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Biomedical subjects

Yan Yu

Publications and source records attributed to Yan Yu.

84 records · Page 5Linked to original sources

[Study on the genic polymorphism of HLA-DRB1 in a population in the north of China].

OBJECTIVE: To investigate at the DNA level the polymorphism of HLA-DRB1 gene in Han population in Beijing of China. METHODS: This study was conducted in the Hans in Beijing. A total of 2810 normal and unrelated neonates were analyzed and subjected to HLA-DRB1 low resolution typing, and from among them 217 neonates were randomly selected for DRB1 high resolution typing by polymerase chain reaction-sequence specific primers technique. RESULTS: Fourteen HLA-DRB1 specificity and 39 alleles were found with HLA-DRB1 *09012, *1501, *07011, *08032 as the most common genes. Their gene frequencies and allelic distributions were compared to those observed in other ethnic populations. CONCLUSION: The results showed the characteristic of HLA-DRB1 distribution, and provided more comprehensive and accurate gene data that may serve as normal reference values for the population in Beijing, China.

Asian People↗

[Changes in Toll-like receptor 2 and 4 gene expression in vital organs in septic rats and their regulation mechanisms].

OBJECTIVE: To investigate the changes in Toll-like receptor (TLR) 2 and 4 gene expression in vital organs in septic rats and their potential regulation mechanism. METHODS: One hundred Wistar rats were randomly divided into normal controls (n=10), sham-operated group (n=10), septic group (n=60), and recombinant bactericidal/permeability increasing protein (BPI)-treated group (n=20). Severe sepsis was replicated by cecal ligation and puncture (CLP). Animals were sacrificed at different time points after CLP, tissue TLR2/4 mRNA expression in the liver, lungs, kidneys as well as intestine were measured by reverse transcription-polymerase chain reaction (RT-PCR). Plasma levels of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) were also determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: TLR2/4 mRNA could be detected in various tissues with low values both in normal controls and sham-operated group, but they were markedly up-regulated at 2 hours after CLP, peaking at 6-12 hours. Tissue TLR4 mRNA was gradually down-regulated 24 hours later, while TLR2 mRNA levels maintained high values up to 72 hours. In comparison with the CLP group, treatment with BPI significantly decreased TLR2 mRNA in various tissues at 12 and 24 hours (P<0.05 or P<0.01), also tissue TLR4 mRNA at 12 hours (P<0.05 or P<0.01), without marked influence on TLR4 mRNA expression at 24 hours in liver, lungs and small intestine (P>0.05). In addition, treatment with BPI could significantly lower plasma TNF-alpha levels at 12 hours post-CLP, on the other hand markedly elevate plasma IL -10 levels 24 hours later (P<0.01). CONCLUSION: These data suggest that severe peritoneal infection could result in up-regulation of TLR2/4 mRNA expression in vital organs, which might play important roles in mediating proinflammatory cytokine synthesis and release. Endotoxemia appears to be involved in the activation of tissue TLR2/4 expression associated with CLP-induced sepsis.

Animals↗

TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing.

Smads are cytoplasmic signal transducers of transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-beta and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-beta, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 were similar to that of BMPs-2 and 7 whereas the expression of Smads2 and 3 was parallel with that of TGF-beta. The Smad family, associated with BMPs and TGF-beta, may play an important role in the early stage of rat fracture healing.

Animals↗

Wound healing and growth factor expression in T lymphocyte deficiency.

BACKGROUND: There are many clinical situations in which immune suppression or deficiency occurs. This may lead to healing impairment. The aim of the present study was to characterize the effect of T lymphocyte deficiency on wound healing, and on -platelet-derived growth factor (PDGF), bFGF (basic fibroblast growth factor) and insulin-like growth factor-1 (IGF-1) expression, using an animal model. METHODS: Nude and normal 10-12-week-old male BALB/c mice were given standard dermal incisions and killed at 1, 2, 4 or 6 weeks postinjury. The pelts were harvested and the wounds cut (perpendicularly) into strips for analysis. Strips from each animal were tested mechanically or processed for histological assessment and immunohistochemical detection of PDGF, bFGF and IGF-1 and colour video image analysis. The data were assessed by analysis of variance (anova). RESULTS: The interaction between species and time resulted in statistically significant differences in mechanical properties. Wound peak load was higher in nude mice at weeks 1 and 2 postinjury, but lower in nude mice at week 6 postinjury. Colour video image analysis demonstrated that the expression of bFGF and IGF-1 was greater in nude mice at week 1 postinjury (P < 0.05). CONCLUSIONS: The mechanical data suggest that the overall effect of the T lymphocyte system on wound healing is initially inhibitory and later stimulatory. This may be associated with corresponding differences in wound growth factor expression.

