Cervical sympathetic block regulates early systemic inflammatory response in severe trauma patients.

BACKGROUND: This aim of this study was to investigate the effects of one-side cervical sympathetic block on early inflammatory response in severe trauma patients. MATERIAL AND METHODS: Thirty severe trauma patients with injury severity score (ISS) of 16 to 25 were randomly divided into treatment and control groups (n=15 each). Patients in the treatment group underwent a right-side stellate ganglion block (SGB) using 8 mL 0.75% ropivacaine for 4 times, with the first injection within 12 hr of admission and the other 3 injections were 12 hr, 24 hr and 48 hr later. The same procedures were performed for the control group except that normal saline was injected instead of ropivacaine. Blood was collected before injection and at 6 hr, 24 hr, and 72 hr after the first SGB for serum interleukin (IL)-1beta, IL-4, IL-6, IL-10 and TNF-alpha measurement. RESULTS: The concentrations of IL-1beta, IL-6, and TNF-alpha between 24 hr to 72 hr after SGB were all significantly lower than those in the control group (all P values <0.01). However, there was no significant difference in the concentrations of anti-inflammatory IL-4 and IL-10 between treatment and control groups. There was no obvious impact of SGB on breathing and circulation except for a slower heart rate 10 to 50 min after injection (P<0.01). CONCLUSIONS: SGB regulates early inflammatory response through inhibition of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha during severe trauma. SGB has no impact on the levels of anti-inflammatory cytokines IL-4 and IL-10.

Effects of SCR-3 on the immunosuppression accompanied with the systemic inflammatory response syndrome.

Steroid receptor coactivator-3 (SRC-3) is a multifunctional protein that plays an important role in mammary gland growth, development, and tumorigenesis. In this study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the immunosuppression accompanied with systemic inflammatory response syndrome (SIRS). Bacterial clearance assay was performed by blood culture and frozen sections, and the results showed that the absence of SCR-3 protein serious damaged the innate immune system and the body's ability to inactivate or phagocytosis of bacteria was significantly decreased, and the absence of SCR-3 protein also weakened phagocytes' ability to degrade bacteria and their metabolites. Furthermore, animal model of inflammatory reaction was established and the immune function was determined, and the results revealed that SRC-3 protein may play an important role in maintenance of T-cells' immune function, and severe T-cell immune function disorder would be resulted once SRC-3 protein is missing. In addition, the results of our study showed the steady-state of lymphocyte subsets was destroyed after SIRS, leading the suppression of cellular immune function, and the absence of SCR-3 protein may aggravate the suppression of T-lymphocyte function. Therefore, the present study demonstrated that the absence of SCR-3 protein would aggravate immunosuppression. In addition, SRC-3 protein is a significant regulator of infection and inflammation, and SRC-3 protein play an essential role in the development of immunosuppression accompanied with SIRS.

Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue.

The efficacy of granulocyte colony-stimulating factor (G-CSF) in mobilizing mesenchymal stem cells (MSCs) into peripheral blood (PB) and the ability of PB-MSCs incorporated into injured brain were tested. Colony forming, cell phenotype and differentiation potential of mouse MSCs mobilized by G-CSF (40 µg/kg) were evaluated. Mortality and pathological changes in mice with serious craniocerebral trauma plus G-CSF treatment (40 µg/kg) were investigated. Bone marrow (BM) cells derived from GFP mice were fractionated into MSCs, hematopoietic stem cells (HSCs), and non-MSC/HSCs using magnetic beads and adherent culture. The resultant cell populations were transplanted into injured mice. The in vivo integration and differentiation of the transplanted cells were detected immunocytochemically. The expression of SDF-1 in injured area of brain was tested by Western blot. G-CSF was able to mobilize MSCs into PB (fourfold increase). PB-MSCs possessed similar characteristics as BM-MSCs in terms of colony formation, the expression pattern of CD73, 44, 90, 106, 31 and 45, and multipotential of differentiation. Accumulative total mice mortality was lower in TG group (5/14) than that in T group (7/14). It was MSCs, not HSCs or non-MSC/HSC cells integrated into the damaged cerebral tissue and differentiated into cells expressing neural markers. Increased SDF-1 expression in injured area of brain was confirmed, which could facilitate the homing of MSCs to brain. G-CSF can mobilize MSCs into PB and MSCs in PB can integrate into injured cerebral tissue and transdifferentiated into neural cells and may benefit the repair of trauma.

The interaction between interferon-induced protein with tetratricopeptide repeats-1 and eukaryotic elongation factor-1A.

