creatinine (r = 0.892, P = 0.0012 and r = 0.9423, P = 0.0015, respectively). These results suggested that thermal injury combined with S. aureus challenge could induce de novo biosynthesis of biopterin, which might play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.

Animals↗

PubMed2003

Optimal marker placement in photogrammetry patient positioning system.

A photogrammetry-based patient positioning system has been used instead of the conventional laser alignment technique for patient set-up in external beam radiotherapy. It tracks skin affixed reflective markers with multiple infrared cameras. The three-dimensional (3D) positions of the markers provide reference information to determine the treatment plan isocenter location and hence provide the ability to position the lesion at the isocenter of the treatment linear accelerator. However, in current clinical practice for lung or liver lesion treatments, fiducial markers are usually randomly affixed onto the patients' chest and abdomen, so that the actual target registration error (TRE) of the internal lesions inside the body may be large, depending on the fiducial registration error (FRE). There exists an optimal marker configuration that can minimize the TRE. In this paper, we developed methods to design the patient-specific optimal configurations of the surface makers to minimize the TRE, given the patient's surface contour, the lesion position and the FRE. Floating genetic algorithm (GA) optimization was used to optimize the positions of the skin markers. The surface curve of the patient body was determined by an automatic segmentation algorithm from the planning CT. The method was evaluated using a body phantom implanted with a metal ball (a simulated target). By registering two CT scans using the surface markers and measuring the displacement of the target, the TRE was measured. The TRE was also measured by taking two orthogonal portal films after positioning the phantom using the photogrammetry based patient positioning system. A 50% reduction in TRE has been achieved by using the optimal configuration compared to the random configuration. This result demonstrates that the optimization of a fiducial configuration can result in improved tumor targeting ability.

Humans↗

PubMed2003

The mRNA expression patterns of tumor necrosis factor-alpha and TNFR-I in some vital organs after thermal injury.

AIM: To investigate changes of tumor necrosis factor-alpha (TNF-alpha) and TNFR-I expression in vital organs and their significance in the pathogenesis of multiple organ damage associated with endogenous endotoxin following major burns. METHODS: Wistar rats subjected to a 35 % full-thickness scald injury were sacrificed at 12 h, 24 h, 48 h, and 72 h postburn, respectively. Meanwhile, eight rats were taken as normal controls. Tissue samples from liver, spleen, kidney, lung and intestine were collected to assay tissue endotoxin levels and measure TNF-alpha and TNFR-I expression. In addition, blood samples were obtained for the determination of organ function parameters. RESULTS: Endotoxin levels in liver, spleen and lung increased markedly after thermal injury, with the highest level in liver. The gene expression of TNF-alpha in liver, lung and kidney was up-regulated after thermal injury, while the TNFR-I mRNA expression in liver, lung, kidney and intestine was shown decreased throughout the observation period. Thus, the mRNA expression ratio of TNF-alpha to TNFR-I was significantly increased postburn, particularly in pulmonary tissue (67-fold). In addition, the significant correlations between the expression of TNFR-I or the expression ratio of TNF-alpha/TNFR mRNA in liver tissue and serum aspartate aminotransferase levels were noted (P<0.05-0.01). Similar results were also obtained between pulmonary TNF-alpha mRNA expression and myeloperoxidase activities (P<0.01), whereas there was a highly negative correlation between levels of renal TNFR-I mRNA expression and serum creatinine. CONCLUSION: Burn injury could result in the translocation of gut-derived endotoxin that was mainly distributed in the liver, spleen and lung. The translocated endotoxin then made the expression of TNF-alpha and TNFR-I mRNA up-regulated and down-regulated respectively in various organs, which might be involved in the pathogenesis of multiple organ damage following burns.

Animals↗

PubMed2003

[Filtration capability of the bio-dynamic membrane].

The filter modules made of common mesh material were submerged in to a bioreactor to form a dynamic-membrane bioreactor. This paper studied the filtration capability of the dynamic bio-membrane forming on 100-micron Dacron mesh material. The outstanding solid-liquid separation capability of the dynamic bio-membrane was mainly contributed to the gel-layer attaching on the mesh material. The dynamic bio-membrane could checked 30%-60% TOC of various molecule weights ranging < 3000 to > 10(5), whereas its separation accuracy was not high enough to intercept all the organics of molecules weights larger than 10(5). The tap water filtration resistance of the dynamic bio-membrane sheet with gel-layer attaching on was about 1.9 x 10(9) m-1, which almost equaled to that of the untapped sheet. The resistance caused by cake-layer contributed about 70% to the total filtration resistance of the dynamic bio-membrane on working. The untapped dynamic bio-membrane sheet showed an initial resistance to tap water permeation, but the one with gel-layer attaching on had little initial resistance. The reason might be that the gel-layer eliminated the hydrophobicity of the mesh material.