Animals↗

Matrix metalloproteinases and their inhibitors in bone remodelling following distraction osteogenesis of the sheep mandible.

AIM: Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen and other matrix substrates in bone and other tissues. This study evaluated the expression of MMPs and TIMPs in bony remodelling in a bilateral sheep mandible model up to 12 months following lengthening by distraction osteogenesis. METHODOLOGY: Sheep mandibles were harvested 3, 6, 9 or 12 months following lengthening by bilateral mandibular distraction (1 mm/day for 20 days). Undistracted sheep mandibles were used as controls. The tissues underwent routine histology and immunohistochemical staining with monoclonal antibodies specific to MMPs 1-3 and TIMP-1, 2. Matrix and cell staining was assessed using a semi-quantitative analysis. RESULTS: Matrix metalloproteinases and their tissue inhibitors (TIMPs) expression levels were marked at 3 months and decreased thereafter becoming similar to undistracted controls by 12 months. The histologic development of mature lamellar cortical bone was similar to undistracted controls by 9 months following distraction. CONCLUSIONS: A temporal expression of MMPs and TIMPs was found in distraction osteogenesis. MMPs and TIMPS may, in part, reflect the state of bony remodelling following mandibular lengthening by distraction osteogenesis. Matrix metalloproteinases and TIMP expression were comparable to undistracted controls by 12 months, suggesting that equilibrium had been achieved and that bony relapse is unlikely.

Animals↗

Effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats.

OBJECTIVE: Guanosine triphosphate-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo biosynthesis of biopterin. The objective of present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP-CHI, on the development of postburn Staphylococcus aureus sepsis. DESIGN: A prospective, controlled animal study. SETTING: A research laboratory in a hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: Fifty-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 = 20), and DAHP treatment group (n = 16). In the scald control group, rats were subjected to a 20% total body surface area third-degree scald injury and then were killed at 24 hrs. In the postburn sepsis group (n = 20), rats were inflicted with 20% total body surface area third-degree scald followed by Staphylococcus aureus challenge, and they were further divided into 2- and 6-hr groups. In the DAHP treatment group (n = 16), animals were intraperitoneally injected with a dose of 1 g/kg DAHP before Staphylococcus aureus challenge and then were further divided into 2- and 6-hr groups. Tissue samples from liver, kidneys, lungs, and heart were collected to determine GTP-CHI, inducible nitric oxide synthase, and tumor necrosis factor-alpha messenger RNA expression. Meanwhile, biopterin and nitric oxide concentrations in these tissues were also measured. MEASUREMENTS AND MAIN RESULTS: After the scald injury followed by Staphylococcus aureus challenge, GTP-CHI messenger RNA expression and biopterin concentrations were significantly elevated in various tissues such as liver, heart, kidneys, and lungs, as were the values of inducible nitric oxide synthase messenger RNA expression and nitric oxide formation (p <.01). Pretreatment with DAHP significantly reduced GTP-CHI/biopterin induction (p <.05-.01), and the up-regulation of inducible nitric oxide synthase/nitric oxide was also suppressed. Furthermore, DAHP administration inhibited the gene expression of tumor necrosis factor-alpha. Two hours after septic challenge, tumor necrosis factor-alpha messenger RNA expression in liver, kidneys, and lungs in the DAHP-treated group was 35.7%, 37.3%, and 33.0% of that in the postburn septic group, respectively. Additionally, in animals without DAHP treatment, the 6-hr mortality rate was 55.6% (20 of 36), whereas it was only 25.0% in DAHP-treated animals (4 of 16, p =.08). CONCLUSIONS: Early treatment with DAHP might be a potential strategy to prevent the development of postburn Staphylococcal sepsis, which appears to be associated with down-regulation of biopterin and nitric oxide formation by DAHP.

Analysis of Variance↗

Lipopolysaccharide-binding protein and lipopolysaccharide receptor CD14 gene expression after thermal injury and its potential mechanism(s).