It has been shown previously that in mammalian cells, interferon-induced protein with tetratricopeptide repeats-1(IFIT1) is rapidly synthesized in response to viral infection, functions as an inhibitor of translation by binding to the eukaryotic initiation factor-3, and consequently assigns resistive activity against viral invasion to cells. It has also been reported that IFIT1 is rapidly produced in response to other cell stress agents with no direct relation to virus such as bacterial lipopolysaccharide and interleukin-1, but its function under these non-viral infection cell stress conditions has yet to be elucidated. Here, we demonstrate an interaction between IFIT1 and eukaryotic elongation factor-1A (eEF1A) both in vitro, using recombinant proteins as bait in pull-down assays, and in vivo, using laser confocal microscopy and immunoprecipitation. In addition, we report the initial determination of the domain of IFIT1 that mediates this interaction. We also display that both IFIT1 and eEF1A protein levels are rapidly elevated, prolonged in tumor necrosis factor alpha pre-treated Raw264.7 cells, and most of those cells are induced to death by the end of investigations. Our results imply that under some stressful stimulations IFIT1 may participate in cell death pathways by interaction with eEF1A.

CXCR4 gene transfer enhances the distribution of dermal multipotent stem cells to bone marrow in sublethally irradiated rats.

Our previous study indicated that systemically transplanted dermal multipotent cells (DMCs) were recruited more frequently to bone morrow (BM) of rats with sublethal irradiation than that of normal rats, and the interactions between stromal-derived factor (SDF-1) and its receptor (CXC chemokine receptor 4, CXCR4) played an important role in this process. In the present study, we aimed to investigate whether CXCR4 gene transfer could promote the distribution of DMCs into irradiated BM and accelerate its function recovery. Firstly, adenovirus vector of CXCR4 (Adv-CXCR4) and green fluorescent protein (Adv-GFP) were constructed. Then male DMCs infected by Adv-CXCR4 (group A), or infected by Adv-GFP (group B), and non-infected DMCs (group C) were transplanted into irradiated female rats, and real-time polymerase chain reaction for the sex-determining region of Y chromosome was employed to determined the amount of DMCs in BM. The functional recovery of BM was examined by hematopoietic progenitor colonies assay. The results showed that the amount of DMCs in BM of group A was greater than that in group B and group C from day 5 after injury (P < 0.05), and the amount of CFU-F, CFU-E and CFU-GM were greater than that in group B and group C from day 14 after injury (P < 0.05). These findings suggest that DMCs infected by Adv-CXCR4 distributed more frequently to the bone marrow of sublethally irradiated rats and could accelerate hematopoiesis function recovery.

Recruitment of transplanted dermal multipotent stem cells to sites of injury in rats with combined radiation and wound injury by interaction of SDF-1 and CXCR4.

Systemic transplantation of dermal multipotent stem cells has been shown to accelerate both hematopoietic recovery and wound healing in rats with combined radiation and wound injury. In the present study, we explored the mechanisms governing the recruitment of dermal multipotent stem cells to the sites of injury in rats with combined injury. Male dermal multipotent stem cells were transplanted into female rats, and using quantitative real-time PCR for the sex-determining region of Y chromosome, it was found that the amounts of dermal multipotent stem cells in irradiated bone marrow and wounded skin were far greater than those in normal bone marrow and skin (P < 0.01). However, incubation of dermal multipotent stem cells with AMD3100 before transplantation, which specifically blocks binding of stromal cell-derived factor 1 (SDF-1) to its receptor CXCR4, diminished the recruitment of dermal multipotent stem cells to the irradiated bone marrow and wounded skin by 58 +/- 4% and 60 +/- 4%, respectively (P < 0.05). In addition, it was confirmed that the expression of SDF-1 in irradiated bone marrow and wounded skin was up-regulated compared to that in their normal counterparts, and in vitro analysis revealed that irradiated bone marrow and wounded skin extracts had a strong chemotactic effect on dermal multipotent stem cells but that the effect decreased significantly when dermal multipotent stem cells were preincubated with AMD3100 (P < 0.05). These data suggest that transplanted dermal multipotent stem cells were recruited more frequently to the irradiated bone marrow and wounded skin than normal bone marrow and skin and that the interactions of SDF-1 and CXCR4 played a crucial role in this process.

Effects of peritoneal lavage fluid from radiation or/and burn injured rats on the growth of hematopoietic progenitor cells.