Bioreactors↗

PubMed2003

[Potential role of JAK/STAT in regulating Toll-like receptor 2 gene expression in rats with postburn Staphylococcus aureus sepsis].

OBJECTIVE: To investigate the potential role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway in regulating Toll-like receptor 2 (TLR2) gene expression in postburn Staphylococcus aureus infection. METHODS: Thirty-eight male Wistar rats were randomly divided into four groups as follows: normal control group (n=6), postburn sepsis group (n=12), AG490 treatment group (n=10) and Rapamycin (RPM) treatment group (n=10). Tissue samples from the liver, kidneys and lungs were collected to determine TLR2 and TNF-alpha mRNA expressions. RESULTS: It was found that, 0.5 and 2 hours after Staphylococcus aureus challenge, TLR2 mRNA expressions in the liver, kidneys and lungs from postburn septic animals were up-regulated rapidly (P<0.05 or P<0.01). Treatment with RPM could effectively inhibit TLR2 mRNA expressions in the liver and kidneys. However, TLR2 mRNA expressions in the above tissues from AG490 treated animals had no significant differences with those from normal controls. Two hours after Staphylococcus aureus challenge, TNF-alpha mRNA expressions in the liver, kidneys and lungs were also increased markedly (all P<0.01). Both treatment with RPM and AG490 could significantly inhibit the up-regulation of all tissue TNF-alpha mRNA expressions (P<0.05 or P<0.01), and AG490 were more significant in liver and kidneys (both P<0.01). CONCLUSION: It is suggested that scald injury combined with Staphylococcus aureus infection can up-regulate TLR2 expression, which appears to be associated with the signal transduction of STAT.

Animals↗

PubMed2003

[Role of Janus kinase/signal transducer and activator of transcription pathway in mediating mRNA expression of high mobility group box1 protein in the liver in septic rats].

OBJECTIVE: To investigate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in mediating mRNA expression of high mobility group box 1 protein (HMGB1) in the liver in septic rats. METHODS: Using a sepsis model of cecal ligation and puncture (CLP), 98 male Wistar rats were randomly divided into normal control group (n=10), CLP group (n=40), AG490 treatment group (n=24), and Rapamycin (RPM) treatment group (n=24). At serial time points animals in each group were sacrificed, and blood as well as hepatic tissue samples were harvested to determine HMGB1 mRNA expression and serum aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents. RESULTS: Compared with normal controls, HMGB1 mRNA levels were significantly increased in the liver during 6-48 hours after CLP (P<0.01), and serum AST and ALT contents were significantly elevated at different time points respectively (P<0.05 or P<0.01). Treatment with AG490 and RPM could markedly inhibit HMGB1 mRNA expression in the liver at 24 hours, 48 hours, 6 hours and 24 hours after CLP, respectively. In addition, compared to CLP group, serum AST and ALT contents in both treatment groups could be markedly reduced at various intervals after CLP (P<0.05 or P<0.01). CONCLUSION: These data suggest that the activation of JAK/STAT pathway might be involved in mediating up-regulation of HMGB1 mRNA expression in the liver in CLP-induced sepsis. Treatment with inhibitors of JAK/STAT pathway could markedly down-regulate HMGB1 mRNA expression and attenuate acute liver injury associated with sepsis.

Alanine Transaminase↗

PubMed2003

[The potential role of high mobility group-1 protein in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome in rats].

OBJECTIVE: To investigate the potential role of high mobility group-1 protein (HMG-1) in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome in rats. METHODS: Using a sepsis model by cecal ligation and puncture (CLP), 80 male Wistar rats were randomly divided into four groups: normal control (n = 10), sham operation (n = 10), CLP (subdivided into 2, 6, 12, 24, 48, 72 h post-CLP, n = 60), and sodium butyrate treatment (subdivided into 12, 24 h post-CLP, n = 20). At serial time points in each group, animals were sacrificed, and blood as well as tissue samples from the liver, lung, kidney and small intestine were harvested to measure organ function parameters and HMG-1 mRNA expression by the reverse transcription polymerase chain reaction (RT-PCR) taking GAPDH as an internal standard. Also, additional experiments were performed to observe the effect of treatment with sodium butyrate on survival rate in septic rats (n = 57). RESULTS: HMG-1 mRNA levels significantly increased in various tissues during 6 - 72 h after CLP (P < 0.05 or 0.01), and were markedly inhibited by sodium butyrate at 12 h and 24 h (P < 0.05 or 0.01). Early treatment with sodium butyrate also could markedly reduce serum alanine aminotransferase, creatinine levels at 12 h post-CLP and pulmonary myeloperoxidase activities at 24 h. Furthermore, treatment with sodium butyrate could significantly improve the 1- to 6-day survival rates in animals subjected to CLP (P < 0.05 or 0.01). CONCLUSIONS: HMG-1 might play an important role in the development of excessive inflammatory response and subsequent multiple organ dysfunction syndrome.

Animals↗