BACKGROUND: We hypothesized that lipopolysaccharide-binding protein (LBP) and lipopolysaccharide receptor CD14 would present a pair of key molecules in pathophysiologic alterations induced by low concentrations of endotoxin after trauma. The aim of this study was to investigate the relationship between endotoxin translocation and tissue LBP/CD14 messenger ribonucleic acid (mRNA) expression after burn injury, and to define the potential role of LBP/CD14 in mediating inflammatory mediator induction, as well as the pathogenesis of organ damage. METHODS: Wistar rats were subjected to a 35% full-thickness scald injury, and tissue samples from liver, kidneys, lungs, and intestine were collected to measure LBP/CD14 and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. Peritoneal macrophages were harvested by peritoneal lavage to determine CD14 mRNA expression. RESULTS: It was found that endotoxin levels in liver, spleen, and lung increased markedly after thermal injury, with the highest level in liver. Both tissue LBP and CD14 mRNA expression increased markedly after burns, peaking at 12 hours, and then decreasing gradually. At 48 hours, LBP gene expression had a tendency to the baseline level, whereas CD14 mRNA expression increased again. Likewise, CD14 mRNA levels were up-regulated markedly in peritoneal macrophages. Conversely, gene expression of TNF-alpha in tissues elevated markedly after acute insults. There were positive correlations between lipopolysaccharide levels and LBP/CD14 mRNA as well as TNF-alpha mRNA expression in tissues. Similar results were also obtained between CD14, TNF-alpha mRNA expression in liver tissue and liver function parameters, and between pulmonary TNF-alpha mRNA and myeloperoxidase activities (p < 0.01). CONCLUSION: Thermal injury per se can markedly up-regulate both LBP and CD14 gene expression in various organs. Excessive LBP and CD14 mRNA expression might be associated with enhanced synthesis and release of TNF-alpha stimulated by endotoxin translocation after major burns.

Acute-Phase Proteins↗

The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury.

There has been a widespread impression that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mediate the toxicity of high doses of lipopolysaccharide (LPS, endotoxin) and are key factors in septic shock. However, the clinical efficacy of treatment with antagonists of TNF-alpha and IL-1beta is still controversial, suggesting that mediators other than TNF-alpha and IL-1beta might contribute causally to endotoxin-induced death. Recent studies implicated high mobility group-1 (HMG-1) protein as a late mediator of endotoxin lethality in mice. However, the role of HMG-1 in mediating multiple organ damage-associating trauma has not been studied. This study was designed to investigate changes in HMG-1 gene expression in vital organs, and its potential role in mediating multiple organ damage following major burns. Wistar rats were subjected to a 35 percent full-thickness thermal injury, and randomly divided into three groups as follows: normal controls (n = 7), thermal injury (n = 24), and recombinant bactericidal/permeability-increasing protein (rBPI21) treatment (n = 12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG-1 mRNA expression. In addition, blood samples were obtained for measurement of organ function parameters. Our data demonstrated a significant increase in HMG-1 gene expression in tissues at 24 h postburn, which remained markedly elevated up to 72 h after thermal injury (P< 0.05-0.01). Treatment with rBPI21 could significantly decrease tissue HMG-1 mRNA expression in the liver and lung (P < 0.01). In addition, there were high positive correlations between hepatic HMG-1 mRNA and serum aminoleucine transferase (ALT) and aspartate aminotransferase (AST) levels, and also between pulmonary HMG-1 mRNA and myeloperoxidase activities (P < 0.05-0.01). Taken together, these findings indicate that thermal injury per se can markedly enhance HMG-1 gene expression in various organs. Up-regulation of HMG-1 expression may be involved in the pathogenesis of endogenous endotoxin-mediated multiple organ damage secondary to major burns.

Alanine Transaminase↗

[The protective effects and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats].

OBJECTIVE: To investigate the protective effect and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP-cyclohydrolase I (GTP-CHI), on postburn Staphylococcus aureus (S. aureus) sepsis in rats. METHODS: Fifty-six Wistar rats were randomly divided into four groups, i.e. normal control, scalding control, postburn sepsis group and DAHP treatment group. Tissue samples from liver, kidneys, lungs and heart were aseptically taken, and in which the GTP-CHI and inducible nitric oxide synthase (iNOS) contents and the mRNA expression of tumor necrosis factor-alpha (TNFalpha) were determined. Furthermore, biopterin (BH(4)) and nitric oxide (NO) levels in these tissue were also measured. RESULTS: After the scalding injury followed by bacterial challenge, the GTP-CHI gene expression and biopterin levels were significantly increased in all tissue sampled, and so were iNOS mRNA expression and NO (P < 0.01), especially in liver and lungs. The expressions of GTP-CHI mRNA and iNOS mRNA and the production of BH(4) and NO in all tissue were evidently inhibited by the pretreatment with DAHP (P < 0.05 approximately 0.01). At the same time, the TNFalpha expression was also obviously decreased. In addition, The mortality at 6 hr in rats of DAHP treatment group was decreased. CONCLUSION: The prognosis of the scalding rats complicated by sepsis caused by G(+) bacteria could be improved by DAHP pretreatment, which might be related to the inhibition of the production of BH(4) and NO by DAHP.