PURPOSE: To evaluate the effects of peritoneal lavage fluids from radiation injury, burn injury and combined radiation-burn injury on the growth of hematopoietic progenitor cells (HPC). MATERIALS AND METHODS: Rats were divided into four groups: A radiation group (RG), a burn group (BG), a combined radiation-burn group (CRBG) and normal control group (NG). RG and CRBG rats were irradiated with 12 Gy, and burns of 30% total body surface area were generated in group BG and group CRBG. Peritoneal lavage fluids were collected and tested for their effects on the growth of erythrocyte progenitor cells or granulocyte-macrophage progenitor cells of BALB/c mice in vitro. RESULTS: The numbers of colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) formed after treatment with lavage fluids from BG or CRBG were significantly higher than those from NG. However, fewer CFU-E, BFU-E or CFU-GM colonies were found after treatment with lavage fluid from the RG. In lavage fluid from BG and CRBG, the concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFalpha) was increased in comparison to NG and RG. Treatment with these cytokines had similar promoting effects on the growth of hematopoietic colonies and neutralizing antibodies inhibited these effects significantly. CONCLUSIONS: Burns increase the responsiveness of the system and help the proliferation of hematipoietic progenitor cells, while radiation decreases all these responses relative to both the controls and the burn plus radiation group.

Identification of G2/M phase transition by sequential nuclear and cytoplasmic changes and molecular markers in mice intestinal epithelial cells.

Although the regulatory network of G2/M phase transition has been intensively studied in mammalian cell lines, the identification of morphological and molecular markers to identify G2/M phase transition in vivo remains elusive. In this study, we found no obvious morphological changes between the S phase and G2 phase in mice intestinal epithelial cells. The G2 phase could be identified by Brdu incorporation resistance, marginal and scattered foci of histone H3 phosphorylated at Ser10 (pHH3), and relatively intact Golgi ribbon. Prophase starts with nuclear transformation in situ, which was identified by a series of prophase markers including nuclear translocation of cyclinB1, fragmentation of the Golgi complex, and a significant increase in pHH3. The nucleus started to move upwards in the late prophase and finally rounded up at the apical surface. Then, metaphase was initiated as the level of pHH3 peaked. During anaphase and telophase, pHH3 sharply decreased, while Ki67 was obviously bound to chromosomes, and PCNA was distributed throughout the whole cell. Based on the aforementioned markers and Brdu pulse labeling, it was estimated to take about one hour for most crypt cells to go through the G2 phase and about two hours to go through the G2-M phase. It took much longer for crypt base columnar (CBC) stem cells to undergo G2-prophase than rapid transit amplifying cells. In summary, a series of sequentially presenting markers could be used to indicate the progress of G2/M events in intestinal epithelial cells and other epithelial systems in vivo.

Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal multipotent cells to sublethally irradiated bone marrow.

Our previous study indicated that dermal multipotent cells (DMCs) could engraft into bone morrow (BM) of rats with sublethal irradiation and promote hematopoietic recovery after being transplanted systemically, but the mechanisms determining the recruitment of DMCs to the irradiation injured BM remain unclear. In the present study, we investigated the role of stromal cellderived factor-1 (SDF-1)/CXCR4 interaction in this process. Male DMCs were isolated and transplanted into female rats systemically, and by employing quantitative real-time TaqMan polymerase chain reaction for the sex-determining region of Y chromosome, it was found that the amount of DMCs in BM of rats with sublethal irradiation was about 3 times more than that of normal rats (P < 0.01). Incubation of DMCs with AMD3100 before transplantation, which specifically blocks binding of SDF-1 to its endogenous receptor CXCR4, diminished recruitment of DMCs to the injured BM by 57.2 +/- 5.5% (P < 0.05). In addition, it was confirmed that the expression of SDF-1 in injured BM was up-regulated when compared with that in normal BM, and in vitro analysis revealed that BM extracts from irradiated rats had a strong chemotactic effect on DMCs, which decreased significantly when DMCs were pre-incubated with AMD3100 (P < 0.05). These data suggest that transplanted DMCs were recruited more frequently to irradiation-injured BM than normal BM and the interactions of SDF-1/CXCR4 played an important role in this process.

Cloning and expression of mouse peroxiredoxin I in IEC-6 Cells.

AIM: To clone and express mouse peroxiredoxin I in IEC-6 cells. METHODS: Total RNAs were isolated from cultured IEC-6 cells, and the coding region of peroxiredoxin I was amplified by RT-PCR. After it was cloned into T-vector and sequenced, pSG5 was used to transiently express peroxiredoxin I in IEC-6 by liposome-mediated transfection, and the expression of peroxiredoxin I was evaluated by RT-PCR and Western blot. RESULTS: A DNA fragment about 750 bp was amplified from total RNAs of IEC-6 cells using specific primers of peroxiredoxin I. The sequencing confirmed the coding region was successfully cloned into T-vector, which was completely coincident with the sequence in GeneBank. After the EcoRI-BamHI fragment of T-vector containing peroxiredoxin I was inserted into pSG5, the recombinant plasmid was transferred to IEC-6 cells. RT-PCR assay showed that a DNA fragment of 930 bp could be amplified, which indicated the transcription of pSG5-Prx. Western blot confirmed the expression of peroxiredoxin I in IEC-6 cells. CONCLUSION: Mouse peroxiredoxin I can be successfully expressed in IEC-6 cells.

Differentially expressed proteins of gamma-ray irradiated mouse intestinal epithelial cells by two-dimensional electrophoresis and MALDI-TOF mass spectrometry.

AIM: To identify the differentially expressed proteins involved in ionizing radiation in mice and to explore new ways for studying radiation-related proteins. METHODS: Bal B/c mice grouped as sham-irradiation, 3 h and 72 h irradiation were exposed to 9.0 Gy single dose of gamma-irradiation. Intestinal epithelia were isolated from mice, and total proteins were extracted with urea containing solution. A series of methods were used, including two-dimensional electrophoresis, PDQuest 2-DE software analysis, peptide mass fingerprinting based on matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and SWISS-PROT database searching, to separate and identify the differential proteins. Western blotting and RT-PCR were used to validate the differentially expressed proteins. RESULTS: Mouse intestine was severely damaged by 9.0 Gy gamma-irradiation. Image analysis of two-dimensional gels revealed that averages of 638 +/- 39, 566 +/- 32 and 591 +/- 29 protein spots were detected in 3 groups, respectively, and the majority of these protein spots were matched. About 360 protein spots were matched between normal group and 3 h irradiation group, and the correlation coefficient was 0.78 by correlation analysis of gels. Also 312 protein spots matched between normal group and 72 h irradiation group, and 282 protein spots between 3 h and 72 h irradiation groups. Twenty-eight differential protein spots were isolated from gels, digested with trypsin, and measured with MALDI-TOF-MS. A total of 25 spots yielded good spectra, and 19 spots matched known proteins after database searching. These proteins were mainly involved in anti-oxidation, metabolism, signal transduction, and protein post-translational processes. Western-blotting confirmed that enolase was up-regulated by gamma-irradiation. Up-regulation of peroxiredoxin I was verified by applying RT-PCR technique, but no change occurred in Q8VC72. CONCLUSION: These differentially expressed proteins might play important roles when mouse intestine was severely injured by gamma-irradiation. It is suggested that differential proteomic analysis may be a useful tool to study the proteins involved in radiation damage of mouse intestinal epithelia.

Transplantation of dermal multipotent cells promotes the hematopoietic recovery in sublethally irradiated rats.

Our previous study indicated that dermal multipotent cells with the differentiation capacity to form cells with the phenotypic properties of osteocytes, adipocytes, chondrocytes, and neurons in specific inducing media could be isolated from the enzymatically dissociated dermal cells of newborn rats by their adherence to culture dish plastic. We have also observed that the systemic transplantation of dermal multipotent cells could not repopulate the hematopoietic system in lethally irradiated rats. In this paper, we found that a transplantation of plastic-adherent dermal multipotent cells into sublethally irradiated rats led to a significant increase of white blood cells in peripheral blood, nucleated cells, CFU-GM, and CFU-F colonies in bone marrow. FISH analysis, using a Y-chromosome specific probe, showed that dermal multipotent cells could engraft into bone marrow in recipients. Flow cytometry (FACS) analysis also showed that the proportion of CD2 and CD25 positive lymphocytes in peripheral blood did not change significantly in two weeks after transplantation. By these results, we infer that dermal multipotent cells may represent an alternative origin of mesenchymal stem cells to restore marrow microenvironment and promote the survival, engraftment, and proliferation of hematopoietic cells.

Downregulation of glucocorticoid receptors of liver cytosols and the role of the inflammatory cytokines in pathological stress in scalded rats.