Animals↗

[The change in CD14 mRNA expression in rats with scald injury and Staphylococcus aureus challenge].

OBJECTIVE: To investigate the potential role and changes in CD14 in postburn Staphylococcus aureus sepsis. METHODS: Wistar rats were subjected to a 20% total body surface area (TBSA) full-thickness thermal injury and followed by Staphylococcus aureus challenge. Plasma and tissue samples from liver, kidneys, lungs and heart were collected to determine endotoxin (lipopolysaccharide, LPS) levels and CD14 mRNA expression. RESULTS: It was found that after thermal injury combined with Staphylococcus aureus sepsis, LPS levels in various tissues were markedly increased, peaking at 2 approximately 6 h (P < 0.05), then returned to baseline at 24 h. Plasma LPS level was also increased significantly at 2hrs after Staphylococcus aureus challenge compared with that in normal control animals (0.3056 EU/ml vs. 0.1250 EU/ml, P < 0.05). In addition, the intestinal diamine oxidase (DAO) activity decreased (P < 0.05). This indicated that the integrity of intestinal mucosa was damaged. Meanwhile, tissue CD14 mRNA expressions were up-regulated in all tissues (P < 0.05), especially in lungs. CONCLUSION: These data suggested that gut-originated LPS translocation and CD14 mRNA expression could be induced by thermal injury with Staphylococcus aureus sepsis. The up-regulation of CD14 gene expression might be associated with the local endotoxin activation secondary to postburn sepsis.

Animals↗

[A submerged dynamic membrane bioreactor for domestic wastewater treatment].

The dynamic membrane forming on the surface of 0.1 mm Dacron mesh was utilized instead of static membrane, e.g. hollow fiber membrane, to develop a submerged dynamic membrane bioreactor (DMBR). The DMBR had high quality effluents when treating domestic wastewater at HRT = 3.5 h. The dynamic membrane could work steadily at a pressure no more than several centimeters water head drop. The highest SS concentration in the effluents was 4.05 mg/L, whereas the measured SS concentrations were zero in most circumstances. At condition of MLSS = 7000-8000 mg/L, the effluent head drop was only 5.8 mm when flux = 14.9 L/(m2.h), and it had little change during a continuous run for 27 days. The dynamic membrane averagely removed 28.74% of COD and 36.9% of TOC in the supernatant of the mixed liquor. The DMBR could remove NH3-N more than 96% when DO in the mixed liquor was no less than 2-3 mg/L.

Bioreactors↗

Expression of the KAI1 metastasis suppressor gene in non-metastatic versus metastatic human colorectal cancer.

BACKGROUND: The importance of KAI1 to colorectal cancer (CRC) progression is unclear, with conflicting data regarding changes in KAI1 expression during tumour progression. MATERIALS AND METHODS: In situ hybridisation and immunohistochemistry, with a semiquantitative scoring system, were used to assess KAI1 mRNA and protein levels, respectively, in normal colon samples (43), and non-metastatic (24) or metastatic (33) primary cancers, and liver metastases (48). RESULTS: There was significant loss of KAI1 mRNA and protein staining in non-metastatic primary tumours versus normal tissues (Bonferroni, p < 0.05) but levels recovered to near normal in metastatic primary tumours and liver metastases. Increased KAI1 expression significantly correlated with distant metastases (Mann-Whitney, p = 0.0001, mRNA; p = 0.033, protein), cancer-specific survival (Cox regression analysis p = 0.0002, mRNA; 0.0493, protein) and overall patient survival (p = 0.0001, mRNA). Multivariate analysis (Cox proportional hazards model) confirmed high KAI1 mRNA expression was an independent prognostic indicator of distant metastasis (p < 0.0001), cancer-specific survival (p < 0.0001) and overall patient survival (p < 0.0001). CONCLUSION: These data indicate a complex relationship between KAI1 and progression of human CRC, in which expression is reduced in localised primary tumours, but regained in disease associated with metastasis.

Analysis of Variance↗