Preliminary experiments indicated that target cells were resistant to glucocorticoid (GC) after pathological stress. This study was designed to investigate the alterations in plasma corticosterone level and GC receptor (GR) of liver cytosols, to assess the relative inflammatory cytokines contribution to GC resistant, and to observe the action of alpha-melanocyte-stimulating hormone (alpha-MSH) on the potential implications of glucocorticord regulatory effects in burned rats. Male Wistar rats (weight range, 180-200g) received a 35% total body surface area immersion scald and were randomly divided to receive either tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), polyclonal antibody (pAb), alpha-MSH, Ac-D-Lys-L-Pro-D-Val (KPV peptide), or saline (control). The binding capacity (Rt) of the steroid-binding sites was measured by radioligand binding assay, using [3H]dexamethasone as the ligand. We examined plasma levels of IL-1beta, TNFalpha, IL-10, and corticosterone following scald challenge in rats. The Rt of GR (208.45+/-30.78fmol/mg of protein) in hepatic cytosol in rats, 12h later the scald was significantly lower than that (306.71+/-27.96fmol/mg of protein) of the control group (P<0.01). The injections of anti-rat TNFalpha (257.80+/-12.82fmol/mg of protein), IL-1beta antibody (254.46+/-21.21fmol/mg of protein), alpha-melanocyte-stimulating hormone (278.32+/-7.76fmol/mg of protein) and KPV peptide (263.46+/-17.46fmol/mg of protein) might prevent the Rt of GR from decreasing in hepatic cytosols of rats with scald, respectively (all of P<0.05) in vivo. Scald-induced robust increases in plasma IL-1beta (214.08+/-27.25pg/ml), TNFalpha (111.18+/-23.97pg/ml), IL-10 (177.50+/-15.79pg/ml) and corticosterone (2680+/-443.23ng/ml) levels after 12h. The administration of TNFalpha, IL-1beta pAb, alpha-MSH and KPV might attenuate these increases. These studies suggest that pro-inflammatory cytokines are involved in downregulation of GRs and thus alpha-MSH and KPV might increase the level of GR in rats with immersion scald.

[Impact of secondary pancreatic infection on the prognosis of patients with severe acute pancreatitis: an analysis of 60 cases].

OBJECTIVE: To investigate the impact of secondary pancreatic infection (SPI) on the prognosis of patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 60 patients with SAP (January 1, 1980-December 31, 1999), especially the data at the onset of SPI, were retrospectively analyzed. RESULTS: Sixty patients were divided into two groups: SPI group (29 cases) and non-SPI group (31 cases). There was no significant difference in gender, average age, scores of Ranson and of high risk factors of China Medical Association between two groups, but the average stay days in hospital, payment, acute physiology and chronic health evaluation II (APACHE II) scores, days of fever, prehospital days, days of high white blood cell (WBC) count, the duration of constipation after the onset of SAP and average times of operation were significantly higher in SPI group than that of non-SPI group. Fatality rate of SPI group (7/29, 24.14 percent) was higher than that of non-SPI (1/31, 3.23 percent). There were 14 cases of infection with single microorganism (48.3 percent) and 15 cases of mixed infection (51.7 percent) in SPI group. Twenty-seven patients were infected with bacteria of Enterobacteriaecae (Escherichia 25, Klebsiella pneumoniae 1, Proteus morgani 1, 8 with bacteria of Pseudomonas (P. aeruginosa 7, P. stanieri 1), 2 with fungus, 5 with other bacteria (Bacillus subtilis 2, Tetracoccus 1, Acetobacteraceae 1, Staphylococcus epidermidis 1) in SPI group. Only in 2 patients with infective pancreatic necrosis the blood culture was positive (Escherichia coli). CONCLUSION: These results showed that the major source of SPI is entergenous, and SPI would affect the prognosis of SAP patients. With the present therapeutic regimes it was hard to prevent entergenous infections. It is necessary to find a new strategy.

Different roles of TGF-ß in the multi-lineage differentiation of stem cells.

Stem cells are a population of cells that has infinite or long-term self-renewal ability and can produce various kinds of descendent cells. Transforming growth factor ß (TGF-ß) family is a superfamily of growth factors, including TGF-ß1, TGF-ß2 and TGF-ß3, bone morphogenetic proteins, activin/inhibin, and some other cytokines such as nodal, which plays very important roles in regulating a wide variety of biological processes, such as cell growth, differentiation, cell death. TGF-ß, a pleiotropic cytokine, has been proved to be differentially involved in the regulation of multi-lineage differentiation of stem cells, through the Smad pathway, non-Smad pathways including mitogen-activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and Rho-like GTPase signaling pathways, and their cross-talks. For instance, it is generally known that TGF-ß promotes the differentiation of stem cells into smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic stellate cells, Th17 cells, and dendritic cells. However, TGF-ß inhibits the differentiation of stem cells into myotubes, adipocytes, endothelial cells, and natural killer cells. Additionally, TGF-ß can provide competence for early stages of osteoblastic differentiation, but at late stages TGF-ß acts as an inhibitor. The three mammalian isoforms (TGF-ß1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Understanding the mechanisms underlying the regulatory effect of TGF-ß in the stem cell multi-lineage differentiation is of importance in stem cell biology, and will facilitate both basic research and clinical applications of stem cells. In this article, we discuss the current status and progress in our understanding of different mechanisms by which TGF-ß controls multi-lineage differentiation of stem cells.

Steroid receptor coactivator-3 differentially regulates the inflammatory response in peritoneal macrophages.

Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator that plays an important role in the regulation of cytokine mRNA translation. In the present study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the regulation of the inflammatory response in peritoneal macrophages induced by lipopolysaccharides (LPS). Peritoneal macrophages (PMs) of SRC-3-/- mice showed a decrease in the release of TNF-α, IL-1ß and IL-6, and an increase in the release of IL-10. Furthermore, results of RT-PCR also showed that levels of TNF-α, IL-1ß and IL-6 mRNA expression were significantly lower, while the level of IL-10 mRNA expression was higher in the SRC-3-/- mice, compared to those of wild-type mice, following treatment with LPS (p < 0.01). In addition, western blotting revealed that: i) the extent of reduction of the glucocorticoid receptor in PMs from SRC-3-/- mice was significantly lower than that in wild-type mice (p < 0.01); ii) the extent of increase of AP-1 in PMS from SRC-3-/- mice was significantly lower than that in wild-type mice (p < 0.01); iii) the extent of increase of NF-κB p65 in PMs from SRC-3-/- mice was significantly higher than that in wild-type mice (p < 0.01). Collectively, our studies revealed that SRC-3 may play a key role in the maintenance of innate immunity. Furthermore, absence of the SRC-3 protein may result in the partial loss of inflammation and phagocytosis barrier function, including suppression of LPS-induced transcriptional activity, release of TNF-α, IL-1ß and IL-6, and obstruction of the function of phagocytes and elimination of bacteria, as well as their production.

Suppression of CX43 expression by miR-20a in the progression of human prostate cancer.

The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. The present study found miR-20a to be significantly upregulated in prostate cancer compared with normal prostate tissues. The proliferation and colony formation assays revealed that the downregulation of miR-20a by miR-20a inhibitor suppresses the proliferation of MDA-PCa-2b cells in vitro and also inhibits tumor growth in vivo. Furthermore, a gap junction protein, α 1 (CX43), was identified as a direct target gene of miR-20a. The upregulation of CX43 was detected in MDA-PCa-2b cells after treatment with miR-20a inhibitor both in vitro and in vivo. In conclusion, the findings show that miR-20a significantly contributes to the progression of prostate cancer by targeting CX43.

Experimental research on the management of combined radiation-burn injury in China.

Combined radiation-burn injury can occur in people exposed to nuclear explosions, nuclear accidents or radiological terrorist attacks. Using different combined radiation-burn injury animal models, the pathological mechanisms underlying combined radiation-burn injury and effective medical countermeasures have been explored for several years in China, mainly at our institute. Targeting key features of combined radiation-burn injury, several countermeasures have been developed. Fluid transfusion and the calcium antagonist verapamil can prevent early shock and improve myocardial function after combined radiation-burn injury. Recombinant human interleukin 4 (rhIL-4) is able to effectively reduce bacterial infection and increase intestinal immunological ability. Chitosan-wrapped human defensin 5 (HD5) and glucagon-like peptide 2 (GLP-2) nanoparticles can increase the average survival time of animals with severe combined radiation-burn injury. After treatment by cervical sympathetic ganglia block (SB), hematopoietic function is promoted and the release of inflammatory cytokines is suppressed. The optimal time for escharectomy and allo-skin grafting is 24 h after injury. Transfusion of irradiated (20 Gy) or stored (4°C, 7 days) blood improves the survival of allo-skin grafting and allo-bone marrow cells. In conclusion, as our understanding of the mechanisms of combined radiation-burn injury has progressed, new countermeasures have been developed for its treatment. Because of the complexity of its pathology and the difficulty in clinical management, further efforts are needed to improve the treatment of this kind of injury.